In this study, we report a new reductive etherification procedure for protection of carbohydrate substrates and its application for one-pot preparation of glycosyl building blocks. The reported procedure features the use of polymethylhydrosiloxane (PMHS) as a sub-stoichiometric reducing agent, which prevents the transilylation side reaction and improves the efficiency of the reductive etherification method. Application of the PMHS reductive etherification procedure for one-pot protecting group manipulation are described.
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http://dx.doi.org/10.1039/d0ob00252f | DOI Listing |
Org Lett
January 2025
School of Science, Faculty of Engineering and Science, University of Greenwich, Chatham, Kent ME4 4TB, U.K.
Traditional etherification methods, although staples in synthetic chemistry, often fall short in the efficient construction of sterically hindered dialkyl ethers, especially under mild and practical conditions. Recent advances have attempted to address these limitations, typically relying on transition metal catalysts, external reductants, or harsh reaction conditions. In this work, we disclose a novel electrochemical approach that enables the synthesis of sterically hindered ethers from economically relevant and readily accessible alcohols without the need for sacrificial oxidants.
View Article and Find Full Text PDFOrg Biomol Chem
July 2024
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India.
Acid catalysed reductive etherification of -propargyl amino alcohols for the stereoselective synthesis of -2,5/2,6-disubstituted morpholines and -2,6/2,7-disubstituted oxazepanes has been developed. Mechanistic studies revealed that terminal alkynols gave morpholines a 6- hydroalkoxylation-isomerization-reduction cascade. Interestingly, an alkyne hydration-cyclization-reduction sequence is found to be involved in the formation of oxazepanes from alkyl substituted internal alkynols.
View Article and Find Full Text PDFAcc Chem Res
June 2024
Department of Applied Chemistry, Waseda University, 513 Wasedatsurumakicho, Shinjuku, Tokyo 162-0041, Japan.
ConspectusAromatic esters are cost-effective, versatile, and commonly used scaffolds that are readily synthesized or encountered as synthetic intermediates. While most conventional reactions involving these esters are nucleophilic acyl substitutions or 1,2-nucleophilic additions─where a nucleophile attacks the carbonyl group, decarbonylative transformations offer an alternative pathway by using the carbonyl group as a leaving group. This transition-metal-catalyzed process typically begins with oxidative addition of the C(acyl)-O bond to the metal.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
June 2024
Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Laboratory of Advanced Materials, Collaborative Innovation Centre of Chemistry for Energy Materials (iChEM), Fudan University, Shanghai, 200433, P. R. China.
J Org Chem
October 2023
Discovery Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
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.
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