Copper-Catalyzed Asymmetric Carbocyanation of 1,3-Dienes and Vinylarenes with Simple Aldehydes and Alkanes

The asymmetric radical carbocyanation of alkenes represents
a powerful
strategy for synthesizing chiral nitriles. While readily available
aldehydes and alkanes are unique and atom-economical carbon radical
precursors via hydrogen atom transfer (HAT), their utilization in
the asymmetric carbocyanation of alkenes remains underdeveloped. Herein,
we report a copper-catalyzed asymmetric radical carbocyanation of
1,3-dienes and vinylarenes, employing both aldehydes and alkanes as
carbon radical sources. This protocol utilizes organic peroxides as
radical initiators in combination with chiral bisoxazoline-based copper
catalysts. The choice of organic peroxide proved critical in controlling
reactivity: tert-butyl hydroperoxide (TBHP) enabled
efficient aldehyde-derived acylcyanation, while di-tert-butyl peroxide (DTBP) under photoinduced conditions was optimal
for alkane-derived alkylcyanation. This strategy provides a practical
and versatile approach to accessing structurally diverse chiral allylic
and benzylic nitriles.