Selective Substitution of POCl₃ with Organometallic Reagents: Synthesis of Phosphinates and Phosphonates

Abstract

The selectivity of the substitution reaction of phosphoryl chloride with organometallic reagents was investigated using NMR spectroscopy. This led to the discovery that the selectivity of the substitution reaction can be tuned by choosing a proper organometallic reagent. A phosphinate could be obtained by using a Grignard reagent whereas an organozinc reagent provided a phosphonate. Based on these results, one-pot synthetic methods for the preparation of phosphinates and phosphonates using commercially available starting materials were developed. Both methods allow the synthesis of a broad range of either phosphinate or phosphonate derivatives in a straightforward and general procedure. Moreover, using these one-pot procedures, mixed systems substituted with different alkyl/aryl groups can be prepared.

Key words

selectivity - substitution - phosphoryl chloride - phosphinate - phosphonate - Grignard reagent - organozinc reagent

• References

• 1a Engel R. Cohen JI. Synthesis of Carbon–Phosphorus Bonds . 2nd ed. CRC Press LLC; Boca Raton: 2004
• 1b Timperley CM. Best Synthetic Methods: Organophosphorus(V) Chemistry. Elsevier Ltd; Salisbury: 2015
• 2a Jain P. Choudhary V. Varma IK. J. Macromol. Sci., Polym. Rev. 2002; 42: 139
• 2b Lu S.-Y. Hamerton I. Prog. Polym. Sci. 2002; 27: 1661
• 2c Braun U. Balabanovich AI. Schartel B. Knoll U. Artner J. Ciesielski M. Döring M. Perez R. Sandler JK. W. Altstädt V. Hoffmann T. Pospiech D. Polymer 2006; 47: 8495
• 2d Levchik SV. Weil ED. In Advances in Fire Retardant Materials: Developments in Phosphorus Flame Retardants . Horrocks AR. Price D. Woodhead Publishing Limited; Cambridge: 2008: 41-66
• 3a Flett DS. J. Organomet. Chem. 2005; 690: 2426
• 3b Xie F. Zhang TA. Dreisinger D. Doyle F. Miner. Eng. 2014; 56: 10
• 4 Binnemans K. Jones PT. J. Sustain. Metall. 2017; 3: 570
• 5a Gao W. Dickinson L. Grozinger C. Morin FG. Reven L. Langmuir 1996; 12: 6429
• 5b Guerrero G. Mutin PH. Vioux A. Chem. Mater. 2001; 13: 4367
• 6a Wadsworth WS. Emmons WD. J. Am. Chem. Soc. 1961; 83: 1733
• 6b Bisceglia JA. Liliana R. Orelli LR. Curr. Org. Chem. 2012; 16: 2206
• 6c Bisceglia JA. Liliana R. Orelli LR. Curr. Org. Chem. 2015; 19: 744
• 7a Murdoch D. McTavish D. Drugs 1992; 43: 123
• 7b Shionoiri H. Naruse M. Minamisawa K. Ueda S. Himeno H. Hiroto S. Takasaki I. Clin. Pharmacokinet. 1997; 32: 460
• 7c Lamb HM. Faulds D. Drugs Aging 1997; 11: 490
• 7d Mita M. Sankhala K. Abdel-Karim I. Mita A. Giles F. Expert Opin. Invest. Drugs 2008; 17: 1947
• 7e Dancey JE. Monzon J. Future Oncol. 2011; 7: 827
• 8a Fung HB. Stone EA. Piacenti FJ. Clin. Ther. 2002; 24: 1515
• 8b De Clercq E. Antiviral Res. 2007; 75: 1
• 8c De Clercq E. Biochem. Pharmacol. 2011; 82: 99
• 8d Pertusat F. Serpi M. McGuigan C. Antiviral Chem. Chemother. 2012; 22: 181
• 8e De Clercq E. Med. Res. Rev. 2013; 33: 1278
• 8f Thornton PJ. Kadri H. Miccoli A. Mehellou Y. J. Med. Chem. 2016; 59: 10400
• 9 Kiss NZ. Keglevich G. Curr. Org. Chem. 2014; 18: 2673
• 10 Edmundson RS. The Synthesis of Phosphonic and Phosphinic Acids and their Derivatives: Non-Functionalized Acids. Wiley; Hoboken: 1996
• 11a Palacios F. Alonso C. de los Santos JM. Chem. Rev. 2005; 105: 899
• 11b Tappe FM. J. Trepohl VT. Oestreich M. Synthesis 2010; 3037
• 11c Glueck DS. Top. Organomet. Chem. 2010; 31: 65
• 12a Xu Y. Zhang J. Synthesis 1984; 778
• 12b Lei H. Stoakes MS. Schwabacher AW. Synthesis 1992; 1255
• 13 Kosolapoff GM. Org. React. 1951; 6: 273
• 14 Bhattacharya AK. Thyagarjan G. Chem. Rev. 1981; 81: 415
• 15a Hirao T. Masunaga T. Ohshiro Y. Agawa T. Synthesis 1981; 56
• 15b Lu X. Zhu J. Synthesis 1987; 726
• 16a Kosolapoff GM. J. Am. Chem. Soc. 1942; 64: 2982
• 16b Kosolapoff GM. J. Am. Chem. Soc. 1950; 72: 5508
• 17 Van Lindhoudt JP. Van den Berghe EV. Van der Kelen GP. Spectrochim. Acta, A 1979; 35: 1307
• 18a Guichard F. Ber. Dtsch. Chem. Ges. 1899; 32: 1572
• 18b Drake LR. Marvel CS. J. Org. Chem. 1938; 2: 387
• 19 Kharasch MS. Jensen EV. Weinhouse S. J. Org. Chem. 1949; 14: 429
• 20 Fox RB. J. Am. Chem. Soc. 1950; 72: 4147
• 21a Lewis CE. J. Occup. Med. 1960; 2: 183
• 21b Craig PJ. Organometallic Compounds in the Environment . 2nd ed. Wiley; Chichester: 2003
• 22a Jones PR. Desio PJ. Chem. Rev. 1978; 78: 491
• 22b Bright KC. R. Joseyphus RS. Cadmium: Organometallic Chemistry. Encyclopedia of Inorganic and Bioinorganic Chemistry. Wiley; Hoboken: 2014