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.
Abstract:
This manuscript describes the development of the first diastereoselective intermolecular synthesis of alkyl ethers via reductive etherification of diverse ketones or aldehydes with alcohols. Key to this development was the use of low-temperature high-throughput experimentation (HTE) technologies that enabled rapid reaction optimizations and parallel synthesis. A broad scope of pharmaceutically relevant substrates was surveyed, which formed alkyl ethers effectively. In addition, we demonstrated that the diastereoselectivity of this transformation can be readily modulated by prudent selection of the reductant.
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