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|Title: ||New gas-phase cascade reactions of stabilising phosphorus ylides leading to ring-fused indoles and quinolines|
|Authors: ||Murray, Lorna|
|Supervisors: ||Aitken, R. Alan (Robert Alan), 1958-|
|Issue Date: ||2010|
|Abstract: ||Synthesis and flash vacuum pyrolysis (FVP) of stabilised phosphorus ylides containing an
o-amino functionalised benzene ring has been examined for the first time. Model studies
using N-methyl-N-tosyl and N-mesyl-N-methyl ylides showed that the ylides could be
prepared, although yields were variable, and had the expected spectroscopic properties.
Upon FVP, however, the expected loss of Ph₃PO and the sulfonyl group was
accompanied by unexpected transfer of the reactive site from nitrogen to carbon giving 3-
substituted quinolines rather than the expected indole products.
Moving to ylides with an α-cinnamoyl group (or heterocyclic analogue) did,
however, result in the originally planned tandem cyclisation leading to ring-fused
carbazole products. N-Benzyl was also found to be a suitable thermally labile group and
a series of α-cinnamoyl N-benzyl-N-methyl ylides were prepared and characterised. For
their synthesis, use of N-cinnamoylbenzotriazoles was found to be preferable to
cinnamoyl chloride, requiring only half the amount of amino-functionalised phosphonium
salt. While FVP of some of these ylides led to benzo-, furo- and thienocarbazoles in good
yield, others again gave quinoline-type products pointing to a fine balance between the
two alternative modes of cyclisation.
It was noted that one of the furocarbazole products was very similar to a natural
product, Eustifoline D, isolated from the medicinally active shrub Murraya euchrestifolia
from Taiwan and its synthesis was planned. With a view to producing the required N-H
carbazole, N,N-dibenzylamino amino ylides were prepared and were found to exhibit
restricted rotation leading to broad NMR signals. Their FVP again led to both quinoline
and carbazole products, with the former having usually, but not always, lost a phenyl
group. Mechanistic pathways for the formation of the various products are proposed.
Complete assignment of the complex ¹H NMR spectra of the various fused-ring
heterocyclic products was achieved, assisted by simulations in many cases.
The ylide precursor required for Eustifoline D was prepared in five steps and 10%
overall yield from 5-methylanthranilic acid. The final FVP step gave a quinoline as the
major product, but the minor product was Eustifoline D, spectroscopically identical to the
|Publisher: ||University of St Andrews|
|Appears in Collections:||Chemistry Theses|
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