989
J. I. Murray et al.
Letter
Synlett
OH
OH
H
H
H2 (1 atm)
O
P
O
O
O
O
H
H
H
H
Pd/C (10 mol%)
MeOH
P
HO
O
HO
5b
11 99%
O
O
OPh
OPh
P
P
H2 (1 atm)
OH
OH
O
O
PtO2 (10 mol%)
MeOH
BocHN
CO2Me
BocHN
CO2Me
8
12 98%
Scheme 2 Deprotection of phosphate esters 5b and 8
duction of phosphate esters for biological applications, e.g.
in the preparation of prodrugs. For difficult alcohol phos-
phorylation cases, for example the site-selective phosphor-
ylation of polyols, the use of a 2-aryl-4-DMAP-N-oxide cata-
lyst will likely be warranted,27 but the commercial availabil-
ity and low cost of pyridine-N-oxide makes it an attractive
first choice catalyst for evaluation.
(14) Fenton, O. S.; Allen, E. E.; Pedretty, K. P.; Till, S. D.; Todaro, J. E.;
Sculimbrene, B. R. Tetrahedron 2012, 68, 9023.
(15) Coppola, K. A.; Testa, J. W.; Allen, E. E.; Sculimbrene, B. R. Tetra-
hedron Lett. 2014, 55, 4203.
(16) Mora, N.; Lacombe, J. M.; Pavia, A. A. 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, B. R.; Miller, S. J. J. Am. Chem. Soc. 2001, 123,
10125.
Acknowledgment
(20) Sculimbrene, B. R.; Morgan, A. J.; Miller, S. J. J. Am. Chem. Soc.
2002, 124, 11653.
(21) Garrett, C. E.; Prasad, K. Adv. Synth. Catal. 2004, 346, 889.
(22) Kucznierz, R.; Dickhaut, J.; Leinert, H.; Von Der Saal, W. Synth.
Commun. 1999, 29, 1617.
We thank the EPSRC and the Imperial College Institute of Chemical
Biology for funding. J.I.M. is also grateful to the Society of Chemical
Industry for a Messel Scholarship.
(23) Guillaume, M.; Cuypers, J.; Dingenen, J. Org. Process Res. Dev.
2007, 11, 1079.
(24) Reeves, J. T.; Tan, Z.; Han, Z. S.; Li, G.; Zhang, Y.; Xu, Y.; Reeves, D.
C.; Gonnella, N. C.; Ma, S.; Lee, H.; Lu, B. Z.; Senanayake, C. H.
Angew. Chem. Int. Ed. 2012, 51, 1400.
Supporting Information
Supporting information for this article is available online at
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
(25) Efimov, V. A.; Chakhmakhcheva, O. G.; Ovchinnikov, Y. A.
Nucleic Acids Res. 1985, 13, 3651.
(26) Efimov, V. A.; Buryakova, A. A.; Dubey, I. Y.; Polushin, N. N.;
Chakhmakhcheva, O. G.; Ovchinnikov, Y. A. Nucleic Acids Res.
1986, 14, 6525.
(27) Murray, J. I.; Woscholski, R.; Spivey, A. C. Chem. Commun. 2014,
50, 13608.
(28) The o-XP group can also be introduced onto non-phenolic alco-
hols (see ref. 27), where its ease of removal can also be advanta-
geous 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.
References and Notes
(1) Corbridge, D. E. C. J. Am. Chem. Soc. 2000, 122, 10742.
(2) Manning, G.; Whyte, D. B.; Martinez, R.; Hunter, T.;
Sudarsanam, S. Science 2002, 298, 1912.
(3) Jessen, H. J.; Ahmed, N.; Hofer, A. Org. Biomol. Chem. 2014, 3526.
(4) Schultz, C. Bioorg. Med. Chem. 2003, 11, 885.
(5) Zawilska, J. B.; Wojcieszak, J.; Olejniczak, A. B. Pharmacol.
Reports 2013, 65, 1.
(6) Rautio, J.; Kumpulainen, H.; Heimbach, T.; Oliyai, R.; Oh, D.;
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(8) Beaucage, S. L.; Iyer, R. P. Tetrahedron 1993, 49, 1925.
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Chem. 2003, 68, 5211.
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)
(11) Jones, S.; Smanmoo, C. Org. Lett. 2005, 7, 3271.
(12) Jones, S.; Selitsianos, D. Tetrahedron: Asymmetry 2005, 16, 3128.
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try 2014, 25, 1298.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 985–990