Conceptual advances in nucleophilic organophosphine-promoted transformations.

Catalysis by trivalent nucleophilic organophosphines has emerged as an essential tool in organic synthesis. Several new organic transformations promoted by phosphines substantiate and complement the existing synthetic chemistry tools. Mere design of the substrate and reagent combinations has introduced new modes of reactivity patterns, which are otherwise difficult to achieve. These design considerations have led to the rapid build-up of complex molecular entities and laid a solid foundation to synthesise bioactive natural products and pharmaceuticals. This article presents an overview of some of the conceptual advances, including our contributions to nucleophilic organophosphine chemistry. The scope, limitations, mechanistic insights, and applications of these metal-free transformations are discussed elaborately.

Phosphine-catalysed denitrative rearomatising (3 + 2) annulation of α,ß-ynones and 3-nitroindoles.

We describe a metal-free strategy to access various α-arylidene cyclopenta[b]indoles via phosphine-catalysed (3 + 2) annulation of α,ß-ynones and 3-nitroindoles. For the first time, the rearomatisation of the indole nucleus was observed in such an annulative transformation. The method was extended to the synthesis of an antimalarial natural product, bruceolline E.

Phosphine-Mediated Redox Cyclization of 1-(2-Nitroaryl)prop-2-ynones to 3-Hydroxyquinolin-4-ones: Formal Intramolecular Oxyamination of α,ß-Ynones.

3-Hydroxyquinoline-4(1H)-ones (3HQs) are privileged structural motifs. The current methods for their synthesis necessitate strongly acidic or basic conditions, which hamper the generality and practicality. Here, we describe phosphine-mediated redox transformation of easily accessible 1-(2-nitroaryl)prop-2-ynones to 3HQs. Besides establishing a new entry to the synthesis of 3HQs under neutral conditions, this method is the first formal intramolecular oxyamination of α,ß-ynones. The synthetic utility of this method is demonstrated in the total synthesis of japonine, its analogs, and rare quinoline derivatives.

Phosphine- and water-promoted pentannulative aldol reaction.

Herein, an efficient metal-free intramolecular aldol reaction for the synthesis of an unusual class of cyclopentanoids is described. The reaction of α-substituted dienones tethered with ketones in the presence of tributylphosphine and water provided aldols. The role of water was realised to be crucial for this transformation. Furthermore, isotopic labeling experiments provided vital information about the reaction mechanism.

Metal- and Hydride-Free Pentannulative Reductive Aldol Reaction.

Traditionally, the reductive aldol reaction is a metal-catalyzed and hydride-promoted coupling between enones and aldehydes. We present a phosphine-mediated diastereoselective intramolecular reductive aldol reaction of α-substituted dienones and aldehydes, which is metal-free and hydride-free. The synthetic utility of the reductive aldol adducts is demonstrated by elaborating them in one step to indeno[1,2- b]furanones, indeno[1,2- b]pyrans, and dibenzo[ a, h]azulen-8-ones.