LETTER
Synthesis of O,O-Diethyl Arylthiophosphonate from O-Aryl-O,O-diethylthiophosphate
3123
action (Table 1, entry 4). The conversion was indeed
increased but the yield stayed quite modest (48%). Final-
ly, a metal-halogen exchange performed by reaction of n-
BuLi with 1b (Table 1 entry 5) allowed us to observe a
full conversion of the substrate affording the pure aryl-
thiophosphonate 2 in good yield (95%). A 31P NMR mon-
itoring of this reaction performed at –80 °C showed the
presence of a single signal at d = 96.01 ppm. This reso-
nance was proved to correspond to that of the lithium phe-
nolate compound (also characterized by 1H and 13C NMR)
resulting from a halogen-metal exchange on 1b followed
by a [1,3]-migration of the thiophosphono group. Hydrol-
ysis of this compound was found to afford quantitatively
2. This experiment demonstrates that, at –80 °C, both the
metal-halogen exchange and the [1,3]-rearrangement are
extremely fast. This rearrangement has been extended to
other phenols displaying one or two bromides in ortho po-
sitions. First, the thiophosphates 1c–i (Table 2) were pre-
pared from their corresponding phenol by reaction with
the commercially available diethylchlorothiophosphate.13
Then the [1,3]-rearrangement was achieved on these com-
pounds by reaction with n-butyllithium in THF at –78
°C.14 This reaction was easily followed by 31P NMR since
the thiophosphates are characterized by a 31P chemical
shift at d = 61.7–63.6 ppm while the resonances of the
formed thiophosphonates are observed at d = 69.7–80.0
ppm (see Table 2). The [1,3]-rearrangements were ac-
complished in good yields (77– 97%, see Table 2). This
rearrangement has been applied on polybromide sub-
strates (Table 2, entries 1–3, 6 and 7) to produce the ex-
pected thiophosphonates in good yields. For the
heteroaromatic substrate 1f, a regiospecific reaction was
observed giving rise to 2f in 85% yield (entry 4). The ef-
ficiency of this reaction is in contrast to that observed for
the method previously reported for the synthesis of com-
pound 2f which was isolated in 30% yield and as a 3:1
mixture of regioisomers.11 The presence of a second bro-
mide atom in the ortho position of the phenol group of
compounds 2c and 2d, has allowed us to introduce, via a
subsequent two-step sequence, a second thiophosphono
group giving rise in good yields to 2g and 2h (entries 5
and 6). The synthesis of compound 2i, resulting from a si-
multaneous double [1,3]-rearrangement, has also been
achieved in good yield (92%) starting from the bisthio-
phosphate 1i (entry 7). In that case, 2.2 equivalents of
BuLi were used.
Acknowledgment
We thank the ‘Service de RMN, UFR Sciences et Techniques, Uni-
versité de Bretagne Occidentale, Brest’ for NMR data recording.
References and Notes
(1) Bibal, B.; Tinant, B.; Declercq, J. P.; Dutasta, J. P. Chem.
Commun. 2002, 432.
(2) (a) Kobayashi, Y.; Morisawa, F.; Saigo, K. Org. Lett. 2004,
6, 4227. (b) Kobayashi, Y.; Morisawa, F.; Saigo, K. J. Org.
Chem. 2006, 71, 606.
(3) (a) Kilian, P.; Slawin, A. M. Z.; Woollins, J. D. Dalton
Trans. 2003, 3876. (b) Zarudnitskii, E. V.; Yurchenko,
A. A.; Merkulov, A. S.; Semenova, M. G.; Pinchuk, A. M.;
Tomachev, A. A. Heteroat. Chem. 2005, 16, 648.
(c) Fernandez, M. F.; Vlaar, C. P.; Fan, H.; Liu, Y. H.;
Fronczek, F. R.; Hammer, R. P. J. Org. Chem. 1995, 60,
7390.
(4) (a) Kobayashi, Y.; Maeda, J.; Saigo, K. Tetrahedron:
Asymmetry 2006, 17, 1617. (b) Carré, F.; Chuit, C.; Corriu,
R. J. P.; Montforte, P.; Nayyar, N. K.; Reyé, C.
J. Organomet. Chem. 1995, 499, 147.
(5) Jayasundera, K. P.; Watson, A. M. J.; Taylor, C. M.
Tetrahedron Lett. 2005, 46, 4311.
(6) (a) Melvin, L. S. Tetrahedron Lett. 1981, 22, 3375.
(b) Dhawan, B.; Redmore, D. J. Org. Chem. 1984, 49, 4018.
(7) Legrand, O.; Brunel, J. M.; Constantieux, T.; Buono, G.
Chem. Eur. J. 1998, 4, 1061.
(8) Au-Yeung, T. L.; Chan, K. Y.; Haynes, R. K.; Williams,
I. D.; Yueng, L. L. Tetrahedron Lett. 2001, 42, 457.
(9) (a) Masson, S.; Saint-Clair, J. F.; Saquet, M. Synthesis 1993,
485. (b) Bonini, B. F.; Femoni, C.; Fochi, M.; Gulea, M.;
Masson, S.; Ricci, A. Tetrahedron: Asymmetry 2005, 16,
3003.
(10) Mauger, C.; Vazeux, M.; Masson, S. Tetrahedron Lett.
2004, 45, 3855.
(11) Onys’ko, P. P.; Suvalova, E. A.; Chudakova, T. I.; Sinitsa,
A. D. Zh. Obshch. Khim. 1994, 64, 610.
(12) Garbers, H. V.; Modro, T. A. Heteroat. Chem. 1990, 1, 241.
(13) Preparation of Thiophosphates 1a–i Represented by the
Preparation of O,O-Diethyl 6-Bromo-2-(diethoxythio-
phosphinyl)-4-methylphenylthiophosphonate (1g): A
solution of the phenolic derivative 2c (3.70 g, 8.85 mmol),
triethylamine (1.48 mL, 10.6 mmol, 1.2 equiv) and DMAP
(0.108 g, 0.88 mmol, 0.1 equiv) in THF (36 mL) was slowly
added (15 min) to a solution of O,O-diethylchlorothio-
phosphate (1.67 g, 8.85 mmol) in THF (10 mL). The solution
was then stirred overnight. The obtained suspension was
filtered on celite and washed with Et2O. The filtrate was
concentrated and redissolved in Et2O (80 mL). The organic
phase was washed with H2O (2 × 20 mL) and brine (15 mL),
dried over MgSO4, filtered and concentrated. The obtained
crude product was purified by column chromatography over
silica gel (70–230 mesh; pentane–EtOAc, 100:5) to produce
1g (87% yield) as a colorless solid; mp 81 °C. 1H NMR (300
MHz, CDCl3): d = 1.33, 1.40 (2 × t, 3JHH = 7.0 Hz, 12 H,
CH3CH2O), 2.34 (s, 3 H, Me), 4.14, 4.31 (2 × m, 8 H,
In the present communication, a [1,3]-phospho-Fries rear-
rangement has been applied to the synthesis of O,O-dieth-
yl 2-hydroxyarylthiophosphonate. This simple method
has allowed the formation of a P–C bond via a two-step
process: (1) an orthometallation achieved by a metal-halo-
gen exchange reaction, and (2) the rearrangement itself.
This methodology has also allowed the introduction of
thiophosphono groups on both ortho positions of a a,a¢-
dibromophenol. A double rearrangement, starting from a
bi-phenol derivative, is also illustrated.
CH3CH2O), 7.57 (d, 5JHP = 1.8 Hz, 1 H, H5), 7.92 (d, 3JHP
19.0 Hz, 1 H, H3). 31P (81.03 MHz, CDCl3): d = 62.2 (d,
4JPP = 2.7 Hz), 83.5 (d, 4JPP = 2.7 Hz). 13C (75.48 MHz,
CDCl3): d = 16.0 (m, CH2CH3), 20.7 (s, Me), 63.3 (d, 3JHP
=
=
5 Hz, OCH2CH3), 65.2 (m, OCH2CH3), 117.6 (dd, 3JCP = 12
Hz, 3JCP = 5 Hz, CBr), 127.6 (dd, 1JCP = 143 Hz, 3JCP = 5 Hz,
CArP), 136.0–136.42 (m, 2 × CAr), 139.0 (s, CArH), 147.3 (m,
CArO). IR (neat): 709, 735, 790, 889, 927, 966, 1018, 1245,
Synlett 2008, No. 20, 3121–3124 © Thieme Stuttgart · New York