New directions for the Breslow intermediate
by McIntosh, Matt
In 1958, as a part of an investigation of the mechanism of thiamine action, Breslow proposed carbene 1a and enol 2a as transient intermediates in the N-methylthiazolium-catalyzed benzoin condensation of benzaldehyde. Enol 2, and heterocyclic variants thereof, have come to be known as Breslow intermediates. In NHC catalyzed reactions of aldehydes, they generally behave as nucleophilic enamines. We have recently reported (Org. Lett. 2013) that N-allyl intermediates 2b participate as a hydroxy-substituted N,S-ketene acetals in novel Claisen rearrangements to provide C2-substituted azoles 3. We will report further advances in the rearrangement chem. as well as addnl. novel reactivity modes of the Breslow intermediate.