Highly stereoselective synthesis of allylic β-lactams via enzymatic C(sp3)-H amidation
Nawal Zahra Jafari1, Zheyuan Wang1, Anwita Chattopadhyay1
1Department of Chemistry and Biochemistry, The University of Texas at Dallas Richardson TX 75080 USA rudi.fasan@utdallas.edu.
Abstract:
β-Lactams are versatile synthons for organic synthesis as well as valuable pharmacophores for drug development. Here, we describe a biocatalytic strategy for the enantioselective synthesis of allylic β-lactams via a hemoprotein-catalyzed intramolecular C(sp3)-H amidation reaction with dioxazolone substrates. Leveraging a stepwise radical mechanism and overriding the typical reactivity of metallonitrenes, this system provides access to a variety of β-lactam products with consistently high enantioselectivity (≥99% ee) by favoring the amination of an allylic C(sp3)-H bond over the more facile functionalization of the adjacent olefin group. This works expands the range of stereoselective strategies for C-N bond formation via C(sp3)-H functionalization and demonstrates the value of new-to-nature biocatalysis to promote chemical transformations not currently accessible through chemocatalysis.
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