Catalytic cross-couplings to forge Csp 2 -Csp 2 bonds have revolutionized organic synthesis, enabling the rapid construction of molecules for the pharmaceutical and agrochemical industries. As target compounds become more complex -correlating with a higher percentage of sp hybridized atoms and stereocenters -there is a need for technologies to forge Csp 3 -Csp 3 bonds stereoselectively. Cross-electrophile couplings (XEC) involving two distinct Csp 3 -electrophiles are an attractive alternative to the traditional cross-couplings because they have broad functional group tolerance and avoid the need for sensitive organometallic reagents. However, these reactions often form homo-coupled products because the metal catalysts struggle to distinguish between the two Csp 3 -electrophiles. Moreover, there are no general strategies for rendering these reactions stereoconvergent (Fig. ). To overcome these limitations, previously unappreciated mechanistic steps and catalytic strategies need to be explored. We questioned whether an enzyme could catalyze an asymmetric Csp 3 -Csp 3 XEC. The high level of selectivity associated with biocatalytic reactions makes them attractive scaffolds for this challenge. However, as natural enzymes do not catalyze cross-coupling reactions, we needed to develop a novel XEC mechanism that is compatible with existing enzymatic machinery. Nitroalkanes are unique and ubiquitous reagents in organic synthesis but are not used as electrophiles for cross-couplings. We recognized that the reactivity of nitronates could be used for a biocatalytic XEC. Nitronates react with open-shell electrophiles to forge a C-C bond and a nitro radical anion. If this intermediate were to cleave mesolytically, the resulting radical could be quenched via hydrogen atom transfer (HAT) to afford the cross-coupled product. The key to achieving this previously unknown reaction is identifying an enzyme to facilitate C-C bond formation, C-N bond mesolytic cleavage, and HAT (Fig. ). We envision a mechanism where reduction of the alkyl halide 1 forms an alkyl radical 4 that can react with an in situ generated nitronate 5 to forge a new C-C bond and a nitro radical anion 6. Enzyme-mediated homolytic cleavage of the C-N bond generates nitrite and an alkyl radical 7 that can be terminated via HAT to afford the cross-coupled product 3 (Fig. ). The proposed mechanism is attractive because the orthogonal reactivity of nitroalkanes and alkyl halides avoids undesired dimerization products.