2012 / 09 / 19 Kazunari Kato Total synthesis seminar O O EtO NH A 1 (1.4eq), THF -78°C ｬ 0°C, 93% 1) cat. KH, TMSEOH B 2) Boc2O (83%, 2step) C Me O O 1 1) Cs2CO3, I(CH2)3Cl 2) NaN3, NaI CuLi-Lil t-Bu 1) cat, Mg(ClO4)2, MeCN, 60°C D 3) TBAF, DBU (89%, 3step) E 2) LiHMDS, NsCl ,THF 0°C rt,ｬ 89% 1) LDA, t-BuOAc, THF -78°C then OLi tBuO HCl THF/H2O F 92% 2) PPh3, PhH, 50°C, 88% K2CO3,MeI, DMF H I then PhSH, (87%) 80°C, 85% Me Me O 1) p-TsOH 2) Ac2O, Et3N (81%, 2step) N Me CF3CH2OH, PhSH N (+)-fastigiatine G J Total synthesis seminar O O EtO NH O O 1) cat. KH, TMSEOH TMSEO NBoc 2) Boc2O (83%, 2step) 1 (1.4eq), THF -78°C ｬ 0°C, 93% NBoc Me O B A O N3 O O t-Bu N3 O E O H N tBuO tBuO 1) LDA, t-BuOAc, THF -78°C then 2 2) PPh3, PhH, 50°C, 88% Me CO2tBu H N HCl THF/H2O Me NHNs O 92% O O NHNs Aza-Wittig Reaction F G Me CO2tBu H N K2CO3,MeI PhSH, (87%) OH NHMe I H Me Me O 2) Ac2O, Et3N (81%, 2step) N Me N (+)-fastigiatine Me CO2tBu H N CF3CH2OH, PhSH 80°C, 85% OH NHNs 1) p-TsOH N Ns O D OLi Me CO2tBu H N O Me 2) LiHMDS, NsCl ,THF 0°C rt,ｬ 89% O decarboxylation C 1) cat, Mg(ClO4)2, MeCN, 60°C NBoc O CuLi Lil E 1 1) Cs2CO3, I(CH2)3Cl Me 2) NaN3, NaI 3) TBAF, DBU (89%, 3step) O 2012 / 09 / 19 Kazunari Kato O TMSEO O Me Retro aldol Mannich reaction Me N J Total Synthesis of (+)- Fastigiatine Me Me O Brian B. Liau and Matthew D. Shair* N Me 1986年にCOLIN竝窿篝粡窶ﾜL蓼㈳Q茵ﾔPﾐ倪ｮ箏窶ﾎﾛﾜ窶竦窶笋竡 N ﾄsﾄﾄSﾄWﾄﾒAﾜy邃ﾑxｵ窶祺粢粹ﾔｾ禊ﾜ蒄Yﾔf箘笋籟ﾏSi筰竝粳竡B (+)-fastigiatine F E Aza-Wittig Reaction R N N N （人名反応参照） R N PPh3 N N R N N N PPh3 N2 R N PPh3 R N PPh3 PPh3 N O tBuO O PPh3 O tBuO N O tBuO O H N PPh3 tBuO N O H F O tBuO Me CO2tBu H N Me H N HCl NHNs O O O O NHNs Me CO2tBu H N Me CO2tBu H N O OH NHNs Me CO2tBu H H N NHNs Me CO2tBu H N CF3CH2OH OH O NHMe NHMe Me CO2tBu H N N Me CO2tBu H N Me N NHNs Me CO2tBu H N OH Retro aldol Mannich reaction J I Me Me CO2tBu H N NHNs