| Spirocyclic?-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 of?-methylene-?-lactams with carbenes represents a convenient and straightforward route to access spirocyclopropyl?-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 to?-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-substituted?-methylene-?-lactams with?-keto esters unde ambient temperature condition,affording a rapid and environment-friendly approach to densely functionalized spirocyclopropyl?-lactams.The experimental results indicated the cyclic structure of the?-methylene-?-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. |
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