LAUSR

Carbon-carbon bond formation is the core of organic synthesis. Transition metal-catalyzed cross-coupling reaction between organohalides and organometallic reagents is one of the most important and straightforward methods for construction of C–C bonds. The catalytic cross coupling between two sp-carbon centers, e.g., aryl-aryl crosscouplings, has become a routine transformation in laboratories and industrial processes for synthesis of drugs and fine chemicals. Metal-catalyzed cross-coupling between two spcarbon centers (Figure 1(a)), in contrast, is less developed, although alkyl-alkyl bonds are even more pervasive in organic molecules than aryl-aryl bonds and incorporation of sp-hydridized carbons, particularly stereogenic carbon centers, can have implications for structure and function in drug discovery [1]. The slow oxidative addition of alkyl halides to low valent transition metals, facile β-hydride elimination of alkylmetal intermediates and slow reductive elimination from dialkyl metal intermediates comprise the main obstacle to efficient cross-coupling of two sp-carbon centers. In addition to construction of the carbon-carbon bond itself, even more challenging is controlling the stereochemistry at one or both carbons of the new bond in the coupling involving secondary or tertiary alkyl partners [2]. In the last two decades, much effort has been devoted to the development of new transition metal catalysts for the alkylalkyl cross coupling reactions and significant advances have been made using various metals including Cu, Ni, Pd, Fe, Co, and Ag. Among them, nickel-based catalysts have proved to be especially effective, which can not only facilitate various alkyl-alkyl cross couplings but also control the stereochemistry at one of the carbon centers of the new carboncarbon bond. However, the stereochemical control is mainly on electrophile partner and the stereochemical control on nucleophile partner is only limited to a single cyclic nucleophile, 2-zincated N-Boc-pyrrolidine (Figure 1(b)) [3]. The simultaneous control of both stereocenters in reactions between two racemic partners is especially challenging (Figure 1(c)). In a new study, published in Science, Fu and his coworkers [4] have demonstrated that a single chiral nickel catalyst can control two vicinal stereocenters simultaneously in coupling of racemic secondary electrophiles with racemic secondary nucleophiles, to give cross-coupling products in high diastereoselectivities and enantioselectivities (Figure 1(d–f)). Acyclic β-zincated amide nucleophiles were disclosed in this method to address the restriction of nucleophiles in enantioconvergent alkyl-alkyl bond formations. Using a chiral nickel/(pyridine-oxazoline) catalyst, both achiral primary and secondary alkyl iodides were able to couple with racemic β-zincated amides through stereoconvergent process. The scope of this family of racemic nucleophiles is fairly broad and the functional group compatibility is particularly remarkable. Based on this dramatic advance in nucleophile partner, the