Enantioselective synthesis of [4]helicenes by organocatalyzed intermolecular C-H amination

Abstract

Catalytic asymmetric synthesis of helically chiral molecules has remained an outstanding challenge and witnessed fairly limited progress in the past decades. Current methods to construct such compounds almost entirely rely on catalytic enantiocontrolled fused-ring system extension. Herein, we report a direct terminal peri-functionalization strategy, which allows for efficient assembling of 1,12-disubstituted [4]carbohelicenes via an organocatalyzed enantioselective amination reaction of 2-hydroxybenzo[c]phenanthrene derivates with diazodicarboxamides. The key feature of this approach is that the stereochemical information of the catalyst could be transferred into not only the helix sense but also the remote C-N axial chirality of the products, thus enabling the synthesis of [4]- and [5]helicenes with both structural diversity and stereochemical complexity in good efficiency and excellent enantiocontrol. Besides, the large-scale preparations and representative transformations of the helical products further demonstrate the practicality of this protocol. Moreover, DFT calculations reveal that both the hydrogen bonds and the C-H---π interactions between the substrates and catalyst contribute to the ideal stereochemical control.

Organocatalyzed double dearomatization reaction of non-functionalized phenols and propargylic alcohols: the important regulating effect of steric hindrance

“…11 Inspired by such a chemical phenomenon, as well as considering the structural characteristics of helicenes, we believed that the aromatic electrophilic substitution occurring at the highly sterically hindered fjord-type area of helical phenols might be employed to validate our conjecture. 12 Accordingly, we report herein an interrupted Friedel–Crafts reaction of polycyclic phenols and propargylic alcohols (Scheme 2B). As expected, the resulting dearomatized helical intermediate failed to recover the aromaticity, but further underwent an intramolecular formal dearomative Diels–Alder reaction to yield structurally complex polycyclic diketones featuring both central and helical chirality elements.…”