Simple and efficient synthesis of 2,2-disubstituted-1,1-difluorophosphonates and phosphonothioates

Tetrahedron Letters

Volumn 37, Issue 13, 1996, Pages 2233-2236

  Piettre, Serge R ^a  

^a SANOFI   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA,ALPHA DIFLUOROMETHYLENE PHOSPHONOTHIOIC ACID DERIVATIVE; PHOSPHONIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS;

EID: 0029878639     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00239-0     Document Type: Article

References (39)

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14. Unpublished results from this laboratory have shown that the synthetic scheme published by Martin and collaborators (reference 2g; reaction between aldehydes and 1-lithio-1,1-difluoromethylphosphonate, followed by Barton dehydroxylation reaction) can not be extended to ketones. Reference 2i describes the obtention of diethyl 1-(2-iodocyclohexyl)methyl-1,1-difluorophosphonate in 69% isolated yield from cyclohexene and diethyl iododifluoromethylphosphonate; however, it is not clear whether hydrogenolysis of the carbon-halogen bond can readily be achieved as, in the paper, this reaction is described only for compounds monosubstituted in β-position. Reference 2j reports two examples of direct obtention of β,β-disubstituted difluorophosphonates, albeit in low yields (18 and 34%).
15. After completion of this work, results obtained by Lequeux and Percy were published, that describe the addition of cerium-mediated conjugate addition of difluorophosphonate carbanion to nitroalkenes, thus resulting in the formation of difluorophosphonates disubstituted in β-position in yields ranging from 25 to 62%; see Lequeux, T. P.; Percy, J. M. Synlett 1995, 361.
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30. The exact amount of radical initiator depends on the starting difluoroolefin. A one-time addition of the total amount of initiator does not result in a complete consumption of the starting olefin.
31. Initiators 5a, 5e and 5f are commercially available. Initiators Sb, 5c and 5d were prepared according to published procedures: 5b: Bourgeois, M.-J.; Campagnole, M.; Filliatre, Cl.; Mailard, B.; Villenave, J.-J. Bull. Soc. Chim. Fr., 1982, II-111; 5c: Bartlett, P. D.; Hiatt, R. R. J. Am. Chem. Soc. 1958, 80 1398; Duismann, W.; Rüchardt, Ch. Chem. Ber. 1976, 1834; 5d: Bartlett, P. D.; Benzing, E. P.; Pincock, R. E. J. Am. Chem. Soc. 1960, 82, 1762.
32. Initiators 5a, 5e and 5f are commercially available. Initiators Sb, 5c and 5d were prepared according to published procedures: 5b: Bourgeois, M.-J.; Campagnole, M.; Filliatre, Cl.; Mailard, B.; Villenave, J.-J. Bull. Soc. Chim. Fr., 1982, II-111; 5c: Bartlett, P. D.; Hiatt, R. R. J. Am. Chem. Soc. 1958, 80 1398; Duismann, W.; Rüchardt, Ch. Chem. Ber. 1976, 1834; 5d: Bartlett, P. D.; Benzing, E. P.; Pincock, R. E. J. Am. Chem. Soc. 1960, 82, 1762.
33. Initiators 5a, 5e and 5f are commercially available. Initiators Sb, 5c and 5d were prepared according to published procedures: 5b: Bourgeois, M.-J.; Campagnole, M.; Filliatre, Cl.; Mailard, B.; Villenave, J.-J. Bull. Soc. Chim. Fr., 1982, II-111; 5c: Bartlett, P. D.; Hiatt, R. R. J. Am. Chem. Soc. 1958, 80 1398; Duismann, W.; Rüchardt, Ch. Chem. Ber. 1976, 1834; 5d: Bartlett, P. D.; Benzing, E. P.; Pincock, R. E. J. Am. Chem. Soc. 1960, 82, 1762.
34. Initiators 5a, 5e and 5f are commercially available. Initiators Sb, 5c and 5d were prepared according to published procedures: 5b: Bourgeois, M.-J.; Campagnole, M.; Filliatre, Cl.; Mailard, B.; Villenave, J.-J. Bull. Soc. Chim. Fr., 1982, II-111; 5c: Bartlett, P. D.; Hiatt, R. R. J. Am. Chem. Soc. 1958, 80 1398; Duismann, W.; Rüchardt, Ch. Chem. Ber. 1976, 1834; 5d: Bartlett, P. D.; Benzing, E. P.; Pincock, R. E. J. Am. Chem. Soc. 1960, 82, 1762.
35. +).
36. Viehe, H.G.; Janousek, Z.; Merényi, R. in "Substituent Effect in Radical Chemistry." NATO ASI Series 1986, 189, 301.
37. 31P-NMR, mass spectra and combustion data) for all compounds are available upon request.
38. This is probably due to the competitive formation of benzylic radicals.
39. Note added in proof: after this work had been completed, Professor W. B. Motherwell (University College, London) brought to our attention similar results obtained by his group, when reacting difluoroenol ethers of carbohydrate lactones with phosphonyl radicals.