Showing papers on "Annulation published in 2020"
TL;DR: A series of l-pyroglutamic acid-derived bifunctional NHCs bearing a free hydroxyl group which can interact with carbonyl or imino groups via hydrogen-bonding worked well for a variety of reactions and could not only improve but also switch the enantioselectivity to get products with opposite stereochemistry through H-bond controlled stereochemical directing.
Abstract: In nature, enzymes are a powerful medium for the construction of enantiomerically pure chemicals, which always inspires synthetic chemists to explore new catalysts to imitate the enzyme machinery for asymmetric transformations. Vitamin B1, a bifunctional thiazolium N-heterocyclic carbene (NHC) precursor, is the coenzyme for transketolase. In the past two decades, a series of chiral NHCs, including monocyclic, bicyclic, tetracyclic, and even bridged ones, have been synthesized and successfully utilized as efficient organocatalysts for a wide variety of asymmetric organic reactions. The utility of bifunctional catalysts can enhance catalytic activity and improve stereochemical control through their synchronous activation of both reaction partners. However, the NHCs possessing multiple activation sites are far less developed.This Account gives an overview of our research on the design, development, and applications of bifunctional NHCs in organocatalysis. We synthesized a series of l-pyroglutamic acid-derived bifunctional NHCs bearing a free hydroxyl group which can interact with carbonyl or imino groups via hydrogen-bonding. Further studies revealed that these bifunctional catalysts worked well for a variety of reactions. We have developed bifunctional NHC-catalyzed aza-benzoin reactions, [2 + 2], [2 + 3], and [2 + 4] cycloadditions of ketenes, [3 + 2] and [3 + 4] annulations of enals, and aza-MBH and Rauhut-Currier reactions of Michael acceptors. In addition to these reactions via nucleophilic Breslow intermediates, enolates, homoenolates, and zwitterionic azolium intermediates, the bifunctional NHC-catalyzed [3 + 3] annulation via 1,3-biselectrophilic α,β-unsaturated acyl azolium intermediates was also developed.In these reactions, bifunctional NHCs showed amazing effects compared to normal nonbifunctional NHCs. In some cases, the bifunctional NHCs facilitated reactions which did not work under normal NHC catalysis, possibly due to additional activation via H-bonding. More interestingly, the bifunctional NHCs could not only improve but also switch the enantioselectivity to get products with opposite stereochemistry through H-bond controlled stereochemical directing. Furthermore, the reaction mode could be totally changed from [3 + 2] to [3 + 4] annulation to give kinetically favored products when bifunctional NHCs were employed. In future, the applications of bifunctional NHCs in other challenging reactions, such as asymmetric reactions with carbon-carbon unsaturated bonds, and the reactions involving alkyl or heteroatom radicals will be the major focus in our group.
192 citations
01 Jan 2020
TL;DR: A catalytic system comprised of an N-heterocyclic carbene and an iridium complex can be used for the asymmetric, diastereodivergent synthesis of γ-butyrolactones and the synthetic utility was illustrated in the concise synthesis of the naturally occurring lignan (−)-hinokinin.
Abstract: The stereodivergent synthesis of natural product frameworks via a single transformation using simple starting materials is a significant challenge. The prevalence of γ-butyrolactones in biologically active natural products has long motivated the development of enantioselective strategies towards their synthesis. Herein, we report an enantio- and diastereodivergent [3 + 2] annulation reaction for the synthesis of α,β-disubstituted γ-butyrolactones through cooperative N-heterocyclic carbene organocatalysis and iridium catalysis. This method overcomes the challenges of merging N-heterocyclic carbene organocatalysis with iridium catalysis by the appropriate choice of ligands. The use of two chiral catalysts allowed control over the relative and absolute configuration of the two formed stereocentres, thereby providing selective access to all four possible stereoisomers of the γ-lactone products. The transformation could be extended to the synthesis of δ-lactams via [4 + 2] annulation. The synthetic utility of this methodology was illustrated in the concise synthesis of the naturally occurring lignan (−)-hinokinin. Methods to allow access to all isomers of a product are both valuable and challenging to achieve. Here the authors report a catalytic system comprised of an N-heterocyclic carbene and an iridium complex, and show that it can be used for the asymmetric, diastereodivergent synthesis of γ-butyrolactones.
154 citations
90 citations
TL;DR: Atroposelective synthesis of biaryl NH isoquinolones via Rh(III)-catalyzed C-H activation of benzamides and intermolecular [4+2] annulation with a broad scope of 2-substituted 1-alkynylnaphthalenes as well as sterically hindered symmetric diarylacetylenes is reported.
Abstract: Reported herein is the atroposelective synthesis of biaryl NH isoquinolones by RhIII -catalyzed C-H activation of benzamides and intermolecular [4+2] annulation for a broad scope of 2-substituted 1-alkynylnaphthalenes, as well as sterically hindered, symmetric diarylacetylenes. The axial chirality is constructed based on dynamic kinetic transformation of the alkyne in redox-neutral annulation with benzamides, with alkyne insertion being stereodetermining. The reaction accommodates both benzamides and heteroaryl carboxamides and proceeds in excellent regioselectivity (if applicable) and enantioselectivities (average 91.8 % ee). An enantiomerically and diastereomerically pure rhodacyclic complex was prepared and offers insight into enantiomeric control of the coupling system, wherein the steric interactions between the amide directing group and the alkyne substrate dictate both the regio- and enantioselectivity.
79 citations
TL;DR: Reactions promoted by fluorinated alcohols, including nucleophilic substitution reactions, annulation reactions, electrophilic reactions, dearomatization reactions, functionalization of multiple bond, epoxidation reactions and miscellaneous reactions have been summarized in this account.
Abstract: Fluorinated alcohols have been widely used in the synthetic organic chemistry over the past decades. The unique properties such as the strong hydrogen-bonding donor ability and low nucleophilicity allow them to promote organic reactions in the absence of any catalyst. These approaches have distinct advantages in terms of operational simplicity, practicability and environmental friendliness. Reactions promoted by fluorinated alcohols, including nucleophilic substitution reactions, annulation reactions, electrophilic reactions, dearomatization reactions, functionalization of multiple bond, epoxidation reactions and miscellaneous reactions have been summarized in this account.
77 citations
TL;DR: In this article, the authors targeted electrochemical annulation reactions involving mediators and mediator-free conditions with generation of new C-C, C-heteroatom and heteroatom heteroatoms, their mechanistic insights, as well as the reactivity of substrates.
75 citations
TL;DR: The electrochemical synthesis of highly functionalized 1-naphthols using alkynes and 1,3-dicarbonyl compounds by (4 + 2) annulation of C-centered radical under electrochemical conditions showed good antitumor activity in vitro, and further studies indicated that compound 3bl induced tumor cell apoptosis.
73 citations
TL;DR: Transition-metal-catalyzed C-H activation followed by oxidative cyclization with unsaturated coupling partners has been a valuable synthetic tool for the multiring molecular scaffolds as mentioned in this paper.
Abstract: Transition-metal-catalyzed C–H activation followed by oxidative cyclization with unsaturated coupling partners has been a valuable synthetic tool for the multiring molecular scaffolds. This Perspec...
71 citations
TL;DR: An electrooxidative protocol for the regioselective dearomatization annulation of indoles and benzofurans under undivided cell conditions and obtain five- to eight-membered fused heterocycles is reported.
Abstract: The dearomatization of arenes represents a powerful synthetic methodology to provide three-dimensional chemicals of high added value. Here we report a general and practical protocol for regioselective dearomative annulation of indole and benzofuran derivatives in an electrochemical way. Under undivided electrolytic conditions, a series of highly functionalized five to eight-membered heterocycle-2,3-fused indolines and dihydrobenzofurans, which are typically unattainable under thermal conditions, can be successfully accessed in high yield with excellent regio- and stereo-selectivity. This transformation can also tolerate a wide range of functional groups and achieve good efficiency in large-scale synthesis under oxidant-free conditions. In addition, cyclic voltammetry, electron paramagnetic resonance (EPR) and kinetic studies indicate that the dehydrogenative dearomatization annulations arise from the anodic oxidation of indole into indole radical cation, and this process is the rate-determining step. Enriching the chemical space of polycyclic heterocycles is of high value in chemical biology. Here, the authors report an electrooxidative protocol for the regioselective dearomative annulation of indoles and benzofurans under undivided cell conditions and obtain five- to eight-membered fused heterocycles.
70 citations
TL;DR: P palladium-catalyzed, regiodivergent[5 + 4] and [5 + 2] annulations of vinylethylene carbonates and allylidenemalononitriles are reported, describing the production of over 50 examples of nine- and seven-membered heterocycles in high isolated yields and excellent regioselectivities.
Abstract: Medium-sized heterocycles exist in a broad spectrum of biologically active natural products and medicinally important synthetic compounds. The construction of medium-sized rings remains challenging, particularly the assembly of different ring sizes from the same type of substrate. Here we report palladium-catalyzed, regiodivergent [5 + 4] and [5 + 2] annulations of vinylethylene carbonates and allylidenemalononitriles. We describe the production of over 50 examples of nine- and seven-membered heterocycles in high isolated yields and excellent regioselectivities. We demonstrate the synthetic utility of this approach by converting a nine-membered ring product to an interesting polycyclic caged molecule via a [2 + 2] transannulation. Mechanistic studies suggest that the [5 + 2] annulation proceeds through palladium-catalyzed ring-opening/re-cyclization from the [5 + 4] adducts.
69 citations
TL;DR: A modular electrochemical synthesis of aza‐PAHs was developed via a rhodium‐catalyzed cascade C−H activation and alkyne annulation through a multifunctional O‐methylamidoxime enabled the high chemo‐ and regioselectivity.
Abstract: Nitrogen-doped polycyclic aromatic hydrocarbons (aza-PAHs) have found broad applications in material sciences. Herein, a modular electrochemical synthesis of aza-PAHs was developed via a rhodium-catalyzed cascade C-H activation and alkyne annulation. A multifunctional O-methylamidoxime enabled the high chemo- and regioselectivity. The isolation of two key rhodacyclic intermediates made it possible to delineate the exact order of three C-H activation steps. In addition, the metalla-electrocatalyzed multiple C-H transformation is characterized by unique functional group tolerance, including highly reactive iodo and azido groups.
TL;DR: A novel Pd(0)-catalyzed asymmetric [4+3] annulation reaction of two readily accessible starting materials has been developed for building seven-membered heterocyclic architectures, leading to valuable tetrahydroazepines and benzo[b]oxepines.
Abstract: A novel Pd0 -catalyzed asymmetric [4+3] annulation reaction of two readily accessible starting materials has been developed for building seven-membered heterocyclic architectures. The potential [3+2] side pathway could be suppressed though fine tuning of the conditions. A broad scope of cycloaddition donors and acceptors participated in the transformation with excellent chemo-, regio-, diastereo-, and enantioselectivtities, leading to valuable tetrahydroazepines and benzo[b]oxepines.
TL;DR: Owing to the mild reaction conditions, the good stereoselectivity profile, and the ready availability of the functionalized precursors, this process constitutes a useful and straightforward strategy for the synthesis of densely functionalized silacycles.
Abstract: A novel and unusual palladium-catalyzed [4+2] annulation of cyclopropenes with benzosilacyclobutanes is reported. This reaction occurred through chemoselective Si-C(sp2 ) bond activation in synergy with ring expansion/insertion of cyclopropenes to form new C(sp2 )-C(sp3 ) and Si-C(sp3 ) bonds. An array of previously elusive bicyclic skeleton with high strain, silabicyclo[4.1.0]heptanes, were formed in good yields with excellent diastereoselectivity under mild conditions. An asymmetric version of the reaction with a chiral phosphoramidite ligand furnished a variety of chiral bicyclic silaheterocycle derivatives with good enantioselectivity (up to 95.5:4.5 er). Owing to the mild reaction conditions, the good stereoselectivity profile, and the ready availability of the functionalized precursors, this process constitutes a useful and straightforward strategy for the synthesis of densely functionalized silacycles.
TL;DR: An efficient synthetic method of 3,4-unsubstituted isocoumarins adopting an electron-deficient CpERh complex as the catalyst is introduced and an unprecedented "rhodium shift" event within the catalytic cycle is found.
TL;DR: The electrosynthesis offers sustainable and efficient access to construct spirocyclohexadienone-containing (E)-indenes without any additional catalyst or oxidant through a sulfonyl-radical-triggered 1,6-addition and an I+-mediated ipso-cyclization cascade.
TL;DR: A Rh-catalyzed C-H/C-H vinylene cyclization adopting vinylene carbonate as a "vinylene transfer" agent achieves the direct annulative π-extension of imidazole- and pyrazole-fused aromatics.
TL;DR: In this article, a critical review highlights the recent advances in coupling of heterocyclic alkenes by transition-metal-catalyzed reactions with special emphasis on arylation, alkenylation, alkylation, hydroarylation, ring-opening addition and annulation/cyclization via the C-H functionalization strategy reported since 2015.
Abstract: Heterocyclic alkenes represent an important class of reactive feedstock and valuable synthons for the synthesis of biologically important heterocyclic scaffolds. Although functionalized heterocyclic alkenes and their derivatives can be accessed via metal-catalyzed cross-coupling reactions, yet the prefunctionalisation of starting materials makes the process a bit cumbersome. On the other hand, transition-metal-catalyzed C–H functionalization is one of the most persuasive and front-line research areas in modern synthetic organic chemistry for atom/step-economy, viability and high efficacy. This critical review highlights the recent advances in coupling of heterocyclic alkenes by transition-metal-catalyzed reactions with special emphasis on arylation, alkenylation, alkylation, hydroarylation, ring-opening addition and annulation/cyclization via the C–H functionalization strategy reported since 2015.
TL;DR: In this article, a three-component annulation-halosulfonylation of 1,6-enynes has been developed for stereoselective synthesis of 33 examples of 1-indanones with generally good yields under environmentally benign conditions.
TL;DR: This C-H activation approach enables the most straightforward and convergent synthesis of C6-substituted isoquinolino[1,2-b]quinazolines reported to date, and operates with exquisite N-lactam cyclization selectivity, thus enabling expedient access to new heterocyclic analogues featuring promising cytotoxic properties.
Abstract: We report the synthesis of C6-substituted isoquinolino[1,2-b]quinazolinones via rhodium(III)-catalyzed C-H annulation with sulfoxonium ylides and evaluation of the cytotoxic activity of the scaffold. This C-H activation approach enables the most straightforward and convergent synthesis of C6-substituted isoquinolino[1,2-b]quinazolines reported to date. This operationally simple method is compatible with a wide variety of the sulfoxonium ylide and arene C-H activation coupling partners, permitting access to diverse isoquinolino[1,2-b]quinazolines. This method shows a high atom economy, generating H2O and dimethyl sulfoxide (DMSO) as by-products. This method is scalable and operates with exquisite N-lactam cyclization selectivity, thus enabling expedient access to new heterocyclic analogues featuring promising cytotoxic properties.
TL;DR: Preliminary mechanism studies indicate that the electrooxidation annulation proceeds through radical-radical cross-coupling between in situ generated indole radical cation and N-centered radical.
Abstract: Dearomative annulation of indoles has emerged as a powerful tool for the preparation of polycyclic indoline-based alkaloids. Compared with well-established methods towards five-membered-ring-fused indolines, the six-membered-ring-fused indolines are rarely accessed under thermal conditions. Herein, a dearomative [4+2] annulation between different indoles is developed through an electrochemical pathway. This transformation offers a remarkably regio- and stereoselective route to highly functionalized pyrimido[5,4-b]indoles under oxidant- and metal-free conditions. Notably, this electrochemical approach maintains excellent functional-group tolerance and can be extended as a modification tactic for pharmaceutical research. Preliminary mechanism studies indicate that the electrooxidation annulation proceeds through radical-radical cross-coupling between an indole radical cation and an N-centered radical generated in situ.
TL;DR: The Co(III)-catalyzed redox-neutral annulation of benzamides and acrylamides with vinylene carbonate for the synthesis of isoquinolinones and pyridinones has been developed, affording the target products with good to excellent yields.
TL;DR: 1,2,3,4-tetrahydroacridine, which is the core skeleton of tacrine (an Alzheimer's disease drug), was conveniently synthesized.
TL;DR: A feasible arylaminomethyl radical-triggered tandem annulation reaction has been developed toward a large variety of poly fused heterocycles, tetrahydroimidazo[1,5-a]quinoxalin-4(5H)-ones, by reacting diverse quinoxalin (1H)ones with various N-arylglycines in green solvent (DMC) in the presence of CsPbBr3.
TL;DR: In this article, the authors report the synthesis and study of two soluble microporous ladder polymers, CANAL-TBs, by combining catalytic arene-norbornene annulation (CANAL) and Troger's base (TB) formation.
Abstract: We report the facile synthesis and study of two soluble microporous ladder polymers, CANAL–TBs, by combining catalytic arene-norbornene annulation (CANAL) and Troger’s base (TB) formation. The poly...
TL;DR: An unprecedented divergent synthesis of pyrazolo[1,2-a]pyrazolones and 2-acylindoles via Rh(III)-catalyzed [4 + 1] or [3 + 2] annulation of 1-phenylpyrazolidinones with alkynyl cyclobutanols through redox-neutral multiple bond activation by using -NH and -OH units as directing groups is presented.
TL;DR: A ruthenium‐catalyzed electrochemical dehydrogenative annulation reaction of imidazoles with alkynes has been established, enabling the preparation of various bridgehead N‐fused [5,6]‐bicyclic heteroarenes through regioselective electrochemical C−H/N−H annulation without chemical metal oxidants.
Abstract: A ruthenium-catalyzed electrochemical dehydrogenative annulation reaction of imidazoles with alkynes has been established, enabling the preparation of various bridgehead N-fused [5,6]-bicyclic heteroarenes through regioselective electrochemical C-H/N-H annulation without chemical metal oxidants. Novel azaruthenabicyclo[3.2.0]heptadienes were fully characterized and identified as key intermediates. Mechanistic studies are suggestive of an oxidatively induced reductive elimination pathway within a ruthenium(II/III) regime.
TL;DR: Twofold C-H annulation of readily available formamides and alkynes without built-in chelating groups was achieved, providing a series of chiral ferrocenes in 40-98% yield and 93-99% ee.
Abstract: Twofold C-H annulation of readily available formamides and alkynes without built-in chelating groups was achieved. Ni-Al bimetallic catalysis enabled by a bulky BINOL-derived chiral secondary phosphine oxide (SPO) ligand proved to be critical for high reactivity and high selectivity. This reaction uses readily available formamides as starting materials and provides a concise synthetic pathway to a broad range of chiral ferrocenes in 40-98 % yield and 93-99 % ee.
TL;DR: The domino C-H alkenylation and chromone annulation of the enaminones are involved, which enables the synthesis of 3-vinyl chromone products using both terminal and internal alkenes via a key process of transient C- H halogenation.
TL;DR: A chiral tertiary amine-catalyzed asymmetric γ-regioselective (4 + 3) annulation reaction of isatin-derived Morita-Baylis-Hillman carbonates and 1-azadienes was developed, delivering chiral azepane spirooxindoles with excellent stereoselectivity.