Enantio- and Diastereoselective Synthesis of Hydroxy Bis(boronates) via Cu-Catalyzed Tandem Borylation/1,2-Addition

Abstract

Catalytic enantioselective synthesis of 1-hydroxy-2,3-bisboronate esters through multicomponent borylation/1,2-addition is reported. Catalyst and substrates are readily available, form both a C–B and C–C bond, and generate up to three contiguous stereocenters. The reaction is tolerant of aryl, vinyl, and alkyl aldehydes and ketones in up to 95% yield, >20:1 dr, and 99:1 er. Intramolecular additions to aldehydes and ketones result in stereodivergent processes. The hydroxy bis(boronate) ester products are amenable to site-selective chemical elaboration.

Copper‐Catalyzed Borylacylation of Activated Alkenes with Acid Chlorides

“…[14] Such a process was viewed as a valuable strategy, as the products would be versatile entities for chemical synthesis and map onto molecules of biological interest (Scheme 1D). [15] Though the direct formation of ketones through a carboboration process is unknown, the Popp group recently reported the borylcarboxylation of vinyl arenes to generate carboxylic acids.…”

Copper‐Catalyzed Tandem Hydrocupration and Diastereo‐ and Enantioselective Borylalkyl Addition to Aldehydes

“…For example, Meek and co‐workers reported copper‐catalyzed enantioselective transmetalation of 1,1‐diborylethane and its addition to aldehydes (Scheme b) . The same group also reported borylative coupling of vinylboronate with aldehydes (Scheme c) . In contrast, hydrometalation of alkenylboronates provides an efficient way to generate boron‐α‐chiral nucleophiles, and successful reactions with electrophiles could establish useful catalytic methodologies for the preparation of chiral organoboron compounds.…”

Sulfonate N‐Heterocyclic Carbene–Copper Complexes: Uniquely Effective Catalysts for Enantioselective Synthesis of C−C, C−B, C−H, and C−Si Bonds

“…Meek has merged regio-and enantioselective Cu-B(pin) addition to alkenyl-B(pin) moieties with trapping of the Cu-alkyl intermediate with aldehydes. [154] Morken has further illustrated that [155] catalytic Si-H addition to an E-alkenyl-B(pin) compound can lead to enantiomerically enriched geminal borosilanes.…”