B. Furman, M. Dziedzic / Tetrahedron Letters 44 (2003) 8249–8252
8251
Table 3. Palladium catalyzed cross-coupling of arylboronic
acids and 4-methylenepiperidine
6. Vice, S.; Bara, T.; Bauer, A.; Evans, C. A.; Ford, J.;
Josien, H.; McCombie, S.; Miller, M.; Nazareno, D.;
Palani, A.; Tagat, J. J. Org. Chem. 2001, 66, 2487–2492.
7. Rubiralta, M.; Diez, A.; Miguel, D.; Remuson, R.; Gelas-
Mialhe, Y. Synth. Commun. 1992, 22, 359–367.
8. Kobayashi, S.; Busujima, T.; Nagayama, S. Chem. Com-
mun. 1998, 19–20.
9. A typical experimental procedure: To a suspension of
Yb(OTf)3 (0.01 mmol, 10 mol%) in CH3CN (5 mL) were
added an aldehyde (0.1 mmol) and an amine 4 (0.1
mmol) at room temperature. The mixture was stirred for
10–15 h, water was added and the product was extracted
with CH2Cl2 (3×5 mL). After the organic layer was dried
and evaporated, the crude product was dissolved in
CH2Cl2 (5 mL) and pyridine (0.1 mL), cooled to 0°C and
TsCl (0.1 mmol) was added in one portion. The mixture
was stirred at rt for 5 h. A solution of aqueous NaHCO3
(10 mL) was added and the product was extracted with
CH2Cl2 (3×10 mL). The combined organic extracts were
dried (MgSO4) and concentrated, and the crude product
chromatographed on silica gel (10% ethyl acetate/hexanes
for elution). Representative data for 4-methylene-1-(tolu-
ene-4-sulfonyl)piperidine (Table 2, entry 1): 1H NMR
(400 MHz, CDCl3) l 7.65–7.29 (m, 4H), 4.69 (s, 2H), 3.05
(t, 4H, J=5.7 Hz), 2.42 (s, 3H), 2.30 (t, 4H, J=5.7 Hz);
13C NMR (100 MHz, CDCl3): 143.5, 133.4, 129.6, 127.6,
109.9, 47.6, 33.8, 21.5; HRMS (EI) calcd for C13H17NO2S
251.09800, found 251.09776.
Entry
Ar
Yield of 8 (%)
1
2
3
4
5
6
C6H5
86
80a
78
88
62
72
4-t-BuC6H4
4-MeOC6H4
4-FC6H4
4-Me2NC6H4
4-MeCOC6H4
a Yield calculated using 1H NMR.
10. (a) Cacchi, S.; Fabrizi, G.; Gallina, C.; Pace, P. Synlett
1997, 54–55; (b) Peng, S.; Qing, F-L.; Guo, Y. Synlett
1998, 859–860; (c) Littke, A. F.; Fu, G. C. J. Am. Chem.
Soc. 2001, 123, 6989–7000.
Scheme 4.
11. Jung, Y. Ch.; Mishra, R. K.; Yoon, Ch. H.; Jung, K. W.
Org. Lett. 2003, 5, 2231–2234.
In conclusion we have reported a simple and efficient
procedure for the synthesis of 4-(substituted benz-
yl)piperidines. The protocol is general in scope and
does not require anhydrous reaction conditions.
12. A typical experimental procedure: 4-Methylenepiperidine
(Table 2, entry 1) (0.1 mmol) was dissolved in DMF, to
the solution were added phenylboronic acid (0.13 mmol),
Na2CO3 (0.3 mmol) and Pd(OAc)2 (0.01 mmol) in one
portion. The flask was fitted with an oxygen balloon and
heated to 50°C for 2 h. After that time the mixture was
diluted with ethyl acetate, washed with brine and dried
over (MgSO4). Evaporation of the solvent followed by
silica-gel column chromatography gave the corresponding
product. Representative data for 4-benzylidene-1-(tolu-
ene-4-sulfonyl)piperidine (Table 3, entry 1): 1H NMR
(400 MHz, CDCl3) l 7.09–7.64 (m, 9H), 6.29 (s, 1H), 3.12
(m, 2H), 2.99 (m, 2H), 2.57 (m, 2H), 2.45 (m, 2H), 2.42
(s, 3H); 13C NMR (100 MHz, CDCl3): 136.9, 136.4,
133.2, 129.6, 128.7, 128.2, 127.7, 126.5, 125.2, 47.7, 41.1,
35.6, 28.4, 21.5; HRMS (EI) calcd for C19H21NO2S
327.12930, found 327.12919.
13. (a) Smith, K. A.; Campi, E. M.; Jackson, W. R.; Marcuc-
cio, S.; Naeslund, Ch. G. M.; Deacon, G. B. Synlett 1997,
131–132; (b) Wong, M. S.; Zhang, X. L. Tetrahedron
Lett. 2001, 42, 4087–4089; (c) Parrish, J. P.; Jung, Y. C.;
Floyd, J.; Jung, K. W. Tetrahedron Lett. 2002, 43, 7899–
7902; (d) Yoshida, H.; Yamaryo, Y.; Ohshita, J.; Kunai,
A. Tetrahedron Lett. 2003, 44, 1541–1544.
Acknowledgements
We wish to thank the State Committee for Scientific
Research (Grant 4 T09A 064 25) for support of this
work.
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14. A typical experimental procedure: To a solution of 4-benz-
ylidene-1-(toluene-4-sulfonyl)piperidine (Table 3, entry 1)
in 10 mL of methanol was added 20 mg of 10% Pd/C.