Chlorotitanium enolate addition to aldimines: A stereoselective route to α-oxy-β-substituted-β-amino esters

Journal of Organic Chemistry

Volumn 65, Issue 19, 2000, Pages 6264-6267

  Adrian Jr , James C ^a   Barkin, Julia L ^a   Fox, Richard J ^a   Chick, Jennifer E ^a   Hunter, Allen D ^b   Nicklow, Rhea A ^b  

^a UNION COLLEGE   (United States)

^b YOUNGSTOWN STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHLORINE DERIVATIVE; ESTER DERIVATIVE; TITANIUM DERIVATIVE;

CHEMICAL ANALYSIS; CHEMICAL REACTION; CHEMICAL STRUCTURE; NOTE; STEREOCHEMISTRY; STEREOSPECIFICITY; STRUCTURE ANALYSIS;

AMINO ACIDS; ESTERS; STEREOISOMERISM; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, NON-P.H.S.; TITANIUM;

EID: 0034703193     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo005555r     Document Type: Note

References (24)

1. Boge, T. C.; Georg, G. I. In Enantioselective Synthesis of β-Amino Acids; Juaristi, E., Ed.; Wiley-VCH: New York, 1996; pp 1-43 and references cited therein.
2. Tamariz, J. In Enantioselective Synthesis of β-Amino Acids; Juaristi, E., Ed.; Wiley-VCH: New York, 1996; pp 45-66 and references cited therein.
3. For examples, see: (a) Seebach, D.; Overhand, M.; Kühnle, F. N. M.; Martinoni, B.; Oberer, L.; Hommel, U.; Widmer, H. Helv. Chim. Acta 1996, 79, 913-941.
4. (b) Appela, D. H.; Christianson, L. A.; Karle, I. L.; Powel, D. R.; Gellman, S. H. J. Am. Chem. Soc. 1996, 118, 13071-13072.
5. For a further review of β-amino acid synthesis, see: D. C. Cole Tetrahedron 1994, 50, 9517-9582.
6. For a comprehensive review, see the other chapters in Enantioselective Synthesis of β-Amino Acids; Juaristi, E., Ed.; Wiley-VCH: New York, 1996.
7. (a) Mukai, C.; Kim, I. J.; Hanaoka, M. Tetrahedron: Asymmetry 1992, 3, 1007-1010.
8. (b) Annunziata, R.; Cinquini, M.; Cozzi, F.; Borgia, A. L. J. Org. Chem. 1992, 57, 6339-6342.
9. Cozzi and co-workers, in ref 6b, use only TEA as the base and report that alkoxy esters such as methyl (benzyloxy)acetate do not enolize. However, M. Bilodeau in his thesis (Bilodeau, M. T. Ph.D. Thesis, Harvard University, November 1993.) reported that methyl (methoxy)acetate is enolizable if DIPEA is used as base. Further, we have found that several other alkoxy esters, including methyl (benzyloxy)acetate, are enolized if DIPEA rather than TEA is used as base.
10. (a) Our results are complimentary to those of Ellman and co-workers in which they obtain the syn-products via the addition of the lithium-titanium-ate enolate of methyl propanoate to a chiral tertbutanesulfanyl imine. Tang, T. P.; Ellman, J. A. J. Org. Chem. 1999, 64,12-13.
11. (b) Kobayashi and co-workers have reported an enantioselective preparation of both syn and anti β-amino esters via the addition of an α-O-benzylsilylketeneacetal to aldimines using a chiral bis-1,1′-bi-2-naphthol zirconium catalyst. In several cases their system was able to achieve anti:syn ratios of 92:8, with ee's as high as 96%. Kobayahi, S.; Haruro, I.; Ueno, M. J. Am. Chem. Soc. 1998, 120, 431-432.
12. Crystal structures and refinement data for esters 3g and 4f are available in the Supporting Information.
13. For example, the anti isomers generally feature larger CH(NHR)-CH(OMe) J values. Also, the CH(OMe) generally resonates at lower field in anti isomers than in syn.
14. In all cases where separation was possible the anti isomer eluted prior to the syn.
15. Adrian, J. C., Jr.; Barkin, J. L.; Hassib, L. Tetrahedron. Lett. 1999, 40, 2457-2460.
16. (a) Ishitani, H.; Ueno, M.; Kobayashi, S. J. Am. Chem. Soc. 1997, 119, 7153-7154.
17. (b) Satio, S.; Hatanaka, K.; Yamamoto, H. Org. Lett. 2000, 2, 1891-1894.
18. Evans, D. A.; Urpí, F.; Somers, T. C.; Clark, J. S.; Bilodeau, M. T. J. Am. Chem. Soc. 1990, 112, 8215-8216.
19. Reetz, M. T. Organotitanium Reagents in Organic Synthesis; Springer: Berlin, 1986.
20. Figueras, S.; Martín, R.; Romea, P.; Urpí, F.; Vilarrasa, J. Tetrahedron Lett. 1997, 38, 1637-1640.
21. 1 substituent in an exo environment, leading to the syn isomer. If the relative imine orientation is reversed, a boat-type complex is not possible.
22. Assuming a Z-enolate, a Zimmerman - Traxler chair-type TS model leading to the anti ester is precisely in accord with the Zimmerman - Traxler chair-type TS model proposed by Ellman and co-workers, ref 8a, leading to the syn-ester, via an E-enolate.
23. Our model predicts that increasing the Lewis basicity of the α-oxygen of the glycolate would be expected to stabilize the formation of the boat TS and thus increase the relative percentage of the syn ester. To test this we generated the enolate of methyl glycolate using 2 equiv of DIPEA, which was added to imine 2g at -80 °C. The subsequent a:s ratio observed for ester adducts was 50:50, in accord with our model (unpublished results from these laboratories).
24. 1 = β-naphthyl) does not significantly effect the diastereoselection (a:s, 92:8).