Mechanistic Evidence for Intermolecular Radical Carbonyl Additions Promoted by Samarium Diiodide

• Published in: Journal of the American Chemical Society 2006-08, Vol.128 (30), p.9616-9617
• Main Authors: Hansen, Anna Mette, Lindsay, Karl B, Sudhadevi Antharjanam, P. K, Karaffa, Jakob, Daasbjerg, Kim, Flowers, Robert A, Skrydstrup, Troels
• Format: Article
• Language: English
• Subjects: Chemistry; Exact sciences and technology; Kinetics and mechanisms; Organic chemistry; Reactivity and mechanisms
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja060553v

In this work, mechanistic studies were performed to understand the SmI2/H2O-mediated coupling of N-acyl oxazolidinones with acrylates and acrylamides, providing γ-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 α,β-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 γ-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.