The first copper(I)-catalyzed enantioselective borylation of racemic benzyl chlorides has been realized by aq uadrant-by-quadrant structure modulation of QuinoxP*type bisphosphine ligands.T his reaction converts racemic mixtures of secondary benzyl chlorides into the corresponding chiral benzylboronates with high enantioselectivity (up to 92 % ee). The results of mechanistic studies suggest the formation of ab enzylic radical intermediate.T he results of DFT calculations indicate that the optimal bisphosphine-copper(I) catalyst engages in noncovalent interactions that efficiently recognize the radical intermediate,a nd leads to high levels of enantioselectivity. Scheme 1. Copper(I)-catalyzed borylation of alkyl electrophiles.

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We report the first copper(i)-catalysed intramolecular alkylboration of terminal allenes with an alkyl halide moiety. The reaction provides alkenylboronates bearing a four-membered ring structure with high regio- and diastereocontrol. A possible reaction mechanism is proposed, involving the facile isomerization of an allylcopper(i) intermediate. A DFT study explains the experimental regio- and diastereoselectivity.

A new C 2-symmetrical P-chirogenic bisphosphine ligand with silyl substituents on the ligand backbone, (R,R)-5,8-TMS-QuinoxP*, has been developed. This ligand showed higher reactivity and enantioselectivity for the direct enantioconvergent borylation of cyclic allyl electrophiles than its parent ligand, (R,R)-QuinoxP* (e.g., for a piperidine-type substrate: 95% ee vs 76% ee). The borylative kinetic resolution of linear allyl electrophiles was also achieved using (R,R)-5,8-TMS-QuinoxP* (up to 90% ee, s = 46.4). An investigation into the role of the silyl groups on the ligand backbone using X-ray crystallography and computational studies displayed interlocking structures between the phosphine and silyl moieties of (R,R)-5,8-TMS-QuinoxP*. The results of DFT calculations revealed that the entropy effect thermodynamically destabilizes the dormant dimer species in the catalytic cycle to improve the reactivity. Furthermore, in the direct enantioconvergent case, detailed calculations indicated a pronounced enantioselective recognition of carbon–carbon double bonds, which is virtually unaffected by the chirality at the allylic position, as a key for the borylation from both enantiomers of racemic allyl electrophiles.

Multisubstituted allylic boronates are attractive and valuable precursors for the rapid and stereoselective construction of densely substituted carbon skeletons. Herein, we report the first synthetic approach for differentially 2,3,3-trialkyl-substituted allylic boronates that contain a stereodefined tetrasubstituted alkene structure. Copper­(I)-catalyzed regio- and stereoselective three-component coupling reactions between gem-dialkylallenes, alkyl halides, and a diboron reagent afforded sterically congested allylic boronates. The allylboration of aldehydes diastereoselectively furnished the corresponding homoallylic alcohols that bear a quaternary carbon. A computational study revealed that the selectivity-determining mechanism was correlated to the coordination of a boryl copper­(I) species to the allene substrate as well as the borylcupration step.

A new series of C 1-symmetric P-chirogenic bisphosphine ligands of the type (R)-5,8-Si-Quinox-tBu3 (Silyl = SiMe3, SiEt3, SiMe2Ph) have been developed. The bulky silyl modulators attached to the ligand backbone fix the phosphine substituents to form rigid chiral environments that can be used for substrate recognition. The ligand showed high performances for a copper­(I)-catalyzed asymmetric borylative cyclopropanation of bulky silyl-substituted allylic electrophiles to afford higher disfavored 1,2-cis-silyl-boryl-cyclopropanes than the other possible isomers, trans-cyclopropane and allylboronate (up to 97% yield; 98% ee; cis/trans = >99:1; cyclopropane/allylboronate = >99:1). Detailed computational studies suggested that the highly rigid phosphine conformation, which is virtually undisturbed by the steric interactions with the bulky silyl-substituted allyl electrophiles, is key to the high stereo- and product-selectivities. Furthermore, the detailed computational analysis provided insight into the mechanism of the stereoretention or -inversion of the chiral alkylcopper­(I) intermediate in the intramolecular cyclization.

A copper­(I)-catalyzed linear-selective allylation of carbonyl compounds with trisubstituted allylboronates has been achieved by capitalizing on the electronic and steric effects of silyl groups. This reaction provides stereodefined trisubstituted homoallyl alcohol derivatives that bear a synthetically useful alkenyl silane moiety. The results of a computational study suggested that the silyl directing group thermodynamically stabilizes the sterically hindered allylcopper­(I) intermediate and kinetically facilitates the carbonyl allylation path for the linear product by lowering the energy of its transition state.

The first copper(I)‐catalyzed enantioselective borylation of racemic benzyl chlorides has been realized by a quadrant‐by‐quadrant structure modulation of QuinoxP*‐type bisphosphine ligands. This reaction converts racemic mixtures of secondary benzyl chlorides into the corresponding chiral benzylboronates with high enantioselectivity (up to 92 % ee). The results of mechanistic studies suggest the formation of a benzylic radical intermediate. The results of DFT calculations indicate that the optimal bisphosphine‐copper(I) catalyst engages in noncovalent interactions that efficiently recognize the radical intermediate, and leads to high levels of enantioselectivity.