Unlocking the C-centered ring-opening of phosphiranium ions for a straightforward entry to functionalized phosphines

Abstract

Phosphorus chemistry occupies a pivotal position in contemporary organic chemistry but significant synthetic challenges still endure. In this report, a class of electrophilic phosphiranium salts, bearing fluorinated benzyl quaternizing groups, is introduced for the direct synthesis of diversely β-functionalized phosphines. We show that, in comparison with regular quaternary phosphiranium salts, these species display the sought balance of excellent stability and high electrophilic reactivity that allow the unlocking of the C-centered ring-opening reactions with different classes of weak nitrogen-, sulfur- and oxygen protic nucleophiles.

Fig. 1. Nucleophilic ring opening of 3-membered phosphorus heterocycles.

a General statements: 3-membered phosphorus heterocycles ring-opening; b Electrophilic phosphonium cations (EPC) as source of inspiration; c Representative examples of polyluorinated organocatalysts refs. ^–; d This work: Ring-opening of Electrophilic Phosphiranium Cations (EPrS) with weak protic nucleophiles.

Fig. 2. Energy of the LUMO (in eV) and global electrophilicity parameter ω for optimized QPrS and EPrS.

MO calculated at the ωB97X-D/6-31 + G(d,p) level, considering the optimized structures calculated at the ωB97X-D/6-31 + G(d,p) (PCM: CHCl₃) level.

Fig. 3. Synthesis of QPrS 1a-1b and EPrS 1c–1f from 1-mesitylphosphirane.

The crude isolated yields were given.^a TfO⁻ anion omitted for clarity.^b Crude yield estimated (2 steps, from Ar-CH₂-OH).

Fig. 4. Ring-opening of QPrS and EPrS 1a–1f with protic nitrogen nucleophiles.

a Ring-opening with N-Me aniline 2. b Empirical reactivity scale of QPrS and EPrS 1a–1f. c Ring-opening with hydroxylamines 4a–4e and tosylamide 6. The isolated yields were given.^a Product isolated as the corresponding phosphine oxide, after treatment of the crude with H₂O₂; ^b nd not detected - although full conversion of the phosphiranium substrate was observed.

Fig. 5. Ring-opening of EPrS 1d–1f with protic sulfur nucleophiles.

The isolated yields were given. ^a Product isolated as the corresponding phosphine oxide, after treatment of the crude with H₂O₂.

Fig. 6. Ring-opening of EPrS 1e-1f with protic oxygen nucleophiles.

The isolated yields were given.

Fig. 7. Ring-opening mechanism.

a Computed energy profiles for the nucleophilic addition of aniline on QPrS model A1 calculated at the ωB97X-D/6-31 + G(d,p) (PCM: CHCl₃) level; b Proposed reaction mechanism.

Fig. 8. Competition experiments with 2-mercaptobenzothiazole 8f as reference nucleophile.

a Competition experiment of EPrS 1f vs. QPrS 1a. b Competition experiment of EPrS 1e vs. QPrS 1a.