Asymmetric Syntheses of 3,4-Substituted Tetrahydroquinoline Derivatives by (-)-Sparteine-Mediated Dynamic Thermodynamic Resolution of 2-(α-Lithiobenzyl)-N-pivaloylaniline

Yongtae Kim; Eun-kyoung Shin; Peter Beak; Yong Sun Park

doi:10.1055/s-2006-950299

PAPER

Asymmetric Syntheses of 3,4-Substituted Tetrahydroquinoline Derivatives by (-)-Sparteine-Mediated Dynamic Thermodynamic Resolution of 2-(α-Lithiobenzyl)-N-pivaloylaniline

Yongtae Kim^a, Eun-kyoung Shin^a, Peter Beak^b, Yong Sun Park*^a
^a Department of Chemistry and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea
Fax: +82(2)34365382; e-Mail: parkyong@konkuk.ac.kr;
^b Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA

Abstract

All articles of this category

Abstract

(-)-Sparteine-mediated dynamic thermodynamic resolution of 2-(α-lithiobenzyl)-N-pivaloylaniline was investigated. A temperature- and concentration-controlled epimerization-substitution sequence provides a simple protocol for the preparation of a highly enantioenriched benzyl-substituted N-pivaloylaniline product (up to 98:2 er). Also, application of this simple methodology to asymmetric syntheses of 1,3,4- and 3,4-substituted tetrahydroquinoline derivatives is demonstrated.

Key words

asymmetric synthesis - enantiomeric resolution - alkylations - quinolines - stereoselective synthesis

Full Text

References

1 Beak P. Anderson DR. Curtis MD. Laumer JM. Pippel DJ. Weisenburger GA. Acc. Chem. Res. 2000, 33: 715

2a Nam J. Lee S.-k. Park YS. Tetrahedron 2003, 59: 2397

2b Laumer JM. Kim DD. Beak P. J. Org. Chem. 2002, 67: 6797

2c Coldham I. Dufour S. Haxell TFN. Howard S. Vennall GP. Angew. Chem. Int. Ed. 2002, 41: 3887

2d Clayden J. Mitjans D. Youssef LH. J. Am. Chem. Soc. 2002, 124: 5266

2e Nakamura S. Nakagawa R. Watanabe Y. Toru T. J. Am. Chem. Soc. 2000, 122: 11340

3a Basu A. Beak P. J. Am. Chem. Soc. 1996, 118: 3757

3b Basu A. Gallagher DJ. Beak P. J. Org. Chem. 1996, 61: 5718

3c Park YS. Yum EK. Basu A. Beak P. Org. Lett. 2006, 8: 2667

The absolute configuration of 6 was assigned, after its conversion into 7, by comparison of its optical rotation with that of an authentic compound, in the following literature:

4a Paquin J.-F. Stephenson CRJ. Defieber C. Carreira EM. Org. Lett. 2005, 7: 3821

4b Dong C. Alper H. Tetrahedron: Asymmetry 2004, 15: 35

5

Reaction of 2-(1-lithioethyl)-N-pivaloylaniline with tert-butyl bromoacetate under the same reaction conditions gave the substituted product in lower enantioselectivity (84:16 er) and yield (22%).

6a Kiau S. Discordia RP. Madding G. Okuniewicz FJ. Rosso V. Venit JJ. J. Org. Chem. 2004, 69: 4256

6b Kosmrlj J. Weigel LO. Evans DA. Downey CW. Wu J. J. Am. Chem. Soc. 2003, 125: 3208

6c Lee S.-K. Lee SY. Park YS. Synlett 2001, 1941

6d Heath H. Wolfe B. Livinghouse T. Bae SK. Synthesis 2001, 2341

6e Vedejs E. Chapman RW. Lin S. Muller M. Powell DR. J. Am. Chem. Soc. 2000, 122: 3047

6f Hoppe I. Marsch M. Harms K. Boche G. Hoppe D. Angew. Chem., Int. Ed. Engl. 1995, 34: 2158

The relative configuration of trans-11 was assigned by comparison of its NMR data with that of an authentic compound, in the following literature:

7a Beifuss U. Ledderhose S. J. Chem. Soc., Chem. Commun. 1995, 2135

7b Katritzky AR. Rachwal B. Rachwal S. J. Org. Chem. 1995, 60: 7631 . The relative configurations of 9, 10, 12, and 13 were assigned by analogy to the formation of trans-11