Synthesis of Alkynes and R-Hydroxyphosphonamides
1
Alkynes 5a, 5e, and 5f are commercial products. Compounds
5b,30 5c,31 5d,32 5g,33 and 5h34 were previously described in the
literature.
Phenyl-2-d-acetylene, 9. H NMR (250 MHz, acetone-d6) δ
7.29-7.34 (m, 3 H), 7.58-7.65 (m, 2 H); 13C NMR (62.5 MHz,
acetone-d6) δ 7.1 (t, JC-D ) 38.1 Hz), 83.6, 122.1, 128.3, 132.1,
1
r-Trimethylsilyloxybenzyl-N,N′-ethylene-N,N′-diisopropyl-
134.4.
phosphonamide, 3a: 430 mg (90%); crystals, mp 74-75 °C (from
4-(1,1-Bis(dimethylamino)-1-r-trimethylsilyloxybenzyl-λ5-
phosphanyliden)-4,5-dihydro-1,2,3-thiadiazole-5-tione, 10a. Dry
CS2 (0.12 mL, 2.0 mmol) and freshly distilled benzaldehyde (0.05
mL, 0.5 mmol) were successively added to a solution of diazo-
phosphine 2 (131 mg, 0.5 mmol) in 1 mL of anhydrous THF, under
a nitrogen atmosphere. The mixture was stirred at room temperature
for 15 min, and then solvent was removed. The residue was
chromatographed (2:1 hexane/EtOAc as eluent) to provide com-
1
ether); H NMR (250 MHz, CDCl3) δ 0.03 (s, 9 H), 1.03 (t-like,
JH-H ) 6.0 Hz, 6 H), 1.12 (d, JH-H ) 6.5 Hz, 3 H), 1.21 (d, JH-H
) 6.5 Hz, 3 H), 2.80-3.47 (m, 6 H), 5.0 (d, JP-H ) 11.1 Hz, 1 H),
7.24-7.48 (m, 5 H); 13C NMR (62.5 MHz, CDCl3) δ 0.4, 21.4,
2
2
21.8, 38.6 (d, JP-C ) 8.3 Hz), 39.6 (d, JP-C ) 8.3 Hz), 74.7 (d,
1JP-C ) 142.4 Hz), 127.4, 127.5, 127.7, 139.3; 31P NMR (101.2
MHz, CDCl3) δ 31.0; MS 366.5 [M+].
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pound 10 as an oil (178 mg, 86% yield): H NMR (250 MHz,
Desilylation of Ethers 4a-d,g: Preparation of Compounds
6a-d,g,h,j. (a) With TBAF. As a typical example, desilylation of
4a is described. A mixture of silyl ether 4a (190 mg, 0.6 mmol)
and TBAF‚H2O (615 mg, 2.4 mmol) in 5 mL of THF was stirred
at room temperature for 4 h. Then, THF was eliminated, and the
residue was poured into CH2Cl2 and washed with water (3 × 10
mL). The organic phase was washed once with CH2Cl2 (10 mL),
and the combined organic layers were dried (MgSO4). Solvent was
evaporated under reduced pressure to afford alcohol 6a (107 mg,
67% yield), which was crystallized to render the analytical sample.
(b) With 5% HCl in MeOH. Desilylation of 4d is described.
A mixture of ether 4d (0.95 g, 3.9 mmol) in 10 mL of methanol
and some drops of aqueous 5% HCl was stirred at room temperature
for 4 h. The solvent was evaporated, and the residue was
chromatographed by using successively EtOAc and methanol as
eluents to afford alcohol 6d (0.63 mg, 66% yield).
3
CDCl3) δ -0.01 (s, 9 H), 2.51 (d, JP-H ) 9.5 Hz, 6 H), 2.95 (d,
3JP-H ) 9.5 Hz, 6 H), 7.09 (d, JP-H ) 7.7 Hz, 1 H), 7.34 (m, 3
2
H), 7.54 (m, 2 H); 13C NMR (62.5 MHz, CDCl3) δ -0.1, 38.4 (d,
2JP-C ) 2.9 Hz), 38.7 (d, 2JP-C ) 1.9 Hz), 73.0 (d, 2JP-C ) 105.9
Hz), 127.8, 127.9, 128.7, 135.6, 138.5 (d, 1JP-C ) 141.1 Hz), 192.2
(d, JP-C ) 26.7 Hz); 31P NMR (101.2 MHz, CDCl3) δ 48.3; MS
2
387.1 [(M + H+) - N2].
5-Phenyl-4-trimethylsilyl-4-(N,N,N′,N′-tetramethylaminothio-
phosphoryl)-4,5-dihydro-1,2,3-oxadiazole, 11a. tert-Butylisonitrile
(0.11 mL, 1.0 mmol) and freshly distilled benzaldehyde (0.10 mL,
1.0 mmol) were successively added to a solution of diazophosphine
2 (131 mg, 0.5 mmol) in 1 mL of anhydrous THF, under a nitrogen
atmosphere. After stirring the mixture at room temperature for 15
min, an excess of elemental sulfur was added and stirring was
continued for 1 h. Then, solvent and phenyl acetylene was removed
under reduced pressure and the residue was chromatographed (2:1
hexane/EtOAc and MeOH as eluents) to afford phosphondiamide
4a (91 mg, 58% yield) and heterocycle 11 as an oil (63 mg, 35%
yield). Spectral data for compound 11 follow: 1H NMR (250 MHz,
(2R)-1,2,3-Trihydroxypropyl-N,N,N′,N′-tetramethylphosphon-
diamide, 7. A mixture of 4h (100 mg, 0.3 mmol) in 2 mL of MeOH
and some drops of aqueous 5% HCl was heated to reflux for 8 h.
Solvent was removed under reduced pressure, and the residue was
poured into EtOAc to afford triol 7 as a solid (61 mg, 90% yield):
3
acetone-d6) δ 0.14 (s, 9 H), 2.45 (d, JP-H ) 13.1 Hz, 6 H), 2.66
3
3
1
(d, JP-H ) 12.9 Hz, 6 H), 5.81 (d, JP-H ) 7.9 Hz, 1 H), 7.38-
crystals, mp 91-94 °C; [R]D -9.6 (c ) 1.25, CH2Cl2); H NMR
7.40 (m, 5 H); 13C NMR (62.5 MHz, CDCl3) δ -0.9, 35.5, 35.8,
(250 MHz, acetone-d6) δ 2.62 (s, 12 H), 3.55-3.80 (m, 4 H); 13
C
1
2
NMR (62.5 MHz, acetone-d6) δ 35.4, 65.1, 71.2, 72.9; 31P NMR
(101.2 MHz, acetone-d6) δ 33.93.
51.6 (d, JP-C ) 142.1 Hz), 71.42 (d, JP-C ) 15.3 Hz), 124.9,
127.3, 128.1, 142.2; 31P NMR (101.2 MHz, CDCl3) δ 81.1; MS
393.1 [M + Na+].
r-d-r-Trimethylsilyloxybenzyl-N,N,N′,N′-tetramethylphos-
phondiamide, 8: yield 0.74 (94%); 1H NMR (250 MHz, acetone-
Acknowledgment. We thank the Ministerio de Educacio´n
y Ciencia (CTQ2004-01067) and DURSI, Generalitat de Cata-
lunya (PICS2005-10, 2005SGR00103) (Spain), and the CNRS
(France) for financial support. Access to computational facilities
of Centre de Supercomputacio´ de Catalunya (CESCA) is
gratefully acknowledged.
3
3
d6) δ 0.02 (s, 9 H), 2.52 (d, JP-H ) 8.7 Hz, 6 H), 2.56 (d, JP-H
) 7.5 Hz, 6 H), 7.30 (m, 3 H), 7.56 (m, 2 H); 13C NMR (62.5
MHz, acetone-d6) δ 0.4, 36.3 (d, 2JP-C ) 2.9 Hz), 37.0 (d, 2JP-C
)
2.9 Hz), 79.5 (t, 1JC-D ) 33.4 Hz), 127.5, 128.1, 128.7, 140.9; 31
P
NMR (101.2 MHz, acetone-d6) δ 32.7; MS (m/e) 316.1 [M + H+],
338.1 [M + Na+].
Supporting Information Available: Analytical and spectro-
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scopic data for products 4a-i, 5b, 5i, 5j, and 6a-j. H and 13C
(30) Takahashi, S.; Kuroyama, K.; Sonogashira, K.; Hagihara, N.
Synthesis 1980, 627.
(31) von der Ohe, F.; Bru¨ckner, R. New J. Chem. 2000, 24, 659.
(32) Alagille, D.; Baldwin, R. M.; Roth, B. L.; Wroblewski, J. T.;
Grajkowska, E.; Tamagnan, G. D. Bioorg. Med. Chem. 2005, 13, 197.
(33) Kobayashi, Y.; Yamashita, T.; Takahashi, K.; Kuroda, H.; Ku-
madaki, I. Tetrahedron Lett. 1982, 23, 343.
NMR spectra for representative synthesized new compounds.
Cartesian coordinates, total energies for all considered structures
computed at the B3LYP/6-31G(d) level of calculation, and the value
of the imaginary frequency at the transition states. This material is
(34) (a) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769. (b)
Ohita, S. Synth. Commun. 1989, 19, 561.
JO060663K
J. Org. Chem, Vol. 71, No. 14, 2006 5327