Synthesis of benzo-fused heterocycles using isometerization and ring-closing metathesis reactions
Date
2011-03-09
Authors
Madeley, Lee Gavin
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Abstract
The first part of the dissertation involves the use of ruthenium mediated isomerization (RMI) followed by ring-closing metathesis (RCM) on a selection of phenols and naphthol-1-ol precursors – that had been subjected to allylation; followed by a heat initiated Claisen rearrangement; followed by re-allylation – to form a selection of benzofurans. This procedure, to the best of our knowledge, represents a novel method for the synthesis of benzofurans, with very good average yields of around 90% overall for the RMI/RCM and allylation steps. The lowest yield of the five synthetic steps, were for the Claisen rearrangements with a range of yields between 50% and 86%, indicating the potential to optimise the yields of these reactions, which were carried out using both conventional and microwave heating. The following five-membered oxygen-containing heterocycles were thus obtained: 4,7-dimethoxybenzofuran, 5-bromobenzofuran, 5-tert-butyl-benzofuran, 7-phenyl-1-benzofuran and naphtho[1,2-b]furan.
The second part of the dissertation involves the use of RMI and RCM on di-allylated; di-allylated di-isomerised; and di-allylated mono-isomerized O,N- (aminophenol) and N,N- (benzene-1,2-diamine) protected precursors. This resulted in the formation of six-, seven- and eight-membered benzo-fused heterocycles respectively. Except in the case of the mono- and di-isomerised N,N-precursor, which failed to undergo RCM, despite several attempts. This failure, which is not unprecedented, is most likely due to the interaction of nitrogen‟s lone pairs and the adjacent saturated bonds of the precursor with the GII catalyst, resulting in de-allylation. Of those reactions that were successful, the average yields for the RMI/RCM steps were in the region of 82% for the N,N-precursors and 95% for the O,N-precursors. All precursors readily submitted to allylation and isomerization, with an average yield of 94%. The following benzo-fused heterocycles were thus obtained: six-membered: 4H-1,4-benzoxazin-4-yl(phenyl) methanone; seven-membered: 1,5-benzoxazepin-5(4H)-yl(phenyl)methanone; eight-membered: 2,5-dihydro-6H-1,6-benzoxazocin-6-yl(phenyl) methanone and 1,1'-[(3Z)-2,5-dihydro-1,6-benzodiazocine-1,6-diyl]diethanone.