Diastereoselective [2+2]-Cycloaddition Reactions of Unsymmetrical Cyclic Ketenes with Imines:  Synthesis of Modified Prolines and Theoretical Study of the Reaction Mechanism

The synthesis of enantiomerically pure modified proline derivatives was achieved by using spiro beta-lactams as starting material that were prepared in turn by the [2+2]-cycloaddition of unsymmetrical cyclic ketenes with optically active imines. A theoretical study of the [2+2]-cycloaddition reaction, using density-functional methods, gave insights on the origin of the observed stereoselectivity of the Staudinger reaction. The spiro beta-lactams were transformed in the N-Boc derivatives and subjected to nucleophilic ring opening, affording the corresponding enantiomerically pure modified proline derivatives, isolated as orthogonally protected compounds.