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Synlett 2002(4): 0643-0645
DOI: 10.1055/s-2002-22712
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New and Convenient Chiral Auxiliary for Asymmetric Diels-Alder Cycloadditions in Environmentally Benign Solvents

Frederick J. Lakner, George R. Negrete*
University of Texas, Department of Chemistry, San Antonio, TX 78249-0663, USA
Fax: +1(210)4584957; e-Mail: gnegrete@utsa.edu;
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Publication History

Received 4 February 2002
Publication Date:
05 February 2007 (online)

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Abstract

Preliminary investigations of asymmetric Diels-Alder reactions using a new chiral auxiliary are presented. The auxiliary is readily prepared from an aldehyde and asparagine in water. The resulting heterocycle is coupled with acryloyl chloride in the same pot to provide chiral dienophiles. These are reacted with cyclopentadiene at room temperature in water or ethanol-water to provide cycloaddition adducts diastereoselectively, as demonstrated by chiral HPLC of saponification products 5-norbornene-2-carboxylic acids (47-64% ee for the endo isomers; endo/exo 82:18).

Key words

Diels-Alder reactions - asymmetric synthesis - dia­stereoselectivity - enantiomeric resolution - green chemistry

5

(R,R)-Whelk-O 1 column, 5% isopropanol-hexane, 1.0 mL/min, 280 nm detection. Endo enantiomers were each baseline separated, but exo enantiomers were not.

9

Kinetic experiments were conducted using 80 µM dienophile 1c and 30 equiv cyclopentadiene at 23 °C with vigorous stirring. Disappearance of 1c was followed by reverse phase HPLC. Each reaction obeyed linear pseudo first-order kinetics in the disappearance of 1c for at least the first 50% of conversion.

10

While it should be possible to reclaim the asparagine which remains in the aqueous solution, its low cost and toxicity is not likely to pose problems for disposal.

11

Amide rotamer populations for 1a and 1b were easily determined to be 2:1 and 1:1 respectively (1H NMR in D2O at room temperature). A complete analysis of configurational considerations shall be forthcoming.