Transition metal catalysed reactions for the synthesis of heteroaromatic compounds
Date
2008-12-22T08:11:20Z
Authors
Pelly, Stephen Christopher
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Abstract
The carbazole and 2-isopropenyl-2,3-dihydrobenzofuran structures are widely found in
many naturally occurring compounds. For example, the naturally occurring anti-cancer
compound, rebeccamycin, contains an indolocarbazole core. Rotenone, which contains an
(R)-2-isopropenyl-2,3-dihydrobenzofuran moiety, is widely used today as an effective
naturally occurring pesticide.
In the carbazole section of this thesis, the synthesis of the naturally occurring
furanocarbazole, furostifoline is described. As key steps in this sequence, a Suzuki
coupling reaction is utilised to couple appropriately functionalised indole and furan
moieties. After further functional group transformations, a metathesis reaction is employed
to construct the carbazole system, leading to furostifoline. The synthesis of the unnatural
thio-analogue of furostifoline was similarly conducted and is described. Finally, in a
somewhat different approach, the synthesis of the indolocarbazole core is described,
utilising a Madelung approach initially to form the bis-indole system, 2,2’-biindolyl. After
several functional group transformations, a metathesis reaction was once again
successfully employed to form the carbazole system, thereby synthesising di(tert-butyl)
indolo[2,3-a]carbazole-11,12-dicarboxylate.
In the benzofuran section of this thesis, the successful chiral synthesis of two 2-
isopropenyl-2,3-dihydrobenzofuran systems is described. As a precursor to rotenone, the
synthesis of (R)-2-isopropenyl-2,3-dihydrobenzofuran-4-ol is described starting from
resorcinol. The key step in this synthesis is a stereoselective intramolecular Pd π-allyl
mediated cyclisation utilising the R,R’-Trost ligand, thereby forming (R)-2-isopropenyl-
2,3-dihydrobenzofuran-4-ol in excellent yield and enantiomeric excess. The alternative
enantiomer, (S)-2-isopropenyl-2,3-dihydrobenzofuran-4-ol, was similarly synthesised.
Finally, a similar approach was utilised to synthesise both (S)- and (R)-2-isopropenyl-2,3-
dihydrobenzofuran, starting from 2-allyl-phenol, and thereby completing a formal
synthesis of the naturally occurring compounds, (S)-fomannoxin and (R)-trematone,
respectively.
Description
Keywords
transition metal, furostifoline, pelladium, benzofuran, carbazole, Rotenone, trematone