Chemoenzymatic route to stereodefined 2-(azidophenyl)oxazolines for click chemistry

TETRAHEDRON LETTERS

卷:63

Article

Monsen, Paige J.¹  Luzzio, Frederick A.¹ 

[1] Univ Louisville, Dept Chem, 2320 South Brook St, Louisville, KY 40292 USA

关键词: Aza-Wittig;    Oxazolines;    Azides;    Click chemistry;    Esterase;   

DOI  :  10.1016/j.tetlet.2020.152717

来源: Elsevier

【 摘 要 】

Aryl-substituted esters of a racemic diprotected 2-azido-1-alkanol were submitted to the Staudinger/azaWittig reaction in order to assess scope and establish conditions for their cyclization to the corresponding 2,4,5-trisubstituted oxazolines. Following the cyclization study, the (2R,3R)-antipode of the azidoalkanol was obtained in high ee by incubation of the corresponding racemic azidoacetate with pig liver esterase (PLE). The p-nitrobenzoate of the enantioenriched 2-azido-1-alcohol was cyclized by the Staudinger/aza-Wittig to give the corresponding (4R,5R)-disubstituted-2-(4-nitrophenyl) oxazoline. Selective reduction of the nitrophenyloxazoline to the corresponding aminophenyloxazoline using aluminum amalgam followed by direct azidation of the 2-(4-aminophenyl) moiety provided the corresponding (4R,5R)-2-(4-azidophenyl) oxazoline derivative. The azidophenyl oxazoline was reacted with a proven click partner 4-ethynylfluorobenzene under copper/sodium ascorbate mediation to provide the click triazole product in high yield. (C) 2020 Elsevier Ltd. All rights reserved.

【 授权许可】

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