Synfacts 2018; 14(04): 0375
DOI: 10.1055/s-0037-1609410
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Tetrahydrofuroindoles by a Palladium-Catalyzed Asymmetric Dearomatization

Mark Lautens
Tamara Beisel
Cheng Q. Zhang F. Cai Y. Guo Y.-L. * You S.-L. * Shanghai Institute of Organic Chemistry and Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, R. P. of China
Stereodivergent Synthesis of Tetrahydrofuroindoles through Pd-Catalyzed Asymmetric Dearomative Formal [3+2] Cycloaddition.

Angew. Chem. Int. Ed. 2018;
57: 2134-2138
Further Information

Publication History

Publication Date:
15 March 2018 (online)



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.