M.-Y. Chang et al. / Tetrahedron Letters 53 (2012) 627–631
631
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10. CCDC 846030 (7a), 846031 (15a), 844450 (16b), 846033 (18), and 846032 (19),
and contain the supplementary crystallographic data for this paper. This data
fax: 44-1223-336033; e-mail: deposit@ccdc.cam.ac.uk).
11. A representative three-step synthetic transformation of skeleton 7 or 8 from
olefin 9 is as follows: NBS (188 mg, 1.05 mmol) was added to a solution of
olefin 9 (1.0 mmol) in methanol (10 mL) at rt. The reaction mixture was stirred
at reflux for 2 h. Saturated NaHCO3(aq) solution (2 mL) was added to the
reaction mixture and the solvent was concentrated. The residue was extracted
with DCM (3 Â 20 mL). The combined organic layers were washed with brine,
dried, filtered and evaporated to afford crude product. Without further
purification, DBU (1.5 g, 10.0 mmol) was added to a solution of the resulting
product in THF (10 mL) at rt. The reaction mixture was stirred at reflux for 10 h.
Water (1 mL) was added to the reaction mixture and the solvent was
concentrated. The residue was extracted with EtOAc (3 Â 20 mL). The
combined organic layers were washed with brine, dried, filtered and
evaporated to afford crude product. Without further purification, a solution
of BF3ÁOEt2 (1 mL) in DCM (5 mL) was added to a stirred solution of the
resulting enamine product in trimethylsilyl cyanide (3 mL) or
allyltrimethylsilane (3 mL) in DCM (10 mL) at rt. The reaction mixture was
stirred at rt for 15 min. Saturated NaHCO3(aq) solution (2 mL) was added to the
reaction mixture and the solvent was concentrated under reduced pressure.
The residue was extracted with EtOAc (3 Â 30 mL). The combined organic
layers were washed with brine, dried, filtered and evaporated to afford crude
product under reduced pressure. Purification on silica gel (hexanes/
EtOAc = 6:1–3:1) afforded skeleton 7 or 8. Representative data for compound
7a: HRMS (ESI, M++1) calcd for C25H23N2O2S 415.1480, found 415.1483; 1H
NMR (400 MHz, CDCl3): d 7.76–7.73 (m, 2H), 7.65–7.61 (m, 1H), 7.56–7.51 (m,
2H), 7.43–7.25 (m, 6H), 7.19–7.16 (m, 2H), 7.07–7.05 (m, 2H), 5.70 (s, 1H), 3.99
(d, J = 12.0 Hz, 1H), 2.97 (dt, J = 3.2, 12.4 Hz, 1H), 2.68 (dq, J = 2.8, 4, 14.8 Hz,
1H), 2.28 (dt, J = 4.4, 14.8 Hz, 1H), 1.86–1.70 (m, 2H); 13C NMR (100 MHz,
CDCl3): d 142.99, 139.99, 139.40, 136.80, 133.55, 129.23 (2Â), 129.10 (2Â),
129.04 (2Â), 128.85 (2Â), 128.33 (2Â), 128.29, 127.72 (2Â), 126.33, 114.87,
49.07, 43.38, 29.68, 26.27, 25.77. Single-crystal X-ray diagram: crystal of
Figure 4. X-ray structure of b-amino acid 19.
Conclusion
A synthetic methodology for producing a series of 2-substituted
3-diarylmethylenylpiperidines 7 (Y = CN) and 8 (Y = allyl) has been
successfully presented using NBS-mediated
a-bromomethoxyla-
tion reaction, DBU-promoted regioselective dehydrobromination
reaction, and BF3ÁOEt2-promoted cross-coupling reaction involving
trimethylsilyl-based nucleophiles. Under the three-step protocol,
-amino ester 18 and b-amino acid 19 were also synthesized. Sev-
eral structures of the target products were confirmed by X-ray
a
crystal analysis.
Acknowledgment
The authors would like to thank the National Science Council of
the Republic of China for its financial support (NSC 99-2113-M-
037-006-MY3).
compound 7a was grown by slow diffusion of EtOAc into
a solution of
Supplementary data
compound 7a in DCM to yield colorless prism. The compound crystallizes in
the triclinic crystal system, space group P-1, a = 8.0292(3) Å, b = 11.2051(4) Å,
c = 11.9519(4) Å, V = 1037.99(6) Å3, Z = 2, dcalcd = 1.326 g/cm3, F(000) = 436, 2h
Supplementary data associated with this article can be found, in
range 1.75–26.52°,
Representative data for compound 8a: HRMS (ESI, M++1) calcd for
27H28NO2S 430.1841, found 430.1841; 1H NMR (400 MHz, CDCl3): d 7.71–
R
indices (all data) R1 = 0.0387, wR2 = 0.0828.
C
7.68 (m, 2H), 7.58–7.53 (m, 1H), 7.49–7.45 (m, 2H), 7.34–7.17 (m, 6H), 7.09–
7.06 (m, 2H), 6.91–6.88 (m, 2H), 5.64–5.53 (m, 1H), 5.08–5.02 (m, 2H), 4.84 (t,
J = 8.0 Hz, 1H), 3.91 (dd, J = 4.8, 14.0 Hz, 1H), 3.24 (dt, J = 3.2, 14.0 Hz, 1H),
2.62–2.55 (m, 1H), 2.49–2.40 (m, 2H), 2.16 (dt, J = 4.8, 14.0 Hz, 1H), 1.64–1.59
(m, 2H); 13C NMR (100 MHz, CDCl3): d 141.87, 141.34, 140.87, 138.39, 134.14,
132.71, 132.12, 129.46 (2Â), 129.14 (2Â), 128.84 (2Â), 128.17 (2Â), 128.06
(2Â), 127.26 (2Â), 127.10, 126.72, 116.94, 55.74, 40.62, 35.73, 26.23, 25.47.
12. (a) Viti, G.; Perrotta, E.; Giannotti, D.; Nannicini, R. Tetrahedron 1997, 53, 8519;
(b) Carey, F. A.; Tremper, H. S. J. Org. Chem. 1971, 36, 758.
References and notes
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