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C. W. Lindsley et al. / Tetrahedron Letters 43 (2002) 4467–4470
11. For the reaction sequence in Scheme 2, 13 required 10 h
5. Conversion and purity were determined by analytical
for 100% conversion of 9 to 10 and 14 required overnight
for complete conversion of 9 to 10. As to why the
reaction rate is depressed to such a degree is unclear. We
observe that as the fluorine content increases on going
from 11 to 14, the solubility in THF decreases; therefore,
the reaction may become heterogeneous (i.e. a fluorous
phase and an organic phase) and demonstrated the kinet-
ics of a biphasic system like those exhibited by 8. Alterna-
tively, the decreased reaction may be due solely to the
increased steric hindrance about the phosphorous in 13
and 14. One other possibility for the diminished reactivity
is decreased electron density of the phosphorous lone pair
and hence decreased nucleophilicity of the phosphine. 31P
NMR spectra of 13 (−5.7 ppm) and 14 (−6.5 ppm)
indicate upfield shifts relative to 11 (−3.3 ppm) indicating
electronics may contribute to the diminished activity.
12. All compounds were fully characterized by LCMS, NMR
and HRMS. Spectral data for Table 1. Entry 1 (1H
NMR, 300 MHz, CDCl3): l 7.75 (d, J=7.2 Hz, 2H), 7.59
(t, J=15 Hz, 1H), 7.4 (m, 3H), 7.13 (s, 1H), 4.40 (s, 2H),
2.63 (s, 2H), 2.1 (s, 3H); HRMS calcd for C15H14NOCl
(M+H), 260.0837; found 260.0845. Entry 2 (1H NMR,
300 MHz, DMSO-d6): l 13.1 (s, 1H), 6.86 (d, J=7.5 Hz,
2H), 6.43 (d, J=7.5 Hz, 2H), 3.93 (m, 1H), 2.77 (m, 1H),
2.62 (m, 1H), 1.31 (s, 9H); HRMS calcd for C14H20N2O4
(M+Na), 303.1315; found 303.1325. Entry 3 (1H NMR,
300 MHz, DMSO-d6): l 8.37 (s, 1H), 8.15 (s, 1H), 7.33 (s,
2H), 6.08 (m, 1H), 5.45 (m, 1H), 4.98 (m, 1H), 4.08 (s,
1H), 2.69 (m, 2H), 1.53 (s, 6H), 1.32 (s, 2H); HRMS
calcd for C13H18N6O3 (M+H), 307.1513; found 307.1510.
Entry 4 (1H NMR, 300 MHz, CDCl3): l 2.14 (s, 4H),
2.03 (s, 6H), 1.67 (s, 6H); HRMS calcd for C10H17N
(M+H), 152.1434; found 152.1437. Entry 5 (1H NMR,
300 MHz, DMSO-d6): l 7.7 (s, 1H), 6.08 (m, 1H), 4.95 (s,
1H), 3.56 (m, 2H), 3.36 (m, 2H), 2.0 (m, 2H), 1.74 (s,
3H); HRMS calcd for C10H15N3O4 (M+H), 242.1149;
found 249.1136. Entry 6 (1H NMR, 300 MHz, DMSO-
d6): l 7.99 (bs, 2H), 7.36 (m, 1H), 7.15 (m, 2H), 5.73 (s,
1H), 4.81 (m, 1H), 4.04 (m, 1H), 3.4 (m, 12H); HRMS
calcd for C13H19NO6 (M+H), 286.1285; found 286.1285.
LCMS and NMR analysis.
6. Lindsley, C. W.; Zhao, Z.; Leister, W. H. Tetrahedron
Lett., submitted.
7. (a) FluoroFlash™ SPE columns and fluorous-tethered
phosphines are commercially available from FTI, Fluo-
or prepared according to Zhang, Q.; Luo, Z.; Curran, D.
P. J. Org. Chem. 2000, 65, 8866–8873.; (c) For excellent
reviews of the area, see: (1) Curran, D. P. Synlett 2001,
1488–1496; (2) Curran, D. P. Pure A Chem. 2000, 72,
1649–1653; (d) Lou, Z. Y.; Williams, J.; Read, R. W.;
Curran, D. P. J. Org. Chem. 2001, 66, 4261–4266.
8. In a typical experiment, 4-azidobenzoic acid 9 (82 mg,
0.50 mmol), 11 (334 mg, 0.55 mmol) and THF (3 mL) are
placed in an 8 mL vial. The vial is placed on a rotator for
50 min. Immediately, gas evolution is observed. After 50
min, 500 mL of water is added, and the vial is placed in a
heater/shaker block at 60°C for 3 h. Analytical LCMS
indicates a 1:1.1 ratio of 10: fluorous-tethered PPh3O.
The crude reaction is applied to a silica transfer column
(Part c: 622-0057S) atop a 5 g FluoroFlash™ column
(Part c: 801-0058S), pre-washed with aqueous methanol
and attached to a multi-port vacuum manifold. Air is
drawn through for 2 min, and then 10 mL of a 15%
aqueous methanol solution is added and slowly eluted
under an ꢀ−5 psi vacuum and collected into a test tube.
The test tube is concentrated in a Genevac HT II-12 to
afford 64 mg (93%) of amine 10 as a white solid. Analyt-
ical LCMS indicated a single peak (0.474 min, CH3CN/
H2O/0.1%TFA, 4 min gradient) >98% pure by UV (214
nm) and 100% pure by ELSD. (1H NMR, 300 MHz,
CDCl3): l 11.9 (s, 1H), 7.58 (d, J=8.7 Hz, 2H), 6.51 (d,
J=9 Hz, 2H), 5.85 (s, 2H). HRMS: calcd for C7H7NO2
(M+H), 137.0477; found 137.0480.
9. Analytical LCMS: 12 a single peak (3.270 min, CH3CN/
H2O/0.1%TFA, 4 min gradient) >98% pure by UV (214
nm) and 100% pure by ELSD, 744.2 (M+1).
10. 31P NMR recorded at 122.7 MHz on a Varian VXR-300
spectrometer.