TfOH-Catalyzed Phosphinylation of 2,3-Allenols into γ-Ketophosphine Oxides

Abstract

The first facile and efficient acid-catalyzed direct coupling of a wide range of unprotected 2,3-allenols with arylphosphine oxides was developed, offering a general, one-step approach for the synthesis of structurally diverse γ-ketophosphine oxides accompanied by concurrent CP/CO bond formation with remarkable functional group tolerance and complete atomeconomy under metal-and additive-free conditions. Mechanistic studies showed that this transformation involved a rearrangement and a phospha-Michael reaction.

“On‐Water” Synthesis of Sterically Congested γ‐Ketophosphine Oxides Featuring a CF3‐ and P(O)‐Tetrasubstituted Carbon Center

“…[8c,17,18] Based on the above studies and literature survey, we propose a reaction mechanism for the "on-water" synthesis of sterically congested γ-ketophosphine oxides (Scheme 4). [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Under basic reaction conditions, the diarylphosphinite anion A, generated in situ from diarylphosphine oxide 2, reacts with the β-CF 3β,β-disubstituted enone 1 through a classic 1,4-addition process, resulting in the formation of the β-phosphorylated anion B. During this step, the water surface presents hydrogen-bonding interactions that activate both substrates.…”

“…[2c-d] Over the past decades, these frameworks have garnered considerable atten-tion, leading to intense research efforts aimed at developing efficient synthetic approaches to access them. [3][4][5][6][7][8][9][10][11][12] Typically, γ-ketophosphine oxides could be synthesized through phospha-Michael reaction, involving the addition of a phosphorus nucleophile to α,β-unsaturated carbonyl compounds (Scheme 1, B, a). [3] However, these classic reactions are generally limited by the requirements of sensitive reagents, [3a,b] high temperature, [3c] complex catalysts, [3d,e] stoichiometric bases, [3f] and non-eco-friendly solvents.…”

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

“…A related mechanistic pathway has been recently proposed by Gao and Xu et al, for the acid-catalyzed synthesis of ketophosphine oxides, although in both cases an alternative mechanistic pathway describing the inverse addition/elimination sequence may not be discarded. 204 , 205 …”

“…Addition of one molecule of water could then generate the metalated complex 225 , evolving to the experimentally observed enones 222 through sequential demetalation/isomerization processes (Scheme ). A related mechanistic pathway has been recently proposed by Gao and Xu et al, for the acid-catalyzed synthesis of ketophosphine oxides, although in both cases an alternative mechanistic pathway describing the inverse addition/elimination sequence may not be discarded. , …”

Heteroaliphatic Dimethylphosphine Oxide Building Blocks: Synthesis and Physico‐Chemical Properties

“…While most known compounds of this class contain the P(O) Me 2 moiety attached to the aromatic ring [15][16][17][18][19][20][21][22] or alkenes, [23][24][25] some examples of sp-and sp 3 -hybridized derivatives have been studied as progesterone receptor agonist and epithelial Na + channel (ENaC) inhibitor, respectively (Figure 1). [26] Meanwhile, introducing the dimethylphosphine oxide fragment into lowmolecular-weight saturated heterocyclic amines (such as azetidine, pyrrolidine, piperidine, or morpholine) was not explored in the literature to date.…”