The catalytic asymmetric construction of Csp3–Csp3 bonds remains one of the foremost challenges in organic synthesis.1 Metal-catalyzed cross-electrophile couplings (XEC) have emerged as a powerful tool for C–C bond formation.2-5 However, coupling two distinct Csp3-electrophiles with high cross- and stereoselectivity continues as an unmet challenge. Here, we report a highly chemo- and enantioselective Csp3–Csp3 XEC between alkyl halides and nitroalkanes catalyzed by flavin-dependent ‘ene’-reductases. Photoexcitation of the enzyme-templated charge-transfer complex between an alkyl halide and flavin cofactor enables the chemoselective reduction of alkyl halide over the thermodynamically favored nitroalkane partner. The key C–C bond-forming step occurs via the reaction of an alkyl radical with an in situ generated nitronate to form a nitro radical anion that collapses to form nitrite and an alkyl radical. An enzyme-controlled hydrogen atom transfer affords high levels of enantioselectivity. This reactivity is unknown in small molecule catalysis and highlights the potential for enzymes to use new mechanisms to address long-standing synthetic challenges.