Convenient Methods for the Preparation of Unsymmetrical Double Aldols

Double aldol reaction proceeded stereoselectively at one (alpha)-carbon of ketones to give (alpha)-(1-hydroxyalkyl)-(beta)-hydroxyalkyl ketones (double aldols) in good to high yields by the following three methods: i) tin(II) trifluoromethanesulfonate-mediated aldol reaction of aldehydes with (beta)-hydroxy ketones (mono-aldols) in the presence of tertiary amines, ii) samarium(II) iodide-mediated aldol reaction of aldehydes with alkyl or aryl oxiranyl ketones, iii) Sn(OTf)2-promoted aldol reaction of (alpha)-bromo ketones with aldehydes giving (alpha)-bromo-(beta)-stannyloxy ketones which were then converted to titanium enolates on treatment with low-valent titanium. Double aldols were formed by subsequent reaction of the above titanium enolates with aldehydes in one-pot procedure. Further, small and medium-sized carbocyclic compounds whose ring skeletons were composed of double aldol structure were synthesized by SmI2-mediated intramolecular cyclization between oxiranyl ketone and aldehyde functions.