Excited-State Copper-Catalyzed [4 + 1] Annulation Reaction Enables Modular Synthesis of α,β-Unsaturated-γ-Lactams
Satavisha Sarkar, Arghya Banerjee, Jagrut A. Shah, Upasana Mukherjee, Nicoline C. Frederiks, Christopher J. Johnson* and Ming-Yu Ngai*
*Department of Chemistry, State University of New York, Stony Brook, New York 11794-3400, United States,
Email: chris.johnson
stonybrook.edu, ming-yu.ngaistonybrook.edu
S. Sarkar, A. Banerjee, J. A. Shah, U. Mukherjee, N. C. Frederiks, C. J. Johnson, M.-Y. Ngai, J. Am. Chem. Soc., 2022, 144, 20884-20894.
DOI: 10.1021/jacs.2c09006
Abstract
A visible-light-induced excited-state copper-catalyzed [4 + 1] annulation reaction of acrylamides and aroyl chlorides provides a wide range of γ-H, -OH, and -OR-substituted α,β-unsaturated-γ-lactams . The procedures offer mild reaction conditions, broad substrate scope, and high functional group tolerance.
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proposed mechanism
Synthesis of γ-alkoxyl, γ-hydroxy α,β-unsaturated-γ-lactams
In a glovebox, to an oven-dried 20 mL screw cap vial was added acrylamide (1.00 equiv), BINAP (20.0 mol%) and a mixture of DCE:p-Xylene in 1:1 ratio (0.100 M, with respect to acrylamide substrate). To this suspension was added aroyl chloride (2.00 equiv), Cu2O (10.0 mol%), and a magnetic stir bar. Next, the vial was capped with septum caps and taken out of the glovebox. Outside the glovebox, alcohol substrate (5.00 equiv) was added under positive pressure. The reaction vial was placed in the photoredox setup and stirred at rt with irradiation of 100 W blue LED light source (450 nm, unless otherwise stated) for 22 h. After that, the reaction mixture was removed from the light source and was directly loaded on to silica column, eluting with EtOAc:Hexane (v/v) to afford the desired product.
Synthesis of γ-hydrogen α,β-unsaturated-γ-lactams
In a glovebox, to an oven-dried 20 mL screw cap vial was added acrylamide (1.00 equiv), BINAP (20.0 mol%) and p-Xylene (0.100 M, with respect to acrylamide substrate). To this suspension was added aroyl chloride (2.00 equiv), CuI (10.0 mol%), and a magnetic stir bar. In case of substrates with low yield, additional phenyl silane (0.500 equiv) was added. Next, the vial was capped and taken out of the glovebox. The reaction vial was placed in the photoredox setup and stirred at room temp with irradiation of 100 W blue LED light source (450 nm, unless otherwise stated) for 22 h. After that, the reaction mixture was removed from the light source and was directly loaded on to silica column, eluting with EtOAc:Hexane (v/v) to afford the desired product.
Key Words
3-pyrrolin-2-ones, photochemistry, multicomponent reactions
ID: J48-Y2022
