Redox-Neutral Photocatalytic Cyclopropanation via Radical/Polar Crossover

Abstract

A benchtop stable, bifunctional reagent for the redox-neutral cyclopropanation of olefins has been developed. Triethylammonium bis(catecholato)iodomethylsilicate can be readily prepared on multigram scale. Using this reagent in combination with an organic photocatalyst and visible light, cyclopropanation of an array of olefins, including trifluoromethyl- and pinacolatoboryl-substituted alkenes, can be accomplished in a matter of hours. The reaction is highly tolerant of traditionally reactive functional groups (carboxylic acids, basic heterocycles, alkyl halides, etc.) and permits the chemoselective cyclopropanation of polyolefinated compounds. Mechanistic interrogation revealed that the reaction proceeds via a rapid anionic 3- exo- tet ring closure, a pathway consistent with experimental and computational data.

Synthesis of Functionalized Cyclopropanes from Carboxylic Acids by a Radical Addition–Polar Cyclization Cascade

“…During the preparation of this manuscript, Molander and co‐workers reported a cyclopropanation of styrene derivatives using iodomethyl silicates that proceeds through a radical‐polar crossover with intramolecular alkylation of an intermediate β‐iodo anion . Our process represents a fragment coupling approach, which is distinct from Molander's, and other, photoredox‐catalyzed cyclopropanations that use carbenoid‐like radicals to introduce a one‐carbon unit in a formal [2+1] cycloaddition …”

“…Herein, we report the successful development of a photoredox‐catalyzed radical–polar crossover cyclopropanation, in which a broad range of readily available carboxylic acids are directly converted to structurally diverse cyclopropanes through decarboxylative reactions with chloroalkyl alkenes. During the preparation of this manuscript, Molander and co‐workers reported a cyclopropanation of styrene derivatives using iodomethyl silicates that proceeds through a radical‐polar crossover with intramolecular alkylation of an intermediate β‐iodo anion . Our process represents a fragment coupling approach, which is distinct from Molander's, and other, photoredox‐catalyzed cyclopropanations that use carbenoid‐like radicals to introduce a one‐carbon unit in a formal [2+1] cycloaddition …”

Bromomethyl Silicate: A Robust Methylene Transfer Reagent for Radical‐Polar Crossover Cyclopropanation of Alkenes

“…Of note, these cyclopropanation reactions based on photooxidative generation of halomethyl radical proceed efficiently via redox‐neutral radical‐polar crossover without any aid of external additives. Due to the superior leaving group ability of iodide over bromide and chloride, the use of high reactive iodomethyl radical has more opportunities to prevent the formation of the undesired noncyclized Giese‐type addition product . During our recent investigation of nucleofuge character of halides, at least 10‐times higher reactivity of bromide compared with chloride was observed in the 3‐ exo ‐ tet cyclization.…”

“…Bis‐catecholato bromomethyl silicate 3 was easily obtained from the reaction of the readily prepared bromomethyltrimethoxysilane 1 with catechol 2 in the presence of 18‐crown‐6 and potassium methoxide in methanol (Equation 1) . Bromomethyl silicate 3 was isolated in 88 % yield without any chromatography as free‐flowing and bench‐stable powder.…”

Photoredox‐Catalyzed Cyclopropanation of 1,1‐Disubstituted Alkenes via Radical‐Polar Crossover Process

“…Based on these results and the competition experiments, a plausible mechanism based on polar-radical crossover process has been postulated in Scheme 6. [9,14] In summary, a diversity of functionalized cyclopropanes was efficiently prepared via photoredoxneutral catalyzed cyclopropanation of 1,1-disubstituted alkenes. With bis-catecholato silicates and 1,4-dihydropyridines as the radical precursors, a range of alkyl and acyl radicals could participate this radical additionanionic cyclization cascade.…”