40
Chemistry Letters Vol.38, No.1 (2009)
Cobalt-catalyzed Oxidative Kinetic Resolution of Secondary Benzylic Alcohols
with Molecular Oxygen
Tohru Yamada,Ã Sho Higano, Takanori Yano, and Yoshihiro Yamashita
Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, Yokohama 223-8522
(Received October 14, 2008; CL-080980; E-mail: yamada@chem.keio.ac.jp)
The oxidative kinetic resolution of secondary alcohols using
2a : R = Me
molecular oxygen and olefins was catalyzed by the optically ac-
tive ketoiminatocobalt(II) complexes. The various secondary
benzylic alcohols were subjected to the aerobic oxidative reac-
tion to afford optically active alcohols of high ee along with
the corresponding ketones in high yield. The oxidation of the
deuterated alcohols revealed that the accompanying olefin medi-
ated the oxidation for conversion to the corresponding ꢀ-deuter-
ated ketones.
2b : R = Mesityl
3a : R = OEt
N
N
O
R
O
N
N
O
R
O
3b : R = OcHex
3c : R = O-2-Adamantyl
Co
Co
O
O
1
Figure 1. Optically active cobalt(II) complexes.
Cat.
RO
O
N
N
O
OR
O
OH
O
OH
Co
O
Molecular oxygen is an abundant and ubiquitous oxidant on
the earth as well as a clean, safe, and easily handled oxidant
compared to peroxides or heavy-metal oxidants, although stereo-
selective oxidation by molecular oxygen remains one of the most
challenging research targets because of its high radical-like reac-
tivity and consequent side reactions. Much effort has been per-
formed to develop reliable complex catalysts containing various
transition metals that would provide efficient and stereoselective
aerobic oxidation systems.1 For example, the oxidative kinetic
resolution of racemic alcohols with molecular oxygen2 was re-
ported to establish one of the most efficient methods to obtain
enantiomerically enriched secondary alcohols.3 Two catalyst
systems using palladium(II) complexes4,5 were independently
reported. The (nitroso)(salen)ruthenium(II)6 complexes have
been developed to perform the highly selective oxidative kinetic
resolution of the allyl and 2-propynyl alcohols using molecular
oxygen as the oxidant. Very recently, it was reported that a
ruthenium or iridium complex with a chiral bifunctional amido
ligand effectively catalyzed the aerobic oxidative kinetic resolu-
tion of benzylic secondary alcohols.7
It has been noted that Schiff-base cobalt(II) complexes can
capture and activate molecular oxygen,8 and various aerobic ox-
idation reactions have been examined in the presence of these
cobalt complexes.9 By using the bis(1,3-diketonato)cobalt(II)
complexes as catalysts, various alkenes were converted into
the corresponding alcohols with molecular oxygen in a secon-
dary alcohol solvent (oxidation–reduction hydration).10 The
catalytic enantioselective version was reported, but the highest
enantioselectivity reached 38% ee using the optically active
salen–cobalt(II) complex catalyst.11 During the course of our
continuous studies on the catalytic enantioselective versions,12
we found out that the oxidative kinetic resolution of racemic
secondary alcohols with the combined use of molecular oxygen
and olefinic compounds was catalyzed by the optically active
ketoiminatocobalt(II) complexes to afford the corresponding
secondary alcohols in high optical purity, while the olefinic com-
pounds were employed as the oxygen acceptor to be converted
into the corresponding ketones.
+
O2(1 atm)
-BuOH, 50 o
t
C
(R)-4a
O
4a
Ph
0.65 equiv.
Ph
Scheme 1. Oxidative kinetic resolution of secondary alcohol.
of 5 mol % of various cobalt(II) complexes (Figure 1) and 0.65
equivalent of styrene under atmospheric pressure of oxygen at
50 ꢀC (Scheme 1). The oxidation reaction proceeded to afford
the corresponding ketone along with the unreacted alcohol. Ma-
terial balance of this reaction (ketone plus the recovered alcohol)
is almost quantitative. The selectivity was evaluated by the krel
value13 calculated from the yield14 and the optical purity15 of
the recovered alcohol. As shown in Table 1, although the
salen–cobalt(II) complex 1 did not catalyze the reaction at all,
the ketoiminatocobalt(II) complexes smoothly converted the 1-
(2-naphthyl)ethanol into the corresponding ketone with kinetic
resolution. The cobalt(II) complexes with the acyl side chain
2a and 2b afforded the optically active alcohol in 60% and
45% yields with 45% ee and 44% ee, and the krel values were cal-
culated to be 7.6 and 3.2, respectively (Entries 2 and 3). The ke-
toiminatocobalt(II) complex possessing an ester side chain 3a
Table 1. Examination of various catalysts and olefinsa
Entry Catalyst
Olefin
styrene
Yield/%b ee/%c krel
1d
No reaction
1
2d
60
45
43
52
43
45
33
39
76
23
45
44
70
60
96
86
83
96
19
97
7.6
3.2
6.7
8.8
2a
3d
2b
4d
3a
5d
3b
6
7
8
22.3
14.6
10.2
16.1
4.6
X = CF
X = F
X = Cl
3
X
9
10e
11e
1-butene
isobutene
6.3
aThe reaction was carried out in 1.5 mL of t-BuOH using 10 mol % CoII com-
plex, 0.25 mmol substrate, and 0.65 equiv of olefin at 50 ꢀC under atmospheric
O2 pressure. bRecoverd alcohol; determined by GC using naphthalene as the
internal standard. cDetermined by HPLC using Chiralpak IA. d5 mol % CoII
complex was employed in m-xylene solvent. eUnder the mixed gas of O2 and
olefin.
A racemic mixture of 1-(2-naphthyl)ethanol (4a) was
subjected to oxidative kinetic resolution (OKR) in the presence
Copyright Ó 2009 The Chemical Society of Japan
Yamada, Tohru
