C O MMU N I C A T I O N S
Table 1. 10‚Cu-Catalyzed Addition of Diorganozinc to Imines
both donor groups is essential to reach high enantioselectivities.
The use of borane adduct 8 as a ligand which is ineffective in this
reaction (<10% conversion) supports this hypohesis. High conver-
sions to racemic product 24 were observed with phosphine 44 or
phosphine oxide 45. Furthermore, an equimolar mixture of 44 and
45 led to good catalytic activity, but no enantioinduction for the
addition of diethylzinc to imine 5 was observed. These observations
are consistent with the conclusion that both groups possessing differ-
ent binding properties are instrumental for high chiral induction.
In conclusion, we have shown that Me-DuPHOS monoxide is a
very effective ligand in the copper-catalyzed addition of dialkylzinc
to N-phosphinoylimines. The major advantages of this process are
high yields and enantioselectivities as well as the mild conditions
for the deprotection of the N-protecting group. The study of further
applications of bis(phosphine) monoxide ligands in asymmetric
catalysis is in progress.
a
Enantiomeric excesses were determined by HPLC on chiral stationary
b
10
phase. The ee’s in parentheses are those obtained with Me-DuPHOS (ref
c
5
(
). 2.8 mol % of Cu(OTf)2 and 3 mol % of 10 were used. d 5 mol % of
CuOTf)2‚toluene, 5 mol % of 10, and 3 equiv of Me2Zn were used (room
e
temperature, 48 h). 2.5 mol % of (CuOTf)2‚toluene, 5 mol % of 10, and
f
3
(
2
equiv of Me2Zn were used (room temperature, 48 h). 5 mol % of
Acknowledgment. This work was supported by NSERC, Merck
Frosst Canada, Boehringer Ingelheim (Canada), and the University
de Montr e´ al. A.A.B. is grateful to NSERC (PGF B) and F.C.A.R.
CuOTf)2‚toluene, 5 mol % of 10, and 2 equiv of Bu2Zn were used (0 °C,
0 h). 10 mol % of Cu(OTf)2, 5 mol % of 10, and 3 equiv of i-Pr2Zn
were used (0 °C, 16 h).
g
(
B2) for postgraduate fellowships.
addition of dialkylzinc reagents to N-phosphinoylimines is quite
general, the main limitation being the availability of the N-
phosphinoylimine precursor. In all cases tested, significant increases
in product ee’s were observed when compared to the related
MeDuPHOS-catalyzed addition (entries 1-11). The most striking
examples are the imine derived from 2-furaldehyde (entry 10) and
from cyclopropane carboxyaldehyde (entry 11), which gave the
corresponding R-chiral amine in much higher enantiomeric excess.
Furthermore, the reaction was shown to be very effective with
imines bearing 2-substituted aryl groups (entries 12-14). Several
Supporting Information Available: Experimental procedures and
data for each reaction (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
References
(
1) Reviews: (a) Enders, D.; Reinhold, U. Tetrahedron: Asymmetry 1997,
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8
Kobayashi, S.; Ishitani, H. Chem. ReV. 1999, 99, 1069-1094.:
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(
other diorganozinc reagents (Me
2 2 2
Zn, n-Bu Zn, and i-Pr Zn) were
(
(
also added with high enantiocontrol (entries 16-19).
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The reaction is also compatible with the use of functionalized
4) (a) Fujihara, H.; Nagai, K.; Tomioka, K. J. Am. Chem. Soc. 2000, 122,
8
diorganozinc reagents (eq 3). It is usually preferable to use copper-
1
2055-12056. (b) Nagai, K.; Fujihara, H.; Kuriyama, M.; Yamada, K.;
(I) triflate when valuable dialkylzinc reagents or Me
2
Zn are used.
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(
(
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3
1
5
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1399-1402.
(
7) Only a few chiral BPMO ligands have been reported thus far: (a) Marshall,
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The rivastigmine precursor 43 is readily available in 88% yield
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precursor. The enantiomeric excess of the product could be
increased to 99% after a single recrystallization (67% yield). A
simple deprotection/methylation/carbamoylation sequence led to
rivastigmine in high overall yield.9
(
58, 417-731.
(9) Amstutz, R.; Enz, A.; Marzi, M.; Boelsterli, J.; Walkinshaw, M. HelV.
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(
The bidentate ligand 10 containing a hemilabile ligand behaves
in a unique manner in this reaction, and the cooperative effect of
JA038291+
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