Torquoselective Mechanochemical Activation of the Staudinger Reaction To Form ß-Lactams.

ABSTRACT

The Staudinger reaction yielding ß-lactam rings via [2 + 2] cycloaddition is a torquoselective reaction where the stereochemistry of the product can be steered by suitable substituents. Although the mechanochemical ring-opening of ß-lactams has been investigated recently, the force-assisted synthesis of this important functional four-ring motif remains unexplored. As it will be computationally demonstrated, mechanochemical activation greatly reduces the barrier of the rate-limiting ring-closure step while, at the same time, preserves its torquoselectivity. This finding strongly suggests that strained four-membered rings can be readily incorporated in chain molecules using sonication techniques that greatly enhance reactivity while conserving selectivity.