Nazarov reactions of 2-furyl vinyl ketones and related heteroaromatic enones, to produce furan-fused cyclopentanones using a flow photochemical approach, are described. Compounds possessing this connectivity between heterocycle and ketone (2-furyl, 2-benzofuryl, 2-thiophene-yl, and 2-benzothiophene-yl) have traditionally proven difficult or impossible to cyclize with typical Brønsted and Lewis acid mediated methods. Using mild flow photochemistry conditions and acetic acid (AcOH) or hexafluoroisopropanol (HFIP) as solvent, these compounds were found to cyclize in 45-97% yields, with typical UV exposure times of 3.4-6.8 min. In all cases, 2-furyl and 2-thiophene-yl enones cyclized, whereas 2-benzofuryl and 2-benzothiophene-yl enones exhibited divergent properties with reactivity patterns tied to the identity of the vinyl group. This report discloses the first photo-Nazarov reactions of tetrahydropyridine-substituted 2-furyl ketones, providing a direct approach to the corresponding fused heterocyclic motifs built around a central cyclopentanone. These motifs constitute the core structures of biologically active natural products, including the marine alkaloid nakadomarin A.

Diels-Alder reactions of tethered vinyl-metal species offer the opportunity to fashion highly functionalized diol intermediates for synthesis. We have developed the first enantioselective boron-tethered Diels-Alder reaction using quinine as a chiral promoter. Quinine recovery, enantioselectivity enhancement, and manipulation of the cyclohexene core are also investigated. DFT modeling calculations confirm the role of quinine as a bidentate ligand enhancing reaction rates. The enantioselectivity of the cycloaddition is proposed to originate from a boron-centered anomeric effect.