Scalable and sustainable electrochemical allylic C-H oxidation.
New methods and strategies for the direct functionalization of C-H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of natural products, medicines and materials. The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C-H functionalization, owing to the utility of enones and allylic alcohols as versatile intermediates, and their prevalence in natural and unnatural materials. Allylic oxidations have featured in hundreds of syntheses, including some natural product syntheses regarded as "classics". Despite many attempts to improve the efficiency and practicality of this transformation, the majority of conditions still use highly toxic reagents (based around toxic elements such as chromium or selenium) or expensive catalysts (such as palladium or rhodium). These requirements are problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. This oxidation strategy is therefore rarely used for large-scale synthetic applications, limiting the adoption of this retrosynthetic strategy by industrial scientists. Here we describe an electrochemical C-H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity. It uses inexpensive and readily available materials, and represents a scalable allylic C-H oxidation (demonstrated on 100 grams), enabling the adoption of this C-H oxidation strategy in large-scale industrial settings without substantial environmental impact.
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Evan J
EJ
Horn
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Brandon R
BR
Rosen
Asymchem Life Science (Tianjin) Co., Ltd., Tianjin Economic-Technological Development Zone, 300457, China.
Yong
Y
Chen
Asymchem Life Science (Tianjin) Co., Ltd., Tianjin Economic-Technological Development Zone, 300457, China.
Jiaze
J
Tang
Chemical Development, Bristol-Myers Squibb, New Brunswick, NJ 08903, USA.
Ke
K
Chen
Chemical Development, Bristol-Myers Squibb, New Brunswick, NJ 08903, USA.
Martin D
MD
Eastgate
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Phil S
PS
Baran
D000498:Allyl Compounds / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D004563:Electrochemistry; D055772:Green Chemistry Technology; D006859:Hydrogen / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry*; D010084:Oxidation-Reduction; D013379:Substrate Specificity
D000498:Allyl Compounds; D001688:Biological Products; D016877:Oxidants; D002244:Carbon; D006859:Hydrogen