Regio- and Diastereoselective Synthesis of 2-Arylazetidines: Quantum Chemical Explanation of Baldwin’s Rules for the Ring-Formation Reactions of Oxiranes
Ervin Kovács, Ferenc Faigl, Zoltán Mucsi
Abstract
A general, scalable two-step regio- and diastereoselective method has been described for the synthesis of versatile alkaloid-type azetidines from simple building blocks with excellent overall yields. In the kinetically controlled reaction, only the formation of the strained four-membered ring can be achieved instead of the thermodynamically favorable five-membered rings under appropriate conditions. Remarkable functional group tolerance has also been demonstrated. In this paper, we give a new scope of Baldwin's rules by density functional theory (DFT) calculations with an explicit solvent model, confirming the proposed reaction mechanisms and the role of kinetic controls in the stereochemical outcome of the reported transition-metal-free carbon-carbon bond formation reactions.