Andrew ratz Daphniphyllum Alkaloids Evans Group Seminar, June 1993 Stepwise vs Concerted Cyclization One-Pot Pentacyclization Reaction: Formation of Protodaphniphylline 2. HyO% Concerted [BuO2C 1.MsCI, EIN 1. Swern 1. Swern Stepwise Other amines TIMel 79% isclated yield 32D0612/110011:43AMAndrew Ratz Daphniphyllum Alkaloids Evans Group Seminar, June 1993 Stepwise vs Concerted Cyclization Concerted Stepwise AcOH 70°C 95% AcOH 25°C 90% NH3 44% 79% isolated yield Concerted Stepwise + + + + +N R Me R’ H N R Me R’ H N H N H R’ R Me R’ R Me BnO R R’ ’ Me R N N HN Me OR Me Me Me N OHC Me OHC Me R’ R’ N Me Me Me N R Me R’ H Me HN Me R’ Me Me R’ OHC Me OHC Me Me H Other amines: 38%y 32%y 1-2%ee 13%y 20-25%ee no reaction Glycine (S)-(+)-Alanine (S)-(+)-Valine (+)-α-Phenylethyl amine 70% One-Pot Pentacyclization Reaction: Formation of Protodaphniphylline 1. Swern 2. MeNH2 3. HOAc, 80°C 65% 1. Swern 2. NH3 3. AcOH, 80°C 15% 1. MsCl, Et3N 2. DBU 3. DIBAL 80% 1. LDA, Br(CH2)3CH(OMe)2 2. H3O+ 83% LDA, THF CH3CO2tBu Me 83% I Me Me Me Me Me OtBu O Me Me Me Me Me Me Me Me Me CO2tBu OH CO2tBu Me Me Me CHO tBuO2C Me Me Me Me HN Me Me Me Me Me OH OH HN Me Me Me Me Me 32D-06 12/11/00 11:43 AM