title: Mechanistic evidence for intermolecular radical carbonyl additions promoted by samarium diiodide.
abstract: In this work, mechanistic studies were performed to understand the SmI2/H2O-mediated coupling of N-acyl oxazolidinones with acrylates and acrylamides, providing gamma-keto esters and amides, respectively. Our results provide experimental evidence that C-C bond formation via intermolecular radical addition reactions to carbonyl substrates can be promoted by samarium diiodide. Coupling reactions with N-cyclopropylcarbonyl-2-oxazolidinone suggest the alpha,beta-unsaturated esters/amides are reduced by the low-valent lanthanide reagent and not the N-acyl oxazolidinones, as originially proposed (J. Am. Chem. Soc. 2005, 127, 6544). Rate measurements support the preferred reduction of an acrylate or acrylamide by SmI2/H2O in the presence of an N-acyl oxazolidinone. In the absence of the N-acyl oxazolidinone, SmI2/H2O promotes dimerization of the acrylates, whereas the C=C bond of the acrylamides is reduced. In addition, coupling of the Pfp ester of Cbz-protected phenylalanine with an acrylamide leads only to reduction of the acrylamide and recovered ester, whereas the same coupling with the N-acyl oxazolidinone derivative provides the gamma-keto amides. These results imply that a pathway involving nucleophilic acyl substitution cannot take place and that a radical mechanism must be invoked to explain the C-C bond formation. We propose that the acrylate/acrylamide is reduced to a conjugated ketyl radical that adds to the exocyclic carbonyl group of the N-acyl oxazolidinone, activated through bidentate coordination to a lanthanide ion.
authors.affiliation: Center of Insoluble Protein Structures (inSPIN), Department of Chemistry, Interdiscplinary Nanoscience Center, University of Aarhus, Langelandsgade 140, 8000 Aarhus C, Denmark.
authors.forename: Anna Mette
authors.initials: AM
authors.lastname: Hansen
authors.forename: Karl B
authors.initials: KB
authors.lastname: Lindsay
authors.forename: P K
authors.initials: PK
authors.lastname: Sudhadevi Antharjanam
authors.forename: Jakob
authors.initials: J
authors.lastname: Karaffa
authors.forename: Kim
authors.initials: K
authors.lastname: Daasbjerg
authors.forename: Robert A
authors.initials: RA
authors.lastname: Flowers
authors.forename: Troels
authors.initials: T
authors.lastname: Skrydstrup