Trading N and O: asymmetric syntheses of ¦Â-hydroxy-¦Á-amino acids via ¦Á-hydroxy-¦Â-amino esters

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• 作者：Stephen G. Davies ; Ai M. Fletcher ; Aileen B. Frost ; James A. Lee ; Paul M. Roberts ; James E. Thomson
• 关键词：Aziridine ; ¦Â-Hydroxy-¦Á-amino acids ; Lithium amide ; Conjugate addition ; Asymmetric synthesis
• 刊名：Tetrahedron
• 出版年：2013
• 出版时间：21 October, 2013
• 年：2013
• 卷：69
• 期：42
• 页码：8885-8898
• 全文大小：1747 K

文摘

Both diastereoisomers of 2-amino-3-hydroxybutanoic acid and 2-amino-3-hydroxy-3-phenylpropanoic acid have been prepared from enantiopure ¦Á-hydroxy-¦Â-amino esters via the intermediacy of the corresponding cis- and trans-aziridines. Aminohydroxylation of two ¦Á,¦Â-unsaturated esters produced enantiopure 2,3-anti-¦Á-hydroxy-¦Â-amino esters in >99:1 dr. Subsequent epimerisation at the C(2)-position via a sequential oxidation/diastereoselective reduction protocol gave the corresponding enantiopure 2,3-syn-¦Á-hydroxy-¦Â-amino esters in >99:1 dr. These syn- and anti-substrates were then converted into the corresponding N-Boc protected cis- and trans-aziridines, respectively, via a three step reaction sequence: (i) hydrogenolysis and in situ N-Boc protection; (ii) OH-activation; and (iii) aziridine formation. Subsequent regioselective ring-opening of the C(3)-methyl-aziridines with Cl<sub>3sub>CCO<sub>2sub>H proceeded with inversion of configuration to give the corresponding 2-amino-3-trichloroacetate esters, whereas the analogous reaction with the C(3)-phenyl-aziridines resulted in rearrangement to the corresponding oxazolidin-2-ones with retention of configuration. In each case, hydrolysis of the products from these ring-opening reactions produced the corresponding enantiopure ¦Â-hydroxy-¦Á-amino acids as single diastereoisomers.