Asymmetric synthesis, characterization of chiral trans and cis-3-chloro/oxo/thio-4-styryl-β-lactams using (R)-(+)-1-phenylethylamine and their efficient column chromatographic separation

Abstract

Diverse chiral trans and cis-3-chloro/oxo/thio-4-styryl-β-lactams were efficiently synthesized using chiral 3′-phenylallylidene-[(R)-1′-phenylethyl] amine and substituted ethanoic acids. Moore ketenes derived from chloro/phenythio/benzylthio ethanoic acids (Cl/PhS/BzS) affords both chiral trans- and cis β-lactams, with a preference for trans-stereochemistry. However, Bose-Evans ketenes obtained from 2-methoxy/phenoxyethanoic acids (MeO/PhO), led to the exclusive formation of cis-diastereomers only. Further, individual diastereomers of trans- and cis-β-lactams were separated via efficient column chromatography. The relative cis and trans configuration of the C-3 and C-4 protons in chiral β-lactams was established using coupling constant value ranging from J = 1.4 to 2.1 Hz (in case of trans) and J = 4.3 to 5.2 Hz (in case of cis) respectively. Structural confirmation of β-lactams was done using FT-IR, NMR (¹H,¹³C,¹H-¹H COSY and ¹H-¹³C HSQC), elemental analysis, ESI-MS and X-ray crystallography.

Graphical Abstract

Keywords:

• Chiral
• β-lactams
• trans and cis
• column chromatography
• diastereomers

Acknowledgments

Anu Kumari greatfully acknowledge the CSIR, India for SRF Award No-F.No.09/135/(0679)/2012/EMR-I. Ankita Garg acknowledges Panjab University, Chandigarh for PhD fellowship. We are grateful to Sophisticated Analytical Instrumentation Facility (SAIF), Panjab University, Chandigarh, India for ¹H NMR, ¹³C NMR and HRMS facilities.

Declaration of interest

The authors declare no conflict of interest.

Data availability statement

The data that support the findings of this study are available in the Supporting Information of this article.

Additional information

Funding

This work was supported by the Department of Science and Technology (DST), New Delhi, Government of India (Grant No. SR/FT/CS-037/2010) FIST II/PURSE II grant (DST) and UGC-CAS, Panjab University, Chandigarh.