# Kinetically-Persistent Carbocations in C-H Insertion Reactions and Biomimetic Cyclization Cascades

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $367,531

## Abstract

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.

## Key facts

- **NIH application ID:** 9964852
- **Project number:** 5R35GM128936-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Hosea Martin Nelson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $367,531
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964852

## Citation

> US National Institutes of Health, RePORTER application 9964852, Kinetically-Persistent Carbocations in C-H Insertion Reactions and Biomimetic Cyclization Cascades (5R35GM128936-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9964852. Licensed CC0.

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