1975, Nair’s paper provides a proof of concept
No further work was published
This project was aimed at an optimisation of the reaction of 2H-azirines and arynes to make indole derivatives
Can other heterocycles be formed with this method?
Optimisation of the reaction
The synthesis of azirines
Changing of the azirine
The synthesis of aryne precursors
Changing the aryne precursor
The synthesis of other heterocycles
The Fischer indole synthesis:
Harsh conditions needed, strong bases or acids, and heat
The proposed mechanism
Azirines - an alternative synthesis?
Scope - Changing the 2H-azirine
effect - EWG
Order of reactivity
Replacing the arene by an alkyl chain
Carbocation intermediate in the mechanism
Order of bond formation
Electron rich azirines are difficult to synthesise
Azirines are less reactive than furanes towards arynes
Strained cumulene hypothesis
Scope - changing the aryne precursor
Aryne precursor synthesis
Azirines and arynes can yield indole derivatives in mild conditions
A model reaction was optimised and examples were synthesised
Future work involves :
- Determining the mechanism
- Expanding scope
- Expanding the other heteroatoms idea
As an extension of our syntheses of fused heterocycles using lithiation methods, we have pursued the synthesis of novel 3,3'-diiodo-2,2'-biindoles, oxazolylindoles, bis(3-indolylacetylene), bisindolylmaleimides, and indolocarbazoles.
A few studies demonstrate the beneficial effects of indole-3-carbinol on lipid synthesis and platelet aggregation, suggesting that this phytochemical could help to .
I3C, 3-hydroxymethyl indole, 3-indole methanol
In our study of the fused heterocycles pyrrolo[3,4-b]indoles and pyrrolo[2,3-b]indoles, we have uncovered a novel ipso acylation�detosylation reaction upon reaction with acid chlorides and aluminum chloride leading to the corresponding acylated heterocycles.
For example, as a route to the trikentrin and herbindole group of biologically active natural products, we have carried out an intramolecular Diels-Alder cycloaddition of the fused heterocycle furo[3,4-b]pyrrole to afford a tricyclic indole embodying the structure of these natural indoles.
Gribble, Dartmouth CollegeThe present project involves the synthesis and exploitation of fused heterocycles as vehicles for the synthesis of biologically important indoles, carbazoles, carbolines, and other natural products.
Direct Coupling of Indoles with Carbonyl Compounds: Short, Enantioselective, Gram-Scale Synthetic Entry into the Hapalindole and Fischerindole Alkaloid Families, J.