The synthesis of enantiopure and structurally unique spiro-type molecules is of utmost significance in catalysis, synthetic chemistry, and related fields. We present here a general solution, a nickel-catalyzed [2 + 2 + 2] cycloaddition, for accessing enantioenriched spiropyridines from readily available nitriles and alkynes in a single synthetic step, including (1) enantio-relay double [2 + 2 + 2] cycloaddition of malononitriles with alkynes and (2) kinetic resolution [2 + 2 + 2] cycloaddition of racemic pyridine-containing nitriles with alkynes. Both strategies feature a broad substrate scope and exclusive regioselectivities, and are scalable to multigram. Remarkably, the double [2 + 2 + 2] cycloaddition integrates enantio-induction by desymmetrizing dinitriles during the initial catalytic cycle with additional enantio-enhancement during the second cycloaddition (enantio-relay), yielding excellent enantioselectivities (>
99% ee for all examined examples). Furthermore, the highly efficient kinetic resolution strategy enables the achievement of exceptionally high enantioselectivities without compromising yields (