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Published on: August 19, 2012
Click Organocatalysis: Acceleration of Azide-Alkyne Cycloadditions with Mutually Orthogonal Click Reactions
Brian J Levandowski1, Brian J Graham1, K N Houk2
1Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307, United States.
Abstract:
"Click organocatalysis" uses mutually orthogonal click reactions to organocatalyze a click reaction. We report the development of an isobenzofuran organocatalyst that increases the rate and regioselectivity of an azide-alkyne cycloaddition. The organocatalytic cycle consists of (1) a Diels-Alder reaction of an alkyne with a diarylisobenzofuran to form a benzooxanorbornadiene, (2) a 1,3-dipolar cycloaddition with an azide to form a 4,5-dihydro-1,2,3-triazole, and (3) a retro-Diels-Alder reaction that releases the triazole product and regenerates the diarylisobenzofuran organocatalyst. The diarylisobenzofuran organocatalyst was computationally designed to catalyze the reaction of perfluorophenyl azide and methyl propiolate to selectively form a 1,4-triazole product. Experimental validation of the designed organocatalyst was obtained with methyl 4-azido-2,3,5,6-tetrafluorobenzoate and methyl propiolate.
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