Enantioselective Synthesis of Trisubstituted Allenyl–B(pin) Compounds by Phosphine–Cu-Catalyzed 1,3-Enyne Hydroboration. Insights Regarding Stereochemical Integrity of Cu–Allenyl Intermediates

Catalytic enantio­selective boron–hydride additions to 1,3-enynes, which afford allenyl–B­(pin) (pin = pinacolato) products, are disclosed. Transformations are promoted by a readily accessible bis-phosphine–Cu complex and involve commercially available HB­(pin). The method is applicable to aryl- and alkyl-substituted 1,3-enynes. Trisubstituted allenyl–B­(pin) products were generated in 52–80% yield and, in most cases, in >98:2 allenyl:propargyl and 92:8–99:1 enantiomeric ratio. Utility is highlighted through a highly diastereo­selective addition to an aldehyde, and a stereospecific catalytic cross-coupling process that delivers an enantiomerically enriched allene with three carbon-based substituents. The following key mechanistic attributes are elucidated: (1) Spectroscopic and computational investigations indicate that low enantio­selectivity can arise from loss of kinetic stereo­selectivity, which, as suggested by experimental evidence, may occur by formation of a propargylic anion generated by heterolytic Cu–C cleavage. This is particularly a problem when trapping of the Cu–allenyl intermediate is slow, namely, when an electron deficient 1,3-enyne or a less reactive boron–hydride reagent (e.g., HB­(dan) (dan = naphthalene-1,8-diaminato)) is used or under non-optimal conditions (e.g., lower boron–hydride concentration causing slower trapping). (2) With enynes that contain a sterically demanding o-aryl substituent considerable amounts of the propargyl–B­(pin) isomer may be generated (25–96%) because a less sterically demanding transition state for Cu/B exchange becomes favorable. (3) The phosphine ligand can promote isomerization of the enantiomerically enriched allenyl–B­(pin) product; accordingly, lower ligand loading might at times be optimal. (4) Catalytic cross-coupling with an enantiomerically enriched allenyl–B­(pin) compound might proceed with high stereospecificity (e.g., phosphine–Pd-catalyzed cross-coupling) or lead to considerable racemization (e.g., phosphine–Cu-catalyzed allylic substitution).