Ti-catalyzed enantioselective addition of cyanide to imines. A practical synthesis of optically pure α-amino acids

Journal of the American Chemical Society

Volumn 121, Issue 17, 1999, Pages 4284-4285

  Krueger, Clinton A ^a   Kuntz, Kevin W ^a   Dzierba, Carolyn D ^a   Wirschun, Wolfgang G ^a   Gleason, John D ^a   Snapper, Marc L ^a   Hoveyda, Amir H ^a  

^a BOSTON COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; CYANIDE; IMINE; TITANIUM;

AMINO ACID SYNTHESIS; ARTICLE; CATALYSIS; CHEMICAL STRUCTURE; ENANTIOMER; REACTION ANALYSIS; STRUCTURE ANALYSIS;

EID: 0033526392     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9840605     Document Type: Article

References (18)

1. Williams, R. M. Synthesis of Optically Active α-Amino Acids; Pergamon: Oxford, 1989.
2. Burk, M. J.; Allen, G. J.; Kiesman, W. F. J. Am. Chem. Soc. 1998, 120, 657-663 and references therein.
3. Iyer, M. S.; Gigstad, K. M.; Namdev, N. D.; Lipton, M. J. Am. Chem. Soc. 1996, 118, 4910-4911.
4. Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 4901-4902.
5. For initial reports on screening of parallel peptide-based libraries, see: (a) Cole, B. M.; Shimizu, K. D.; Krueger, C. A.; Harrity, J. P.; Snapper, M. L.; Hoveyda, A. H. Angew. Chem., Int. Ed. Engl. 1996, 35, 1668-1671.
6. (b) Shimizu, K. D.; Cole, B. M.; Krueger, C. A.; Kuntz, K. W.; Snapper, M. L.; Hoveyda, A. H. Angew. Chem., Int. Ed. Engl. 1997, 36, 1704-1707.
7. (c) Shimizu, K. D.; Snapper, M. L.; Hoveyda, A. H. Chem. Eur. J. 1998, 4, 1885-1889.
8. (d) Hoveyda, A. H. Chem. Biol. 1998, 5, R187-R191.
9. 3- SnCN to imines was reported (highest ee = 92%): Ishitani, H.; Komiyama, S.; Kobayashi, S. Angew. Chem., Int. Ed. Engl. 1998, 37, 3186-3188.
10. 3-SnCN to imines was reported (highest ee = 92%): Ishitani, H.; Komiyama, S.; Kobayashi, S. Angew. Chem., Int. Ed. Engl. 1998, 37, 3186-3188.
11. In the absence of a metal salt, <5% product is observed.
12. 2AlCN, acetone cyanohydrin, tert-butyl isocyanide, and HCN.
13. Other alcohols also provided enhanced catalytst turnover; as an example, with 15 as the substrate, catalytic addition proceeds to 98% conversion in the presence of 1 equiv of p-MeO-phenol. See entry 7 of Table 1.
14. Initial studies indicate that the C=N bond of the chiral ligand remains largely unreacted. As an example, 85% of 9 is recovered from the reaction with 7; the identity of the products arising from the remainder of 9 and whether they are involved in any catalytic CN addition remains to be determined.
15. i-PrOH must be added over 20 h to achieve high selectivity and efficiency. As an example, initial treatment of 10 with 1 equiv of i-PrOH affords the desired adduct in 70% conversion after 20 h but only in 20% ee (vs 93% ee with slow addition). It is likely that rapid addition leads to (i) formation of large amounts of HCN which at 4°C add to imines in the absence of a catalyst and (ii) displacement of the chiral ligand from the transition metal center.
16. Mai, K.; Patil, G. J. Org. Chem. 1986, 51, 3545-3548.
17. Boc-t-Leu is obtained in 85% ee and 85% yield from the derived amino nitrile; single recrystallization affords the optically pure α-amino acid.
18. This research was supported by the NIH (GM-57212 to A.H.H. and M.L.S.), ArQule, ArQule Catalytics and the NSF (CHE-9632278 to A.H.H.). Additional funds were provided by Albemarle and DuPont (to A.H.H.). K.W.K. is a Department of Education GAANN Fellow. W.G.W. is a Deutsche Forschungsgemeinschaft postdoctoral fellow. J.D.G. is supported by fellowships from Pfizer and the Dreyfus Foundation. M.L.S. is a Sloan Research Fellow, a DuPont Young Investigator, an Eli Lilly Grantee, and a Glaxo-Wellcome Young Investigator. A.H.H. and M.L.S. are Camille Dreyfus Teacher-Scholars.