Catalytic methods for the synthesis of spirooxindoles, pyrroloindolines, and flavanones

Gerten, Anthony
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This thesis discloses catalytic, enantioselective dipolar cycloadditions to deliver new nitrogen-containing heterocycles and formal hydroarylations of olefins that have previously not been possible.

Catalytic, enantioselective, dearomative cycloadditions of stabilized, α-substituted azomethine ylides with 3-nitroindoles occur in the presence of a catalytic complex generated from Cu(OTf)2 and (R)-Difluorphos. These reactions set four contiguous stereocenters, two of which are fully substituted. Overcoming the barrier of breaking aromaticity, this catalyst system delivers pyrrolo[3, 4b]indoles with exoà ´-selectivity in moderate-to-good yields (39-85%) with high diastereoselectivity (up to 98 : 1 : 1 dr) and enantioselectivity (up to 96% ee).

Catalytic, enantioselective, dipolar cycloadditions of highly reactive nitrile imines with methyleneindolinones occur in the presence of a catalyst generated from Mg(NTf2)2 and a chiral aminoindanol-derived bisoxazoline ligand. The catalyst system designed overcomes a rapid competing background reaction to deliver spiro[pyrazolin-3,3′-oxindoles] in up to 98% yield and 99% ee.

Conjugate additions of arylboronic acids to challenging 2-alkylchromones occur in aqueous medium in the presence of a catalyst system generated from Pd(TFA)2 and 1,10-phenanthroline. This system overcomes the problem of competing protodeboronation and biaryl-forming reactions to deliver 2-alkyl-2-aryl-chromanones in up to 90% yield, providing a new and effective means of generating a fully substituted carbon center.

In all of these projects, effective catalyst design principles were established to overcome challenges that made these types of reactions previously impossible.

Catalyst, Enantioselective, Flavanone, Lewis Acid, Pyrroloindoline, Spirooxindole