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.