3858
J. Hang, L. Deng / Bioorg. Med. Chem. Lett. 19 (2009) 3856–3858
1973, 26, 389; (c) Kuroda, Y.; Okuhara, M.; Goto, T.; Kohsaka, M.; Aoki, H. J.
Antiobiot. 1980, 33, 132.
3. (a) Rando, R. R. Science 1974, 185, 320; (b) Rando, R. R. Acc. Chem. Res. 1975, 8,
combined isolated yields (Table 1). This is the first general and
non-enzymatic kinetic resolution method for the asymmetric syn-
thesis of b,c-unsaturated a-amino acids. It should be noted that
optically active amino acids 3a–c had not been reported
previously.
281.
ˇ
4. For a review, see: Havlícek, L.; Hanuš, J. Collect. Czech. Chem. Commun. 1991, 56,
1365.
5. For examples of synthesis of b,c-unsaturated a-amino acids from L-amino
We found that enantioenriched UNCA 1 underwent racemiza-
tion in the presence of (DHQD)2AQN at room temperature. This
raised the possibility of realizing a dynamic kinetic resolution
(DKR) with (DHQD)2AQN as a dual-function catalyst, promoting
both the racemization and the enantioselective alcoholysis of
UNCA 1.22b,c,25 It is noteworthy that, to our knowledge, the only lit-
acids, see: (a) Afzali-Ardakani, A.; Rapoport, H. J. Org. Chem. 1980, 45, 4817; (b)
Hanessian, S.; Sahoo, S. P. Tetrahedron Lett. 1984, 25, 1425; (c) Griesbeck, A. G.;
Mauder, H. Angew. Chem., Int. Ed. Engl. 1992, 31, 73; From D-mannitol, see:
Badorrey, R.; Cativiela, C.; Díaz-de-Villegas, M. D.; Gálvez, J. A. Synthesis 1997,
747.
6. For Heck-coupling of L-vinylglycine with vinyl and aryl halides and triflates,
see: Crisp, G. T.; Glink, P. T. Tetrahedron 1992, 48, 3541.
7. For examples by Wittig reaction, see: (a) Itaya, T.; Shimomichi, M.; Ozasa, M.
Tetrahedron Lett. 1988, 29, 4129; (b) Sibi, M. P.; Rutherford, D.; Renhowe, P. A.;
Li, B. J. Am. Chem. Soc. 1999, 121, 7509; (c) Rose, N. G. W.; Blaskovich, M. A.;
Wong, A.; Lajoie, G. A. Tetrahedron 2001, 57, 1497.
8. For alkylation–elimination of bislactim ethers, see: (a) Schöllkopf, U.; Nozulak,
J.; Groth, U. Tetrahedron 1984, 40, 1409; For alkynylation–reduction of glycine
derivatives, see: (b) Williams, R. M.; Zhai, W. Tetrahedron 1988, 44, 5425.
9. (a) Porter, J. R.; Wirschun, W. G.; Kuntz, K. W.; Snapper, M. L.; Hoveyda, A. H. J.
erature precedent of DKR of a racemic b,
acid involved an amidase-catalyzed but incomplete hydrolysis of
3,4-dehydro- -prolinamide, from which -3,4-dehydroproline
was generated in 75% yield and 80% ee.26
c-unsaturated a-amino
D
,L
L
Our initial attempts to develop an efficient DKR of
a-aryl UN-
CAs22b revealed that, during a slow addition of a solution of allyl
0
Am. Chem. Soc. 2000, 122, 2657; For asymmetric Strecker synthesis of b,
unsaturated -amino nitriles without further converting to the corresponding
b, -unsaturated -amino acids, see: (b) Takamura, M.; Hamashima, Y.; Usuda,
c-
alcohol in Et2O to a mixture of UNCA 1c, (DHQD)2AQN and 4 ÅA
molecular sieves in Et2O, amino ester 4c was formed in 86% ee at
13% conversion, and the ee of 4c decreased to 75% ee when the
alcoholysis proceeded to 97% conversion. This slight ee deteriora-
tion over the course of the reaction indicated that the rate of the
(DHQD)2AQN-catalyzed racemization was still slower than the rate
of alcoholysis of UNCA 1c (krac/kslow < 1). Subsequently, we found
that the overall efficiency of the DKR could be improved by
increasing the reaction temperature (34 °C in Et2O) while extend-
ing the addition time of the alcohol (Table 2, entry 3 vs 1). Under
the optimized conditions, amino esters 4c, 4f and 4a were obtained
in 81–88% ee and 76–94% isolated yields from their respective
racemic counterparts. Importantly, we also established that the al-
lyl amino ester 4c (81% ee) could be converted into the correspond-
ing amino acid 3c in 93 % yield without migration of the double
bond and deterioration of the optical purity (81% ee).27
a
c
a
H.; Kanai, M.; Shibasaki, M. Angew. Chem., Int. Ed. 2000, 39, 1650; (c) Masumoto,
S.; Usuda, H.; Suzuki, M.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2003, 125,
5634; (d) Sigman, M. S.; Vachal, P.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2000,
39, 1279.
10. Armstrong, A.; Challinor, L.; Moir, J. H. Angew. Chem., Int. Ed. 2007, 46, 5369.
ˇ
ˇ
ˇ
11. Havlícek, L.; Hanuš, J.; Nemecek, J. Collect. Czech. Chem. Commun. 1989, 54,
3381.
12. For a recent review, see: Berkowitz, D. B.; Charette, B. D.; Karukurichi, K. R.;
McFadden, J. M. Tetrahedron: Asymmetry 2006, 17, 869.
13. For the synthesis of b,c-alkenylglycines from glycine equivlents: (a) Ben-Ishai,
D.; Moshenberg, R.; Altman, J. Tetrahedron 1977, 33, 1533; (b) Castelhano, A. L.;
Horne, S.; Billedeau, R.; Krantz, A. Tetrahedron Lett. 1986, 27, 2435; (c) Angst, C.
Pure Appl. Chem. 1987, 59, 373; (d) O’Donnell, M. J.; Li, M.; Bennett, W. D.;
Grote, T. Tetrahedron Lett. 1994, 35, 9383.
14. For synthesis by Strecker reaction, see: Greenlee, W. J. J. Org. Chem. 1984, 49,
2632.
15. For synthesis of b,c-alkenylglycines by Wittig reaction with good control of
double-bond geometry, see: Bicknell, A. J.; Burton, G.; Elder, J. S. Tetrahedron
Lett. 1988, 29, 3361.
16. For synthesis of b,c-alkenylglycines by a variant of Mannich reaction, see:
Petasis, N. A.; Zavialov, I. A. J. Am. Chem. Soc. 1997, 119, 445.
17. For synthesis of racemic (E)-alkenylglycines by deconjugation of
dehydroamino acids, see: Alexander, P. A.; Marsden, S. P.; Subtil, D. M. M.;
Reader, J. C. Org. Lett. 2005, 7, 5433.
18. For general synthesis of cycloalk-1-enylglycine, see: Suzuki, M.; Nunami, K.;
Yoneda, N. J. Chem. Soc., Chem. Commun. 1978, 270.
In summary, we have established a general catalytic method for
the asymmetric synthesis of b,c-unsaturated a-amino acids via a
cinchona alkaloids-catalyzed kinetic resolution. This mild method
effectively circumvented the problematic racemization and double
bond isomerization associated with the optically active b,
c-unsat-
urated -amino acids, thereby providing a useful access to these
a
19. For general synthesis of b,
Aldous, S. C. J. Org. Chem. 1990, 55, 4657.
20. For synthesis of quaternary -vinyl amino acids, see: (a) Berkowitz, D. B.; Wu,
c-alkynylglycine, see: Williams, R. M.; Aldous, D. J.;
sensitive but important amino acids.
a
Acknowledgment
B.; Li, H. Org. Lett. 2006, 8, 971; (b) Jones, M. C.; Marsden, S. P.; Subtil, D. M. M.
Org. Lett. 2006, 8, 5509.
21. (a) Friis, P.; Helboe, P.; Larsen, P. O. Acta Chem. Scand. Sect. B 1974, 28, 317; (b)
Baldwin, J. E.; Haber, S. B.; Hoskins, C.; Kruse, L. I. J. Org. Chem. 1977, 42, 1239;
(c) Keith, D. D.; Yang, R.; Tortora, J. A. J. Org. Chem. 1978, 43, 3711; (d) Hallinan,
K. O.; Crout, D. H. G.; Errington, W. J. Chem. Soc., Perkin Trans. 1 1994, 3537.
22. (a) Hang, J.; Tian, S.-K.; Tang, L.; Deng, L. J. Am. Chem. Soc. 2001, 123, 12696; (b)
Hang, J.; Li, H.; Deng, L. Org. Lett. 2002, 4, 3321; (c) Hang, J.; Deng, L. Synlett
2003, 1297; (d) Tian, S.-K.; Chen, Y.; Hang, J.; Tang, L.; McDaid, P.; Deng, L. Acc.
Chem. Res. 2004, 37, 621; (e) Chen, Y.; McDaid, P.; Deng, L. Chem. Rev. 2003, 103,
2965.
We gratefully acknowledge the financial support from NIH
(GM-61591) and Daiso.
Supplementary data
Supplementary data associated with this article can be found, in
23. For preparation of the corresponding amino acids and N-Z amino acids, see
Supplementary data for details.
24. For converting enantioenriched UNCAs to amino acids and separation of amino
esters from amino acids, see Supplementary data for details.
25. Tang, L.; Deng, L. J. Am. Chem. Soc. 2002, 124, 2870.
26. (a) Robertson, A. V.; Witkop, B. J. Am. Chem. Soc. 1960, 82, 5008; (b) Robertson,
A. V.; Witkop, B. J. Am. Chem. Soc. 1962, 84, 1697.
References and notes
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27. For this conversion, see Supplementary data for details.