Photoredox-Catalyzed Cyclobutane Synthesis by a Deboronative Radical Addition-Polar Cyclization Cascade

Abstract

Photoredox-catalyzed methylcyclobutanations of alkylboronic esters are described. The reactions proceed through single-electron transfer induced deboronative radical addition to an electron-deficient alkene followed by single-electron reduction and polar 4-exo-tet cyclization with a pendant alkyl halide. Key to the success of the methodology was the use of easily oxidizable arylboronate complexes. Structurally diverse cyclobutanes are shown to be conveniently prepared from readily available alkylboronic esters and a range of haloalkyl alkenes. The mild reactions display excellent functional group tolerance, and the radical addition-polar cyclization cascade also enables the synthesis of 3-, 5-, 6-, and 7-membered rings.

Keywords: boronic esters; cascade; cyclobutanes; photoredox catalysis; radical-polar crossover.

Figure 1

a) Bioactive cyclobutanes. b) Photoredox‐catalyzed decarboxylative radical addition–polar cyclization cascades. c) Boronate complexes as alkyl radical precursors. Reduction potentials are versus SCE in MeCN. EWG=electron‐withdrawing group; PC=photocatalyst; SET=single‐electron transfer; PMP=4‐methoxyphenyl.

Scheme 1

Mechanistic studies. [a] Boronate 36 was prepared in situ from 35 (1.0 equiv) and PhLi (1.1 equiv). [b] Intermediate 51 was prepared in situ from hex‐1‐en‐6‐yl boronic acid pinacol ester (1.1 equiv) and PhLi (1.2 equiv). [c] Using 1.1 equiv of 36 prepared in situ from 35 (1.1 equiv) and PhLi (1.2 equiv).

Scheme 2

Proposed mechanism.