Iridium-Catalyzed Regioselective Synthesis of Trifluoromethylated Isocoumarins through Annulation of Benzoic Acids with Trifluoromethylated Alkynes

Abstract

An unprecedented Ir-catalyzed oxidative coupling of benzoic acids with trifluoromethylated alkynes was successfully developed to provide diverse trifluoromethylated isocoumarins in moderate to good yields. This new practical procedure was highlighted by mild reaction conditions, broad substrate scope, good regioselectivity, high efficiency, and easy operation.

Synthetic Methods of Isocoumarins and Phosphaisocoumarins through CH Activation

“…Ir(III)‐catalyzed oxidative cyclization of aromatic acids with trifluoromethyl‐substituted internal alkynes took place smoothly for the synthesis of diverse trifluoromethyl‐substituted isocoumarin derivatives in high yields along with good regioselectivities under mild conditions. This method was highlighted for its wide substrate scope with good functional group compatibility (c) . Benzoic acids underwent regioselective Ir(III)‐catalyzed oxidative cyclization with propargyl alcohols, producing functionalized isocoumarin derivatives with a wide substrate scope and high functional group tolerance.…”

Recent advances in transition-metal catalyzed directed C–H functionalization with fluorinated building blocks

“…In 2019, Zhou et al developed a highly efficient Ir-catalyzed oxidative coupling of benzoic acids 60 with trifluoromethylated alkynes 230 to furnish trifluoromethylated isocoumarins 232 and 233 . 177 The coupling was with reversed regioselectivity for the trifluoromethyl alkyne substrate. The trifluoromethylated isocoumarins were obtained under mild conditions with moderate to excellent yields along with good regioselectivities (Scheme 43).…”

Six-membered ring systems: with O and/or S atoms

“…Polyfunctionalized 3,4-disubstituted isocoumarins can be synthesized through cobalt(III)-catalyzed oxidative annulation reactions of benzaldehydes with internal alkynes in the presence of copper(I) oxide in poly(ethylene glycol) (19JOC6807) and through ruthenium(II)-mediated electrochemical [4 þ 2] annulation reactions of benzylic alcohols (19CC1124) or arylglyoxylic acids (Scheme 65) (19CC7251) with internal alkynes. Regioselective annulation reaction of benzoic acids with trifluoromethylated alkynes promoted by an iridium(III) complex and silver acetate as oxidant in TFE affords 3-trifluoromethyl-4-substituted isocoumarins as major products along with small amounts of 3-substituted 4-trifluoromethylisocoumarins (19OL3043). The same iridium complex catalyzes regioselective oxidative cyclization of benzoic acids with propargyl alcohols carried out in the presence of lithium acetate and silver carbonate in DCE to give 3,4-disubstituted isocoumarins (19JOC2699).…”