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Synlett 2003(13): 2037-2041  
DOI: 10.1055/s-2003-41482
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Daniel L. Fox, Nathan R. Whitely, Richard J. Cohen, Ralph Nicholas Salvatore*
Department of Chemistry, Western Kentucky University, 1 Big Red Way, Bowling Green, KY, 42101-3576, USA
Fax: +1(270)7455361; e-Mail: ralph.salvatore@wku.edu;
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Publication History

Received 21 August 2003
Publication Date:
08 October 2003 (online)

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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

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.