Conspectus Indole-based chiral heterocycles constitute a class of important heterocyclic compounds that are found in numerous pharmaceuticals, functional materials, and chiral catalysts or ligands. Catalytic asymmetric synthesis, for which the 2001 Nobel Prize in Chemistry was awarded, has been demonstrated to be the most efficient method for accessing chiral compounds. Therefore, the catalytic asymmetric synthesis of indole-based chiral heterocycles has attracted great interest from the scientific community. However, the strategies toward this goal are rather limited, and great challenges remain in this field, such as metal contamination in the products, the limited number of platform molecules with versatile reactivity, and the limited number of catalytic asymmetric reactions that offer high step economy, atom economy, and excellent enantiocontrol. Therefore, novel strategies for the catalytic asymmetric synthesis of indole-based chiral heterocycles are urgently needed. To achieve this goal, our group has developed a series of unique strategies, such as designing and developing versatile platform molecules and their corresponding organocatalytic asymmetric reactions to access indole-based chiral heterocycles. In this Account, we describe our efforts to address the remaining challenges in this research field. Namely, we have designed and developed vinylindoles, indolylmethanols, arylindoles and indole derivatives as versatile platform molecules for the construction of indole-based chiral heterocyclic scaffolds with structural diversity and complexity. Based on the reactivities of these platform molecules, we have designed and accomplished a series of organocatalytic asymmetric cycloaddition, cyclization, addition and dearomatization reactions with a high step economy, atom economy and excellent enantiocontrol. Using these strategies, a wide range of indole-based chiral heterocycles, including five-membered to seven-membered heterocycles, axially chiral heterocycles and tetrasubstituted heterocycles, have been synthesized with high efficiency and excellent enantioselectivity. In addition, we have investigated the properties of some indole-based chiral heterocycles, including their bioactivities and catalytic activities, and showed that these chiral heterocycles have potent anticancer activities and promising catalytic activities in asymmetric catalysis. These results help elucidate the potential applications of indole-based chiral heterocycles in drug development and chiral catalysts. The organocatalytic asymmetric synthesis of indole-based chiral heterocycles has undoubtedly become and will continue to be a hot topic in the field of asymmetric catalysis and synthesis. Our efforts, summarized in this Account, will not only open a window for the future development of innovative strategies toward organocatalytic asymmetric synthesis of indole-based chiral heterocycles but also inspire chemists worldwide to confront the remaining challenges in this field and prompt further advances.

Chiral indole derivatives such as indolines and indolenines are important heterocyclic frameworks which constitute the core structures of many natural products and bioactive molecules. So, intensive attentions from chemists have...

An ew strategy for enantioselective synthesis of axially chiral naphthyl-indoles has been established through catalytic asymmetric addition reactions of racemic naphthylindoles with bulky electrophiles.Under chiral phosphoric acid catalysis,a zodicarboxylates and o-hydroxybenzyl alcohols served as bulky but reactive electrophiles that were attacked by C2-unsubstituted naphthyl-indoles,w hich underwent ad ynamic kinetic resolution to affordt wo series of axially chiral naphthyl-indoles in good yields (up to 98 %) and high enantioselectivities (up to 98:2 er).

of main observation and conclusion A new class of axially chiral aryl-alkene-indole frameworks have been designed, and the first catalytic asymmetric construction of such scaffolds has been established by the strategy of organocatalytic (Z/E)-selective and enantioselective (4+3) cyclization of 3-alkynyl-2-indolylmethanols with 2-naphthols or phenols (all >95 : 5 E/Z, up to 98% yield, 97% ee). This reaction also represents the first catalytic asymmetric construction of axially chiral alkene-heteroaryl scaffolds, which will add a new member to the atropisomeric family. This approach has not only confronted the great challenges in constructing axially chiral alkene-heteroaryl scaffolds but also provided a powerful strategy for the enantioselective construction of axially chiral aryl-alkene-indole frameworks.

Atroposelective synthesis of axially chiral molecules has attracted substantial attention from chemists because of the importance of such molecules. However, catalytic asymmetric synthesis of axially chiral styrenes or vinyl arenes is underdeveloped and challenging due to the low rotational barrier and weak configurational stability of such molecules. Therefore, the development of powerful strategies for the catalytic atroposelective synthesis of axially chiral styrenes or vinyl arenes is of great importance. In this work, we have accomplished the first atroposelective access to oxindole-based axially chiral styrenes by the strategy of catalytic kinetic resolution, and this strategy offered two kinds of oxindole-based axially chiral styrene derivatives in good diastereoselectivities (up to 94:6 dr) and excellent enantioselectivities (up to 98% ee) with high selectivity factors (S up to 106). This strategy not only provides easy access to oxindole-based axially chiral styrenes but also offers a robust method for synthesizing bisamide derivatives bearing both axial and central chirality. More importantly, this strategy has added a new class of members to the atropisomeric family, especially to the family of axially chiral styrenes.