Swift, Michael D.
Investigation of metal mediated reactions for natural product synthesis.
PhD thesis, University of Glasgow.
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During the course of the studies outlined in this thesis, an ether-directed Pd(II)-catalysed aza-Claisen rearrangement reaction that had previously been developed by the Sutherland group was expanded to include more functionalised rearrangement substrates. This methodology has been applied for the synthesis of several natural products including dihydroxylated-amino acids.
Further investigation of substrates for the rearrangement led to the synthesis of other substituted trichloroacetimidates. Rearrangement of these compounds demonstrated the role of steric strain on the stereocontrol of the rearrangement and also highlighted the role that solvent can have upon the diastereoselectivity of ether-directed rearrangements.
In addition to this, a novel tandem aza-Claisen rearrangement and ring closing metathesis reaction has been developed. This reaction allows the synthesis of cyclic allylic trichloroacetamides in excellent yields from simple allylic alcohols. The use of commercially available chiral rearrangement catalysts allowed a highly enantioselective tandem process to be developed.
Further development of this process has provided an ether-directed tandem aza-Claisen rearrangement and RCM reaction which occurs with high yield and diastereoselectivity to provide functionalised cyclic products. The use of these compounds for the total synthesis of the amaryllidaceae alkaloid (+)-gamma-lycorane was also investigated.
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