Utilizing the intramolecular heck reaction. Studies towards the total synthesis of Stemodia and Strophanthus natural products.

摘要

In Chapter 1 the intramolecular Heck cyclization is introduced as one of the most significant reactions for the construction of quaternary carbon centers. Natural products such as the stemodia plant extracts represented by stemodinone (7) and stemarin ( 8) are two representive diterpenes that have been targeted for total synthesis using an intramolecular bis-Heck cyclization. During the investigation described in Chapter 1, we present the synthesis of two complex tricycles 34 and 35 that are thought to be stepping stones to the stemodia natural products.; In Chapters 2–3 we turn to the use of an intramolecular Heck cyclization as a means to construct the steroid framework of complex strophanthus steroids. In specific, our investigations determined that the Heck cyclization of 45 afforded ample quantities of steroid 46, a potential intermediate for the total synthesis of the strophanthus steroid ouabain (1). Functionalization studies of steroids 46 and 47 are presented in Chapter 3, accomplishing introduction of C1 and C3 oxidation in the form of ketone 64 and enone 59, respectively. As well, further investigation of the intramolecular Heck cyclization is presented utilizing substrates such as vinyl triflates 81(a-c) that contain α-oxygen substitution.; In Chapter 4 of this dissertation a degradation study of ouabain is presented that was specifically geared for assisting our synthetic efforts towards the strophanthus natural products.