Nucleophile-catalyzed asymmetric acylations of silyl ketene imines: Application to the enantioselective synthesis of verapamil

Angewandte Chemie - International Edition

Volumn 44, Issue 6, 2005, Pages 949-952

  Mermerian, Ara H ^a   Fu, Gregory C ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Acylation; Asymmetric synthesis; Cyanides; Homogeneous catalysis; Total synthesis

Indexed keywords

ACYLATION; DRUG PRODUCTS; NITROGEN COMPOUNDS; SYNTHESIS (CHEMICAL);

ENANTIOSELECTIVITY; NUCLEOPHILE-CATALYZED ASYMMETRIC ACYLATIONS; STEREOCENTERS;

CATALYSIS;

ACETAL DERIVATIVE; CARBONYL DERIVATIVE; CYANIDE; IMINE; KETENE DERIVATIVE; NITRILE; SILYL KETENE IMINE; TRIMETHYLSILYL DERIVATIVE; UNCLASSIFIED DRUG; VERAPAMIL;

ACYLATION; ARTICLE; ASYMMETRIC CATALYSIS; ASYMMETRIC SYNTHESIS; CHEMICAL REACTION; DRUG SYNTHESIS; ENANTIOSELECTIVITY; REACTION ANALYSIS; ROOM TEMPERATURE; STEREOCHEMISTRY;

ACYLATION; CALCIUM CHANNEL BLOCKERS; CATALYSIS; IMINES; STEREOISOMERISM; VERAPAMIL;

EID: 13744263466     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200461886     Document Type: Article

References (30)

1. As an example, the drug verapamil, which is the oldest known calcium-channel blocker, belongs to this category. For reviews of verapamil, see: a) L. M. Prisant, Heart Dis. 2001, 3, 55-62;
2. b) R. N. Brogden, P. Benfield, Drugs 1996, 51, 792-819.
3. As noted in a recent review, "only a few catalytic asymmetric C-C bond-forming reactions have been shown to be useful for constructing all-carbon quaternary stereocenters." See: C. J. Douglas, L. E. Overman, Proc. Natl. Acad. Sci. USA 2004, 101, 5363-5367.
4. For examples of catalytic asymmetric methods for the synthesis of cyano-substituted, all-carbon quaternary stereocenters, see: a) M. Sawamura, H. Hamashima, Y. Ito, J. Am. Chem. Soc. 1992, 114, 8295-8296;
5. b) M. S. Taylot, E. N. Jacobsen, J. Am. Chem. Soc. 2003, 125, 11204-11205.
6. a) For a review of cyclization reactions of nitrile anions, see : F. F. Fleming, B. C. Shook, Tetrahedron 2002, 58, 1-23;
7. 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.
8. 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.
9. For early studies of the silylation of nitrile anions, see: a) G. A. Gornowicz, R. West, J. Am. Chem. Soc. 1971, 93, 1714-1720;
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12. 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;
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16. For a few examples of total syntheses that employ such α-cyano carbonyl compounds (wherein the α 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;
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20. 2, and toluene furnish 5-10% lower ee values;
21. b) A decrease in reaction temperature results in a decrease in enantioselectivity;
22. c) After an extended reaction time, the ee value of the product is unchanged, which is consistent with irreversible C-C bond formation.
23. 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.
24. For recent discussions of acylation reactions of nitrile anions, see: a) F. F. Fleming, Z. Zhang, P. Knochel, Org. Lett. 2004, 6, 501-503;
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27. b) The Merck Index, 13th ed., Merck, Whitehouse Station, 2001, pp. 1771-1772.
28. 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.
29. 6 is employed as the solvent.
30. 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.