# Asymmetric Synthesis of Nitrogen Heterocycles

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2024 · $334,575

## Abstract

Principal Investigator/Program Director (Last, First, Middle): Rovis, Tomislav
Asymmetric Synthesis of Nitrogen Heterocycles
Abstract
 Nitrogen is ubiquitously found in biologically active molecules and pharmaceuticals, the fourth most
common element after carbon, hydrogen and oxygen. Its presence impacts interactions with biological targets,
pharmacokinetics and pharmacodynamics, as well as myriad physical properties. Given the increased
importance of saturation in drug-like molecules, carbon-nitrogen bonds are increasingly stereogenic and thus,
methods to incorporate nitrogen should likewise address doing so in stereocontrolled fashion. We have long
been interested in constructing saturated nitrogen heterocycles from commonly available feedstocks to
address synthetic challenges associates with the most common rings such as piperidines and pyrrolidines.
With this competitive renewal, we seek support to address problems associated with acyclic nitrogen
containing molecules.
 Herein we propose a multi-pronged approach to synthesize complex structures containing nitrogen
substitution from simple precursors. We focus on using the most commonly available starting materials such as
alkenes and dienes, and forge a union to a modestly activated nitrogen coupling partner. Ideal among the latter
is the dioxazolone moiety, trivially assembled from carboxylic acids, hydroxylamine and a phosgene
equivalent. Importantly, after C-N bond formation, the product is the amide, thereby avoiding subsequent
derivatization. We further illustrate that this union can be conducted in an exceedingly complex setting.
PHS 398/2590 (Rev. 09/04) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10907789
- **Project number:** 5R01GM080442-18
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Tomislav Rovis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $334,575
- **Award type:** 5
- **Project period:** 2007-09-21 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907789

## Citation

> US National Institutes of Health, RePORTER application 10907789, Asymmetric Synthesis of Nitrogen Heterocycles (5R01GM080442-18). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10907789. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*