Studies on the Reaction of Aryl Glyoxals with L-Prolinol: Unexpected Formation of Morpholin-2-one Derivatives and Stereoselective Trifluoromethylation of the Bicyclic System

Reactions of L-prolinol with aryl glyoxals lead to labile bicyclic 2-aryloyl-1,3-oxazolidines, which smoothly undergo isomerization in the presence of an acid via a cascade of reactions involving a 1,2-aryl shift. The products formed thereby were identified as bicyclic derivatives of morpholin-2-one. Both 1,3-oxazolidines and morpholin-2-ones were used for the nucleophilic trifluoromethylation by treatment with trifluoromethyltrimethylsilane (Ruppert-Prakash reagent) in the presence of a catalytic amount of CsF. Whereas in the case of the 1,3-oxazolidines only modest diastereoselectivity was achieved, the reactions with the morpholinone derivatives occurred with complete stereoselectivity.