Development of New Chiral Auxiliary Derived from (S)-(-)-Phenylethylamine for a Synthesis of Enantiopure (R)-2-Propyloctanoic Acid

Abstract

A new chiral auxiliary, {[(1S)-1-phenylethyl]amino}phenol, derived from (S)-(-)-1-phenylethylamine was developed for asymmetric synthesis of (R)-2-propyloctanoic acid (1) with moderate diastereoselectivity and good crystalline property.

Key words

asymmetric synthesis - chiral auxiliary - crystallinity - {[(1S)-1-phenylethyl]amino}phenol - (R)-2-propyloctanoic acid

References

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1

Current address: Department of Chemistry, University of Chicago, 5735 South Ellis Avenue Chicago, IL 60637, USA.

6

See Ref. [3]

9

The absolute configuration of the product was determined after conversion to the carboxylic acid 1. See Ref. [4d]

13

The Cerius-2 version 4.0 software package (Accerlys Inc., San Diego, CA.) was used for the conformational analysis. The systematic conformation search was performed utilizing the UNIVERSAL 1.02 force field, which possesses the parameters for lithium atom. A dielectric constant of 8.20 was used to simulate the THF solvent. Two dihedral angles, which construct the enolate face was fixed at 0º or 180º, and the remaining five dihedral angles were varied systematically at 30º steps. Each conformer was energy-minimized, and conformation energy was evaluated.