Chinese Journal of Organic Chemistry >
Preparation of Aryl Fused Pyrrolizidines via Intramolecular Schmidt Reaction of Acyl Chlorides with Alkyl Azides
Received date: 2015-06-26
Revised date: 2015-09-07
Online published: 2015-09-15
Supported by
Project supported by the National Natural Science Foundation of China (No. 21262024), and the Program for New Century Excellent Talents in University (No. NCET-13-0874).
The intramolecular Schmidt reaction of acyl chlorides with alkyl azides was explored. Thirteen aryl substituted azido carboxylic acids were prepared and applied to the Schmidt rearrangement. Activation of the carboxylic acids with oxalyl chloride generated the acyl chlorides in situ, which would enhance the reactivity of the carbonyl group. The intramolecular attack of azido group to the acyl chloride initiated the rearrangement, and the isocyanate ion intermediate was obtained from the migration with the designed substrates. Finally, the nucleophilic addition of aromatic ring to the isocyanate ion furnished the aryl fused pyrrolizidines. The substituents on the para-position of the aromatic ring would have obvious influence with the conversion. The azido carboxylic acid prepared from the ethyl p-methoxyphenylacetate, with a methine carbon attaching to the carbonyl group, gave the desired pyrrolizidine in very poor yield. Introducing an alkyl group to the methine carbon afforded the substrate with a quaternary carbon next to the carboxylic acid, and Schmidt reaction of such substrate could efficiently produce the aryl fused pyrrolizidine. The possible mechanism process was proposed to account for the different reactivity. In summary, a wide arrange of aryl fused pyrrolizidines were efficiently prepared from the intramolecular Schmidt reaction of acyl chlorides with alkyl azides followed by intramolecular capture of aryl rings to the isocyanate ion intermediates.
Key words： Schmidt reaction; azides; aryl fused pyrrolizidines; carboxylic acids
Li Qingfang , Li Rui , Li Xueqiang , Gu Peiming . Preparation of Aryl Fused Pyrrolizidines via Intramolecular Schmidt Reaction of Acyl Chlorides with Alkyl Azides[J]. Chinese Journal of Organic Chemistry, 2015 , 35(11) : 2326 -2332 . DOI: 10.6023/cjoc201506031
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