Nickel-catalyzed carbazenation of vinylboronic esters to obtain chiral α-boron zinc reagents
Organozinc reagents are widely used in the construction of carbon-carbon and carbon-heteroatom bonds due to their good functional group tolerance and stability as well as low toxicity. Although powerful reactions have allowed asymmetric synthesis using racemic reagents in recent years, transition metal catalysis has further broadened the application of non-racemic organozinc
reagents. A common method for preparing organozinc reagents is the insertion of zinc into an organohalide, but this process typically passes through a radical intermediate, which makes asymmetric synthesis challenging. Other methods of preparing chiral organozinc reagents have been developed.Knochel’s team developed a borohydride and subsequent boron-zinc exchange strategy to obtain chiral organozinc reagents (Fig. 1a); Campos obtained heterocyclic organozinc reagents by deprotonation/transmetalation (Fig. 1b), a strategy that was later modified by Gawley to use catalytic quantities of lithiated diaminol salts (Fig. 1c); more recently, Knochel’s team obtained chiral dialkyl zinc reagents by lithium-halogen atom exchange and subsequent transmetalation (Fig. 1d). direct carbon-zincation of π-bonds is one of the very special methods, but has been reported very rarely and is only possible for alkenes with stress and activation (Fig. 1e). In this paper, James P. Morken of Boston College developed the carbon-zincation of vinylboronic esters involving chiral nickel catalysts to obtain chiral α-boron zinc reagents, which are conformationally stable products that can be reacted with a variety of electrophilic reagents to obtain chiral alkylboronic esters
In the authors’ previous studies of nickel-catalyzed tandem radical addition/cross-coupling
reactions, some products were found to be consistent with the process of carbon zincation. On this basis, the reaction conditions were screened. The addition of alkyl iodides promotes the oxidation of inactive low-valent nickel. The obtained α-boron zinc compounds were allylated under Cu(I)-mediated oxidation of borate esters to obtain homoallylic alcohols 4, which still had high enantiomeric purity, suggesting that the intermediate α-boron zinc reagent is not only
conformationally stable during the reaction, but also reacts in a stereospecific manner. Under the reaction conditions, the authors proceeded to expand the substrate, in which allyl bromide was involved as an electrophilic reagent in the subsequent transformation. The nucleophilic aryl reagents reacted better when alkyl or aryl groups were present in both the meso- and para-positions, and functional group tolerance was also better, with condensed ketones, alkynyls, alkenyls, and -TBS-protected alcohols all being compatible. However, the reactivity and selectivity of the aliphatic and alkenyl zinc reagents were significantly reduced when reacted.
The authors then used different electrophilic reagents. Both free alcohols) and amines were able to be compatible without protonation with the C-Zn bond. In addition, conjugated alkenones (26) and alkenyne (27) were able to give the target products with high stereoselectivity. In addition to allyl bromide, alkyne chloride 32 can also participate in the reaction as an electrophilic reagent. α-Boron zinc intermediates can also undergo Pb-catalyzed Negishi cross-coupling. α-Boron zinc reagents can also undergo direct bromination
