Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 15475-15487 |
| Number of pages | 13 |
| Journal | ACS Catalysis |
| Volume | 15 |
| Issue number | 17 |
| DOIs | |
| State | Published - 5 Sep 2025 |
Keywords
- acyl radical
- alkyl radical
- asymmetric carbocyanation
- copper-catalyzed
- hydrogen atom transfer