Catalytic Asymmetric Conjugate Addition of a Borylalkyl Copper Complex for Chiral Organoboronate Synthesis

Abstract

We report the catalytic enantioselective conjugate addition of ab orylalkyl copper nucleophile generated in situ from a1 ,1-diborylmethane derivative to a,b-unsaturated diesters.I nt he presence of ac hiral N-heterocyclic carbene (NHC)-copper catalyst, this method facilitated the enantioselective incorporation of aCH 2 Bpin moiety at the b-position of the diesters to yield b-chiral alkylboronates in up to 86 %yield with high enantioselectivity.T he alkylboron moiety in the resulting chiral diester products was converted into various functional groups by organic transformation of the CÀBbond.

Asymmetric Conjugate Addition of Chiral Secondary Borylalkyl Copper Species

“…[12,13] More recently, our group described the enantioselective catalytic conjugate addition of a primary borylalkyl NHC-copper complex generated by transmetalation from 1,1-diborylmethane. [14] While it was the first asymmetric conjugate addition of a catalytically generated borylalkyl copper, the conjugate addition of a branched borylalkyl copper species derived from 1,1-diborylethane was not successful under our previous reaction conditions. Pursuing the diastereo-and enantioselective conjugate addition of chiral secondary borylalkyl copper complexes, we tried to access the chiral borylalkyl copper species via enantioselective hydrocupration of prochiral borylalkenes in the presence of Michael acceptors (Scheme 1 B).…”

“…We initiated our study with vinylboronic acid pinacol ester (1 a-Bpin) and diethyl benzylidenemalonate (2 a) in the presence of copper chloride with chiral NHC ligand (L1), which was the optimal ligand in our previous asymmetric conjugate addition [14] ( Table 1, entry 1). Under the reaction conditions, only reduced diethyl benzylmalonate was obtained without the desired product 3 a, which suggests low chemoselectivity of the NHC-Cu catalyst.…”

Recent developments in the asymmetric synthesis and functionalization of symmetrical and unsymmetricalgem-diborylalkanes

“…In 2019, the Yun group developed an enantioselective conjugate addition protocol using gem-bis[( pinacolato)boryl]alkanes and an α,β-unsaturated diester (Scheme 13c). 48 When the N-heterocyclic carbene L14 ligated copper catalyst reacted with gem-bis[( pinacolato)boryl]methane, it endured an oxidative addition and furnished the soft nucleophilic boryl-alkylcopper species, which partakes in a 1,4-addition with an α,β-unsaturated diester 82. Among a wide variety of Michael acceptors screened for this reaction, the mono ester was found to be unreactive, whereas the dinitrile and the other diesters resulted in decreased enantioselectivity, promoting the diethyl diester as the optimal one.…”

Borata‐Alkene Species as Nucleophilic Reservoir

“…A S N 2 mechanism has been suggested as the most plausible for the alkylation of copper stabilized α‐pinacolboryl carbanions. The copper complex can be modified with a diverse type of ligands, even chiral ligands to perform the corresponding asymmetric alkylation [75–78] . The addition of LiO t Bu favors the reaction outcome, probably by activation of the diborylmethane reagent and stabilization of the borata‐alkene intermediate.…”