Use of optically active cyclic diethyl sulfamidate 2-phosphonates as chiral synthons for the synthesis of β-substituted α-amino phosphonates

• Published in: Tetrahedron: asymmetry 2005-05, Vol.16 (9), p.1583-1594
• Main Authors: Dolence, E. Kurt, Mayer, Gabriele, Kelly, Brenda D.
• Format: Article
• Language: English
• ISSN: 0957-4166; 1362-511X
• DOI: 10.1016/j.tetasy.2005.02.014

[Display omitted] Optically active protected sulfamidate 2-phosphonates have been synthesized from either ( R)- or ( S)- N-benzyl-2-phosphonoserine for use as chiral synthons. These sulfamidates have been shown to undergo nucleophilic substitution with select nucleophiles, to afford following N-sulfate removal, the β-substituted α-amino-2-phosphonates. N-Sulfate removal was accomplished using boron trifluoride etherate in the presence of either n-propylthiol or N-hydroxysuccinimide allowing retention of the diethylphosphonate ester groups. Replacement of the unpleasant smelling n-propylthiol with N-hydroxysuccinimide provides higher yields of the desired products. Synthesis of β- S-substituted analogues required the use of cesium carbonate as a base. The sulfamidates described have excellent stability and have been demonstrated, using chiral HPLC, to be greater than 97% enantiomerically pure.