Total synthesis of (+)-cassaine via transannular Diels-Alder reaction.
A full account of the total synthesis of (+)-cassaine ( 1) using the transannular Diels-Alder (TADA) reaction as the pivotal construction is described. The strategy began from Evans' oxazolidine 8, the only chiral source used for the total stereochemical outcome of the target molecule. The key intermediate 3 was obtained from 8 in 10 steps in 40% overall yield. Following extensive optimization, the coupling of 3 on both ends with another densely functional partner 2 followed by TADA reaction on macrocycle 4 cleanly furnished the tricycle 5. The stereochemical outcome in 5 was expected via a least-energetic transition state T4. A stereoselective reduction, hydroboration, and methyl cuprate 1,4-addition along with a few other functional interconversions transformed 5 into the key intermediate 37. Final tethering of dimethylaminoethyloxycarbonyl along with epimerization at C8 and alcohol deprotection at C3 yielded the natural product 1.
Phoenix
Serge
S
Laboratoire de Synthèse Organique, Département de Chimie, Institut de Pharmacologie, Université de Sherbrooke, 3001, 12e ave nord, Sherbrooke, Québec J1H 5N4, Canada.
Reddy
Maddi Sridhar
MS
Deslongchamps
Pierre
P
D045784:Abietanes; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
D045784:Abietanes; D000470:Alkaloids; C010696:cassaine