Chemodivergent Photocatalytic Synthesis of Dihydrofurans and β,γ‐Unsaturated Ketones

Abstract

A synthetic procedure, catalysed by Ir(ppy)3 under visible‐light irradiation, for the chemodivergent synthesis of 2,3‐dihydrofurans (3) or β,γ‐unsaturated ketones (7) starting from α‐halo ketones (1) and alkenes (2) has been developed. The mild reaction conditions and the redox‐neutral nature of the process make it particularly sustainable avoiding the use of both sacrificial reactants and stoichiometric strong oxidants. Careful experimental investigations, supported by DFT calculations, allowed to disclose in details a possible mechanistic pathway and to direct the synthesis chemodivergently either toward 3 or 7, depending not only on the nature of the substrates, but also on the choice of the experimental conditions.

Green Metrics and Sustainability in Photocatalysis

“…[53] Among the recently proposed photocatalytic methods, one of the most employed involves the generation of sp 3 À carbon-centered radicals as key intermediates, obtained through the displacement of CÀ halogen bonds. [54] As an example of application of this strategy, we reported in 2021 the visible light promoted synthesis of 2,3dihydrofurans (Scheme 8), [55] five-membered heterocyclic scaffolds widely present in medicinally relevant compounds, [56] materials, dyes [57] and synthetic intermediates. [58] The process is redox-neutral, acting the Ir-catalyst (A) as both reductant and oxidant in two different steps of the catalytic cycle.…”

A formal (3 + 2) annulation–Cannizzaro cascade of bifunctional peroxides for the synthesis of dihydrofurans

“…5 In particular, such annulation strategies have been improved to eco-friendly catalytic, photocatalytic, or electrochemical conditions in recent years. 6 Although these methods provide a direct protocol to construct 2,2-disubstituted dihydrofuran structures, it is generally difficult to incorporate functional side chains into such cores. In our view, 2,2-bifunctionalized DHFs bearing two modifiable handles would be more attractive to synthetic and medicinal chemists for structural derivatization.…”

Diethyl (5-Benzyl-2-(4-(N′-hydroxycarbamimidoyl)phenyl)-5-methyl-4,5-dihydrofuran-3-yl)phosphonate

“…Among heterocyclic compounds, dihydrofurans are important scaffolds that frequently appear in natural products [4] and are extensively studied in various biological applications, serving as intermediates in organic synthesis [5]. However, the derivatives of dihydrofuran derivatives bearing both the phosphonyl and amidoxime groups are relatively rare [6].…”

“…J H-H = 14.1 Hz, 2 J H-H = 40.1 Hz, 2H, H-(CH 2 )), 2.80 (dd,4 J H-H = 3.3 Hz, 2 J H-H = 15.5 Hz, 1H, H-(CH 2 )), 1.50 (s, 3H, CH 3 ), 1.18 (t,3 J H-H = 7.0 Hz, 3H, CH 3 ), 1.13 (t, 3 J H-H = 7.0 Hz, 3H, CH 3 ) 13. C NMR (100 MHz, CDCl 3 ) δ (ppm) 161.7 (d, J = 26.2 Hz, C), 136.5 (C), 134.5 (C), 131.7 (2CH Ar ), 130.6 (2CH Ar ), 129.6 (2CH Ar ), 128.4 (2CH Ar ), 127.0 (CH Ar ), 118.7 (C), 113.6 (C), 97.3 (d, J = 213.8 Hz, C), 88.1 (d, J = 11.8 Hz, C), 61.7 (t, J = 6.3 Hz, 2CH 2 ), 46.8 (CH 2 ), 44.3 (d, J = 8.6 Hz, CH 2 ), 27.1 (CH 3 ), 16.3 (t, J = 6.4 Hz, 2CH 3 ).…”