Brunen Sebastian, Mitschke Benjamin, Leutzsch Markus, List Benjamin
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim an der Ruhr, Germany.
J Am Chem Soc. 2023 Jul 26;145(29):15708-15713. doi: 10.1021/jacs.3c05148. Epub 2023 Jul 13.
Since its discovery more than a century ago, the Friedel-Crafts reaction has manifested itself as a powerful method for the introduction of carbon substituents to arenes. Despite its potential generality, the scope of the reaction is intrinsically limited by the arene's nucleophilicity, which has previously restrained the applicability of asymmetric variants to activated substrates. To overcome this fundamental limitation, we report herein an asymmetric Friedel-Crafts reaction of unactivated, purely hydrocarbon arenes, alkoxybenzenes, and heteroarenes with ,-acetals to give enantioenriched arylglycine esters. Highly regio- and stereoselective C-C bond formation was achieved using strong and confined Brønsted acid organocatalysts, enabling the first asymmetric catalytic Friedel-Crafts reaction of simple alkylbenzenes.
自一个多世纪前被发现以来，傅克反应已成为向芳烃引入碳取代基的一种强大方法。尽管该反应具有潜在的通用性，但其反应范围本质上受到芳烃亲核性的限制，这一限制此前阻碍了不对称变体在活性底物上的应用。为克服这一基本限制，我们在此报告了未活化的纯烃芳烃、烷氧基苯和杂芳烃与α,α-缩醛的不对称傅克反应，以生成对映体富集的芳基甘氨酸酯。使用强酸性且受限的布朗斯特酸有机催化剂实现了高度区域和立体选择性的碳-碳键形成，从而实现了简单烷基苯的首例不对称催化傅克反应。
