This thesis describes a novel approach to diversity-oriented synthesis. The approach involves the iterative assembly of building blocks onto a purification handle using temporary diisopropylsilylene tethers; this approach yields substrates for a ring-c1osing-ring-opening olefin metathesis cascade. The metathesis cascade results in a skeletal transformation and a range of scaffolds have been generated using only a few simple building blocks and a small number of common reactions. The use of a fluorous tag as a purification handle minimised labour-intensive purification steps and rendered the approach appropriate for library synthesis. The structures ofthe diverse final compounds are reminiscent ofpolyketide natural products. Chapter 1 describes alternative approaches for varying molecular scaffolds and places our generic approach in context. In Chapter 2, .the syntheses of.enant.iome~cally enriched building . blocks are described in· which an enzymatic desymmetrisation· is often used to induce asymmetry. Our investigations to conduct our methodology on solid support our described in Chapter 3. The potential of individual building blocks to participate in simple metathesis cascades is described in Chapter 4. In addition, this Chapter describes our studies to optimise the formation of unsymmetrical silaketals using diisopropylsilyl ethers as storable precursors. The thesis culminates with the preparation of36 metathesis substrates in which pairs of building blocks have been appended to the fluorous tag. The metatheses of some ofthese substrates are described and leads to natural product-like ligands.