Enantiopure 2,6-disubstituted piperidines bearing one alkene- or alkyne-containing substituent: preparation and application to total syntheses of indolizidine-alkaloids.
A general and efficient procedure for the preparation of 2,6-disubstituted piperidines bearing one alkene- or alkyne-containing substituent was developed by using non-racemic Betti base as a chiral auxiliary. Many chiral benzylamines are excellent auxiliaries, but they were rarely used for this purpose because of the inefficient removal of the N-benzyl auxiliary residue under non-hydrogenative conditions. We found that N,N-disubstituted Betti base derivative has a typical Mannich structure of o-naphthol. When it carried out a base-catalyzed formation of o-quinone methide, an efficient non-hydrogenative N-debenzylation was achieved, and the alkene and alkyne groups survived. To demonstrate the efficiency of the method and the versatility of the products, asymmetric total syntheses of indolizidine-alkaloids (-)-167B, (-)-195H, (-)-209D and (-)-223AB were accomplished.
Liu
Hui
H
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, PR China.
Su
Deyong
D
Cheng
Guolin
G
Xu
Jimin
J
Wang
Xinyan
X
Hu
Yuefei
Y
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry; D054836:Indolizidines / Q000138:chemical synthesis* / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D000475:Alkenes; D000480:Alkynes; D054836:Indolizidines; D010880:Piperidines