有機合成路线设计书原理--159883038.pptVIP

Introduction to Organic Synthesis有机合成路线设计原理初步 Biomimetic Synthesis仿生合成21世纪 （4）1,3-bicarbonyl （5）1,4-bicarbonyl （6）1,5-bicarbonyl ——迈克尔（Michael）加成反应 （7）1,6-bicarbonyl Birch还原 4. Rearrangment 嚬哪醇重排： 5. Examples A synthesis of N-ethyl-2-aminomethylspiro[3.3]heptane from starting compounds having no more than three contiguous carbon atoms is required. A synthesis of 2-acetyl-2-methylbicyclo[2.2.2]octane from cyclohexene and other starting compounds having no more than four contiguous carbon atoms is required. * 合成化学家在旧的自然界旁又建起了一个新的自然界 R. B. Woodward E. J. Corey Retro-synthetic analysis 逆合成分析 The Noble Prize in 1990 20世纪 《The Logic of Chemical Synthesis》 1. Retrosynthetic analysis (逆合成分析) In this procedure the target molecule is transformed progressively into simpler structures by disconnecting selected carbon-carbon bonds. These disconnections rest on transforms, which are the reverse of plausible synthetic constructions. Each simpler structure, so generated, becomes the starting point for further disconnections, leading to a branched set of interrelated intermediates. A retrosynthetic transform is depicted by the = symbol, as shown in next slide. Once a complete analysis has been conducted, the desired synthesis may be carried out by application of the reactions underlying the transforms. Synthon Equivalent Disconnection rest on transforms Synthon Equivalent Polar Inversion 极性反转 Polar Inversion Symbol Functional Group transforms 2. Disconnection on TMs without FG —— adding FG TM： targeted molecule 目标分子 3. Disconnection on TMs with mono FG Application of Malonic ester 80% 99% 80% 酮式 烯醇式 Application of Ethyl Acetoacetate pKa ＝ 11 Application of Epoxy （环氧）compounds Disconnection on Cyclohexene Birch还原 4. Disconnection on Bifunctional groups （1）?, ?-unsaturated compounds （2）?, ?-unsaturated carboxylic acid （3）?-Hydroxyester * * *