Hydroalkylation of Unactivated Alkenes with Amides via Photoredox Catalysis and Triple Hydrogen Atom Transfer
Abstract
AbstractRadical‐mediated hydroalkylation of alkenes offers a more direct and atom‐economical route to α‐alkylated carbonyl compounds, enabling the construction of various drug scaffolds, natural products, and functional molecules. However, traditional protocols are generally restricted to active 1,3‐dicarbonyl compounds and often require oxidants, large excesses of substrates, and harsh reaction conditions. Herein, we present a photoinduced, general, and practical hydroalkylation of unactivated alkenes with amides. Both inter‐ and intramolecular hydroalkylation reactions are achieved under mild and metal‐free conditions. This method demonstrates excellent chemo‐, regio‐, and diastereoselectivity, along with broad substrate scope and excellent functional group tolerance. A range of short‐chain gaseous olefins, including ethylene, can also undergo the reaction successfully. Its versatility is further highlighted by diverse late‐stage modification and synthesis of structurally complex bioactive molecules. Mechanistic investigations reveal that the reaction proceeds via a triple hydrogen atom transfer (HAT) process involving both intra‐ and intermolecular steps. The success of this chemistry is attributed to the controlled generation of relatively weak electrophilic α‐carbonyl radicals and the strategic application of radical polarity‐match/mismatch effect to finely tune the reactivity between distinct radical species and unactivated alkenes or the HAT donor.
Article Details
Authors (12)
Beibei Yi
State Key Laboratory of Green Pesticide Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction Ministry of Education College of Chemistry Central China Normal University (CCNU) 152 Luoyu Road Wuhan Hubei 430079 P.R. China
He Zhang
Chunxiang Pan
State Key Laboratory of Green Pesticide, Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan, Hubei 430079, P. R. China
Jianzhong Lu
CCNU-uOttawa Joint Research Centre, State Key Laboratory of Green Pesticide, Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan, Hubei 430079, P. R. China
Quanzhe Li
CCNU-uOttawa Joint Research Centre, State Key Laboratory of Green Pesticide, Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan, Hubei 430079, P. R. China
Kaiyao Yuan
State Key Laboratory of Green Pesticide Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction Ministry of Education College of Chemistry Central China Normal University (CCNU) Wuhan Hubei P. R. China
Qian Xing
State Key Laboratory of Green Pesticide Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction Ministry of Education College of Chemistry Central China Normal University (CCNU) 152 Luoyu Road Wuhan Hubei 430079 P.R. China
Wenxuan Chen
State Key Laboratory of Green Pesticide Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction Ministry of Education College of Chemistry Central China Normal University (CCNU) 152 Luoyu Road Wuhan Hubei 430079 P.R. China
Xiaoya An
State Key Laboratory of Green Pesticide Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction Ministry of Education College of Chemistry Central China Normal University (CCNU) 152 Luoyu Road Wuhan Hubei 430079 P.R. China
WMWW Kandegama
Department of Horticulture and Landscape Gardening Faculty of Agriculture and Plantation Management Wayamba University of Sri Lanka Makandura Gonawila (NWP) 60170 Sri Lanka
Guozhu Zhang
State Key Laboratory of Green Pesticide, Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan, Hubei 430079, P. R. China
Rui Guo