Part I. Synthesis of delavatine A, incarviatone A, and fascaplysin natural products. Part II. Total synthesis of calyciphylline B-type alkaloids

This dissertation details work in two categories: (1) development of novel annulation strategies enabled by regioselective ring-opening of 2-pyrone derivatives and showcasing the utility of such transformations in total synthesis (Chapters 1–4). (2) total synthesis of calyciphylline B-type alkaloids and evolution of a novel methodology to access oxazaborinine heterocycles (Chapters 5–6). Chapter 1 is an introduction to known annulation reactions employing the versatile reactivity of 2-pyrone derivatives. This chapter provides a comprehensive summary of such strategies to highlight the key areas where further development is needed.Chapter 2 describes the evolution of our symmetry-inspired unified strategy for the synthesis of delavatine A and incarviatone A. Key features of our final synthetic route include an electrocyclization cascade sequence involving five transformations occurring in a single pot. This sequence was initiated by a regioselective 1,6-ring opening of a 2-pyrone derivative, which was synthesized by employing site-selective cross-couplings of 3,5-dibromo-2-pyrone. Chapter 3 details experimental and computational studies conducted to gain insight into the mechanism of the observed site-selective cross-coupling of 3,5-dibromo-2-pyrone. These insights may prove valuable in developing a more general understanding of the effects of solvents and additives on site-selective cross-coupling of other polyhalogenated heterocycles.Chapter 4 describes an extension of our interest in exploiting annulation strategies enabled by the regioselective ring-opening of 2-pyrone derivatives. Specifically, this chapter discusses the development of an annulation strategy that relies on 1,2-ring opening of N-heterocycle–pyrone adducts. The scope of this strategy was extended to access diverse N-fused heterocycles including pyrido[1,2-a]indoles. Additionally, the utility of this methodology was demonstrated in a concise formal synthesis of three fascaplysin congeners. Chapter 5 focuses on our early approach toward the synthesis of calyciphylline B-type natural products, a subfamily of the polycyclic Daphniphyllum alkaloids. While this strategy did not prove fruitful to access the target molecules, the approach revealed a wealth of interesting reactivity surrounding oxazaborinine heterocycles.Chapter 6 highlights our successful route to access calyciphylline B-type alkaloids. Specifically, the synthetic studies culminated in the first total synthesis of daphlongamine H, gave access to isodaphlongamine H, and also led to revision of the reported structure of deoxyisocalyciphylline B