Synthesis of Regiospecifically Fluorinated Conjugated Dienamides

Molecules

Mohammad Chowdhury¹  Samir K. Mandal¹  Shaibal Banerjee¹ 

[1] id= "af1-molecules-19-04418">Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, NY 10031, U

关键词: fluoro dienamides;    Julia-Kocienski olefination;    Weinreb amide;    fluoro dienes;   

DOI  :  10.3390/molecules19044418

来源: mdpi

【 摘 要 】

Modular synthesis of regiospecifically fluorinated 2,4-diene Weinreb amides, with defined stereochemistry at both double bonds, was achieved via two sequential Julia-Kocienski olefinations. In the first step, a Z-α-fluorovinyl Weinreb amide unit with a benzothiazolylsulfanyl substituent at the allylic position was assembled. This was achieved via condensation of two primary building blocks, namely 2-(benzo[d]thiazol-2-ylsulfonyl)-2-fluoro-N-methoxy-N-methylacetamide (a Julia-Kocienski olefination reagent) and 2-(benzo[d]thiazol-2-ylthio)acetaldehyde (a bifunctional building block). This condensation was highly Z-selective and proceeded in a good 76% yield. Oxidation of benzothiazolylsulfanyl moiety furnished a second-generation Julia-Kocienski olefination reagent, which was used for the introduction of the second olefinic linkage via DBU-mediated condensations with aldehydes, to give (2Z,4E/Z)-dienamides in 50%–74% yield. Although olefinations were 4Z-selective, (2Z,4E/Z)-2-fluoro-2,4-dienamides could be readily isomerized to the corresponding 5-substituted (2Z,4E)-2-fluoro-N-methoxy-N-methylpenta-2,4-dienamides in the presence of catalytic iodine.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.