Phosphine-Catalyzed [3 + 2] Annulations of γ-Functionalized Butynoates and 1C,3O-Bisnucleophiles: Highly Selective Reagent-Controlled Pathways to Polysubstituted Furans

Abstract

In this paper, a reagent-controlled [3+2] annulation of γ-functionalized butynoates 1 and 1C,3O-bisnucleophiles 2 is reported, which leads to three distinct furan skeletons 3-5. A PPh(3) catalyst preferentially attached the β-position of 1a, facilitating α-addition to furnish Type I annulations. With the assistance of Ag(2)O, Type II annulations were achieved via selective γ-substitution. In the absence of the PPh(3) catalyst, the reagent Cs(2)CO(3) promoted β-addition to realize Type III annulations.

Phosphine Organocatalysis

“…In 2011, Tong reported the first example of phosphine-catalyzed furan synthesis from an alkynoate and a carbon pronucleophile. 518 In Tong’s proposed mechanism, addition of triphenylphosphine generates the familiar vinyl phosphonium enoate 292 , which further activates the pronucleophile 293 through deprotonation (Scheme 447). Subsequent net α -umpolung addition, accompanied by the loss of acetate, gives the intermediate 294 .…”

“…Tong demonstrated that functionalized trisubstituted furans could be constructed through an alternative route (Scheme 449). 518 From methyl 4-bromo-2-butynoate, similar activation of the carbon pronucleophile occurs to generate the ion pair 298 . Upon coordination with a silver salt, formal γ -umpolung addition occurs to afford the intermediate 299 .…”

Organocatalytic transformations of alkynals, alkynones, propriolates, and related electron-deficient alkynes

“…91 Later, Tong's group has reported the synthesis of polysubstituted furans following similar strategies to those aforementioned, from g-functionalized butynoates and 1,3-dicarbonyl compounds, catalyzed by triphenylphosphine. 92 The authors were able to control the substitution pattern by reagent-controlled pathways. Thus, when the leaving group in the alkyne was an acetoxy group (173), the annulation leaded to a furan by an initial a-addition followed by a Michael reaction (left-Scheme 77).…”

A DFT study on the competing mechanisms of PPh3-catalyzed [3+3] and [3+2] annulations between 5-acetoxypenta-2,3-dienoate and 1C,3O-bisnucleophiles

“…In 2003, Zhu et al firstly reported the [4 + 2] annulation reaction of allenoates and N-tosylbenzaldimines to form functionalized tetrahydropyridines [25], which leads to the large-scale applications of the phosphinecatalysts. Since the pioneer work of Lu and Kwon are reported, many efforts have been devoted to improve and develop various kinds of the phosphine-catalyzed reactions [2,12,[26][27][28][29][30][31][32][33][34][35][36][37][38][39]. In 2009, Kwon reported phosphine-catalyzed [3 + 3] annulations of aziridines and allenoates to get azidirines in room temperature [40].…”