1714
G. F. Busscher et al. / Tetrahedron: Asymmetry 21 (2010) 1709–1714
3. Charlton-Menys, V.; Durrington, P. N. Exp. Physiol. 2007, 93, 27–42.
4. (a) Juaristi, E. Enantioselectivie Synthesis of b-Amino Acids; Wiley-VCH: New
York, 1997; (b) Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069–1094; (c)
Ma, J.-A. Angew. Chem., Int. Ed. 2003, 42, 4290–4299.
171.5, 158.6, 158.1, 155.0, 143.17, 137.3, 134.4, 128.9, 128.4, 127.9,
116.12, 115.8, 115.5, 77.8, 77.6, 77.4, 77.0, 70.5, 61.2, 55.8, 43.1,
14.5. HPLC enantiomeric purity of 74% ee (AD-H column, 1.0 mL/
5. For a review, see: Drexler, H. J.; You, J.; Zhang, S.; Fischer, C.; Baumann, W.;
Spannenburg, A.; Heller, D. Org. Process Res. Dev. 2003, 7, 355.
min, 2-propanol/n-heptane, (1/9), 5 lL): retention times (min):
18.4 (major) and 23.6 (minor).
6. Tertiary enamines: (a) Lee, N. E.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116,
5985–5986; (b) Tararov, V. I.; Kadyrov, R.; Riermeier, T. H.; Holz, J.; Börner, A.
Tetrahedron Lett. 2000, 41, 2351–2355; (c) Hou, G.-H.; Xie, J.-H.; Wang, L.-X.;
Zhou, Q.-L. J. Am. Chem. Soc. 2006, 128, 11774–11775; (d) Cheruku, P.; Church,
T. L.; Trifonova, A.; Wartmann, T.; Andersson, P. G. Tetrahedron Lett. 2008, 49,
7290–7293; (e) Hou, G.-H.; Xie, J. H.; Yan, P.-C.; Zhou, Q.-L. J. Am. Chem. Soc.
2009, 131, 1366–1367; (f) Yan, P.-C.; Xie, J.-H.; Hou, G.-H.; Wang, L.-X.; Zhou,
Q.-L. Adv. Synth. Catal. 2009, 351, 3243–3250; (g) Baeza, A.; Pfaltz, A. Chem. Eur.
2009, 15, 2266–2269.
7. Secondary enamines: Wang, X.-B.; Wang, D.-W.; Lu, S.-M.; Yu, C.-B.; Zhou, Y.-G.
Tetrahedron: Asymmetry 2009, 20, 1040–1045.
8. (a) Enamino esters and amides: (a) Matsumura, K.; Zhang, X.; Saito, T. U.S.
Patent 7,015,348 B2, 2004.; (b) Matsumura, K.; Hori, K.; Kakizawa, T.; Saito, T.
In Proceedings of the Summer Symposium, Tokyo, July 28–29, 2005, The Japanese
4.3. Preparation of ethyl 3-amino-3-(4-(benzyloxy)phenyl)
propanoate 4 via D.A.R.A. of 2 (S/C = 5000)
A
100 mL Hastelloy autoclave was filled with [Me2NH2]
{RuCl(R)-dm-segphos)}2(
l
-Cl)3]27 (6.2 mg, 0.0033 mmol), ammo-
nium salicylate (10.4 g, 67.0 mmol), and salicylic acid (0.463 g,
3.35 mmol). The atmosphere was replaced with nitrogen (purging:
5 cycles of filling to 3 bar N2/emptying) followed by addition of
ethyl
3-(4-benzyloxy)phenyl)-3-oxopropanoate
(10.0 g,
33.5 mmol) in EtOH (50 mL). The reaction mixture was stirred for
10 h at 85 °C, with 50 bar hydrogen pressure. After cooling down
to ambient temperature and filtration, EtOH was evaporated and
the crude reaction mixture was stirred with satd aq NaHCO3 for
30 min. Next, the product was extracted with toluene
(3 ꢁ 250 mL). The toluene layer was washed with satd aq Na2CO3.
Evaporation of the toluene yielded the product as a brownish solid
(8.0 g, 80%). 1H NMR (CDCl3, 300 MHz, ppm) d: 7.3–7.10 (m, 7H),
6.84 (d, J = 8.4 Hz, 2H), 4.94 (s, 2H), 4.27 (t, J = 6.9 Hz, 1H), 4.02
(q, J = 6.9, 7.3 Hz, 2H), 2.53 (d, J = 7.3 Hz, 2H), 1.13 (t, J = 6.9 Hz,
3H). HPLC: enantiopurity of 96.6% ee (AS-H column, 0.5 mL/min,
Society for Process Chemistry: Tokyo;
p 146.; (c) Saito, T.; Zhang, X.;
Matsumura, K.; Yokozawa, T.; Shimizu, H. In 19th North American Meeting,
Philadelphia, PA, May 22–27, 2005, North American Catalysis Society Home
Rivera, N. R.; Rosner, T.; Krska, S. W.; Njolito, E.; Wang, F.; Sun, Y.-K.;
Armstrong, J. D.; Grabowski, E. J. J.; Tillyer, R. D.; Spindler, F.; Malan, C. J. Am.
Chem. Soc. 2004, 126, 9918–9919; (e) Clausen, A. M.; Dziadul, B.; Cappuccio, K.
L.; Kaba, M.; Starbuck, C.; Hsiao, Y.; Dowling, T. M. Org. Process Res. Dev. 2006,
10, 723–726; (f) Kubryk, M.; Hansen, K. B. Tetrahedron: Asymmetry 2006, 17,
205–209; (g) Hansen, K. B.; Hsiao, Y.; Xu, F.; Rivera, N.; Clausen, A.; Kubryk, M.;
Krska, S.; Rosner, T.; Simmons, B.; Balsells, J.; Ikemoto, N.; Sun, Y.-K.; Spindler,
F.; Malan, C.; Grabowski, E. J. J.; Armstrong, J. D., III J. Am. Chem. Soc. 2009, 131,
8798–8804.
9. Halpern, J. Science 1982, 217, 401–407.
10. (a) Lubell, W. D.; Kitamura, M.; Noyori, R. Tetrahedron: Asymmetry 1991, 2,
543–554; For a review, see: (b) Halpern, J. In Asymmetric Synthesis; Morrison, J.
D., Ed.; Academic Press: Orlando, FL, 1985; p 41.
2-propanol/2-hexane/diethylamine = 60/40/0.1,
times (min): 12.4 (minor) and 14.0 (major).
5 lL): retention
11. (a) Moroi, T.; Sotoguchi, T.; Matsumura, K.; Takenaka, M.; Kuriyama, W.;
Murayama, T.; Nara, H.; Yokozawa, T.; Yagi, K. WO 2004/074255.; (b) Dai, Q.;
Yang, W.; Zhang, X. Org. Lett. 2005, 7, 5343–5345.
12. Hebbache, H.; Hank, Z.; Bruneau, C.; Renaud, J. L. Synthesis 2009, 15, 2627–
2633.
4.3.1. Ethyl 3-(4-(benzyloxy)phenyl)-3-(4-fluorophenylamino)
propanoate 1b
A
round-bottomed flask was charged with CuCl (1.03 g,
13. (a) Matsumura, K.; Saito, T. WO 2005/028419.; (b) Bunlaksananusorn, T.;
Rampf, F. Synlett 2005, 2682–2684; (c) Shimizu, H.; Nagasaki, I.; Matsumura,
K.; Sayo, N.; Saito, T. Acc. Chem. Res. 2007, 40, 1385–1393; For a similar
approach using aryl ketones, see: Kadyrov, R.; Riermeier, T. H. Angew. Chem.,
Int. Ed. 2003, 42, 5472–5474.
14. Steinhuebel, D.; Sun, Y.-K.; Matsumura, K.; Sayo, N.; Saito, T. J. Am. Chem. Soc.
2009, 131, 11316–11317.
15. de Lange, B.; Lambers-Verstappen, M. H.; Schmieder-van de Vondervoort, L.;
Sereinig, N.; de Rijk, R.; de Vries, A. H. M.; de Vries, J. G. Synlett 2006, 3105–
3109.
10.4 mmol) and crushed KOH (17 g, 0.31 mol). Amino ester 4
(20.0 g, 66.8 mmol in 110 mL DMF), acetylacetone (1.65 mL,
16.1 mmol), and 4-fluoro-bromobenzene (12 mL, 0.11 mol) were
successively added. The resulting mixture was heated at 120 °C un-
der N2 for 20 h. The reaction was allowed to cool down to room
temperature and 100 mL of water was added. The suspension
was filtered over Celite and extracted with pentane (4 ꢁ 150 mL).
The aqueous layer was acidified to pH 2 with HCl (1 M) and ex-
tracted again with EtOAc (4 ꢁ 150 mL). The combined organic lay-
ers were extracted with water (10 ꢁ 175 mL). After drying over
Na2SO4 and concentration in vacuo, 1a was obtained as a brown
oil (25 g, 96%, 96.6% ee).
A round-bottomed flask was charged with the amino acid 1a
(56.8 g, 155 mmol) and EtOH (277 mL). The solution was cooled to
5 °C and stirred for 30 min. Subsequently, SOCl2 (22.2 g, 186 mmol)
was added in such a way that the temperature was kept between 10
and 15 °C. The mixture was heated to 60 °C for 1.5 h and then cooled
to room temperature. To the reaction mixture was added toluene
(283 mL). The reaction mixture was cooled with an ice bath while
NaHCO3 (362 g, 9 wt %, 388 mmol) was added and stirred for one
hour. After phase separation the toluene phase was concentrated
in vacuo to yield the b-amino ester 1b (53 g, 87%, 96.6% ee). Analyt-
ical data were in agreement with the data shown above.
16. Krapcho, A. P.; Diamanti, J.; Cayen, C.; Bingham, R. Org. Synth. Coll 1973, 5, 198–
201.
17. Heller, D.; de Vries, A. H. M.; de Vries, J. G. In Handbook of Homogeneous
Hydrogenation; de Vries, J. G., Elsevier, C. J., Eds.; Wiley: Weinheim, 2007.
18. (a) Lefort, L.; Boogers, J. A. F.; de Vries, A. H. M.; de Vries, J. G. Org. Lett. 2004, 6,
1733–1736; (b) Lefort, L.; Boogers, J. A. F.; de Vries, A. H. M.; de Vries, J. G. Top.
Catal. 2006, 40, 185–191; (c) de Vries, J. G.; Lefort, L. Chem. Eur. J. 2006, 12,
4722–4734.
19. (a) Monnier, F.; Taillefer, M. Angew. Chem., Int. Ed. 2009, 48, 6954–6971; (b)
Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400–5449.
20. (a) Ma, D.; Zhang, Y.; Yao, J.; Wu, S.; Tao, T. J. Am. Chem. Soc. 1998, 120, 12459–
12467; (b) Ma, D.; Xia, C. Org. Lett. 2001, 3, 2583–2586; (c) Ma, D. W.; Cai, Q. A.
Acc. Chem. Res. 2008, 41, 1450–1460.
21. Compare: 4-bromo-fluorobenzene 214, -€/kg and 4-iodo-fluorobenzene 4660, -
€/kg according to prices obtained from Sigma Aldrich.
22. No desired product (1a and 1b) is formed when acac is omitted.
23. Shi, L.; Wang, M.; Fan, C.-A.; Zhang, F.-M.; Tu, Y.-Q. Org. Lett. 2003, 5, 3515–
3517.
24. Busscher, G. F.; de Vries, J. G.; Lefort, L. WO2010006954 to DSM IP Assets BV.
25. CAS number: [35138-22-8].
26. CAS number: [155830-69-6].
27. MDL
number:
MFCD09753038,
dimethylammonium
dichlorotri(l-
References
chloro)bis[(R)-(+)-5,50-bis[di(3,5-xylyl)phosphino]-4,40-bi-1,3-
benzodioxole]diruthenate(II). Ligand obtained from Takasago. JP Registration
No. 3148136, 3549390, SEGPHOS is a registered trademark of Takasago.
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