(c) C. V. Galliford and K. A. Scheidt, J. Org. Chem., 2007, 72,
1811–1813.
3 For selected reviews, see: (a) D. F. Taber, in Comprehensive
Organic Synthesis, ed. G. Pattenden, Pergamon Press,
Oxford, 1991, vol. 3; (b) H. M. L. Davies, Curr. Org. Chem.,
1998, 2, 463–488; (c) M. P. Doyle and D. C. Forbes, Chem. Rev.,
1998, 98, 911–935; (d) M. P. Doyle, M. A. McKervey and
T. Ye, Modern Catalytic Methods for Organic Synthesis with Diazo
Compounds: From Cyclopropanes to Ylides, Wiley, New York,
1998.
4 (a) C. R. Holmquist and E. J. Roskamp, J. Org. Chem., 1989, 54,
3258–3260; (b) C. R. Holmquist and E. J. Roskamp, Tetrahedron
Lett., 1992, 33, 1131–1134.
5 A. Padwa, S. F. Hornbuckle, Z. Zhang and L. Zhi, J. Org. Chem.,
1990, 55, 5297–5299.
ð1Þ
ð2Þ
Further evidence for a b-silyloxy allenolate generated in this
process is obtained when silyl enol ether 17 was treated with
LDA and then exposed to MeI (eqn (2)), with compound 8
isolated as the product. Additionally, when we employ cinam-
myl diazoacetate 2c in the reaction, smooth conversion to the
b-ketoester 7 is obtained in 95% yield with no products
resulting from a possible carbenoid intermediate (Table 1,
entry 5).
6 (a) Y. H. Zhao, Z. H. Ma, X. M. Zhang, Y. P. Zou, X. L. Jin and J.
B. Wang, Angew. Chem., Int. Ed., 2004, 43, 5977–5980; (b) D.
Uraguchi, K. Sorimachi and M. Terada, J. Am. Chem. Soc., 2005,
127, 9360–9361; (c) T. Hashimoto and K. Maruoka, J. Am. Chem.
Soc., 2007, 129, 10054–10055.
7 (a) L. Casarrubios, J. A. Perez, M. Brookhart and J. L. Templeton,
J. Org. Chem., 1996, 61, 8358–8359; (b) H.-J. Ha, K.-H. Kang, J.-
M. Suh and Y.-G. Ahn, Tetrahedron Lett., 1996, 37, 7069–7070; (c)
K. G. Rasmussen and K. A. Jørgenson, J. Chem. Soc., Perkin
Trans. 1, 1997, 1287–1292; (d) S. Nagayama and S. Kobayashi,
Chem. Lett., 1998, 27, 685–686; (e) J. C. Antilla and W. D. Wulff,
J. Am. Chem. Soc., 1999, 121, 5099–5010; (f) J. C. Antilla and W.
D. Wulff, Angew. Chem., Int. Ed., 2000, 39, 4518–4521.
8 (a) W. G. Yao and J. B. Wang, Org. Lett., 2003, 5, 1527–1530; (b)
S. Arai, K. Hasegawa and A. Nishida, Tetrahedron Lett., 2004, 45,
1023–1026.
9 (a) A. E. Mattson, A. R. Bharadwaj and K. A. Scheidt, J. Am.
Chem. Soc., 2004, 126, 2314–2315; (b) A. E. Mattson, A. R.
Bharadwaj, A. M. Zuhl and K. A. Scheidt, J. Org. Chem., 2006,
71, 5715–5724; (c) R. B. Lettan II, T. E. Reynolds, C. V. Galliford
and K. A. Scheidt, J. Am. Chem. Soc., 2006, 128, 15566–15567; (d)
T. E. Reynolds, A. R. Bharadwaj and K. A. Scheidt, J. Am. Chem.
Soc., 2006, 128, 15382–15383; (e) T. E. Reynolds, C. Stern and K.
A. Scheidt, Org. Lett., 2007, 7, 2581–2584; (f) T. E. Reynolds and
K. A. Scheidt, Angew. Chem., Int. Ed., 2007, 46, 7806–7809; (g) R.
B. Lettan, II, C. C. Woodward and K. A. Scheidt, Angew. Chem.,
Int. Ed., 2008, 120, 2326–2329.
The combination of lithiated diazo esters and acylsilanes
provides a new and general way to access a useful and
unprecedented dianion equivalent. This straightforward com-
bination is presumed to generate a b-silyloxy allenolate inter-
mediate by a 1,2-Brook rearrangement followed by loss of
nitrogen gas. The addition of two electrophiles, either simul-
taneously or sequentially, results in a multicomponent synth-
esis of substituted b-keto esters. The dual anion aspects of this
process are unique and have potential for the efficient synthesis
of highly functionalized 1,3-carbonyl compounds. The combi-
nation of reactive nucleophiles and acylsilanes continues to
provide innovative routes to atypical nucleophiles which
facilitate the synthesis of target molecules by unconventional
means.
10 A. G. Brook, Acc. Chem. Res., 1974, 7, 77–84.
11 For reviews of acylsilane chemistry, see: (a) A. Ricci and A.
Degl’Innocenti, Synthesis, 1989, 647–660; (b) P. F. Cirillo and J.
S. Panek, Org. Prep. Proced. Int., 1992, 24, 553–582.
12 For early examples, see: (a) D. Hoppe, Angew. Chem., Int. Ed.
Engl., 1970, 9, 300–306; (b) E. Wenkert, J. Am. Chem. Soc., 1972,
94, 8084–8090.
13 (a) N. F. Woolsey and M. H. Khalil, J. Org. Chem., 1972, 37,
2405–2408; (b) R. Pellicciari and B. Natalini, J. Chem. Soc., Perkin
Trans. 1, 1977, 1822–1824; (c) R. Pellicciari, B. Natalini, B. M.
Sadeghpour, M. Marinozzi, J. P. Snyder, B. L. Williamson, J. T.
Kuethe and A. Padwa, J. Am. Chem. Soc., 1996, 118, 1–12; (d) D.
F. Taber, R. J. Herr and D. M. Gleave, J. Org. Chem., 1997, 62,
194–198.
Support has been provided in part by the NSF (CHE-
0348979), the PRF (Type G) and the Elizabeth Tuckerman
Foundation (fellowship to C. V. G.). We thank Abbott
Laboratories, Amgen, AstraZeneca, GlaxoSmithKline and
Boehringer-Ingelheim for generous research support and
Wacker Chemical Corp. and FMCLithium for reagent sup-
port. Funding for the NU Integrated Molecular Structure
Education and Research Center (IMSERC) has been furn-
ished in part by the NSF (CHE-9871268). K. A. S. is an Alfred
P. Sloan fellow.
14 (a) C. J. Moody and C. N. Morfitt, Synthesis, 1998, 1039–1042; (b)
F. Sarabia and F. J. Lopez-Herrera, Tetrahedron Lett., 2001, 42,
8801–8804.
Notes and references
15 (a) J. F. Arnett and H. Walborsky, J. Org. Chem., 1972, 37, 3678;
(b) N. A. Petasis and K. A. Teets, J. Am. Chem. Soc., 1992, 114,
10328–10334.
1 (a) G. Dyker, Angew. Chem., Int. Ed. Engl., 1997, 36, 1700–1702;
(b) I. Ugi, Pure Appl. Chem., 2001, 73, 187–191, and references
cited therein; (c) W. H. Moser, Tetrahedron, 2001, 57, 2065–2084;
(d) Multicomponent Reactions, ed. J. Zhu and H. Bienayme, Wiley-
VCH, Weinheim, 2005.
2 (a) C. V. Galliford, M. A. Beenen, S. T. Nguyen and K. A. Scheidt,
Org. Lett., 2003, 5, 3487–3490; (b) C. V. Galliford, J. S. Marten-
son, C. Stern and K. A. Scheidt, Chem. Commun., 2007, 631–633;
16 2,2-Dimethyl-4-methylene-1,3-dioxolane has been used as a pre-
cursor to an a-vinyl enolate, see: (a) M. A. Tius, D. P. Astrab and
X. Q. Gu, J. Org. Chem., 1987, 52, 2625–2627; (b) M. A. Tius and
H. Hu, Tetrahedron Lett., 1998, 39, 5937–5940.
17 See ESIw for details.
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