A general, modular method for the catalytic asymmetric synthesis of alkylboronate esters

Abstract

Alkylboron compounds are an important family of target molecules, serving as useful intermediates, as well as end points, in fields such as pharmaceutical science and organic chemistry. Facile transformation of carbon-boron bonds into a wide variety of carbon-X bonds (where X is, for example, carbon, nitrogen, oxygen, or a halogen), with stereochemical fidelity, renders the generation of enantioenriched alkylboronate esters a powerful tool in synthesis. Here we report the use of a chiral nickel catalyst to achieve stereoconvergent alkyl-alkyl couplings of readily available racemic α-haloboronates with organozinc reagents under mild conditions. We demonstrate that this method provides straightforward access to a diverse array of enantioenriched alkylboronate esters, in which boron is bound to a stereogenic carbon, and we highlight the utility of these compounds in synthesis.

Fig. 1. Alkylboranes

(A)–(E) Background. (F)–(H): This study.

Fig. 2. Nickel-catalyzed asymmetric synthesis of alkylboranes

(A)–(B) Variation in the coupling partners. (C) Functional-group compatibility. (D) Comparison of the enantioselectivity-determining step using a chiral auxiliary versus a chiral catalyst. (All data are the average of two experiments. ^aDetermined after oxidation to the alcohol. ^bYield of purified product. ^cThe α-iodoborane was used. ^dReaction temperature: 10 °C. ^eCatalyst loading: 12% NiBr₂•diglyme, 16% L*.).

Fig. 3. Catalyst-controlled stereoselectivity in the asymmetric synthesis of alkylboranes

(A) Complex coupling partners. (B) Iterative homologation.

Fig. 4. Enantioenriched alkylboranes as versatile intermediates

Conversion to diverse families of organic molecules via C–C, C–N, C–O, and C–halogen bond formation. (ArLi = (3,5-bis(trifluoromethyl)phenyl)lithium).