Pd-Catalyzed Alkene Difunctionalization Reactions of Enolates for the Synthesis of Substituted Bicyclic Cyclopentanes

Abstract

Palladium-catalyzed alkene difunctionalization reactions between alkenes bearing tethered aryl or alkenyl triflates and enolate nucleophiles are described. The transformations form two C−C bonds, a ring, and up to two stereocenters while producing substituted cyclopentane derivatives that contain appended carbonyl functionality. Products are formed with up to >20:1 diastereoselectivity, and the formation of sterically congested bonds between quaternary carbon atoms is feasible.

Pd‐Catalyzed C−C, C−N, and C−O Bond‐Forming Difunctionalization Reactions of Alkenes Bearing Tethered Aryl/Alkenyl Triflates

“…With only slight modifications to our reaction conditions (use of LiHMDS as base instead of an alkoxide), ketone and ester enolates proved to be suitable nucleophiles in alkene difunctionalization reactions of 22. [22] Low yields of 23 were obtained with methyl ketones or acetate esters (e. g., 23 a) due to competing Pd-catalyzed C-arylation or -alkenylation of the starting material. [19a] However, products 23 were generated in good to excellent yields with mono-or di-substituted ketones or esters.…”

Synthesis of Biindene Derivatives via Pd-Catalyzed Alkene Difunctionalization Reactions

“…We recently described a new Pd-catalyzed cross-coupling (alkene difunctionalization) reaction between nitrile nucleophiles and 2-allylphenyl triflate derivatives or related alkenyl triflates. − During the course of these studies, we found that transformations of relatively bulky α-branched nitriles were generally effective (Scheme , eq 1). However, yields decreased as the size of the alkyl chain decreased, with competing direct α-arylation of the nitrile becoming increasingly problematic.…”

Synthesis of 2-Cyanomethyl Indane Derivatives via Pd-Catalyzed Alkene Difunctionalization Reactions of Alkyl Nitriles

“…Our group recently reported a new method for the synthesis of indane derivatives bearing ester, ketone, or malonate groups through Pd-catalyzed cross-coupling (alkene difunctionalization) reactions of enolate nucleophiles with 2-allylphenyl triflate derivatives or related alkenyl triflates. − In a representative example, the Pd/BrettPhos-catalyzed coupling of 1a with diethyl malonate afforded a 93% yield of substituted indane product 2a (Scheme , eq 1) . However, when ethyl cyanoacetate was used in place of diethyl malonate, only trace formation of product 2b was observed.…”