[2+2] Cycloaddition Reactions of Bestmann’s Ylide with Imines

Organophosphorus compounds are useful reagents in synthetic chemistry and biochemistry with applications ranging from small molecule synthesis to polymers and pharmaceutical intermediates. A notable example of such organophosphorus reagents is Bestmann’s ylide, (Ph3P=C=C=O), a phosphonium ylide with cumulated double bonds. In addition to be utilized as a linchpin reagent in the synthesis of various natural products, it is capable of undergoing various [2+2], [2+3] and [2+4] cycloaddition reactions. Herein, we report new cycloaddition reactions of Bestmann’s ylide with a wide range of imines to give new β-lactams and acrylamides. Bestmann’s ylide reacts with various N-Cbz/N-Boc imines to selectively form β-lactams with exocyclic phosphonium ylide functionalities, which can react with various aldehydes to undergo Wittig reactions to give β-lactams with exocyclic double bonds under mild reaction conditions. On the other hand, Bestmann’s ylide can also undergo [2+2] cycloaddition with the N-tosyl imines to undergo a formal [2+2] cycloaddition, followed by a new ring-opening reaction to produce isolable triphenylphosphonium zwitterions. These zwitterionic species can be subjected to Michael addition at the β-carbon to selectively form amides with reactive α-phosphonium ylide moieties, which upon addition of selected aldehydes undergo Wittig reactions to give α-substituted acrylamides in good to excellent yields.

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