D. A. Evans. M. Calter The Aza-Cope Rearrangement Chem 115 Mechanism and Stereochemistry. 2-aza-Cope vs Pinacol Overman JACS 1988. 110 4329: Overman JOC 1988. 53. 685 Mechanism: 1.5hr,79% Mannich Homo-chrial Pinacol Pinacol Mannich Mannich reaction is slow compared to these bond rotations(activation energy for bond rotation -3-5 kcal mol), then the compound will racemize before cyclization and the product will be racemic. Since the intermediates in the Pinacol mechanism are all chiral, the product should be chiral if it is formed by that mechanism. The product formed was racemic, so this is further evidence for the 2-aza-Cope/Mannich mechanism Path C discarded because no fragmentation products ever found in the rxn mixtures To test for a)vs. b), substrates 1-5 were prepared and subjected to the rn conditions. AgNO,, EtOH, Me 64% 1 hr.. rt Et37% 5 sO_Ph 20% The fact that 3 and 5 rearranged under the same conditions, even though ther djacent positive charge, argues strongly against mechanism b(assuming that the cyclization step is rate limiting) 32B0411/2493937AMHomo-chrial achiral The iminium-enol derived from the 2-aza-Cope is an achiral compound in a chiral conformation. It can be racemized by two rotations around single bonds. If the Mannich reaction is slow compared to these bond rotations(activation energy for bond rotation ~3-5 kcal/mol), then the compound will racemize before cyclization and the product will be racemic. Since the intermediates in the Pinacol mechanism are all chiral, the product should be chiral if it is formed by that mechanism. The product formed was racemic, so this is further evidence for the 2-aza-Cope/Mannich mechanism. + Mannich Pinacol chiral + : 2-aza-Cope cyclization + CSA, 60oC, 1.5 hr, 79% ■ 2-aza-Cope vs. Pinacol: The fact that 3 and 5 rearranged under the same conditions, even though there is an approximately seventeen orders of magnitude difference in their ability to stabilize an adjacent positive charge, argues strongly against mechanism b(assuming that the cyclization step is rate limiting). 4 OEt 37% 5 SO2Ph 20% 3 SPh 76% 2 H 64% 1 Me 78% Compound R Yield AgNO3, EtOH, 1 hr., rt Path C discarded because no fragmentation products ever found in the rxn mixtures. To test for a) vs. b), substrates 1-5 were prepared and subjected to the rxn conditions. c) b) a) [3 + 2] Pinacol Mannich frgmt. cycln. [3,3] + + - + + + Mechanism: Overman JACS 1988, 110, 4329; Overman JOC 1988, 53, 685. Mechanism and Stereochemistry: D. A. Evans, M. Calter The Aza-Cope Rearrangement Chem 115 N R R' HO R'' R R'' HO N R' N R' HO R'' R R R'' HO N R' N R' OHC R R'' N HO H R Me CN O N H Me R O N Me Me Ph Ph N Ph Me Ph OH Me Me OH Ph N Me Ph Me N Me Ph N Me OH Ph Ph Ph O Me OH Ph N Me Ph Ph OH Me N Ph Me Me 32B-04 11/24/93 9:37 AM