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 been paid to the construction of such frameworks. Among different approaches, organocatalytic asymmetric dearomatization (organo-CADA) reactions of indole derivatives have become powerful methods toward this goal. Consequently, a variety of enantioenriched heterocyclic frameworks containing indoline, indolenine and the related cores have been constructed via organo-CADA reactions of indole derivatives, and a series of important natural products with structural complexity and enantiopurity have been synthesized based on these methodologies. This review summarizes the progresses in organo-CADA reactions of indole derivatives since 2004 and their applications in total synthesis of natural products, and gives some insights into challenging issues in this research field, which will enlighten the future development of this field.

Progresses in organocatalytic asymmetric dearomatization reactions of indole derivatives

The development of novel synthetic strategies to form new chemical entities in a stereoselective manner is an ongoing significant objective in organic and medicinal chemistry. This review analyses the development of new stereoselective approaches to spirocyclic oxindoles with spiro-3- to 8-membered rings. It highlights the importance of these structures for applications in medicinal chemistry, as intermediates or final products in total synthesis and as model compounds for the development of enantioselective catalytic methodologies.

Stereoselective synthesis and applications of spirocyclic oxindoles

Phosphorus-based organocatalysis encompasses several subfields that have undergone rapid growth in recent years. This Outlook gives an overview of its various aspects. In particular, we highlight key advances in three topics: nucleophilic phosphine catalysis, organophosphorus catalysis to bypass phosphine oxide waste, and organophosphorus compound-mediated single electron transfer processes. We briefly summarize five additional topics: chiral phosphoric acid catalysis, phosphine oxide Lewis base catalysis, iminophosphorane super base catalysis, phosphonium salt phase transfer catalysis, and frustrated Lewis pair catalysis. Although it is not catalytic in nature, we also discuss novel discoveries that are emerging in phosphorus(V) ligand coupling. We conclude with some ideas about the future of organophosphorus catalysis.

Phosphorus-Based Catalysis.

Atropisomers beyond the C–C axis (denoted as X–Y herein) are important addition to the repertoire of axially chiral compounds, which have received much attention in recent years. Compared with conventional C–C axial chirality around biaryl and olefin axes, atropisomerism portrayed by C–N, C–O, C–B, or N–N bond was deemed to be challenging due to the relatively low rotational barriers. However, the intrinsic shorter bond length and electron-repelling effect lead to a congested hetero X–Y axis, resulting in stable axially chiral frameworks. The past two decades, especially the past few years have witnessed a rapid progress of this emerging area. A range of catalytic atroposelective approaches have been reported for the efficient synthesis of these challenging skeletons. The X–Y axially chiral compounds are valuable molecules, and they may be used as new ligands or catalysts in asymmetric catalysis or evaluated for their potential biological activities. We believe that the chemistry of atropisomers beyond C–C axial chirality will be forthcoming and blooming in the near future, taking up an important position in organic chemistry and beyond. Atropisomers beyond the C–C axis (denoted as X–Y herein) are important addition to the repertoire of axially chiral compounds, which have received much attention in recent years. Compared with conventional C–C axial chirality around biaryl and olefin axes, atropisomerism portrayed by C–N, C–O, C–B, or N–N bond was deemed to be challenging due to the relatively low rotational barriers. However, the intrinsic shorter bond length and electron-repelling effect lead to a congested hetero X–Y axis, resulting in stable axially chiral frameworks. The past two decades, especially the past few years have witnessed a rapid progress of this emerging area. A range of catalytic atroposelective approaches have been reported for the efficient synthesis of these challenging skeletons. The X–Y axially chiral compounds are valuable molecules, and they may be used as new ligands or catalysts in asymmetric catalysis or evaluated for their potential biological activities. We believe that the chemistry of atropisomers beyond C–C axial chirality will be forthcoming and blooming in the near future, taking up an important position in organic chemistry and beyond. 

Atropisomers beyond the C–C axial chirality: Advances in catalytic asymmetric synthesis

This review summarizes the advances in the catalytic enantioselective construction of vicinal quaternary carbon stereocenters, introduces major synthetic strategies and discusses their advantages and limitations, highlights the application of known protocols in the total synthesis of natural products, and outlines the synthetic opportunities.

/pdf/catalytic-enantioselective-construction-of-vicinal-3q48qps17d.pdf

Catalytic enantioselective construction of vicinal quaternary carbon stereocenters

Construction of contiguous all-carbon quaternary stereogenic centers is a long-standing challenge in synthetic organic chemistry. In this report, a phosphine-catalyzed enantioselective (3+2) annulation reaction between allenes and isoindigos, containing either two identical or different oxindole moieties, is introduced as a powerful strategy for the construction of spirocyclic bisindoline alkaloid core structures. The reported reactions feature high chemical yields, excellent enantioselectivities, and very good regioselectivities, and are highly useful for creating structurally challenging bisindoline natural products.

Phosphine‑Catalyzed (3+2) Annulation of Isoindigos with Allenes: Enantioselective Formation of Two Vicinal Quaternary Stereogenic Centers

Rational design and atroposelective synthesis of N–N axially chiral compounds

Pyrroloindolines are important and privileged polycyclic indoline motifs that are widely present in natural products and bio-significant molecules. From an organic chemistry perspective, their rigid tricyclic molecular architectures with a fully substituted carbon center at the C3a-position pose a great challenge to synthetic chemists. In a biological context, pyrroloindoline-containing alkaloids display a plethora of promising activities, making them significant in biological sciences and drug development. In the past few decades, pyrroloindoline and its analogues have emerged as appealing synthetic targets, attracting tremendous attention from the synthetic community. In this review, we summarize the state-of-the-art catalytic asymmetric synthesis of pyrroloindolines, as well as the related applications to the total synthesis of natural products.

Catalytic asymmetric preparation of pyrroloindolines: strategies and applications to total synthesis.

A highly enantioselective [4 + 2] cycloaddition reaction of aurone-derived 1-azadienes with 3-vinylindoles has been developed. In the presence of chiral phosphoric acids, a wide range of benzofuran-fused tetrahydropyridines with three contiguous stereogenic centers were obtained in good yields, and with excellent diastereo- and enantio-selectivities.

Facile access to benzofuran-fused tetrahydropyridines via catalytic asymmetric [4 + 2] cycloaddition of aurone-derived 1-azadienes with 3-vinylindoles

Phosphine-Catalyzed Asymmetric Allylic Alkylation of Achiral MBH Carbonates with 3,3′-Bisindolines: Enantioselective Construction of Quaternary Stereogenic Centers

Guang-Jian Mei

Papers

Phosphine‑Catalyzed (3+2) Annulation of Isoindigos with Allenes: Enantioselective Formation of Two Vicinal Quaternary Stereogenic Centers

Rational design and atroposelective synthesis of N–N axially chiral compounds

Catalytic asymmetric preparation of pyrroloindolines: strategies and applications to total synthesis.

Facile access to benzofuran-fused tetrahydropyridines via catalytic asymmetric [4 + 2] cycloaddition of aurone-derived 1-azadienes with 3-vinylindoles

Phosphine-Catalyzed Asymmetric Allylic Alkylation of Achiral MBH Carbonates with 3,3′-Bisindolines: Enantioselective Construction of Quaternary Stereogenic Centers