A Convenient Method for the Preparation of Unsymmetrical Bis-Aldols by Way of Sequential Two Aldol Reactions

Unsymmetrical alkyl 2-hydroxy-1-(1-hydroxyalkyl)alkyl ketones (bis-aldols) are successfully synthesized by way of sequential two aldol reactions using α-bromo ketones and two different aldehydes. In the first reaction, α-bromo-β-stannyloxy ketones are formed by tin(II) trifluoromethanesulfornate-promoted aldol reaction of α-bromo ketones with several aldehydes. Bis-aldols are then formed via the second aldol reaction between another aldehydes and dianionic enolates generated by the reduction of α-bromo-β-metalloxy ketones with titanium(IV) iodide and copper.