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Synlett 2015; 26(07): 985-990
DOI: 10.1055/s-0034-1379993
letter
© Georg Thieme Verlag Stuttgart · New York

Organocatalytic Phosphorylation of Alcohols Using Pyridine-N-oxide

James I. Murray
a   Department of Chemistry, South Kensington Campus, Imperial College London, SW7 2AZ, UK
,
Rudiger Woscholski
a   Department of Chemistry, South Kensington Campus, Imperial College London, SW7 2AZ, UK
b   Institute of Chemical Biology, Imperial College London, London, SW7 2AZ, UK   Email: a.c.spivey@imperial.ac.uk
,
Alan C. Spivey*
a   Department of Chemistry, South Kensington Campus, Imperial College London, SW7 2AZ, UK
› Author Affiliations
Further Information

Publication History

Received: 08 December 2014

Accepted after the revision: 06 January 2015

Publication Date:
10 February 2015 (online)

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Abstract

Phosphorylation of alcohols by phosphoryl chlorides catalysed by pyridine-N-oxide is reported. The utility of this method is demonstrated through phosphorylation of primary, secondary and a tertiary alcohol as well as phenols under mild reaction conditions and with low catalyst loading (5 mol%).

Key words

phosphorylation - alcohols - pyridine-N-oxide - organocatalysis

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1379993.
  • Supporting Information
 

  • References and Notes

  • 1 Corbridge DE. C. J. Am. Chem. Soc. 2000; 122: 10742
    Search in Google Scholar
  • 2 Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. Science 2002; 298: 1912
    CrossrefSearch in Google Scholar
  • 3 Jessen HJ, Ahmed N, Hofer A. Org. Biomol. Chem. 2014; 3526
  • 4 Schultz C. Bioorg. Med. Chem. 2003; 11: 885
    CrossrefSearch in Google Scholar
  • 5 Zawilska JB, Wojcieszak J, Olejniczak AB. Pharmacol. Reports 2013; 65: 1
    Search in Google Scholar
  • 6 Rautio J, Kumpulainen H, Heimbach T, Oliyai R, Oh D, Järvinen T, Savolainen J. Nat. Rev. Drug Discovery 2008; 7: 255
    CrossrefPubMedSearch in Google Scholar
  • 7 Uphues G, Ploog U. US Patent US4921990A, 1990
  • 8 Beaucage SL, Iyer RP. Tetrahedron 1993; 49: 1925
    CrossrefSearch in Google Scholar
  • 9 Jones S, Selitsianos D. Org. Lett. 2002; 4: 3671
    CrossrefSearch in Google Scholar
  • 10 Jones S, Selitsianos D, Thompson KJ, Toms SM. J. Org. Chem. 2003; 68: 5211
    CrossrefSearch in Google Scholar
  • 11 Jones S, Smanmoo C. Org. Lett. 2005; 7: 3271
    CrossrefSearch in Google Scholar
  • 12 Jones S, Selitsianos D. Tetrahedron: Asymmetry 2005; 16: 3128
    CrossrefSearch in Google Scholar
  • 13 Crook S, Parr NJ, Simmons J, Jones S. Tetrahedron: Asymmetry 2014; 25: 1298
    CrossrefSearch in Google Scholar
  • 14 Fenton OS, Allen EE, Pedretty KP, Till SD, Todaro JE, Sculimbrene BR. Tetrahedron 2012; 68: 9023
    CrossrefSearch in Google Scholar
  • 15 Coppola KA, Testa JW, Allen EE, Sculimbrene BR. Tetrahedron Lett. 2014; 55: 4203
    CrossrefSearch in Google Scholar
  • 16 Mora N, Lacombe JM, Pavia AA. Tetrahedron Lett. 1993; 34: 2461
    CrossrefSearch in Google Scholar
  • 17 Sabesan S, Neira S. Carbohydr. Res. 1992; 223: 169
    CrossrefSearch in Google Scholar
  • 18 Pisarek S, Bednarski H, Gryko D. Synlett 2012; 23: 2667
    Thieme ConnectSearch in Google Scholar
  • 19 Sculimbrene BR, Miller SJ. J. Am. Chem. Soc. 2001; 123: 10125
    CrossrefSearch in Google Scholar
  • 20 Sculimbrene BR, Morgan AJ, Miller SJ. J. Am. Chem. Soc. 2002; 124: 11653
    CrossrefSearch in Google Scholar
  • 21 Garrett CE, Prasad K. Adv. Synth. Catal. 2004; 346: 889
    CrossrefSearch in Google Scholar
  • 22 Kucznierz R, Dickhaut J, Leinert H, Von Der Saal W. Synth. Commun. 1999; 29: 1617
    CrossrefSearch in Google Scholar
  • 23 Guillaume M, Cuypers J, Dingenen J. Org. Process Res. Dev. 2007; 11: 1079
    CrossrefSearch in Google Scholar
  • 24 Reeves JT, Tan Z, Han ZS, Li G, Zhang Y, Xu Y, Reeves DC, Gonnella NC, Ma S, Lee H, Lu BZ, Senanayake CH. Angew. Chem. Int. Ed. 2012; 51: 1400
    CrossrefSearch in Google Scholar
  • 25 Efimov VA, Chakhmakhcheva OG, Ovchinnikov YA. Nucleic Acids Res. 1985; 13: 3651
    CrossrefSearch in Google Scholar
  • 26 Efimov VA, Buryakova AA, Dubey IY, Polushin NN, Chakhmakhcheva OG, Ovchinnikov YA. Nucleic Acids Res. 1986; 14: 6525
    CrossrefSearch in Google Scholar
  • 27 Murray JI, Woscholski R, Spivey AC. Chem. Commun. 2014; 50: 13608
    CrossrefSearch in Google Scholar
  • 28 The o-XP group can also be introduced onto non-phenolic alcohols (see ref. 27), where its ease of removal can also be advantageous for certain applications.
  • 29 General Method: To a solution of alcohol component (0.9 mmol), pyridine-N-oxide (0.045 mmol, 5 mol%) and Proton-sponge® (1.8 mmol) in CH2Cl2 (0.2 M) was added the specified phosphoryl chloride (1.0 mmol). The reaction mixture was stirred at r.t. for the time specified before the addition of MeOH (2 mL). The reaction mixture was then concentrated in vacuo and the crude material was purified by flash chromatography to afford the product. 17-β-3-xylenylphosphoryl estradiol (5b): According to the general method, 17-β-estradiol (246 mg, 0.9 mmol), pyridine-N-oxide (5 mg, 5 mol%), Proton-sponge® (392 mg, 2.0 mmol) and xylenyl phosphoryl chloride (217 mg, 1.0 mmol) followed by flash chromatography (eluent: 0–50% EtOAc–hexanes) afforded xylenylphosphate 5b as a white solid (290 mg, 0.64 mmol, 71%); mp 146–147 °C; [α]D 19 –87 (c = 0.99, CHCl3). IR: 3314, 3033, 3001, 2936, 1707, 1612, 1536, 1286, 1211, 1097, 875, 736, 467 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.41–7.43 (m, 2 H), 7.34–7.36 (m, 2 H), 7.28–7.30 (m, 1 H), 7.05–7.08 (m, 1 H), 5.38–5.44 (m, 2 H), 5.19–5.28 (m, 2 H), 3.76 (t, J = 8.5 Hz, 1 H), 2.88 (m, 2 H), 2.31–2.39 (m, 1 H), 2.11–2.26 (m, 2 H), 1.99 (dt, J = 12.5, 3.3 Hz, 1 H), 1.89–1.94 (m, 1 H), 1.69–1.77 (m, 1 H), 1.18–1.55 (m, 9 H), 0.81 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 138.8, 135.2, 129.4, 129.1, 126.8, 119.6, 119.5, 116.8, 114.2, 81.9, 68.9, 50.1, 44.1, 43.2, 38.5, 36.7, 30.6, 29.6, 27.0, 26.2, 23.1, 11.1. 31P NMR (161 MHz, CDCl3): δ = –6.94. HRMS (ES): m/z [M + H+] calcd for C26H32O5P: 455.1987; found: 455.1988. (S)-Methyl 2-[(tert-butoxycarbonyl)amino]-3-[(diphenoxyphosphoryl)oxy]propanoate (8): According to the general method, Cbz-Ser(OH)-OMe (200 mg, 0.9 mmol), pyridine-N-oxide (5 mg, 5 mol%), Proton-sponge® (392 mg, 2.0 mmol) and diphenyl phosphoryl chloride (0.21 mL, 1.0 mmol) followed by flash chromatography (eluent: 0–10% EtOAc–hexanes) afforded diphenylphosphate 8 as a white solid (311 mg, 0.69 mmol, 77%); mp 61–63 °C; [α]D 19 + 161 (c = 0.96, CHCl3). IR: 3313, 3067, 3039, 2957, 1721, 1590, 1514, 1488, 1456, 1288, 1185, 1163, 948, 754, 688 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.20–7.40 (m, 10 H), 5.40 (d, J = 7.9 Hz, 1 H), 4.65–4.67 (m, 1 H), 4.51–4.60 (m, 1 H), 3.71 (s, 3 H), 1.46 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 169.4, 155.1, 150.4, 129.9, 129.8, 125.6, 120.1, 120.0, 80.4, 68.8, 53.8, 52.8, 28.3. 31P NMR (161 MHz, CDCl3): δ = –12.34. HRMS (ES): m/z [M + Na] calcd for C21H26NO8PNa: 474.1294; found: 474.1300.
  • 30 Yamago S. US Patent US2008177049A1, 2008
  • 31 Toth G, Kele Z, Varadi G. Curr. Org. Chem. 2007; 11: 409
    CrossrefSearch in Google Scholar
  • 32 Jarowicki K, Kocienski P. J. Chem. Soc., Perkin Trans. 1 1998; 1: 4005
    Search in Google Scholar
  • 33 McMurray JS, Coleman DR, Wang W, Campbell ML. Biopolymers 2001; 60: 3
    CrossrefSearch in Google Scholar