Ball-milling-enabled nickel-catalyzed radical relayed reductive cross-coupling

Nickel-catalyzed radical relayed dicarbofunctionalizations of olefins, utilizing carbon electrophiles as coupling partners, present a powerful strategy for the streamlined construction of aliphatic structures. However, traditional solution-phase methods encounter challenges such as the need for bulk solvents, limited coupling partners, long reaction times, and air-/moisture-sensitive reagents. As an alternative strategy, ball-mill-enabled metal-catalyzed cross-coupling reactions have gained attention due to their high reactivity and atomic efficiency. While many ball-mill-enabled cross-coupling reactions are limited to single- and two-component methodologies, three-component solid-state cross-coupling reactions remain relatively scarce. In this work, we report the first, to our knowledge, ball-milling-enabled Ni-catalyzed reductive dicarbofunctionalization of alkenes. Two distinct readily available electrophiles, Csp2 and Csp3 halides, are simultaneously installed across a variety of olefins at room temperature in a highly regioselective manner withing 1.5 h. By harnessing the benefits of ball milling and radical relayed reactions, we anticipate further advancements in sustainable and efficient synthetic methodologies.