- Application of a recyclable fluorous oxime in the convenient synthesis of 3-amino-1,2-benzisoxazoles and 4-amino-1H-2,3-benzoxazines
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A microwave-assisted, fluorous synthetic route to 3-amino-1,2- benzisoxazoles and 4-amino-1H-2,3-benzoxazines has been developed. The strategy comprises linking the respective 2-fluorobenzonitrile or 2-(bromomethyl) benzonitrile to a fluorous oxime tag to give an aryloxime intermediate which then undergoes cyclization with concomitant cleavage of the substrate-tag in acidic conditions to provide the desired product in good to moderate yields. In addition, the aryloxime intermediate could be subjected to further reactions to expand the compound library. The product could be easily separated using fluorous solid-phase extraction (F-SPE) and the fluorous ketone recovered could be converted back to the fluorous oxime and reused in the next run of the synthesis.
- Ang, Wei Jie,Chu, Chi-Yuan,Chou, Tzyy-Chao,Lo, Lee-Chiang,Lam, Yulin
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p. 780 - 785
(2013/04/10)
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- Studies on the synthetic compatibility of aryloxime linkers in the solid-phase synthesis of 3-aminobenzisoxazoles
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Further exploration of the scope of our solid-phase method for the synthesis of 3-aminobenzisoxazoles (using the Kaiser oxime resin 1) is described. The effects of base, leaving group, and solvent on the nucleophilic aromatic substitution based resin-loading reaction are discussed. Representative aryloxime intermediates were subjected to a variety of acidic conditions commonly used in protecting group removal to establish the acid stability profile of this linker. Regioselectivity was evaluated with various di- and trifluorobenzonitriles, which gave single benzisoxazole products after loading and cyclorelease reactions. Substituent effects observed in the course of the acid stability and regioselectivity studies suggest that the nitrile plays a critical role in the oxime hydrolysis mechanism. Finally, to establish the compatibility of the aryloxime linker with a variety of useful on-resin synthetic transformations, functionalized substrates were loaded onto resin 1, and carbon-nitrogen, carbon-oxygen, and carbon-carbon bond-forming reactions were successfully executed.
- Lepore, Salvatore D.,Wiley, Michael R.
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p. 2924 - 2932
(2007/10/03)
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