Diastereoselective Reductive Etherification Via High-Throughput Experimentation: Access to Pharmaceutically Relevant
Jiantao Fu1, Zoe Vaughn1, Andrew F Nolting2
1Discovery Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
The Journal of Organic Chemistry
|September 7, 2023
Summary
This study presents the first diastereoselective synthesis of alkyl ethers using reductive etherification. Low-temperature high-throughput experimentation enabled rapid optimization for diverse pharmaceutical substrates.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Alkyl ethers are important in pharmaceuticals.
- Existing methods for alkyl ether synthesis are limited.
Purpose of the Study:
- To develop the first diastereoselective intermolecular synthesis of alkyl ethers.
- To explore the use of reductive etherification for alkyl ether synthesis.
Main Methods:
- Utilized low-temperature high-throughput experimentation (HTE) for reaction optimization.
- Employed reductive etherification of diverse ketones or aldehydes with alcohols.
Main Results:
- Achieved the first diastereoselective intermolecular synthesis of alkyl ethers.
- Demonstrated effective formation of alkyl ethers from a broad scope of pharmaceutically relevant substrates.
- Showed that diastereoselectivity can be modulated by reductant choice.
Conclusions:
- The developed method provides a novel and efficient route to diastereoselective alkyl ether synthesis.
- HTE technologies are crucial for rapid optimization in synthetic chemistry.
- The ability to modulate diastereoselectivity offers precise control over product formation.
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