Copper-Photoredox-Catalyzed C(sp3)-C(sp3) Reductive Cross-Coupling of Alkyl Bromides with BCP-Thianthrenium Reagents

Abstract

Herein, we report a reductive cross-coupling reaction of bicyclo[1.1.1]pentyl (BCP)-thianthrenium reagents and alkyl bromides. The reaction is catalyzed by a copper/photoredox catalyst system. The approach is the first example of a cross-coupling between BCP-based reagents with alkyl electrophiles.

Keywords: Bicyclopentylation; Bioisosteres; Copper catalysis; Reductive coupling; Thianthrenium salt.

Figure 1

Reductive coupling of alkyl bromides with BCP‐thianthrenium salts. X, halides; PC, photocatalyst.

Figure 2

Proposed mechanism.

Scheme 1

Substrate scope of the reductive cross‐coupling between alkyl bromides and BCP‐thianthrenium salts. General reaction conditions: alkyl bromide (0.25 mmol, 1.0 equiv.), 1b–1d (2.0 equiv.), 4CzIPN (5.0 mol%), CuCl (20 mol%), TMS₃SiOH (2.0 equiv.), K₂HPO₄ (4.0 equiv.), DMA (c = 0.1 M), blue LED (460 nm, 40 W), 12 hr, 30 °C. ^{a )}CuCl₂ (20 mol%) was used as catalyst, Na₂CO₃ (4.0 equiv.) was used as base, and DMSO (c = 0.05 M) was used as solvent. d.r., diastereomeric ratio.

Scheme 2

Synthesis of BCP analog of tesmilifene.