TiCl₄−n-Bu₄NX (X = I, Br, and Cl) Combination-Induced Coupling of α,β-Unsaturated Ketones with Aldehydes

A three-component coupling reaction between vinyl ketones, aldehydes, and halides has been developed with TiCl₄−n-Bu₄NX combined reagents. Treatment of vinyl ketones with a TiCl₄−n-Bu₄NI combination followed by an addition of a variety of aldehydes provides syn-α-iodomethyl-β-hydroxy ketones with high stereoselectivity. Methyltriphenylphosphonium iodide as well as n-Bu₄NI acts efficiently as a halide source. The combination of TiCl₄−n-Bu₄NBr provides the corresponding bromo compounds in good yields. syn-α-Chloromethyl-β-hydroxy ketones are obtained with the TiCl₄−n-Bu₄NCl combination. A competitive experiment reveals that the order of relative reactivity of the combinations is TiCl₄−n-Bu₄NI > TiCl₄−n-Bu₄NBr > TiCl₄−n-Bu₄NCl.