Direct Regio- and Diastereoselective Diphosphonylation of Cyclic Enamines: One-Pot Synthesis of α,α′-Bis(diphenylphosphoryl)- and α,α′-Bis(diphenylphosphorothioyl)cycloalkanones

Abstract

A straightforward regio- and diastereoselective process has been developed for the synthesis of unprecedented symmetrical trans-α,α′-bis(diphenylphosphoryl)- and α,α′-bis(diphenylphosphorothioyl)-cycloalkanones, through the reaction of cyclic enamines with excess P-chlorodiphenylphosphine in the presence of triethylamine, followed by oxidation or sulfurization and hydrolytic workup.

Key words

enamines - P-chlorodiphenylphosphine - α,α′-bis(diphenylphosphoryl)cycloalkanones - α,α′-bis(diphenylphosphorothioyl)cycloalkanones - P-ligands

• References and Notes

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• 29 General Procedure for the Synthesis of α,α′-Bis(diphenylphosphoryl)- and α,α′-Bis(diphenylphosphorothioyl)cycloalkanones 2 To a well-stirred solution of enamine 1 (1 mmol) and Et₃N (6.6 mmol) in dry MeCN (15 mL), maintained under an inert atmosphere (N₂) and cooled at 0 °C, P-chlorodiphenylphosphine (1 mmol) in dry MeCN (3 mL) was added dropwise within 15 min. The resulting solution was warmed up to r.t. and stirred for 1 h. The reaction mixture was cooled again at 0 °C, and the second portion of P-chlorodiphenylphosphine (5 mmol) in dry MeCN (15 mL) was added in the same manner as before. The mixture was allowed to warm up to r.t. and then refluxed for an extra 2 h. The reaction mixture was then cooled and treated with DMSO or sulfur as follows. Oxidation DMSO (6 mmol) was added, and the mixture was heated under reflux for 2 h. After cooling, 2 N aq HCl solution (30 mL) was added dropwise at 0 °C and stirring was continued at r.t. for 12 h. The mixture was then extracted with CH₂Cl₂ (3 × 10 mL). The organic phase was dried over MgSO₄ and concentrated under vacuum. The residue obtained was chromatographed on a silica gel column using CH₂Cl₂ as eluent or recrystallized from toluene (in the case of compounds 2a and 2c). Sulfurization Ground sulfur (6 mmol) was added, and the reaction mixture was stirred at r.t. until complete dissolution of the sulfur in 2 h. 2 N aq HCl solution (30 mL) was then added dropwise at 0 °C and stirring was continued at r.t. for 12 h. The mixture was then extracted with CH₂Cl₂ (3 × 10 mL). The organic phase was dried over MgSO₄ and concentrated under vacuum. The residue obtained was chromatographed on a silica gel column using CH₂Cl₂ as eluent. The compounds obtained were characterized by various spectroscopic tools including IR, NMR (¹H, ³¹P, ¹³C) spectroscopy, mass spectrometry, and single-crystal X-ray diffraction (see the Supporting Information). trans-2,6-Bis(diphenylphosphoryl)cyclohexanone (2a) Yield 51%; white solid; mp 249–250 °C. IR (neat): ν_P=O = 1245 cm^–1; ν_C=O = 1706 cm^–1. ³¹P NMR (161.97 MHz, CD₃OD): δ = 33.3 (s, 2 P). ¹H NMR (400.13 MHz, CD₃OD): δ = 2.01–2.22 (m, 6 H, 3 CH₂), 4.15–4.20 (m, 2 H, 2 CHP), 7.38–7.83 (m, 20 H, ArH). ¹³C NMR (100.61 MHz, CD₃OD): δ = 21.7 (t, CH₂, ³J _C–P = 6.0 Hz), 27.1 (s, 2 CH₂), 51.7 (d, 2 CHP, ¹J _C–P = 66.4 Hz), 201.7 (s, C=O); ArC: δ = 128.3, 128.4, 128.7, 128.8, 130.4, 129.9, 130.4, 130.5, 130.6, 130.9, 131.4, 131.8, 131.9,132.2. ESI-HRMS: m/z calcd for C₃₀H₂₈O₃P₂ [M + H]⁺: 499.15864; found: 499.15796.