37. Intermolecular Crossed [2 + 2] Cycloaddition Promoted by Visible-Light Triplet Photosensitization: Expedient Access to Polysubstituted 2-Oxaspiro[3.3]heptanes
Philip R. D. Murray, Willem M. M. Bussink, Geraint H. M. Davies, Farid W. van der Mei, Alyssa H. Antropow, Jacob T. Edwards, Laura Akullian D’Agostino, J. Michael Ellis, Lawrence G. Hamann, Fedor Romanov-Michailidis, Robert R. Knowles
J. Am. Chem. Soc. 2021, 143, 4055–4063. DOI: 10.1021/jacs.1c01173
ABSTRACT: This paper describes an intermolecular cross-selective [2 + 2] photocycloaddition reaction of exocyclic arylidene oxetanes, azetidines, and cyclobutanes with simple electron-deficient alkenes. The reaction takes place under mild conditions using a commercially available Ir(III) photosensitizer upon blue light irradiation. This transformation provides access to a range of polysubstituted 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, and spiro[3.3]heptane motifs, which are of prime interest in medicinal chemistry as gem-dimethyl and carbonyl bioisosteres. A variety of further transformations of the initial cycloadducts are demonstrated to highlight the versatility of the products and enable selective access to either of a syn– or an anti-diastereoisomer through kinetic or thermodynamic epimerization, respectively. Mechanistic experiments and DFT calculations suggest that this reaction proceeds through a sensitized energy transfer pathway.