9762
S. K. Talluri, A. Sudalai / Tetrahedron 63 (2007) 9758–9763
was distilled off under reduced pressure, and the crude prod-
uct was purified by column chromatography over silica gel
using CHCl3 as eluant to yield the corresponding pure
N-methyl amine 10.
Acknowledgements
S.K.T. thanks CSIR, New Delhi, for financial support. The
authors thank Dr. B. D. Kulkarni, Head, CE-PD Division,
for his constant encouragement and support.
Yield: 137 mg (92%); gum; [a]2D5 ꢁ10.87 (c 1.0, EtOH);
{lit.13 [a]D21 ꢁ10.9 (c 4.2, EtOH)}; IR (CHCl3, cmꢁ1): 771,
878, 1036, 1130, 1219, 1344, 1458, 1541, 1651, 2829,
2928, 3252; 1H NMR (200 MHz, CDCl3) d: 1.07 (d,
J¼6.1 Hz, 3H), 2.38 (s, 3H), 2.52–2.85 (m, 3H), 7.16–7.33
(m, 5H); 13C NMR (50 MHz, CDCl3) d: 19.2, 33.4, 43.0,
56.1, 126.0, 128.2, 129.0, 139.0; Mass (m/z, % rel intensity):
149 (M+, 4), 134 (10), 119 (5), 117 (5), 91 (45), 65 (16), 58
(100). Analysis: C10H15N requires C, 80.49; H, 10.12; N,
9.38%; found C, 80.41; H, 10.12; N, 9.45%.
References and notes
1. (a) Mizutta, I.; Ohta, M.; Ohta, K.; Nishimura, M.; Mizutta, E.;
Hayashi, K.; Kuna, S. Biochem. Biophys. Res. Commun. 2000,
279, 751; (b) Vaglini, F.; Pardini, C.; Cavalletti, M.; Maggio,
R.; Corsini, G. U. Brain Res. 1996, 741, 68.
2. Sano, M.; Ernesto, C.; Thomas, R. C.; Klauber, M. R. N. Engl.
J. Med. 1997, 336, 1216.
3. (a) Abu-Raya, S.; Blaugrund, S.; Tremblower, V.; Shilderman,
E.; Shohami, E. J. Neurosci. Res. 1999, 58, 456; (b) Paterson,
I. A.; Tatton, W. G. Adv. Pharmacol. 1998, 42, 312.
4. (a) Flower, J. S. J. Org. Chem. 1977, 42, 2637; (b) Gyogy,
B.; Jozsef, K.; Eva, S.; Sandor, V.; Ferenc, Z. Chem. Abstr.
1988, 110, 44960; (c) Plenevaux, A.; Flower, S. F.; Dewey,
S. L.; Wolf, A. P.; Guillaume, M. Appl. Radiat. Isot. 1991,
42, 121.
5. (a) Josef, H.; Jiri, H.; Pavel, P.; Bohumila, B.; Milan, F.; Jiri, K.;
Lubomir, K.; Josef, P. Chem. Abstr. 1989, 113, 5900; (b) Josef,
H.; Jiri, H.; Pavel, P.; Bohumila, B.; Milan, F.; Jiri, K.; Lubomir,
K.; Josef, P. Chem. Abstr. 1991, 117, 150680; (c) Silvia, O.;
Richard, C.; Jeorg, S.; Hans, W. Chem. Abstr. 1996, 124,
288969x; (d) Sterling, J.; Herzig, Y.; Goren, T.; Finkelstein;
Lerner, D.; Goldenberg, W.; Miskolezi, I.; Molnar; Rantal, F.
J. Med. Chem. 2002, 45, 5260.
(2) a-Amination approach: to a stirred solution of N-Boc
protected amino alcohol 12 (251 mg, 1 mmol) in CH2Cl2
(5 mL) were added triethylamine (153 mL, 1.1 mmol) and
p-toluenesulfonyl chloride (210 mg, 1.1 mmol) at 0 ꢀC.
The reaction mixture was stirred at 0 ꢀC for 1 h and then
quenched by addition of 10% NaHCO3. The aqueous layer
was extracted with CH2Cl2 (3ꢂ20 mL) and the combined
organic layers were dried over anhyd Na2SO4, concentrated
on rotavapour to give the crude tosylate, which dissolved in
THF (5 mL), and added dropwise to a suspension of LiAlH4
(114 mg, 3 mmol) in THF (20 mL). The reaction mixture
was refluxed for 4 h and then cooled to 0 ꢀC and the excess
LiAlH4 was quenched by addition of EtOAc. The reaction
mixture was treated with 20% NaOH (0.5 mL), the white
precipitate formed was filtered off, and the residue was
washed with EtOAc (3ꢂ10 mL). The combined EtOAc
layers were dried over anhyd Na2SO4, solvent was distilled
off under reduced pressure, and the crude product was
purified by column chromatography over silica gel using
CHCl3 as eluant to yield the corresponding pure N-methyl
amine 10; [a]D25 ꢁ10.36 (c 4.0, EtOH); {lit.13 [a]2D1 ꢁ10.9
(c 4.2, EtOH)}.
6. Sayyed, I. A.; Sudalai, A. Tetrahedron: Asymmetry 2004, 15,
3111.
7. (a) George, S.; Narina, S. V.; Sudalai, A. Tetrahedron 2006,
62, 10202; (b) Kotkar, S. P.; Sudalai, A. Tetrahedron:
Asymmetry 2006, 17, 1738; (c) Narina, S. V.; Sudalai, A.
Tetrahedron Lett. 2006, 47, 6799; (d) Kotkar, S. P.; Sudalai,
A. Tetrahedron Lett. 2006, 47, 6813; (e) Narina, S. V.;
Talluri, S. K.; George, S.; Sudalai, A. Tetrahedron Lett.
2007, 48, 65.
8. (a) List, B.; Seayad, J. Org. Biomol. Chem. 2005, 3, 719; (b)
Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43,
5138; (c) Houk, K. N., List, B., Eds.; Acc. Chem. Res. 2004,
37, 487; (d) List, B., Ed.; Adv. Synth. Catal. 2004, 346,
1021; (e) Bolm, C., Ed.; Adv. Synth. Catal. 2004, 346, 1022;
(f) Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2001, 40,
3726.
4.1.12. N-Methyl-N-((R)-1-phenylpropan-2-yl)prop-
2-yn-1-amine: (R)-selegiline (1). (1) a-Aminooxylation
approach: to a stirred solution of (R)-2-(methylamino)-1-
phenylpropane (10) (200 mg, 1.34 mmol) in CH3CN
(10 mL) were added anhyd K2CO3 (277 mg, 2.01 mmol)
and propargyl bromide (478 mg, 4.02 mmol). The reaction
mixture was then stirred for 12 h at 25 ꢀC, the solid residue
formed was then filtered off, and the solvent was distilled off
under reduced pressure to give the crude product, which was
purified by column chromatography over silica gel using
CHCl3 as eluant to give pure (R)-selegiline 1.
9. For a review of proline-catalyzed asymmetric reactions, see:
List, B. Tetrahedron 2002, 58, 5573.
10. (a) Hayashi, Y.; Yamaguchi, J.; Hibino, K.; Shoji, M.
Tetrahedron Lett. 2003, 44, 8293; (b) Zhong, G. Angew.
Chem., Int. Ed. 2003, 42, 4247; (c) Hayashi, Y.; Yamaguchi,
J.; Sumiya, T.; Shoji, M. Angew. Chem., Int. Ed. 2003, 43,
1112; (d) Brown, S. P.; Brochu, M. P.; Sinz, C. J.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125, 10808;
(e) Cordova, A.; Sunden, H.; Bøgevig, A.; Johansson, M.;
Himo, F. Chem.—Eur. J. 2004, 10, 3673.
11. (a) List, B. J. Am. Chem. Soc. 2002, 125, 5656; (b) Bogevig, A.;
Juhl, K.; Kumaragurubaran, N.; Zhuang, W.; Jorgensen, K. A.
Angew. Chem., Int. Ed. 2002, 41, 1790; (c) Kumaragurubaran,
N.; Juhl, K.; Zhuang, W.; Bogevig, A.; Jorgensen, K. A. J. Am.
Chem. Soc. 2002, 124, 6254; (d) Vogt, H.; Vanderheiden, S.;
Brase, S. Chem. Commun. 2003, 2448; (e) Iwamura, H.;
Yield: 0.18 g (72%); gum; [a]2D5 ꢁ10.7 (c 6.5, EtOH);
1
{lit.12 [a]2D5 ꢁ10.8 (c 6.4, EtOH)}; H NMR (200 MHz,
CDCl3) d: 0.95 (d, J¼6.0 Hz, 3H), 2.25 (t, J¼2.0 Hz,
1H), 2.35 (s, 3H), 2.40–2.55 (m, 1H), 2.80–3.10 (m, 2H),
3.40 (d, J¼2.0 Hz, 2H), 7.00–7.50 (m, 5H); 13C NMR
(50 MHz, CDCl3) d: 21.1, 31.4, 46.8, 51.9, 60.8, 68.1,
82.2, 125.6, 128.3, 128.6, 140.2. Analysis: C13H17N re-
quires C, 83.37; H, 9.14; N, 7.47%; found C, 83.34; H,
9.11; N, 7.53%.
(2) a-Amination approach: [a]2D5 ꢁ10.28 (c 6.5, EtOH);
{lit.12 [a]2D5 ꢁ10.8 (c 6.4, EtOH)}.