# Stereoselective Reactions of Oxocarbenium Ions and Related Intermediates

> **NIH NIH R01** · NEW YORK UNIVERSITY · 2021 · $261,951

## Abstract

Project Summary/Abstract
 Although stereoselective bond-forming reactions involving oxocarbenium ions are important methods in
carbohydrate chemistry and organic synthesis, these reactions often do not proceed with the expected
stereochemistry. For example, in many cases stereochemistry cannot be predicted either because there are no
models to understand stereoselectivity (as in the case of medium-ring oxocarbenium ions) or that these models
fail to accommodate deviations from expected selectivity (as observed for neighboring-group participation). To
address the gaps in our understanding of these stereochemical models, the following specific aims will be
pursued: (1) we will examine neighboring-group participation in stereoselective reactions of cyclic
oxocarbenium ions; (2) we will extend the concept of neighboring-group participation to encompass systems
that are not related to carbohydrates, including to solve problems in acyclic stereocontrol; and (3) we will
establish that seven-membered ring electrophiles (oxocarbenium ions) and nucleophiles (enolates) can react
stereoselectively. In the first Aim, we will use systems that share structural characteristics with carbohydrates
to explain why neighboring group effects are not as strong as may be anticipated, a fact suggested by our
preliminary studies. We will also extend our preliminary studies that suggest the CO2R group of sialic acids
exerts little influence on the stability of oxocarbenium ions and the stereochemistry of their reactions. The
second Aim will use systems that are not closely related to carbohydrates to address mechanistic questions in
carbohydrate chemistry. The third Aim will pursue a stereochemical model to understand the reactions involved
in seven-membered ring sugars, and we will expand preliminary studies that reactions involving seven-
membered ring enolates are more selective than analogous reactions of six-membered ring enolates. These
studies will be performed in collaboration with a theoretical chemist, Professor Jeffery Evanseck (Duquesne
University), who is skilled in using computational methods to investigate reaction mechanisms. The proposed
research is significant because it will enable researchers to predict the stereochemistry of bond-forming
reactions commonly used for the synthesis of carbohydrates, natural products, and other biologically active
compounds. The proposed research is innovative because we use systems that are not carbohydrates to
develop stereoselective reactions that can be used in carbohydrate chemistry, medicinal chemistry, and natural
product synthesis. These studies are relevant to human health because they will help medicinal chemists plan
and execute the synthesis of biologically active compounds such as carbohydrates with precise control of
three-dimensional structures.

## Key facts

- **NIH application ID:** 10198948
- **Project number:** 5R01GM129286-04
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** KEITH ALLEN WOERPEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $261,951
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198948

## Citation

> US National Institutes of Health, RePORTER application 10198948, Stereoselective Reactions of Oxocarbenium Ions and Related Intermediates (5R01GM129286-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10198948. Licensed CC0.

---

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