2320
M. Ge, E. J. Corey / Tetrahedron Letters 47 (2006) 2319–2321
O
O
O
–78 o
C
H
Me
N2
Me
Me
1. LiN(SiMe3)2;
Et3SiH
0.65 mol %
CO2
Et3Si
then
CF3CO2Et
2
3, 94% ee
2. TsN3,
Et3N, CH3CN
Rh2
N
H
4
SO2
n-C4F9
4
Scheme 1. Enantioselective synthesis of 6-(S)-triethylsilyl-2-methyl-2-cyclohexenone (3) by catalytic hydrosilylation of a-diazoketone 2.
see Ref. 5b). Slow addition of the a,b-enone 2 to a
solution of 2.6 equiv of triethylsilane and the catalyst,
O
O
H
H
Me
R3Si
N-nonafluorobutanesulfonylproline (Nf-proline)–Rh(II)
complex (4, Nf-proline4 Rh2, 0.65 mol %) in CH2Cl2 at
ꢀ78 °C gave (+)-(S)-6-triethylsilyl-2-methyl-2-cyclohex-
enone 3 in 70% yield and 94% ee (for experimental
details see Ref. 6). In a similar way the dextrorotatory
tert-butyldimethylsilyl analog of 3 was synthesized in
80% ee. The absolute configuration of this product
was determined to be S by hydrogenation (1 atm H2,
R3Si
R3 = Et3, 83% ee,
OR +75
R3 = Et3, 77% ee,
OR +170
R3 = t-BuMe2, 86% ee,
OR +71
R3 = t-BuMe2, 80% ee,
OR +181
Pd–C, MeOH) to 2-tert-butyldimethylsilylcyclohexa-
O
23
none, ½aꢁD +150 (c 0.45, CHCl3) by comparison with
H
the known levorotatory R-enantiomer.2b
Et3Si
We studied a number of different Rh(II) N-sulfonylated
proline salts to determine the optimal group on nitro-
gen. Mesitylsulfonyl-, pentafluorobenzenesulfonyl-, tri-
fluoromethanesulfonyl, and 4-tert-butylbenzenesulfonyl
all proved inferior to the N-nonaflyl catalyst 4 with
regard to enantioselectivity. With regard to the silane
component, triethylsilyl was optimum with regard to
yield and enantioselectivity with tert-butyldimethylsilyl
a close second. Trimethylsilane worked well but the
volatility of the product resulted in lower yields. Triphen-
ylsilane and phenyldimethylsilane gave distinctly lower
yields of product and also somewhat lower enantio-
selectivities. At higher reaction temperatures enantio-
selectivities were lower, as might have been anticipated.
However, the yields of product were also lower. At
23 °C, for example, the reaction of 2, Et3SiH, and cata-
lyst 4 gave 3 in 28% yield and 69% ee. Changing solvent
from CH2Cl2 to pentane increases the enantioselectivity
of the reaction 2!3, but decreases the yield. Thus, we
regard the conditions shown in Scheme 1 as close to
optimal.
90% ee
With a serviceable method for the enantioselective
synthesis of 6-triethylsilyl-2-methyl-2-cyclohexenone (3)
we next evaluated this compound as a dienophile in
Lewis acid-catalyzed Diels–Alder reactions. Measure-
ments of infrared absorption using an internal IR probe
(REACT-IR) in CH2Cl2 solution at ꢀ78 °C showed that
the carbonyl stretching frequency of 3 at 1632 cmꢀ1 was
replaced by an absorption band at 1546 cmꢀ1 when
1 equiv of MeAlCl2 was added. Despite this indication
of complexation there was very little reaction of the
complex with 1,3-cyclopentadiene at ꢀ78 °C over the
course of a few hours. Although this result is some-
what surprising since cyclopentadiene is one of the most
reactive dienes, and methylaluminum dichloride is one
of the most powerful catalytic Lewis acids, it can be
understood as a consequence of the powerful electron-
donating effect of the triethylsilyl group into the Lewis
acid–carbonyl complex, as indicated below. It should
be noted that there is a considerable measure of elec-
tron donation from the a-triethylsilyl group into the
carbonyl group of 3 even without Lewis acid com-
plexation, as is clear from the carbonyl stretching
frequencies of 3 (1653 cmꢀ1) and 2-methyl-2-cyclohexe-
none (1676 cmꢀ1) (D 23 cmꢀ1). Since the strong electron
donation by the triethylsilyl substituent diminishes the
electrophilicity of C(b) of the a,b-enone, it can be
expected to reduce Diels–Alder reactivity with a p-
electron-rich diene such as cyclopentadiene. The Diels–
Alder reaction did proceed to the extent of 50% conver-
sion with MeAlCl2 in CH2Cl2 at ꢀ20 °C after 12 h.
Although the endo–exo selectivity was good (17:1), the
facial selectivity for addition to the a,b-double bond of
A number of other examples of enantioselective hydro-
silylation of a0-diazo-a,b-enones using the catalyst 4
were studied leading to the following results. The optical
rotations (OR) shown are at 23 °C for c = 1 in CHCl3.
The enantioselectivities were determined by HPLC anal-
ysis using chiral columns (Whelk 01, Chiralcel OD, or
Chiralcel OJ). The absolute configurations of the a0-
silylated-a,b-enones obtained by the use of catalyst 4
are based on the good enantioselectivity in each
case, the analogy with 3 whose absolute configuration
has been established, and the observation of strong
dextrorotation in each case, which also leads to the
stereochemistry shown by application of the octant
rule.