Mechanochemical Mitsunobu Reactions

A Mitsunobu process performed under neat grinding conditions, using a mixer mill, is reported. It proceeds in the absence of reaction solvent and in short reactions times (10–20 min). A broad substrate scope encompassing primary and secondary alcohols, as well as oxygen, nitrogen, sulfur, and carbon...

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Published inAdvanced synthesis & catalysis Vol. 366; no. 10; pp. 2220 - 2225
Main Authors Williams, Matthew T. J., Adarve Cardona, Laura, Bolm, Carsten
Format Journal Article
LanguageEnglish
Published WEINHEIM Wiley 21.05.2024
Wiley Subscription Services, Inc
Subjects
Alcohols
Ball milling
Chemistry
Chemistry, Applied
Chemistry, Organic
mechanochemistry
Mitsunobu
Nucleophiles
Physical Sciences
Science & Technology
solvent-free
stereochemistry
Stereoselectivity
Substrates
mechanochemistry
REAGENTS
MECHANISM
DIETHYL AZODICARBOXYLATE
Ball milling
solvent-free
Mitsunobu
OPPORTUNITIES
MEDICINAL MECHANOCHEMISTRY
TRIPHENYLPHOSPHINE
MAGNESIUM
PHOSPHORIC-ACID
ESTERS
stereochemistry
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Summary:A Mitsunobu process performed under neat grinding conditions, using a mixer mill, is reported. It proceeds in the absence of reaction solvent and in short reactions times (10–20 min). A broad substrate scope encompassing primary and secondary alcohols, as well as oxygen, nitrogen, sulfur, and carbon‐centered nucleophiles is demonstrated. Application to the functionalization of a selection of APIs is shown, also. The developed process is amenable to scale up on a planetary ball‐mill, yielding over 2 grams of product. Finally, a representative alcohol is inverted with excellent stereoselectivity.
Bibliography:These authors contributed equally to this work.
Horizon Europe - Pillar II
ISSN:1615-4150
1615-4169
DOI:10.1002/adsc.202400296