Enantioselective Radical Addition/Cross‐Coupling of Organozinc Reagents, Alkyl Iodides, and Alkenyl Boron Reagents

Abstract

A hybrid transition‐metal/radical process is described that results in the addition of organozinc reagents and alkyl halides across alkenyl boron reagents in an enantioselective catalytic fashion. The reaction can be accomplished both intermolecularly and intramolecularly, providing useful product yields and high enantioselectivities in both manifolds.

Nickel-Catalyzed Dicarbofunctionalization of Alkenes

“…Stereocontrol of the subsequent coupling with an organozinc reagent is dictated by the chiral diamine ligand. 28 Stereospecific oxidation of the boronic ester affords the corresponding chiral alcohols.…”

“…51 The 1,2-dialkylation and 1,2-arylalkylation of alkenyl boronic acid pinacol esters (BPin) take advantage of α-boryl radical stabilization (Scheme 13). 28 In the presence of NiBr 2 •glyme and a chiral diamine ligand, alkyl zinc halides and tertiary alkyl halides are added across a vinyl boron reagent in good yield and enantioselectivity. Following oxidation of pinacol borane easily generates chiral secondary alcohol products with a retention of the stereochemistry…”

Ni- and Pd-Catalyzed Enantioselective 1,2-Dicarbofunctionalization of Alkenes

“…Also in 2019, the Morken group reported a 1,2-DCF of vinylboronic acid pinacol ester with alkyl iodides and alkyl/aryl zinc reagents using a NiBr 2 /chiral diamine L2 catalytic system (Scheme 12 ). 31 Enantioenriched secondary alcohols were obtained in yields up to 73% yield and enantio­selectivity up to 98:2 e.r. following oxidative workup.…”

“…Radical-based two-component enantioselective 1,2-DCF is rare, and only one example has been reported by the Morken group in 2019, employing substrates containing both alkenylboronic ester and alkyl iodide motifs (Scheme 10 ). 31…”

Alkenylboronic Ester Activation to Nucleophilic Addition and Electrophilic Trapping with Carbonyl Groups

“…1 2 However, the vinylborane functional group represents an additional synthetic opportunity for reaction through the alkene π-system, due to the adjacent empty p-orbital on the boron atom. The formation of a stable α-boryl radical 3 4 5 6 7 8 9 and α-boron ‘ate’ radical 10 11 12 13 intermediates has been postulated to be involved in 1,2-difunctionalization of alkenylboronic esters (Scheme 1 ). However, the alternative nucleophilic addition to the alkene π-system in vinylboranes has been rarely successful due to the competitive formation of a boron ‘ate’ ( A-ate ).…”