Metal-Free Deoxygenation of Chiral Nitroalkanes: An Easy Entry to α-Substituted Enantiomerically Enriched Nitriles

A metal-free, mild and chemodivergent transformation involving nitroalkanes has been developed. Under optimized reaction conditions, in the presence of trichlorosilane and a tertiary amine, aliphatic nitroalkanes were selectively converted into amines or nitriles. Furthermore, when chiral beta-substituted nitro compounds were reacted, the stereochemical integrity of the stereocenter was maintained and alpha-functionalized nitriles were obtained with no loss of enantiomeric excess. The methodology was successfully applied to the synthesis of chiral beta-cyano esters, alpha-aryl alkylnitriles, and TBS-protected cyanohydrins, including direct precursors of four active pharmaceutical ingredients (ibuprofen, tembamide, aegeline and denopamine).

Automated summary

A metal-free, mild and chemodivergent transformation has been developed, selectively converting aliphatic nitroalkanes into amines or nitriles. The methodology maintains the stereochemical integrity of the stereocenter and provides alpha-functionalized nitriles with diverse functionalities. It has been successfully applied to the synthesis of key pharmaceutical ingredients.