有机合成路线设计原理.ppt

introduction to organic synthesis 有机合成初步 date1 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 date2 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. date3 synthonequivalent disconnection rest on transforms date4 date5 synthon equivalent polar inversion 极性反转 date6 polar inversion date7 symbol date8 functional group transforms date9 date10 2. disconnection on tms without fg adding fg tm： targeted molecule 目标分子 date11 date12 date13 3. disconnection on tms with mono fg application of malonic ester date14 date15 date16 80% 99% 80% date17 酮式 烯醇式 application of ethyl acetoacetate pka 11 date18 date19 date20 date21 application of epoxy （环氧）compounds date22 date23 date24 disconnection on cyclohexene date25 date26 birch还原 date27 4. disconnection on bifunctional groups （1）, -unsaturated compounds date28 date29 （2）, -unsaturated carboxylic acid date30 （3）-hydroxyester date31 date32 （4）1,3-bicarbonyl date33 date34 （5）1,4-bicarbonyl date35 （6）1,5-bicarbonyl 迈克尔（michael）加成反应 date36 date37 date38 date39 （7）1,6-bicarbonyl date40 date41 birch还原 date42 4. rearrangment date43 嚬哪醇重排： date44 date45 5. examples date46 date47 date48 date49 date50 date51 date52 date53 date54 date55 a synthesis of n-ethyl-2-aminomethylspiro3.3heptane from starting compounds having no more than three contiguous carbon atoms is required. date56 a synthesis of 2-acetyl-2-methylbicyclo2.2.2octane from cyclohexene and other starting compounds having no more than four contiguous carbon atoms is required. date57 date58 date59 a synthesis of 2,7-dimethyl-4-octanone from starting compounds having no more than four contiguous carbon atoms is required. date60 a synthesis of 1,4,6-trimethylnaphthalene from para-xylene and other starting compounds having no more than four contiguous carbon atoms is required. date61 date62 biom