Intermolecular Photocatalytic Chemo‐, Stereo‐ and Regioselective Thiol–Yne–Ene Coupling Reaction

Abstract

The first example of an intermolecular thiolyne-ene coupling reaction is reported for the one-pot construction of CÀ S and CÀ C bonds. Thiol-yne-ene coupling opens a new dimension in building molecular complexity to access densely functionalized products. The employment of Eosin Y/DBU/MeOH photocatalytic system suppresses hydrogen atom transfer (HAT) and associative reductant upconversion (via CÀ S threeelectron σ-bond formation). Investigation of the reaction mechanism by combining online ESI-UHRMS, EPR spectroscopy, isotope labeling, determination of quantum yield, cyclic voltammetry, Stern-Volmer measurements and computational modeling revealed a unique photoredox cycle with four radical-involving stages. As a result, previously unavailable products of the thiol-yneene reaction were obtained in good yields with high selectivity. They can serve as stable precursors for synthesizing synthetically demanding activated 1,3-dienes.

In situ Reaction Monitoring in Photocatalytic Organic Synthesis

“…To support their mechanistic rationale, an alkyne with an ionizable sulfate group ( 7 ) was synthesized to study the formation of the desired product ( 8 ) and an undesired side product ( 9 ) via photoflow ESI‐MS reaction monitoring (Figure 9, A). More recently, the same groups extended this photocatalytic method to an intermolecular thiol‐yne‐ene reaction [46] . The reaction was studied using alkyne 7 , 2‐fluorothiophenol ( 10 ) and vinylsulfide 11 in presence of (tert‐butyl)‐N‐(perfluorobiphenyl‐4‐yl)oxylamine ( 12) as radical trap with a high resolution photoflow ESI‐UHRMS monitoring setup (Figure 9, B).…”

“…More recently, the same groups extended this photocatalytic method to an intermolecular thiol-yne-ene reaction. [46] The reaction was studied using alkyne 7, 2-fluorothiophenol (10) and vinylsulfide 11 in presence of (tert-butyl)-N-(perfluorobiphenyl-4-yl)oxylamine ( 12) as radical trap with a high resolution photoflow ESI-UHRMS monitoring setup (Figure 9, B). In presence of green light, radical adduct 13 was detected, indicating that 14 is a reactive intermediate.…”

Studying Photochemical Transformations using Electrospray Ionization Mass Spectrometry (ESI‐MS)

“…The trapped radicals in the three‐component thiol‐yne‐ene photocatalytic reaction have been recently observed using ESI‐HRMS (Figure 2). [41] The reaction mixture was irradiated by green light in a transparent PTFE capillary coupled with an ESI‐MS source. The ions corresponding to trapped intermediates responsible for the formation of the target compound and byproducts were registered.…”

“…ESI mass spectrometry is a valuable tool for detecting stable spin‐trapped radical adducts and characterizing them using the MS/MS technique [47,48] . It is an elegant way of detecting short‐lived radicals in photochemical processes [41] . This approach is widely used to detect hydroxyl, superoxide, CH 3 , and CH 2 OH free radicals [49] …”

“…[47,48] It is an elegant way of detecting short-lived radicals in photochemical processes. [41] This approach is widely used to detect hydroxyl, superoxide, CH 3 , and CH 2 OH free radicals. [49] The application of mass spectrometric tags to enhance the ionization level of studied substrates is useful for MS investigation of reaction mechanisms.…”