The need and desire to recreate the structures of natural products by chemical synthesis have served as a continuous inspiration for scientists to drive the field of organic chemistry forward. The total synthesis of natural products not only tests and challenges existing chemical reactions and strategies in complex molecular settings, but can also offer an incentive to think about potentially new, or improved ways to approach structural elements in organic molecules. Following this motivation, the work outlined in this thesis focused on the investigation and development of organic reactions that allow to access specific structural motifs found in natural products, and on the application of such reactions in total synthesis.The tandem Nazarov–ene cyclization was discovered during investigations toward thesynthesis of the neuroprotective Illicium sesquiterpenoid illisimonin A, which features an unprecedented pentacyclic structure. The tandem cyclization allows the diastereoselective synthesis of spirocyclic ketones with a quaternary spirocenter from linear trienones, by using a tertiary alcohol as stereocontrolling element. The mechanism of the reaction was investigated by cyclization experiments with a deuterium-labeled substrate. These experiments supported the hypothesis that the reaction proceeds via a sequence of a Nazarov cyclization and a concerted ene reaction.The reaction was applied in the asymmetric total synthesis of illisimonin A. Startingfrom a spirocyclic scaffold, generated by the tandem Nazarov–ene cyclization, a strategy for the construction of the strained tricyclic carbon backbone of the natural product, which combines a trans-pentalene and norbornane ring system, was developed. A silicon-based homologation sequence and an allylic oxidation, afforded a substrate for a titanium-mediated reductive cyclization, which first generated a tricyclic ring system containing a cis-pentalene substructure. A subsequent semipinacol rearrangement allowed access to the carbon backbone of illisimonin A with its characteristic trans-pentalene subunit. The synthesis was concluded with a White–Chen oxidation that built up a gamma-lactone moiety to complete the pentacyclic structure of the natural product. Overall, the established route allowed the synthesis of (–)-illisimonin A in 28 steps from commercially available starting materials.The oxazaborolidinone-mediated asymmetric bisvinylogous Mukaiyama aldol reactionwas investigated as method for the rapid assembly of zeta-hydroxy-alpha,beta,gamma,delta-unsaturated carbonyl motifs, which can be found in unsaturated polyketide natural products. The method uses a tryptophan-derived oxazaborolidinone as chiral Lewis acid for the synthesis of enantioenriched bisvinylogous aldol products from double vinylogous O-silyl ketene acetals and aldehydes. To explore the scope of the reaction, various achiral and chiral aldehydes were examined as substrates. The method proved to be particularly useful for aliphatic aldehydes, allowing the preparation of reaction products with enantiomeric, or diastereomeric ratios of up to 95:5.