Communications
a) M. Sawamura, H. Hamashima, Y. Ito, J. Am. Chem. Soc. 1992,
114, 8295 – 8296; b) M. S. Taylor, E. N. Jacobsen, J. Am. Chem.
Soc. 2003, 125, 11204 – 11205.
[4] a) For a review of cyclization reactions of nitrile anions, see: F. F.
Fleming, B. C. Shook, Tetrahedron 2002, 58, 1 – 23; b) For a
recent example of a catalytic asymmetric acylation process that
involves a nitrile anion intermediate, see: D. A. Nicewicz, C. M.
Yates, J. S. Johnson, Angew. Chem. 2004, 116, 2706 – 2709;
Angew. Chem. Int. Ed. 2004, 43, 2652 – 2655.
[5] For early studies of the silylation of nitrile anions, see: a) G. A.
Gornowicz, R. West, J. Am. Chem. Soc. 1971, 93, 1714 – 1720;
b) D. S. Watt, Synth. Commun. 1974, 4, 127 – 132.
[6] A. H. Mermerian, G. C. Fu, J. Am. Chem. Soc. 2003, 125, 4050 –
4051.
[7] We are aware of very few studies of reactions of silyl ketene
imines with electrophiles. See: a) P. Cazeau, J.-P. Llonch, F.
Simonin-Dabescat, E. Frainnet, J. Organomet. Chem. 1976, 105,
145 – 156; b) P. Cazeau, J.-P. Llonch, F. Simonin-Dabescat, E.
Frainnet, J. Organomet. Chem. 1976, 105, 157 – 160; c) S. Meier,
E.-U. Wꢀrthwein, Chem. Ber. 1990, 123, 2339 – 2347.
[8] For leading references, see: G. C. Fu, Acc. Chem. Res. 2004, 37,
542 – 547.
[9] For a few examples of total syntheses that employ such a-cyano
carbonyl compounds (wherein the a position is an all-carbon
quaternary stereocenter) as intermediates, see: a) F. E. Ziegler,
C. A. Metcalf III, A. Nangia, G. Schulte, J. Am. Chem. Soc. 1993,
115, 2581 – 2589; b) D. G. Batt, N. Takamura, B. Ganem, J. Am.
Chem. Soc. 1984, 106, 3353 – 3354; c) R. V. Stevens, F. C. A.
Gaeta, D. S. Lawrence, J. Am. Chem. Soc. 1983, 105, 7713 – 7719;
d) R. M. Coates, S. K. Shah, R. W. Mason, J. Am. Chem. Soc.
1982, 104, 2198 – 2208.
[10] Notes: a) Solvents such as Et2O, CH2Cl2, and toluene furnish 5–
10% lower ee values; b) A decrease in reaction temperature
results in a decrease in enantioselectivity; c) After an extended
reaction time, the ee value of the product is unchanged, which is
À
consistent with irreversible C C bond formation.
[11] If both substituents on the silyl ketene imine are alkyl groups, no
acylation is observed under our standard conditions. We believe
that the key reactive intermediate in processes catalyzed by 3 is a
nitrile anion (intermediate 2 in Scheme 1), the formation of
which is facilitated by the presence of an anion-stabilizing
aromatic substituent on the silyl ketene imine.
[12] For recent discussions of acylation reactions of nitrile anions,
see: a) F. F. Fleming, Z. Zhang, P. Knochel, Org. Lett. 2004, 6,
501 – 503; b) A. R. Katritzky, A. A. A. Abdel-Fattah, M. Wang,
J. Org. Chem. 2003, 68, 4932 – 4934.
[13] a) J. A. Longstreth in Clinical Pharmacology, Dekker, New
York, 1993, pp. 315 – 336; b) The Merck Index, 13th ed., Merck,
Whitehouse Station, 2001, pp. 1771 – 1772.
[14] For leading references regarding the synthesis of nonracemic
verapamil, see: R. M. Bannister, M. H. Brookes, G. R. Evans,
R. B. Katz, N. D. Tyrrell, Org. Process Res. Dev. 2000, 4, 467 –
472.
[15] Use of C6F6 rather than 1,2-dichloroethane as the solvent leads
to improved enantioselectivity. This solvent effect on ee values
appears to be general. For example, for the reaction illustrated in
entry 1 of Table 2, the product is generated in 90% ee when C6F6
is employed as the solvent.
[16] Brunner reported a method that furnishes a precursor to
verapamil in up to 11% ee: H. Brunner, H. Zintl, Monatsh.
Chem. 1991, 122, 841 – 848.
952
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Angew. Chem. Int. Ed. 2005, 44, 949 –952