Dedicated to Professor Victor Snieckus on the occasion of his 80th birthday
Abstract
This account describes an overview of the asymmetric syntheses of pyrrolizidines,
indolizidines and quinolizidines via a common double reductive cyclisation protocol.
The highly diastereoselective conjugate addition of an enantiopure lithium amide to
an α,β-unsaturated ester incorporating a terminal C=C bond installed the nitrogen-bearing
stereogenic centre and was followed by enolate functionalisation to introduce the
second olefinic functionality. Alternatively, conjugate addition to the corresponding
α-alkenyl α,β-unsaturated ester followed by α-protonation of the intermediate enolate
may also be used to access the cyclisation precursor. After oxidation of the two terminal
olefinic units to give the corresponding dialdehyde, tandem hydrogenolysis/hydrogenation
was employed to efficiently construct the azabicyclic core of each target molecule.
This double reductive cyclisation strategy was successfully utilised in the syntheses
of 13 azabicyclic alkaloids or closely related analogues.
1 Introduction
2 Asymmetric Syntheses of (–)-Isoretronecanol and (–)-Trachelanthamidine
3 Asymmetric Syntheses of (+)-Trachelanthamidine [(+)-Laburnine], (+)-Tashiromine
and (+)-epi-Lupinine
4 Asymmetric Syntheses of (–)-Hastanecine, (–)-Turneforcidine and (–)-Platynecine
5 Asymmetric Syntheses of (–)-Macronecine, (–)-Petasinecine, (–)-1-epi-Macronecine, (+)-1-epi-Petasinecine and (+)-2-epi-Rosmarinecine
6 Conclusion
Key words
asymmetric synthesis - pyrrolizidines - indolizidines - quinolizidines - conjugate
addition - lithium amide - reductive cyclisation
