Alkylnitriles serve as key structural motifs in cyano-substituted natural products and pharmaceuticals, acting as valuable precursors for the synthesis of functional molecules, including carboxylic acids, esters, amides, and amines. Notably, chiral allylic and allenylic nitriles represent versatile synthetic building blocks, which can be readily converted into N- or O-heterocycles (e.g., lactones, lactams, pyrrolines, and piperidines), thereby facilitating the construction of core scaffolds in bioactive molecules. Transition-metal-catalyzed asymmetric allylic alkylation is a reliable and powerful strategy for constructing chiral alkylnitriles. By employing α-(2-hydroxyisopropyl) vinyl azide as an acetonitrile enolate surrogate via an allylic substitution and Grob fragmentation mechanism, it overcomes the hard-soft mismatch between the acetonitrile enolate surrogate and allylic electrophiles, thereby enabling the efficient construction of chiral alkylnitriles. Based on this strategy, we herein report an Ir(I)/LA-cocatalyzed asymmetric allenylic cyanomethylation of allenylic esters. The reaction proceeds under mild conditions, exhibiting good functional-group tolerance and wide substrate scope. Gratifyingly, the protocol demonstrates excellent scalability, affording the product on a gram scale with high yield and enantioselectivity. Furthermore, the resulting β-chiral non-racemic allenylic nitriles could be readily converted into chiral lactones, lactams, and ketones, demonstrating significant synthetic utility. This methodology provides a valuable approach for the synthesis of chiral nitriles. General procedure is as follows: in the glove box, to a dried tube was added [Ir(COD)Cl]₂ (2.5 mol%, 3.4 mg), L1 (10 mol%, 10.1 mg), anhydrous PhEt (0.2 M, 1 mL), then stirred for 15 min to obtain a dark red solution. To the solution was added 1 (1.0 eq., 0.2 mmol) to get a yellow mixture. Then 2 (1.5 eq., 0.3 mmol) and Y(OTf)₃ (5 mol%, 5.4 mg) or Sm(OTf)₃ (30 mol%, 35.9 mg) were added into the solution. The tube was tightly capped, taken outside the glove box, and stirred for 12 hr. After completion of the reaction, as indicated by TLC, the solution was filtered through a pad of silica gel. Then the resulting mixture was evaporated under the reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 30/1) to give β-chiral allenylic nitriles 3.

Key words: Allenylic Cyanomethylation, Vinyl Azides, β-Chiral Allenylic Nitriles