Ni-Catalyzed Enantioselective Dialkyl Carbinol Synthesis via Decarboxylative Cross Coupling: Development, Scope, and Applications

Abstract

The first enantioselective decarboxylative Negishi-type alkylations of a-oxy carboxylic acids is reported via the intermediacy of redox-active esters (RAEs). This transformation enables a radical-based retrosynthesis of seemingly trivial enantiopure dialkylcarbinols. This article includes a discussion of the history of such couplings, the retrosynthetic ramifications of such a coupling, the development of general conditions, and an extensive series of applications that vividly demonstrate how it can simplify synthesis.

Enantioselective C(sp3)–C(sp3) Reductive Cross-Electrophile Coupling of Unactivated Alkyl Halides with α-Chloroboronates via Dual Nickel/Photoredox Catalysis

“…Reaction of alkyl iodide bearing a conjugated ester can readily proceed to give the target product (16). In addition, when alkyl electrophiles that contain heterocyclic or multicyclic skeletons, such as thiophene (17), furan (18), purinedione (19), naphthalene (20), or steroid (21), were treated with the above-described coupling conditions, comparable yields and enantioselectivities were also observed. Meanwhile, with this protocol, secondary alkyl iodides can be utilized to give chiral boronic ester products in acceptable yields and enantioselectivities (22−24).…”

“…17 Although an elegant nickel-catalyzed enantioselective decarboxylative Negishi coupling was utilized to improve the efficiency of the formation of compound 38, several extra steps were still required to reach the target. 18 In contrast, with our method, this intermediate can be smoothly obtained in good yield and enantioselectivity after simple oxidation. Identically, this newly developed C(sp 3 )−C(sp 3 ) coupling can also be leveraged following intramolecular transesterification to rapidly access the lactone 41.…”

“…Identically, this newly developed C(sp 3 )−C(sp 3 ) coupling can also be leveraged following intramolecular transesterification to rapidly access the lactone 41. Compared with previous synthetic routes, 18,19 our protocol represents one of the most efficient methods to construct this structure.…”

Recent Advances in Nonprecious Metal Catalysis

“…Dev. XXXX, XXX, XXX−XXX alkylzinc chlorides to prepare enantiopure dialkyl carbinols (Scheme 18) 31. NiCl 2 •glyme in combination with a chiral BOX ligand (L6) was found to be the optimal catalyst.…”