D. A. Evans. M. Calter The Aza-Cope Rearrangement Chem 115 Fused Pyrrolidines: Stereochemical Issues (*)-Gephyrotoxin: Overman JACS 1980, 102, 1454 T1982.23 d2737 The rearrangement procedes through a chair giving the expected stereochemistry 1)Ph3 P=C(H)CHO 2)MeOH, H NHCbz 45% overall OMe When an aliphatic aldehyde is used instead of formaldehyde, the R group ends u syn to the newly expanded rin TsOH aminoalcohols give the same products as the cis, although This can be rationalized by the fact that the trans compound can on state. However, the amount of slippage into the boat transition 79%,32 diastereomers 32B-0611/2493954AM6 steps, 11% overall + 2-aza-Cope 79%, 3:2 ratio of diastereomers + TsOH , NaBH4, 92% 1:1 1)Ph3P=C(H)CHO 2)MeOH, H+ 3)H2, Pd/C 45% overall (±)-Gephyrotoxin: Overman JACS 1980, 102, 1454. (± )-Perhdrogephyrotoxin Fused Pyrrolidines: Stereochemical Issues Overman TL 1982, 23, 2733 and 2737. Overman JOC 1983, 48, 3393. Overman JOC 1985, 50, 2403. The rearrangement procedes through a chair giving the expected stereochemistry. + + + When an aliphatic aldehyde is used instead of formaldehyde, the R group ends up syn to the newly expanded ring. + + + The trans aminoalcohols give the same products as the cis, although usually in lower selectivity. This can be rationalized by the fact that the trans compound can access the boat transition state. However, the amount of slippage into the boat transition state is usually small. + + + + + Boat Chair D. A. Evans, M. Calter The Aza-Cope Rearrangement Chem 115 N R' H HO R OH N O H R OH N R R' N R R' R' N R HO H R' R'' N OH R' R R'' OH R'' N R R' R' H N R O R'' N R'' R' H HO R N R' HO R H N R HO R' H R'' R'' R'' N R HO R' H R'' N R HO R' H R'' N O H R R' R' H N R O R'' CHO NHCbz BnO BnO NH2 OMe OMe OMe OMe NH2 BnO Me OMe OHC Me OMe Me OMe N BnO N BnO Me OMe N BnO O N C5H11 HO 32B-06 11/24/93 9:54 AM