# Alkali Metal Chemistry-Structures, Mechanisms, and Applications

> **NIH NIH R35** · CORNELL UNIVERSITY · 2021 · $557,614

## Abstract

Summary and Abstract
 Organoalkali metal-based reagents are used in both academic and industrial
laboratories to carry out syntheses of medicinally important compounds. The underlying
aggregates and central importance of solvation cause these reagents to be as
structurally and mechanistically confounding as any subdiscipline in organometallic
chemistry. Through a combination of structural and mechanistic studies we address key
issues pertaining to reactivity and selectivity. The program is fully integrated starting
from a synthetic goal, observation, or question, proceeding through structural,
mechanistic, and computational studies, and finishing with synthetically useful insights
and methods. Treating solvation as a molecular rather than bulk phenomenon is central
to all of our studies.
 We will emphasize the role of non-covalent auxiliaries and focus on two subsets
of alkali metal chemistry that have proven virtually impenetrable to careful scrutiny:
lithium enolates and sodium amides. Both arenas require a combined effort involving (1)
the elucidation of profoundly lacking basic structural and mechanistic principles, and (2)
pushing a mechanism-driven approach to develop new strategies for controlling
reactivity and selectivity. In the enolate program, we emphasize the role of mixed
aggregates with chiral lithium alkoxides as vehicles to control relative and absolute
stereochemistry. In the organosodium chemistry, we will continue studying the principles
of structure and mechanism to develop completely absent principles of reactivity and
selectivity. Among a multitude of differences of sodium- versus lithium-based reagents
discovered so far, it is the capacity to catalyze organosodium reactions with triamines
that stands out. We will focus on catalytically active chiral triamines to induce
stereocontrol via kinetic resolutions by sodium amides and catalyzed asymmetric
functionalizations of the resulting sodiated intermediates. The Holy Grail for us is finding
universal additives—amino alkoxides for lithium enolates and chiral triamines for the
organosodium reactions.

## Key facts

- **NIH application ID:** 10146423
- **Project number:** 5R35GM131713-03
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** DAVID B. COLLUM
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $557,614
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146423

## Citation

> US National Institutes of Health, RePORTER application 10146423, Alkali Metal Chemistry-Structures, Mechanisms, and Applications (5R35GM131713-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10146423. Licensed CC0.

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