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

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

References

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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%).