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, that has been utilized as a linchpin reagent in the synthesis of natural products and 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 acrylamides and β-lactams. Bestmann’s ylide reacts with various imines to undergo a formal [2+2] cycloaddition, which at 75°C is followed by a new ring-opening reaction to produce isolable triphenylphosphonium acrylamides. 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 carbonyl compounds undergo Wittig reactions to give α-substituted acrylamides in good to excellent yields. On the other hand, the tributyl analogue of Bestmann’s ylide, (Bun)3P=C=C=O, can also undergo [2+2] cycloaddition with the same imines to selectively form β-lactams with exocyclic phosphonium ylide functionalities, which upon reacting with formaldehyde undergo Wittig reactions to selectively give β-lactams with exocyclic double bonds under mild conditions. Key features of both the reactions are (a) catalyst-free (b) two/three step-one pot (c) chlorinated solvent-free workup (d) good to excellent yields.

Cycloaddition reactions of Bestmann’s ylide with imines

ACS Spring 2022

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