5196
J . Org. Chem. 1996, 61, 5196-5197
Sch em e 1
Diu r ea s a s Liga n d s in Asym m etr ic
Red u ction of Keton es
Patrick Gamez, Branko Dunjic, and Marc Lemaire*
Institut de Recherches sur la Catalyse, Universite´ Claude
Bernard Lyon I, CPE, Laboratoire de Catalyse et Synthe`se
Organique, Baˆt. 308, 43, Boulevard du 11 Novembre 1918,
69622 Villeurbanne, France
Received March 27, 1996
Although phosphines have received more attention
during the last three decades, recent papers have dem-
onstrated the usefulness of nitrogen-containing ligands
in asymmetric catalysis. Sharpless1 and J acobsen2 have
nicely illustrated the potential uses of such ligands in
C-O bond formation. More recently, Pfaltz,3 Noyori,4
Mukaiyama,5 as well as reports from our laboratory6 have
shown that nitrogen-containing ligands can be used in
asymmetric reductions with similar or even higher enan-
tioselectivities than those obtained with the best chiral
phosphines. The hydride transfer reduction of ketones
is one of the reactions where they have been used.7 We
recently reported on the successful utilization of poly-
ureas as ligands and as supports in a heterogeneous
reduction of ketones.8 On the basis of these results, we
chose to prepare and evaluate the monomeric analogs of
the polymers (i.e., diureas) with the aim of attaining
solution phase chemistry. Indeed, considering the diurea
function as an efficient ligand for hydride transfer
reduction, the possibility to associate different com-
mercially available diisocyanates with diamines allows
a rapid preparation of a great number of new ligands.
Diureas were prepared by the sequence depicted in
Scheme 1. Treatment of diamine 1 or 2 in the presence
of an isocyanate (2 equiv) in dichloromethane overnight
under argon gave diureas 3 in 80-95% yields.9
Sch em e 2
Ta ble 1. Hyd r id e Tr a n sfer Red u ction of Keton es Usin g
3a a n d 3b a s Liga n d s10
entry
R
metal L* convsn (time, d) ee,a % (confign)
1
2
3
4
5
6
a
Me
Et
Rh
Rh
Rh
Rh
Rh
Ir
3a
3a
3a
3a
3b
3a
97 (7)
87 (7)
93 (11)
100 (4)
98 (1)
43 (R)b
80 (R)b
74 (R)b
28 (S)c
37 (R)
57 (R)
(CH3)2CH
(CH3)3C
Et
Et
97 (9)
Enantiomeric excesses were determined by GC (estimated
error: (1%) on a chiral Cydex B SGE column (25m × 0.25 mm
Asymmetric reductions using 3a and 3b as ligands
were performed on a series of aromatic ketones (Scheme
2), and the results are collected in Table 1.
Entries 1-4 (Table 1) highlight the utilization of a
rhodium-ligand 3a complex as catalyst. Reduction of
acetophenone (Table 1, entry 1) led to a 43% ee of (R)-
1-phenylethanol. The best result was obtained with
b
L). Absolute configurations were determined by GC by compari-
son with the commercial optically pure products ((R)-1-phenyl-
ethanol, (R)-1-phenyl-1-propanol, (R)-2-methyl-1-phenyl-1-pro-
panol: Aldrich). c Absolute configuration of (R)-2,2-dimethyl-1-
phenyl-1-propanol was determined by polarimetry ([R]23 +30.6°
D
(c 4, acetone)).11
propiophenone (Table 1, entry 2), which was reduced in
80% ee. Except for the 2,2-dimethylpropiophenone (Table
1, entry 4), a (S,S) ligand configuration resulted in (R)-
alcohols (the hydride addition occurs by the Si face of
the ketones). This result can be explained by a bulky
tert-butyl group forcing the substrate to approach the
rhodium catalyst by its Re face (Scheme 3, A and B). The
use of ligand 3b in the reduction of propiophenone (Table
1, entry 5) showed a decrease of enantioselectivity from
80 to 37%, although better catalytic efficacy (Table 1,
entries 2 and 5) was noted. This lower enantioselectivity
may be due to a steric effect of the naphthyl group leading
to a weak complexation of rhodium. An attempt using
iridium as the metal was explored with propiophenone
(Table 1, entry 6) showing that the catalytic iridium
complex was both less active and enantioselective.
We also evaluated the diureas synthesized from di-
amines 1 and 2 and optically pure isocyanates. The use
of such diastereoisomeric ligands permitted us to study
* To whom correspondence should be addressed. Tel: (33) 72 43 14
07. Fax: (33) 72 43 14 08.
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(6) (a) Gamez, P.; Fache, F.; Mangeney, P.; Lemaire, M. Tetrahedron
Lett. 1993, 34, 6897. (b) Gamez, P.; Fache, F.; Lemaire, M. Tetrahe-
dron: Asymmetry 1995, 6, 705. (c) Gamez, P.; Dunjic, B.; Fache, F.;
Lemaire, M. Tetrahedron: Asymmetry 1995, 6, 1109.
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(9) Ur ea Syn th esis. Typical procedure is described in the support-
ing information.
(10) Hyd r id e Tr a n sfer Red u ction . Typical procedure is described
in the supporting information.
(8) Gamez, P.; Dunjic, B.; Fache, F.; Lemaire, M. J . Chem. Soc.,
Chem. Commun. 1994, 1417.
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