Nonprecious metal catalysts are cost-effective and sustainable alternatives to other commonly used, expensive transition metals. Therefore, process chemists across various industries have invested in this technology, harnessing iron, cobalt, nickel, copper, as well as other metals to catalyze well-studied and novel transformations. This review continues a series highlighting industry-relevant literature published in the field of nonprecious metal catalysis between November 2020 and February 2021.

Due to their inherent ring strain and electrophilicity, epoxides are highly attractive building blocks for fundamental organic reactions. However, controlling the regioselectivity of disubstituted epoxide transformations is often particularly challenging. Most Lewis acid-mediated processes take advantage of intrinsic steric or electronic substrate bias to influence the site of nucleophilic attack. Therefore, the scope of many of these systems is frequently quite limited. Recent efforts to generate catalysts that can overcome substrate bias have expanded the synthetic utility of these well-known reactions. In this Perspective, we highlight various regioselective transformations of disubstituted epoxides, emphasizing those that have inspired the production of challenging, catalyst-controlled processes.

We report the regioselective carbonylation of 2,2-disubstituted epoxides to β,β-disubstituted β-lactones. Mechanistic studies revealed epoxide ring-opening as the turnover limiting step, an insight that facilitated the development of improved reaction conditions using weakly donating, ethereal solvents. A wide range of epoxides can be carbonylated to β-lactones, which are subsequently ringopened to produce ketone-based aldol adducts, providing an alternative to the Mukaiyama aldol reaction. Enantiopure epoxides were demonstrated to undergo the carbonylation/ringopening process with retention of stereochemistry to form enantiopure β-hydroxy esters.

Reactions facilitating inversion of alkene stereochemistry are rare, sought-after transformations in the field of modern organic synthesis. Although a number of isomerization reactions exist, most methods require specific, highly activated substrates to achieve appreciable conversion without side product formation. Motivated by stereoinvertive epoxide carbonylation reactions, we developed a two-step epoxidation/deoxygenation process that results in overall inversion of alkene stereochemistry. Unlike most deoxygenation systems, carbon monoxide was used as the terminal reductant, preventing difficult postreaction separations, given the gaseous nature of the resulting carbon dioxide byproduct. Various alkyl-substituted cis- and trans-epoxides can be reduced to trans- and cis-alkenes, respectively, in >99:1 stereospecificity and up to 95% yield, providing an alternative to traditional, direct isomerization approaches.

Catalytic enantioselective conjugate addition (ECA) reactions with readily accessible and stereochemically defined E-, Z-, di-and trisubstituted alkenyl aluminum compounds are disclosed. Transformations are promoted by various NHCcopper catalysts (NHC = N-heterocyclic carbene), which are derived from enantiomerically pure sulfonate imidazolinium salts. The desired products were obtained in up to 89% yield and > 99:1 e.r.; the alkenyl moiety was transferred with complete retention of its stereochemical identity in all instances. The scope and limitations of the approach, key mechanistic attributes, and representative functionalization are presented as well.