literature seminar 2

H. Mitsunuma (M1)
2010/09/08

Transition Metal Catalyzed
Carbon-Carbon Bond Activation

0. Introduction
Currently, selective C-H and C-C bond activation by transition metal complexes has attracted much attentions.
Advantages: Ubiquitousness of C-H bond and C-C bond, atom economically good ...
This seminar's topic
C-H bond activation
CC-C bond activation

HCC

Transition
metalCCMCTransition
metalInsertion

FG
StracturalchangeCC

RCFG
etc...

Compared to C-H activations, the development of related C-C activation
reactions lags behind.
Difficult point in C-C bond activation
Rarely developed...

1. High directionality of C-C bond
2. Steric effect (substituents)
3. Statistical abundance of C-H bond

90kcal mol-1 per bond

20~30kcal mol-1 per bondContents
1. Basic strategy
2. Activation of strained molecules

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2.1 Direct cleavage of C-C bond by transition metal catalysis
2.2 b-alkyl elimination of strained molecules

3. Activation of unstrained molecules
3.1 -alkyl elimination of unstrained molecules
3.2 C-C bond activation by chelation assistance3.2.1 Milstein's work
3.2.2 Pyridine directed type reaction
3.3 Other methods

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4. Summary
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1. Basic strategy
In order to facilitate C-C bond activation, two basic strategies can be applied.
1. Increase the energy state of the starting materials
2. Lower the energy state of the C-C bond cleaved complexesa. Strained starting materials

Tipper et al. J. Chem. Soc. 1955, 2043.
Chatt et al. J. Chem. Soc. 1961, 738.

Halpern et al. J. Chem. Soc. Chem. Commun. 1970, 1082.
Halpern et al. J. Am. Chem. Soc. 1970, 92, 3515.

b. Aromatization

Chaudret et al. Organometallics. 1993, 12, 955.
c. Chelation assistance

Milstein et al. J. Am. Chem. Soc. 2000, 122, 9848.

Eilbracht et al. J. Organomet. Chem. 1977, 135, C2.

Suggs et al. J. Organomet. Chem. 1981, 221, 199.

Metal C-C bond interaction (agostic interaction)
What is agostic interaction?
Interaction of a coordinately-unsaturated transition metal with a C-H bond (sometimes C-C bond), when the two electrons
involved in the C-H(C-C) bond enter the empty d orbital of a transition metal, resulting in a two electron
three center bond
Structural and spectroscopic features (C-H bond)exampleelectrophilic metalsteric influenece
etc

Brookhart et al. PNAS. 2007, 104, 6908.
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C-H activation (sp3 C-H bond)

Examples of metal C-C agostic interaction

Agostic interaction assists non-acidic
C-H bond deprotonation.
Fagnou et al. J. Am. Chem. Soc. 2010, 132, 10706.

C-C agostic interaction is very rare...

C-C bond is lengthened by ~0.1 Å.
Coordinated C-C single bond with atransition metal has been characterized
structurally, spectroscopically, and by theoretical calculations.

Weller et al. Angew. Chem. Int. Ed. 2006, 45, 452.

Classification of catalytic C-C activation
Strained molecules (summry)
catalyst

C-C activation

Main topic

Unstrained molecules

2. Activation of strained molecules
2.1 Direct cleavage of C-C bond by transition metal catalysis
OMetal(cat)Strained starting materials

MM

Catalyst turnoverTM

4- or 5-membered metallacycles

3/15Chirik et al. J. Am. Chem. Soc. 2003, 125, 886.

Murakami et al. J. Am. Chem. Soc. 2007, 129, 12596.

Murakami et al. Nature. 1994, 370, 18.

2.2 -alkyl elimination of strained molecules
R1R2R3OH

Metal(cat)

R1R2M

R3O M

R12RO

Futher conversion
R3-alkyl elimination
Currently,many enantioselective -alkyl eliminations are reported.

Uemura et al. J. Am. Chem. Soc. 2003, 125, 8862.

Murakami et al. J. Am. Chem. Soc. 2007, 129, 12086.

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Cramer et al. Angew. Chem. Int. Ed. 2009, 48, 6320.

Cramer et al. J. Am. Chem. Soc. 2010, 132, 5340.

3. Activation of unstrained molecules
3.1 -alkyl elimination of unstrained molecules
Ruthenium-Catalyzed -Allyl Elimination Leading to Selective Cleavage of a Carbon-Carbon Bond in Homoallyl Alcohols

Mitsudo et al. J. Am. Chem. Soc. 1998, 120, 5587.

C-C bond activation
allyl transiton chemistry
irreversible

Role of carbon monoxide and allyl acetate
The presence of both carbon monoxyde and allyl acetate was crucial.
Carbon monoxyde: -acid
After the reaction, RuCl2(PPh3)3 was quantitatively converted into
cis-RuCl2(CO)2(PPh3)2.
In the case of maleic anhydride

Allyl acetate: unclear(it is required for generation andstabilization of a catalytically active ruthenium species?)

maleic anhydride
65% y.
50eq
Carbon monoxyde and maleic anhydride may coordinate to an active
ruthenium center and promote the reductive elimination of propene
from a (hydro)(allyl)ruthenium intermediate, as well as control theelectronic condition of an active ruthenium center.
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Mechanistic study

Proposed catalytic cycle(5): First step of the reaction is oxidative addition of a hydroxy group to ruthenium.
(6): Driving force of this reaction is the formation of an allylruthenium species.
(7): In the presence of -hydrogen, unsaturated ketone is formed predominantly.
(8): Formation of an allylruthenium intermediate

Palladium-Catalyzed Oxidative Alkynylation of Alkenes via C-C Bond Cleavage under Oxygen Atmosphere
Uemura et al. Org. Lett. 2003, 5, 2997.
In precedent work...
sp3-sp bond cleavage occured in preference to sp3-sp3
bond cleavageof the cyclobutane ring.
Uemura et al. J. Am. Chem. Soc. 1999, 121, 2645.

Pd(acac)2 was found to be the most effective palladium source.
DMF was the best solvent.

What is the role of pyridine?

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The effect of pyridine
Uemura oxidation
Without pyridine, only stoichiometric alcohol oxidation
is observed with concomitant formation of palladium
black.

Stahl et al. Or g. Lett. 2002, 4, 4179.

Result-hydrogen elimination

Cleavage rate
sp3-sp > sp3-sp3(cyclobutanol) > sp3-sp2, sp3-sp3

Rhodium-Catalyzed Asymmetric Rearrangement of Alkynyl Alkenyl Carbinols: Synthetic Equivalent to Asymmetric
Conjugate Alkynylation of Enones
Hayashi et al. J. Am. Chem. Soc. 2007, 129, 14158.
Steric Tuning of Silylacetylenes and Chiral Phosphine Ligands for Rhodium-Catalyzed Asymmetric Conjugated
Alkynylation of Enones
Hayashi et al. J. Am. Chem. Soc. 2008, 130, 1576.
Under one of the standard reaction conditions for the rhodium-catalyzed asymmetric addition...

Wrong reaction pathway is caused by the presence of a terminal
alkyne as a stoichiometric reagent, which is more reactive than substituted enone toward the insertion.
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New approach ~asymmetric 1,3-rearrangement~

Free terminal alkynes are minimized in the reaction media.
ResultProposed stereochemical pathway

Toward asymmetric conjugate alkynylation of enones...

Sterically bulky substituents on the silicon and phosphorus atoms
should hinder the acetylene from approaching the alkynyl-rhodium
intermediate?
(R)-DMM-binap
Me
PAr2
PAr2

Ar =OMeOMe

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Result

Streric bulkness of silicon and phosphorus part reduces
dimerization.

3.2 C-C bond activation by chelation assistance3.2.1 Milstein's chemistry (PCP system)
For an unclear demonstration and mechanistic evaluation of metal insertion into a C-C bond,it is desirable that this process would be irreversible and that the C-C activation product would
be stable and readily characterized.

MePR2
MeMe

PR2

Scematic representationof the PCP ligands
PCP ligand
Mearm: metal can chelate
PR2

Disire structure for C-C bond activation

MeMe

PR2

Strong CMe-Caryl bond (~102kcalmol-1)

Demonstration of the process Milstein et al. Nature. 1993, 364, 699.
1. CMe-Caryl bond is not weakened
relative to 1.
2. There is no distortion fromaromaticity.
rtTHF

3. To maintain a fovorable squareplaner arrangement around therhodium atom, a relatively weak Rh-Cbond is formed.
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C-C activation pathway

irreversibleProposed mechanism

In this reaction, C-C activation process isthermodynamically more favorable than theoverall C-H activation sequence.
C-C versus C-H activation ~thermodynamics~

Milstein et al. J. Am. Chem. Soc. 1995, 117, 9774.

Employment of hydrogen in the above mentioned process masks the relative thermodynamic stability of the C-H and C-C
activation product...
Direct observation of oxidative addition of a strong unactivated C-C bond to a metal is needed.
X-ray structure of 480 °C

Rh insertion into the C-C bond in this system is thermodynamicallymore favorable than insertion into the C-H bond.
Reaction 3 to 5 indicates that C-H activation is kinetically favorable
in this system.
Total stability(caluculated from bond strength) and strong Rh-arylbond is a driving force.
C-C versus C-H activation ~mechanism~

Milstein et al. J. Am. Chem. Soc. 1996, 118, 12406.

How about reaction mechanism?
Is the mechanism polar or nonpolar?
What is the role of the aromatic ring in this process?
Is it a direct process or does it require prior C-H activation followed by some rearrangement to the C-C activation product?
Experiment1: Comparison of different rhodium olefin precursors Result
1. Initially, parallel formation of the twocomplexes occured (3a:4a = ~1.25:1).

See Figure 2(next page)

2. 3a was converted into 4a withinseveral hours.
3. In NMR analysis of crude mixture, only 1a, 3a and 4a wasobserbed.
4. Ligand reactivity order: 2b>2a>>2c

Initial coordination of the diphosphine ligand to the rhodium
olefin complexes is the rate-determining step .
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Experiment2: C-C and C-H bond activation by iridium

Result1. Parallel formation of 6a and 7a, in approximate 2:1 ratio was observed.
2. In 6a, COE is coordinated to the metal(stable in benzene or THF).
3. 6a is converted into 7a and free COE at 100° C.
From experiments above...
3a and 6a are irreversibly converted into 4a and 7a.

Experiment3: Solvent and temperature effects

Iridium and rhodium insertion into the C-C bond isthermodynamically more favorable than their insertion
into the C-H bond.

ResultThe ratio between the products is constant at differenttemperatures during the reaction course and remain thesame after the reaction is complete.

C-C and C-H activation processes are kineticallycontrolled, while the constant ratio demonstrates thatthe complexes are formed in two independent
concurrent processes.

Postulated route
The temperature independence of the ratio between the C-C and C-H activation
products (iridium) and value of the ratio (~1:2)

Overall processes leadind to C-C and C-H activation proceed by very
similar pathway (via a common intermediate).
In the case of rhodium, the reaction proceedas via the intermediate Y.
Rhodium complexes bearing two bulky phosphine ligands in trans configuration
are unlikely to coordinated bulky olefin. (as some precedents show)
Both COE and ethylene rhodium dimers give the same ratio of C-C and C-H
activated products at the beginning of the reaction.
In the case of iridium, the reaction proceedas via the intermediate Y.
An excess of free COE did not affect the ratio between 6a and 7a.
Sterics in X is unfavorable for approaching the hidden C-C bond.
Unsaturated three-coordinated Ir has high reactivity in oxidative addition.

11/15C-C and C-H activation proceeds via Y, the ratio between 6a and 7a
is equal to the ratio between the rate constants.

Thermodynamics caluculation
Surprisingly, the C-C bond activation process is slightly
kinetically more favorable than C-H bond activation.
1. Specific directionality of C-C and C-H bond in the Y
2. Interaction of the metal with the -system of the aryl ring
3. Ring strain difference in the transition state (different chelating size)

Experiment4: Toward insights into transition state ~effect of ligand~
MePt-Bu2

MeMeMePt-Bu2MeO

Pt-Bu2Same reaction condition

MeMe

1a

No change in the reaction rateor in the products ratio
was observed.

Pt-Bu2

1bSmall substituent effect+Independence of solvent polarity

1a(1eq), 1b(1eq), 5(1eq)

C-C bond cleavage most probably proceeds through athree-center nonpolar transition state.
almost 1:1

3.2.2 Pyridine directed type activation
There are mainly two types.
1.
MetalNR

Futher conversion

NMOOR

Temporal directing group
2.
NO
R1N

NH2

catalystN

R2MetalN
R1R2R1NMNNH2Futher conversion
R2

See Shimizu-san's lit sem (D3)

Most of the reaction above are just fragmentation reactions...
Direct trappingNM
RNRO

Atom econoically goodOInsertion
RN
M
R'O

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Catalytic Carbon-Carbon s Bond Activation: An Intramolecular Carbon-Acylation Reaction with Acylquinolines
Douglas et al. J. Am. Chem. Soc. 2009, 131, 412.

Working hypothesis

Intramolecular trapping by alkene group
ResultPhosphine did not gave positive ffect.
In the case of BINAP, alkene isomerization took placerather than C-C activation.
Steric bulkness around metal center?
Other late-transition metals did not gave TM.
The cyclization of 7 required the addition of 10mol% ofhydroquinone to inhibit thermal polymerization of methacrylateester.
In the case of 11, -hydride elimination did not appear to be
the main problem. Rather, cleavage of the allyl ester to phenol
proved to be the dominant decomposition pathway.
In the case of 13, diminished reactivity of the phosphine freecatalysts was obtained.
1. C-C bond activation is slower because ketone is less electrophilic, owing to electron donation.
2. Anthranilic ketone coordinates to the catalyst, inhibiting C-C activation.
Total comsumption of 1 and the formation of 2 was obtained even in the presence of 13.
Chemoselectivity in Catalytic C-C and C-H Bond Activation: Controlling Intermolecular Carboacylation andHydroarylation of Alkenes
Douglas et al. J. Am. Chem. Soc. 2009, 131, 412.
How about intermolecular reaction?

No syn -hydrides

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Result

Screening

In the screening, addition of phosphine gave lower reactivity.
Alkene 13 and 15 did not undergo carboacylation.
(diol 15 cyclized)
Selectivity was compete under condition A and B (18,19).
More electron rich aryl ketones undergo C-H activation more
rapidly under condition B.

Mechanistic consideration
is simply more apt toward migratory insertion than I
when chloride is present in a nonpolar solvent.
By switching to a more polar solvent with OTf as thecounteranion, the C-C activation pathway is selcted
exclusively.

3.3 Other methods
C-CN activation[4+2] Benzannulation

Alkene, alkyne metacesis
etc...

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4. Summary
Current situation of C-C bond activation
Various types of C-C bond activation have emerged.

Recently, enantioselective reactions or tandem type reactions appear especially in the C-C bond activation ofstrained molecules.

Still, there are many hardships in this field.
1. In many cases harsh condition is needed.
2. C-H activation, -hydride elimination
3. Substrate scopes are limited in many cases.
4. Mechanism is usually unclear.
5. In some cases stoichiometric waste is produced.

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