Isomerization of allylic alcohol and its relevant reactions

Gree R. et al Chem. Rev. 2003, 103, 27-51

Mazet C. et al Chem. Lett. 2011, 40, 341 344

1. introduction
2. isomerization reaction
2.1 Rh complexes
2.2 Ru complexes
2.3 Ir complexes
2.4 other metal complexes
3. assymetric isomerization of allyl alcohol
4. relevant reaction af ter isomerization
5. summary

1
1
1
3
7
7
8
10
13

May 10, 2011
Luqing Lin

Isomerization of allylic alcohol and its relevant reactions
1 Introduction
1.2. Mechanism of isomerization of allylic alcohol

1.1 isomerization of allylic alcohol
R3
R1

OH
R2

a: Metal-hydride addition-elimination

R3

M

R1
R2

R4

b: -allyl-metal-hydride mechanismOc: Alcoholate species mechanism

R4

One pot internal redox reaction to synthesize carbonyl compounds.

Cristina G., et al Organometallics 2010,29, 2166-2175

2 Isomerization Reactions
2.1 Rh complexes
RhCl3. 3H2O

RhH(CO)(PPh3)
3

Scheme 1

Scheme 2
RhH(CO)(PPh3)3 0.6 mol %H

H

CF3CH2OH, 70 oC, 3 hyield 100%

OH

RhCl3 . 3H2O

H

O

OH

O

RhCl3 . 3H2O 2mol%OH

Wietrich, M. et al. J. Or ganomet. Chem. 1975, 86, C17HsolventO.

benzene/water
RhCl3 or Rh2(SO4)3 + TPPTS(tri(m-sulfophenyl)phosphane)

when solvent is dioxane, the yield is 30% (accompanied decarbonylation).
Better result was obtained under biphasic conditionin the presence of onium salts; complete conversion of
1-octen-3-ol to 3-octanone only need 2 mol % RhCl3 3H2O

Scheme 3
R3
R2

R4
R1

R3

catalyst

R2

OH

R4
R1

Blum, J. et al J. Mol. Cat. 1981, 11, 293

O[Rh(CO)2Cl]2

1. Biphasic(n-heptane/water) Catalysts.
2. no substitution on C-2 of allylic alcohol was inverstigatedExcept for geraniol, that gave citronellal in 44% yield,
most of other reactions were quantitative.
3. This catalyst can be recycled for several times,
using 1-hexane-3-ol as model
4. As extend carbon chain, reactivity decrease due tosolubility of allylic alcohol

Scheme 4
R1[Rh(CO)2Cl]2

R4

NaOH, CH2Cl2, BnEt3Cl
rt,6-10h

OH

R1

R4
O

[Rh(CO)2OH]2 was postulated to be the true active species
Alper. H.; Hachem, K. J. Org. Chem. 1980, 45, 2269

Kuntz, E. G. C. R. Acad. Sci. Pair, IIc, Chem. 2000, 3, 607[Rh(diphosphine)Ln]ClO4]
Tripenyl phosphite derived ligands

Table 1

Ziolkowski J. et al Gazz. Chim. Ital. 1994, 124, 403(Sulphos)Rh(cod)
R3
R4

R2
R1

OH

(Sulphos)Rh(cod)Cl2CH2CH2Cl
H2O/octane 100oC

R3
R2

R4
R1

O

[Rh(diphosphine)Ln]ClO4]
An efficent catalysts for transposition of allyl alcohol, even for thechallenging examples(two alkyl groups in terminal position and 2cycohexen-1-ol), also giving excellent conversion yield.

Scope was limited to no more than two substitutions
on olefin of allylic alcohol
Bianchini, C,; Oberhauser, W. New J. Chem. 2001, 25, 11.

Tani. K. Pure & Appl. Chem. 1985, 57, 1845.

1[Rh(diphosphine)Ln]ClO4]
Table 2

Table 3The nature of ligand has strong effect on kinetic of the reaction.
[Rh(Cyphos)]+ catalysted reaction is quite rapid even at -80 oC

NC

CN

H

NC

CN

H

N

Tos-N=C=O

I

OH

OH

O

NC CN O
NC

N

H

O
Tos

H

CN

OH

D

H

D

OH

D D

O

N
H

O
Postulated mechanism of formation of enol from allylic alcohol

D

D

Equal deuterium distribution between the 1- and 3-position
implied the reaction of formation of enol is irreversible.

Deuterated substrate decrease reaction speed.
Turnover limiting step is not sure, but suggested
by author, maybe is initial hydrogen obstractionD
OD [Rh(cyphos)]++O

OD [Rh(cyphos)]H
Exclusive product

Ph
OH

Ph

[Rh(-)binap)]+[Rh(-)binap)]+

Ph
O

OH

-oxyallyl mechanism for catalytic
ketonization of enols

H
18% eeBergens, S.; Bosnich, B. J. Am. Chem. Soc. 1990, 113. 958
Rh hydride catalysts (RhH(PPh3)3, RhH(PPh3)4)
RhH(PPh3)3 could be prepared easily and used in situ.
RhH(PPh3)3 also could be used for isomerization of highly
sterically hindered derivatives
RhH(PPh3)4 could be used for primary and sencondary alcohol,
but is sensitivie to oxygen and moisture

R3
R2

R4
R1

OH

Rh(NBD)2BF4
L1
H2 then degssed

R3
R2

R4
R1

O

P
L1

Table 4
Entry

R1

R2

R3

R4

solvent

temp.

time

Conv.

Selectivity(%)

1
2
3
4
5
6
7
8
9
10

H
H
H
H
H
H
H
Propyl
Me
H

H
H
H
Ph
Me
Propyl
Butyl
H
Me
Ph

H
H
Ph
H
H
H
H
H
H
Me

Me
Ph
Me
H
Me
H
Me
H
H
Me

CH2Cl2
DioxaneDioxaneDioxane
CH2Cl2CH2Cl2
dioxane
CH2Cl2CH2Cl2
dioxane

23
60
60
60
23
23
60
23
23
60

0.5
1
1
3.5
0.5
0.5
1
0.5
16
2

100
100
100
100
100
100
100
100
100
100

100
93
100
100
100
98
97
100
90
100

Rh(L1)[H]nBF4 could isomerize momosubstituted,disubstituted, trisubstitued allylic alcohol.
Manfred T. R.; Honhchao Guo letter 2006, 2127
Metal hydride addition-elimination mechanism maybe be suitable for Rh-H catalystic reaction.

2

R3
R2

R4

Rh(cod)(CH3CN)2BF4(2 mol %)PTA(4 mol%)
H2O, rt
PH 4~11

R1

OH

Entry

R1

R2

1
2
3
4
5
6
7
8
9
10
11
12

H
H
H
H
H
H
H
H
H
H
H
H

H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
Me
H
H
Me
-(CH2)3 - HbenzylH

Table 5

R4
R1

R4

R3

R3
R2
O

time/minPh5
p-F-Ph15
p-MeO-Ph15
naph60
p-CF3-Ph15
Et
80
phenylethylene 180
Me
80
Ph
5
Ph
5
connecting to R2 720
H
45

yield
1, 3-hydride migration

>99
99
>99
>99
>99
>99
92
>99
>99
>99
>99
>59

Entry 8, 9, 10 Temp. is, 50oC, 50oC, 80oC respectivly.

intramolecular reaction

Proposed mechanisem
Martin-Matute, et al. Gr een Chemistry 2010, 12, 1628-1633
2.2 Rhthenium complexes
RuCl3, RuCl3-NaOH
RuCl3 can be employed for isomerizationof various allylic alcohol and glycols.
RuCl3-NaOH can be used for chirality transfer.

37~41%

J. Or ganomet. Chem. 1975, 86, C17
J. Chem. Soc., Chem. Commun., 1980, 594-595
Pascal, J.-Y. et al J. Mol. Catal. 1980, 9, 59

Ru(acac)3

Ru3O(OCOCH3)7 & RuCl2(PPh3)3
R4

catalyst

R4

85oC or 140oC

OH

O

it is only operative for isomerization allyl alcohol
wihout substituted group on double bondRu3O(OCOCH3)7 can be recycled for several times

E. Drent, et al Inorg.Chim. Acta 1994, 222, 225-233

OH
D D

1

OH
1eq

Ru(II)2 eq

Ru(H2O)6(tos)2

Even In the presence of butadiene, the process
could performed (R3=H).
transformation of butadiene to ketone.

Blum, J. et al J. Mol. Cat 1979, 6, 289
Blum, J. et al J.Or g. Chem 1981, 46, 255

Ru(H2O)6(tos)2 or Ru(H2O)6(tirf)2

Scope is limited to less hindered allylic alcoholDHO

Ru(H2O)6(tos)2

H

Ru(IV)-HOH

D

D2O, rtH2O(0.34%)

Ru(II)

Ru(IV)-H

Possibility for generating Ru-H

2OH

D2O, rtDO

D
OH Ru(H2O)6(tos)2

3

D D

D

D

D2O, rtO

Ru(H2O)6(tos)2H

intermolecular reaction
OH

4

D

D2O, rtO
1, 2 step is irreversible

OH

5

D D

Ru(H2O)6(tos)2D

H2O, rtDO
1, 3-hydride migration

6

D

OH Ru(H2O)6(tos)2
H2O, rtH

D

O D
no oberserved

Modified metal-hydride addition-elimination mechanism
Exclusive Markovnikov addition

McGrath, D. V.; Grubbs. R. H. Or ganpmetallics 1994, 13, 224

3

CpRu(PPh3)2Cl

Chemoselectivity

OH

O

8

8

OH O

OH OH

Table 18

8

Remote double bond migrate slowly compared to that of allyl alcohol
Indenyl-ruthenium complex is better thancyclopentadiene-ruthenium complex

.

Ph3P

.

Ru Cl

Ph3P

PPh3

Ru Cl
PPh3

it is easier to open coordinated site of indenyl
complex than Cp complex. So indenyl complex
has higher reactivity.
Increase the reactivity of catalyst complex by using
AgOTf instead of Et3NHPF6 due to Ag+ is easy tosequesting chloride anion. But it has lewis acid charater
often leading to nucleophilic addition by solvent.
Deuterium labeling experiments

OH
Ph

O

Catalyst

Ph

D

O

OH
sterically hindered allylic alcohol andsix memerbered allyl alcohol did not react

Ph

Ph
D
OH

CatalystO

geraniolO

1,3 hydride migration and itramolecular reaction

H3CO2C

H3CO2C

O

OH

OH

D

9

9

OH

D

O

Cat.

O

O

O

NH4PF6O
detectable

OH

O
9

9

Proposed mechanism
detectable

RuCl2(PPh3)3[RuCl2(p-cymene)]2

Efficent catalysts for isomerization of allyl
alcohol in presence of base such as K2CO3
Bimetallic catalyst which itself can serve
as a base led to a rapid reaction without
adding base.

excellent yield was in case of 7, 8 ring allyl alcohol.
lowe yield was obtained in case of 6 ring allyl alcohol.
Backvall, J.-E.; Andreasson, U. T etrahedr on Lett. 1993, 34, 5459
Ruthenium hydride complex
RuClH(PPh3)3
Those Ruthenium complexes can be generated
RuClH(PPh3)3
in situ.Only used for isomerization of less
RuClMe(PPh3)3
hindered secondary allyl alcohol.
RuClPh(PPh3)3
Primary allyl alcohol did not react in theRuH2(PPh3)3
presence of catalyst.
RhMe2(PPh3)3
RuPh2(PPh3)3
RuH2(PnBu3)4 Sasson, Y.; Rempel, G. L. Tetr ahedron Lett. 1974, 47, 4133
Uma, R.; Gre ´e,R. et al. Eur . J. Or g. Chem. 2001, 3141

Trost, B. M.; Kuliawec, R. J. J. Am. Chem. Soc. 1993, 115, 2027
RuCp(PR3)(CH3CN)[PF6]This catalyst was easy to form 16+ cationic ruthenium species
compared to the CpRu(PPh3)2Cl.
i.
But it was operative for allyl alcohols of whichless one substituted group on 1 and 3 position.
Slugovc, C.;Kirchner, K. et al Or ganometallics 1999, 18, 4230
HRu3(CO)11-K+
O(CO)4Ru

Ru(CO)3
H
Ru(CO)3

limited in scope to simple, sterically less hindered allylic alcohols
Langenbahn, M.;Suss-Fink, G. et al J. Organomet. Chem. 1989, 379, 165

4

Catalyst 1 can be using for isomerizationof most of secondary alcohols except
disubstituted group at the terminal carbon
of double bond.
it seems not to isomerize the pramary alcohol.

Grubb's catalyst

it is very interesting that catalyst 2 couldhydrogenate aldehyde to aldohol.

Though only unsubstituted allyiic alcohol have been tested,ester and ether funtionalities are compatible in this condition.

IPA was added as hydrogen source and solvent.

O

Gurjar, M. K.; Yakambram, P. Tetrahedr on Lett. 2001, 42, 3633
Hoye, T. R.; Zhao, H. Or g. Lett. 1999, 1, 1123

ROH

2: KOBut=1:25

H

IPA(0.5M)

R

H

Lau C. P. et al Adv. Synth. Catal. 2011, 353, 275 – 280
Pr4NRuO4
Table 4
5b
R3
R2

R4
R1

4a or 5b
THF, 60oC

OH

R

R

R3
R2

H

R4
R1

OH O

O

R4=H, R2=Me or H
R1=R2=H, R=Me or H

it is promising to isomerize the challenging allylic alcohol

No base was added.
it is interesting that some aldol type product was observed.
Substrate scope was wide.
It was able to isomerize secondary alcoholand primary alcohol (including cyclohex-2-enol)

Proposed mechanism
Marko, I. E. et al Angew. Chem., Int. Ed. 1999,38, 1960.

Cristina G., et al Or ganometallics 2010,29, 2166-2175
R1

OH 3 or 4, AgOTf
R2

R1

THF or H2O
55 or 75 oC

O
OH

R2

R1

yield(60-99%)

O

1 or 2
H2O/ 100oC, 2h

R1

R2=H, or Et, or nPr, or n Bu

R1=H, R2=H, or CH3, or Et, or nPr, or n Bu
R2=CH3, R1=CH3

Recycability was high.
Water soluble catalyst
no base was need.

no base was need.
Water soluble catalyst
limited to less hindered allyl alcohol

Peris E. et al Organometallics, 2010. 29, 3661-3664.

Costa, A. P. Peris E. et al Organometallics, 2010. 29, 1832-1838.

reactivity
Me
Me

Me

Bu
Ru

N
N

Cl
Cl

Me

R2
R1
OH

Cat. 1 bar H2
aq phosphatebuffer, 80 oC

high

R2

0.2 M(NaCl)
PH=7

R1
O

low

OH

R2=H, R1=H, CH3, Et, nPr, nBu, nPentyl
R1=H, R1=CH3

R1

1mol % 2aO

5 mol % KOtBu, H2O

R1
R1= n-Pent, Ph, 4-ClC6H4, 4-BrC6H4, 4-Me2NlC6H4, 4-MeOC6H4

Joo, F. et al Catalysis Communications 2006, 7. 783–786

Scope of substrate is limited to momosubstituted on C1.
Crochet P. et al Green Chem., 2009, 11, 1681–1686
Me
Me

Me
Ru

(EtO)3PCl

1cThose catalysts are effecient for isomerization simple,
less hindered allyl alcohol in water
Joo, F. et al J. Or ganometallic Chem. 2008, 693 468–474

Clyield >97%
Noteworthy, trisubstituted substrate
are readily converted at 35oC, forexample R1= Ph, R2=Me, R3=Ph

Crochet P. et alOr ganometallics 2006, 25, 4846 4849

6

Table 2

2 X = Cl R = Ph
3a X = Cl R = Me
14 X = H R = Ph

Was 5 ruthenium hydride intermediates acitive species ?
2. Involve ruthenium alkoxide for the reaction or not ?
Table 3

ee% of 4a decreased as readtion time increased.
Reversible 1,2 addition takes place, which was reason of slow
isomerization of primary alcoho (aldehyde was more elctrophilic species).

Mechanism of isomerization of allyl alcohol byruthenium cyclopentadienyl complexes,
Martin-Matute, B. et al Chem. Eur. J. 2005, 11, 5832 – 5842
5

Catalyst could isomerizes momosubstituted on
double bond of allyl alcohol to aldehyde, but fails toisomerization in the presence of conjugated diene.
An efficent catalyst in organic or aqueous media
was able to recycle for three times at least.

water-soluble catalyst
recycling at 8 times at least

Cadierno V. et al Chem. Commun., 2004, 232–233.
Cadierno V. et al Dalton Tr ans., 2004,3635–3641

Extend the substrate scope to disubstituted
at the terminal of double bond and cycloallyl
alcohol.Entry 13, at 90oC 3-methyl-butyraldehyde
could be obtained at 89% yield.

Catalyst remained active in presence of diene
for example isoprene.
3-oxo-allyl mechanism was proposed.

Cadierno V. et al JACS., 2006, 1360–1370

2.3 Iridium complexes[(cod)Ir(PMePh2)2][PF6](10mol %) IrCl3 4H2O

H

CF3OOH, 70 oC
yield 100%

OH

Table 1HO

J. Organomet. Chem. 1975, 86, C17

R1

R1(0.25 10 mol %), THF

R2

OH
R3

1 min H2degassed, 23oC

R2

O
R3

An efficent catalyst for isomerization of primary allyl
alcohol in mild condition with almost quantitative yield

High yield was obtained for less hindered allyl alcohol compareed todisubstituted on the olefin and trisubstituted derivatives.
Similar catalysts: [(cod)Ir(PPh2)2][ClO4] and [(cod)Ir(PhCN)(PPh3)][ClO4]Felkin, H et al. Nouv. J. Chim. 1978, 2, 355

Mazet C. et al Chimia 2009, 63,35–37

2.4 Other metal complexes
Cobalt complexes: HCo(CO)4Iron complexes
Fe(CO)5, Fe2(CO)9 & Fe3(CO)12

palladium complexes
Pd(OH)2/C, H2 pre-actived
Gowravaram Sabitha* et al Or g. Lett., 2011, 13 (3), pp 382–385
n-Bu4NBr + PdCl2 or Pd(OAc)2
Ganchegui B. et al. J. Mol. Cat. A: Chem. 2004, 214, 65–69

Disubstitutent and trisubstitutent on olefine of allyl
alcohol can be isomerized to ketone or aldehyde.
primary allylic alcohol without a-substitutent give low yeild.
It appears to be due to aldolizaiton
Gree, R. et al T etrahedron 2001, 57,2379.

7

3 Asymmetr ic isomerization of allylic alcohol[Rh((ligand)(cod)]+CF3SO3-[Rh((R)-BINAP)(cod)]+ClO41%(R)-BINAP-Rh
NEt2

THF, 60oC, 24h

NEt2
97% yield, 92% ee

Rh+ Cat.

GeraniolOH

O

Rh+ Cat.

Nerol

O

5 give best result: 88% yield, 60%ee for Geraniol
90% yield, 51%ee for Nerol

Compared to asymmetric isomerization of allyl amine, asymmetricisomerization of allylic alcohol was far away from success.
Tani, K. Pur e & Appl. Chem. 1985, 57, 1845

OH

Changing perchlorate to triflate, ee increased ,but not satisfied.
C. Chapuis, M. Barthe, J.-Y. de Saint Laumer, Helv. Chim. Acta 2001, 84, 230

G. Fu's catalyst.
Table 2

Table 1

cationic planar chiral phosphaferrocene-rhodium complexes
Catalyst 1 performed well only for Z-configuration.
Catalyst 2 is more general and displayed acitivities
for E and Z isomers.
Satisfactory isomerization yield and enantioselectivity
was obtained for most substrated surveyed.
Labeling and crossover experiment was investegated,verifiying 1,3 migration of hydrogen and intramolecular
reaction mechanism
Aromatic ring group seems to be requried for the allyl
alcohol. Only one with aliphatic disubstituted groups
on the terminal of the double was investigated.

Reaction needs to preform in high temperature more thanboiling point of solvernt(typically at 100-150oC)
Reactivity is not high enough, even in such forcing conditions, the reaction
time ranged from 24-28 hs, with yield varying from 60-90%
G. Fu et al JACS 2000, 122, 9870-9871
G. Fu et al JOC 2001, 66, 8177-8186

Crevisy C. et al Tetrahedr on letters 2006, 47, 5021-5024
Compared to Fu's catalyst, no improment in activity, selectivity, scope was achieved.
8

C. Mazet's work

R1

R1

(0.25 10 mol % [Ir]), THF

R2R2

1 min H2degassed, 23oC

OH
R3

O
R3

An efficent catalyst for isomerization of allylic alcohol
Table 3
Performing reaction at room temperature
Accessible to get high yield for Z/E isomers of substrates
Wide range from monosubstituted to Tetrasubstituted olefin
Mazet C. et al T etrahedron Letters 2009, 50, 4141–4144

Highly active and selective iridium catalysts
for the asymmetric isomerization of primaryalcohol were developed.

First generation ligand

As R1 alkyl substituent become small, a decrease
was observed in conv. yield and enantioselectivity(entry 8-17)
Z-configuration primary allyl alcohol did notprovide satisfatory results.(entry 21-22)
Acompanied isomerization of the allylic alcohol double
was observed for Z-configuration (entry 10, 21)

Mazet C. et al Angew. Chem. Int. Ed. 2009, 48, 5143 –5147
Table 4

They dispaly similar reactivity and selectivity with fisrt
generation catalysts.
This second generation of catalysts is available
from dialkylphosphine precursors and inexpensive
L- or D- Serine.
This second generation outperformed first
generation catalyst in isomerization of 3,3-dialkyl
primary allyl alcohol.
Second generation ligand

Low conversions and enatioselectivites along with
substantial competing(E/Z) isomerization for Z-primary
allyl alcohol still existed.
Mazet C. et al Chem. Commun., 2010, 46, 445–447

note: 1a = 6j
Table 5
Aromatic primary allyl alcohol with small alkyl
groups(entry 5, 6) were isomerized in modest
yields but with a significant improvement of theenantioselectivity value.
Electron-rich aromatic ring of substrate had abeneficial impact both on the activity and theenantioselectivity.
or tho position was barely tolerated in term ofcatalyst activity.(entry 10)

Third generation ligand

Some challenging substrate for example Geraniol
also give modest yield and satisfactory result.
Z-configuration primary alcohols are remainchallenging problem.
R1

R1

7.5 mol% 3i

R2

OH
5a-d

H2, then degassed
THF, 35oC, 22hO

6a60%, 70%ee

R2

O
6a-d
O
7.5 mol% 3i

6bE/Z isomerization
was detected

43%, 87% ee

5fOH

H2, then degassed
THF, 35oC, 22hO

6f26%, 31% ee

O
O
6c

6d

96%, 86% ee

49%, 82% ee

Mazet C. et al Chem. Eur . J. 2010, 16, 12736 – 12745
9Though those catalysts was efficent for isomerization of
disbustituted at terminal double bond of primary allylic
alcohol, not operative for tetrasubstituted or 2,3-disubstituted primary allylic alcohol.
Homoallylic alcohol and secondary allylic alcohols
were not isomerized
Scope of substrate was limited to the E-configuration
For Z-configuration of primary allylic alcohols were
not obtained satisfactory result.
i

Mechanism for the isomerization of primary allylic alcohols using iridium catalysts
Secondary allylic alcohols

Rh[(S)-binap(cod)]ClO4

Catalyst 7 was used for kinetic resolution. R enantiomer was obtained in
91% ee and 27% yield.
Noyori R. et al Tetr ahedron Letters,1987, 28,4 4719-4720,

n=1, R=H, yield =100% 43.3% ee
n=1, R=TES, yield= 86% 98% ee
Ogasawara K. Angew. Chem. Int. Ed. 1995, 34, 2287 –2288

Though the ee% was low, phosphoramidite ligand was developed.
It will beneficial to generate new catalyst analogus to 9
Pascale Crochet et al Dalton Trans., 2010, 39, 7780–7785
OHO

Z, 62%ee
E, 66%ee

Ikariya T. et al J. Am. Chem. Soc. 2005, 127, 6172

4 Relevant reaction af ter isomerizationisomerization-aldolizaiton reaction

1.(bda)Fe(CO)3 show higher activity than Fe(CO)5 (table 1)2.(COT)Fe(CO)3 gives better result than Fe(CO)5 for thebulky aldehyde but is inefficient in the case of allylic
alcohols(table 3 entry i and j)
3. (CHD)Fe(CO)3 is less reactive than Fe(CO)5Gree R. et al Tetrahedr on Letter s 2003, 44, 6187–6190

10

Three mechanism were proposed by Gree R.

Mechanism A : First, formaldehyde coordinate to the iron atom of [(enol)Fe(CO)3] complex 7,
second, formation of key C-C bond for the aldolization process occurs at alater stage.
Mechanism B: Formaldehyde was attacked directly by the enol of [(enol)Fe(CO)3] complex 7.
Mechanism C: Formaldehyde reacts with free enol 2 after enol decoordination from complex 7

Key step: an efficent transfer from enol
proton transfer from enol to aldehyde

Mechanism C is highly favored.
Carbonyl-ene-type reaction was suggested

Gree R. et al Chem. Eur. J. 2004, 10, 5795 – 5803

Gree R. et al Chem. Eur . J. 2006, 12, 3261–3274
11

(5 mol %)Rh(cod)Cl dimer(2.5 mol%)

R2

HO
R1
yield 64~97%,
almost no dr
9 example

only aromatic
aldehyde substrates

H

Ar

KOtBu (7 mol %)toluene 35oC

R1=Ar or alphatic group

R1

OH

Ar
R2
yield 69~99%,
dr 1.5~5:1
10 exam5ple,

Rh(cod)Cl dimer(2.5 mol%)Rh(cod)Cl dimerO

O

yield 64~95%,
dr is low
9 example

Martin-Matute B. et al Chem. Eur. J. 2008, 14, 10547 – 10550

Sequential Ir Isomerization/ enamine catalysis

Martin-Matute B. et al Adv. Synth. Catal. 2009, 351, 2657 – 2666
Tandem Isomerization/ C-H activation

13 examples
dr=4~49:1
yield=46~94
base on 4

100~140oC
yield (64~99%)
16 examples

Martin-Matute B. et al Org. Lett., 2009, 11, 1749~1752

Mazet C. et al Angew. Chem. Int. Ed. 2011, 50, 2354 –2358
12

Summary:

1. Many different catalysts were developed for isomerization of allyl alcohol, but corresponding
Metals(for instance Rh, Ru, Ir) are very expensive. So issues concerning recycling need to beaddressed or develop some efficent first-row transition Metal catalysts.
2. As the substitutents increases, the reaction become more difficult. So far, only one catalyst
can isomerize the tetrasubstitutent of primary allylic alcohol, No catalyst is operative for the
tetrasubstitutents olefin of secondary alcohol. Lot of efficent catalysts need harsh conditions
which limit the application of them.
3. Assymetric isomerization is still a chanllenging issue, abeit efficent catalysts for assymetricisomerization of primary allylic alcohol developed by G. Fu and C. Mazet. More efficent assymetriccatalysts for isomerization of allylic alcohol at broad scope were highly required.
4. Many new tandem reactions were developed from allylic alcohol. Expecially,Tandem
isomerization/aldolization was conducted in different metals and different conditions,giving different mechanisms. So such kind reaction and mechanism need to be studied extensively.

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