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Tetrahydrofuroindoles by a Palladium-Catalyzed Asymmetric Dearomatization
Stereodivergent Synthesis of Tetrahydrofuroindoles through Pd-Catalyzed Asymmetric Dearomative Formal [3+2] Cycloaddition.
Angew. Chem. Int. Ed. 2018;
15 March 2018 (online)
Key wordspalladium catalysis - catalytic asymmetric dearomatization - [3+2] cycloaddition - tetrahydrofuro-indoles
The authors developed a palladium-catalyzed diastereoselective and enantioselective dearomative formal [3+2] cycloaddition for the synthesis of tetrahydrofuroindoles. Remarkably, the polarity of the solvent was found to play a key role in the diastereoselectivity. Compared with toluene, the reactions in acetonitrile occurred faster and produced the reversed diastereoisomer with higher enantioselectivity.
Mechanistic studies were conducted to illustrate the origin of the diastereodivergency. The kinetic experiments indicate that the reactions in different solvents proceed by the same pathway with different rate-limiting steps, thereby leading to a reversed stereocontrol. ESI-MS experiments support the existence of key palladium complex intermediates and the proposed catalytic cycle. Several transformations of one of the products were also demonstrated.