Visible‐Light‐Induced C4‐Selective Functionalization of Pyridinium Salts with Cyclopropanols

Abstract

The site-selective C À Hf unctionalization of heteroarenes is of considerable importance for streamlining the rapid modification of bioactive molecules.H erein, we report ag eneral strategy for visible-light-induced b-carbonyl alkylation at the C4 position of pyridines with high site selectivity using various cyclopropanols and N-amidopyridinium salts.I nt his process,hydrogen-atom transfer between the generated sulfonamidyl radicals and OÀHb onds of cyclopropanols generates b-carbonyl radicals,p roviding efficient access to synthetically valuable b-pyridylated (aryl)ketones,a ldehydes,a nd esters with broad functional-group tolerance.I na ddition, the mild method serves as an effective tool for the site-selective late-stage functionalization of complex and medicinally relevant molecules.

Sequential Ring Opening/In Situ SO2-Capture/Alkynylation of Cyclopropanols with Alkynyl Triflones Initiated by Energy Transfer

“…Fragmentation of the newly formed radical II produces a trifluoromethyl radical III, along with the generation of SO 2 . Thanks to the relative high bond dissociation energy (BDE) of fluoroform (106 kcal/ mol) 23 as compared to the O−H bond in cyclopropanols (BDE ≈ 90 kacl/mol), 24 subsequent HAT of the trifluoromethyl radical III against cyclopropanol 1 would occur to generate an alkoxy radical species IV, 25 followed by the radical β-scission to give β-keto radical species V. At this stage, the resulting radical V could be trapped by released SO 2 to afford the thermodynamically more stable alkyl sulfonyl radical VI. Radical addition across the C−C triple bond of alkynyl triflone 2, followed by a β-elimination, furnishes the final product 3 or 4, accompanied by the regeneration of radical II that makes the radical chain reaction operative.…”

N-Amino pyridinium salts in organic synthesis

“…The scope of C4 functionalization was extended by utilizing cyclopropanols as the precursors of β-keto radicals (Scheme 27b). 66 Similar to the mechanism depicted in Scheme 27a, the β-keto radicals are generated from the N-centered radicals 87 and eventually add to the C4 position of N-aminopyridinium salts to afford β-pyridylated carbonyls 92.…”