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Highly enantioselective mukaiyama aldol reaction of alpha,alpha-dichloro ketene silyl acetal: an efficient synthesis of a key intermediate for diltiazem.
J Org Chem. 2003 Feb 07; 68(3):974-9.JO

Abstract

An efficient synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (-)-2, a key intermediate for diltiazem (1), has been developed on the basis of the highly enantioselective Mukaiyama aldol reaction of p-anisaldehyde (4a) with alpha,alpha-dichloro ketene silyl acetal 5. Thus, the reaction using a stoichiometric amount of chiral oxazaborolidinone catalyst 12a proceeded to excellent yield (83%) and high enantioselectivity (96% ee), together with the chiral ligand 13a in nearly quantitative recovery. The reaction using a substoichiometric amount of 12e (20 mol %) also proceeded to excellent yield (88%), with somewhat lower enantioselectivity (77% ee). The aldol product 3a thus obtained was easily converted to (-)-2 in excellent yield (80%) and high optical purity (>99% ee). The highly enantioselective Mukaiyama aldol reaction with 5 catalyzed by 12a proved to be applicable to various aldehydes. An efficient preparation of 5 from inexpensive starting materials was also described.

Authors+Show Affiliations

Imashiro R
CMC Research Laboratory, Tanabe Seiyaku Co., Ltd., 3-16-89 Kashima, Yodogawa-ku, Osaka 532-8505, Japan.
Kuroda T
No affiliation info available

MeSH

CatalysisCombinatorial Chemistry TechniquesDiltiazemEpoxy CompoundsMagnetic Resonance SpectroscopyMolecular StructurePropionatesSilanesStereoisomerism

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12558423

Citation

Imashiro, Ritsuo, and Tooru Kuroda. "Highly Enantioselective Mukaiyama Aldol Reaction of Alpha,alpha-dichloro Ketene Silyl Acetal: an Efficient Synthesis of a Key Intermediate for Diltiazem." The Journal of Organic Chemistry, vol. 68, no. 3, 2003, pp. 974-9.
Imashiro R, Kuroda T. Highly enantioselective mukaiyama aldol reaction of alpha,alpha-dichloro ketene silyl acetal: an efficient synthesis of a key intermediate for diltiazem. J Org Chem. 2003;68(3):974-9.
Imashiro, R., & Kuroda, T. (2003). Highly enantioselective mukaiyama aldol reaction of alpha,alpha-dichloro ketene silyl acetal: an efficient synthesis of a key intermediate for diltiazem. The Journal of Organic Chemistry, 68(3), 974-9.
Imashiro R, Kuroda T. Highly Enantioselective Mukaiyama Aldol Reaction of Alpha,alpha-dichloro Ketene Silyl Acetal: an Efficient Synthesis of a Key Intermediate for Diltiazem. J Org Chem. 2003 Feb 7;68(3):974-9. PubMed PMID: 12558423.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Highly enantioselective mukaiyama aldol reaction of alpha,alpha-dichloro ketene silyl acetal: an efficient synthesis of a key intermediate for diltiazem. AU - Imashiro,Ritsuo, AU - Kuroda,Tooru, PY - 2003/2/1/pubmed PY - 2003/8/13/medline PY - 2003/2/1/entrez SP - 974 EP - 9 JF - The Journal of organic chemistry JO - J Org Chem VL - 68 IS - 3 N2 - An efficient synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (-)-2, a key intermediate for diltiazem (1), has been developed on the basis of the highly enantioselective Mukaiyama aldol reaction of p-anisaldehyde (4a) with alpha,alpha-dichloro ketene silyl acetal 5. Thus, the reaction using a stoichiometric amount of chiral oxazaborolidinone catalyst 12a proceeded to excellent yield (83%) and high enantioselectivity (96% ee), together with the chiral ligand 13a in nearly quantitative recovery. The reaction using a substoichiometric amount of 12e (20 mol %) also proceeded to excellent yield (88%), with somewhat lower enantioselectivity (77% ee). The aldol product 3a thus obtained was easily converted to (-)-2 in excellent yield (80%) and high optical purity (>99% ee). The highly enantioselective Mukaiyama aldol reaction with 5 catalyzed by 12a proved to be applicable to various aldehydes. An efficient preparation of 5 from inexpensive starting materials was also described. SN - 0022-3263 UR - https://www.unboundmedicine.com/medline/citation/12558423/Highly_enantioselective_mukaiyama_aldol_reaction_of_alphaalpha_dichloro_ketene_silyl_acetal:_an_efficient_synthesis_of_a_key_intermediate_for_diltiazem_ DB - PRIME DP - Unbound Medicine ER -