Vicinal diboronates in high enantiomeric purity through tandem site-selective NHC-Cu-catalyzed boron-copper additions to terminal alkynes

Abstract

A Cu-catalyzed protocol for conversion of terminal alkynes to enantiomerically enriched diboronates is reported. In a single vessel, a site-selective hydroboration of an alkyne leads to the corresponding terminal vinylboronate, which undergoes a second site-selective and enantioselective hydroboration. Reactions proceed in the presence of 2 equiv of commercially available bis(pinacolato)diboron [B(2)(pin)(2)] and 5-7.5 mol % loading of a chiral bidentate imidazolinium salt, affording diboronates in 60-93% yield and up to 97.5:2.5 enantiomeric ratio (er). The enantiomerically enriched products can be functionalized to afford an assortment of versatile organic molecules. Enynes are converted to unsaturated diboronates with high chemo- (>98% reaction of alkyne; <2% at alkene) and enantioselectivity (e.g., 94.5:5.5 er).

Scheme 1. Initial Investigations

Scheme 2. Influence of NHC Structure on Site Selectivity and Enantioselectivity of Boron–Copper Additions^a

^a Conversions for reactions with 0.9 equiv 1 are based on the amount of this reagent and determined by ¹H NMR analysis. Mes = (2,4,6)-trimethylphenyl.