Remodeling and Enhancing Schmidt Reaction Pathways in Hexafluoroisopropanol

The effect of carrying out two variations of the Schmidt reaction with ketone electrophiles in hexafluoroisopropanol (HFIP) solvent has been studied. When TMSN3 is reacted with ketones in the presence of triflic acid (TfOH) promoter, tetrazoles are obtained as the major products. This observation is...

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Bibliographic Details
Published in:Journal of organic chemistry 2016-02, Vol.81 (4), p.1593-1609
Main Authors: Motiwala, Hashim F, Charaschanya, Manwika, Day, Victor W, Aubé, Jeffrey
Format: Article
Language:English
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Summary:The effect of carrying out two variations of the Schmidt reaction with ketone electrophiles in hexafluoroisopropanol (HFIP) solvent has been studied. When TMSN3 is reacted with ketones in the presence of triflic acid (TfOH) promoter, tetrazoles are obtained as the major products. This observation is in contrast to established methods, which usually lead to amides or lactams arising from formal NH insertion as the major products. The full product profiles of several examples of this reaction are also reported and found to include mechanistically interesting products (e.g., double ring expansion). Application of TfOH promoter in HFIP was also found to promote the reaction of a hydroxyalkyl azide with a ketone, which affords lactams following nucleophilic opening of initially formed iminium ether more efficiently than previously reported methods.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.5b02764