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Published on: February 20, 2020
A Lewis acid-promoted Pinner reaction
Dominik Pfaff1, Gregor Nemecek, Joachim Podlech
1Institut für Organische Chemie, Karlsruher Institut für Technologie (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
Beilstein Journal of Organic Chemistry
|August 16, 2013
Summary
This study details a Lewis acid-promoted Pinner reaction between carbonitriles and alcohols, efficiently forming carboxylic esters. Trimethylsilyl triflate proved optimal, yielding good results with various alcohols and nitriles.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- The Pinner reaction is a classical method for synthesizing imino esters from nitriles and alcohols.
- Developing efficient and versatile methods for carboxylic ester synthesis remains a key area in organic chemistry.
Purpose of the Study:
- To investigate the efficacy of a Lewis acid-promoted Pinner reaction for the synthesis of carboxylic esters.
- To optimize reaction conditions using trimethylsilyl triflate and explore substrate scope.
Main Methods:
- Reaction of carbonitriles with primary alcohols in the presence of trimethylsilyl triflate (TMSOTf) as a Lewis acid.
- Utilized two equivalents of TMSOTf for optimal results.
- Investigated the synthesis of aliphatic and benzylic esters, including acrylates and benzoates.
Main Results:
- Achieved good yields of carboxylic esters from primary alcohols and aliphatic or benzylic carbonitriles.
- Demonstrated the straightforward synthesis of acrylates from acrylonitrile and benzoates from benzonitrile.
- Observed that phenols are unreactive under these conditions.
- Reported the successful application of this method in the total synthesis of the natural product monaspilosin.
- Identified a competing Ritter-type side reaction forming amides with benzyl alcohols.
Conclusions:
- The Lewis acid-promoted Pinner reaction using TMSOTf offers an effective route to carboxylic esters.
- The method exhibits good functional group tolerance and is applicable to diverse substrates, including those relevant to natural product synthesis.
- Potential side reactions, such as amide formation, should be considered when using benzyl alcohols.
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