Nucleophilic Ring-Opening of Epoxide and Aziridine Acetates for the Stereodivergent Synthesis of β-Hydroxy and β-Amino γ-Lactams

• Published in: Journal of organic chemistry Vol. 76; no. 3; pp. 948 - 962
• Main Authors: Bisol, Tula B, Bortoluzzi, Adailton J, Sá, Marcus M
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 04.02.2011; Amer Chemical Soc
• Subjects: Acetates - chemistry; Aziridines - chemistry; beta-Lactams - chemical synthesis; beta-Lactams - chemistry; Chemistry; Chemistry, Organic; Epoxy Compounds - chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Indicators and Reagents - chemistry; Magnetic Resonance Spectroscopy; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Pyrrolidinones - chemical synthesis; Pyrrolidinones - chemistry; Science & Technology; Stereoisomerism; CONVENIENT SYNTHESIS; REGIOCHEMICAL CONTROL; CHELATING PROCESSES; ASYMMETRIC-SYNTHESIS; ENANTIOSELECTIVE SYNTHESIS; ALPHA-METHYLENE; EFFICIENT SYNTHESIS; CARBOXYLIC ESTERS; STEREOSELECTIVE-SYNTHESIS; DIFUNCTIONALIZED CIS; Chemical reagent; Regioselectivity; Organic azide; Mild operating conditions; Nitrogen heterocycle; Relative configuration; Lactam; Three membered ring; Chiral compound; Aziridine derivatives; Oxygen heterocycle; Ring cleavage; Pyrrolidine derivatives; Chemical reduction; Stereoselectivity; Ester; Amine; Cyclization; Functionalization; Asymmetric synthesis; Epoxide; Chemical synthesis; Nucleophile
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo102267h

A highly regio- and stereoselective synthesis of novel β,γ-disubstituted γ-lactams with either an anti or syn relative configuration was developed from readily available epoxide and aziridine acetates. The key steps include the regio- and diastereocontrolled nucleophilic ring-opening of these three-membered heterocycles followed by mild reductive cyclization of the γ-azido ester intermediate. The method was also extended to an asymmetric synthesis of (4R,5S)-4-hydroxy-5-phenylpyrrolidin-2-one from a chiral epoxide acetate. The main features of this versatile synthesis of functionalized γ-lactams include the involvement of inexpensive reagents and mild conditions together with high chemical efficiency.