Access to Alkenyl Cyclobutanols by Ni‐Catalyzed Regio‐ and Enantio‐Selective <i>syn</i> ‐Hydrometalative 4‐ <i>exo</i> ‐ <i>trig</i> Cyclization of Alkynones

Abstract Enantioselective synthesis of (spiro)cyclobutane derivatives poses significant challenges yet holds promising applications for both synthetic and medicinal chemistry. We report here a nickel‐catalyzed asymmetric syn ‐hydrometalative 4‐ exo ‐ trig cyclization of 1,4‐alkynones to synthesize alkenyl cyclobutanols with a tetrasubstituted stereocenter. This strategy features a broad substrate scope, delivering a variety of trifluoromethyl‐containing rigid (spiro)carbocycle skeletons in good yields with high enantioselectivities (up to 84 % yield and 98.5 : 1.5 er). The synthetic utility is demonstrated through stereospecific transformations into fused spiro molecules. Experimental and computational mechanistic studies indicate that the reaction is initiated by an active Ni−H species, with carbonyl‐directed hydrometalation as the key for regioselective control. This catalytic method provides a general solution for regioselective hydrofunctionalization of alkynes and represents an efficient reaction pattern for assembling highly strained enantioenriched bioisosteres.