Dearomatization Reaction Research Articles

Palladium-Catalyzed Asymmetric Dearomative Carbonylation of Indoles.

Herein, we disclose a strategy for the asymmetric dearomatization of N-arylacyl indoles via a palladium-catalyzed tandem Heck/carbonylation, leading to an array of indoline-3-carboxylates bearing vicinal C2-aza-quaternary and C3 tertiary stereocenters in high yields and excellent enantio- and diastereoselectivities. This study is an important advance in the field of asymmetric carbonylation and enantioselective dearomatization reactions.

Hyper-Crosslinked Porous Chiral Phosphoric Acids: Robust Solid Organocatalysts for Asymmetric Dearomatization Reactions

Hyper-Crosslinked Porous Chiral Phosphoric Acids: Robust Solid Organocatalysts for Asymmetric Dearomatization Reactions

Concise Enantioselective Total Synthesis of Daphenylline Enabled by an Intramolecular Oxidative Dearomatization.

Daphenylline is a structurally unique member of the triterpenoid Daphniphyllum natural alkaloids, which exhibit intriguing biological activities. Six total syntheses have been reported, five of which utilize aromatization approaches. Herein, we report a concise protecting-group-free total synthesis by means of a novel intramolecular oxidative dearomatization reaction, which concurrently generates the critical seven-membered ring and the quaternary-containing vicinal stereocenters. Other notable transformations include a tandem reductive amination/amidation double cyclization reaction, to assemble the cage-like architecture, and installation of the other two chiral stereocenters via a highly enantioselective rhodium-catalyzed challenging hydrogenation of the diene intermediate (90% e.e.) and an unprecedented remote acid-directed Mukaiyama-Michael reaction of the complex benzofused cyclohexanone (13:1 d.r.).

Cover Feature: Asymmetric Direct/Stepwise Dearomatization Reactions Involving Hypervalent Iodine Reagents (Chem. Asian J. 4/2022)

Cyclic unsaturated ketone frameworks, which are obtained as the dearomatized products of phenols and their derivatives, are valuable to the synthesis of complex molecules and also contribute to the generation of products that can be readily employed for further transformations. Herein, the use of hypervalent iodine compounds to access enantioenriched compounds through direct and stepwise dearomatization reactions have been elaborated. More information can be found in the Review by Ravi Kumar, Fateh V. Singh, Naoko Takenaga, and Toshifumi Dohi.

Chemo-, regio- and enantioselective dearomative (3+2) reaction of non-functionalized 1-naphthols

The catalytic asymmetric dearomatization reaction of non-functionalized arenes poses a long-standing synthetic challenge to organic chemists because of the relative ease of rearomatization via the departure of a proton. In this work, the direct dearomatization of non-functionalized 1-naphthols was achieved through a phosphoric acid-catalyzed asymmetric (3+2) annulation reaction with azoalkenes. The reported convergent method allows the use of readily available simple 1-naphthols without pre-functionalization under mild conditions, furnishing a variety of tricyclic hexahydrobenz[e]indole derivatives in good yields and excellent enantioselectivities (75%–96% yields and 92%–99% ee). Density functional theory (DFT) calculations were performed to gain insights into the origins of the observed chemo-, regio-, and enantioselectivities. It is noteworthy that using azoalkenes as 1,3-dipole surrogates, in combination with powerful chiral phosphoric acid (CPA) catalysis, was key to the success of current reaction.

A tandem asymmetric oxidation-oxa-Michael sequence for dearomatization of β-naphthols

A catalytic asymmetric hydroxylative dearomatization reaction has been disclosed, and the products can smoothly transform into spiroannulation adducts by simply treated with a base under mild conditions. Novel in-situ generated magnesium catalytic methods are developed by application of combinational ligands. Related concise transformaitons of the spiroannulation adducts have been carried out.

Оптимальные условия одновременного протекания реакций гидрирования ароматических углеводородов и изомеризации в процессе депарафинизации дизельного топлива

This paper presents research to determine optimal conditions for simultaneous reactions of dearomatization and hydrodewaxing to evaluate high margin production of low viscosity hydrocarbon base for drilling fluids at dewaxing section of unit LCH-24/7 without recycle. Influence of one of the key factors, namely temperature, on the course of reaction has been studied. This research has been performed with the use of platinum containing dewaxing catalyst at laboratory unit for the study of hydorprocesses. It has been determined that the key factor is temperature 280°С when hydrodewaxing reactions start to prevail over dearomatization reactions. In course of research the content value of aromatics compounds in diesel fuel has been reduced to level of 7%, which is the basis for further research to evaluate the influence of other parameters, such as pressure and volumetric feed rate.

Visible-light induced dearomatization reactions

Dearomatization reactions provide rapid access to structurally complex three-dimensional molecules from simple aromatic compounds. Plenty of reports have demonstrated their utilities in the synthesis of natural products, medicinal chemistry, and materials science in the last decades. Recently, visible-light mediated photocatalysis has emerged as a powerful tool to promote many kinds of transformations. The dearomatization reactions induced by visible-light have also made significant progress during the past several years. This review provides an overview of visible-light induced dearomatization reactions classified based on the manner in which aromaticity is disrupted.

Merging dearomatization with redox-neutral C(sp3)–H functionalization via hydride transfer/cyclization: recent advances and perspectives

This review highlights the encouraging advances in hydride transfer-involved dearomatization reaction during the past decade, the content of which is categorized according to the hydride acceptors, namely vinylogous imines and quinone methides.

Metal-free dearomatization reactions of naphthol-ynamides for the divergent and enantioselective synthesis of azaspirocycles

An efficient Brønsted acid (BA) catalyzed intramolecular dearomatization cyclization of naphthol-ynamides has been developed, enabling the practical and divergent synthesis of two azaspirocycles in high yields.

Anodic dearomatization of 2-alkynylanilines for the synthesis of multi-functionalized indoles.

An anodic oxidative dearomatization reaction of 2-alkynylanilines was developed. The formed dearomatized compounds were used as versatile precursors in the synthesis of a variety of benzenoid ring multi-functionalized indoles through simple conversions.

Chiral Brønsted Acid-Catalyzed Dearomatization Reactions by Direct Activation of Ynamides

Key words dearomatization - Brønsted acids - asymmetric catalysis - ynamides - alkynes

Asymmetric Direct/Stepwise Dearomatization Reactions Involving Hypervalent Iodine Reagents.

A remarkable growth in hypervalent iodine-mediated oxidative transformations as stoichiometric reagents as well as catalysts has been well-documented due to their excellent properties, such as mildness, easy handling, high selectivity, environmentally friendly nature, and high stability. This review aims at highlighting the asymmetric oxidative dearomatization reactions involving hypervalent iodine compounds. The present article summarizes asymmetric intra- and intermolecular dearomatization reactions using chiral hypervalent iodine reagents/catalysts as well as hypervalent iodine-mediated dearomatization reactions followed by desymmetrization.

Silylpyrrole Oxidation En Route to Saxitoxin Congeners Including 11-Saxitoxinethanoic Acid.

Saxitoxin (STX) is the archetype of a large family (>50) of architecturally distinct, bisguanidinium natural products. Among this collection of isolates, two members, 11-saxitoxinethanoic acid (11-SEA) and zetekitoxin AB (ZTX), are unique, bearing carbon substitution at C11. A desire to efficiently access these compounds has motivated the development of new tactical approaches to a late-stage C11-ketone intermediate 26, designed to enable C-C bond formation using any one of a number of possible reaction technologies. Highlights of the synthesis of 26 include a metal-free, silylpyrrole oxidative dearomatization reaction and a vinylsilane epoxidation-rearrangement cascade to generate the requisite ketone. Nucleophilic addition to 26 makes possible the preparation of unnatural C11-substituted STXs. Olefination of this ketone is also demonstrated and, when followed by a redox-neutral isomerization reaction, affords 11-SEA.

Development of Novel Methodology Using Diazo Compounds and Metal Catalysts.

The ability to control the reactions of highly active chemical species to enable straightforward synthesis of valuable compounds such as bioactive natural products and pharmaceuticals is a continuing challenge in synthetic organic chemistry. This review describes the development of a methodology using reactive metal-carbene species and its synthetic application in our laboratory. First, regioselective synthesis of γ-amino acid equivalents to take advantage of their metal-dependent reactivities and the mechanistic rationale are presented. Chemoselective and enantioselective dearomatization reactions of several arenes with silver-carbene are also discussed. In the second half of the review, we discuss a carbene-insertion reaction into an amide and urea C-N bond for the assembly of nitrogen-bridged cyclic molecules.

Dinuclear Zinc Catalyzed Enantioselective Dearomatization [3+2] Annulation of 2-Nitrobenzofurans and 2-Nitrobenzothiophenes.

The application of dinuclear zinc catalysts in a dearomatization reaction has been developed. Catalytic asymmetric dearomatization [3+2] annulations of 2-nitrobenzofurans or 2-nitrobenzothiophenes with CF3 -containing N-unprotected isatin-derived azomethine ylides catalyzed by dinuclear zinc catalysts are realized with excellent diastereomer ratios (dr) of >20 : 1 and enantiomeric excess (ee) of up to 99 %. This protocol provides a practical, straightforward access to structurally diverse pyrrolidinyl spirooxindoles containing a 2,3-fused-dihydrobenzofuran (or dihydrobenzothiphene) moiety, and four contiguous stereocenters. Reactions can be performed on a gram scale. The absolute configuration of products is confirmed by X-ray single crystal structure analysis, and a possible mechanism is proposed.

Direct Cyclopropanation of Quinolinium Zwitterionic Thiolates via Dearomative Reactions.

A one-pot, two-step protocol for the synthesis of libraries of remarkable functionalized sulfone analogues of 9b,10,10a,10b-tetrahydro-1H-cyclopropa[c][1,4]thiazino[4,3-a]quinolines is described. A class of various functionalized molecular skeletons was obtained by cyclopropanation of quinolinium zwitterionic thiolates. The reaction pathway involves the formation of a [2 + 1] cycloaddition intermediate followed by a [5 + 1] cycloaddition.

Asymmetric dearomatization catalysed by chiral Brønsted acids via activation of ynamides.

Chiral Brønsted acid-catalysed asymmetric synthesis has received tremendous interest over the past decades, and numerous efficient synthetic methods have been developed based on this approach. However, the use of chiral Brønsted acids in these reactions is mostly limited to the activation of imine and carbonyl moieties, and the direct activation of carbon-carbon triple bonds has so far not been invoked. Here we show that chiral Brønsted acids enable the catalytic asymmetric dearomatization reactions of naphthol-, phenol- and pyrrole-ynamides by the direct activation of alkynes. This method leads to the practical and atom-economic construction of various valuable spirocyclic enones and 2H-pyrroles that bear a chiral quaternary carbon stereocentre in generally good-to-excellent yields with excellent chemo-, regio- and enantioselectivities. The activation mode of chiral Brønsted acid catalysis revealed in this study is expected to be of broad utility in catalytic asymmetric reactions that involve ynamides and the related heteroatom-substituted alkynes.

Organocatalytic Asymmetric Dearomatization Reaction for the Synthesis of Axial Chiral Allene-Derived Naphthalenones Bearing Quaternary Stereocenters.

The highly regio-, diastereo-, and enantioselective dearomatization reaction of 1-substituted 2-naphthols and β,γ-alkynyl-α-imino esters with complete atom economy is disclosed via chiral phosphoric acid catalysis. This protocol provides facile and efficient access to asymmetric construction of a broad range of axially chiral allene-derived naphthalenones bearing quaternary stereocenters in good yields with high diastereoselectivities and enantioselectivities.

Silver‐Catalyzed Asymmetric Dearomatization of Electron‐Deficient Heteroarenes via Interrupted Barton–Zard Reaction

AbstractHerein we report a catalytic asymmetric dearomatization reaction of electron‐deficient heteroarenes with α‐substituted isocyanoacetates through an interrupted Barton–Zard reaction. A range of optically active pyrrolo[3,4‐b]indole derivatives was obtained in good yields (up to 97 %) with high stereoselectivities (up to >20:1 dr and 97 % ee), using a catalytic system consisting of a cinchona‐derived amino‐phosphine and silver oxide. This reaction features wide substrate scope and mild conditions, and provides a new strategy for developing asymmetric dearomatization reactions.