.
Angewandte
Communications
DOI: 10.1002/anie.201303423
Asymmetric Catalysis
Enantioselective Isomerization of Primary Allylic Alcohols into Chiral
Aldehydes with the tol-binap/dbapen/Ruthenium(II) Catalyst**
Noriyoshi Arai, Keisuke Sato, Keita Azuma, and Takeshi Ohkuma*
Asymmetric isomerization of primary allylic alcohols is
a direct and simple transformation to afford optically active
aldehydes (Scheme 1).[1] In the presence of an appropriate
chiral catalyst, one of the a hydrogens of a prochiral allylic
alcohol 1 is formally transposed to the g position (1,3-
workers reported that the Ir complexes with chiral phos-
phane–oxazoline ligands activated by addition of H2, cata-
lyzed the transformation of E-configured aryl-substituted
alcohols 1 with large alkyl groups (R = aryl, R’ = secondary or
tertiary alkyl) at an S/C of 20 at 238C to give products 2 with
> 98% ee.[4,5] However, the Z isomers and aliphatic substrates
reacted with moderate enantioselectivity. Andersson and co-
workers modified the chiral ligand of this catalyst; the use of
this modified catalyst resulted in high enantioselectivity for
the reactions of the Z substrates.[6] However, the insufficient
catalytic activity and limited substrate scope remain as
unsolved problems. Recently, Sowa and co-workers reported
asymmetric reduction of primary allylic alcohols 1 to satu-
rated alcohols 3 through the tandem process of asymmetric
isomerization of 1 into the aldehydes 2 with a subsequent
transfer hydrogenation of 2 catalyzed by the {RuCl2(cod)}n–
tol-binap system or [RuCl(p-cymene)(tol-binap)]Cl in a basic
solution of 2-propanol at 83–1008C with an S/C of 10–33.[7,8]
Geraniol derivatives were reduced with high enantioselectiv-
ity, but this process could not selectively give the chiral
aldehydes 2 as products because the RuH species, formed
in situ, catalyzed both isomerization and reduction.[9,10]
We have studied the asymmetric hydrogenation of aryl
vinyl ketones to the chiral allylic alcohols catalyzed by the
[RuCl2(tol-binap)(dmapen)]–tC4H9OK system in 2-propa-
nol.[11–13] The corresponding saturated ketone was obtained
in a small amount as a by-product through isomerization
(achiral in this case) of the allylic alcohol. This finding
prompted us to investigate asymmetric isomerization of
primary allylic alcohols into the chiral aldehydes with the
tol-binap/1,2-diamine/RuII catalysts.
We primarily focused on the influence of the structure of
diamine, the second ligand, on the reactivity and enantiose-
lectivity of the isomerization. The use of 2-dibutylamino-1-
phenylethylamine (dbapen), gave an excellent result in the
isomerization of (E)-4-methyl-3-phenyl-2-penten-1-ol (1a;
Table 1). Thus, the reaction of 1a (3 mmol) in the presence
of (SP,RN)-4a (3 mmol, S/C = 1000) and KOH (15 mmol) in
ethanol at 258C for 1 h afforded the R aldehyde 2a in 90%
yield with > 99% ee and a small amount of the saturated
alcohol 3a with > 99% ee (Table 1, entry 1). The aldehyde
product 2a was oxidized, and converted into the ethyl ester in
ethanol in < 2%.[14] Owing to the significantly high catalytic
activity a turnover number (TON) of about 1550 in 1 h was
achieved without loss of enantioselectivity in the reaction
with an S/C of 2000 (Table 1, entry 2). To our knowledge, this
is the highest TON and also TOF (TON hꢀ1) for the
asymmetric isomerization of primary allylic alcohols with
a trisubstituted alkene moiety. Ethanol was the best solvent;
the use of 2-propanol, methanol, or tert-butyl alcohol resulted
Scheme 1. Reaction pathway in the enantioselective isomerization of
primary allylic alcohols.
ꢀ
hydrogen shift) with migration of the C C double bond to
give the chiral enol intermediate. The following keto–enol
tautomerism produces the desired aldehyde 2 with a stereo-
genic center at the b position. Undesired reduction of 2 to
afford the saturated alcohol 3 is a significant problem under
reductive conditions. High reactivity (resulting in low catalyst
loading), enantioselectivity, and chemoselectivity are major
requirements to achieve an efficient isomerization, leading to
highly productive environmentally benign reaction.
Studies on this asymmetric reaction with Rh catalysts
bearing planar chiral phospha ferrocene ligands were
reported by Fu and co-workers.[2,3] The isomerization of
1 (R = C6H5, R’ = iC3H7) with a substrate-to-catalyst molar
ratio (S/C) of 100 in THF at 1008C for 67 h gave the aldehyde
2 in 94% yield and 90% ee.[2] A range of E- and Z-configured
aryl-substituted alcohols 1 (R or R’ = aryl group) and a non-
aromatic substrate 1 (R = cyclohexyl, R’ = CH3) were reacted
with an S/C of 20 to afford 2 with 57–92% ee. Mazet and co-
[*] Prof. Dr. N. Arai, K. Sato, K. Azuma, Prof. Dr. T. Ohkuma
Division of Chemical Process Engineering and Frontier Chemistry
Center, Faculty of Engineering, Hokkaido University
Sapporo, Hokkaido 060-8628 (Japan)
E-mail: ohkuma@eng.hokudai.ac.jp
[**] This work was supported by a Grant-in-Aid from the Japan Society
for the Promotion of Science (JSPS) (No. 24350042) and by a MEXT
(Japan) program, “Strategic Molecular and Materials Chemistry
through Innovative Coupling Reactions,” of Hokkaido University.
dbapen=2-dibutylamino-1-phenylethylamine, tol-binap=2,2’-
bis(di-4-tolylphosphanyl)-1,1’-binaphthyl.
Supporting information for this article is available on the WWW
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ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 7500 –7504