Chiral β‐ketonitriles bearing a stereogenic carbon center at the α‐position are an important class of compounds, many of which serve as useful synthetic intermediates for the preparation of chiral 1,3‐aminoalcohols, β‐hydroxy nitriles, and related derivatives. Although the enantioselective electrophilic cyanation of enolate equivalents is one of the most promising approaches for the synthesis of chiral β‐ketonitriles, the available methods are largely limited to reactions of 1,3‐dicarbonyl compounds. Herein, we report on enantioselective electrophilic cyanation of boron enolates, which are readily prepared from α,β‐unsaturated ketones and diisopinocampheylborane (Ipc2BH) to afford chiral β‐ketonitriles with a high level of enantioselectivity. The present method is scalable and provides facile access to both enantiomers of chiral β‐ketonitriles. Analysis of the in situ generated boron enolates by NMR revealed that hydroboration proceeds in a stereospecific manner, providing α,α‐disubstituted boron enolates in the form of single isomers. Furthermore, the results of DFT calculations suggest that the cyanation of the boron enolates with p‐toluenesulfonyl cyanide (TsCN) proceeds in a highly enantioselective manner through a unique six‐membered ring transition state.

The picture shows the unique six‐membered ring transition state of the umpolung reaction described in the Full Paper by K. Kiyokawa, M. Yamanaka, S. Minakata, et al. on page 17027. Enantioselective electrophilic cyanation with chiral boron enolates and p‐toluenesulfonyl cyanide (TsCN) has been achieved, providing an efficient access to acyclic chiral β‐ketonitriles with a high degree of enantioselectivity. The cyanation was found to proceed via the six‐membered ring transition state, in which TsCN is effectively activated by the coordination of its cyano group to the Lewis acidic boron center of the boron enolate. The reaction is figuratively represented by the motif of a vampire sucking the blood of a woman (who will then turn into a vampire).