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

• Published in: Tetrahedron letters Vol. 61; no. 29; pp. 152098 - 152101
• Main Authors: Bhalla, Aman, Modi, Garima, Yadav, Pooja, Kumar, Pankaj, Bari, S.S., Hundal, Geeta
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 16.07.2020; Elsevier
• Subjects: Alkyl-3-phenylsulfonyl-β-lactams; C-3 alkylation; Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; Single crystal X-ray; Stereoselectivity; β-Lactams; C-3 alkylation; Stereoselectivity; Alkyl-3-phenylsulfonyl-β-lactams; Single crystal X-ray; β-Lactams; DESIGN; Alkyl-3-phenylsulfonyl-beta-lactams; beta-Lactams; INHIBITORS
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2020.152098

[Display omitted] •Sulfonyl group activate C-3 alkylation of trans-3-phenylsulfonyl-β-lactams.•Mild reaction conditions, cost effective and functional group tolerance.•Exploration of steric bulk on C-3 alkylation of β-lactams.•Stereoselective synthesis of cis- +/or trans-alkyl-β-lactams with organic halides.•Stereochemistry at C-3 of β-lactam 7d was confirmed by X-ray structural analysis. A sulfonyl promoted synthetic protocol for the C-3 alkylation of trans-3-phenylsulfonyl-β-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-β-lactams as major and minor isomers respectively with alkyl halides while arylalkyl/unsaturated halides yield only cis-β-lactams exclusively. Further, the effect of sterically bulky group on the C-3 substitution was investigated by the reaction of 3-phenylsulfonyl-β-lactams 6(d-e) with crotyl chloride (predominantly E) to achieve diastereomeric mixture of β-lactams 7/7ʹ and 8. This strategy reveals advantages in terms of cost effectiveness, functional group tolerance and ease of operation.