Direct, practical, and powerful crossed aldol additions between ketones and ketones or aldehydes utilizing environmentally benign TiCl4–Bu3N reagent

An efficient TiCl4–Bu3N—(cat. TMSCl)-promoted aldol addition between ketones and ketones or aldehydes was performed. This environmentally benign method is advantageous from a green chemical viewpoint with regard to yield, substrates variation, reagent availability, and simple procedures. This method was applied to a short step formal synthesis of (R)-muscone, a natural macrocyclic musk.