We report a highly efficient, general and practical method for the aldol condensation of acetone with aromatic and aliphatic aldehydes, using morpholinium trifluoroacetate as a catalyst.

We report on the tetraethylphosphorodiamidate (−OP­(O)­(NEt2)2) group as an effective directed metalation group (DMG). Lithiation-electrophile quench of 1 provides a general synthesis of ortho-substituted aryl and naphthyl phosphorodiamidates 4–8. We also describe the phospha anionic ortho-Fries (AoF) rearrangement of the phosphorodiamidates 1a,1b → 2 or 3 and its vinylogous counterpart to the ortho-tolyl phosphorodiamidates 5b → 13. Intermolecular competition experiments demonstrate the approximately equal DMG strength of the −OP­(O)­(NEt2)2 and the most powerful OCONEt2 groups.

The proline-catalyzed asymmetric aldol reaction between aliphatic aldehydes and acetone has, to date, remained underdeveloped. Challenges in controlling this reaction include avoiding undesired side reactions such as aldol condensation and self-aldolization. In recent years we have developed optimized conditions, which enable high yields and good to excellent enantioselectivities, and which are presented in this communication

It provides a general and efficient method to prepare α,β‐unsaturated ketones.

Improved Conditions for the Proline-Catalyzed Aldol Reaction of Acetone with Aliphatic Aldehydes. -The reaction can be scaled up. -(MARTINEZ, A.; ZUMBANSEN, K.; DOEHRING, A.; VAN GEMMEREN, M.; LIST*, B.; Synlett 25 (2014) 7, 932-934, http://dx.