# Catalytic Asymmetric Amine Synthesis using Ni/Photoredox Decarboxylations

> **NIH NIH F32** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $9,192

## Abstract

PROJECT SUMMARY/ABSTRACT
 The asymmetric synthesis of amines is of critical importance in organic chemistry. Amines are common
motifs in pharmaceutical molecules and impart useful properties on bioactive molecules (e.g., solubility,
hydrogen bonding). General catalytic methods for the asymmetric synthesis of amines are highly desirable,
particularly when they make use of widely available starting materials. The proposed research seeks to
synthesize amines from widely available carboxylic acids and alcohols by employing a dual catalytic
Ni/photoredox strategy and using hydroxylamine ester reagents as amine sources and oxidants. Photoredox
catalysis provides access to organic radicals via decarboxylation under mild reaction conditions, while the Ni
catalyst serves as a catalytic aminating reagent. The first reaction in Aim 1 seeks to convert carboxylic acids
into chiral amines using the strategy described above. A second reaction will target an alcohol-to-amine
conversion by using oxalyl chloride to generate alkyl oxalates that undergo decarboxylation to furnish an
organic radical under photocatalytic conditions. This transformation will complement classical methods for
alcohol-to-amine conversion (e.g., SN2, reductive amination, Mitsunobu reactions), but will exhibit advantages
of increased selectivity and scope, reduced stoichiometric waste, along with a fundamentally distinct
mechanism whereby enantioselectivity will be achieved. The final point is especially appealing because achiral
alcohol starting materials may be transformed into enantioenriched amines through the stereoconvergent
reaction of a prochiral radical with a chiral Ni catalyst. Aim 2 seeks to generalize the reaction conditions to
replace pre-generated hydroxylamine esters with amine coupling partners and exogenous oxidants. This
modification will allow for all of the reagents to be purchased from commercial vendors, which should expedite
the incorporation of the method into organic synthesis. With the adaptation that utilizes commercial reagents, it
is hoped that the proposed research will impact pharmaceutical synthesis, including medicinal chemistry efforts
wherein commercial availability of coupling partners should enable rapid drug library diversification, and
process chemistry applications in which the ability to purchase large amounts of inexpensive commercial
reagents will facilitate adoption in large-scale applications.

## Key facts

- **NIH application ID:** 9925798
- **Project number:** 5F32GM128238-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Scott D McCann
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $9,192
- **Award type:** 5
- **Project period:** 2018-05-11 → 2020-06-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925798

## Citation

> US National Institutes of Health, RePORTER application 9925798, Catalytic Asymmetric Amine Synthesis using Ni/Photoredox Decarboxylations (5F32GM128238-03). Retrieved via AI Analytics 2026-06-04 from https://api.ai-analytics.org/grant/nih/9925798. Licensed CC0.

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