Research Seminar 2014.1.20!
Takaya Ukai (B4)

0. Introduction“Pincer”-A New Paradigm of Ligand DesignOverview of Dehydrogenation Chemistry!2

Goals of This Seminar

Metal!Ligand Cooperation Gunanathan and Milstein

What is “Pincer”?

SCHEME 14
1. Understand the characteristic properties of pincer complexes

R

Y

X

Z

MLn

Y

X

2. Understand the development of dehydrogenative bond activation

UPDATESR

XH

Metal salts+ Oxidants

FIGURE 5
Substrate
X = CH 2, CH, N, O

R

X

R

XH

Catalyst

Y

X

Z

MLn

Y

X

Sanaa Musa et al.
R

X

+

R

H

Wastes2[15]
cross-coupling results.[a–c]imines (TON =+ 830).
These catalysts can activate/ Table 1. Representative
Additives
form chemicalbonds via intramolecularinteractions
Substrate
Product
Product
between the metal center and the ligand!sfunctional
X = CH 2, CH, N, O
sidearm (Figure 1).
SCHEME 15

SCHEME13
3. Understandthe new concept of ligand design

X = NR2, PR’3, etc…
Y = CH2, O
Z = C, N, B
R = EDG, EWG, etc…

#99 Kingler“Pincer” = mer Tridentate Ligand

SCHEME 16!3

Figure 1. Catalysts used in this work.

Goldman, A. S., et al. Chem. Rev. 2011, 111, 1761

!4

Pincer’s Diversity
Y

X

Group

Major Effects

Z

MLn

X (Arm)Steric control,
Electron density

YX

Y (Joint)

Indirect steric control,
Ligand’s Cooperativity

Z (Core)Trans effect

R (Tail)Remote control ofelectron density

Backbone(Body)

Flexibility,
Other functional groups

M (Center)

Selectivity in activation ofmolecules (C-H, O-H, etc)R

X = NR2, PR’3, OR, SR
Y = CH2, O, NH
Z = C, N, B
R = EDG, EWG

Goldman, A. S., et al. Chem. Rev. 2011, 111, 1761

Pincer Complexes

Common features:• Stable to moisture and air (high valent)• Stable to high temperature• Controllable electronic and steric properties• Ligand’s Non-innocence of bond activation!5

Contents!6

1. Dehydrogenation of
Alkanes and Goldman’s
Basic Studies on Pincer

0. Introduction!
1. Dehydrogenation of Alkanes and Goldman’s Basic Studies on Pincer!
2. Dehydrogenation of Alcohols and Milstein’s Advanced Studies on Pincer!
3. Gelman’s Cooperative Catalysts for Acceptorless Dehydrogenation!
4. Summary!7!8

r steric andﬀects and0,26

es derived
positions,inﬂuence
electronic
xert wellmplicating
nic eﬀects,
s in Y canric eﬀects.
rise a very
literature.
ated comave been
ydrogenaomplexes,
996, when
for alkane
nto threeations, (2)d (3) reacum pincer
ydrogenae found in

Main Character of This Chapter

Dehydrogenation of Alkanes
Alkene: versatile feedstock for…
• Fine chemicals• Transportation fuels!
Alkene: versatile functional group for…
• Electrophilic attack• Pericyclic reaction• Metathesis

1980 B.A at Columbia University
1985 Ph.D at Caltech under theguidance of David R. Tyler
then; postdoc in Jack Halpern’s lab
1987 Assistant professor at Rutgers
1993 Associate professor at Rutgers
2000 Professor at Rutgers
2005REVIEW
Professor (II) at Rutgers

cyclooctadiene complexes (eq 1). Subsequently, Felkin and coworkers reported similar types of dehydrogenation of cycloalkKeywords:
AlanwithGoldmananes(PPh3)2ReH7.47,48 Soon thereafter, the ﬁrst examples• Organometallicsofcatalytic atalkanetransfer-dehydrogenation
byJerseyhomogeneous• Alkane dehydrogenation
Professor
Rutgers,
State University of New
complexes
werereported andindependently
by Felkin49-51 •andDepartmentofChemistry
Chemical
Biology
Alkane metathesis
Crabtree,52-54 with both researchers having the greatest success• Sustainable Fuel Chemistrywith bis(trialkylphosphine) complexes of iridium. Crabtree also
!9reported that IrH2(O2CR)(PCy3)2 eﬀected acceptorless dehydrogenation of cyclooctane, to give up to 36 turnovers of
cyclooctene in 48 h.55 Turnover numbers were limited in thesesystems by catalyst decomposition due to the high temperatures
required and the tendency of the metal centers, which arenecessarily highly reactive, to attack their own ligands via either
intra- or intermolecular paths. The rhodium complex Rh(PMe3)2(CO)Cl, by contrast, was found to be a very robust
catalyst for photochemical alkane dehydrogenation56 and subseHeterogeneous
catalysis
quently for thermochemicaltransfer-dehydrogenation with awide range of alkanes and hydrogen acceptors. ThermochemiCr, Pd,
Rh, Pt,operative
etc...
cally, however, it was
only(surprisingly) undera Limited scope+ H2
C 2H 6 or
57,58 C2H 4 or&
The requirement of a H2
dihydrogen atmosphere500~900(eq 2).
°C
atmosphere severely limited the utility of this system as more Severe Condition
than 1 mol of acceptor was inevitably hydrogenated per mole ofGoldman, A. S., et al. Chem. Rev. 2011, 111, 1761
dehydrogenated product.

Dehydrogenation of Alkanes

Homogenenous catalysis

Dehydrogenation of Alkanes
R

What is an “ideal” synthesis?
R

R

Catalyst

+
R

R

H2

R

!10

Chemical Reviews
Chemical Reviews
never shown any signiﬁcant diﬀerence from use of the corresponding
than requiring
additional
molecorreof
neverdihydrides,
shown anyothersigniﬁcantdiﬀerenceone
from
use of thehydrogen
acceptor
in
the
case
of
transfer-dehydrogenation.
sponding dihydrides, other than requiring one additional mole ofhydrogen acceptor in the case of transfer-dehydrogenation.

1. Proposed Mechanism of nFirst Reports on An Ir-PincerScheme
Complex
Dehydrogenation by 3-H

2
Scheme 1. Proposed Mechanismof nDehydrogenation by 3-H2

PCP-Metal-H2 complexes

PPh 3
H
H

Ir

O

TBE (50 eq)
150 °C, 14 days

TBE =stoichiometricCrabtree, R. H., et al. JACS, 1979, 101, 7738

First transfer dehydrogenation by the Ir-pincer complex(3)

CF3

O
PPh 3

Catalyst Turnovers / h (150 °C)~ 34 turnovers

t-Bu

Crabtree, R. H., et al. JACS, 1987, 109, 8025RhðPMe3 Þ2 ClðCOÞ

Lows
turnover is due
instability
alkane þ hydrogen acceptor ðAÞþ AH2
f toalkene
H atm

2
of catalysts
at high temperature

ð2Þ

!11

3-H2
4-H2

82
<1

No decomposition over 1 weekat 200 °C, highTBE and N2 inhibit
theJensen,C. M., Kaska,
W. C.,
al. Chem. 3
Commun.
1996,
2083
The high
thermalstability
ofetcatalyst
enableddemonstrationof reaction
during COA/TBE transfer-dehydroThe high thermal stability of catalyst 3 enabled demonstration of
the ﬁrst
of eﬃcient
acceptorlessdehydrogenation
the example
ﬁrst example
of 61
eﬃcient
acceptorlessdehydrogenationunder
under
61 sterically less crowded isopropylThe
reﬂuxreﬂux
conditions
(eq
5).
The
stericallylesscrowdedisopropyl
conditions
(eq
5).
iPr
i
close to 1000 turnovers inanalogue( 4PCP)IrH
4 (5-H4) aﬀorded
analogue( Pr4PCP)IrH
4 (5-H4) aﬀorded close to 1000 turnovers induring COA/TBEt transfer-dehydro
!12
t
lim
(PCP)Ir(CHdCH
Bu)(H). In
In thatthat lim(PCP)Ir(CHdCHBu)(H).
stepishydrogenation
of
TBE
and
the
step is hydrogenation
of
TBE
and
the
63
[T
order
Inthe
the limit
limit ofof highhigh [Torderinin[TBE].
[TBE].63In

tion ofunder
propylvers inmple of
e).62

on by
ituentnation,ll catnd of
on ofn spe3 thenalkanee oleﬁnwever,
idativegroup
re in adentlyrecentatalystP)Ir(1her by
oleﬁn,
ct, candehyectivity
vity forof thethere-

entra3 andg state

48

360

78
be expected to be less electron-rich than their PCP analogues.
This transfer-dehydrogenation
expectation was supported by ismeasurementa Conditions: catalyst, 1.0 m
The high thermal stability of catalyst 3 enabled demonstration ofduring COA/TBE
3-H2, notof the C-Otstretchingfrequenciesoftherespective
CO adducts,12 theconcentrations determined by GC
the ﬁrst example of eﬃcient acceptorless dehydrogenation under(PCP)Ir(CHdCH Bu)(H). In that limit, the turnover-limiting
ChemicalReviews
standard
electronrichnessof metal
centers.
These
REVIEW
ChemicalReviews
stericallylesscrowded isopropyl
reﬂux conditions(eq 5).61 The
step is hydrogenationof indicator
TBE andforthe
catalytic
reaction
is ﬁrstREVIEW
iPr
tBuPCP complex (158 turno
63
4
observations
seemed
at
odds
with
the
greater
catalytic
effectiveanalogue ( PCP)IrH4 (5-H4) aﬀorded close to 1000 turnovers inorder in [TBE]. In the limit of high [TBE], the resting state is
never
shown
any
signiﬁcantdiﬀerence
from
use
of
the
correScheme
1.
Proposed
Mechanismofn-Alkane/TBE
Transfer
After 24 h, the p-methoxy-su
nessp-methoxy-PCP
derivatives(as described
below),t of 1.theProposed
never isshownany
diﬀerence
fromofthe correScheme
ofturnover-limiting
n-Alkane/TBE
Transfer
the COA/TBE
dehydrogenationof cyclodecane
andﬁrstsigniﬁcantreportedexampleof useBu)(H).
In thatMechanism
the(PCP)Ir(CHdCH
duringtransfer-dehydrogenation
3-Hthe2, notsponding
dihydrides,
otherthan requiring
one additional
mole
of Dehydrogenation
Dehydrogenation
bycase,3-Haret
2 more electron-rich than the parent
ascompared with 360 TO fro
62 one additionalsince
the latter complexes
sponding
dihydrides,
other
than
requiring
mole
of
by
3-H
Acceptorless
DehydrogenationofCyclicAlkane2
Bu)(H).
Inthat
limit,
theturnover-limiting(PCP)Ir(CHdCH
acceptorless dehydrogenation of anhydrogen
acyclic alkane(n-undecane).
step is the reaction with COA, which follows a pre-equilibrium • Transfer Dehydrogenation
acceptorthe ofcaseof transfer-dehydrogenation.
hydrogen
acceptorin theincase
transfer-dehydrogenation.
step is hydrogenation of TBE and the catalytic
reaction
is ﬁrstobtained using the MeO-tBu
catalysts. Computational results, however, resolve this apparent
loss of TBE; the contradiction.
rate is therefore
inversely dependent on [TBE].
TBE
Rate Determining
Steporder in [TBE].63 In the limit of high [TBE], the resting state is(within20%)tothoseprevious
We demonstrate in this work that key thermo(PCP)Ir(CHdCHtBu)(H). In that case, the turnover-limiting
In the case of dynamic
acceptorlessdehydrogenation,
theactivecomLowalkene insertion
phosphino) catalyst (with n
and kinetic properties are affected similarly by thestep is the reaction with COA, which follows a pre-equilibriumHigh
C-H addition
thissubstitution
isplex 3 is generated
via thermolytic
loss substituentsof H2 fromor3-H
IrH4. The latter complex waspresenceof p-methoxy
by2;theofloss of TBE; the rate is therefore inversely dependent on [TBE].
the turnover-limiting
step of the cyclein the limit
of by
eﬀective
In the case of acceptorless dehydrogenation, the active comRestingstate (TONs)
differs according
higher than any pre
the phosphorus-linked
methylenesofPCP
oxygen
atoms
(to
68-71
plex 3 is generated via thermolytic loss of H2 from 3-H2; this isto the concentrationof olefin.
the system.
Catalytic
activity isaffectin- νCO values
removal of H2 fromgenation
catalyst.14
give
POCOP),
eventhoughthesesubstitutions
the turnover-limiting step of the cycle in the limit of eﬀective
hibited by the buildup
of oleﬁn
product
to theformationof thermodyin opposite
directions.
Wedue
believethesekinetic andthe system.68-71(200Catalytic
removalCatalystof H2 fromTurnovers/20h°C) activity is inSincep-methoxy subGoldman, A. S., et al. JACS,
2003,the125, 7770
Steric hindrance: iPr < tBu tBu4
hibited The
by3-H
the2mechanism
buildup of oleﬁn of
productdue
totheformationofPCP)Ir(oleﬁn)andperhapsdue
toanincreased
rate
of
back(
namic
similarities
areclosely
linkedtothegreater
catalytic
COA/TBEtransfer
dehydrogenationby163
presenceofi-Pr
groups on
tBu
and perhaps 700
due to an increased rate of back- Goldman, A. S., et al. Chem. Commun. 1997, 2273
( Bu PCP)Ir(oleﬁn)
4 5-H2
reaction(oleﬁnhydrogenation).
activity
of
both
POCOP
and
MeO-PCP
catalysts.
• Acceptorlesslead
Dehydrogenation
PCP)Irwasdeterminedbyakinetic
study
of
its
constituent(
tosignificant
improvem
reaction (oleﬁn hydrogenation).
Catalysts 3 and
5
show
high
kinetic
selectivity
fordehydrowished
Rate Determining
Steptois explore the effectCatalysts
3 and 5TBE
show highkinetic selectivity andfor dehydrosegments,hydrogenation
COA dehydrogenation,
Results and Discussion
5-H4 ofalso
acceptorlessdehydrogenation
genation
thecatalyzed
terminal position
ofdetailed
n-alkanes
tokinetic
give R-oleﬁns.
H2 liberation (dissociative)
genation of the terminal position of n-alkanes to give R-oleﬁns.
same complex. (MeO-iPrPCin
conjunction
with
study
of
the
full
catRPCP)Ir Catalysts. 1.1. AccepThisofregioselectivity
holds
promisewith respect to then-alkane (n-undecane:turnovers/h)
63 great 70
1. Experimentswith (X-with
Resulted olefin
also inhibits
perimental
Section) and indeThisregioselectivity
holds
great
promiserespect
totheTBE
alyticformationof reaction.
valuable R-oleﬁnsInsertionand productsof
derivedfrominto
them an Ir-H bond oftBu
thereaction
torless
Dehydrogenationof
Cyclodecane.
Acceptorless
dehy4
for CDA dehydrogenation. U
in tandem
catalytic systems.
Unfortunately,
however,by
subsequent
formation of valuable R-oleﬁns and products derived from them
reductive elimination of( PCP)IrH
2 (3-H2) followed
drogenation
is a reaction thathowever,is potentiallyeven more valuable
Inhibitionby thermodynamicallyn-Alkene is bigger than that by Cycloalkene
isomerization leads to the formationof thedescribed above, 360 TO aintandemcatalytic
systems.
Unfortunately,subsequent
tert-butylethane(TBA)
the ofreactive
14-electron speGoldman, A. S., et al. JACS, 2002, 124, 11404
The mechanism
this
more
stableinternal
oleﬁns(eq 6).72generates
tBu
than transfer dehydrogenation.4,13,14 Cyclodecane (CDA)
is aGoldman,
IrH48 after 1 h of reflux. Afte
4 A. S., et al. Chem. Commun. 1997, 2273
isomerization
leads
to
the
formationofthethermodynamically(3).hasWithincomplex 3 thencies oleﬁn( PCP)Ir
observedisomerization
therefore thebeen catalytic
the subject cycle,
of
!13
!14
convenient
substratefor
screening
thisreaction
owing
to
the
72
The highbythermal stability of catalyst 3 enabledmore
demonstrationofafter 72 h a total of 3050 TO
during
COA/TBEtransfer-dehydrogenationis 3-H2, notcarefulstudy. It wasoxidative
initially assumed
that oleﬁnThe
Themechanismof
thisstableoleﬁns(eq
6).
highthermalbond
stabilityofof catalyst
3 enabled demonstrationof internal
undergoes
addition
ofisomerization
a
C-H
the
alkane,notduring
COA/TBEtransfer-dehydrogenationis
3-Ht
2 point (201of allunits
highthefollowed
ﬁrst example of eﬃcient acceptorless dehydrogenation under equivalence
Bu)(H).
In andthat its
limit,
theboilingturnover-limiting(PCP)Ir(CHdCH
3-H2 occurred via 2,1-insertion of the terminal oleﬁn,t HCCHare the highest turnover
the ﬁrstelimination
examplebyof eﬃcient
acceptorlessdehydrogenation
underoleﬁn (PCP)Ir(CHdCH
Bu)(H).
In thatlimit,thethe subject
turnover-limiting
observedisomerizationhas
therefore
of tBu61 the oleﬁn
substrate,and subsequentβ-hydride
produces
4,14 istBubeenβ-hydrideeliminationfrom carbon-3(addition-eliminationThe
stericallylesscrowdedisopropyl
reﬂux conditions
(eq
5).
°C).
CDA
solutionsof(
PCP)IrHand(MeOstephydrogenation
of
TBE
and
the
catalytic
reaction
is PCP)ﬁrst
61
2
reported to date for homog
iPr(eq 5).
72
The
stericallylesscrowdedisopropyl
reﬂux
conditions
step initiallyis hydrogenation
TBE oleﬁnand theisomerization
catalytic reaction
63 of that4careful study. It was
assumedbyis ﬁrst
However, 3-H
recent2 studies
indicatemechanism,
iPr 1).
(SchemeproductSchemeand 2a).
regenerates
PCP)IrH4 (5-Hhowever,analogue(thatSigniﬁcantly,
the limit andof high[TBE], theresting
state
is
inmM)
[TBE].
4) aﬀorded close to 1000 turnovers in IrH2order
63 wereIn(1.0
preparedsubjected
tovigorous
reflux4
Budrogenation.
PCP)IrH(5-H)
aﬀorded
close
to
1000
turnoversinanalogue
(
In
the
limit
of
high
[TBE],
theresting
state
is
order
in
[TBE].
t4
PCP)Ir- 4 of cyclodecane
isomerization proceeds predominantly throughthe( dehydrogenationand the ﬁrst reported
example ofviawith
2,1-insertionoft theterminal
oleﬁn,
followedby loss of H2,
3-H
Bu)(H).
Incondenser
that case,theturnover-limiting(PCP)Ir(CHdCH
the 14-electron species 3 canthealso
undergoout-of-cycle
oxidative
2 occurredargon flowing
above
the
to permit
dehydrogenationofcyclodecane
and
the
ﬁrst
reportedexampleof
62
Bu)(H).
In
that
case,
the
turnover-limiting(PCP)Ir(CHdCH
which
then
(1-alkene), which forms ( Bu PCP)Ir(η3-allyl)(H),
1.2. Acceptorless Dehyd
acceptorlessdehydrogenationof anacyclic alkaneβ-hydride(n-undecane).
step isfrom
the previously.
reactionwith4,14
COA,
which follows a pre-equilibrium
Bu TBE vinylic C-H bondcarbon-3(addition-elimination
additionof (thetransto the tert-butyl
group
as described
PCP)Ir(2-alkene). This
π-allylic mechanrearranges
to give
acceptorlessdehydrogenationof an acyclicalkane (n-undecane).62 elimination
stepis theof72
reaction
with
COA,
whichinversely
follows dependent
a pre-equilibrium
superiorityof (MeO-tBuPC
66
loss
TBE;
the
rate
is
therefore
on[TBE].
ism asis shown
SchemeHowever,recentinversely
studiesdependent
indicatethat[TBE].
mechanism, Schemeloss of2a).
TBE;
the
rate
is
thereforeon
indicated
in2b.
Scheme 1. The resulting vinyl hydride and 3 are in at
In the case of acceptorless dehydrogenation,
the active comreproduced with the acceptor
Inplexthe 3caseof acceptorless dehydrogenation,
the active comisomerization proceeds
through ( Bu4PCP)Irrapid pre-equilibrium, the kinetics of Isomerization
which weretoindependently
ispredominantly
tgenerated via thermolytic loss of H2 from 3-H2; this isinternal olefin was observed(bp 196 °C). There was little
Bu
3
64
3-H
is
plexforms
3 is turnover-limiting
generated
via thermolytic
losscycleof Hwhich22;ofthisthen( 4PCP)Ir(ηthestep-allyl)(H),of theinfromthe limit
eﬀective
p-MeO group makes Ir center
Likewise,recentalkane (1-alkene), whichquantiﬁed by dynamic NMR at low temperature.
in Dehydrogenationof acyclicttimes(18 vs 23 TO, respecti
the turnover-limiting
step theof thecycle68-71
in thelimit ofactivity
eﬀective
4
system.
Catalytic
is in-electron rich and enhances
removalof H2 from
more
PCP)Ir(2-alkene).
This
π-allylicmechanrearranges to give
( Bu
68-71
experimental
have shown that the resting state tof the catalyst
Chemicalresults
Reviews
advantageat longer times (10REVIEWfromthesystem.
Catalytic
activityisinremovalofH
66
Bu4Alkane Dehydrogenation ism is shown Scheme
hibitedby2 the buildup of oleﬁn product due toPincer-Ligated
Ir Catalysts
A formation
Rthe
T Iformation
C L EOxidative
S of Addition step
2b.
tBu
PCP)Ir(1during the transfer-dehydrogenationof n-octane
is ( forhibitedbythebuildupof
oleﬁn
product
due
to
the
of
4
more
disappointing,(MeO
and perhaps due to an increased rate of backThe mechanism of COA/TBE transfer dehydrogenation by tBu4 ( PCP)Ir(oleﬁn)
65,66
74
tBu
PCP)Ir(oleﬁn)andperhapsdue
toanincreasedrateofback( TableThus,
in general,
oleﬁn
can
bind
to
(PCP)Ir,eitherbyoctene).
Scheme 2.
Possible
Pathways
forthe
Ir-Catalyzed
IsomeriIndeed,
the
which
was
expectedtobethermally
very
stable.
aThemechanism
of
COA/TBEtransfer
dehydrogenationby
C-H
activationby
low-valent
Ir
complex
4 Allylicpoorerresultsforacceptorles
1. Acceptorless
Dehydrogenation of CDA (bp 201 °C)
reaction(oleﬁn hydrogenation).
recently,
Brookhart byanda co-workers
that the
PCP)Irwas determinedkinetic studyreportedof its constituent( Veryt
RPCP)IrHareaction(oleﬁnhydrogenation).
Catalyzedby (Xtemperatures
to 5250
but kinetic selectivity for dehydrozation of Terminal
to Internal
complex
PCP)Irwasdeterminedbya isomerization
kinetic
studyof 2its7a-H( Bu4Oleﬁns
n !C, hightBu
Rconstituent
responsible
formode,the
2 tolerated
π-coordination
or by C-H
addition;in iseither
binding
oleﬁn,
did either of the tBuPCP-bas
Catalysts
3up
and
show
bis-phosphinite
catalysts(XPOCOP)IrH(dehydrogenation,
POCOP) κ3-reaction
segments,
TBE
hydrogenation
and
COA
As
seen
in
Table
1,
the
initialrate
of dehydrogenation
was
Catalysts
3
and
5
show
high
kinetic
selectivity
forgivedehydrounder
was
found
to
be
signiﬁcantly
lessreactivethan
3-H
segments,
TBE
hydrogenation
andCOA
dehydrogenation,
tBuPCP)IrH for2
catalyst;
total
turnovers()mM)
genationoftheterminal
positionofn-alkanestoR-oleﬁns.
CH-2,6-(OPR
)
)
are
more
effectivethan(
in6 dehydrogenatedconjunction
detailed
as either the sacriﬁcial acceptor or
product,kinetic
can study of the fulltBuPCP complex than with the parent
3
2 with22 cat1.3. Transfer Dehydroge
greaterproposed
with
MeOgenation
the theterminalofXn-alkanes
towithgiveXrespect
R-oleﬁns.
comparable
conditions.
that
theposition
inﬂexible
indehydrogenation
conjunction
with63 detailed
kinetic
study
theIr-H
fulldehydrocat- The
This ofregioselectivity)promise
MeO;) MeO; to theX ) H; holds great
cyclooctane/tert-butylethylenetransfer
Insertionof(COA/TBE)
TBE
intoofanbond
of authors
alyticreaction.
Inthereby
part to develop
improved inhibit
catalysts for
signiﬁcantly
activity.
Indeed,faciledehy63ofthe morepoor
results obtained for
tBu
This phosphinoregioselectivity
greattopromise
to thethemanthraphos
backbone
Insertion
of
TBE
into
an Ir-Hbond mightof forced
reaction.
4
11 The) t-Bugroups
Bu with respect
R holds
R ) t-products
R ) i-Prtime/hformation
oftert-butyl
valuable
R-oleﬁns
andderivedfromalkanes, a wide range of modiﬁed PCP pinceralytic
ligandswithvarying
metal2)centersof thecomplexes
PCP)IrH
followed
byPOCOP
reductive
eliminationof the(genation.
tBu
2 (3-H(7)
Goldman,A.
S.;
Czerw,
M.;
Renkema,K.
B.;
Singh,B.;
Zhu,
K.;
Krogh4drogenation of cyclooctane
vsn-alkane
is
not
due
to
any
selectivity
n-alkane,(MeO-iPrPCP)IrH2
formationofvaluable
R-oleﬁns
andproducts
derived
from
them
block
the
metal
centermore so than
case
of 60
pincerswithfollowedby reductive
eliminationof spe( PCP)IrH
2 (3-H2)
inJespersen,
tandemcatalytic
systems.
Unfortunately,
however,
subsequenttBu
1in the K.
158 ACS National357
tert-butylethane(TBA)
generatesthereactive
14-electron
AbstractsofPapers;222nd
Meeting,
Chicago,4
tBu
1763 for the former
dx.doi.org/10.1021/cr1003503|Chem.
Rev. 2011,
1761–1779
in tandem
catalytic
systems.
Unfortunately,
however,
subsequentPCPm-xylylbackbone,thus
inhibiting
accessof formation
the Washington,
catalyst for transfer dehydroin111,fact
6:1
selectivity
forthe simple
alkane (( PCP)Ir
tert-butylethane(TBA)
generates
the catalytic
reactive
14-electron
spe4 shows
2American
110
275 of450INOR-016 AN
IL;
Chemical
2001;
isomerization
leads
to Society:
thetheDC,
thermodynamically
PCP)Ir(3).
Withinthecycle,
complex
3 thentcies
Bu4 (72 thermodynamically
2001:639203.
4
170
430
714
isomerization
leads
to
the
formationofthealkanesubstrate
to
the
metal
center.
It
wasproposed
that
thePCP)Ir(3).
Withinthecatalytic
cycle,
complex
3
then
cies
(
other
n-alkyl group containin
mechanismof this ofstableinternal oleﬁns(eq6). Then-octane vs cyclooctane) but rather
due to oxidative
weaker bindingof atheundergoes
addition of
C-H bond of the alkane (8) more
tBuPCP)IrH
tBu72
Both
(X(X-6).
PCP)IrH
are suitable
6isopropyl
220575
868ofprecursors
4 and(eq2mechanism
The
this
more
stableinternal
oleﬁnsreplacementoftert-butylgroupswithgroups(complex
undergoesoxidative
addition
of
a
C-H
bond
of
the
alkanetBu
observed
oleﬁn
isomerizationhas
therefore
been
thesubjectofwith 0.79 M norbornene (substrate,(cyclooctene)
and subsequent β-hydride
elimination produces the oleﬁn“(Xand rapidly under
24 PCP)Ir”. The
360 tetrahydrides lose
820 H2 reversibly 2120
corresponding dehydrogenated productand thereobserved
isomerization
thesubjectinofcatalytic
7b)
would
enhancereactivity
bycareful
reducing
stericcrowding.
Intherefore
substrate,and subsequentβ-hydridethe oleﬁnevenambient
conditions.
We has
have
never
any
difference
study.
It wasinitially
assumedthatbeen
oleﬁn
isomerization
by48 oleﬁn
360
820observed
2970(Scheme1).produces
Signiﬁcantly,
however,
product
and regenerates
3-H2 elimination
fore lesser inhibition.67
activity
withtheviatwo(althoughpresumably
an followed
additionalmole
study.
It wasinitially
assumedthatisomerization
by byanothereﬀort
to oxidative
prepare acarefulmorestablecomplex782thermally-precursors- oleﬁn3050
Signiﬁcantly,
product
regenerates
3-H2electron-richoccurred
2,1-insertionoftheterminal
oleﬁn,
3-H
the
14-electron
species3(Scheme
can also 1).
undergoout-of-cycle
be andexpected
to be
less
than
their
PCPhowever,analogues.
of sacrificial
acceptor
is consumed
withthe tetrahydrides).
The tetrahydrides(11) Göttker-Schnetmann, I.; WhiteThe kinetic dependence onsacriﬁcial
acceptor
concentraoccurredvia
2,1-insertionoftheterminal
oleﬁn,
followedby
3-H
without
sacriﬁcing
catalytic
activity,
Punji
et
al.
recently
reportedthethe14-electron
species3
canalso
undergoout-of-cycle
oxidative2β-hydrideeliminationfromcarbon-3(addition-elimination
additionof the TBE
vinylic
C-H bondtrans to the tert-butyl
groupmore stable
and aremore
conveniently.
The
126, 1804-1811.
This expectation
was
supportedby measurementof the C-O
aare
Conditions:catalyst,
1.0storedmM;
1.5 mLof
CDA;
250°Cdifference
oil bath; in ease72
iPrβ-hydrideeliminationfromcarbon-3(addition-elimination
thermally
stableadamantyl-substituted
iridium
pincercomplex,additionof theTBE
vinylic
bond
trans
to
theCO
tert-butyl
groupofimproved
isolation
isScheme
more
pronounced
forthe X(12) Göttker-Schnetmann, I.; White
PCPstudies
complexes;
preliminary
12 to
Inand
part
catalysts
dehydrogenationoftion
is notsimple.
For
example,TBE
canC-Hadd
toresulting
3respective
andaAdHowever,recentindicatethatmechanism,
2a).
Goldman,A. S., etal. Abstractsof Papers,
239th
ACS although
National
Meeting,asindicated
in2010Scheme1.
Thevinylhydrideindevelopastretchingfrequencies
oftheadducts,
theconcentrations
determinedbyGC.for!15 753 areGoldman, A. S., et al. JACS, 2004, 126, 13044
!16
72
tBu
iPr
4
23, 1766-1776.
attempts
towas
isolatethe (MeOPCP)IrH
were
unsuccessful.
Thus, all
4 thatHowever,recent2withstudies
indicatemechanism,
Scheme
2a).
(8).
The
expectedtobeligands
indicatedin Scheme
1.for
Theelectron
resultingvinylhydrideand
3independently
are ina adamantyl
PCP)Irisomerization
proceeds
predominantly
through
rapid
pre-equilibrium,thekineticsof (which
were
tBu (
alkanes,aThesewide
range
ofgroup
modiﬁed
PCP
pincervarying
inhibit activity, in the limit ofaslow[TBE],
the catalyst
resting
state
iPrPCP)Ir”
standard
indicatorrichnessofPCP)Ir
metal
centers.
t(13)(a)
Fujii,
T.;
Saito,Y. J. Chem
reactionsof“(MeOreported
in
this
work
use
4 the tetrahydrideBu3
4
64a tert-butyl groupproceeds
predominantly( PCP)IrsimilartowithrespecttobothsterictBu(1-alkene),
rapid quantiﬁed
pre-equilibrium,
the atkinetics
oflowwhich
werecatalytic
independently
PCP)Ir(η
which
which
( and
Likewise,recent isomerization
by dynamic
NMR
temperature.
Fujii, T.; Higashino, Y.; Saito,
precursor.
PCP
complex(158forms
turnovers(TO) 3vsthrough60-allyl)(H),
TO after
1 h15). thentobservations
seemedodds atwith
thegreater
effectivetBu Bu464
4PCP)Ir(η-allyl)(H),
which
then
(1-alkene),
which
forms
electronic
properties,
more
resistance
520. (c) Aoki, T.; Crabtree, R(9)oﬀer
Renkema,K.
B.;
Kissin,Y.cycloV.; Goldman,
A. ThisS. J. Am.
Chem.
Soc. 2003,
Likewise,recent but could
quantiﬁed by dynamic NMR at low temperature.
PCP)Ir(2-alkene).
π-allylicmechanrearranges
to
give
( (to

First Acceptorless dehydrogenationtDemystify The Mechanism

4tDemystify The Mechanism
t

t

4

4

4

Modification of Pincer -Tail-In the case of ( POCOP)IrH
the rate-determining
stepcomplex,
in alkane-to-metal hydrogen trans2, however,athermalthermally
stablea productadamantyl-substituted
iridiuminto
pincerstability
at 250 mixture!C, whichtranslated
improved
block the metal center more so thanofin predominantly
the case of pincers
withadamantyl-substituted
iridium ispincercomplex,Ad
75 thea thermally
4 olefinsfer.
C!H
additionis in all
cases
more
terminal phosphino-t-butyl groups isinternal
wasobservedeven
at stablethegap
betweentheat theopposing
thegap
between
opposing
phosphino-t-butylgroups
PCP)Ir(8).
Theadamantyl
groupwasexpectedtobe favorable(
catalytic
activityfortheacceptorlessdehydrogenationofcycloAd75
4
the simple PCP m-xylyl backbone, thus
inhibiting
accessof theTheadamantylgroup wasexpected
tolessbe(tBu PCP)Ir
position;
therefore,
R-olefinformation
is favoredby thesethe earliest
times
at whichdehydrogenation
product
waswith(8).
tBu
tBu
tBu
similartoatert-butyl
grouprespecttobothstericanddecane.
turnoverfrequencies
obtainedwith
8-H
substantiallylessincrowded( steric
PCP)Ir
2 weresubstantiallylessin (regioselecPCP)Ir
inspecies.
( group
POCOP)Ir(Figure34
alkane substrate to the metal center.detectable.
It was proposed
that
the Initial
to athantert-butyl
with
to4).
both
andthan in ( POCOP)Ir (Figure 4).
crowdedIn thecase respectof the moderately
species
Additional
evidence
for the different similarelectronic
properties,
but
could
oﬀer
more
resistancetocycloand5-H,butoverallturnoverslightly
less
than
those
with
3-H
2
4
tBu
replacement of tert-butyl groups withtivity
isopropylgroups (complex
but
could
oﬀer
more investigations
resistanceto iscyclo75
of (tBuPOCOP)Ir
versuseither (tBuPCP)Iror (iPrelectronic
PCP)Ir was properties,
POCOP)Ir,β-hydrogen
eliminationis slower and
rate-of the origin of the respective
DFT-based
investigationsof(fromtheoriginofDFT-basedtherespective
exceeded
both
3-H
5-H
numbers
from
8-H
metalation
and/orbondthosecleavage,
which
might
respon2P-C
2 andbe4.
7b) would enhance reactivity by reducing
crowding.
Incompetition
metalation
P-Cβ-Hbondcleavage,mightolefin
be responobtained stericfrom intermolecularexperiments
be- and/or
determining;elimination
to whichgive internal
is moreOne
the most
modiﬁcationsofthe regioselectivity
PCP
ligandisof thedifferent
sible
for ofcatalyst
decomposition.
Complex
8 indeed
showedhighof notablethedifferent
fragmentsareongoing,but
another eﬀort to prepare a more tween
thermally
stableregioselectivity
complexsible
for catalyst
decomposition.
Complex
8 indeed
showedhigh fragments are ongoing, but
the dehydrogenationof n-alkane and cycloalkanes.
β-H elimination
represented
by thebisphosphinitefavorable
iridium thanpincercomplexesto give terminal olefin in thisthermalstability
attBu 250 !C, which translated into improved
without sacriﬁcing catalytic activity, Punjietal.
recently
reportedthermalstability
at
250
!C,
which
translated
into
improvedpreliminary
resultssuggestR4 ( suggest
results
terminal
selectivity
can arise
Consistent with thepreliminary
apparent
preferenceofcase,
for reasons
based on electronic
effects (including, thatper- terminal selectivity can arise
POCOP)Ir forthat
POCOP= κ3-2,6-C(R4POCOP)Ir
6H3(OPR2)2) indepencatalytic
activity(offor
thecatalytic
acceptorlessdehydrogenation
ofstabilize
cycloa thermally stable adamantyl-substituted
iridium pincer
complex,activityforthedehydrogenationofcyclot acceptorless
20
haps,
the
same
factors
that
the
free
internal
olefin,but
dehydrogenation
attheinternal
positionn-alkanes,
dehyand8-H
Jensendentlyby theBrookhart(9,obtained
R = Bu)withdecane.
Initialturnoverfrequencies
was ofexpected
to be prepared(Ad4PCP)Ir (8).75 The adamantyl group
2 werei mixtures21
decane.
obtained
withcase
8-H
thisturnoverremains to frequencies
be determined).
Finally in theof 2thewereverydrogenation
n-alkane/cycloalkaneby (tBuPOCOP)IrInitialPr)
groups.
Bothcatalysts
displayed
highercatalytic
(10,
R
=
5-H
turnoverslightly
than thosewith 3-H
similar to a tert-butyl group with respect
bothpreference
stericand2 and4, butbulky
species(tBuoverall
showed atostrong
forless
cycloalkane(cyclooctane
or
PCP)Ir,eliminationis stillrate-determining
5-H
overallturnoverslightly
less
than
those
with
3-Hβ-H
2 and754, but
activityinthe benchmark
COA/TBEtransfer
dehydrogenation
75
electronic properties, but could oﬀercyclotetradecane)more resistance
tonumbers
cycloexceeded
those
from
both
3-H
and
5-H
from
8-Ha2tBustrong2
4. both 3-H
whereas(tBuPCP)Ir
but
severecrowding
leads
tofromdominationof steric
effects
showedpreferexceeded
those
5-Handfrom
8-H
4 numbers
2
2 and
4.
POCOP)Ir
in
particularshowedactivity
reactionsthan
3;(
34 most notable modiﬁcations of the PCP ligand is34
metalation and/or P-C bond cleavage,
which
might
be
responOneoftheformation
ismodiﬁcations
again favored. of the PCP ligand is P-Ir-P angle is more acute than PCP
ence for dehydrogenation of n-alkane.
One ofthan
theR-olefin
mostofnotablean highorder of magnitude greaterthat
3 for thisalkane/13,29
sible for catalyst decomposition. Complex
8 indeed
showedrepresented
thestructuresbisphosphinite
iridium
pincer complexes
Inspectionof DFT-basedmodels orby
crystalrepresentedbythebisphosphinite
iridium pincer complexes POCOP-Ir metal center is more open
oleﬁn
couple. Conveniently,
theactiveRtBu
R4
3 catalytically
4R4R4 H (OPR
3speciestBu
thermal stability at 250 !C, whichoftranslated
into
improved
Heterogenized
AlkaneMetathesis
Systems
POCOP)Ir
(
POCOP
=
κ
-2,6-C))(( POCOP)Ir and ( PCP)Ir complexes reveals
that
6POCOP3
2=2 κ indepenPOCOP)Ir( reaction-2,6-C( situ6H3(OPR2)2) indepenis
easilygenerated
in
from
the
of
air-stable
t
20
t
20
catalytic activity for the acceptorless thedehydrogenationtcycloBu)
and
Jensendentlythe
Brookhart(9,R=large-scale
applications,theAM
catalyst
systems
be Steric Crowdedness:
Bu4 ofpreparedt For
Caryl!O and O!Pof
bonds
POCOP are byshorter
than
the
Bu)
and must
Jensendentlypreparedby
theBrookhart(9,
R=
POCOP)Ir(H)(Cl)with NaO
Bu.
Variation of the substit( werei
21
FIGURE
4. Space-f
Space-filling models of structures of (tBu
PCP)Ir anddecane. Initial turnover frequencies corresponding
obtained with
21 displayedfor
22 andheterogeneous
easeofcatalyst
separation
andFIGURE
recycling. 4. iPr4Pr)bonds
groups.
Bothcatalysts
highercatalytic
(10,
RCH
=2the
Caryl8-H!CH!P
of PCP,(10,whilegroups.
Bothcatalysts
displayed
highercatalytic
Rthe= iPr)
uents
at
para
position
of
the
aryl
ring
of
9
was
investigated,( PCP)Ir < (tBu4POCOP)Ir < (tBu4PCP)IrtBu
tBu
5-H
,
but
overallturnoverslightly less than those with 3-H2 andCaryl( POCOP)Ir(calcul(
POCOP)Ir(calculated using DFT with PBE functional)
with closest
H
4!O-P What
angle isgreater
than
the
C
!CH
!P
angle
activityinthebenchmark
COA/TBEtransfer
dehydrogenationaryl
2
activityinthebenchmark
COA/TBEtransfer
dehydrogenation
factor
75 direct correlation
but determinesnobetween dehydrogenation
activity and
tBu
tBu
those
from
both
3-Ha2 result,and
5-H
numbers
8-Hcomplexes
42 exceeded4
distancesindicated
FIGURE
3.
From
ref
33.
(Figure3). Asthe4.P!Ir!Pangle
issmaller,anddistancesindicated.
From
ref
33.
FIGURE
3.
From
ref
33.
Figure 2. Various
iridiumfrom
pincerused
for alkane
dehydroPOCOP)Ir
in
particularshowedactivity
reactionsthan
3;(
in particularshowed activity
reactionsthan 3;Interestingly,( POCOP)Ir
electron-donating
ability
was observed.
in spiteofthereactivity?
One of the most notable modiﬁcations
the PCPis of magnitudegenation.
the gapof
betweenthe ligand
opposingangreaterthanthat of 3greaterfor thisthan
alkane/angroups
orderis ofmagnitudethat of 3 for this alkane/
its order
high phosphino-t-butyl
activity
for COA/TBE
transfer-dehydrogenation,
9a
tBu
tBu
represented by the bisphosphinite substantiallyiridium pincer
complexes
less in ( oleﬁn
PCP)Ir thanin ( POCOP)Ir(Figure 4).
couple.
Conveniently,
the catalytically
activeoleﬁncouple.
Conveniently,
thespecies
catalytically
active speciesshowssigniﬁcantly
lower
reactivity
than
3 3 for n-alkane/TBE
2-2,6-CDFT-based
indepen(R4POCOP)Ir (R4POCOP = κ3tBu4
SCHEME
6. Formationof (POCOP)Ir(H)(η3-allyl) and (POCOP)Ir(η2-propene)
Formationofrespective(POCOP)Ir(H)(η
(POCOP)Ir(η-propene)
6H3(OPRinvestigations
2)2)SCHEME
65,76fromof6.
thegenerated
origin of thein
Lower reactivityelectronic
High stability
980 turnoversiseasilysitu
the -allyl)
reaction
air-stableiseasilygeneratedin andsitu offromthe reactionof air-stable Steric environment around the metal centert
20(
POCOP)Ir
transfer-dehydrogenation.
anddently
steric preparedproperties
have
been
exploredsynthetically
tBu
tBu
Bu)
and
Jensenby the Brookhart (9,
R
=
t
4
4
regioselectivity of the (different
fragments are ongoing,but(low flexibility andatcomputationally.
250 °C andPOCOP)Ir(H)(Cl)
withof NaO
Bu. Variation of the substit- determines the rate determining step
( with
POCOP)Ir(H)(Cl)NaOtBu.
the substiti transfer
While
the mechanism
proposed
for Variation
COA/TBEtransferDFT
indicated
thatelectronGreater
reactivityPr)21calculationsgroups. Bothcatalysts
displayed
highercatalytic(10, R =in
resultssuggestthat
terminal
selectivity
canof
arise
tBuPCP such as methoxy groups in thepreliminary
uents
at
the
para
position
of
the
aryl
ring
uents
at
the
para
position
the
aryl
ring
of
9
was
investigated,
dehydrogenation
by
9(Scheme3)
issimilartothatof of 9 was investigated,
donating
substituentspara
positionof arms)
exceeds
dehydrogenationin transfer
activity in the benchmark
COA/TBEtransfer
dehydrogenation
tBu
tBu
iPrPCParyl ring favor oxidative
but
no aredirectcorrelation
betweendehydrogenation
activity and
PCP)Ir1),
there
subtlebut signiﬁcantmechan( 4noof andthe ligand
additionofalkaneC-H
but
direct(Scheme
correlation
betweendehydrogenation
activity
and4afterofthann-Octane
POCOP)Ir
in
particularshowedactivity
reactions
3;(
dehydrogenationtBu
20
2. Various usediridium
complexes
alkanedehydro-between
4
Figure2. Various
iridiumofFigure
pincercomplexes
forpincer
alkanedehydro- used forelectron-donating
abilitywas( observed.
in spite of
WhilePCP)Iristic
diﬀerencesthecatalysts.
Experimenbonds
to derivatives
the14-electroncomplex3.26t thatelectron-donating
ability
wastwoobserved.
Interestingly,inspite Interestingly,of(Acceptorless
an
order
of
magnitude
greater
than
of
3
for
this
alkane/
5h
at
150
°C
of
Cyclooctane
ChemicalReviews
Bu
genation.
4
genation.
REVIEW(3)highreversibly
reactswithgive aforvinylic
C-H addition
PCP)IrHactive
tally,
the p-methoxy-substitutedcomplex (MeOits TBE
high toactivity
COA/TBEtransfer-dehydrogenation,
9a
its
activity
for
COA/TBEtransfer-dehydrogenation,
9a
2
tBu4
oleﬁn couple.
Conveniently,
thecatalyticallyspeciestBu4
t
Dehydrogena(96 for
PCP and than ( PCP)Ir but
Bu4
POCOP)Ir
formsaπ-coordinatedcomplex.
More
product,((6a-H2; Figure
2)
gave
a
2-3-foldincreaseinturnoversforshowssigniﬁcantly
lower
reactivity
than
3
for
n-alkane/TBE
shows
signiﬁcantly
lower
reactivity
than
3
for
n-alkane/TBE
ist easily 208
generatedin situ fromthe reaction forof air-stable
iPr4PCP)tion)
for of
65,76 by 3 or 9a and 15: Distribution of n-Alkanes and Selectivity for Decanea
no
65,76
Table
1.
Metathesis
timprovement
isn-Hexane
much
more facile
importantly,
alkene hydrogenationby 9b-Hofacceptorlessdehydrogenation
cyclodecane
as compared3- exploredtransfer-dehydrogenation.
electronicandstericproperties
have tobeen
syntheticallytBu4POCOP)Ir
2 tBu4
electronicand steric
have
been
exploredsynthetically
POCOP)Ir(H)(Cl)
with
NaO
Bu.
substit( Bu4properties
PCP)IriPr Variation of the transfer-dehydrogenation.
FIGURE 4.( Space-fillingmodels of structures( of (tBu
PCP)Ir and73
4n-Alkane’s
reaction
TBEhydrogenations
by proposed
9b-H
and
3- PBEthanby electron3-H
In particular,thestericallyless bulky(MeOPCP)IrH
HGoldman, A. S., etal. Chem.
2011,uents
111, 1761
the(tBumechanism
for
COA/TBE
andcomputationally.
DFT
calculations
indicatedthat2
2. Rev.
4 investigated,!17 example,While
Goldman, A. S., et al. Acc. Chem. Res. 2012, 45, 947
!18
While
the2. Formechanismproposed
for COA/TBE
transferandcomputationally.
DFT
calculations
indicated
thatelectronPOCOP)Ir(calculatedusing
DFT with
functional)
withtransferclosest
at
the
para
positionof thearyl
ringof 9 wasproductconcnH!H(mM)
proceedwithcomparable
rates
at
-70
and
55
!C,
respecH(6b-H)
was
extremely
eﬀectiveintheacceptorlessdehydrogenadehydrogenation
by
9(Scheme3)
issimilarto that of
donating
substituentssuchasmethoxygroupsintheparaposition
distancesindicated.
From
ref
33.
FIGURE
3.
From
ref
33.
2
4
but nodirectcorrelation
betweenanddehydrogenation
by
9
3)
is
similartothatofdonating substituentssuchas methoxy
groupsin thedehydrogenationpara position activitytBu(SchemetBu
4tively.
DFT 1),
calculations
indicatethat
these
diﬀertionligandof cyclodecane,withaoxidative
total
of 3050
turnovers
obtainedafter
pincer complexes used for alkane
dehydro4alkane
PCP)Ir(Schemethere
subtlebut5 signiﬁcantmechan( thereof theligandaryl
ringobserved.
favor
oxidative
addition
of
C-H
C7-C
C10
>C11
total product concn (M)C10/(C7-C10) (%)
Ir catalyst
time(h)aremechanC2-C
9abilitywasInterestingly,in (spiteof Recent
PCP)Ir(Schemeare subtlebut1),
signiﬁcantof thearylelectron-donating
ring favor
additionof alkane
C-H
t
26
3
2
tBu
ences
are
attributable
to
the
fact
that
the
metal
centerof 20 While ( Bu4PCP)Ir
72
h
under
reﬂux
conditions
(201
!C).
However,
methoxy
SCHEME
6. Formationof (POCOP)Ir(H)(η
-allyl)and (POCOP)Ir(η-propene)
20
26
4
istic
diﬀerences
betweenthetwocatalysts.
Experimenbonds
toderivativesofthe14-electroncomplex3.
its high
for COA/TBE
transfer-dehydrogenation,
9a
Bu the two catalysts.
t t diﬀerences
While(
PCP)Iristic
betweenExperimenbonds to derivativesof theactivity
14-electroncomplex 3.
Bu
4 4( PCP)IrH
23
740
241
232
38
1.25
49.0
n (3)
t
POCOP)Ir
stericallyhinderedthan that(t Bu
substitution did
not greatly
catalytic
activity(3)less
reversibly
reactswith TBE
giveofa vinylic C-H addition
4 in acceptorPCP)IrH2 is muchtally, enhance
the complex
p-methoxy-substitutedcomplex(MeOshowssigniﬁcantly
lower
reactivity
3 for2 n-alkane/TBE
(3)
with
TBE
to
a vinylic
C-Htoaddition
PCP)IrH
tally, the p-methoxy-substituted(MeO- ButhantBugiveBu4reversibly reacts
65,66,76
24
1350
548
95
53
2.05
14.8
( BuinPOCOP)IrH
42 (9a)tBu as indicated
65,76
PCP)Ir,Figure3.
Thelesser
crowding(
lessdehydrogenationofn-alkanesorinthetransfer
dehydrogenaPOCOP)Ir
formsaπ-coordinatedcomplex.
More
product,((6a-H;
Figure2)gavea2-3-foldincreaseinturnoversfor4transfer-dehydrogenation.
perties have been explored syntheticallytBuaformsconditions:a π-coordinatedMore
product,( POCOP)Ir(6a-H
Figure2)gave a 2-3-foldincrease in turnovers for
732
4
2; of
Reaction
3 orby9aKoridze’s(10complex.
mM),crystal15 (16mM), TBE (20 mM) in 7.6 M n-hexane at 125 !C.
POCOP)Iris
supported,forexample,
in
(
tion
COA
or
n-alkanes.
importantly,
alkenehydrogenationby 9b-H2 is much more facile
dehydrogenationof COA/TBE
cyclodecane
asimportantly,
compared
toalkene
3- hydrogenation
Whileacceptorlessthe ofmechanismproposedfortransferFT calculations indicated thatelectron- dehydrogenation
t
more
by
9b-H
acceptorless
cyclodecane
as excellent
compared
to 3iPr
2 is much
73 complexes
4
which
can facilebelographiccharacterizationof ( Bu4POCOP)Ir(CO),pincerhave
thermaliPr
73 Although iridium
than
In particular,
the stericallybulky to
(MeOPCP)IrH
Hdehydrogenationby 9 (Scheme
3)4PCP)IrH
islesssimilarthatofh as methoxy groups in the paratBu by 3-H2. For example, TBE hydrogenations by 9b-H2 and 32.
4 example,
.
For
TBE
hydrogenations
by
9b-H
3than
by
3-H
In
particular,
H2.position
4
tButhe sterically less bulky (MeO2
2 and
4at
PCP)Ir(CO)(P-Ir-P
anglesare-70comparedwiththat Scheme
ofH(2 proceedstability,they( are4PCP)Ir
still
generally
subject
toare
decomposition
withcomparable
rates
atand 55!C, Metathesis
respec(6b-H)
wasextremely
eﬀectiveintheacceptorlessdehydrogena(Scheme
1),
there
subtlebut
signiﬁcantmechanvor oxidative addition of alkane
C-H
4.
Proposed
MechanismofDual-Catalyst
Alkane477
eﬀective
infor
theextended
acceptorlessdehydrogenatBu H2 proceed with comparable rates at -70 and 55 !C, respec4) was extremely
20 This26 (6b-H
A
more
acute
Ptemperatures
above
ca.
200
!C
periodsoftime.
4 157.55(3)! and 164.510(8)!, respectively).
Recentindicate
DFT calculations
indicatethat these diﬀertionof cyclodecane,
total of 3050
turnovers
obtained
afterDFT tively.
While( tively.
PCP)Iristicwith
diﬀerences
betweenthewithtwo acatalysts.
he 14-electron complex
3. t ExperimenRecent
calculations
that
these
diﬀertionofcyclodecane,
a
total
of
3050
turnovers
obtainedafter
ConversionofFeedstocktoLiquidFuel
Fischer-Tropsch
Process:
Ir-P angle
results inencesa moregeometryin POCOP
decompositionof 72
particularconcernfor
acceptorlessdehyare open
attributable
to thefact that the metal center ofh underreﬂuxTBE
conditions!C).
However,
methoxy(3)is reversibly
reactswithto give a (201
vinylic
C-H
additionstituted complex (MeO- Bu4PCP)IrH
2t to the fact that the metal center of
t
ences
are
attributable
72 hdrogenation,
under
reﬂux
conditions
(201
!C).
However,
methoxy!highercomplexes;
this is attributable
to the shorter
bonds
oxygen hindered than that ofwhich
requiresmuch
andt Moreforms
atemperatures
π-coordinatedcomplex.
product,( Bu4POCOP)Ir
a 2-3-fold increase in turnovers
foris muchless tosterically(tBu4POCOP)Ir
substitution
did not
greatlyenhance catalytic
activity
Bu4 in acceptorPOCOP)Ir
is
much
less
stericallyhinderedthanthatas of(substitution
did
notgreatlyenhance
catalytic
activity
inacceptorVol.RESEARCH
45, No. 6 ’’209
Vol. 45, No. 6 ’ 2012 ’ 947–958 ’ ACCOUNTS OF CHEMICAL
Bu
(P-O
and
C-O)
and
the
wider
bond
angle
(P-O-C)
longerreactiontimeslessto overcomethehighenthalpic
barrier
of
4
(2n
+
1)H
+
nCO
→
C
H
+
nH
O
2
n
(2n+2)
2
t
is
much
more
facileimportantly,
alkenehydrogenation
by
9b-H
ation of cyclodecane as comparedto
3indicated in Figure 3.65,66,76
The lesser crowding( t PCP)Ir, as65,66,76
dehydrogenation of n-alkanes or2 in the transferBudehydrogena4
iPrless dehydrogenation of n-alkanes or in the transfer dehydrogenaPCP)Ir,
as
indicatedin
Figure3.
Thelesser
crowding(
Bu
73
comparedwiththeanalogous
bondlengthsandanglesofthethisreaction.
Haenel,Kaska,
Hall,
andco-workers
developedan4
4
Cohydrogenations
or Ru as a catalyst)
t 3. For
example,TBE
by 9b-H2 andthan by 3-Hterically less bulky (MeO- PCP)IrH4
for example, by Koridze’s crystalin ( POCOP)Ir is supported,tion
COAor (Fe,n-alkanes.
73 2of
4
tBu
POCOP)Ir
is supported,for example, by Koridze’s
crystalin( Bumethylene
tion anthraphos-supportedof COA or n-alkanes.
PCP; Figure
iridium
complex
(7a-H
4
2-70
withpincercomparable
rates
atcomplexesand2),
55!C,excellent
respecH2 proceed
ﬀective in the acceptorless dehydrogena!
tBucharacterization of (POCOP)Ir(CO),which can belographic
Althoughiridium
pincerhave
thermalcarbons.
4t
POCOP)Ir(CO),which
can be (P-Ir-P angles arelographiccharacterizationof(
Althoughiridium
pincercomplexes
have
excellent
thermalBu
4tively. Recent
that
diﬀera total of 3050 turnovers obtained aftertBuPCP)Ir(CO)compared
with
that
of
(
stability,DFT
they calculations
arestill generally
subject
to1764decompositionatSourcesofindicate
CO andH2: these|Chem. Rev. 2011, 111, 1761–1779(P-Ir-Prespectively).
angles are 77 more acute Pcomparedwith thatdx.doi.org/10.1021/cr1003503
of157.55(3)!
( 4PCP)Ir(CO)stability,
they areences
still aregenerally
subject
toca.decompositionat periods
attributable
to
fact
that
the
metal
centeroftime.
ditions (201 !C). However,methoxy
and Vol.
164.510(8)!,temperatures
above
200
extendedofof
C +the
H 2O
→!C
H
+ CO
(Gasificationcoal)This776 2012 947–958 ACCOUNTS OF A
2fort
45, No.
CHEMICAL RESEARCH 953
Buca.
4
A
more
157.55(3)!
and
164.510(8)!,respectively).
temperatures
above
200
!C
for
extended
periods
of
time.
This
is muchis lesssterically concern
hindered forthanthat of dehy(t POCOP)Ir
ly enhance catalytic activity in acceptorIr-P angle results in a moreacute
openPgeometry in POCOP
decompositionof2-particular
acceptorless
-CH
+
H
→
CO
+
2H
2O
2 (Gasification ofBu
65,66,76
4
Ir-P angle andresults incomplexes;a more open
decomposition is( of PCP)Ir,
particularconcern
forFigureacceptorlessdehyas indicatedin
3. muchThehigher
lesser crowding-alkanes or in the transfer dehydrogenathis is geometry
attributableintoPOCOP
the shorter bonds to oxygen
drogenation,
which
requirestemperaturest-CH2-temperatures+ 1/2O+ H2 naturalgases)this is attributable to the shorter bonds to oxygen
2 → COand4complexes;
drogenation, whichhigher
POCOP)Ir
is supported,
example,bycrystalin ( Burequires
s.73(P-O and C-O) and Hydrogenthe wider Autotransferbond angle (P-O-C) as
longer muchreactiontimestBu
toforovercome
theKoridze’s
high enthalpic
barrier of4
andthe widerangle (P-O-C)
as and angles of thelongerreaction times
to thisovercome
theHaenel,highbarrier
POCOP)Ir(CO),which(P-O
candeveloped
be and C-O)
lographiccharacterizationof (enthalpic
cer complexes have excellent
thermalcompared
withbond
the analogous
bond lengths
reaction.
Kaska,
Hall,
and ofco-workers
an
tBu
tBu
4
4
comparedwiththe analogous
bondcatalysts
lengthsandanglesof thethis reaction.
Kaska,Hall,
andofco-workers
developed
an angles(P-Ir-Parecompared
withthat( PCP)Ir(CO)generally subject to decomposition
at Haenel,(
POCOP)Ir
via
three
diﬀerent
methods:(1) covafraction
into the diesel range, along with lesser amounts (byPCPmethylenecarbons.
;
Figure2),anthraphos-supported
iridium
pincercomplex(7a-H
Product Concn
(mM)
2
77
A2),more acute157.55(3)!
and
164.510(8)!,00 !C for extended periods ofanthraphos-supported
time. This
PCPPmethylene carbons.
iridium
pincercomplexrespectively).
(7a-H2; Figure
lent attachment to a Merriﬁeld
covalent
bondingtoweight)of ethane.
Ir catalystresin, (2)time(h)tBu4C
C7 - C 9
C10> C11 total (M)C10/(C7 - C10)
2 - C5can convert
a surplus of 1764
Ir-P angle results in Alkane
a more Metathesis
open geometryin POCOP
ticular concern for acceptorless dehydx.doi.org/10.1021/cr1003503|Chem.
2011, 111, 1761–1779
silica, and (3) adsorption
on γ-alumina. The( Rev.POCOP)Ir
The ﬁrst example of alkane metathesis was achieved by(tBu4PCP)IrH
23
740
241
232
38
1.25
49.0
82
2
1764
dx.doi.org/10.1021/cr1003503|Chem.
Rev.
2011,
111,
1761–1779
complexes; this is attributable
totheshorterbonds
tooxygenuires much higher temperatures anda mixture of two heterocatalysts on Merriﬁeld resin and silica showed low to moderate
Burnett and Hughes in 1973 using
alkanes to those of more desirable numbers
2.05
14.8
(tBu4
POCOP)IrH2 of cyclooctane
241350
548 geneous
95
53(P-O and C-O) and (e.g.
the widerangle(P-O-C)asovercome the high enthalpic barrier ofcatalysts.
At
400
!C,
platinum/alumina
acted as anactivityforthetransfer
dehydrogenation
andwere
C9 - Cbond
isvaluableasaclean-burning
19
compared with the analogousdieselbond lengths
and angles of theska, Hall, and co-workers developed an
alkaneand tungsten oxide/
reported
to decompose
underthe reaction
conditions.
Reactionconditions:
Ir catalyst(10 However,mM), 15 (16 mM),
TBEtransfer-dehydrogenation(20 mM) in 7.6M n-hexanecatalyst,
at 125 °C
component)tBu
tBu
PCP methylene carbons.
dium pincer complex (7a-H2; Figure 2),
silica catalyzed the metathesis of the resulting oleﬁns. The( 4PCP)Ir and ( 4POCOP)Ir derivatives possessing Lewis
to γ-alumina
basic para substituents(e.g.,A.NMe
Goldman,S., Brookhart.
M., et al. Science
2006, 312, 257 reaction gave primarily n-alkanes, with a broad distribution of2) bind strongly1764
dx.doi.org/10.1021/cr1003503
Rev.Chem.
2011, 111,
1761–1779
Goldman, A. S., et|Chem.
al. Acc.
Res.
2012, 45, 947!19!20
and form thermally robust and recyclable catalysts. These γchain lengths. Later, Basset reported that silica-supported
tantaalumina-supported catalysts showed excellent activity toward
lum hydride complexes catalyzed alkane metathesis at lower
COA/TBE transfer-dehydrogenation, with turnover numbers
temperatures (typically 150 !C).88,89 However, reports have

The Structure of POCOP-Ir Complex

Modification of Pincer -Arm and Joint-t

Alkane Metathesist4
4

Alkane Metathesis

’

’

’

’

Product Distribution: Selectivity Crisis

Chemical Reviews

Future Outlook

REVIEW

Scheme 5. Product Formation Pathways for n-Hexane Metathesis: (a) Ideal Pathway To Produce n-Decane and Ethane
Selectively, (b) Possible Pathway for Formation of n-Pentane and n-Heptane
Product Formation Pathways

Y PR 2
Ir

X

+

α

?

Y PR 2

Problems of Dehydrogenation, Alkane Metathesis chemistry••(tBu4POCOP)Ir’s poor selectivity in Alkane Metathesis
2 conceivable reasons
Rate of isomerization doesn't differ• Isomerization to internal olefin
from (tBu4PCP)Ir complex• Internal C-H activation to give internal olefin

Poor selectivity in Alkane Metathesis products
Poor reactivity at lower temperature(Metathesis catalysts decomposes at high temperature)

Modification of pincer catalysts has more potential to overcome these problems
Tasks of Other Chemists•••

Utilization of Pincer-Ir for other reactions
Utilization of C-H activation chemistry
Utilization of wisdom about pincer for other catalysts

Goldman, A. S., Brookhart. M., et al. Science 2006, 312, 257
!21

!22

Figure 4. Iridium pincer complexes immobilized on alumina.

In what may be viewed as the ideal case, the pincer iridium
catalyst eﬀects dehydrogenation of Cn n-alkane at the terminal
position to give R-oleﬁn (as given in Scheme 4). Oleﬁn metathesis then yields ethylene and the C2n-2 oleﬁn, which arehydrogenated to the corresponding alkanes. When 9a was usedas the dehydrogenation catalyst, however, there was no selectivity
for such products; instead the most abundant products were theCnþ1 and Cn-1 n-alkanes with decreasing amounts as the carbon
number either increased or decreased from the carbon number ofthe substrate. In the case of 3, the most abundant heavy productwas in fact the C2n-2 n-alkane (speciﬁcally, n-decane from nhexane) although selectivity was far from complete. The ndecane represented 49% of the total of “primary” heavy products(n-heptane, n-octane, n-nonane, and n-decane; higher MWs
presumably result from the secondary metathesis of the primaryalkane products).
It was initially proposed that primary products other thanC2n-2 and ethane were predominantly formed via isomerization,prior to oleﬁn metathesis, of the presumed R-oleﬁn dehydrogenation product (Scheme 5b). Indeed, the known terminal
regioselectivity72 of n-alkane dehydrogenation by 3 would seemto require isomerization to account for the relatively modest
selectivity observed in the alkane metathesis. However, thecomplete lack of MW selectivity in alkane metathesis by 9a
may be more attributable to a lack of regioselectivity in the initial
n-alkane dehydrogenation by this catalyst.65,76
Diﬀerences in catalyst resting states were observed for alkane
metathesis
reactions catalyzed by 3-H2 and 9a-H2. For
tBu( 4PCP)Ir, the corresponding dihydride complex was observed
to be the catalyst resting state, implying thatt oleﬁn hydrogenation
is likely the turnover-limiting step. For ( Bu4POCOP)Ir, oleﬁncoordinated complexes were found to be the resting state, so loss

upon the concentration of TBE, the turnover-limiting step could
be either half of the overall cycle. (Note that under the alkane
metathesis reaction conditions the steady-state concentration of
oleﬁn is very low and, accordingly, the hydrogenation part of thecycle is turnover-limiting in the case of alkane metathesis
using 3.)
Turnover numbers resulting from alkane metathesis by 3 and15, or by 9a and 15, are limited by the decomposition of theoleﬁn metathesis catalyst 15; this is not unexpected in view of therequired high temperatures and long reaction times. This conclusion was conﬁrmed by experiments in which addition of 15 toalkane metathesis reaction samples reinitiated catalytic activity
after it had ceased. Therefore, a more thermally stable oleﬁnmetathesis catalyst, Re2O7/Al2O3, was investigated in lieu of 15.
This heterogeneous system was less reactive than the homogeneous Schrock complex 15, requiring a higher temperature(175 !C) to achieve similar (although still slower) reaction rates.
However, the reaction system indeed maintained catalytic activity for a longer period of time. The combination of 3-H2 (9 mM)
and Re2O7/Al2O3 (16 mM eﬀective Re2O7 concentration)yielded 3.62 M total n-alkane products (from C2 to C28) from
5.1 M n-decane after 11 days at 175 !C. The p-methoxysubstituted catalyst 6b-H4 gave even higher conversion, 4.37 M
after 9 days.91
As noted above, Lewis basic substituents at the para positionof the pincer ligands allow binding to γ-alumina without
inhibiting catalytic dehydrogenation activity (Figure 4). Suchsystems, in combination with Re2O7/Al2O3, have been investigated for alkane metathesis and have aﬀorded !2even
greater3
turnover numbers.94 Quite interestingly, the γ-alumina-supported dehydrogenation catalysts are compatible not only with
Re2O7/Al2O3, but also with the Schrock catalyst 15. Under these

2. Dehydrogenation of
Alcohols and Milstein’s
Advanced Studies on Pincer

Main Character of This Chapter
1976 Ph.D at Hebrew University ofJerusalem under the guidance ofProf. Blumthen; postdoc in Stille’s lab
1979 Group leader in Dupont Company
1987 Professional appointment at theWeizmann Institute of Science
1996 Israel Matz Professor at Weizmann
Institute of Science

David Milstein
Weizmann Institute of Science
Israel Matz Professor of Organic Chemistry

Keywords:• Organometallics• Metal-ligand cooperation• Green catalysis• Water splitting!24

Chart 3. Representative Activated Nucleophiles Employed in Alcohol Activation Reactions

Dehydrogenation of Alcohols

Dehydrogenation of Alcohols

Dehydrogenation of Alcohols

Dehydrogenation of Alcohols

which catalytic steps require base, a basic moiety (locatedwithin a bifunctional ligand, or as a reactant) is seen as arequirement for a dehydrogenation mechanism via a mono41
hydride intermediate.
Scheme 28. Alkylation
Activated NucleophilesbyScheme 29. An Oxidation-Wittig-Reductio“HydrogenofAutotransfer”
strategy
Ru-catalyzed amination
The
first
reportofN-alkylation
via homogeneous catalysis
Alcohols
Alcohols
Alcohol’s activation is usually limited;was
co-workers
1981.48 Heterogeneous Pathway for
Scheme 28. Alkylation of Activated Nucleophiles
by by Grigg andScheme
29. An in
Oxidation-Wittig-Reduction
49
50
Alcohols
catalysts such as CuAlcohols
and Pd had previously shown activity
H+
for Nucleophilic substitution
Rfor this reaction. After finding that imines could be hydrogenated by alcohols via hydrogen transfer catalyzed by
OH[RhH(PPh3)4],51 Grigg and co-workers attempted an Nalkylation of alcohols, no doubt with the expectation thatR
the aldehyde generated from oxidizing the alcohol wouldO
react with an amine to form an imine in situ. Several iridium,
Murahashi, S. I., et al. Chem. Rev. 1998, 98, 2599
for Electrophilic substitution
rhodium, and ruthenium complexes were shown to be
OHR
Watanabe identified
a selectivity
advantageProcesses
in an early
Scheme30. Wittig-Typewithin ancompetent
fortheformationofsecondaryandtertiaryaminesScheme30.
Wittig-Type
Processes
withinan
Alcoholcatalyst
imine
isapparently
reducedtotheamine;
N-alkylation
report.55c
SelectivitySequence
for conventional
Ru-catalyzed
Wittig-type
process
86,127b monoalkyR,β unsaturated imine is apparently reduced to the amine;R,β unsaturated
86,127b
Activation
Activation
Sequencefromalcohols
andprimaryor
secondaryalkyl
amines
under
113
113
694 Chemical Reviews,
2010, Vol.is110,
No. 2
Dobereiner andCrabtreelation of primary amines poses a challenge
where
the
no quinoline is isolated.
no quinoline
isolated.
mild conditions (Scheme 9).48 The synthesis of N-heterocymonosubstituted amine product from the first alkylation,146
cles from amino alcoholsSelectivity
was alsoin reported.
an Acetal Watanabe
andSchemeLactamSynthesis basefrom thanAminotheAlcohols
being a40.more
nucleophilic
amine starting
3.3.2. Activated Methylene Nucleophiles Scheme 38. Base-Dependent
3.3.2.
Activated Methylene
Hydrogen Autotransfer type reactions
145
demonstrated
an N-alkylationof an azoleNucleophiles
with methanol
Ester
Formationmaterial,canpreferentiallyattacktheelectrophile.
ThiseffectBeyond enolate chemistry, several Knoevenagel-typead- 3)4] under harsh conditions.52 Several rutheusing [RhH(PPhbeen well developedO
is seen haveinadconventional
N-alkylations using alkyl halides,
Beyondenolatechemistry,
severalKnoevenagel-type
+
H2
have
been performed within the contextniumof dehydrocomplexes and iridium catalysts were also capable of
Dehydrogenativeditions
Alcohol
Activation
to a mixture of differently alkylated products. A great
havehigher
been yields.
performed within the context leadingof dehydroR
genative activation (Chart 3 and Scheme 28).theEarly
workditionswith
transformationof the alcohol activation strategy is that the initialfound that fluorene alkylation could be achieved with ethanolgenative activation (Chart 3 and Scheme 28). advantage
Early worksecondaryamines formed by alkylation of a primary amine
114
using sodium ethoxide at high temperatures (210-220°C). found Catalysis
that fluorene alkylation could be Williams,
achieved
with
J. M.,
et al.ethanol
Chem.
Commun.
2004, 1072 Amide Bond Formation via
3.2.1.!25Ruthenium
Williams, J. M., et al. Adv. Synth. Catal. 2007, 349, 1555
Scheme41.toIntermolecular!26 thetend
notthis would require
114react further because148,149
Grigg and co-workers reported some of the first examples
using sodium ethoxide at high temperatures (210-220°C).
Dehydrogenative
Alcohol
Activation
formationofaniminium
cationasanintermediate;
its
Severalruthenium
compounds(Chart1)
give
N-alkylationofhomogeneoustransition-metal-catalyzed
C-C
bond
forActivating Strategy
Chemical Reviews, 2010, Vol. 110, No. 2 693
Grigg and co-workers reported some of the firstexamplesformation
tends to be unfavorable, particularly in theof alcohols,
mation via alcohol activation.115 An aryl acetonitrile
waswith much early work performed by Murahashi
transition-metal-catalyzed
bond fornonpolar
solvents often used for N-alkylation reactions.
alkylated byprimary Products
alcohols inintheof co-workers
stoichio-of homogeneousand Watanabe andco-workers (Scheme
10).53 C-C
fication of Primary
Scheme 36. Dehydrogenative
Activation
thepresenceand
115
139
Watanabedemonstrated that different ruthenium catalysts
mationvia
alcohol
activation.
Anarylacetonitrile
wasmetricbase
usingseveralrhodium
catalysts
as
well
as
A
wide
varietyofamineshave
beenutilizedinN-alkylation
Carboxylic Acid Oxidation Stateshow
widely varying selectivity in N-alkylations with both
[RuH2(PPh3)4]. Grigg later reported this transformation
using
alkylatedby primaryin thepresence of
stoichioreactions.
In
1982, Murahashi
andalcohols
co-workers
showed116
andasdialkylated amines possible, depending on the[Cp*IrCl2]2 withstoichiometric
KOH,
andaliphatic
it 2has693
been
as a Substrate-Activating Strategy
ChemicalReviews, 2010,
Vol. 110,No.
aminesare basecompetent
N-alkylation
metricusingsubstrates
several for
rhodium
catalysts monoas well117
complexemployed and the conditions used (Scheme 11).57
reported elsewhere using iridium and rheniumusing
hydrides.
a [RuH(3).54later
Curiously,
amines2(PPh3)4] catalyst
sidearyl
reactionin transferhydro[RuH
(PPh
Grigg
reported
this
transformation
using
2inhibiting
3)4]. decarbonylation
Grigg
and
co-workers
also
reported
the
use
of
other
activated
Additionally,
it was shown that more sterically encumberedidative Esterification of Primary
Scheme 36. Dehydrogenative Activation Products in
the ineffective
were
substrates
forstoichiometricthisofcatalytic
genationreactionsprimary system,
alcohols.
Williams
saw[Cp*IrCl
KOH,116as
and ithas debeen
118
1192]2 with
139
nucleophiles,
includingindoles.
Madsenrecentlyre“Net Oxidation” strategy
Acceptorless
Dehydrogenation
aminesaregenerally
poorer substrates
for N-alkylation.
Carboxylic
Acid
Oxidation
State
what
extenttheN-alkylation
andalcoholamidation
pathways
Ru-catalyzed
acceptorlessamidation
they
were
for
Grigg’sRhhydridecomplex.
However,
Rh-catalyzed carboxylic acid synthesis
carbonylation
the active
exposed 117
reportedelsewhereproducts
using when
iridiumand catalysts
rheniumwas
hydrides.
ported an analogous addition using oxindoles
asactivatedinhibiting
decarbonylationside reaction inmay
overlap.
The
numberofcomplexes
so
far
found
to
be
Selectivity
formonoalkylation
has
been
well establishedaminoarenes
were
used
with
successbothbyWatanabeettoanaldehyde
andsuggestedthat
theabilityofacomplex
Grigg
and [RuCl
co-workers
also
reported
the use of otheractivatednucleophiles.120
activefor amide
formation
is 118far2(PPhsmaller(PPh3)3] complex
was shownin several
systems. The[RuCl2reactions
al. andby othersusing(4)55 theandiswidemonophosgenationof primaryalcohols. W3)3] thantoperform
decarbonylation
relatedtoits
capacityfor
119array
Ishii and co-workers also investigatedofthe
activity
ofnucleophiles,
includingindoles. of Madsen
recently
re- convert primary amines to N,N-dialkylated
56
catalysts
activeforN-alkylation(Chart5).
to support
selectively
phinecomplexesoftype alcohol[RuCl
N-Alkylation
het- results
3L].
certainactivation
processes.
Othercarbonylation
products
whentheactivecataly[Ir(cod)Cl2] in the presence of PPh3 for alkylationand found
55a
portedananalogous
additionusing
oxindoles asactivatedamineswith longertoreaction
times andexcessalcohol;erocyclicaryl
amineshas
also[Ir(cod)Cl]
been
using
a variety
Murahashi
saw
thethisformationof anreported
amide
from
alcohol
claim:
2, a precursor to catalysts active foranaldehyde
andsuggested
that
the
abili
120
that several activated methylene species, including alkylnucleophiles.
Dehydrogenationas
Substrate-Activating
ChemicalReviews,
2010, Vol.
11
57
conversely,amines can begeneratedin goodruthenium
complexes.
Ammoniumsalts
haveinStrategy
been
andofamine
using [RuH
theapresenceof ausedhydrogen2(PPh3)activation,4] inalcoholhas beena decarbonylationof monoalkylated
cyanoacetates and β-keto nitriles, could be utilized in thetoperform
decarbonylationisrelatedto55c
146
125 yieldbyutilizing
equimolar
amountsofalcohol.
WatanabeutilizedasanitrogensourceinaN-alkylation
reactionusing
acceptor(Scheme40).
Fiveandsix-memberedlactamIshii
andco-workers
also
investigatedtheactivityof
121
aldehydes
under similar
reaction conditions.
absence of base, albeit at slightly higher temperatures. The 58Scheme
34. Oxidative
Esterificationof Primary Ruthenium
SchemeDehydrogenative
Activation
certainactivationcomplexes,
processes.Products
Other
co-workers
that 36.
ofalcohol
severalruthenium[RuH)4]. phosphine
rings
were
synthesizedfromalcohols
insimilar
an intramo2(PPh3[Ir(cod)Cl
inaminothepresenceofPPhalkylationand
andfound foundhydridespecies,
to complexes
employed2]132c,136
3 forability of this catalyst to function without basesuggeststhat
rs for the Oxidative
Alcohols
Carboxylic Acid Oxidation State139
thisclaim:[Ir(cod)Cl],aprecursor
tocat
2
lecularprocess.
The
additionoftwoequivalents
of
water
to
in
alcohol
activation
reactions,
have
also
been
seen
to
Chart
1.
Ruthenium
Catalyst
Precursors
fortheAlkylationofAmineswith
Alcohols
unlike many other alcohol activation catalysts, a metalthat several activated methylene species, including alkyl
coholsDobereiner and Crabtree
32b
alcohol activation, has been used in a dec
thecatalytic
reactioncycle,
mixturewas
requiredto β-ketoform thenitriles,
lactamproduct;
perform
decarbonylation.
Williams
andco-workers
later
dihydride intermediatemaybeformedinthecyanoacetates
and
could
be
utilizedintheGrutzmacher, H., et al. ACIE, 2009, 48, 559
without it, the authorsattempted
reportforming
cyclicamines.
Assynthesizing
both121
to albeit
improvethereactionhigher
bya Ru-NHC
aldehydes under similar reaction conditionofRu-catalyzed
base,
atslightly
temperatures.
The
Scheme 40.
Lactam Synthesis
from Amino Alcohols146 with hydride now acting as an internal base. Williamsabsence
Ru-catalyzed
lactam formation
acceptorless
Madsen, R., et al. JACS, 2008, 130, 17672
and amidation
likelyproceedthrougha lactonization
hemi- complexes wereachieved a similar result with [Ru(PPhN-alkylation
xantphoscatalyst
but
found
that
the
resulting3)3(CO)H2] andphosphine hydride species, similar to compability of this catalyst to function without base suggests thatlyst Precursors for the Oxidative
xantphos in the presence of a mild base.122aminal intermediate,susceptible
presumably
the presence C-Hof waterabsenceof base or catalyst activators. The authors think thatto intramolecular
activation of
the NHCin alcohol activationhasreactions, have also
unlikesidemanyother alcohol activation catalysts,
a metalScheme 37. Asymmetric
LactoneFormation
fromaldola reaction
f Primary Alcohols
Acceptorless
Williams
explored
the nitroin the context
inhibits
dehydrationtogenerate
the pincer
ligand,which Dehydrogenation
contains an unusual dearomatized
chains.126 the imine. Instead, the32b
Meso-Diol143
perform
decarbonylation.
Williams
dihydride
intermediatemaybeformedinthecatalytic
cycle,
of hydrogen transfer reactions as well as analogous
reactionsfew examples
and suffersfrom harsh during
hemiaminal
is irreversibly
dehydrogenated,
forming
an
ring,
can
alternatively
aromatizeand dearomatize
the andAninteresting
advancefrom
Williams
andco-workers
uses
122,123
with hydride
now properties
acting aspredispose
an internal
base.
Williams
attempted
to
improvethereactionbysynthesi
withother cases,
nucleophiles.
[Ir(cod)Cl] anddppf areadded
2reactions
amide.
Itiscurrently
unclearwhatacatalytic
cycle
tofacilitate
theformationofdihydrogen.
This
In
many
Net
Oxidation
type
O
generated aldehydes as coupling partners in Wittig-type condition or poor reactivity
toneedformhydrogenthe activeacceptor
catalyst insitu
in the presenceof
mildachieveda thesimilarresultwith[Ru(PPh3)3(CO)Handxantphoscatalyst
but
found
that
the
resulting2] cancomplexforone
pathwayorother,
andmoremechanistic
reactionalso
beperformedinthepresenceofa
Ru-NHC
123a,127
toreactivate
catalysts
reactions (Scheme 29).
The nascent aldehyde
generated
Scheme 41. Intermolecular Amide Bond Formation viabase. It was found that the addition of a suitable hydrogen
xantphosthepresence effectof a mild
base.
Scheme 37. Asymmetric Lactone Formation fromastudiesare needed.
Water
has
an inhibitoryon thesame122 complex,by Madsen to
andintramolecularco-workers (Scheme
C-H activat
Dehydrogenative Alcohol Activation148,149
fromindehydrogenation
reactswitha 131
phosphonium
ylide,
andas reportedsusceptible
143
acceptor,suchascrotononitrile,allowsaccesstotheunsatur149
126
Meso-Diol
catalyst
inthe
Tishchenko
reactionofaldehydes.
A
They
form
the
activecomplexin situ from [Ru41).
128
Williams
explored
the
nitro
aldol
reactioninthecontext
124
side
chains.
the resulting
adductisreduced.
By
theaza-Wittig
reaction,
Murahashi, S. I., et al. Synlett, 1991, ated
693 products prior to their reduction.
Hartwig,F., et al.to
Organometallics,cyclic
2005, 24, 2441 (cod)Cl ] (34, Chart 5), imidazolium salt 35, phosphine 36,
benzalacetone
rhodium-basedwaslater J.found
2 byofcatalyst
hydrogentransfer
reactions
asfor
well
analogous
reactions!27 com!28
Chart
4. products
Catalyst
Precursors
theas
Oxidative
amine
were
alsogenerate
generatedusing
this strategy
Williams and co-workers also explored ruthenium
Antointeresting
Williams and122,1235-, 6-, and 7-memberedlactamsfromaromaticamino
and arecatalytic
base added
the reactionadvancemixture.from
Secondary86
EsterificationofPrimary
Alcohols
analogous
reactionwithaniminophosphorane(Scheme
30).
with
other
nucleophiles.
[Ir(cod)Cl
]
and
dppf
added
2
plexes for alkylation of activated methylene species
with147
generatedaldehydes
ascoupling
partners
alcohols.
[Cp*RhCl]was
employedasacatalyst
intheamideswere
formedingoodtoexcellentyields,andasingle2
In2 addition
to [Ir(cod)Cl]
al. also utilized
alcohols.32e Mild base, [Ru(PPh3)3(CO)H2], and xantphosto form
theactivecatalyst 2/dppf,
in situWilliams
in the etpresenceof mild
123a,127 reaction
presence of acetone as a hydrogen acceptor and mild base.
tertiary amide was reported
fair yield.
Longerreactionsin(Scheme
29).
The nascent ald

experiment, an excellent catalyst for H2O2 disproportionation)complete
cycle forgeneration
andtoward
dioxygeninto dioxygen
andthewater.
This isofa dihydrogen
new approach
a
from
water
promotedbyasolublemetal
complex.
Inaddition,complete cycle for the generation of dihydrogen and dioxygenisotopiclabeling
experiments
usingmetal
H217O
and H218
demonfrom waterpromotedby a soluble
complex.
InO
addition,
17
18
strateunequivocallythat the processoxygen!oxygenbondisotopiclabeling experiments
using HofO
andHO
demon22
formationisintramolecular,
establishingafundamentally
strate unequivocally that the process of oxygen!oxygen bondnewmode ofO!O bond formation,by photolytic
coupling
formationis intramolecular,
establishinga fundamentallyofOHmodegroups.
DFTbondcalculations
show couplingthat thenewof O!O
formation,bybyHallphotolyticOphotolytic
reductiveof
can takeof OH groups.
DFT elimination
calculations Catalyst
by HHallthat placethe
2O2 showN H P tBu 2
ROH
Rsinglet!triplet
OR
photolytic
reductive
elimination
of
H
O
can
take
place
from
a
dissociative
tripletstate
viaaMilstein’s
PNP-Rucomplex2
2
R = alkyl,
Ru
tBu P
aryl
(0.4 mol%)(stable under air)from a 18b
dissociative
tripletstateviaaconcludes
singlet!triplet
2crossing.
Another DFT
study
by Fangthat aCOClO
No H2 acceptor, High turnover18b
crossing.
DFT
concludesthat alower
energyAnotherpathway
forstudy
tripletbyO2Fang
formation,
consistent
NaOiPr (0.4 mol%)lowerallenergy
pathway findings,
for triplet involves
O2 formation,
consistentwithexperimental
a nonadiabatic
dioxane, 100 °C, 70 h
228 TONwithallexperimental
findings,
involvesanonadiabatic
two-step process in which concerted hydrogen transfer
David Milstein, et al. Organometallics, 2004, 23, 4026
two-step
process involving
in which twoconcertedhydrogentransferanddehydration
moleculesof complex
29
anddehydration
involvingtwomoleculesofcomplex29
take place. This O!O bond formation is intramolecular, andDr. Milstein started to investigate Ru-Pincer complexes
take place. This O!O bond formation is intramolecular, and“Serendipity” Strikes without Warning

First Report on A Ru-Pincer ComplexeOH

for acceptorless dehydrogenation reactions
SCHEME 10
SCHEME 10!29“Serendipity” Strikes without Warning
Not reduced to Ru(0)electron-poor anilines, N!H activation took place with protof the tocentralpyridine ring
(Scheme10).19to4-Nitroanilintransfer
the unsaturated
ligandarm, leading
aromatizati
reactedat roomwithof2-chloro-4-nitroaniline
the central pyridine ring
(Scheme10).19temperature
4-Nitroanilineaprovide the complexes
32a and32b, temperature
respectively. with
Reactio2-chloro-4-nitroaniline
reactedat room
82-bromoaniline
and 32a3,4-dichloroaniline
resultedin equprovidethe complexesand 32b, respectively.
Reactionsinvolvingtheactivatedaromatic
complexes32cand2-bromoaniline and 3,4-dichloroaniline resulted in equilib
and the starting
8, evenin the presenceof 32can excessinvolving
the activatedaromatic
complexes
and 32
halogenatedTheof N!Handthe startinganilines.
8, even in
thereversibility
presence of anexcessbondof tvation at room
temperaturein theseofcomplexes
halogenatedanilines.
The reversibility
N!H bondsugacvationat room
temperaturein thesecomplexessuggesthat thebarrier
for this process
is lowand thatpot
that
the barrier
this onprocess
low andthat readilypotentcatalytic
cyclesfor
basedsuch issystems
could
catalytic
cycles basedon such systems could readily elim
inate productamines.
inateThermodynamically,
product amines.
coordinated amine complex
Thermodynamically,
coordinatedamine
complexes
type 31 are the preferred forms forelectronrich amtype
are the preferred
forms
for
electronrich
amin
and 31ammonia.
When ND
wasreacted
with
compl
3
and
ammonia.
When
ND
was
reactedwithcomplex3formation of the deuterated complex 33 was observed
formationof thedeuterated
complex
33 wasobserved
aft
Metal!Ligand
Cooperation
Guna
5 min atroom
temperature,indicating
N!D activ
5(Scheme
min at 11).
room
temperature,indicating
N!D
activatio
The reaction is highly stereospecific, and(Scheme 11). The reaction is highly stereospecific, and1onone of the two CH2 arm hydrogen signals in theH
14base,one of the twoSCHEME
CH2 armhydrogensignals in the 1H NM
No
No H2 acceptor,
spectrum disappeared.
No exchangeof the vinylic hydreactive
spectrum disappeared.and
NoHighlyexchangeof the vinylic hydrog
took place. Such dramatic selectivity suggests that the atook place. Such dramatic selectivity suggests that the activ!30 the ligand
tion David
process
occurson2005,
only
Milstein,
et al. JACS,
127,one10840 face oftion process occurs on only one face of the ligand in
intramolecular manner with one coordinated molecu
intramolecular manner with one coordinated molecule
ND3. The reverse reaction would affect only the (ND3. The reverse reaction would affect only the (endhydrogen on the same face as the coordinated ND3 m
hydrogen on the same face as the coordinated ND3 moieThis result also suggests that N!H activation, and peThis result also suggests that N!H activation, and perha
O!H activation (see below) of other substrates, might oc
O!H activation (see below) of other substrates, might occur
stereoselective
fashion.
SCHEME15
a astereoselective
fashion.
Upon
heatingcomplex8 withexcessof isopro
Upon heating complex
8 withanan
excessof isopropy
mine
at
80
!C
in
a
closedNMR
tube,
formationof theO-H
is cleaved
bytube,Ru formation of themine at 80!Cbondin a closed
NMR
tran
and
Ligandcooperatively,
dihydride
9
wasobserved.
Presumably,
after
N!H
a
dihydride 9 was observed. Presumably, after N!H activ
as well as N-H bondtion,
Helimination
involvingthehydrideligandtion, H2 2elimination involving the hydride ligand an
SCHEME 16
anarm
armproton
protontakes
place,
suggested for comple
antakes
place,
as assuggestedNew
mode
of bondactivationfor complex 2

Metal-Ligand Cooperation

FIGURE 5

SCHEME 13 Alcohol Activation•

Deprotonate to dearomatize
the ligand (Ru(II) complex)

Metal-Ligand Cooperation
H2 can easily dissociate upon
SCHEME 11
coupling of hydride andSCHEME
proton 11
on the ligand

David Milstein, et al. JACS, 2005, 127, 10840!31•

Ammonia Activation

Interestingly, dearomatization of the central acridine ring
was also observed upon reaction of 34 with ammonia,
leading to complex 37 (Scheme 12). The X-ray structure of
37 shows an unusual fac configuration of the PNP ligand.
Refluxing a toluene solution of primar
Presumably, decoordination of the acridine nitrogen folcomplex 11 (0.1 mol %) as catalyst result
lowed by NH3 coordination places the bent acridine ring inof the corresponding esters in excellent yielda favorable position for hydride transfer to C9. The flexibilityof H2 (Scheme 14).7 Ester yields of over 90of the acridine PNP ligand enables formation of both
mer
David
Milstein, et al. ACC. Chem. Res. 2011, 44, 588!32
were obtained under mild, neutral
condition(i.e., 34!36) and fac (i.e., 37) PNP complexes.
aldehydes
wereformed.
As
opposedto thVol. 44, No. 8 ’ 2011 ’ 588–602 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 5

Vol. 44, No. 8 ’ 2011 ’ 588–602 ’ ACCOUNTS OF CHEMICAL RESEARCHSCHEME

Metal!Ligand Cooperation Gunanathan and Milstein

C-H and H-H Activation by PNP-Ir

Metal!Ligand Cooperation Gunanathan and Milstein

4
SCHEMESCHEME
4SCHEME 6

Ir(I)-Ir(III) Equilibrium: Aqua Bridge
Metal!Ligand Cooperation Gunanathan and Milstein

SCHEME 6

SCHEME 4

SCHEME 6

Metal!Ligand Cooperation Gunanathan and Milstein

2 H2O involved

No H2O involved

SCHEME 7

SCHEMESCHEME 8

SCHEME 7

Metal-Ligand Cooperationin C-H, H-H activation

FIGURE 3. M06/SDD optimized structures of TS(30 !230 ) þ nH2O (from top
to bottom: n = 0, 1, 2). Symbol (0 ) indicates the model complexes with PMe2
SCHEME8 ‡ are omitted for clarity. Structures modified
ligands. H's on methylgroupsΔGby permission
298 = 20.7
from ref 14. Reproducedof Thekcal
Royal Society of Chemistry.

‡

ΔG 298 = 35.9 kcal

Involvement of 2 moleculesof water in deprotonation
reactions, a stepwise cycle in which H2 and O2 are released in
is more likely (deciphered
by DFTsteps
calculation)consecutive
is attained (Scheme 9). Following the
SCHEME 5

thermal reaction of complex 28 with water to liberateDavid Milstein, et al. JACS, 2006, 128, 15390

SCHEME 5David Milstein, et al. Dalton. Trans. 2009, 9433

!33

dihydrorelease!34

592 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 588–602 ’ 2011 ’ Vol. 44, No. 8

position. Mechanistically, H2 and D2 activation proceed via
intermediacyof the Mechanistically,Ir(III) complex 21.HDFT
studies reveal
position.
2 and D2 activation proceed via

similar reactivity
patterns ofand acetonyl
intermediacy
ofphenylthe Ir(III)complexcomplexes
21. DFT studies reveal
3 and 19. similar reactivity patterns of phenyl and acetonyl complexes
Cooperative H2 activation and catalytic ammonia borane
3 and 19.
SCHEME 5dehydrogenation
SCHEME 9
by aliphatic pincer PNP-Ru complexes
Cooperative
H2 activation and catalytic ammonia borane
16
were recently reported.
position.
Mechanistically, H2 and D2 activation proceed via
SCHEME
9

H2O Activation by PNN-Ru
SCHEME 8

Water Splitting

dehydrogenation by aliphatic pincer PNP-Ru complexes
16intermediacy of the Ir(III) complex 21. DFT studies reveal
recently
reported.
O!H andwere
N!H
Activation
Based on

Metal!Ligand Cooperation

O!H and N!H Activation Based on

similar reactivity patterns of phenyl and acetonyl complexes

3 and 19.
a. Water Splitting. The dearomatized PNN complex 11
Sunlight driven water splitting
Metal!Ligand
Cooperation
readily cleaves the
O!H
bond
of
water.
Upon
reactionwith
FIGURE 3.
M06/SDD
optimized structuresof TS(30 !230 ) þ nHborane
O (from
Cooperative H2 activation
andcatalytic
ammonia
is topone of the goals in sustainable
Amine arm easily dissociates0
to bottom: n = 0, 1, 2). Symbol ( ) indicates the model complexes with PMe
Water Splitting.
The dearomatizedwater at rooma.temperature,aromatization
takes placePNN
to complex 11
ligands. H's on methyl groups are omitted for clarity. Structures modified
chemistry of H2 production
to open a site for 2nd H2O
dehydrogenationbyaliphatic
pincerPNP-Rucomplexes
from ref 14. Reproduced by permission of The Royal Society of Chemistry.
methylene carbon). Deprotonation Metal-Ligandof the arm methylene byreadily
the O!H bond of water.
Upon
quantitatively
formcleaves
the trans-hydrido!hydroxo
complex
28 reaction withcoordinationand H2 liberation
were recently reported.16reactions, a stepwise cycle in which H and O are released in
17
Cooperation
Ir (30 !230 ) is endergonic (ΔG298 = 11.1
kcal mol!1). Transitionat compoundroom temperature,aromatization(Scheme 8).waterThis
is probably
formed by atakes place to22‡
dihydrogen and give complex 29, photolysis of 29 mayconsecutive steps is attained (Scheme 9). Following thestates involvedin thedirectDeprotonation
deprotonation by
Ir (ΔG=
methylenecarbon).
of thearm
methyleneby298
mechanism
involving water
coordination
at the vacant site complex 28
quantitatively
form
the trans-hydrido!hydroxo
release hydrogen peroxide by reductive elimination,
thermalreactionofcomplex
28
with
water
to liberate
!1
‡
!1=
0
0) involving one water molecule (ΔG
Complex
11 turned out to17
35.9 kcal
mol
Ir (3 !23 ) is endergonic (ΔG298 = 11.1 kcal mol
298 ). Transitiontrans to the(Scheme
hydride, 8).
followed
proton migration
to the formed by
O!Hand N!H Activation Based on
Thisbycompoundis probably
a
!1
18
be
a
good
catalyst for26.5 kcal
molinvolved) and twowater
molecules(ΔG‡298 =by
20.7
592
ACCOUNTSOFCHEMICALRESEARCH
588–602
2011
Vol.
44,
No.
8
statesin thedirectdeprotonation
Ir (ΔG‡side=
indicated byinvolving
DFT studies.
298 arm, as
mechanism
water coordination at the vacantMetal!Ligand
site
Cooperation!1!1
dispropotionationof H2O2
kcal molweremol
identified
as depicted
in Figure3. The (ΔG‡ Interestingly,
furtherreactionofcomplex
28
with
water
at
35.9) kcal
) involving
one water
molecule=
0298 optimized
transstructures
to the hydride,
followedbyproton migration to the
FIGURE 3. M06/SDD
of TS(30 !23) þ nH
2O (from top
a. Water Splitting. The dearomatized PNN complex 11‡
smaller26.5
barrier
involvingis reasonable
18
100
!C
releases
H
and
forms
the
cis-dihydroxo
complex29.
kcal
mol!1)two
andwater
two molecules
water molecules
(ΔG
=
20.7
2
0
arm, as indicated
DFT studies.
to bottom: n =298
0, 1, 2). Symbolside( ) indicatesthe modelby
complexes
with PMe2
for a room
reaction.
readily cleaves the O!H bond of water. Upon reaction with
DFT
studies, independently carried out by Yoshizawa et
kcaltemperature
mol!1) wereidentified as depicted
3.
The
Interestingly,
furtherreactionofcomplex
28 with water atligands.inH'sFigure
on methylgroupsareomittedforclarity.
Structuresmodified
18b
Like the Ir(I) phenyl complex 3, the320
Ir(I)~acetonyl420
nm complex
sunlight
caninduce!
al.18a and Hall Even
and Yang,
indicatethat this process
at room temperature, aromatization takes place tosmaller barrier involving two watermoleculesisreasonable
100 !C releases
H2Royaland forms
the29.
from ref 14. Reproduced by permissionof TheSocietyofcis-dihydroxo
Chemistry. complexwater
19 also reacts with H2 (1 equiv) in benzene-d6 to provide
involves
H2 liberationfrom 28 byofcouplingof methylene
the hydride bymethylenecarbon).
Deprotonation
the arm
for a room temperature reaction.
quantitatively
form the trans-hydrido!hydroxo complex 28
DFT
studies,
independently
carriedout
byYoshizawa
etexclusively the trans-dihydride Ir(III) complex 26, whose
ligandwith a proton
from the side arm, followedby addition!1
0 complex
0
18a
18b
17
Like the Ir(I) phenyl complex 3, the Ir(I) acetonyl
Ir
(3
!23
)
is
endergonic
(ΔG
=
11.1
kcal
mol
).
Transition
al.
and
Hall
and
Yang,
indicatethat
thisprocess
298(Scheme 8). This compound is probably formed by astructure was corroborated by an X-ray diffraction
studyof H2O cycle
to the ingenerateddearomatizedintermediate.
Sigreactions,a stepwise
which
H
and O
releasedin
2 are
19 also reacts with H (1 equiv) in benzene-d
provide ininvolvesDavid
etdeprotonation
al.2Science,from
2009,
324,
!35 ‡ of theDavid Milstein, et al. Science, 2009, 324, 74!36
6 to involved
H2 liberation
28 74
by couplingstatesthe Milstein,
directIr (ΔG
298 = hydride(Scheme 7).13 Further, reaction2 of 19 with D2 in benzene
nificantly, irradiationof complex
29 in the by
320!420nm
mechanism
involvingwater coordination
at thesite
dihydrogen
andgive complex
29, photolysis
ofvacant
29 mayconsecutive(Scheme9).theFollowingtheexclusively the trans-dihydride Ir(III)complex 26,steps
whoseis!1attained‡
ligandwithaproton
from
side
arm,
followedbyadditionleads to formation of the trans-H!Ir!D complex 27,35.9
with kcal
range
in O2 liberation
regenerationof complex
molresults) involving
onewithwater
molecule(ΔG 298 =trans to the hydride, followed by proton migration to thestructure was corroborated by an X-ray
diffraction
study
releasereactionof!1complex
with
water
to
liberateof8).
H2Combining
O to 28
the generated
dearomatizedintermediate.
Sig- hydrogen peroxide by reductive elimination,‡
incorporation of one deuterium atom inthermal
the benzylic
28 (Scheme
these separate
stoichiometric
18
2

2

’

’

’

’

Angewandte

Chemieanol reacted
nes was lesshibited veryg 2-methoxyAlthough theis still to be
the synthesis
ng the stericminished thendary aminesof primary
hy that thehol (Table 1,yield of theively also in
e 1, entries 6,

unt of water
catalysis by
g water as amination ofd “on water”
mines. Whilet, its current
nce of waterve led to thetions of thevity towards
nzyl alcohols
ater at roomheating andr”. Aliphatic

alcohols such as 1-hexanol were not miscible with water evenon heating and the reaction took place “on water” (Table 2,entry 4).[26] Surprisingly, when water-soluble alcohols (pyridin-2-yl-methanol and 2-methoxyethanol) were subjected todirect amination reaction “in water”, the reaction becamevery sluggish even after prolonged heating (30 h) and theconversions were minimal,[27] in sharp contrast to excellent(*H28).
Autotransfer)
R
NH
2
reactionsin R
toluene (Table 2, entries
4 and
O
1
Although reactions in water alone do not improve theselectivity
haveR
O to theR 2 linear aliphatic primary amines, theyRN
NH 3
several practical advantages as the aqueousandorganic layers
(7.5
atm),
H
O
2
4
separate at the OH
end of the reaction upon cooling, and further
purification of products3 could be carried1 outH 2Nby vacuumR'R2
1
distillation. RTheselectivity
for the linear primary amines is
improved by the use of co-solvents such as toluene or dioxaneOin water (Table 2, entries 5–7).
3
2
Althoughinsufficient dataRexist OH
at present to describe aR
R
OH
H
O,
OH
2
detailed mechanism,a possible mechanism fordirectH 2Nthe R'
amination of alcohols with ammonia by complex 1 could
involve intermediate aldehydes as delineated in Scheme 4.
3
4
The aldehyde
2 HOcan Rreact with ammonia to generate a hemiaminal intermediate D. Upon water
3 elimination, the hemiOH
aminal forms a terminal imine
OH E which is reduced to a
O
RR'
primaryamine
by the ruthenium dihydrideintermediate
C
NH
2
NH 2
(transfer hydrogenations R'or “borrowinghydrogen”).R'[28]Magic Arm

Applications of Acceptorless Dehydrogenation

R

O

R

N

R'

N
H

R

•
H

H
P tBu 2R'N

Ru

P tBu 2CONRu

P tBu 2

NEt 2

1

2

R'
H
P tBu 2
N

Ru

N

CO

N

P

Ru
Cl

R

3

P

H

CO

4

This step generates an intermediate aldehydeDavid Milstein, et al. ACC. Chem. Res. 2011, 44, 588!37

FIGURE 6. Proposed simplified catalytic cycle for the synthesis of esters,
amides, and imines from alcohols, catalyzed by PNP and PNN ruthenium pincer complexes. Note that mechanisms not involving amine
arm dissociation are also possible (see text).

Magic Armand ammonia

•

Yield
[%][b]David
Milstein,
et al. Science, 2007,
317, 790!38 9, or 12, resp
known
trans-dihydridecomplexes(6,

which were demonstrated to liberate H2 and regendearomatized complexes. The generated aldehy
equilibrium with the corresponding hemiacetal

Short Summary

which undergoes a similar catalytic cycle provi

Amine Synthesis(*H2 Autotransfer)

imine hydrogenation taking place (Scheme 20). A range ofester.7 In the presence of amines, the course ofalcohols and amines containing either electron-donating or -differs based on L2 (i.e., PtBu2 or NEt2). With the PNN

withdrawing substituents react to yield the correspondingH
imines in very good yields.
Sterically hindered amines are

11, the intermediate hemiaminal (X = NH, but

P tBu 2Acridine-based PNP ligand
Flexible 6-membered ring

95.4 (86)

M

N

91.7

CO

•

•
•

paragraph) undergoes dehydrogenation to provide a

Dearomatized ligand can cooperatively
Vol.=44,O,
No.NH,
8 ’ 2011
activate various X-H bonds (XCH’n)588–602 ’ ACCOUNTS OF CHEMICAL RESEA
Certain metal can preferably activate certain bonds
Variable arm can adjust the openness of metal centerL

80.4[c]54.8[d]74.3

Nucleophilic attack by Alcoholand Alcohol-Amine exchange
becomes facile

79.7
70.0

(7.5 atm), andrter reactor.[23]alyzed by GC;
imine was the
he byproduct inaqueous layer.
of 2 mL watermL water andthe challenging synthesis of unstable aliphatic iminvenient to practical applications, the reaction can b
Coordination Strength:out
in air.35
Pyridine≤ NEt2 < PtBu2! A common, simplified catalytic cycle for the direification,amidation, and imination reactions based
Steric Hindrance:
hols
with
is proposed in
Pyridine <liberation
NEt2 < Ptof
Buhydrogen
2
Upon reaction of dearomatized complexes (5, 8, or
alcohols, facile O!H activation takes place to pro
saturated hydrido-alkoxy complexes. This is follow
Dehydrogenation of this
hydrideelimination,mechanism of which is nointermediateneedsthesterically
thisstage.
Itmayoccur
by armless hindered coordination
siteopening to prov
coordination site, as depicted in Figure 6, but otherisms are also possible, including alkoxide dissociat
the saturated complex accompanied by hydride abstr

CO

O
N
H

also tolerated. This new catalytic reaction works ve

Ester, Amide and Imine Synthesis

Tasks of other chemists•••

Scheme 4. Proposed mechanism for the direct amination of alcohols
with ammonia catalyzed by complex 1.

2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.angewandte.org

David Milstein, et al. ACIE, 2008, 47, 8661

8663

!39

Utilization of new concepts of ligand design
Investigation of new ligand-metal combinations and their reactivity
Establishment of new catalytic reactions inspired by the studies above!40

Main Character of This Chapter
3. Gelman’s Cooperative Catalysts
for Acceptorless Dehydrogenation

DOI: 10.1002/chem.201303311

1996 B.Sc at Hebrew University
1997 M.Sc under the guidance ofProf. Aizenshtat and Prof. Blum
2002 Ph.D under the guidance ofProf. Blumthen; postdoc in Buchwald’s lab
2004 Senior lecturer at Hebrew University
2009 Associate professor

Ligand–Metal Cooperating PCACHTUNGRE(sp3)P Pincer Complexes as Catalysts in Olefin
Hydroformylation
Sanaa Musa,[a] Oleg A. Filippov,[b] Natalia V. Belkova,*[b] Elena S. Shubina,[b][c]Gleb A. Silantyev,[b] Lutz
and Dmitri Gelman*[a]Keywords:
DimitriAckermann,
Gelman• Organometallics• C(sp3) metalated catalyst
Associate Professor at Hebrew University• Metal-ligand cooperationof Jerusalem, Department of Organic Chemistry[9]
In recent years, metal complexes, in which both the metal
complexes,Dehydrogenation
species in electron rich CACHTUNGRE(sp3)-metalated pincer• Acceptorlesscenter and the ligand play active and cooperative roles, haveas well as on keto–enol[10] or lactam–lactim tautomerism.[11]!41 catalysts, capable of activating!42
Chemical Reviews
emerged as very promising
These systems establishedREVIEWa basis for the design of mild catand forming chemical bonds through nonoxidative pathways
alysts for nonoxidative (de)hydrogenation processes[12] and(i.e., alternative to the conventional oxidative addition/rechemoselective H/D exchange.[13]complex 33 was synthesized and displayed eﬃcient
catalytic
hydride.
In
analogy
to
metal
acyl
decarbonylation (COductive elimination sequence). The key mechanistic steps
The examples are impressive, however, they provide only
activity for transfer dehydrogenation of alcoholsusuallyin theinclude
presence
deinsertion),
migration
of
the
imino
methylgroup
to iridium
a reversible switching between the coordinaa hint of the real
synthetic
potential concealed in ligand–withmodes
this systemof a base (eq 23).143 Advantages associated tion
gives
isomeric
isonitrile
complexes
34a
and
34b.
Formationof strongly believe that furof the ligands that are bound to the catalyticallymetal cooperation. Therefore, we
activemetaltocenter1). species, which are stable therof thiscatalyticallyconcept to new reaction schemes will
include high functional group tolerance and theabilityper-(Schemetheseandextension
presumably
eventuallylead to theof conceptually novel catalform the reaction in air.
inactive at ambient temperature,
can explain
thediscovery
need forelevated temperatures observed 1byysis.
JensenandMorales-Morales(0.1mol%) we wish to report on the development of IrIII- andHerein,OH
O
and the less than quantitative
yieldsofmol%)
simple dehydrogenatedCsCO
3 (0.1
III
Rh -based catalysts that areof promoting olefin+ capable
H2
product.144
RR'
R throughR'hydroformylation
the unprecedented metal–ligand
p-xylene,
refluxThe
transfer-dehydrogenation
amines
6 ~ 36ofh primarycooperating
mechanism.
In ourbyprevious work, we develt
Scheme 1. Ligand–metal cooperationin bond activation/formation.
III to3
has
been
reported
yield
nitriles( Bu4POCOP)Ir (9a)• No H2 acceptor
oped
the Ir PCADehydrogenation)
CHTUNGRE(sp )P pincer
complex 1, which forms mo(Acceptorless• 1°
lecularhydrogenbyanintramolecularinteraction that inmechanismof
thisreactionwas
extensively(Scheme 12).148 The
and 2° alcohols can be dehydrogenated1
For example, metal–amide/metal–amine
volvesboth
the metal
center(hydride) and a polar O-based• Aliphatic
alcohol
canisotopic
be dehydrogenatedinvestigated in interconversion,a seriesof kinetic
andlabeling
experi[1][14]originally described by Noyori
and Oxidative
Ikariya, ledligand N-Hsidearmbond,(Scheme2). Theto the disments.
additionof an amine
followed
bycatalyst showed very high3)P-Ir complex
PC(spPrimary and secondary amines are also
subject
toofdehydrocovery
very efficient asymmetric hydrogenation cataturnover-limiting
β-hydrideelimination,
producedintermediate
Advantages
Disadvantages[2]synthesizedtobelysts.
Aromatization/dearomatizationin heteroaromatic
genation by pincer
iridium complexes.• Easy
JensenandMorales37, which was readily converted to nitrile complex 38 via• Stableunder
PNP andairPNN pincerof ligands made nonoxidative activation
Morales reported that 3-H2 catalyzed the dehydrogenation
An equilibrium
study and kinetic isotope eﬀect
144!H,[3] possible
Not planarof H
C!H,[4] and N!dehydrogenation.
H[5] bonds possible anda familyTwosecondary amines
to form
imines (eq• 24).
RequiresHydrogenArm-closed
measurementsthat pre-equilibria (among 38, 35, andof hydrogenation/dehydrogenation
catalysts indicated
was established
Carried out under air
pathways for dehydrogenation
proacceptor (acetone)of secondary amines were
Ir-alkoxide species[6]
before PNP
the turnover-limiting
β-hydride elimination signiﬁby Milstein. Nonaromatic36)
switchable
pincer systems
posed: (1) initial N-H addition followed by haveβ-H(alkyl)
elimbeen proven to facilitate
heterolyticbondandcantlyaﬀectedthecleavage
overall reaction
rate. Surprisingly, the converor (2)Limited
initial toC-H
addition followedcatalyzeby β-H(amino)
1transfer[7] and acceptorlessdehydrogenation/hydroHigh FGination
tolerance
secondarysionofiminestonitriles(37
to38)
was apparently a rapid step.
elimination.
Thebenzyl
authorsfavored the N-H genationbond activation
Scheme 2. H2 activation/formation through ligand–metal cooperation inreactions.[8](-Br, -CN,-OMe)
alcoholbifunctional
IrIII PCACHTUNGRE(sp3)P pincer complexes.
pathway, which may receive some support
fromSo Hartwig
and cooperation relies on a dynamic infar, ligand–metal
Gelman. D., et al. Catal. Commun, 2009, 11, 298 !43
Gelman. D., et al. ACIE, 2011, 50, 3533
!44
terplay between
carbometalated
and a- orREACTIONS
b-H eliminated
4. RELATED
Goldman’s reports of facile N-H bond activation
by pincer

1st Generation

iridium complexes.145,146 Unlike the dehydrogenation of tertiary111

2nd Generation

4.1. Hydrogenation of CdO Bonds
activity in the acceptorless dehydrogenation of primary andns

Dual Metal-Ligand Cooperation

torless dehydrogenation of alcohols[13, 20–23] may proceed, thus
ne-pot operation and without isolation of) an essentially quantitative reaction offollowing this sequence of mechanistic events (Scheme 2):hine with [{IrCl(cod)}2]. 31P{1H} NMRa) H2-forming step, leading to the formation of the arm-closed
he expected set of doublets at around d =iridium species 8; b) ligand exchange step, leading to the armdue to the presence of two different
JP-P = 10 Hz), whilst the hydride signal
Metal-ligated alkoxide becomestively simple triplet at d = !19.86 ppm
strong base by d-π repulsion
H NMR spectrum. The remarkably small
DOI: 10.1002/chem.201303311(Metal-Ligand Cooperation)g constants suggest a cisoid arrangement
around the metal center, which is atypical
Ligand–Metal Cooperating PCACHTUNGRE(sp3)P Pincer Complexes as Catalysts in Olefin
PCP complexes.[16] In addition, a room
Hydrideand proton
cancrossbe easily
ESY experiment
displayed
a clearHydroformylation
to getfree as Hatoms
2!H and the coupledmethylenehydrogen(Metal-Ligand
Cooperation)hich is consistent
with the expected
close
Sanaa Musa,[a] Oleg A. Filippov,[b] Natalia V. Belkova,*[b] Elena S. Shubina,[b]Metal!Ligand Cooperation Gunaact between the hydride ligand and the[17]
Gleb A. Silantyev,[b] Lutz Ackermann,[c] and Dmitri Gelman*[a]sidearm.
These NMR data indicate
ike geometry around the metal centeride and phosphine groups, as depicted in
Scheme 2. Possible mechanism for dehydrogenation of alcohols by 7
SCHEME 14

4. Summaryor 8.

In recent years, metal complexes, in which both the metal

species in electron rich CACHTUNGRE(sp3)-metalated pincer complexes,[9]grow single crystals of 7 for more detailed
center and the ligand play active and cooperative roles, haveas well as on keto–enol[10] or lactam–lactim tautomerism.[11]ons revealed that it is moderately stableopen iridium alkoxide species
9;
and
c)
regenerationofthe
Iremerged
as very
promising
These systems established a basis for the design of mild cat!46
Gelman. D., etal. ACIE, 2011,
50, 3533!45 catalysts, capable of activating
dually, but selectively, transforms into a
H catalyst 7 by b-hydride elimination
subsequentand formingwith
chemicalbonds through nonoxidative pathways
alysts for nonoxidative (de)hydrogenation processes[12] and(i.e., alternative to the conventional oxidative addition/rechemoselective H/D exchange.[13]ich features no hydride signals in theformation of the oxidized product.
ductive elimination
sequence).
The examples are impressive, however, they provide only
Indeed, this fascinating transformation
was realized
under The key mechanistic steps
nd a different set of doublets at d = 15.8
usuallyinclude a reversible
switching between the coordinaa hint of the real synthetic potential concealed in ligand–catalytic conditions. Thus, oxidationof 1-phenylethanol
under= 13 Hz) in the 31P{1H} NMR spectrum.
tion
modes ofthat
metal cooperation. Therefore, we strongly believe that furacid- or base-free conditions in thepresenceof the0.1 ligands
mol % of7 are bound to the catalyticallyof the product led to the conclusion that
activeandmetal(Scheme 1).
ther extension of this concept to new reaction schemes will
FIGURE 5
in p-xylene, with heating under reflux
in acenterN2 atmosphere
extrusion of molecular hydrogen, which
eventually lead to the discovery of conceptually novel catales from the intramolecular hydride–
led to the formation of the desired acetophenone as the sole
ysis.
SCHEME 15This decomposition gives rise to the
product after 10 hours. Similar activity was essentially demHerein,
we wish to report on the development of IrIII- andSCHEME Various
13
Metal-Ligand
Cooperation
rm-closed species 8, which featuresa
onstratedbythecomplex8(Table1,entry1),whilst
none
of
III
Group
Major Effects
Rh -based catalysts that are capable of promoting olefin
gonal bipyramidal geometry around thethe iridium hydride complexes that lack acidic sidearms,
hydroformylation through the unprecedented metal–ligand
Y
X
[19]
[15]
Stericcontrol,
accessibility
eme 1).
which
werereported by us earlier,Adjust
The presence of H2 in thewerethefound
to be active
cooperating mechanism. In our previous
work, wedevelX (Arm)Scheme 1. Ligand–metal cooperation in bond activation/formation.
Metal-Ligand
Cooperation
ElectronIII3e heated sample of 7 in [D6]DMSO was
under
thesedensity
reaction conditions. to metal center
oped
the
Ir
PCA
(
E
R
G
N
U
T
H
C
sp
)P
pincercomplex
1,
which
forms
moZ MLnprovides new mechanistic
Indirectstericcontrol, revealedAllows
Metal-Ligand
Further
optimizationthat theemployment of ated using GC
SCHEME 16 that inlecular hydrogen by an intramolecular interaction
R (TCD) and IR-MS Ytech(Joint)
insight into catalyst design
Ligand’s
Cooperativity
Cooperation
catalyticbaseimproves the performanceof our metal–amide/metal–amine
catalyst andstingly, addition of isopropyl alcohol to
For example,
interconversion,
volves both the metal center (hydride) and a polar O-based
Y
X
[1]
[14]
the best results were obtained using
5 mol% of Csby
MSO solution of 8 recovers the parent 7 as
Allows
Metal-Ligand
originallydescribed
Noyoriligand sidearm (Scheme 2). The catalyst showed very highled to the dis2CO
3 to and Ikariya,
Z (Core)Trans effect13
give the corresponding ketones in
excellent
yield
after only
P{1H} NMR
are
Cooperation
coveryof very
efficientasymmetric hydrogenation cataX =spectroscopy
NR2, PR’3, OR, patterns
SR
Interestingly,
dearomatization of the central acridine ringY = CH2, O, NH
lysts.
Aromatization/dearomatizationin heteroaromatic
6 hours(Table1, ofentries 3 and 6);
K3[2]
POAdjust
andFinelytheelectronRemotecontrol
4, K2CO3, KOHR (Tail)
Z
=
C,
N,
B
PNP
and
PNN
pincerligands
madenonoxidative
activation
was
also
observed
upon reaction of 34 with ammonia,
simple stoichiometric experiment points
Etelectron
N
were
found
to
be
much
less,
if
at
all,
effective.
Wedensityofthecomplexdensity3= EDG, EWG!H[5] bondsleadingofAllows
H!H,[3]C!H,[4] by
andCsN2CO
possibletoanda family37 (Scheme 12). The X-ray structure of
atalytic cycleR throughwhich the Backbone
accepspeculated
inducedcomplex
Metal-Ligand
Flexibility,that the superior acceleration
3ofCooperationhydrogenation/dehydrogenation
catalysts was establishedindicatethat theformation ofthearm-opened
species 9(Body) may
Otherfunctionalgroups37 shows an unusual fac configuration of the PNP ligand.
[6]
byMilstein.
Nonaromatic
switchable
PNP pincer systems
Refluxing a toluene solution of primar(Scheme2, stepb) is difficult
benefits groups
from theSelectivity
in activationof and, therefore,
Various functional
Presumably, decoordination of the acridine nitrogen folbeen proven to facilitate[24] heterolytic bond cleavage andM (Center) formation of a more nucleophilichavecomplex
11 (0.1 mol %) as catalyst result
cesiumalkoxide
species.
molecules (C-H, O-H, etc)
can be transfer
targeted[7] and acceptorless dehydrogenation/hydrolowed by NH31 coordination places the bent acridine ring in
catalyze
Alternatively, the positive effect of the base could[8] originateofthecorresponding
esters in excellent yield
Scheme transfer
2. H2 activation/formation
through ligand–metal cooperation in
genation reactions.
a favorable position for hydride
to C9.
The flexibility
7
III3
frombiga competingmechanism
thatnew
involves
interaction of thePincer complexes havepotential ascompletely
catalysts!
bifunctional
Ir
PCA
(
E
R
G
N
U
T
H
C
sp
)P
pincercomplexes.
of H2 (Scheme 14). Ester yields of over 90
So far, ligand–metal cooperation relies on a dynamic inof the acridine PNP ligand enables formation of both mer
cesium alkoxide with the axial chloride
in carbometalated
7 leading!47 to!48
terplay ligand
betweenand a- or b-H eliminatedwere obtained under mild, neutral
condition(i.e., 34!36) and fac (i.e., 37) PNP complexes.
the formation of the cisoid dihydride species capable of thealdehydes
wereformed.
As
opposedto ththermal H2 loss.[21, 25] However,[a] when
the stoichiometricactivity in the acceptorless dehydrogenation of primary andS. Musa, Prof. D. Gelman

Summary

Summary

Exercise
Ir (III)

H2

Bifunctional cooperative ligand

PR 2
N

ExerciseCl

O•

Core: Activate C-H bond by Metal-Ligand Cooperation•

O-Arm: Strongly basic for deprotonation•

Gem-Me Joint: Stabilize the complex•

Ir-Center: Electron rich for C-H activation

PR 2

Metal-Ligand
Cooperation

Ir (III)

N

R1
Cl

O

H

H

PR 2
Ir (I)

N*solvent or olefin ligand should be incorporated
because this is still an unstable 14 e- species

R1
PR 2

Cl

Ir (III)NO
R1

PNO-Ir(III) complex

O

R2

Metal-Ligand
Cooperation

Target reaction: Dehydrogenative C-C Coupling
Target bonds:
R1

H

Reductive
Elimination

Allylic C-H and Acidic C-H

+

H

R2

PNO-Ir(III)H 2O or ROH

R1

R2 +

Cl

H

R1

H

Ir (III)

N

H2

PR 2
Cl

Ir (III)

N

OH

Cl

O

R2

!49

R1

H

PR 2

H

R2

Deprotonation!50

Thank You Very Much!!
Bye Bye

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Appendix!51!52

Syntheses of Pincer Complexes•(tBu4PCP)IrH2 complex

Syntheses of Pincer Complexes

Communication•

Gelman’s PC(sp3)P-Ir complex

pubs.acs.org/JACS
Br

P( tBu) 2

1. ( tBu) 2PH
acetone, reflux

P( tBu) 2
IrCl 3

2. NaOAc
H 2O

H

LiEt 3BH

Cl

pentane, H 2

Ir

iPrOH/H 2O
reflux

+

H
Ir

PPh 2

H

Acceptorless Dehydrogenation of C−C Single Bonds Adjacent toFunctional Groups by Metal−LigandJensen,
Cooperation
C. M., Kaska, W. C., et al. Chem. Commun. 1996, 2083
Br

P( tBu) 2

P(tBu) 2

CO 2EtO

P( tBu) 2

P(tBu) 2

PPh 2

OEt

EtO
O

xyleneEtO 2CCH 2OH
LiAlH 4

reflux

THF
Ph 2P

Ph 2P

Ph 2P

[IrCl(COE) 2]2

Milstein’s PNN-Ru complex

CH3CN/iPrOH

Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku,
HTokyo 113-8656, Japan
1. NBS, AIBNS Supporting Information
CCl 4, reflux
N
2. Et 2NH, THF*

P( tBu) 2

nBuLi; ( tBu) PCl
2

N
NEt 2
acceptorless

ABSTRACT: Unprecedented direct
dehydrogenation of C−C single bonds adjacent to functionalgroups to form α,β-unsaturated compounds has beenaccomplished by using a new class of group 9 metal
complexes. Metal−ligand cooperation operated by thehydroxycyclopentadienyl ligand was proposed to play amajor role in the catalytic transformation.

S

P tBu 2

HOH 2C
H
Ph 2P

Ir

PPh 2

Cl

HClRu(PPh 3)3(CO)N-78 °C to rt

Ph 2P

CH 2OH

Shuhei Kusumoto, Midori Akiyama, and Kyoko Nozaki*•

HOH 2C

Scheme 1

NEt 2

THF, 65 °C

N

Ru

Gelman. D., et al. ACIE, 2011, 50, 3533

CO

NEt 2
Cl

David Milstein, et al. JACS, 2005, 127, 10840!53

ince the ﬁrst report by Bergman, Graham, and Jones in theearly 1980s, cyclopentadienyl rhodium or iridium phosphinecomplexes have been known to undergo oxidative addition ofunactivated sp3 C−H bonds to form alkylmetal hydride species.1
Because the resulting alkylmetal hydride is a coordinatively
saturated 18-electron complex (complex B in Scheme 1a),• transformation• Nozaki’s CpOH-Rh/Ir catalyst
Yamaguchi’s
Cp*Irfurther chemicalof thealkylcatalyst
group was rather
limited, and examples have been conﬁned to a few stoichiometric
reactions.1a Hence, catalytic functionalization of a sp3 C−H bondhad required photoirradiation to make vacant site(s) except for a
few thermal dehydrogenations.2,3 In 1996, Jensen reported a
PCP-type pincer iridium dihydride 16-electron complex, whichshows quite high activity in thermal alkane dehydrogenation
reaction.4 Intensive eﬀorts have been devoted to further
development of pincer-type complexes by Jensen, Goldman
and Brookhart in alkane and amine dehydrogenation.5−7 Asanother type of sp3 C−H functionalization, rhodium-catalyzed
alkane borylation via σ-bond metathesis established by Hartwig
may be also referred.8
In the ﬁeld of dehydrogenation of alcohols or hydrogenation
Nozaki, K., et al. JACS, 2013, 135, 18726
18-electron alkyl hydride complex F having a hydroxyl group onof carbonyl groups, metal−ligand cooperation has attracted
9
the Cp ring would release dihydrogen via metal−ligandmuch attention. A pioneering work by Shvo with cyclocooperative heterolytic bond formation to form a 16-electron
pentadienone−hydroxycyclopentadienyl based ruthenium comalkyl complex G (Scheme 1c). Coordinatively unsaturated G isplex established a heterolytic formation of dihydrogen fromexpected to be active for further functionalizations, e.g., βproton and hydride (from complex D to C in Scheme 1b) andhydride elimination to aﬀord an alkene and hydride complex H,
heterolytic cleavage of dihydrogen into proton and hydride
which would exist under equilibrium with E.13 By developing(from C to D).10 As another example of eﬃcient metal−ligand
these hydroxycyclopentadienyl group 9 metal complexes, we
cooperation, highly active acceptorless dehydrogenation of
the ﬁrst direct acceptorless dehydrogenation
Yamaguchi, R., et al. JACS,have2012,accomplished
134, 3643!55
alcohols was reported by Fujita with pyridone−hydroxypyridineof C−C single bonds adjacent to functional groups with metal−
based iridium catalyst, which can release hydride on the metal as
ligand cooperation. In the precedents for α,β-dehydrogenation of
dihydrogen by the assistance of proton on the hydroxypyridine
carbonyl compounds, stoichiometric oxidants such as DDQ,14
ligand.11,12

Other Cooperative Catalysts!54