Synthesis of Oxazolones by a β-Selective Oxidative Heck Coupling

Significance

Bäckvall and co-workers report the first palladium(II)-catalyzed oxidative Heck coupling between aryl boroxines and cyclic sulfonyl enamides to afford substituted oxazolones. The cyclic sulfonyl enamide intermediates are prepared by in situ condensation of propargylic alcohols with tosylisocyanate followed by a Z-selective 5-exo cyclization. The oxidative Heck reaction affords β-selective arylated oxazolones in which a new tertiary stereogenic center is installed with modest to excellent yields. Oxidative Heck-type couplings are typically narrow in scope; in contrast, this methodology covers a broad range of electronically different boroxines and two structurally different cyclic sulfonyl enamides.

Comment

As a result of steric interference in the transmetalation step, the only apparent limitation of this robust methodology is the coupling of ­ortho-substituted aryl boroxines. The authors report one failed example of the oxidative Heck coupling with a furan boroxine which warrants further investigation into heteroaryl couplings. Optimization studies showed that addition of anhydrous DMSO as a co-solvent was crucial for reactivity; however, too much DMSO inhibited the reaction. Through careful observation of solvent effects, it is proposed that the transmetalation step is aided by DMSO. The chemistry was demonstrated on a >60 mmol scale in a one-pot sequential fashion.