Enantioselective Synthesis of 2-Substituted 5-, 6- and 7-Membered Lactams via α-Alkylation of Their Chiral N-Dialkylamino Derivatives

Dieter Enders; Robert Gröbner; Gerhard Raabe; Jan Runsink

doi:10.1055/s-1996-4443

Synthesis 1996; 1996(8): 941-948
DOI: 10.1055/s-1996-4443

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Enantioselective Synthesis of 2-Substituted 5-, 6- and 7-Membered Lactams via α-Alkylation of Their Chiral N-Dialkylamino Derivatives

Dieter Enders^* , Robert Gröbner, Gerhard Raabe, Jan Runsink

^*Institut für Organische Chemie, Rheinisch-Westfälische Technische Hochschule, Professor-Pirlet-Straße 1, D-52074 Aachen, Germany, Fax +49(241)8888127; E-mail: Enders@RWTH-Aachen.de

Abstract

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2-Alkyl-substituted lactams 4 were synthesized in good overall yields and high enantiomeric purities (ee =71-99%) by α-alkylation of chiral N-(dialkylamino)lactams 2 and subsequent reductive N-N bond cleavage of the resulting lactams 3 with lithium in liquid ammonia. The lactams 2, in turn, were prepared in good yields by cyclization of ω-chloroalkanohydrazides 1 with sodium hydride. Acidic hydrolysis of lactams 4 leads to γ-aminobutanoic acid (GABA) derivatives 5 (ee ≥ 99%). The absolute configuration was determined by polarimetry and an X-ray structure analysis of (S,S)-3e’.

asymmetric synthesis - lactams - α-alkylation - reductive N-N bond cleavage - proline auxiliaries

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