Influence of Ring Size in the Nickel-Catalyzed Arylation of Cyclic Sulfones

Abstract

Sulfones are valuable scaffolds found in organic molecules, important for pharmaceuticals, polymers, and agrochemicals. The development of a new metal-catalyzed cross-coupling method with the activation of a C-SO2 bond, affording novel, functionalized sulfone-containing products has been reported. Herein, the influence of the ring size in a Csp2-Csp3 Kumada-type nickel-catalyzed cross-coupling of α-substituted cyclic sulfones as Csp3-electrophiles and aryl Grignard reagents is investigated. A simple NiII precatalyst [NiBr2(2MePMA)] is capable of affecting the cross-coupling reaction without any additives. The resulting sulfinate intermediate, derived from the ring opening reaction, can be used for further functionalization with a wide range of electrophiles. Mechanistic analyses and reaction monitoring experiments suggest that one of the driving forces of the reaction is related to the steric strain on the ring. Four- and six-membered cyclic sulfones were made and tested to investigate this hypothesis. Differing reactivities for the sulfones were observed. The four-membered ring was very reactive towards the cross-coupling, the six-membered analog showed slow consumption, with the five-membered ring being in between those trends. The use of chiral sulfones was also investigated by comparing the five- and six-membered ring.