α-Arylation and Ring Expansion of Annulated Cyclobutanones: Stereoselective Synthesis of Functionalized Tetralones

Abstract

α-Arylcyclobutanones display unique reactivity that makes them valuable synthetic intermediates and target molecules. We describe the preparation of α-aryl- and α-heteroarylcyclobutanones through a direct α-arylation reaction. Problematic fragmentations are avoided by the use of LiO^t Bu, which promotes a rapid but reversible self-aldol reaction that slowly releases the enolate required for α-arylation. We also demonstrate the ring expansion of α-arylcyclobutanones, a process that is highlighted in the stereoselective synthesis of 1-methoxy coniothyrinone D.

Keywords: cyclobutanones; homogeneous catalysis; ring expansion; synthetic methods; α-arylation.