3872
H.-X. Wei et al. / Tetrahedron 57 ꢀ2001) 3869±3873
1
136±1388C; H NMR ꢀ200 MHz, DMSO-d ) d 8.91 ꢀd,
without puri®cation and their stoichiometries were calcu-
lated based on the reported purities from the manufacturers.
Flash chromatography was performed on E. Merck silica gel
6
J10 Hz, 1H), 7.30±7.53 ꢀm, 8H), 5.42 ꢀd, J10 Hz, 1H),
1
3
4.64 ꢀt, J10 Hz, 1H), 3.35 ꢀs, 3H), 2.37 ꢀs, 3H); C NMR
6
0 ꢀ230±400 mesh). High-resolution mass spectral analysis
ꢀ75 MHz, CDCl ): d 168.9, 143.0, 137.3, 133.6, 133.3,
3
was conducted by the URC mass spectrometry facility of the
University of California at Riverside.
130.8, 129.9, 129.4, 127.5, 126.4, 126.3, 59.2, 56.1, 52.1,
21.0.
1
3.1.5. Compound 7. Colorless oil ꢀ344 mg, 77% yield); H
The representative procedure is demonstrated by the
dichloro-ꢀ1,10-phenanthroline)-palladium
aminochlorination reaction of methyl trans-cinnamate
with N,N-dichloro-p-toluenesulfonamide as described in
Scheme 2. Into a dry vial was added methyl cinnamate
ꢀII)-catalyzed
NMR ꢀ200 MHz, DMSO-d
7.21±7.46 ꢀm, 8H), 5.03 ꢀd, J12.0 Hz, 1H), 4.25 ꢀdd,
6
) d 8.80 ꢀd, J9.8 Hz, 1H),
1
3
J12.0, 9.8 Hz, 1H), 3.35 ꢀs, 3H), 2.37 ꢀs, 3H); C NMR
ꢀ75 MHz, CDCl ): d 169.3, 142.8, 137.3, 136.0, 131.3,
3
ꢀ81.0 mg, 0.50 mmol) and acetonitrile ꢀ1.5 mL). The reac-
tion vial was immersed in a room temperature bath, and
131.0, 130.2, 130.0, 129.3, 129.2, 126.3, 126.2, 122.4,
61.2, 59.0, 52.2, 21.1.
loaded with TsNCl ꢀ144 mg, 0.60 mmol, 1.20 equiv.) and
2
dichloro-ꢀ1,10-phenanthroline)-palladium ꢀII) ꢀ14.3 mg,
8
3.1.6. Compound 8. Colorless oil ꢀ239 mg, 56% yield);
1
mol%). The resulting solution in the capped vial was
H NMR ꢀ200 MHz, DMSO-d
6
) d 8.84 ꢀd, J8.0 Hz,
stirred at room temperature for 22 h without inert gas
protection. The reaction was ®nally quenched by dropwise
addition of saturated aqueous Na S O solution ꢀ2 mL). The
1H), 8.3 ꢀm, 2H), 8.14 ꢀm, 1H), 7.57 ꢀm, 1H), 7.35 ꢀd,
J8.0 Hz, 2H), 7.17 ꢀd, J8.0 Hz, 2H), 5.25 ꢀd,
J10.0 Hz, 1H), 4.31 ꢀdd, J10.0, 8.0 Hz, 1H), 3.92 ꢀm,
C
2
2
3
1
3
phases were separated, and the aqueous phase was extracted
with ethyl acetate ꢀ3£10 mL). The combined organic layers
were washed with 10% aqueous ammonia chloride and
brine, dried over anhydrous magnesium sulfate and concen-
trated to dryness. Puri®cation by ¯ash chromatography
2H), 3.34 ꢀs, 1H), 2.30 ꢀs, 1H), 1.07 ꢀt, J6.0 Hz, 3H);
NMR ꢀ75 MHz, CDCl ): d 168.6, 147.3, 142.8, 138.8,
3
137.5, 135.0, 130.1, 129.3, 126.1, 123.8, 123.2, 61.4, 61.3,
58.5, 20.9, 13.7.
ꢀ
2
8
EtOAc/hexane, 1:3, v/v) provided trans methyl 3-chloro-
-ꢀp-toluenesulfonamido)-3-phenylpropionate 1 ꢀ0.123 g,
Acknowledgements
1
1% yield) as white solid. Mp 142±1448C; H NMR
ꢀ
7
1
200 MHz, DMSO-d ): d 8.75 ꢀd, J9.93 Hz, 1H), 7.24±
The ®nancial support from National Institutes of Health
ꢀNIHGM), The Robert A. Welch Foundation and Texas
Tech University are gratefully acknowledged.
6
.52 ꢀm, 9H), 5.04 ꢀd, J10.3 Hz, 1H), 4.29 ꢀt, J10.3 Hz,
H), 3.35 ꢀs, 3H), 2.25 ꢀs, 3H); C NMR ꢀ75 MHz, CDCl ):
3
1
3
d 169.3, 142.8, 137.3, 136.7, 129.4, 128.9, 128.5, 128.2,
26.3, 61.1, 60, 52.0, 21.0. HRMS ꢀDCI) m/z
1
ꢀ
1
M 1NH ) found 385.0986, calcd for C H ClN O S
1
4
17 22
2
4
References
3
85.0988.
1
. Kemp, J. E. G. Comprehensive Organic Synthesis, Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3,
pp 471±513.
3
1
.1.1. Compound 2. White solid ꢀ266 mg, 70% yield); mp
43±1458C; H NMR ꢀ200 MHz, DMSO-d ) d 8.74 ꢀd,
1
6
J10 Hz, 1H), 7.06±7.50 ꢀm, 8H), 4.99 ꢀd, J10.4 Hz,
2. Evans, D. A.; Faul, M. M.; Bilodeau, M. T.; Anderson, B. A.;
Barnes, D. M. J. Am. Chem. Soc. 1993, 115, 5328.
3. Li, Z.; Conser, K. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1993,
115, 5326.
1
2
1
5
3
H), 4.25 ꢀt, J10 Hz, 1H), 3.35 ꢀs, 3H), 2.35 ꢀs, 3H),
1
.25 ꢀs, 3H); C NMR ꢀ75 MHz, CDCl ): d 169.5, 142.7,
3
3
38.5, 137.4, 133.7, 129.3, 129.0, 128.0, 126.3, 61.2, 60.2,
2.0, 21.0, 20.8. HRMS ꢀDCI) m/z ꢀM 1NH ) found
1
1
4
4. Jeong, J. U.; Tao, B.; Henniges, H.; Sharpless, K. B. J. Am.
Chem. Soc. 1998, 120, 6844.
99.1141, calcd for C H ClN O S 399.1145.
4
1
8
25
2
5
. Qiu, J.; Silverman, R. B. J. Med. Chem. 2000, 43, 706.
3.1.2. Compound 3. White solid ꢀ285 mg, 75% yield);
mp 132±1348C; H NMR ꢀ200 MHz, DMSO-d ) d 8.77
6. ꢀa) Grif®th, D. A.; Danishefsky, S. J. J. Am. Chem. Soc. 1991,
113, 5863. ꢀb) Corey, E. J.; Chen, C.-P.; Reichard, G. A.
Tetrahedron Lett. 1989, 30, 5547. ꢀc) Barton, D. H. R.; Brit-
ten-Kelley, M. R.; Ferreira, D. J. Chem. Soc., Perkin Trans. 1
1978, 1090. ꢀd) Driguez, H.; Vermes, J.-P.; Lessard, J. Can. J.
Chem. 1978, 56, 119. ꢀe) Lessard, J.; Driguez, H.; Vermes,
J.-P. Tetrahedron Lett. 1970, 4887. ꢀf) Dumic, M.; Vinkovic,
M.; Filic, D.; Jamnicky, B.; Eskinja, M.; Kamenar, B. J. Med.
Chem. 1995, 38, 3034.
1
6
ꢀ
d, J10 Hz, 1H), 7.20±7.58 ꢀm, 8H), 5.22 ꢀd, J10.7 Hz,
1
3
1
NMR ꢀ75 MHz, CDCl ): d 169.5, 143.0, 137.3, 136.7,
H), 4.48 ꢀt, J10.4 Hz, 1H), 3.31 ꢀs, 3H), 2.36 ꢀs, 3H);
C
3
1
5
34.6, 129.3, 130.7, 129.4, 128.8, 126.5, 126.4, 126.3,
9.8, 56.4, 52.0, 21.0, 18.6; HRMS ꢀDCI) m/z
1
1
ꢀ
M 1NH ) found 399.1148, calcd for C H ClN O S
4 18 25 2 4
3
99.1145.
.1.3. Compound 5. Colorless oil ꢀ331 mg, 82% yield); H
7
. ꢀa) Daniher, F. A.; Butler, P. E. J. Org. Chem. 1968, 33, 4336.
ꢀb) Daniher, F. A.; Butler, P. E. J. Org. Chem. 1968, 33, 2637.
ꢀc) Daniher, F. A.; Melchior, M. T.; Butler, P. E. J. Chem.
Soc., Chem. Commun. 1968, 931. ꢀd) Seden, T. P.; Turner,
R. W. J. Chem. Soc. ꢀC) 1968, 876.
1
3
NMR ꢀ200 MHz, DMSO-d ) d 8.80 ꢀd, J9.6 Hz, 1H),
6
7
.21±7.39 ꢀm, 8H), 5.05 ꢀd, J10.4 Hz, 1H), 4.26 ꢀdd,
1
3
J10.4, 9.6 Hz, 1H), 3.32 ꢀs, 3H), 2.37 ꢀs, 3H); C NMR
ꢀ
75 MHz, CDCl ): d 169.3, 142.7, 137.4, 135.6, 133.7,
3
8. ꢀa) Li, G.; Wei, H.-X.; Kim, S. H.; Neighbors, M. Org. Lett.
1999, 1, 395. For NsNCl ±NsNHNa-based aminohalogena-
1
30.0, 129.3, 128.4, 126.2, 61.2, 59.0, 52.2, 21.0.
2
tion see: ꢀb) Li, G.; Wei, H.-X.; Kim, S. H. Org. Lett. 2000,
2, 2249.
3
.1.4. Compound 6. White solid ꢀ249 mg, 62% yield); mp