Chiral N-acylethylenediamines as new modular ligands for the catalytic asymmetric addition of alkylzinc reagents to aldehydes

Christopher M Sprout; Christopher T Seto

doi:10.1021/jo0347516

Chiral N-acylethylenediamines as new modular ligands for the catalytic asymmetric addition of alkylzinc reagents to aldehydes

J Org Chem. 2003 Oct 3;68(20):7788-94. doi: 10.1021/jo0347516.

Authors

Christopher M Sprout¹, Christopher T Seto

Affiliation

¹ Department of Chemistry, Brown University, 324 Brook Street, Box H, Providence, Rhode Island 02912, USA.

PMID: 14510556
DOI: 10.1021/jo0347516

Abstract

Chiral N-acylethylenediamines represent a new class of modular ligands for the catalytic asymmetric addition of alkylzinc reagents to aldehydes. The N-acylethylenediamine moiety serves as a metal binding site, while attached amino acids provide the source of chirality. Three sites of diversity on the ligands were optimized to enhance the enantioselectivity of the catalysts using an iterative optimization procedure. The most effective ligand, 4k, was synthesized in a single reaction step from inexpensive and commercially available starting materials. This ligand (10 mol %) catalyzed the addition of Me2Zn to 2-naphthaldehyde, benzaldehyde, and 4-chlorobenzaldehyde to give the corresponding alcohol products in 86%, 84% and 81% ee, respectively.