Stereoelectronic control of oxazolidine ring-opening: structural and chemical evidences

Ring opening of oxazolidines derived from tris(hydroxymethyl)aminomethane, l-serine and l-threonine was investigated. It was shown that n(N)→σ ∗(C–O) electron delocalization ( endo-anomeric effect) occurring in the five-membered ring plays a major role in the cleavage of the intracyclic C–O bond. The present work establishes that when the nitrogen lone pair is conjugated with a carbonyl group ( n(N)→π(CO) delocalization) as happens in N-acyloxazolidines, both hydrolysis and reductive ring-opening become much more difficult as a consequence of a concomitant decrease of oxygen basicity and of an increase of the intracyclic C–O bond strength. In A , endo-anomeric effect favours ring-opening, whereas in B reverse motion of electrons makes ring-opening considerably more difficult.