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Retrosynthetic analysis

123.312 Organic Chemistry

Gareth
Rowlands

sources

massey.html Organic synthesis is a creative science .sources http://www.ac.nz/~gjrowlan/teaching.

Chem. 59.PhS Me N OP2 P1 Synlett 1997. 1998. Org. 259 Me PausonKhand N OP2 P1 J. 1994. Chem. 275 the difficulty in this synthesis is producing the syn relationship between the 3 & 4 substituents 3 radical H H Me CO2H N H CO2H (–)-!-kainic acid Me OTBS EtS CN CO2t-Bu Pure Appl. 6968 different approaches which one is best? . 70.

how do you plan a synthesis? retrosynthesis .

retrosynthesis methodology Strategy Experiment Knowledge understanding reagents protecting groups terminology .

target molecule Me O Me S Me N O HO Me Me O © UCLA in the LA Times 05/12/07 Me Me OH O epothilone B retrosynthetic analysis O Me HO Me Me O OH O Me Me O S Me N Me HO Me Me O OTBS O Me Me OH OH S Me N .

retrosynthetic arrow H HO Me Me O OTBS Me Me CO2H Me O OTBS O Me Me CO2H Me retrosynthetic arrow HO Me Me O Me Me CO2H OTBS “ ...” .. Me H O Me Me Me CO2H O OTBS ..could be made from.

disconnection Me O HO O O Me OH Me Me Me O HO O O Me Me OH Me Me Me N S N S Me Me epothilone C synthons HO N H O Ph HO N H O Ph .

synthons are not real synthon O reagent O HO O Cl Ph O O O H Ph (and oxidation) Ph Ph Ph O Ph .

retrosynthesis Me HO Me Me O Me Me O OH O epothilone C S Me N know your reactions .

Me HO Me Me O Me Me O OH O epothilone C S Me N R1 R2 R1 R2 R1 R2 R1 R2 R1 R2 Br R1 R1 R2 reduction elimination R2 R1 O Ph P 3 R2 Wittig O O R1 McMurry R2 R1 R2 alkene metathesis guidelines .

C–X bonds only guideline ! .

disconnections must correspond to known. reliable reactions Cl O CO2H C–O O Cl CO2H Cl Cl ! SN2 Cl Cl OH CO2H NaOH O CO2H Cl Cl Cl .

guideline " for compounds consisting of two parts joined by a heteroatom. disconnect next to heteroatom Cl O CO2H C–O O Cl CO2H Cl Cl " .

Cl S Cl chlorbenside Cl C–S route A Cl possibilities S Cl 2 S Cl Cl C–S route B S Cl .

Cl HS Cl ! " Route A Cl C–S S S Cl Cl guideline 2 Route A NaOEt Cl Cl S Cl Cl guideline 1 .

Catal. Cs2CO3 MeO S Si(iPr)3 chemical research Adv.Cl " Route A Cl Cl S guideline 1 overcome limitations Br MeO Me HS Si Me Me Me Me Me Pd(OAc)2. PPh3. Synth. 313 . 2005. 47.

Cl ! Route B Cl Cl C–S S ! ! Cl Br S SH Cl Cl guidelines 1 & 2 Route B Cl SH Cl Br Cl Cl NaOEt S .

University of Tokyo OMe Me Me OH Me OMe O Me Me OH OH O OH O HO O Me Me Me O OH HO OH O HO Me Me Me O OMe ! O MeO Me OH OH OH the problem .2 works for all molecules OMe Me Me OH Me OMe O Me Me O OH Me O O HO OH O OH O O Me OH Me Me MeO O Me OH Me Me OH OMe swinholide A Picture ©Yoichi Nakao.