Organocatalytic Enantioselective Construction of Heterocycle-Substituted Styrenes with Chiral Atropisomerism.

We have developed a novel π-π interaction and dual H-bond concerted control strategy to construct axially chiral naphthylamine heterocycles. With ortho-alkynyl-naphthylamines as the electrophile, indoles and 4-hydroxycoumarins were efficiently employed to construct axially chiral skeletons in good yields and with excellent enantioselectivities (up to 97% enantiomeric excess). Furthermore, the resulting products could be converted to potential squaramides featuring organic catalysts.

Highly Chemo-, Site-, and Enantioseletive para C-H Aminoalkylation of N-Monosubstituted Aniline Derivatives Affording 3-Amino-2-oxindoles.

In general, enantioselective C-H functionalization of N-monosubstituted anilines is a highly challenging task owing to the competitive chemoselective N-H bond insertion reactions. In this paper, we reported a direct highly chemo-, site-, and enantioselective para C-H aminoalkylation of N-monosubstituted aniline derivatives with isatin-derived ketimines in the presence of chiral phosphoric acids (CPAs) and offered a practical strategy for para asymmetric C-H functionalization of anilines containing N-H bonds.

Remote C6-Enantioselective C-H Functionalization of 2,3-Disubstituted Indoles through the Dual H-Bonds and π-π Interaction Strategy Enabled by CPAs.

A versatile dual H-bonds and π-π interaction strategy that enables enantioselective remote C6-selective C-H functionalization of 2,3-disubstituted indoles was first reported. The N-H bond of indole was pivotal to achieve the C6 functionalization with excellent yield and enantioselectivity. Furthermore, this methodology leads to the efficient construction of numerous enantioenriched C6-functionalized indole products under mild reaction conditions employing different electrophiles. Preliminary cell proliferation investigations revealed that the synthesized chiral C6-substituted indole derivatives had potential anticancer activities.

Highly atroposelective synthesis of nonbiaryl naphthalene-1,2-diamine N-C atropisomers through direct enantioselective C-H amination.

Nonbiaryl N-C atropisomer is an important structural scaffold, which is present in natural products, medicines and chiral ligands. However the direct enantioselective C-H amination to access optically pure N-C atropisomer is still difficult and rare. Here we report a π-π interaction and dual H-bond concerted control strategy to develop the chiral phosphoric acids (CPAs) catalyzed direct intermolecular enantioselective C-H amination of N-aryl-2-naphthylamines with azodicarboxylates as amino sources for the construction of atroposelective naphthalene-1,2-diamines. This type of N-C atropisomers is stabilized by intramolecular hydrogen bond and the method features a broad range of substrates, high yields and ee values, providing a strategy to chirality transfer via the modification of N-C atropisomers.