Stereoselective Nucleophilic Additions to α-Amino Aldehydes: Application to Natural Product Synthesis
Sammanfattning: This thesis deals with the development and application of new synthetic methodology for stereo- or regioselective construction of carbon-carbon bonds in organic synthesis.The first part of this thesis describes the development of a divergent protocol for stereoselective synthesis of chiral aminodiols by employing Mukaiyama aldol additions to syn- and anti-α-amino-β-silyloxy aldehydes. The stereoselectivity of the nucleophilic attack is governed by either chelation to the α-amino moiety or by nucleophilic attack in the Felkin-Anh sense. This study is also directed towards the elucidation of the factors that dictate aldehyde π-facial selectivity in substrate-controlled nucleophilic additions to these and similar systems.In the second part, a highly stereoselective [3 + 2]-annulation reaction of N-Ts-α-amino aldehydes and 1,3-bis(silyl)propenes for stereoselective construction of densely functionalized pyrrolidines is presented. In addition, this methodology is also implemented as a keystep in a synthetic approach towards the polyhydroxylated pyrrolidine and pyrrolizidine alkaloids DGDP and (+)-alexine from a common late pyrrolidine intermediate.Finally, a divergent protocol for regioselective opening of vinyl epoxides using alkyne nucleophiles is described, in which the regioselectivity of the nucleophilic attack is controlled by the choice of reaction conditions. The regioselectivities of the SN2 and SN2’ processes are, however, significantly influenced by the nature of the alkyne substituents and the best results are obtained using ethoxyacetylene. The SN2 opening of vinyl epoxides with ethoxyacetylene as nucleophile is also shown to provide a straightforward entry to functionalized γ-butyrolactones.
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