Deoxygenative Cyclopropanation Of α-methylene-β-Lactams With α-Keto Esters

Spirocyclicβ-lactams（azetidine-2-ones）are structurally unique framework present in a wide range of bioactivitie compounds.They are also promising nonclassical bioisosteresin drug discovery and development.The cyclopropanation ofα-methylene-β-lactams with carbenes represents a convenient and straightforward route to access spirocyclopropylβ-lactams,its application has been restricted by the inconvenience associated with the manipulation of diazo compounds.On the other hand,the Kukhtin–Ramirez adducts,formed from the addition of trivalent phosphorus toα-dicarbonyl,have functioned as a versatile 1,1-amphilic intermediate to effect epoxidation,cyclopropanation and[4+1]cycloaddition.However,the electron-decificent substrates used in these examples all restrict to achiral and planar structures.As a continuation of our interest in discovering interesting strained-ring synthons for phosphine-promoted reactions,wereported herein the P（NMe₂）₃-mediated cyclopropanation of C3-substitutedα-methylene-β-lactams withα-keto esters unde ambient temperature condition,affording a rapid and environment-friendly approach to densely functionalized spirocyclopropylβ-lactams.The experimental results indicated the cyclic structure of theα-methylene-β-lactam together with its C3-substituent not only significantly impact the reaction efficiency and stereochemistry but also played a pivotal role in determining the chemoselectivity of the reaction.