Convergent Synthesis of Polysubstituted Furans via Catalytic Phosphine Mediated Multicomponent Reactions

Abstract

Tri- or tetrasubstituted furans have been prepared from terminal activated olefins and acyl chlorides or anhydrides by a multicomponental convergent synthesis mode. Instead of stoichiometric nBu3P, only catalytic nBu3P or nBu3P=O is needed to furnish the furans in modest to excellent yields with a good functional group tolerance under the aid of reducing agent silane. This synthetic method features a silane-driven catalytic intramolecular Wittig reaction as a key annulation step and represents the first successful application of catalytic Wittig reaction in multicomponent cascade reaction.

Synthesis of Trisubstituted Furans from Activated Alkenes by P(III)/P(V) Redox Cycling Catalysis

“…Based on the work of He and co-workers, two reaction pathways are plausible for the reaction of diketone 1 with acyl chloride 2 using the phosphetane catalyst 3a and phenylsilane as the terminal reductant . In the first reaction pathway, after Michael addition of reduced phosphine 5 to activated alkene 1 , formed enolate I-1 reacts with acyl chloride under C -acylation and subsequent deprotonation to form enolate I-2 (Figure , reaction pathway I ).…”

“…Based on the work of He and co-workers, two reaction pathways are plausible for the reaction of diketone 1 with acyl chloride 2 using the phosphetane catalyst 3a and phenylsilane as the terminal reductant. 30 In the first reaction pathway, after Michael addition of reduced phosphine 5 to activated alkene 1, formed enolate I-1 reacts with acyl chloride under C-acylation and subsequent deprotonation to form enolate I-2 (Figure 2, reaction pathway I). A nucleophilic attack of the enolate leads to a ring closure reaction, and the subsequent deoxygenation results in the formation of trisubstituted furan 4 and phosphine oxide 3, which can be reduced by the terminal reductant.…”

“…21,29 He and co-workers updated their synthesis of tetrasubstituted furans starting from acrylates toward the use of catalytic amounts of tributylphosphine at elevated temperatures with the same terminal reductant (Scheme 1b). 20,30 Recently, Lin and co-workers also revised their method toward the synthesis of furo[2,3-f ]dibenzotropones. 31 In the field of activated alkenes, neither the use of 1,2diacylethenes nor 3-acyl acrylates has been explored for the metal-free, catalytic synthesis of substituted furans, and only few examples can be found in the literature under stoichiometric conditions.…”

Synthesis of Polysubstituted Furans: An Update Since 2019

“…[85][86][87] In this context, He and his co-workers in 2019 demonstrated a catalytic phosphine mediated multi component cascade reaction for the synthesis of tri-or tetrasubstituted furans 146 from terminal activated olefins 141 and acyl chlorides 142 or anhydrides in good to excellent yields. [88] Only catalytic n Bu 3 P or n Bu 3 P=O is needed to obtain the products instead of stoichiometric n Bu 3 P. For the formation of tetrasubstituted furans, the catalytic cycle initiates with the nucleophilic addition of In the search for a transition-metal free approach to polysubstituted furans, [89][90][91][92] Zhao et al in 2020 described the synthesis of polysubstituted furans 155 from β-keto compounds 148 and vinyl dichlorides 149 via a basepromoted domino reaction in moderate to excellent yields. [93] The mechanism initiates with the elimination of 1,1-dichloroalkene under basic conditions to form alkynyl Multisubstituted furans are still underdeveloped due to limited scope of subunits for furan ring construction while multisubstituted pyrroles were efficiently synthesized based on the [3 + 2] cycloaddition strategy.…”

“…It is a challenging task to develop a catalytic version of phosphine‐mediated Wittig reaction by in‐situ recycling of by‐product phosphine oxide under the aid of a reducing agent [85–87] . In this context, He and his co‐workers in 2019 demonstrated a catalytic phosphine mediated multi component cascade reaction for the synthesis of tri‐ or tetra‐substituted furans 146 from terminal activated olefins 141 and acyl chlorides 142 or anhydrides in good to excellent yields [88] . Only catalytic n Bu 3 P or n Bu 3 P=O is needed to obtain the products instead of stoichiometric n Bu 3 P. For the formation of tetrasubstituted furans, the catalytic cycle initiates with the nucleophilic addition of n Bu 3 P to an activated alkene 141 like acrylates.…”