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Issue 21, 2003
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Asymmetric synthesis of anti-(2S,3S)- and syn-(2R,3S)-diaminobutanoic acid

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Conjugate addition of homochiral lithium N-benzyl-N-α-methylbenzylamide to tert-butyl (E)-cinnamate or tert-butyl (E)-crotonate and in situ amination with trisyl azide results in the exclusive formation of the corresponding 2-diazo-3-amino esters in >95% de. Amination of the lithium (E)-enolates of tert-butyl (3SR)-3-N-benzyl-N-α-methylbenzylamino-3-phenylpropanoate or tert-butyl (3SS)-3-N-benzyl-N-α-methylbenzylaminobutanoate with trisyl azide gives the (2R,3RR)- and (2S,3SS)-anti-2-azido-3-amino esters in good yields and in 85% de and >95% de respectively. Alternatively, tert-butyl anti-(2S,3SS)-2-hydroxy-3-N-benzyl-N-α-methylbenzylaminobutanoate may be converted selectively to tert-butyl anti-(2S,3SS)-2-azido-3-N-benzyl-N-α-methylbenzylaminobutanoate by aziridinium ion formation and regioselective opening with azide. Deprotection of tert-butyl (2S,3SS)-2-azido-3-aminobutanoate via Staudinger reduction, hydrogenolysis and ester hydrolysis furnishes anti-(2S,3S)-diaminobutanoic acid in 98% de and 98% ee. The asymmetric synthesis of the diastereomeric syn-(2R,3S)-diaminobutanoic acid (98% de and 98% ee) was accomplished via functional group manipulation of tert-butyl anti-(2S,3SS)-2-hydroxy-3-N-benzyl-N-α-methylbenzylaminobutanoate in a protocol involving azide inversion of tert-butyl (2S,3S)-2-mesyloxy-3-N-Boc-butanoate and subsequent deprotection.

Graphical abstract: Asymmetric synthesis of anti-(2S,3S)- and syn-(2R,3S)-diaminobutanoic acid

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Publication details

The article was received on 17 Jun 2003, accepted on 22 Jul 2003 and first published on 11 Aug 2003

Article type: Paper
DOI: 10.1039/B306936M
Citation: Org. Biomol. Chem., 2003,1, 3708-3715
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    Asymmetric synthesis of anti-(2S,3S)- and syn-(2R,3S)-diaminobutanoic acid

    M. E. Bunnage, A. J. Burke, S. G. Davies, N. L. Millican, R. L. Nicholson, P. M. Roberts and A. D. Smith, Org. Biomol. Chem., 2003, 1, 3708
    DOI: 10.1039/B306936M

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