Stereoselective Traceless Borylation–Allenation of Propargylic Epoxides: Dual Role of the Copper Catalyst

Abstract

Chiral α-allenols are prepared with high diastereocontrol through an unprecedented and spontaneous β-oxygen elimination of an α-epoxy vinyl boronate. Stochiometric experiments and DFT calculations support a dual role of the copper catalyst, which orchestrates the hydroboration and the syn-elimination step.

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

“…The proper phosphine-base combination seemed to be crucial for the axial selectivity toward allenols 52 ( Scheme 11 , reaction a). 117 On the other hand, enynyl oxiranes 53 have been reported to react through a formal S N 2′ mechanism in the presence of aryl boronic esters and palladium catalysts to provide enantioenriched allenols 54 ( Scheme 11 , reaction b). 118 …”

“…Propargyl epoxides 51 undergo a ring-opening through a syn -hydride borane addition using MeOH as proton shuttle, followed by selective syn -elimination catalyzed by copper salts. The proper phosphine-base combination seemed to be crucial for the axial selectivity toward allenols 52 (Scheme , reaction a) . On the other hand, enynyl oxiranes 53 have been reported to react through a formal S N 2′ mechanism in the presence of aryl boronic esters and palladium catalysts to provide enantioenriched allenols 54 (Scheme , reaction b) …”

Copper‐Mediated Dichotomic Borylation of Alkyne Carbonates: Stereoselective Access to (E)‐1,2‐Diborylated 1,3‐Dienes versus Traceless Monoborylation Affording α‐Hydroxyallenes

“…In 2017, Tortosa et al. demonstrated that propargylic epoxides can be conveniently transformed into their formally reduced α‐hydroxyallenes by Cu‐catalysis in the presence of B 2 pin 2 and methanol (Scheme 1 a), [4a] with a syn ‐elimination of the Bpin group playing a pivotal role in this process. The combination of B 2 pin 2 and an alcohol as a reducing medium mimics the utilization of copper hydride chemistry reported independently by Krause (Scheme 1 b) [5] and Ito/Sawamura (Scheme 1 c).…”

“…Inspired by the pioneering work described in Scheme 1 [4a, 5, 6] and the structural versatility of alkynyl cyclic carbonates, [8a–e, 9] we envisioned that borylation of a new type of propargylic surrogate could significantly expand the diversity of functional and highly substituted α‐hydroxyallene scaffolds, which are useful building blocks for heterocyclic chemistry and natural product synthesis [10] . In the course of these studies, we discovered an unexpected though unique dichotomic behavior of the borylating agent providing selective pathways leading either to an ( E )‐diborylated 1,3‐diene or α‐hydroxyallene product with the same catalytic system.…”

Harnessing the Elusive 1,4-Reduction of Vinyl Epoxides through Copper Catalysis

“…We hypothesized that, in the presence of a proton source such as MeOH, intermediate A would be intercepted before cyclization to afford epoxy boronate C . This intermediate could undergo a base-promoted β-oxygen elimination to give the formal reduction product . This approach would provide a mild and catalytic method to reduce vinyl epoxides in a 1,4-manner, without using superstoichiometric amounts of a strong reductant.…”