TfOH-Catalyzed [4 + 1] Annulation of p-Quinone Methides with α-Aryl Diazoacetates: Straightforward Access to Highly Functionalized 2,3-Dihydrobenzofurans

Abstract

We have developed a methodology for the greatly efficient construction of significant 2,3-dihydrobenzofuran scaffolds bearing a quaternary carbon center at the C2 position by means of [4 + 1] annulation reactions between p-quinone methides and α-aryl diazoacetates as C1 synthons through organocatalysis by readily accessible TfOH catalyst under mild and transition metal-free conditions. This metal-free protocol furnishes an operationally simple and swift process for the free assembly of diverse highly functionalized 2,3-dihydrobenzofurans and also features broad substrate scope, excellent functional group compatibility, and environmental friendliness. Mechanistic investigation suggested that the reaction undergoes a rapid cascade protonation/intermolecular Michael addition/intramolecular substitution process.

TfOH-catalyzed regioselective N2-alkylation of indazoles with diazo compounds

“…Grounded in these experiment data and the literature reports, 27–29 we propose a plausible mechanism for the N–H insertion reaction (Fig. 1).…”

Recent Advances Towards the Synthesis of Dihydrobenzofurans and Dihydroisobenzofurans

“…In 2021, Fener Chen and co‐workers disclosed the synthesis of 2,3‐DHBs 91 containing a quaternary carbon centre at the C‐2 position by the [4+1] annulation reaction of para ‐quinone methides 89 and α ‐aryl diazoacetates 90 by utilizing a catalytic amount of TfOH [105] . Some of the selected examples are as presented in Schemes 27 and 28.…”

“…In 2021, Fener Chen and co-workers disclosed the synthesis of 2,3-DHBs 91 containing a quaternary carbon centre at the C-2 position by the [4 + 1] annulation reaction of para-quinone methides 89 and α-aryl diazoacetates 90 by utilizing a catalytic amount of TfOH. [105] Some of the selected examples are as presented in Schemes 27 and 28. Significantly, the presented strategy has shown broader substrate scope and is amenable under mild, eco-friendly, and transition metal-free reaction conditions.…”

Recent advances in the application of ylide-like species in [4 + 1]-annulation reactions: an updated review

“…A racemic version of this annulation was performed using TfOH as the catalyst. 106 The reactivity of diazo compounds as carbene equivalents (Scheme 51, mechanism 2) has been exploited in a number of recently reported [4 + 1]-annulation processes. In the work of Yu et al, the reaction of tosylhydrazones 158 with unsaturated thioketones 12 in the presence of t BuOLi gave trisubstituted thiophenes 161 in high yields (Scheme 55).…”