Showing papers on "Annulation published in 2019"
TL;DR: This review concentrates on the advances made in the last five years in CO2-incorporated cyclization triggered by N-, O-, and C-nucleophiles.
Abstract: Carbon dioxide (CO2) has emerged as a sustainable, feasible, abundant one-carbon synthon and displays great potential in the synthesis of heterocycles such as lactones, lactams, and 2-oxazolidinones, which are privileged motifs in pharmaceutical chemistry demonstrating bioactivities. Although the fixation of CO2 is restricted due to its thermodynamic stability and kinetic inertness, multiple breakthroughs have been realized in annulation chemistry. This review concentrates on the advances made in the last five years in CO2-incorporated cyclization triggered by N-, O-, and C-nucleophiles. Three transformation modes of CO2 including carboxylative cyclization, carbonylative cyclization, and reductive cyclization have been summarized. Moreover, typical mechanisms and significant applications of these reactions are also described.
221 citations
TL;DR: This Account is aimed at highlighting the recent developments in the N-heterocyclic carbene (NHC)-catalyzed generation of α,β-unsaturated acylazolium intermediates and their subsequent reactivity with (bis)nucleophiles thereby shedding light on the power of this NHC-bound intermediate in organocatalysis.
Abstract: ConspectusThis Account is aimed at highlighting the recent developments in the N-heterocyclic carbene (NHC)-catalyzed generation of α,β-unsaturated acylazolium intermediates and their subsequent reactivity with (bis)nucleophiles thereby shedding light on the power of this NHC-bound intermediate in organocatalysis. This key intermediate can be generated by the addition of NHCs to α,β-unsaturated aldehyde or acid derivatives. A wide variety of bisnucleophiles can add across the α,β-unsaturated acylazoliums to form various five and six-membered heterocycles and carbocycles. Moreover, suitably substituted nucleophiles can add to this intermediate and result in valuable products following cascade processes. Employing chiral NHCs in the process can result in the enantioselective synthesis of valuable compounds.In 2013, we developed a unified strategy for the enantioselective synthesis of dihydropyranones and dihydropyridinones by the NHC-catalyzed formal [3 + 3] annulation of 2-bromoenals with readily available...
217 citations
154 citations
145 citations
TL;DR: A ‘click’ reaction is developed for the simple and rapid formation of azides from primary amines, and is used to prepare a library of over 1,200 azides for subsequent use in the existing triazole annulation click reaction.
Abstract: Click chemistry is a concept in which modular synthesis is used to rapidly find new molecules with desirable properties1. Copper(i)-catalysed azide–alkyne cycloaddition (CuAAC) triazole annulation and sulfur(vi) fluoride exchange (SuFEx) catalysis are widely regarded as click reactions2–4, providing rapid access to their products in yields approaching 100% while being largely orthogonal to other reactions. However, in the case of CuAAC reactions, the availability of azide reagents is limited owing to their potential toxicity and the risk of explosion involved in their preparation. Here we report another reaction to add to the click reaction family: the formation of azides from primary amines, one of the most abundant functional groups5. The reaction uses just one equivalent of a simple diazotizing species, fluorosulfuryl azide6–11 (FSO2N3), and enables the preparation of over 1,200 azides on 96-well plates in a safe and practical manner. This reliable transformation is a powerful tool for the CuAAC triazole annulation, the most widely used click reaction at present. This method greatly expands the number of accessible azides and 1,2,3-triazoles and, given the ubiquity of the CuAAC reaction, it should find application in organic synthesis, medicinal chemistry, chemical biology and materials science. A ‘click’ reaction is developed for the simple and rapid formation of azides from primary amines, and is used to prepare a library of over 1,200 azides for subsequent use in the existing triazole annulation click reaction.
138 citations
TL;DR: The scope of biaryl synthesis with arenediazonium salts has enormously expanded in recent years through applications of transition metal/photoredox-catalysed cross-coupling, thermal/photosensitized radical chain CH-arylation of (hetero)arenes and arylative radical annulation reactions with alkynes.
Abstract: The rich legacy of arenediazonium salts in the synthesis of unsymmetrical biaryls, built around the seminal works of Pschorr, Gomberg and Bachmann more than a century ago, continues to make important contributions at various evolutionary stages of modern biaryl synthesis. Based on in-depth mechanistic analysis and design of novel pathways and reaction conditions, the scope of biaryl synthesis with arenediazonium salts has enormously expanded in recent years through applications of transition metal/photoredox-catalysed cross-coupling, thermal/photosensitized radical chain CH-arylation of (hetero)arenes and arylative radical annulation reactions with alkynes. These recent developments have provided facile synthetic access to a wide variety of unsymmetrical biaryls of pharmaceutical, agrochemical and optoelectronic importance with green scale-up options and created opportunities for late-stage modification of peptides, nucleosides, carbon nanotubes and electrodes, the details of which are captured in this review.
129 citations
TL;DR: The formation of large π-conjugated systems on the organic linker dramatically enhanced the photoresponsive properties of PCN-136, which was employed as an inherent photocatalytic system for CO2 reduction under visible-light irradiation, which showed increased activity compared with pbz-MOF-1.
Abstract: The incorporation of large π-conjugated ligands into metal-organic frameworks (MOFs) can introduce intriguing photophysical and electrochemical properties into the framework. However, these effects are often hindered by the strong π-π interaction and the low solubility of the arylated ligands. Herein, we report the synthesis of a porous zirconium-based MOF, Zr6(μ3-O)4(μ3-OH)4(OH)6(H2O)6(HCHC) (PCN-136, HCHC = hexakis(4-carboxyphenyl)hexabenzocoronene), which is composed of a hexacarboxylate linker with a π-conjugated hexabenzocoronene moiety. Direct assembly of the Zr4+ metal centers and the HCHC ligands was unsuccessful due to the low solubility and the unfavorable conformation of the arylated HCHC ligand. Therefore, PCN-136 was obtained from aromatization-driven postsynthetic annulation of the hexaphenylbenzene fragment in a preformed framework (pbz-MOF-1) to avoid π-π stacking. This postsynthetic modification was done through a single-crystal-to-single-crystal transformation and was clearly observable utilizing single -crystal X-ray crystallography. The formation of large π-conjugated systems on the organic linker dramatically enhanced the photoresponsive properties of PCN-136. With isolated hexabenzocoronene moieties as photosensitizers and Zr-oxo clusters as catalytic sites, PCN-136 was employed as an inherent photocatalytic system for CO2 reduction under visible-light irradiation, which showed increased activity compared with pbz-MOF-1.
120 citations
TL;DR: A chiral Brønsted base-catalyzed asymmetric annulation of ortho-alkynylanilines has been developed to access axially chiral naphthyl-C2-indoles through vinylidene Ortho-quinone methides intermediates, providing a unique organocatalytic atroposelective route to axiallychiral aryl-C1-indole skeletons with excellent enantioselectivity and functional group tolerance.
Abstract: A chiral Bronsted base catalyzed asymmetric annulation of ortho-alkynylanilines has been developed to access axially chiral naphthyl-C2-indoles via vinylidene ortho-quinone methide (VQM) intermediates. This strategy provides a unique organocatalytic atroposelective route to axially chiral aryl-C2-indole skeletons with excellent enantioselectivity and functional-group tolerance. This transformation was applicable to decagram-scale preparation (50.0 g) with perfect enantioselectivity through simple recrystallization. Moreover, the utility of this reaction was demonstrated by a variety of transformations towards chiral naphthyl-C2-indoles for a series of carbon-heteroatom bond formations. Furthermore, the prepared axially chiral naphthyl-C2-indoles were applied as a chiral skeleton for organocatalytic aza-Baylis-Hillman reaction and asymmetric formal [4+2] tandem cyclization to give the corresponding adducts in high yields with improved enantioselectivity and diastereoselectivity.
99 citations
TL;DR: This method makes use of readily available 3-nitroindoles as an aromatic feedstock and rapidly delivers a wide range of cyclopentaindoline alkaloid scaffolds in a highly enantioselective manner.
Abstract: The dearomatization of 3-nitroindoles through a chiral-phosphine-mediated [3+2] annulation reaction is described. This method makes use of readily available 3-nitroindoles as an aromatic feedstock and rapidly delivers a wide range of cyclopentaindoline alkaloid scaffolds in a highly enantioselective manner. Notably, phosphine-triggered cyclization has not been utilized previously in a dearomatization process.
96 citations
TL;DR: The Ru-catalyzed enantioselective annulation of 1,4,2-dioxazol-5-ones to furnish γ-lactams in up to 97% yield and 98% ee via intramolecular carbonylnitrene C-H insertion is reported.
Abstract: We report the Ru-catalyzed enantioselective annulation of 1,4,2-dioxazol-5-ones to furnish γ-lactams in up to 97% yield and 98% ee via intramolecular carbonylnitrene C—H insertion. By employing chiral diphenylethylene diamine (dpen) as ligands bearing electron-withdrawing arylsulfonyl substituents, the reactions occur with remarkable chemo- and enantioselectivities; the competing Curtius-type rearrangement was largely suppressed. Enantioselective nitrene insertion to allylic/propargylic C—H bonds was also achieved with remarkable tolerance to the C═C and C≡C bonds.
93 citations
TL;DR: Interestingly, the selectivity to form the fused or spiro compounds could be switched by resorting to different additives, and the notable features of this protocol include simple substrates and excellent atom economy and regioselectivity.
TL;DR: The first enantioselective annulation of α-arylidene pyrazolones through a formal C(sp3 )-H activation under mild conditions enabled by highly variable RhIII -Cpx catalysts is reported.
Abstract: Herein, we report the first enantioselective annulation of α-arylidene pyrazolones through a formal C(sp3 )-H activation under mild conditions enabled by highly variable RhIII -Cpx catalysts. The method has a wide substrate scope and proceeds with good to excellent yields and enantioselectivities. Its synthetic utility was demonstrated by the late-stage functionalization of drugs and natural products as well as the preparation of enantioenriched [3]dendralenes. Preliminary biological investigations also identified the spiropyrazolones as a novel class of Hedgehog pathway inhibitors.
TL;DR: A monomeric streptavidin (mSav) Rh(III) ArM permits asymmetric synthesis of α,β-unsaturated-δ-lactams via a tandem C-H activation and [4+2] annulation reaction and results in improved stereocontrol and a 7-fold enhancement in reactivity relative to the isolated biotinylated Rh( III) cofactor.
Abstract: Reliable design of artificial metalloenzymes (ArMs) to access transformations not observed in nature remains a long-standing and important challenge. We report that a monomeric streptavidin (mSav) Rh(III) ArM permits asymmetric synthesis of α,β-unsaturated-δ-lactams via a tandem C-H activation and [4+2] annulation reaction. These products are readily derivatized to enantioenriched piperidines, the most common N-heterocycle found in FDA approved pharmaceuticals. Desired δ-lactams are achieved in yields as high as 99% and enantiomeric excess of 97% under aqueous conditions at room temperature. Embedding a Rh cyclopentadienyl (Cp*) catalyst in the active site of mSav results in improved stereocontrol and a 7-fold enhancement in reactivity relative to the isolated biotinylated Rh(III) cofactor. In addition, mSav-Rh outperforms its well-established tetrameric forms, displaying 11-33 times more reactivity.
TL;DR: This review highlights recent examples of natural product total syntheses employing transition metal-mediated/catalyzed carbonylative cyclization strategies to build key ring systems including cyclic ketones and phenols.
TL;DR: Selective synthesis of indole and quinazoline products was achieved through a precise control of the C-H activation/annulation by changing the additives from NaOAc to CuF2/CsOAc.
TL;DR: A novel ruthenium-catalyzed [5 + 1] annulation of 2-alkenylanilines with sulfoxonium ylides was developed for the rapid assembly of highly functionalized quinolines and could be obtained with good yields and excellent functional group tolerance.
TL;DR: The first (3+3)-annulation process of donor-acceptor cyclopropanes using synergistic catalysis is reported, to afford multiply substituted pyran scaffolds in high yield and diastereoselectivity.
Abstract: The first (3+3)-annulation process of donor-acceptor cyclopropanes using synergistic catalysis is reported. The Rh2 (OAc)4 -catalyzed decomposition of diazo carbonyl compounds generated carbonyl ylides in situ. These 1,3-dipoles were converted with donor-acceptor cyclopropanes, activated by Lewis acid catalysis, to afford multiply substituted pyran scaffolds in high yield and diastereoselectivity. Extensive optimization studies enabled access to 9-oxabicyclo[3.3.1]nonan-2-one and 10-oxabicyclo[4.3.1]decen-2-ol cores, exploiting solvent effects on intermediate reactivity.
TL;DR: A one-pot synthetic strategy for the synthesis of 2-alkylaminoquinolines through sequential dehydrogenative annulation and N-alkylation reaction has also been demonstrated.
TL;DR: The cleavage of the C-N bond in enaminones is confirmed by the experiment using 15 N-labeled enaminone and the reactions proceed well in the medium of pure water in the presence of molecular iodine, TBHP, and NaHCO3 via cascade C-H sulfonylation and pyrazole annulation.
Abstract: The cascade reactions between NH2-functionalized enaminones and sulfonyl hydrazines have been developed for the synthesis of fully substituted pyrazoles. By making use of the hydrophilic primary amino group in the enaminones, the reactions proceed well in the medium of pure water in the presence of molecular iodine, TBHP, and NaHCO3 via cascade C-H sulfonylation and pyrazole annulation. The cleavage of the C–N bond in enaminones is confirmed by the experiment using 15N-labeled enaminone.
TL;DR: A 4-HO-TEMPO-catalyzed redox strategy for the synthesis of pyridines through the annulation of cyclopropanols and oxime acetates has been developed in this article.
Abstract: A 4-HO-TEMPO-catalyzed redox strategy for the synthesis of pyridines through the annulation of cyclopropanols and oxime acetates has been developed. This protocol features good functional group tol...
TL;DR: A rhodium-catalyzed annulation between aroyl sulfoxonium ylides and anthranils has been developed to synthesize 10H-indolo[1,2-a]indol-10-one derivatives and the Aldol condensation constructed the second indole ring.
TL;DR: Rh(III)-catalyzed transannulation of arenes with 7-azabenzonorbornadienes for enantioselective synthesis of cis -dihydrocarbazoles and a chiral rhodacycle has been isolated as an active intermediate.
Abstract: C-H bond activation is mostly limited to ortho selectivity. Activation of both ortho and meta C-H bonds constitutes a particularly important strategy for annulation, but has rarely been studied in enantioselective systems. Reported herein is rhodium(III)-catalyzed asymmetric [3+2] transannulation of arenes with 7-azabenzonorbornadienes. Two distinct classes of arenes have been identified as substrates, and the coupling proceeded with high enantioselectivity and excellent diastereoselectivity through sequential activation of ortho and meta C-H bonds.
TL;DR: 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.
Abstract: 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.
TL;DR: In this article, a versatile, inexpensive, and nontoxic Cu(OAc)2 catalyst for isoindolones was accessed by cupraelectro-catalyzed C-H activation with electricity as terminal oxidant.
Abstract: Synthetically meaningful isoindolones were accessed by cupraelectro-catalyzed C–H activation with electricity as terminal oxidant Thus, a versatile, inexpensive, and nontoxic Cu(OAc)2 catalyst ena
TL;DR: A Co(III)-catalyzed novel [4 + 2] annulation of N-chlorobenzamides with maleimides with developed methodology is compatible with a variety of functional groups and featured in some biologically active molecules.
TL;DR: Ruthenium-catalyzed selective C–H bond activation of imidamides and annulation of sulfoxonium ylides were achieved, which afforded a series of 3-ketoindole derivatives in good yields, with good functional group compatibility.
Abstract: Ruthenium-catalyzed selective C–H bond activation of imidamides and annulation of sulfoxonium ylides were achieved, which afforded a series of 3-ketoindole derivatives in good yields, with good functional group compatibility. The catalytic system generated an indole scaffold by C–N and C–S bond cleavage. This reaction constitutes the first intermolecular coupling of ylides with arenes to afford a 3-ketoindole skeleton by ruthenium-catalyzed C–H activation and annulation cascade.
TL;DR: In this article, a review of the recent development of C-H bond functionalization with various ruthenium-based catalysts is presented, covering arylation reactions covering N−Heteroaryl groups, oxidative arylation, dehydrative arylated and arylations involving decarboxylative and sp3-C-H-bond forming reactions.
Abstract: The past decades have witnessed rapid development in organic synthesis via catalysis, particularly the reactions through C–H bond functionalization. Transition metals such as Pd, Rh and Ru constitute a crucial catalyst in these C–H bond functionalization reactions. This process is highly attractive not only because it saves reaction time and reduces waste,but also, more importantly, it allows the reaction to be performed in a highly region specific manner. Indeed, several organic compounds could be readily accessed via C–H bond functionalization with transition metals. In the recent past, tremendous progress has been made on C–H bond functionalization via ruthenium catalysis, including less expensive but more stable ruthenium(II) catalysts. The ruthenium-catalysed C–H bond functionalization, viz. arylation, alkenylation, annulation, oxygenation, and halogenation involving C–C, C–O, C–N, and C–X bond forming reactions, has been described and presented in numerous reviews. This review discusses the recent development of C–H bond functionalization with various ruthenium-based catalysts. The first section of the review presents arylation reactions covering arylation directed by N–Heteroaryl groups, oxidative arylation, dehydrative arylation and arylation involving decarboxylative and sp3-C–H bond functionalization. Subsequently, the ruthenium-catalysed alkenylation, alkylation, allylation including oxidative alkenylation and meta-selective C–H bond alkylation has been presented. Finally, the oxidative annulation of various arenes with alkynes involving C–H/O–H or C–H/N–H bond cleavage reactions has been discussed.
TL;DR: A highly diastereo- and enantioselective cycloaddition of para-quinone methides to α-halogenated ketones was realized by bifunctional phosphonium salt catalysis, furnishing functionalized 2,3-dihydrobenzofurans in high yields and excellent stereoselectivities.
TL;DR: A new ruthenium(ii)-catalyzed electrooxidative [4+2] annulation of primary benzylic alcohols with internal alkynes is described, which enables benzyLic alcohols as weakly directing group precursors to access isocoumarins via multiple C-H functionalization.