title: Enantiomerically pure trans-beta-lactams from alpha-amino acids via compact fluorescent light (CFL) continuous-flow photolysis.
abstract: Photolysis of alpha-diazo-N-methoxy-N-methyl (Weinreb) beta-ketoamides derived from enantiomerically pure (EP) alpha-amino acids affords the corresponding EP beta-lactams via an intramolecular Wolff rearrangement. The photochemistry is promoted with either standard UV irradiation or through the use of a 100 W compact fluorescent light; the latter affords a safe and environmentally friendly alternative to standard photolysis conditions. A continuous-flow photochemical reactor made from inexpensive laboratory equipment reduced reaction times and was amenable to scale-up. The diastereoselectivity (cis or trans) of the product beta-lactams has been shown to vary from modest to nearly complete. An extremely facile, atom-economical method for the epimerization of the product mixture to the trans isomer, which is generally highly crystalline, has been developed. Evidence for C3 epimerization of Weinreb amide structures via a nonbasic, purely thermal route is presented. Subsequent transformations of both the Weinreb amide at C3 (beta-lactam numbering) and the amino acid side chain at C4 are well-tolerated, allowing for a versatile approach to diverse beta-lactam structures. The technology is showcased in the synthesis of a common intermediate used toward several carbapenem-derived structures starting from unfunctionalized aspartic acid.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
authors.forename: Yvette S Mimieux
authors.initials: YS
authors.lastname: Vaske
authors.forename: Maximillian E
authors.initials: ME
authors.lastname: Mahoney
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Konopelski
authors.forename: David L
authors.initials: DL
authors.lastname: Rogow
authors.forename: William J
authors.initials: WJ
authors.lastname: McDonald
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry*; D008029:Lighting / Q000379:methods*; D010782:Photolysis; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000596:Amino Acids; D007769:Lactams