Nonacidic and Highly Chemoselective Protection of the Carbonyl Function. 3-Methylbenzothiazolines as a Base- and Acid-Resistant Protected Form for the Carbonyl Groups

Article abstract of DOI:10.1246/bcsj.62.1215

A simple and useful new type of protection method for carbonyl groups by conversion into 3-methylbenzothiazoline derivatives with o-(methylamino)benzenethiol was describe.With this method, 3-methylbenzothiazolines were conveniently obtained in excellent yields from various aldehydes and ketones.This method allows efficient protection and deprotection under mild and neutral conditions and affords protection of the carbonyl group against both basic and acidic conditions.The difference in reactivity between different carbonyl groups was successfully utilized for the chemoselective benzothiazolination of the formyl group of 4-oxopentanal and also for the chemoselective conversion of 4-androstene-3,17-dione and progesteron into the corresponding benzothiazolines with the nonconjugated keto groups remaining intact. 2-Substituted benzothiazolines derived from aldehydes were efficiently converted into 2,2-disubstituted benzothiazolines via alkylation, with a varity of Grignard or organolithium reagents, of 2-substituted 3-methylbenzothiazolium salts which were readily obtained by the treatment of the former thiazolines with trityl perchlorate in acetonitrile.These salts were also obtained in good yields from aldehydes in one-pot syntheses by the treatment with o-(methylamino)benzenethiol in acetonitrile followed by addition of trityl perchlorate. 3-Methylbenzothiazolium iodide was found to be also effective as a formyl cation equivalent and the reactions with Grignard or organolithium reagents produced the corresponding 2-substituted benzothiazolines in good yields.With this reaction, 2-deutero-3-methylbenzothiazolium iodide was effectively applied as a deuterated formyl cation equivalent for the synthesis of aldehyde-d.