有机合成路线设计原理

1、2021-11-21introduction to organic synthesis有机合成初步2021-11-22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. woodwarde. j. coreyretro-synthetic analysis逆合成分析 the noble prize in 1990 20世纪the logic of chemical synthesis 2021-11-231. retrosynthetic analysis (逆合成分析) in this procedure the target molecule is transformed progr

2、essively 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

3、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. 2021-11-24ohphphc-phohcph+ohphcmgbrph合成子 等价试

4、剂合理的切割synthonequivalentdisconnection rest on transforms2021-11-25ohphphc+phohcph不合理的切割-2021-11-26c+rocrclocroror+ rxohc+rrhooc-rssrlir- rmgxc-rc-na+rcmgxrsynthon equivalentpolarinversion极性反转极性反转2021-11-27ooc-+brsslissh+choossnbsaq. acetonepolar inversion2021-11-28chocho1.o32.zn/acohsymbol2021-11-29n

5、h2cnh2pd/cbrnacnohohfunctional group transforms2021-11-210oohpcc1. b2h62. h2o2 naoh2021-11-2112. disconnection on tms without fg adding fg+-brnachbrhh+tm： targeted molecule 目标分子2021-11-212oclo+alcl32021-11-213brbrbrbrbrbrnh21. nano2, hcl2. etohnh2nh2nh2cn+cn2021-11-2143. disconnection on tms with mo

6、no fg application of malonic esteroohrco2etco2etrco2etco2et-r+rbrco2etc-co2et1. naoh, h2o2. h3o+, -co2etona2021-11-215ch2(co2et)21. etona2. rxrch(co2et)21. oh-2. h3o+, rch2co2h1. etona2. rxrrc(co2et)21. oh-2. h3o+, rrchco2h2021-11-216ch3(ch2)4chco2hch3ch3(ch2)4ch(co2et)2ch3ch3(ch2)4br+ch3ch2(co2et)2

7、ch3i+ch2(co2et)22021-11-2171. oh-2. h3o+, ch3(ch2)4c(co2et)2ch3ch3(ch2)4chco2hch380% 99%ch2(co2et)21. etona, etoh2. n-c5h11brch3(ch2)4ch(co2et)21. etona, etoh2. ch3i80% 2021-11-218oc2h5oooc2h5ooh酮式酮式 烯醇式烯醇式application of ethyl acetoacetate pka 112021-11-219och3ch2ooetetonaooetoch3chooetch3chona+rxoo

8、etoch3chrnax+ooetoch3chroohoch3chr1. naoh, h2o2. h3o+-co2ch3cch2ro2021-11-220och3ch2ooet1. etona2. rxooetoch3chr1. etona2. r2xooetoch3crr1. naoh, h2o2. h3o+-co2ch3cchorroohoch3crr2021-11-221ophophco2etophco2etcl+oetoobr+2021-11-222application of epoxy （环氧）compoundsr1r2ohr1-r2oh+or1r2mgbr2021-11-223h

9、oo+ch2mgx2021-11-224hoo+cmgxc4h9-nn-c4h9ho1. et2o2. h3o+h2pd/c2021-11-225disconnection on cyclohexene+diels-alder reacton2021-11-226co2etco2etco2et+2021-11-227birch还原还原orli, liq. nh3 etohorco2rco2rna, liq. nh3etohli, liq. nh3 etoh2021-11-2284. disconnection on bifunctional groups（1） , -unsaturated c

10、ompoundsorr1r2ro+or1r2aldolcondesationooo2021-11-229orli, liq. nh3 etohorohclmeohomeomeoli, liq. nh3 etohhclmeoh2021-11-230arco2harcho +(ch3co)2operkinreactionochoac2o, acona 150ocochchco2h（2） , -unsaturated carboxylic acid2021-11-231（3） -hydroxyesterrco2etoohrohrr+co2eto-rr(h)o(h)(h)co2etobr+znrefo

11、rmatsky反应2021-11-232ohco2etobrch2co2et+o+-ch2mgbrcocl2021-11-233（4）1,3-bicarbonyl roetooc+rooeto-rooetoetorrooc+roro-rooetroclaisen缩合2021-11-234oco2etco2etco2et1. naoet2. h3o+1.kmno42. etoh,h+2021-11-235（5）1,4-bicarbonylrororohroco2etoreto2cor+2021-11-236（6）1,5-bicarbonyl ch2(co2et)2 + ch3cochch2ch3

12、coch2ch2ch(co2et)2kohetoh迈克尔（michael）加成反应 rroorrooco2etrrooco2et+2021-11-237ooco2etoco2etooooeto+oooetbr+2021-11-238ooooo+2021-11-239ome+ch2chcch3oetonamichael加成meoonaoh羟醛缩合54%meoho草酸meo86%2021-11-240chocho1.o32.zn/acoh（7）1,6-bicarbonyl2021-11-241omemechoco2meomeme2021-11-242omeme1. o3, meoh2. me2sc

13、hoco2meomemeli, liq. nh3etohbirch还原还原2021-11-2434. rearrangmento-o+ho+hooh2021-11-244嚬哪醇重排：嚬哪醇重排： h3c cch3ohcohch3ch3h3c cch3ohcoh2ch3ch2h3c cch3ohcch3ch3cch3cch3ch3ch3ohcch3cch3ch3ch3ohhh2ohcch3cch3ch3ch3o（i）（ii）（iii）2021-11-245ohohoclaisen重排o-na+br+2021-11-2465. examplesohoohhc c-na+oh2so4hgso4202

14、1-11-247oclo+zn-hghcl2021-11-248ohoh+ch3mgio+ ch3mgic+ococlco2et2021-11-249oomeohomeo+ meoma+2021-11-250ohco2etchobrch2co2et+zncoclco2hco2etco2et2021-11-251nh2n-c3h7no2n-c3h7h2, r-nin-c3h7n-c3h7on-c3h7cocl+2021-11-252mebrmebrnh2mebrnhacmenhacmenh22021-11-253oomeooohoohohohco2ho2n2021-11-2542021-11-2

15、552021-11-256a synthesis of n-ethyl-2-aminomethylspiro3.3heptane from starting compounds having no more than three contiguous carbon atoms is required. 2021-11-257a synthesis of 2-acetyl-2-methylbicyclo2.2.2octane from cyclohexene and other starting compounds having no more than four contiguous carbon atoms is required. 2021-11-2582021-11-2592021-11-260a synthesis of 2,7-dimethyl-4-octanone from starting compounds having no more than four contiguous carbon atoms is required. 2021-11-261a synthesis of 1,4,6-trimethylnaphthalene from para-xylene and other starting compounds having n