# Selective N-alkylation of azoles via anion-binding catalysis

> **NIH GM F32** · HARVARD UNIVERSITY · 2026 · $76,300

## Abstract

Project Summary
Azoles are ubiquitous amongst bioactive molecules, present in approximately one third of commercial
pharmaceuticals. However, selective preparation of N-alkylated azoles is an outstanding synthetic challenge. As
a result, stereochemistry and N-regioselectivity are often achieved through the separation of isomeric mixtures
or introduced during de novo ring synthesis. This approach creates a significant synthetic barrier when evaluating
analogs of bioactive molecules during drug discovery campaigns. Therefore, a selective method to install alkyl
fragments on existing azoles is poised to advance the fields of chemical biology and medicinal chemistry.
This proposal leverages anion-binding catalysis to induce enantio- and N-regioselectivity in azole alkylation. We
will study how hydrogen-bond-donor catalysts engage azole nucleophiles through a network of noncovalent
interactions to control selective nucleophile delivery.
Aim 1. We are advancing an enantioconvergent SN1 reaction to form a-tertiary azoles.
Aim 2. We are developing a novel method for N-regiocontrol to form the contra-thermodynamic azole product.
The methods developed through this work will address long-standing challenges in azole chemistry, enabling
the synthesis of medicinally relevant frameworks that are currently inaccessible. Additionally, the research plan
will develop a deep understanding of the structural features required to engage azoles as competent
nucleophiles in anion-abstraction catalysis, introducing a new class of nucleophiles to this approach.
Beyond tackling a significant challenge in modern synthesis, I also designed my research plan to provide me
with training in multiple important areas that I had limited exposure to in during my doctoral career. Through
performing the proposed experiments, I will become proficient in asymmetric catalysis, supramolecular
chemistry, carbohydrate chemistry, computational analysis, and mechanistic investigation. Furthermore, I will
both en

## Key facts

- **NIH application ID:** 11315402
- **Project number:** 1F32GM156017-01A1
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Sara  Alektiar
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** GM
- **Fiscal year:** 2026
- **Award amount:** $76,300
- **Award type:** 1
- **Project period:** 2026-03-01T00:00:00 → 2029-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11315402

## Citation

> US National Institutes of Health, RePORTER application 11315402, Selective N-alkylation of azoles via anion-binding catalysis (1F32GM156017-01A1). Retrieved via AI Analytics 2026-07-08 from https://api.ai-analytics.org/grant/nih/11315402. Licensed CC0.

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