Phosphonodithioformates: Efficient Three-Component Coupling of Dialkyl phosphites, Carbon Disulfide, and Alkyl Halides in the Presence of Cesium Carbonate and Tetrabutylammonium Iodide

Abstract

A mild one-pot, three-component coupling reaction uniting­ a dialkyl phosphite, carbon disulfide (CS₂) and an alkyl halid­e for the mild and efficient synthesis of phosphonodithio­formates using cesium carbonate (Cs₂CO₃) and tetrabutyl­ammonium iodide (TBAI) was developed. Various dialkyl phosphites were examined using a diverse array of alkyl halides, and these improved reaction conditions were found to be highly selective­ producing the title compounds exclusively in moderate to high yields.

Key words

alkylations - alkyl halides - cesium carbonate - phosphono­dithioformate - phosphorus

References

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13

General Experimental Procedure: To a solution of diethyl phosphite 4 (0.12 g, 0.85 mmol, 1 equiv) in anhyd DMF (5 mL) was added Cs₂CO₃ (0.83 g, 2.55 mmol, 3 equiv) and TBAI (0.94 g, 2.55 mmol, 3 equiv) with vigorous stirring for 10 min at r.t. under a N₂ atmosphere. CS₂ (0.15 mL, 2.55 mmol, 3 equiv) was added and the fuchsia colored mixture was stirred for 1 h. After this time period, benzyl bromide (0.30 mL, 2.55 mmol, 3 equiv) was added and stirred for an additional 24 h. The resultant yellow reaction suspension was then poured into water (30 mL) and extracted with EtOAc (3 × 30 mL). The organic layer was washed with water (2 × 30 mL), brine (30 mL), and dried over anhyd Na₂SO₄. Evaporation of the solvent followed by flash chromatography (hexanes-EtOAc, 9:1) afforded benzyl diethoxyphosphoryldithioformate(5) as a dark red oil (0.25 g, 97%).
¹H NMR (270 MHz, CDCl₃): δ = 1.36 (t, J _1,2 = 7.6 Hz, 6 H), 4.26 (m, 4 H), 4.46 (s, 2 H), 7.30 (s, 5 H). ¹³C NMR (100 MHz, CDCl₃): δ = 16.20 (d, J _CP = 6.34 Hz), 40.63 (d, J _CP = 2.72 Hz), 64.70 (d, J _CP = 6.94 Hz), 128.00 (s), 128.77 (s), 129.26 (s), 133.53 (s), 228.16 [d, J _CP = 174.54 PC(S)S]; ³¹P NMR (85 MHz, CDCl₃)δ from 30% H₃PO₄-H₂O: -4.57. MS: m/z = 91, 121, 182, 248, 276, 304 (M⁺). Anal. Calcd for C₁₂H₁₇O₃PS₂: C, 47.35; H, 5.63. Found: C, 47.42; H, 5.64.

18

Since dithioesters are known to be very good thioacylating agents for amines due to the high electrophilicity of the C=S which is activated by the phosphono-substituent (an electron-withdrawing group), amino bromides 13 and 15 were used as the corresponding hydrobromide salts, since a spontaneous intermolecular reaction to give thioamides or cyclization to the phosphonothiazoline can readily occur. Neither the aforementioned thioacylation reaction (which usually occurs with the alkyl group in the phosphono-moiety) or cyclization was seen. Therefore, we wish to strongly emphasize product structures for aminodithioesters from 13 and 15 were isolated and assigned without ambiguity from the exact mass (MS), ¹H, ¹³C, and ³¹P NMR spectroscopy.

20

¹H NMR, ¹³C NMR, ³¹P NMR and 2D NMR analysis indicate the product as a single diastereomer.