# Catalytic Processes for Stereoselective Radical Cyclization Reactions

> **NIH NIH R01** · BOSTON COLLEGE · 2021 · $344,300

## Abstract

Cyclic structures, including both carbocycles and heterocycles, are common motifs of natural
products and synthetic compounds with important biomedical activities. Among different approaches
for preparing cyclic molecules, radical cyclization represents one of the most powerful approaches for
construction of ring structures. Among a number of inherent synthetic advantages, radical reactions
typically proceed at fast reaction rates under mild and neutral conditions in a broad spectrum of
solvents and exhibit significantly high functional group tolerance. Furthermore, radical processes have
the capability to perform in a cascade fashion, allowing for the rapid construction of complex molecular
structures with generation of multiple stereogenic centers. To further enhance the synthetic applications
of radical cyclization, new approaches will be needed for achieving high control of their reactivity as well
as stereoselectivity, especially enantioselectivity, challenging issues that are intrinsically associated
with the “free” nature of radical chemistry.
Guided by the concept of metalloradical catalysis (MRC), this proposed research explores a
fundamentally new approach for controlling stereoselectivity of both C- and N-centered radical
reactions. Cobalt(II) porphyrins [Co(Por)], as stable 15e metalloradicals, can enable the activation of
diazo compounds and organic azides to cleanly generate C- and N-centered radicals, respectively, with
N2 as the only byproduct in a controlled and catalytic manner. The initially-formed C- and N-centered
radicals, which are termed as a-Co(III)-alkyl radicals and a-Co(III)-aminyl radicals, respectively, remain
covalently bonded with [Co(Por)]. They can undergo common radical reactions, such as radical addition
to alkenes and hydrogen-atom abstraction, but with effective control of reactivity and stereoselectivity
by the porphyrin ligand environment. In addition to the radical nature of [Co(Por)], the low dissociation
energy of Co–C and Co–N bonds plays a key role for the successful turnover of the Co(II)-based
catalytic processes, resulting in effective radical cyclization reactions. Through the support of D2-
symmetric chiral porphyrin ligands with tunable electronic, steric, and chiral environments, Co(II)-based
metalloradical catalysis (Co(II)-MRC) will be applied for the development of various radical cyclization
processes for stereoselective construction of both carbocylic and N-heterocyclic compounds with
different ring sizes and varied degrees of molecular complexity.
We hope these studies will ultimately lead to the development of cost-effective and environmentally
benign radical cyclization processes that can be successfully applied for the stereoselective synthesis
of biologically important natural products and pharmaceutically interesting small molecules.

## Key facts

- **NIH application ID:** 10248461
- **Project number:** 5R01GM102554-07
- **Recipient organization:** BOSTON COLLEGE
- **Principal Investigator:** X. Peter ZHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $344,300
- **Award type:** 5
- **Project period:** 2015-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248461

## Citation

> US National Institutes of Health, RePORTER application 10248461, Catalytic Processes for Stereoselective Radical Cyclization Reactions (5R01GM102554-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10248461. Licensed CC0.

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