Stereochemistry of the Three-Component Reaction Between the Ley′S Aldehyde, Benzyl Amines, and Trialkyl Phosphites. A New Approach to the Protected Enantiomerically Pure 1-Amino-2,3-Dihydroxypropylphosphonates

Abstract

Enantiomerically pure orthogonally protected dimethyl 1-aminophosphonates (2R,5R,6R,1′R)- and (2R,5R,6R,1′S)-10, phosphonate analogs of 4-hydroxythreonine, were prepared employing the three-component reaction between trimethyl phosphite, (2R,5R,6R)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxane-2-carbaldehyde (Ley’s aldehyde), and benzhydrylamine. Since both aminophosphonates 10 exist in a chloroform solution as single rotamers, the absolute configurations at C1′ were unequivocally established based on ¹H and ¹³C NMR spectral data. Studies on stereochemistry of the addition of trialkyl phosphites showed that in chloroform in all cases the nucleophile preferentially attacks the si-face of the C˭N bond, while in alcohols the 1,2-stereoinduction is negligible, and sense of chirality of phenylethylamines is solely responsible for a π-facial discrimination in the 1,3-asymmetric inductions.

GRAPHICAL ABSTRACT

Keywords:

• Chiral auxiliaries
• conformation
• configuration
• reaction mechanism
• Schiff bases

Additional information

Funding

Financial support from the Medical University of Łódź (503-3014-01) is gratefully acknowledged.