D. A. Evans. M. Calter The Aza-Cope Rearrangement Chem 115 Stereochemistry: Overman JOC 1988, 53, 685 Fused Pyrrolidines Overman TL 1982. 23 2733 and 2737 What does the transition state look like? Overman JOC 1983. 48 3393 Overman JOC 1985. 50. 2403 -Me H*/(cH2) (CH2)n Works for n=2 to 4 (CH2)n Chair Product Boat Product The reaction gives a 90% yield of a 93 7 mix of the Chair Product to the Boat Product. Normal Preparation of Amino Alcohol Substrates Chair cHo <h This nxn gives a 77% yield of a 74: 26 mixture of the Chair Product to the Boat he chair tranistion state for the z-olefin is destabilized relative to the chair tra ate for the E-olefin by a syn-pentane interaction between the Me and the ring n to lower chair selectivity Addition of vinyllithium usually occurs from side opposite nitrogen group in good Rearrangement of trans-aminoalcohol is less selective than that of cis developing syn-pentane 32B0511/2493948AMAddition of vinyllithium usually occurs from side opposite nitrogen group in good yields. Rearrangement of trans-aminoalcohol is less selective than that of cis. (CH2) (CH n 2) (CH n 2)n Normal Preparation of Amino Alcohol Substrates: Works for n=2 to 4 (CH2)n + (CH2)n (CH2)n + + (CH2)n R'CHO, H+ (CH2)n Overman TL 1982, 23, 2733 and 2737. Overman JOC 1983, 48, 3393. Overman JOC 1985, 50, 2403. Stereochemistry: Overman JOC 1988, 53, 685. Fused Pyrrolidines: ■ What does the transition state look like? HCl, 65o C + chair boat + + + + Chair Product Boat Product The reaction gives a 90% yield of a 93:7 mix of the Chair Product to the Boat Product. + Chair Boat This rxn gives a 77% yield of a 74:26 mixture of the Chair Product to the Boat Product. The chair tranistion state for the Z-olefin is destabilized relative to the chair transition state for the E-olefin by a syn-pentane interaction between the Me and the ring, leading to lower chair selectivity. + developing syn-pentane D. A. Evans, M. Calter The Aza-Cope Rearrangement Chem 115 Me N OH NH OMe OMe OH N Me HO Me HO Me N OH N H Me N H Me CHO CHO HO N Me H N HO N Me Me N CHO Me H N H Me CHO HO Me N H H NH R' H R HO HO N R H R' N R' H R HO HO N R H R' N R R'' R'' R'' R'' O H R' HO Li R' NR2 O H R' NR2 NH R' H R HO 32B-05 11/24/93 9:48 AM