Stereoselective C-3 alkylation of trans-3-phenylsulfonyl-β-lactams with organic halides to access C-3 substituted β-lactams using sulfonyl moiety as an activating group

A sulfonyl promoted synthetic protocol for the C-3 alkylation of trans-3-phenylsulfonyl-beta-lactams 6(a-e) with active organic halides in presence of K2CO3 as mild base and DMF as solvent is described. This protocol furnished cis- and trans-beta-lactams as major and minor isomers respectively with alkyl halides while arylalkyl/unsaturated halides yield only cis-beta-lactams exclusively. Further, the effect of sterically bulky group on the C-3 substitution was investigated by the reaction of 3-phenylsulfonyl-beta-lactams 6(d-e) with crotyl chloride (predominantly E) to achieve diastereomeric mixture of beta-lactams 7/7' and 8. This strategy reveals advantages in terms of cost effectiveness, functional group tolerance and ease of operation. (C) 2020 Elsevier Ltd. All rights reserved.