Cyclic imidate salts in acyclic stereochemistry: Diastereoselective syn-epoxidation of 2-alkyl-4-enamides to epoxyamides

Reaction of 2-alkyl-4-enamides 1 with I + and aq. NaHCO 3 results in the diastereoselective formation of syn-iodohydrins 2, which are converted to the epoxides 3 with base. The reaction appears to proceed through a cyclic imidate type intermediate 4, followed by addition of water and ring opening. R...

Full description

Saved in:
Bibliographic Details
Published inTetrahedron Vol. 52; no. 9; pp. 3327 - 3338
Main Authors Maligres, P.E., Weissman, S.A., Upadhyay, V., Cianciosi, S.J., Reamer, R.A., Purick, R.M., Sager, J., Rossen, K., Eng, K.K., Askin, D., Volante, R.P., Reider, P.J.
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier Ltd 26.02.1996
Elsevier
Subjects
Chemistry
Chemistry, Organic
Enamide
Epoxidation
Imidate
Indinavir
Iodohydrin
Physical Sciences
Science & Technology
Enamide
Epoxidation
Iodohydrin
Imidate
Indinavir
iodohydrin
indinavir
enamide
epoxidation
ACID
imidate
Online AccessGet full text

Cover

More Information
Summary:Reaction of 2-alkyl-4-enamides 1 with I + and aq. NaHCO 3 results in the diastereoselective formation of syn-iodohydrins 2, which are converted to the epoxides 3 with base. The reaction appears to proceed through a cyclic imidate type intermediate 4, followed by addition of water and ring opening. Reaction of 2-alkyl-4-enamides with 1 + and aqueous sodium bicarbonate results in the diastereoselective formation of the corresponding iodohydrins with essentially no iodolactone by-product. The reaction appears to proceed through a cyclic imidate type intermediate. This methodology has been successfully employed for the synthesis of the epoxide intermediate of the orally active HIV-1 protease inhibitor MK-639 (indinavir sulfate).
ISSN:0040-4020
1464-5416
DOI:10.1016/0040-4020(95)01114-5