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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;
Further Information

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

    References

  • For recent leading references, see:
  • 1a Halazy S. Ehrhard A. Eggenspiller A. Berges-Gross V. Danzin C. Tetrahedron  1996,  52:  8619 
    CrossrefGoogle Scholar
  • 1b Kawamoto AM. Campbell MM. J. Chem. Soc. Perkin Trans. 1  1997,  1249 
    CrossrefGoogle Scholar
  • 1c Caplan NA. Pogson CI. Hayes DJ. Blackburn GM. J. Chem. Soc. Perkin Trans. 1  2000,  421 
    CrossrefGoogle Scholar
  • 1d Yokomatsu T. Hayakawa Y. Kihara T. Koyanagi S. Soeda S. Shimeno H. Shibuya S. Bioorg. Med. Chem.  2000,  8:  2571 
    CrossrefGoogle Scholar
  • 2a Levillain J. Masson S. Hudson A. Alberti A. J. Am. Chem. Soc.  1993,  115:  8444 
    CrossrefGoogle Scholar
  • 2b Alberti A. Benaglia M. Della Bona A. Macciantelli D. Luccioni-Heuze B. Masson S. Hudson A. J. Chem. Soc., Perkin Trans. 2  1996,  1057 
    CrossrefGoogle Scholar
  • 2c Alberti A. Benaglia M. Bonora M. Borzatta V. Hudson A. Macciantelli D. Masson S. Polym. Degrad. Stab.  1998,  62:  559 
    CrossrefGoogle Scholar
  • 2d Albert A. Benaglia B. Hapiot P. Hudson A. Le Coustumer G. Macciantelli D. Masson S. J. Chem. Soc., Perkin Trans. 2  2000,  1908 
    CrossrefGoogle Scholar
  • 3a Bulpin A. Masson S. Sene A. Tetrahedron Lett.  1989,  30:  3415 
    Google Scholar
  • 3b Bulpin A. Masson S. Sene A. Tetrahederon Lett.  1990,  31:  1151 
    Google Scholar
  • 3c Bulpin A. Masson S. Sene A. J. Org. Chem.  1992,  57:  4507 
    Google Scholar
  • 3d Masson S. Phosphorus, Sulfur Silicon Relat. Elem.  1994,  95:  127 
    Google Scholar
  • 4 Laus M. Papa R. Sparnacci K. Alberti A. Benaglia M. Macciantelli D. Macromolecules  2001,  34:  7269 
    CrossrefGoogle Scholar
  • 5a Heuze B. Gasparova R. Heras M. Masson S. Tetrahedron Lett.  2000,  41:  7327 
    CrossrefGoogle Scholar
  • 5b Masson S. Saquet M. Marchand P. Tetrahedron  1998,  54:  1523 
    CrossrefGoogle Scholar
  • 5c Makomo H. Saquet M. Simeon F. Masson S. Aboutjaudet E. Collignon N. Gulea-Purcarescu M. Phosphorus, Sulfur Silicon Relat. Elem.  1996,  110:  445 
    CrossrefGoogle Scholar
  • 5d Mikolajczyk M. Mikina M. Graczyk PP. Balczewski P. Synthesis  1996,  1232 
    CrossrefGoogle Scholar
  • 5e Bulpin A. LeRoy-Gourvennec S. Masson S. Phosphorus, Sulfur Silicon Relat. Elem.  1994,  89:  119 
    CrossrefGoogle Scholar
  • 5f Makomo H. Masson S. Saquet M. Tetrahedron  1994,  50:  10277 
    CrossrefGoogle Scholar
  • 6 Grisley DW. J. Org. Chem.  1961,  2544 
    Google Scholar
  • 7 Bulpin A. Masson S. Sene A. Tetrahedron Lett.  1989,  30:  3415 
    CrossrefGoogle Scholar
  • 8 Zimin MG. Dvoinishnikova TA. Konovalova IV. Pudovik AN. Zh. Obshch. Khim.  1978,  48:  2790 
    Google Scholar
  • 9a Blackburn GM. England DA. Kolkmann F. J. Chem. Soc., Chem. Commun.  1981,  930 
    Google Scholar
  • 9b Blackburn GM. Eckstein F. Kent DE. Perree TD. Nucleosides Nucleotides  1985,  4:  165 
    Google Scholar
  • 10 For a general overview for the synthesis of phosphono- and phosphinopeptides, see: Kafarski P. Lejczak B. In Aminophosphonic and Aminophosphinic Acids, Chemistry and Biological Activity   Kukhar VP. Hudson HR. Wiley; England: 2000.  p.173-203  ; and references cited therein
    Google Scholar
  • 11 Cs2CO3 offered a higher yield than previously reported, see: Alberti A. Benaglia M. Laus M. Sparnacci K. J. Org. Chem.  2002,  67:  7911 
    CrossrefGoogle Scholar
  • 12 Inverse addition (cesium salt of dialkylphosphite to CS2) was also tried and did not result in a higher yield. Also, formation of secondary products resulting from the reaction between dialkylphosphite salts with the in situ generated cesium phosphonodithiocarboxylate leading to the expected desulfurization forming methylene diphosphonates did not arise as previously described for sodium salts. See: Masson S. Reviews in Heteroatom Chemistry   Vol. 12:  Oae S. VCH; Weinheim: 1995.  p.69-84  
    Google Scholar
  • For reviews on the ‘cesium effect’, see:
  • 14a Ostrowicki A. Vogtle F. In Topics in Current Chemistry   Vol. 161:  Weber E. Vogtle F. Springer Verlag; Heidelberg: 1992.  p.37 
    CrossrefGoogle Scholar
  • 14b Galli C. Org. Prep. Proced. Int.  1992,  24:  287 ; and references therein
    CrossrefGoogle Scholar
  • 14c Blum Z. Acta Chem. Scand.  1989,  43:  248 
    CrossrefGoogle Scholar
  • 15 Formation of ‘naked anions’ by solvation of cesium ions has been previously postulated and studied extensively: Dijstra G. Kruizinga WH. Kellogg RM. J. Org. Chem.  1987,  52:  4230 
    Google Scholar
  • For examples of efficient cesium-promoted alkylations, see:
  • 16a Parrish JP. Dueno EE. Kim S.-I. Jung KW. Synth. Commun.  2000,  30:  2687 
    CrossrefPubMedGoogle Scholar
  • 16b Salvatore RN. Flanders VL. Ha D. Jung KW. Org. Lett.  2000,  2:  2797 
    CrossrefPubMedGoogle Scholar
  • 16c Dueno EE. Chu F. Kim S.-I. Jung KW. Tetrahedron Lett.  1999,  40:  1843 
    CrossrefPubMedGoogle Scholar
  • 16d Salvatore RN. Nagle AS. Schmidt SE. Jung KW. Org. Lett.  1999,  1:  1893 
    CrossrefPubMedGoogle Scholar
  • 16e Salvatore RN. Shin SI. Nagle AS. Jung KW. J. Org. Chem.  2001,  66:  1035 
    CrossrefPubMedGoogle Scholar
  • 16f Salvatore RN. Sahab S. Jung KW. Tetrahedron Lett.  2001,  42:  2055 
    CrossrefPubMedGoogle Scholar
  • 16g Salvatore RN. Schmidt SE. Shin SI. Nagle AS. Worrell JH. Jung KW. Tetrahedron Lett.  2000,  41:  9705 
    CrossrefPubMedGoogle Scholar
  • 16h Salvatore RN. Ledger JA. Jung KW. Tetrahedron Lett.  2001,  42:  6023 
    CrossrefPubMedGoogle Scholar
  • 16i Kim S.-I. Chu F. Dueno EE. Jung KW. J. Org. Chem.  1999,  64:  4578 
    CrossrefPubMedGoogle Scholar
  • 16j Salvatore RN. Chu F. Nagle AS. Kapxhiu EA. Cross RM. Jung KW. Tetrahedron  2002,  58:  3329 
    CrossrefPubMedGoogle Scholar
  • 16k Salvatore RN. Shin SI. Flanders VL. Jung KW. Tetrahedron Lett.  2001,  42:  1799 
    CrossrefPubMedGoogle Scholar
  • 16l Salvatore RN. Nagle AS. Jung KW. J. Org. Chem.  2002,  67:  674 
    CrossrefPubMedGoogle Scholar
  • TBAI is strongly believed to act as a phase-transfer catalyst in the reaction, therefore, facilitating alkylations producing high product yields. For other phase-transfer catalyzed phosphorus alkylations, see:
  • 17a Kem KM. Nguyen NV. Cross DJ. J. Org. Chem.  1981,  46:  5188 
    CrossrefGoogle Scholar
  • 17b Weber WP. Gokel GW. Phase Transfer Catalysts in Organic Synthesis   Springer Verlag; New York: 1977. 
    CrossrefGoogle Scholar
  • 17c Starks CM. Liotta C. Phase Transfer Catalysis: Principles and Techniques   Academic Press; New York: 1978. 
    CrossrefGoogle Scholar
  • 17d However, we cannot rule out an internal Finkelstein-type reaction for the in-situ generation of alkyl iodides from bromides and chlorides, hence improving yields. Although, the use of alkyl iodides directly, without TBAI gave lower product yields. Therefore, we propose TBAI minimizes or prohibits direct alkylation of the phosphite with an alkyl halide presumably enhancing the rate of CS2 incorporation/and or stabilizing the phosphoryl dithioformate anion through conjugation with the tetrabutylammonium cation. Whereas, the cesium ion tends to weakly coordinate to the conjugate anions, making them more nucleophilic. Prior to addition of the halide, the phosphite and CS2 were reacted to pre-form the incipient dithioformate anion, which is belived to suppress direct alkylation of the phosphite. For a similar example, see ref. for a mechanistic interpretation and for the use of TBABr and other onium salts in the formation of urethanes: Yoshida M. Hara N. Okuyama S. Chem. Commun.  2000,  151 
    CrossrefGoogle Scholar
  • 19 Nagle AS. Salvatore RN. Chong BD. Jung KW. Tetrahedron Lett.  2000,  41:  3011 
    CrossrefGoogle Scholar
  • For new biologically active phosphonates, see:
  • 21a Hildebrand R. The Role of Phosphonates in Living Systems   CRC Press; Boca Raton: 1983. 
    CrossrefGoogle Scholar
  • 21b Engel R. Chem. Rev.  1977,  77:  349 
    CrossrefGoogle Scholar
  • 21c Kafarski P. Leczak B. Phosphorus, Sulfur Silicon Relat. Elem.  1991,  63:  193 
    CrossrefGoogle Scholar
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.