rhodium-catalyzed double intramolecular hydrosilylation
of olefins to prepare axially chiral spirosilanes,6 iridium-
catalyzed SiꢀH insertion with diazo compounds to
prepare triorganosilanes,7 palladium-catalyzed desym-
metrization of alkyne-tethered silacyclobutanes to give
tetraorganosilacycles,8 and palladium-catalyzed intra-
molecular CꢀH bond arylation of prochiral 2-(diarylsilyl)
aryl triflates to produce silicon-stereogenic dibenzosiloles.9
As a continuation of our research program toward
expansion of the catalytic asymmetric methods for
creating chiral silicon stereocenters, here we describe
a palladium-catalyzed intermolecular desymmetriza-
tion of silacyclobutanes with electron-deficient alkynes
to give silicon-stereogenic 1-sila-2-cyclohexenes with
high enantioselectivity.
Table 1. Palladium-Catalyzed Desymmetrization of Silacyclo-
butane 1a with Alkyne 2a: Ligand Effect
As we recently reported,8 alkyne-tethered silacyclobu-
tanes undergo enantioselective desymmetrization at 30 °C
in the presence of a palladium catalyst coordinated with
chiral phosphoramidite ligand (S,S,S)-L1 to give silacycles
possessing a tetraorganosilicon stereocenter in high yield
and ee (eq 1). When we applied these conditions to an
intermolecular reaction of 1-(4-methoxyphenyl)-1-methyl-
silacyclobutane (1a)10 with dimethyl acetylenedicarboxyl-
ate (2a), a nonasymmetric variant of which was first
reported by Sakurai and Imai in 1975,11ꢀ13 the corre-
sponding silicon-stereogenic 1-sila-2-cyclohexene 3aa
was obtained in 94% yield with 90% ee as shown in
Table 1, entry 1.8 In comparison, ligand (S,S,S)-L214 with
the 1,10-binaphthyl backbone instead of 5,50,6,60,7,70,8,
80-octahydro-1,10-binaphthyl was also similarly effective,
giving 3aa in high yield but with a somewhat lower ee
(86% ee; entry 2). On the other hand, the use of (S,S,S)-
L315 having no methyl groups at the 3,30-positions or
(S,R,R)-L4, a diastereomeric ligand to (S,S,S)-L1, gave
3aa with significantly lower enantioselectivity along with
substantial formation of ring-opened byproduct 4aa
(entries 3 and 4).12
ratio of
yield of
ee of
entry
ligand
3aa/4aaa
3aa (%)b
3aa (%)c
1
2
3
4
(S,S,S)-L1
(S,S,S)-L2
(S,S,S)-L3
(S,R,R)-L4
99/1
98/2
88/12
95/5
94
87
75
87
90
86
23
67
a Determined by 1H NMR. b Isolated yield. c Determined by chiral
HPLC on a Chiralpak AS-H column with hexane/2-propanol = 100/1.
We subsequently found that a slightly improved result
can be achieved by using 5.5 mol % of (S,S,S)-L1 at 10 °C
for this intermolecular reaction of 1a with 2a (95% yield,
92% ee; Table 2, entry 1).16 Under these conditions, several
other electron-deficient alkynes can also be employed in
the reaction with silacyclobutane 1a to give the corre-
sponding 1-sila-2-cyclohexenes 3 with good to high enan-
tioselectivity (77ꢀ91% ee; entries 2ꢀ5).17 It is worth
noting that the use of unsymmetrical alkynes such as 2d
and 2e gives products 3 as single regioisomers (entries 4
and 5).18 With regard to the substituent on the silicon
atom of the silacyclobutane, various 1-alkyl-1-(hetero)
arylsilacyclobutanes are well tolerated for the reaction
with alkyne 2a, giving 1-sila-2-cyclohexenes 3 with uni-
formly high yield and enantioselectivity (89ꢀ97% yield,
(8) Shintani, R.; Moriya, K.; Hayashi, T. J. Am. Chem. Soc. 2011,
133, 16440.
(9) Shintani, R.; Otomo, H.; Ota, K.; Hayashi, T. J. Am. Chem. Soc.
2012, 134, 7305.
(10) 1a can be readily prepared from commercially available 1,1-
dichlorosilacyclobutane by successive treatment with 4-methoxyphenyl-
magnesium bromide and methylmagnesium iodide. See Supporting
Information for details.
(11) Sakurai, H.; Imai, T. Chem. Lett. 1975, 8, 891.
(12) The same reaction was also reported by Oshima and Utimoto:
Takeyama, Y.; Nozaki, K.; Matsumoto, K.; Oshima, K.; Utimoto, K.
Bull. Chem. Soc. Jpn. 1991, 64, 1461.
(13) For other examples of transition-metal-catalyzed synthetic
reactions using silacyclobutanes, see:(a) Tanaka, Y.; Yamashita, H.;
Tanaka, M. Organometallics 1996, 15, 1524. (b) Chauhan, B. P. S.;
Tanaka, Y.; Yamashita, H.; Tanaka, M. Chem. Commun. 1996, 1207.
(c) Tanaka, Y.; Nishigaki, A.; Kimura, Y.; Yamashita, M. Appl. Organo-
metal. Chem. 2001, 15, 667. (d) Tanaka, Y.; Yamashita, M. Appl.
Organometal. Chem. 2002, 16, 51. (e) Hirano, K.; Yorimitsu, H.;
Oshima, K. Org. Lett. 2006, 8, 483. (f) Hirano, K.; Yorimitsu, H.;
Oshima, K. J. Am. Chem. Soc. 2007, 129, 6094. (g) Hirano, K.;
Yorimitsu, H.; Oshima, K. Org. Lett. 2008, 10, 2199. See also:
(h) Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999, 121, 5821.
(i) Denmark, S. E.; Wu, Z. Org. Lett. 1999, 1, 1495. (j) Denmark, S. E.;
Wang, Z. Synthesis 2000, 999.
(16) The reaction at 0 °C results in a slightly lower yield (89% yield)
with the same enantioselectivity (92% ee).
(17) Less electron-deficient alkynes such as phenylacetylene and
diphenylacetylene are not suitable substrates under the current reaction
conditions.
(14) (a) Rimkus, A.; Sewald, N. Org. Lett. 2003, 5, 79. (b) Watanabe,
€
T.; Knopfel, T. F.; Carreira, E. M. Org. Lett. 2003, 5, 4557.
(15) Shintani, R.; Park, S.; Duan, W.-L.; Hayashi, T. Angew. Chem.,
(18) For these reactions, the lower yield is mostly due to the incom-
plete conversion of 1a.
Int. Ed. 2007, 46, 5901.
Org. Lett., Vol. 14, No. 11, 2012
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