D. A. Evans. M. Calter The Aza-Cope Rearrangement Chem 115 The 1-aza-Cope Rearrangement The 1-aza-Cope Rearrangement Fowler Joc1988,53,963: Fowler Joc1988,53,5998 Application to Aspidospermine Precursor The Basic Reaction 33] bomyl, the amide resonance energy should act s to favor the enamine product. 500°C, MeDco CO Me yield of l-aza-Cope product CO-Me 61% As you can see, not the greatest reaction, but it has been used to make an aspidospermine precursor aspidospermine 32B-1111/24/9310:30AM4)ClCO2Me 33% The 1-aza-Cope Rearrangement aspidospermine t-BuOK 72% H2, Rh/C 81% 1-aza￾Cope Application to Aspidospermine Precursor + MeAlCl2, 47% 1)NH2OH 2)BH3 3) FVT, 31% H+ As you can see, not the greatest reaction, but it has been used to make an aspidospermine precursor. Me OMe 61% Me CO2Me 33% Me Me 46% Me H 5% H H 0% R R' yield of 1-aza-Cope product The 1-aza-Cope Rearrangement Fowler JOC 1988, 53, 963; Fowler JOC 1988, 53, 5998 [3,3] The Basic Reaction In order to reverse the 3-aza-Cope rearrangement, Fowler put an acyl group on the imine nitrogen. Since the imine has negligible interaction with the carbonyl, the amide resonance energy should act to favor the enamine product. 500oC, FVT D. A. Evans, M. Calter The Aza-Cope Rearrangement Chem 115 O R O N N N MeO2CO CO2Me N MeO2CO CO2Me R' R R' R R N R' CO2Me N CO2Me R R' Et OMe O H Et MeOCHO N Cl O Cl MeO Et N OCO2Me O Cl Cl N O Et MeO OMe Et Cl O Cl O N Et O N O Et O Cl O N Et O N O Et O N Et N Ac MeO 32B-11 11/24/93 10:30 AM