Asymmetric Synthesis of ( R )- and ( S )-α-Amino-3-piperidinylphosphonic Acids via Phosphite Addition to Iminium Ions

Abstract

α-Amino-3-piperidinylphosphonates were conveniently prepared from 3-piperidinone, by nucleophilic addition of phosphite to the iminium ion formed by in situ condensation of this ketone with chiral benzylic amines. Subsequent deprotection of N-Boc group, cleavage of the benzyl groups and acidic hydrolysis of the resulting α-amino-3-piperidinylphosphonates gave, in a four-step sequence­ from piperidinone, the enantiopure α-amino-3-piperi­dinylphosphonic acids. The absolute configuration has been established by X-ray crystal structure analysis of the N-(4-nitro­-benzoyl)aminophosphonate derivative.

Key words

amino acids - heterocycles - piperidines - asymmetric synthesis - addition reaction

References

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13

Crystallographic data for compound (+)-11B has been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 614693. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: [phone]; E-mail: [e-mail].