Showing papers on "Annulation published in 2010"

Rhodium(III)-Catalyzed Arene and Alkene C−H Bond Functionalization Leading to Indoles and Pyrroles

Abstract: Recently, the rhodium(III)-complex [Cp*RhCl(2)](2) 1 has provided exciting opportunities for the efficient synthesis of aromatic heterocycles based on a rhodium-catalyzed C-H bond functionalization event. In the present report, the use of complexes 1 and its dicationic analogue [Cp*Rh(MeCN)(3)][SbF(6)](2) 2 have been employed in the formation of indoles via the oxidative annulation of acetanilides with internal alkynes. The optimized reaction conditions allow for molecular oxygen to be used as the terminal oxidant in this process, and the reaction may be carried out under mild temperatures (60 °C). These conditions have resulted in an expanded compatibility of the reaction to include a range of new internal alkynes bearing synthetically useful functional groups in moderate to excellent yields. The applicability of the method is exemplified in an efficient synthesis of paullone 3, a tetracyclic indole derivative with established biological activity. A mechanistic investigation of the reaction, employing deuterium labeling experiments and kinetic analysis, has provided insight into issues of reactivity for both coupling partners as well as aided in the development of conditions for improved regioselectivity with respect to meta-substituted acetanilides. This reaction class has also been extended to include the synthesis of pyrroles. Catalyst 2 efficiently couples substituted enamides with internal alkynes at room temperature to form trisubstituted pyrroles in good to excellent yields. The high functional group compatibility of this reaction enables the elaboration of the pyrrole products into a variety of differentially substituted pyrroles.

An Enantioselective Claisen Rearrangement Catalyzed by N-Heterocyclic Carbenes

Abstract: In the presence of a chiral azolium salt (10 mol %), enols and ynals undergo a highly enantioselective annulation reaction to form enantiomerically enriched dihydropyranones via an N-heterocyclic carbene catalyzed variant of the Claisen rearrangement. Unlike other azolium-catalyzed reactions, this process requires no added base to generate the putative NHC-catalyst, and our investigations demonstrate that the counterion of the azolium salt plays a key role in the formation of the catalytically active species. Detailed kinetic studies eliminate a potential 1,4-addition as the mechanistic pathway; the observed rate law and activation parameters are consistent with a Claisen rearrangement as the rate-limiting step. This catalytic system was applied to the synthesis of enantioenriched kojic acid derivatives, a reaction of demonstrated synthetic utility for which other methods for catalytic enantioselective Claisen rearrangements have not provided a satisfactory solution.

Cooperative N-heterocyclic carbene/Lewis acid catalysis for highly stereoselective annulation reactions with homoenolates.

Abstract: A new approach that takes advantage of N-heterocyclic carbene/Lewis acid cooperative catalysis provides access to cis-1,3,4-trisubstituted cyclopentenes from enals and chalcone derivatives with high levels of diastereoselectivity and enantioselectivity. The presence of Ti(OiPr)4 as the Lewis acid allows for efficient substrate preorganization, which translates into high levels of diastereoselectivity. Additionally, we demonstrate the possibility of controlling the absolute stereochemistry of NHC-catalyzed reactions by employing a catalytic amount of a chiral Lewis acid as the unique source of optically active promoter.

Palladium-Catalyzed Intermolecular Decarboxylative Coupling of 2-Phenylbenzoic Acids with Alkynes via C−H and C−C Bond Activation

Abstract: A novel protocol for palladium-catalyzed intermolecular formal [4 + 2] annulation of 2-phenylbenzoic acids with alkynes is described. Acridine is shown to be essential for the high reaction efficiency. Phenanthrene derivatives are formed in moderate to good yields without coupling (pseudo)halides or organometallic species.

Rhodium-Catalyzed [3 + 2] Annulation of Indoles

Abstract: An effective Rh2(S-DOSP)4-catalyzed asymmetric cyclopentannulation of indolyl rings has been developed. Depending on the substitution pattern of the indole, two distinct regioisomeric products can be generated. These studies demonstrate that rhodium-catalyzed reactions of donor/acceptor carbenoids proceeding by means of zwitterionic intermediates can be carried out with very high asymmetric induction.

Organocatalytic Tandem Reaction to Construct Six-Membered Spirocyclic Oxindoles with Multiple Chiral Centres through a Formal [2+2+2] Annulation

Abstract: An efficient tandem reaction for the asymmetric synthesis of six-membered spirocyclic oxindoles has been successfully developed through a formal [2+2+2] annulation strategy. The amine-catalysed stereoselective Michael addition of aliphatic aldehydes to electron-deficient olefinic oxindole motifs gave chiral C3 components, which were further combined with diverse electrophiles (activated olefins or imines) to afford spirocyclic oxindoles with versatile molecular complexity (up to six contiguous stereogenic centres, high diastereo- and enantioselectivities).

2-(Acetoxymethyl)buta-2,3-dienoate, a versatile 1,4-biselectrophile for phosphine-catalyzed (4 + n) annulations with 1,n-Bisnucleophiles (n = 1, 2).

Abstract: A novel PPh(3)-catalyzed (4 + n) annulation of 2-(acetoxymethyl)buta-2,3-dienoates 1c-e with 1,n-bisnucleophiles (n = 1, 2) has been developed to provide a facile synthetic method for cyclopentene and 1,2,3,6-tetrahydropyridazine derivatives. The acetate group of 2-(acetoxymethyl)buta-2,3-dienoate is crucial for the formation of 1,4-biselectrophilic intermediate C, which is recognized to be a 1,4-biselectrophile that can react with 1,n-bisnucleophiles. Deuterium studies also suggest that the reaction pathway involves a proton-transfer process.

Pyridine activation via copper(I)-catalyzed annulation toward indolizines.

Abstract: The copper(I)-catalyzed regioselective [3 + 2] cyclization of pyridines toward alkenyldiazoacetates leading to functionalized indolizine derivatives is reported. A broad range of pyridine derivatives (including quinoline and isoquinoline) is compatible with this cyclization reaction. The process represents the first successful example of metal-catalyzed cyclization of a π-deficient heterocyclic system with alkenyldiazo compounds.

Synthesis of Naphtho[1,8‐bc]pyran Derivatives and Related Compounds through Hydroxy Group Directed CH Bond Cleavage under Rhodium Catalysis

Abstract: The straightforward and efficient synthesis of naphtho[1,8-bc]pyran derivatives and related polycyclic compounds is achieved by the rhodium-catalyzed oxidative coupling of 1-naphthols or other phenolic and alcoholic substrates with alkynes. In these annulation reactions, the hydroxy groups effectively act as the key function for the regioselective CH bond cleavage.

Tertiary Carbinamine Synthesis by Rhodium‐Catalyzed [3+2] Annulation of N‐Unsubstituted Aromatic Ketimines and Alkynes

Abstract: A convenient and waste-free synthesis of indene-based tertiary carbinamines by rhodium-catalyzed imine/alkyne [3+2] annulation is described. Under the optimized conditions of 0.5-2.5 mol % [{(cod)Rh(OH)}(2)] (cod=1,5-cyclooctadiene) catalyst, 1,3-bis(diphenylphosphanyl)propane (DPPP) ligand, in toluene at 120 degrees C, N-unsubstituted aromatic ketimines and internal alkynes were coupled in a 1:1 ratio to form tertiary 1H-inden-1-amines in good yields and with high selectivities over isoquinoline products. A plausible catalytic cycle involves sequential imine-directed aromatic C-H bond activation, alkyne insertion, and a rare example of intramolecular ketimine insertion into a Rh(I)-alkenyl linkage.

Synthesis of 3-trifluoromethylbenzo[b]furans from phenols via direct ortho functionalization by extended Pummerer reaction.

Abstract: A concise and diversity-oriented route to trifluoromethylbenzo[b]furans has been devised. A variety of phenols are directly converted to the corresponding 2-methylthio-3-trifluoromethylbenzo[b]furans by new triflic-anhydride-mediated extended Pummerer annulation reactions with trifluoromethylketene dithioacetal monoxide. The methylthio group of the products undergoes further transformations, which increase the diversity of available trifluoromethylbenzo[b]furans.

Enantioselective synthesis of 3,4-dihydroisoquinolin-1(2H)-ones by nickel-catalyzed denitrogenative annulation of 1,2,3-benzotriazin-4(3H)-ones with allenes.

Abstract: A denitrogenative annulation reaction of 1,2,3-benzotriazin-4(3H)-ones with allenes catalyzed by a nickel−phosphine complex to produce a variety of substituted 3,4-dihydroisoquinolin-1(2H)-ones in a regioselective manner is described. A highly enantioselective version, as well as structural evidence for the mechanistic course of this reaction, is also presented.

An Unexpected Phosphine-Catalyzed Regio- and Diastereoselective [4+1] Annulation Reaction of Modified Allylic Compounds with Activated Enones

Abstract: Nucleophilic phosphines are known to be useful mild catalysts for the synthesis of cyclic and heterocyclic compounds. Generally, tertiary-phosphine-mediated annulations are triggered by nucleophilic addition of phosphines to activated compounds. The resultant zwitterionic intermediates can react with various electrophiles such as aldehydes, imines, and activated polarized C=C bonds to furnish cyclic compounds. Herein, we report a phosphine-catalyzed highly diastereoselective synthesis of tetrasubstituted 2,3-dihydrofurans, which are subunits of a range of biologically active compounds (e.g., aflatoxin B1 and clerodin), [4] via [4+1] annulations of Morita–Baylis–Hillman carbonates with activated enones. In these annulations, Morita–Baylis– Hillman carbonates act as the one-carbon unit, which is distinguished from the modified allylic compounds reported by Lu et al. as the three-carbon units, such as in [3+2], [3+3], [3+4], and [3+6] annulation reactions. In recent years, Morita–Baylis–Hillman adducts have been illustrated as suitable starting materials for the synthesis of a variety of multifunctional compounds. During our study of the new chemistry of electron-deficient enynes, we became interested in the annulation between Morita– Baylis–Hillman carbonate 1a and conjugated yne-enone 2a. We were pleased to find that the reaction proceeded smoothly in toluene at room temperature under catalysis with 10 mol% PPh3, leading to a [4+1] adduct, 2,3-dihydrofuran 3a, in 72% yield of isolated product with 20:1 diastereoselectivity (Table 1, entry 1). The structure of 3a was established by X-ray crystallography analysis of the analogous product 3f (R=p-BrC6H4; Figure 1). [7] To improve the yield of 3a, various solvents and tertiary phosphines were tested and the results are summarized in Table 1. A higher product yield was obtained when the reaction was performed in CH2Cl2, while the selectivity was slightly decreased (Table 1, entry 2). Good yields with high selectivity were also obtained in DCE, Et2O, and 1,4-dioxane, albeit the reactions require a longer time to go to completion (Table 1, en-

Catalytic enantioselective alkylative dearomatization-annulation: total synthesis and absolute configuration assignment of hyperibone K.

Abstract: The asymmetric total synthesis of the polyprenylated acylphloroglucinol hyperibone K has been achieved using an enantioselective alkylative dearomatization−annulation process. NMR and computational studies were employed to probe the mode of action of a chiral phase-transfer (ion pair) catalyst.

Synthesis of Functionalizable Boron‐Containing π‐Electron Materials that Incorporate Formally Aromatic Fused Borepin Rings

Abstract: Boron-containing p-electron systems have emerged as exciting subjects in contemporary organic materials chemistry. The strong Lewis acidity of tricoordinate boron has been utilized for the detection of biologically or environmentally relevant anions. 9] Anionic and neutral boron heteroaromatic molecules are important p-donor ligands for organometallics, and the aromaticity of boroncontaining molecules has inspired substantial experimental and theoretical investigations, thus suggesting that the heteroaromaticity of boron will play will play a key role in other areas where polarization may need to distort p-electron frameworks, such as during operation in electronic devices. The vast majority of boron-based p-electron materials was built with mainchain or lateral 18, 19] tricoordinate boron substitution or from locally antiaromatic four-p-electron fragments such as the borole nucleus within 9-borafluorene. Herein, we present the syntheses and characterization of polycyclic aromatic molecules built around the neutral and formally aromatic six-p-electron borepin ring system that is structurally poised for synthetic elaboration into complex molecular structures. The dibenzo[b,f]borepin (DBB) framework continues to attract substantial attention. 22] Van Tamelen et al. reported the first isolation of DBB as its ethanolamine adduct, and Piers and co-workers very recently reported a B-mesityl DBB that slowly oxidized under ambient conditions. Theoretical studies have revealed planarity throughout the B-H DBB; thus planarity was attractive to us as a means to enhance p-electron delocalization, and nucleus-independent chemical shift (NICS) values reveal a weak degree of aromatic character within the borepin ring of benzo-annelated molecules. However, no synthetic routes for robust and stable tricoordinate borepins that could be tailored into complex p-electron systems have been reported to date. The synthesis of the parent compound DBB 1a is shown in Scheme 1. The stilbene precursor 2a was constructed by a Wittig-type process using reactants derived from a-bromo-o-

Nickel‐Catalyzed Regio‐ and Enantioselective Annulation Reactions of 1,2,3,4‐Benzothiatriazine‐1,1(2H)‐dioxides with Allenes

Abstract: A wide range of benzothiazine dioxides is smoothly prepared by Ni-catalyzed asymmetric recyclization of title benzothiatriazine dioxides (I), (VII) with allenes.

Gold-Catalyzed Annulation/Fragmentation: Formation of Free Gold Carbenes by Retro-Cyclopropanation

Abstract: The gold(I)-catalyzed cyclization of 1-(prop-2-yn-1-yl)-2-alkenylbenzenes substituted at the benzylic position with OR groups gives 1,3-disubstituted naphthalenes with concomitant fragmentation of the alkene. One of these annulations proceeds by a retro-cyclopropanation that leads to free gold(I) carbenes.

Tuning Electronic and Steric Effects: Highly Enantioselective [4+1] Pyrroline Annulation of Sulfur Ylides with α,β‐Unsaturated Imines

Abstract: The reaction of atropisomeric sulfur ylides (I) with unsaturated imines bearing a bulky sulfonyl group at the nitrogen provides pyrroline-2-carboxylates with excellent stereocontrol.

Biginelli and Hantzsch-type reactions leading to highly functionalized dihydropyrimidinone, thiocoumarin, and pyridopyrimidinone frameworks via ring annulation with β-oxodithioesters.

Abstract: An efficient and highly convergent route to dihydropyrimidinones (DHPMs) and hitherto unreported dihydropyridopyrimidinones has been developed by one-pot, three-component cyclocondensation of aromatic aldehydes, β-oxodithioesters, and urea/6-amino-1,3-dimethyluracil in the presence of recyclable SiO2-H2SO4. On the other hand, salicylaldehyde, β-oxodithioester, and urea reacted under similar conditions to afford the 3-aroyl/heteroaroyl-2H-chromen-2-thiones in high yields instead of Biginelli product. The attractive feature of this approach is the synthesis of three important bioactive heterocyclic frameworks from the same β-oxodithioester under the similar reaction conditions, making this new strategy highly useful in diversity-oriented synthesis (DOS).

Diverse Asymmetric Quinolizidine Synthesis: A Stereodivergent One‐Pot Approach

Abstract: A diverse stereodivergent organocatalytic one-pot addition/cyclization/annulation sequence to optically active quinolizidine derivatives from easily available starting materials is presented. The one-pot sequence relies on a pyrrolidine-catalyzed enantioselective Conjugate addition of electron-deficient amide alpha-carbons to alpha,beta-unsaturated aldehydes, spontaneous hemiaminal formation and acid-catalyzed/mediated N-acyliminium ion cyclization to give the quinolizidine framework. Simple tuning of the reaction conditions in the N-acyliminuim ion cyclization step provides a diastereomeric switch, which gives access to both of the two bridgehead epimers through kinetic, thermodynamic or chelation control. The methodology display a broad substrate scope that is demonstrated by the stereoselective formation of indolo-, thieno-, benzofuro-, furo- and different benzoquinolizidine derivatives with high atom efficiency, up to >99% ee and up to >95:5 dr. Due to its efficiency, synthetic diversity and operational simplicity, this protocol has the potential to find important use as a key step in natural product Synthesis, biochemistry and pharmaceutical science. The stereochemical Outcome of the one-pot sequence was investigated. and the mechanism and origin of stereoselectivity of the different steps is discussed.

Synthesis of Acridines by the [4 + 2] Annulation of Arynes and 2-Aminoaryl Ketones

Abstract: The reaction of 2-aminoaryl ketones and arynes generated by the treatment of various o-(trimethylsilyl)aryl triflates with CsF results in [4 + 2] annulation to afford substituted acridines in good yields.

Iridium-catalyzed annulation of N-arylcarbamoyl chlorides with internal alkynes.

Abstract: An iridium complex successfully catalyzed the annulation of various N-arylcarbamoyl chlorides with internal alkynes to afford 2-quinolones in good to excellent yields. The present reaction is widely applicable to substrates with various functionalities. An amide−iridacycle complex was isolated, and it is likely that such an iridacycle species is a key intermediate in the catalytic reaction.

Catalytic Asymmetric Intramolecular Cascade Reaction for the Construction of Functionalized Benzobicyclo[4.3.0] Skeletons. Remote Control of Enantioselectivity

Abstract: A catalytic asymmetric version of the intramolecular ylide annulation has been developed which affords high ee values and diastereoselectivities and which further shows that spirobiindane-based chiral phosphines can be excellent organocatalysts. Both optically active benzobicyclo[4.3.0] compounds 2 and 2' with three continuous stereogenic centers could be obtained as major products selectively under neutral and mild conditions just by a choice of an additive.

Copper-Catalyzed Annulation of 2-Formylazoles with o-Aminoiodoarenes

Abstract: In the presence of catalytic CuI and sparteine, 2-formylpyrroles can be annulated with o-aminoiodoarenes to give substituted pyrrolo[1,2-a]quinoxalines and related heterocycles. The reaction also works for annulation of 2-formylindoles, 2-formylimidazole, 2-formylbenzimidazole, and a 3-formylpyrazole.

Fischer Indole Synthesis with Organozinc Reagents

Abstract: Primary and secondary alkylzinc reagents add to various aryldiazonium salts leading to polyfunctional indoles by means of a [3,3]-sigmatropic shift and subsequent aromatization.