Abstract
Cyclic imine marine toxins have attracted considerable attention from the synthetic
community in the past two decades due to their unique chemical structures and clinically
relevant biological activities. This review presents recent efforts of our group in
the development of various strategies to efficiently construct the common spirocyclic
imine fragments of the cyclic imine toxins. In particular, the use of α,β-unsaturated
N-acyl iminium ion dienophiles in Diels–Alder reactions are highlighted, whereby direct
access to spirocyclic imine motifs was obtained and important mechanistic details
were discovered. Alternative approaches to spirocyclic imine systems involving hydroamination
of amino alkynes are also summarized. One such approach led to serendipitous access
to N-vinyl amide products, while our most recently reported approach involving an intermolecular
Diels–Alder/cross-coupling sequence using novel 2-bromo-1,3-butadienes to access
5,6-spirocyclic imines is also discussed. Additionally, the development of a novel
method to construct another challenging motif present in the portimines is also introduced.
1 Introduction
2 Strategies towards the Spirocyclic Imine Fragment of Cyclic Imine Toxins
2.1 Diels–Alder Cycloadditions of α,β-Unsaturated N-Acyl Iminium Dienophiles
2.2 Early Studies Using in situ-Generated Iminium Ion Dienophiles
2.3 Use of More Stable Iminium Ion Dienophiles for Diels–Alder Reactions
2.4 Other Notable Strategies towards Spirocyclic Imines
2.5 Recent Efforts towards the 5,6-Spirocyclic Imine Marine Toxin Portimine A
2.6 Construction of Another Challenging Motif of Portimine A
3 Conclusion and Future Perspectives
Key words
spiroimines - Diels-Alder reaction - N-acyl iminium ions - Mukaiyama Michael addition
- iminium dienophiles
