Three-component 3-(phosphoryl)methylindole synthesis from indoles, H-phosphine oxides and carbonyl compounds under metal-free conditions

Abstract

The first facile and efficient acid-catalyzed three-component reaction of indoles, H-phosphine oxides and carbonyl compounds has been developed, providing a general, one-pot approach to structurally diverse C3-alkylated indole derivatives.

Synthesis of 2‐Phosphoryl‐3‐Monofluorovinylindoles under Catalyst‐ and Additive‐Free Conditions

“…Not surprisingly, numerous synthetic methods for accessing 2‐phosphorylindoles have been developed, including palladium‐catalyzed annulation of 1‐alkynylphosphine sulfides or oxides with 2‐iodoanilines (Scheme 1a), [6] transition metals‐catalyzed direct C−H phosphorylation of indoles, [7] photoredox phosphorylation/cyclization of 1‐isocyano‐2‐styrylbenzenes (Scheme 1b), [8] and acid‐catalyzed dehydrative coupling reactions (Scheme 1c) [9] . Very recently, an efficient TfOH‐catalyzed three‐component reaction of indoles, carbonyl compounds and H ‐phosphine oxides has also been successively realized (Scheme 1d) [10] . Despite notable advances, however, some of the reported methods still suffer from certain drawbacks such as the need for various noble metals or acid catalysts, poor C2/C3 site selectivity and, in some cases, harsh reaction conditions (e. g., strictly inert and anhydrous conditions).…”

“…[9] Very recently, an efficient TfOH-catalyzed three-component reaction of indoles, carbonyl compounds and Hphosphine oxides has also been successively realized (Scheme 1d). [10] Despite notable advances, however, some of the reported methods still suffer from certain drawbacks such as the need for various noble metals or acid catalysts, poor C2/C3 site selectivity and, in some cases, harsh reaction conditions (e. g., strictly inert and anhydrous conditions). Consequently, the development of a green and practical method to access highly functionalized 2-phosphorylindoles from readily available starting materials is highly desirable.…”

Recent Studies of Bifunctionalization of Simple Indoles

“…The Deng group [17a,c,d] developed several elemental sulfur‐mediated reactions for synthesis of thieno[2,3‐b]indoles. For example, during three component reactions of indoles, alkenes (or alkynes), three‐membered ring intermediates would be generated from unsaturated compounds, DMF and sulfur powder (Willgerodt‐Kindler reaction).…”

Recent Advances in the Construction of Phosphorus‐Substituted Heterocycles, 2009–2019

“…Recently, Gao and Xu established an efficient protocol for the synthesis of C‐2 phosphinoylated indoles via a TfOH‐catalyzed three‐component reaction of substituted indoles, aryl alkyl ketones and disubstituted phosphine oxides (Scheme ) . By running the reaction at 120 °C in toluene for 10 h, the desired products were obtained in moderate yields.…”