Organocatalytic Phosphorylation of Alcohols Using Pyridine-N-oxide

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

• References and Notes

• 1 Corbridge DE. C. J. Am. Chem. Soc. 2000; 122: 10742
• 2 Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. Science 2002; 298: 1912
• 3 Jessen HJ, Ahmed N, Hofer A. Org. Biomol. Chem. 2014; 3526
• 4 Schultz C. Bioorg. Med. Chem. 2003; 11: 885
• 5 Zawilska JB, Wojcieszak J, Olejniczak AB. Pharmacol. Reports 2013; 65: 1
• 6 Rautio J, Kumpulainen H, Heimbach T, Oliyai R, Oh D, Järvinen T, Savolainen J. Nat. Rev. Drug Discovery 2008; 7: 255
• 7 Uphues G, Ploog U. US Patent US4921990A, 1990
• 8 Beaucage SL, Iyer RP. Tetrahedron 1993; 49: 1925
• 9 Jones S, Selitsianos D. Org. Lett. 2002; 4: 3671
• 10 Jones S, Selitsianos D, Thompson KJ, Toms SM. J. Org. Chem. 2003; 68: 5211
• 11 Jones S, Smanmoo C. Org. Lett. 2005; 7: 3271
• 12 Jones S, Selitsianos D. Tetrahedron: Asymmetry 2005; 16: 3128
• 13 Crook S, Parr NJ, Simmons J, Jones S. Tetrahedron: Asymmetry 2014; 25: 1298
• 14 Fenton OS, Allen EE, Pedretty KP, Till SD, Todaro JE, Sculimbrene BR. Tetrahedron 2012; 68: 9023
• 15 Coppola KA, Testa JW, Allen EE, Sculimbrene BR. Tetrahedron Lett. 2014; 55: 4203
• 16 Mora N, Lacombe JM, Pavia AA. Tetrahedron Lett. 1993; 34: 2461
• 17 Sabesan S, Neira S. Carbohydr. Res. 1992; 223: 169
• 18 Pisarek S, Bednarski H, Gryko D. Synlett 2012; 23: 2667
• 19 Sculimbrene BR, Miller SJ. J. Am. Chem. Soc. 2001; 123: 10125
• 20 Sculimbrene BR, Morgan AJ, Miller SJ. J. Am. Chem. Soc. 2002; 124: 11653
• 21 Garrett CE, Prasad K. Adv. Synth. Catal. 2004; 346: 889
• 22 Kucznierz R, Dickhaut J, Leinert H, Von Der Saal W. Synth. Commun. 1999; 29: 1617
• 23 Guillaume M, Cuypers J, Dingenen J. Org. Process Res. Dev. 2007; 11: 1079
• 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
• 25 Efimov VA, Chakhmakhcheva OG, Ovchinnikov YA. Nucleic Acids Res. 1985; 13: 3651
• 26 Efimov VA, Buryakova AA, Dubey IY, Polushin NN, Chakhmakhcheva OG, Ovchinnikov YA. Nucleic Acids Res. 1986; 14: 6525
• 27 Murray JI, Woscholski R, Spivey AC. Chem. Commun. 2014; 50: 13608
• 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
• 32 Jarowicki K, Kocienski P. J. Chem. Soc., Perkin Trans. 1 1998; 1: 4005
• 33 McMurray JS, Coleman DR, Wang W, Campbell ML. Biopolymers 2001; 60: 3