Intramolecular Cycloadditions of Dendralenes

Abstract

[3]Dendralenes are synthetically useful building blocks in the rapid construction of polycyclic frameworks owing to their ability to undergo two consecutive Diels-Alder reactions (i.e. a diene-transmissive Diels-Alder sequence). Previous studies focused on the use of intermolecular cycloadditions in such sequences. Only six DTDA sequences involving at least one intramolecular reaction have been previously reported. This thesis focuses on the utilisation of one intramolecular Diels-Alder reaction in DTDA sequences of [3]dendralenes, and is comprised of four chapters. Chapter 1 presents a comprehensive review of intramolecular Diels-Alder reactions, which cover synthetic methodologies and applications in natural product syntheses. A short background, theoretical and stereochemical aspects of the reactions are discussed. The exploitation of type 1 and type 2 IMDA reactions in the construction of fused multicycles (i.e. 6,5- and 6,6-ring systems) is elaborated. The total synthesis of natural products the IMDA reactions is highlighted. Chapter 2 reviews previous syntheses, DTDA reactivity and stability of four types of dendralenes, namely, monosubstituted [3]dendralenes, monocyclic [3]dendralenes, heterosubstituted-[3]dendralenes and [3]dendralenes carrying two tethered dienophiles. Insights into the diene site selectivity, regioselectivity and diastereofacial selectivity of DTDA sequence are detailed. The final part of this chapter highlights natural products synthesised through DTDA and related sequences. Chapter 3 reports the first systematic investigation of intra-/intermolecular DTDA sequences of 1E-, 2- and 3'-substituted [3]dendralenes. IMDA precursors consist of two main reacting components: (1) the dendralene framework, which is constructed by cross-coupling reactions, and (2) the tethered dienophiles, which are installed using 1-lithio-1-methoxyallene and 3-lithio-1-trimethylsilyl-1-methoxyallene, respectively. This methodology enables the synthesis of structurally-diverse polycyclic frameworks i.e. sterane, D-homo sterane, A-nor sterane, podocarpane, helical tetracycles, 1,7-bridged tetracycle and 7,10-bridged tetracycles. Chapter 4 provides experimental procedures and spectroscopic characterisation of the synthesised compounds. Show more