# Cycloadditions of Strained Cyclic Intermediates

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $16,137

## Abstract

Project Summary/Abstract
 Nitrogen-containing heterocycles are prevalent in bioactive natural products and
pharmaceuticals, with piperidine serving as the most prevalent heterocycle found in
drug scaffolds. Although largely understudied, strained azacyclic allenes have the
potential to serve as building blocks for the construction of densely functionalized
piperidines. The manipulation of azacyclic allenes in a controlled manner would offer
new opportunities for making arrays of heterocycles with valuable applications in the
pharmaceutical industry and in organic synthesis. The primary goal of this proposal is to
develop a model for predicting the regioselectivities and steroselectivities of azacyclic
allenes in Diels–Alder cycloadditions, thereby accelerating their application in the
synthesis of highly functionalized nitrogen-containing heterocycles. The research
environment in the Garg and Houk laboratories at UCLA is ideal for achieving this goal.
The laboratories have a track record of collaboration at the interface of synthetic
chemistry and mechanism. Both Professor Garg and Professor Houk are leaders in their
respective fields and are also known to have excellent track records of mentoring
graduate students and ensuring their success. Thus, the trainee would become an
expert in both the fields of organic synthesis and computational chemistry.
 The proposal will be accomplished through two specific aims involving a
combination of computations and experiments. In Aim 1, a predictive model for
regioselective Diels–Alder cycloadditions with 3’ and 5’ substituted azacyclic allenes will
be developed. This effort will involve high accuracy DFT calculations and experimental
testing of computational predictions to confirm the reliability of the model. Aim 2 will
involve the development of enantiospecific Diels–Alder cycloadditions of azacyclic
allenes. The role of substituents in these reactions will be studied computationally, and
a simple model to predict stereospecificity will be developed. Computational predictions
will be tested experimentally and will establish the reliability of the predictive model for a
variety of azacyclic allenes. This work would ultimately demonstrate the utility of
strained cyclic allenes in asymmetric synthesis.

## Key facts

- **NIH application ID:** 10111529
- **Project number:** 5F31GM130099-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Melissa Ramirez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $16,137
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111529

## Citation

> US National Institutes of Health, RePORTER application 10111529, Cycloadditions of Strained Cyclic Intermediates (5F31GM130099-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10111529. Licensed CC0.

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