sation product (eq 1); reactions occurred at -78 °C, and 1,2-
addition was competitive with 1,4-addition. In view of this,
Scheme 1
a Mukaiyama-Michael reaction between 1 and R,â-unsatur-
ated carbonyl compounds using catalytic amounts of Lewis
acid under milder conditions would be desirable. Herein, we
report that highly functionalized diazo compounds (6 and
8) can be prepared by an efficient Lewis acid catalyzed
Mukaiyama-Michael reaction between 1 and enones 5
(Scheme 2) under mild conditions with low catalyst loading
reactions proceeded to form 3 in high yield without
decomposition of the diazo group. Their success is due, at
least in part, to the stability of the vinyldiazonium ion
intermediate (4) that is formed by electrophilic addition to
1. However, the low Lewis acidity of scandium(III) triflate
required relatively long reaction times and limited application
to aldehydes with strong electron-withdrawing groups.
The Mukaiyama-Michael reaction, the condensation
between enolsilanes and R,â-unsaturated carbonyl com-
pounds,11 is a suitable extension of the Mukaiyama-aldol
reaction. Reactions mediated by stoichiometric amounts of
strong Lewis acid catalysts have been reported,12 and the
use of various lanthanides and other Lewis acids as catalysts
has been extensively studied.13,14 In the only report of a
Mukaiyama-Michael reaction to form diazoacetoacetates,8c
TiCl4 is used in stoichiometric amounts to form the conden-
Scheme 2
(8) (a) Calter, M. A.; Sugathapala, P. M.; Zhu, C. Tetrahedron Lett. 1997,
38, 3837-3840. (b) Calter, M. A.; Zhu, C. J. Org. Chem. 1999, 64, 1415-
1419. (c) Deng, G.; Tian, X.; Qu, Z.; Wang, J. Angew. Chem., Int. Ed.
2002, 41, 2773-2776.
of inexpensive zinc triflate. As in previous examples of
Mukaiyama-Michael reactions with enolsilanes, silyl group
transfer across seven atoms was considered to be a major
challenge.
(9) Davies, H. M. L.; Ahmed, G.; Churchill, M. R. J. Am. Chem. Soc.
1996, 118, 10774-10780.
(10) Doyle, M. P.; Kundu, K.; Russell, A. E. Org. Lett. 2005, 7, 5171-
5174.
(11) Narasaki, K.; Soai, K.; Mukaiyama, T. Chem. Lett. 1974, 1223-
1224.
In catalyst screening with cyclohexenone, we found that
scandium(III) triflate, the previously preferred catalyst for
Mukaiyama-aldol reactions of 1,10 was relatively ineffective
for the Michael reaction with the same nucleophile. Thus,
reaction of 1 with 1.1 equiv of cyclohexenone in the presence
of 3.0 mol % Sc(OTf)3 gave the Mukaiyama-Michael
reaction product (6a) in only 43% isolated yield after
subsequent hydrolysis (entry 1, Table 1). The low yield was
determined to be caused by slow reaction as unreacted
cyclohexenone and hydrolyzed silyl enol ether from 1 were
also isolated. Lanthanum(III) triflate increased the yield
slightly to 50%; however, the reaction was not significantly
faster (entry 2). The use of boron trifluoride-etherate8b under
the same conditions resulted in decomposition of 6a (entry
3).
(12) For representative examples, see: (a) Heathcock, C. H.; Norman,
M. H.; Uehling, D. E. J. Am. Chem. Soc. 1985, 107, 2797-2799. (b) Sato,
T.; Wakahara, Y.; Otera, J.; Nozai, H.; Fukuzumi, S. J. Am. Chem. Soc.
1991, 113, 4028-4030. (c) Fujita, Y.; Fukuzumi, S.; Otera, J. Tetrahedron
Lett. 1997, 38, 2117-2120. (d) Sankararaman, S.; Sudha, R. J. Org. Chem.
1999, 64, 2155-2157. (e) Bellassoued, M.; Mouelhi, S.; Fromentin, P.;
Gonzalez, A. J. Organomet. Chem. 2005, 690, 2172-2179.
(13) For representative examples of Mukaiyama-Michael reactions using
catalytic amounts of Lewis acids, see: (a) Matsuda, I.; Makino, T.;
Hasegawa, Y.; Itoh, K. Tetrahedron Lett. 2000, 41, 1409-1412. (b) Miura,
K.; Nakagawa, T.; Hosomi, A. Synlett 2003, 2068-2070. (c) Jaber, N.;
Assie, M.; Fiaud, J.; Collin, J. Tetrahedron 2004, 60, 3075-3083. (d) An,
D. L.; Peng, Z.; Orita, A.; Kurita, A.; Man-e, S.; Ohkubo, K.; Li, X.;
Fukuzumi, S.; Otera, J. Chem. Eur. J. 2006, 12, 1642-1647. (e) Suga, H.;
Takemoto, H.; Kakehi, A. Heterocycles 2007, 71, 361-371. (f) Attanasi,
O. A.; Favi, G.; Filippone, P.; Lillini, S.; Mantellini, F.; Spinelli, D.; Stenta,
M. AdV. Synth. Catal. 2007, 349, 907-915.
(14) For representative examples of asymmetric Mukaiyama-Michael
reactions using Lewis acid catalysts, see: (a) Evans, D. A.; Rovis, T.;
Kozlowski, M.; Dowey, C. W.; Tedrow, J. S. J. Am. Chem. Soc. 2000,
122, 9134-9142. (b) Evans, D. A.; Scheidt, K. A.; Johnston, J. N.; Willis,
M. C. J. Am. Chem. Soc. 2001, 123, 4480-4491. (c) Desimoni, G.; Faita,
G.; Filippone, S.; Mella, M.; Zampori, M.; Zema, M. Tetrahedron 2001,
57, 10203-10212. (d) Sibi, M. P.; Chen, J. Org. Lett. 2002, 4, 2933-
2936. (e) Wang, X.; Adachi, S.; Iwai, H.; Takatsuki, H.; Fujita, K.; Kubo,
M.; Oku, A.; Harada, T. J. Org. Chem. 2003, 68, 10046-10057. (f) Suga,
H.; Kitamura, T.; Kakehi, A.; Baba, T. Chem. Commum. 2004, 1414-1415.
(g) Harada, T.; Adachi, S.; Wang, X. Org. Lett. 2004, 6, 4877-4879. (j)
Ishihara, K.; Fushimi, M. Org. Lett. 2006, 8, 1921-1924. (h) Takenaka,
N.; Abell, J. P.; Yamamoto, H. J. Am. Chem. Soc. 2007, 129, 742-743.
In related studies of the Cu(II)-catalyzed Mukaiyama-
aldol reactions, silylation of the metal aldolate (silyl transfer)
had been proposed to be the rate-limiting step.15a Further-
more, Ellis and Bosnich concluded that a Lewis acid having
(15) (a) Evans, D. A.; Murry, J. A.; Kozlowski, M. C. J. Am. Chem.
Soc. 1996, 118, 5814-5815. (b) Ellis, W. W.; Bosnich, B. Chem. Commun.
1998, 193-194.
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