Kinetically-Persistent Carbocationsin C-H Insertion Reactions and Biomimetic Cyclization Cascades

点击翻译按钮获取中文摘要

Project Summary Nearly all bioactive compounds, whether drug or tool molecule, are built upon frameworks composed of carbon-to-carbon (C–C) bonds. This is evidenced by extensive efforts from the synthetic community aimed at expanding the scope, efficiency, and selectivity of established C–C bond forming reactions. Many of the most commonly employed methods, such as transition metal-catalyzed cross-coupling or nucleophilic substitution reactions, rely on the multi-step conversion of simple building blocks into reactions partners that are appropriately functionalized to partake in C–C bond forming events. Furthermore, many of the transition metal catalysts that are used in these processes are expensive, toxic, and unsustainable due to their low natural abundance. While these existing C–C bond forming processes are powerful, new methods that address the aforementioned shortcomings would facilitate the development of therapeutic compounds. The long-term goal of the proposed research activities is to address this challenge at the fundamental level through the development of novel C–C bond forming reactions. This proposal outlines the first step in achieving this goal through the development of new electrophilic reactions that feature Earth-abundant and biologically benign catalysts. Specifically, we describe C–H arylation processes that are catalyzed by silicon/boron salts. Moreover, we propose new methods for the synthesis of polycyclic terpenes catalyzed by silicon/boron salts. The proposed research is innovative because it describes approaches to C–C bond formation that challenge dogmas in the methodology field. It is innovative because it leverages the tools and concepts of several field of chemistry (reactive intermediate chemistry, total synthesis and fundamental inorganic chemistry) into the development of practical organic transformations. The described studies are significant because they disclose several new strategies to form C–C bonds that are premised on new concepts in catalysis. These concepts will spur diverse and innovative practical applications, and inspire theoretical study. Ultimately the research proposed in this document will contribute to medicine through chemical synthesis and to society through an improved understanding of fundamental chemical reactivity.