Carbon Dioxide Directing Group for Selective C-H Functionalization

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Solution Overview

Problem

The agrochemical industry faces challenges in developing new herbicides with new modes of action due to rising health concerns and environmental issues with existing compounds, and current methods for C—H functionalization are inefficient and costly, requiring additional synthetic steps and low atom economy.

Innovation Solution

A method using carbon dioxide as a directing group for transition metal-catalyzed C—H functionalization to convert C—H bonds into various functional groups, such as C—C, C—B, C—N, C—O, C—F, C—Cl, C—Br, C—I, or C—S bonds, facilitating the rapid synthesis of structurally diverse compounds without the need for costly directing groups.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional stoichiometric directing groups are used for C—H functionalization, then the C—H bond can be selectively functionalized, but additional synthetic steps for installation and removal of directing groups are required, increasing time and cost

Engineering Contradiction:

Improveselectivity of C—H functionalizationVSAvoidtime for installation and removal of directing groups

Core Design Contradiction:

Manufacturing precisionVSLoss of time

Solution Approach 1:

The directing group is installed in advance by reacting the substrate with carbon dioxide under the reaction conditions before the C—H functionalization occurs. This preliminary installation eliminates the need for separate pre-installation steps while maintaining selectivity throughout the process.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

Carbon dioxide acts as an intermediary directing group that temporarily coordinates to the metal catalyst during the reaction, enabling selective C—H functionalization, then is removed in situ without requiring separate removal steps. The CO2 facilitates the transformation and then departs as a gas.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Manufacturing precision

If conventional stoichiometric directing groups are used for C—H functionalization, then the C—H bond can be selectively functionalized, but the atom economy is reduced due to the need for directing group installation and removal

Engineering Contradiction:

Improveselectivity of C—H functionalizationVSAvoidatom economy

Core Design Contradiction:

Manufacturing precisionVSLoss of substance

Solution Approach 1:

Carbon dioxide serves as a transient intermediary that enables the C—H functionalization but is not incorporated into the final product structure. It coordinates during the reaction then is released as a gas, meaning no atoms from the directing group are wasted in the final product or require separate removal steps.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The carbon dioxide directing group is discarded as a gas after facilitating the reaction, eliminating the need for energy-intensive purification steps to remove directing group fragments. The gaseous CO2 simply escapes from the reaction mixture, leaving a clean product.

Inventive Principle:

Principle #34Discarding and recovering

3Loss of substance

If imines are used as in situ-installed directing groups, then atom economy is improved, but they are less tolerant of oxidizing conditions and require formation from primary amines only

Engineering Contradiction:

Improveatom economyVSAvoidtolerance to oxidizing conditions

Core Design Contradiction:

Loss of substanceVSReliability

Solution Approach 1:

Instead of using imines which are sensitive to oxidation, the patent employs carbonic esters formed by CO2 coordination to the amine. This parameter change in the directing group structure provides oxidation tolerance while maintaining the benefits of in situ formation and good atom economy.

Inventive Principle:

Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach enables the rapid and efficient synthesis of new herbicides and pesticides by selectively functionalizing C—H bonds, improving atom economy and reducing production costs, while being applicable to a wide range of substrates, including amines, alcohols, and phosphines.

Implementation Method 1

Conventional directing groups have been used for the directed C—H functionalization of amines and other heteroatom-bearing substrates... Numerous directing groups have been used for the directed C—H functionalization of amines and other heteroatom-bearing substrates

Methodology Applied

Scientific EffectChelation:

Implementation Method 2

A method using carbon dioxide as a directing group for transition metal-catalyzed C—H functionalization to convert C—H bonds into various functional groups

Methodology Applied

Scientific EffectCatalysis: Catalysis

Implementation Method 3

the substrate compound comprises an amine, alcohol, thiol, or phosphine functional group... using CO2 as a directing group to convert a C—H bond in a substrate compound

Methodology Applied

Scientific EffectAdduct formation:

Data Source

PatentUS10865163B2Carbon dioxide as a directing group for C—H functionalization reactions involving Lewis basic amines, alcohols, thiols, and phosphines for the synthesis of compounds

Publication Date: 2020.12.15 UNIVERSITY OF TOLEDO

AI summary

Methods of synthesizing compounds using CO2 as a directing group for C—H functionalization, and compounds made thereby, are described.