Design, Preparation, and Implementation of Axially Chiral Benzotetramisoles as Lewis Base Catalysts for Asymmetric Cycloadditions

• Published in: Angewandte Chemie Vol. 136; no. 30
• Main Authors: Lin, Zitong, Yu, Ying, Liu, Rixin, Zi, Weiwei
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 22-07-2024
• Subjects: catalyst design; Catalysts; Chemical reactions; Chirality; Cycloaddition; cycloadditions; Esters; fluorinated compounds; Imines; Lewis base; Lewis base catalysis; Microenvironments; quaternary stereocenter; Stereochemistry; Stereoselectivity
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202401181

Developing novel catalysts with potent activity is of great importance in organocatalysis. In this study, we designed and prepared a new class of benzotetramisole Lewis base catalysts (AxBTM) that have both central and axial chirality. This unique feature of these catalysts results in a three‐dimensional microenvironment with multi‐layers of chirality. The performance of the developed catalysts was tested in a series of cycloaddition reactions. These included the AxBTM‐catalyzed (2+2) cycloaddition between α‐fluoro‐α‐aryl anhydride with imines or oxindoles, and the sequential gold/AxBTM‐catalyzed (4+2) cycloaddition of enynamides with pentafluorophenyl esters. The interplay between axial and central chirality had a collaborative effect in regulating the stereochemistry in these cycloadditions, leading to high levels of stereoselectivity that would otherwise be challenging to achieve using conventional BTM catalysts. However, the (2+2) and (4+2) cycloadditions have different predilections for axial and central chirality combinations.
A new class of benzotetramisole Lewis base catalysts (AxBTMs) that have both central and axial chirality were developed. This unique feature of these catalysts results in a three‐dimensional microenvironment with multi‐layers of chirality. The performance of the developed catalysts were tested in a series of cycloaddition reactions, giving cycloaddition products with high stereoselectivities that are otherwise difficult to achieve with conventional BTM catalysts. Control experiments indicated that the axial and central chirality played a synergistic role in controlling the stereochemistry.