Showing papers on "Annulation published in 2008"
TL;DR: This tutorial review summarizes the recent achievements in nucleophilic phosphine catalysis and describes how phosphines can be easily tailored to efficient annulation reactions with good control over reaction selectivity.
Abstract: Nucleophilic phosphine catalysis has proven to be a powerful tool in organic synthesis, which can provide easy access to cyclic, bicyclic or polycyclic carbocycles and heterocycles. Owing to their comparatively strong and readily tunable nucleophilicity, phosphines can be easily tailored to efficient annulation reactions with good control over reaction selectivity. This has resulted in a tremendous increase in their scope and in a concomitant number of reports where phosphine-triggered annulation reactions occur. This tutorial review summarizes the recent achievements in this area.
622 citations
TL;DR: The versatility of NHC-bound homoenolate is illustrated by its annulation with various carbonyl compounds leading to gamma-butyrolactones, spiro-gamma- butyrolactsones, and delta-lactones.
Abstract: Homoenolate, a species containing anionic carbon β to a carbonyl group or a moiety that can be transformed into a carbonyl group, is a potential three carbon synthon. Recent introduction of a protocol for the generation of homoenolate directly from enals by NHC (nucleophilic heterocyclic carbene) catalysis has made it possible to explore the synthetic utility of this unique reactive intermediate. The versatility of NHC-bound homoenolate is illustrated by its annulation with various carbonyl compounds leading to γ-butyrolactones, spiro-γ-butyrolactones, and δ-lactones. Interception of homoenolate with imines afforded γ-lactams and bicyclic β-lactams. Formation of cyclopentenes and spirocyclopentanones respectively by reaction with enones and dienones is also noteworthy. This tutorial review focuses on these and other types of reactions which attest to the synthetic potential of NHC-bound homoenolates in organic synthesis.
557 citations
TL;DR: Two copper-catalyzed approaches complement existing strategies for benzoxazole synthesis, which typically utilize 2-aminopheonls as precursors, and an alternative more versatile one-pot domino annulation strategy was developed.
Abstract: Two domino annulation approaches for benzoxazole synthesis have been developed. In the first approach, copper-catalyzed intermolecular cross-coupling of 1,2-dihaloarenes with primary amides initially forms the Ar−N bond of the benzoxazole ring, followed by copper-catalyzed intramolecular cyclization to form the Ar−O bond. Benzoxazoles were formed in good yields for the reaction of 1,2-dibromobenzene, but the reaction was not regioselective for the reaction of 3,4-dibromotoluene. Furthermore, the method is limited by the availability of 1,2-dihaloarenes. As a result of these limitations, an alternative more versatile one-pot domino annulation strategy was developed involving reaction of 2-bromoanilines with acyl chlorides in the presence of Cs2CO3, catalytic CuI, and the non-acylatable ligand 1,10-phenanthroline. Under these conditions initial acylation of the aniline is followed by copper-catalyzed intramolecular cyclization of the resultant 2-haloanilide to form the Ar−O bond of the benzoxazole ring. Opt...
234 citations
TL;DR: Planar chiral phosphines displaying a new ferrocenophane scaffold displaying high levels of asymmetric induction in the organocatalytic annulation reaction between allenes and electron-poor olefins are prepared via a stereoselective approach.
Abstract: Planar chiral phosphines displaying a new ferrocenophane scaffold have been prepared via a stereoselective approach. The P-cyclohexyl substituted phosphine affords high levels of asymmetric induction in the organocatalytic [3 + 2] annulation reaction between allenes and electron-poor olefins.
234 citations
TL;DR: Two unique methodologies exploiting the reactivity of arynes are developed, one for the total synthesis of the opiate alkaloid papaverine and the other for the modification of related enamine derivatives modified as amides.
Abstract: Described in this report is the development of two unique methodologies exploiting the reactivity of arynes. Reaction of N-carbamoyl-functionalized enamine derivatives with benzyne affords substituted indolines. An orthogonal reactivity is uncovered when related enamine derivatives are modified as amides, such that isoquinolines are formed as the product of condensation with benzyne. This latter transformation is applied to a concise total synthesis of the opiate alkaloid papaverine.
208 citations
TL;DR: A convenient gold(III)-catalyzed synthesis of azepines from the intermolecular annulation of propargyl esters and alpha,beta-unsaturated imines is reported.
Abstract: A convenient gold(III)-catalyzed synthesis of azepines from the intermolecular annulation of propargyl esters and α,β-unsaturated imines is reported (19 examples, 55−95% yield). This formal [4 + 3]-cycloaddition reaction is proposed to proceed via a stepwise process involving intramolecular trapping of an allyl−gold intermediate.
199 citations
TL;DR: A novel concept of Au-containing all-carbon 1,n-dipoles is advanced from 1-(1-alkynyl)cyclopropyl ketones, which are presumably generated in situ and can efficiently...
Abstract: A novel concept of Au-containing all-carbon 1,n-dipoles is advanced. From 1-(1-alkynyl)cyclopropyl ketones, Au-containing all-carbon 1,4-dipoles are presumably generated in situ and can efficiently...
190 citations
TL;DR: The development of the annulation with a wide substrate scope provided a unique opportunity to evaluate photophysical properties of a series of aryl- and heteroaryl-annulated[a]carbazoles, which were found to emit purple to green light in the visible region.
Abstract: Treatment of 2-aryl- and 2-heteroarylindoles with propargyl ethers in the presence of a catalytic amount of indium nonafluorobutanesulfonate [In(ONf)3] gave aryl- and heteroaryl-annulated[a]carbazoles in good yields. The synthetically attractive feature is reflected by its applicability to a wide range of 2-aryl- and 2-heteroarylindoles. In the annulation reaction, propargyl ethers act as C3 sources (HC≡C−CH2OR). Among these, two carbon atoms are incorporated into the product as members of a newly constructed aromatic ring and the remaining carbon atom forms a methyl group on the aromatic ring, where the methyl group is always located next to the C3 position of the indole nucleus. The methyl group can be easily removed through SeO2 oxidation followed by decarbonylation with RhCl(CO)(PPh3)2−Ph2P(CH2)3PPh2 as a catalyst. The new annulation strategy is applicable also to symmetrical dimers such as bithiophene and bifuran derivatives. Mechanistic studies suggest that the first step is addition reaction initia...
179 citations
TL;DR: The application of a novel concept to prepare these pharmacologically important heterocycles from b-amino alcohols/thiols/amines in one step and high yield with the possibility of employing Michael acceptors is described.
Abstract: The nitrogen-containing heterocycles comprising morpholines, thiomorpholines, and piperazines are some of the most important pharmacophores in medicinal chemistry. However, the direct synthesis of such compounds by alkylation of b-amino alcohols/thiols/amines with 1,2-dihalo derivatives is often fraught with low yields and side reactions. 1,2Dihalogen derivatives are generally poor electrophiles and reactions are often accompanied by competing elimination processes. A solution to this problem is to carry out a threestep sequence employing an a-halogen acid halide as the electrophile. Following amide formation and intramolecular alkylation, reduction finally furnishes the required heterocycles. Herein, we describe the application of a novel concept to prepare these pharmacologically important heterocycles from b-amino alcohols/thiols/amines in one step and high yield. We reasoned that soft electrophiles operating under less basic conditions would minimize competing elimination pathways and therefore considered the possibility of employing Michael acceptors. This led us to vinyl onium salts (e.g., 1). We expected that, following conjugate addition of one of the heteroatoms, an ylide 4 would be generated that could undergo proton transfer with the other heteroatom (Scheme 1). The heteroatom anion generated, 5, would then attack the onium ion electrophile to effect ring-closure and produce the required heterocycle. Although vinyl onium salts have been employed in three-component coupling reactions with nucleophiles and electrophiles, their potential to react according to the pathway shown in Scheme 1 has not previously been recognized. Of the readily available vinyl onium salts, it was thought that sulfonium and phosphonium would be better at promoting the conjugate addition step than ammonium since the ylide intermediate is better stabilized. However, to promote cyclization leaving group ability of the onium is critical and this falls in the order S>N @ P. These considerations led us to examine vinyl sulfonium salts, and in particular diphenyl vinyl sulfonium salt 1. This salt was easily prepared through a modified procedure as shown in Scheme 2. In this
158 citations
TL;DR: A phosphine-catalyzed annulation of modified allylic ylides with various aromatic imines to form 3-pyrrolines was developed and (E)-dienylimines will be produced via the dimerization of the allylic compounds.
135 citations
TL;DR: The divergent arene syntheses involve a Au-catalyzed, two-pot, multistep process proceeding by cis-diastereoselective cyclopropanation, cycloisomerization, and, finally, annulation or elimination.
Abstract: Intermolecular annulation of enynes and propargyl esters to selectively produce styrenes or fluorenes is reported. The divergent arene syntheses involve a Au-catalyzed, two-pot, multistep process proceeding by cis-diastereoselective cyclopropanation, cycloisomerization, and, finally, annulation or elimination.
TL;DR: This phosphine-catalyzed annulation of methyl allenoate with various aromatic aldehydes to form 6-aryl-4-methoxy-5,6-dihydro-2-pyrones provides an efficient, one-step route toward disubstituted dihydropyrones from simple, stable starting materials.
TL;DR: A direct oxidative coupling of salicylaldehydes with internal alkynes proceeds efficiently with cleavage of the aldehyde C--H bond to produce the corresponding chromone derivatives.
Abstract: A direct oxidative coupling of salicylaldehydes with internal alkynes proceeds efficiently with cleavage of the aldehyde C--H bond to produce the corresponding chromone derivatives. A rhodium catalyst in combination with a cyclopentadiene ligand and a copper oxidant promote this straightforward annulation reaction. Solid-state luminescence was observed for certain chromone products.
TL;DR: The disclosed procedures broaden significantly the synthetic applicability of the oxidative intramolecular diamination of alkenes with tethered ureas and related groups as the nitrogen source.
Abstract: The oxidative intramolecular diamination of alkenes with tethered ureas and related groups as the nitrogen source has been investigated both with the iodonium reagent IPy(2)BF(4) (Py=pyridine) and under palladium catalysis in the presence of copper(II) bromide as a reoxidant. For terminal alkenes, the two procedures enable selective and high-yielding transformations. Studies with deuterated material led to the conclusion that the reactions proceed through different stereochemical pathways. An advanced protocol for palladium-catalyzed diamination through six-membered-ring annulation was also developed, and the first examples of the intramolecular diamination of internal alkenes are described. In this case, the same stereochemical outcome was observed for the iodonium-promoted and palladium-catalyzed transformations. On this basis, it was possible to determine the importance of aminohalogenated intermediates in both diamination reactions. Overall, the disclosed procedures broaden significantly the synthetic applicability of the oxidative intramolecular diamination of alkenes.
TL;DR: An unexpected phosphine-catalyzed [3 + 2] annulation from electron-deficient allenes and substituted alkylidenemalononitriles was realized in which the allylic moiety of the substituted alkies served as the three carbon unit of the cyclopentenes instead of the electron-defense allenes.
TL;DR: This report describes a rapid asymmetric total synthesis of the tetrahydroisoquinoline antitumor antibiotic (-)-quinocarcin using a mild fluoride-induced aryne annulation developed in the laboratories to build a key isoquinoline-containing intermediate comprising the entire carbon scaffold of the natural product.
Abstract: Described in this report is a rapid asymmetric total synthesis of the tetrahydroisoquinoline antitumor antibiotic (−)-quinocarcin. The sequence employs a mild fluoride-induced aryne annulation developed in our laboratories to build a key isoquinoline-containing intermediate comprising the entire carbon scaffold of the natural product. This intermediate is advanced through six additional steps to the target alkaloid, providing the shortest synthetic route to (−)-quinocarcin reported to date.
TL;DR: In this paper, an efficient copper-free Sonogashira coupling of 2-chloroquinolines with phenyl acetylene to 2-ethynylquinoline was described, and the one-pot facile annulation of 3-carboxaldehydes to 3-phenylbenzo[b][1,6]naphthyridines in aqueous ammonia was discussed.
TL;DR: A norbornene-mediated palladium-catalyzed sequence is described in which an alkyl-aryl bond and an aryl-heteroaryl bond are formed in one reaction vessel.
Abstract: A norbornene-mediated palladium-catalyzed sequence is described in which an alkyl-aryl bond and an aryl-heteroaryl bond are formed in one reaction vessel. The aryl-heteroaryl bond-forming step occurs via a direct arylation reaction. A number of six-, seven-, and eight-membered ring-annulated indoles, pyrroles, pyrazoles, and azaindoles were synthesized from the corresponding bromoalkyl azole and an aryl iodide.
TL;DR: On the basis of the reactions of camphor-derived sulfur ylide with alpha-ylidene-beta-diketones, highly efficient and selective synthesis of optically active dihydrofurans has been achieved.
Abstract: On the basis of the reactions of camphor-derived sulfur ylide with alpha-ylidene-beta-diketones, highly efficient and selective synthesis of optically active dihydrofurans has been achieved.
TL;DR: Highly potent bryostatin analogues which contain the complete bRYostatin core structure have been synthesized using a pyran annulation approach as a key strategic element.
Abstract: Highly potent bryostatin analogues which contain the complete bryostatin core structure have been synthesized using a pyran annulation approach as a key strategic element. The A ring pyran was assembled using a pyran annulation reaction between a C1−C8 hydroxy allylsilane and an aldehyde comprising C9−C13. This pyran was transformed to a new hydroxy allylsilane and then coupled with a preformed C ring aldehyde subunit in a second pyran annulation, with concomitant formation of the B ring. This tricyclic intermediate was elaborated to bryostatin analogues which displayed nanomolar to subnanomolar affinity for PKC, but displayed properties indistinguishable from a phorbol ester in a proliferation/attachment assay.
TL;DR: Combining the oxidative addition and reductive elimination steps into a single cycle, in the presence of an alkene, provides of a novel and potentially exciting, atom efficient catalytic C-C bond forming process for the substitution, and annulation of heterocyclic rings.
Abstract: N-Heterocyclic carbenes (NHCs) are commonly regarded as strong donor ligands that are valuable in coordination chemistry and catalysis. Many reports describing this aspect of their chemistry have been published. The alternative view of NHCs as reaction intermediates has been little explored, and yet excellent examples exist and will be reviewed in this perspective. Group 10 hydrocarbyl complexes of NHCs [(R)(NHC)ML2 where R = H, alkyl, aryl, acyl; M = Ni, Pd, Pt] undergo a facile reductive elimination to generate M(0) and R-substituted-azolium salt as products. On the other hand, 2-Hazolium salts will oxidatively add to M(0) complexes to afford reactive NHC–M–H compounds, suitable as catalysts for selected reactions. Combining the oxidative addition and reductive elimination steps into a single cycle, in the presence of an alkene, provides of a novel and potentially exciting, atom efficient catalytic C–C bond forming process for the substitution, and annulation of heterocyclic rings.
TL;DR: A variety of six-membered-ring annulated 2H-indazoles and 1,2,3- and 1-2,4-triazoles were synthesized in good to excellent yields from the corresponding bromoethyl azoles and aryl iodides.
Abstract: A variety of six-membered-ring annulated 2H-indazoles and 1,2,3- and 1,2,4-triazoles were synthesized in good to excellent yields from the corresponding bromoethyl azoles and aryl iodides. The annulation process involves a one-pot norbornene-mediated palladium-catalyzed sequence whereby an alkyl-aryl bond and an aryl-heteroaryl bond are successively formed through two C-H bond activations. Subsequent functionalizations of the resulting polycyclic through cross-coupling reactions are also presented.
TL;DR: This new gold catalysis is applied to a short synthesis of natural compounds of the bBrazilane family, including brazilane, O-trimethyl-, and O-tetramethyl brazilanes, giving polycyclic carbo- or oxacyclic compounds with controlled stereochemistry.
Abstract: Treatment of 2,4-dien-1-als with allylsilanes and PPh3AuSbF6 (3 mol %) led to formation of 1,4-bis(allyl)cyclopentenyl products; this gold catalyst is superior to commonly used Lewis acids according to catalyst screening. Such gold-catalyzed deoxygenative cyclizations are compatible with various oxygen-, amine-, sulfur-, hydrogen-, and carbon-based nucleophiles. The value of this new catalysis is demonstrated by the diverse annulations of 2,4-dien-1-als with electron-rich alkenes and arenes, providing an easy access to complicated cyclopentenyl frameworks. Structural analysis of annulation products reveals evidence for the participation of Nazarov cyclization. This deoxygenative cyclization is extensible to a tandem intramolecular cyclization/nucleophilic addition cascade, giving polycyclic carbo- or oxacyclic compounds with controlled stereochemistry. This new gold catalysis is applied to a short synthesis of natural compounds of the brazilane family, including brazilane, O-trimethyl-, and O-tetramethyl ...
TL;DR: A simple oxidative process is described that generates the N9 C10 bond of guanidine 5 and leads to the first enantioselective synthesis of members of the phakellin family of marine alkaloids, namely (+)-monobromophakeLLin and (+)-phakell in.
Abstract: The phakellin group of natural products (1a–c) belong to the pyrrole–imidazole family of marine sponge derived alkaloids and are proposed to be biosynthetically derived from oroidin (3) and related congeners (Scheme 1). This family of marine alkaloids has attracted great interest from both synthetic and biological perspectives because of their intriguing structural features and, in some cases, potent biological activities. The monomeric pyrrole–imidazole members ( )-dibromophakellin (1a) and ( )-monobromophakellin (1b) were isolated in 1969 by Burkholder and Sharma from the marine sponge Phakellia flabellata. Subsequently, enantiomeric (+)-dibromophakellin (ent-1a) was isolated from Pseudoaxinyssa cantharella in 1985. Phakellins (1c and ent-1c) have not been isolated but were obtained by hydrogenolysis of ( )and (+)-dibromophakellin, respectively. The phakellstatin (2) group of natural products are related members of this alkaloid family and bear a cyclic urea rather than a cyclic guanidine group. The dimeric pyrrole–imidazole alkaloids palau-amine (4) and related congeners contain a phakellin subunit within their structure, and a stereochemical revision of this molecule was recently proposed. The concise biomimetic synthesis of rac-dibromophakellin reported by Foley and B/chi stands as a benchmark for syntheses of these alkaloids. In fact, most subsequent syntheses of racemic phakellins and phakellstatin alkaloids have used related oxidative cyclization strategies. We have previously reported an enantioselective synthesis of (+)-dibromophakellstatin that employed a Hoffman rearrangement to simultaneously introduce the second aminal center (C10; Scheme 2) and cyclize the incipient isocyanate to deliver the cyclic urea. In connection with our synthetic efforts toward palau-amine (4), we have sought expedient strategies to annulate the phakellin substructure onto a cyclopentane core. In our previous studies, we recognized the stability of C6 aminals in these tricyclic systems and this enabled us to consider an enantioselective strategy involving a key C H amination disconnection at N9 C10. This strategy was based on recent studies by Du Bois and co-workers, and employed guanidine 5 (Scheme 2) as a substrate, which is accessible from the known carbinolamines 6 derived from l-proline. This procedure would enable installation of the cyclic guanidine in a stereospecific fashion, thus giving synthetic entry to the phakellin alkaloids. Herein we describe a simple oxidative process that generates the N9 C10 bond of guanidine 5 and leads to the first enantioselective synthesis of members of the phakellin family of marine alkaloids, namely (+)-monobromophakellin and (+)-phakellin. This annulation strategy is potentially applicable to the preparation of the complex spiro alkaloid palau-amine (4). Initially, we set out to synthesize a guanidine substrate, for example 5, with a prerequisite of obtaining the required syn arrangement between the guanidine group and the adjacent C H bond for subsequent intramolecular amination. Accordingly, l-proline was converted into the known compound 6 in three steps as an inconsequential (see below) mixture of diastereomers (d.r. 3:1; Scheme 3). CarbinolScheme 1. Structures of tetracyclic marine alkaloids from the phakellin (1) and phakellstatin (2) families, oroidin (3), and a more complex member, palau’amine (4).
TL;DR: A highly convergent strategy involving the sequential annulation of vinyl iodide 5 with indole 6 exploits varying modes of indole reactivity to provide aspidophytine in 23% over six steps from 5.
Abstract: An expedient asymmetric total synthesis of aspidophytine is reported. A highly convergent strategy involving the sequential annulation of vinyl iodide 5 with indole 6 exploits varying modes of indole reactivity to provide aspidophytine in 23% over six steps from 5.
TL;DR: Stereoselective total synthesis of natural product crisamicin A was accomplished for the first time via the Pd/TMTU-catalyzed alkoxycarbonylative annulation to generate a unique cis-pyran-fused lactone.