Showing papers on "Annulation published in 2003"
TL;DR: Mechanistic reasoning for this new annulation has led to an expansion of the reaction scope by employing ethyl 2-(substituted-methyl)-2,3-butadienoates to give Ethyl 2,6-cis-disubst ituted-1-(4-tosyl)-1,2,5, 6-tetrahydro-pyridine-3-carboxylates with high diastereoselectivities.
Abstract: Ethyl 2-methyl-2,3-butadienoate acts as a 1,4-dipole synthon and undergoes [4 + 2] annulation with N-tosylimines in the presence of an organic phosphine catalyst. The resulting adducts, ethyl 6-substituted-1-(4-tosyl)-1,2,5,6-tetrahydro-pyridine-3-carboxylates, are formed in excellent yields with complete regioselectivity. Mechanistic reasoning for this new annulation has led to an expansion of the reaction scope by employing ethyl 2-(substituted-methyl)-2,3-butadienoates to give ethyl 2,6-cis-disubstituted-1-(4-tosyl)-1,2,5,6-tetrahydro-pyridine-3-carboxylates with high diastereoselectivities.
397 citations
TL;DR: A palladium-catalyzed aerobic oxidative annulation of indoles is described, and it is shown that the mechanism most likely involves initial indole palladation followed by migratory insertion and beta-hydrogen elimination.
Abstract: A palladium-catalyzed aerobic oxidative annulation of indoles is described. We have demonstrated that a variety of factors influence these cyclizations, and in particular the electronic nature of the pyridine ligand is crucial. It is also remarkable that these oxidative cyclizations can proceed in good yield despite background oxidative decomposition pathways, testament to the facile nature with which molecular oxygen can serve as the direct oxidant for Pd(0). We have also shown that the mechanism most likely involves initial indole palladation (formal C−H bond activation) followed by migratory insertion and β-hydrogen elimination.
330 citations
TL;DR: On screening, 1-butylimidazolium tetrafluoroborate [Hbim]BF4 was found to be the best ionic liquid for the heteroannulation reaction, and the reasons to this effect are well explained.
Abstract: Several room-temperature ionic liquids (ILs) based on 1-butylimidazolium salts with varying anions were synthesized and evaluated for the preparation of biologically active substituted quinolines and fused polycyclic quinolines using the Friedlander heteroannulation reaction. On screening, 1-butylimidazolium tetrafluoroborate [Hbim]BF4 was found to be the best ionic liquid for the heteroannulation reaction, and the reasons to this effect are well explained. The reactions proceed very well under relatively mild conditions without any added catalyst. The IL acts as a promoter for this regiospecific synthesis and can be recycled. By this green approach, various quinolines were prepared in excellent yields and purity and well-characterized.
261 citations
199 citations
TL;DR: In this article, a new approach to the Friedlander synthesis of quinolines is described, which is readily prepared under milder conditions than in other existing methods through a gold(III)-catalysed sequential condensation/annulation reaction of o-amino aromatic carbonyls and ketones containing active methylene groups.
Abstract: A new approach to the Friedlander synthesis of quinolines is described. Polysubstituted quinolines are readily prepared under milder conditions than in other existing methods through a gold(III)-catalysed sequential condensation/annulation reaction of o-amino aromatic carbonyls and ketones containing active methylene groups.
148 citations
TL;DR: The formation of the pyridines 4 is suggested to proceed through the sequential amination of carbonyl compounds followed by regioselective 6-endo-dig cyclization of the N-propargylenamine intermediate 3(5) and aromatization reaction.
Abstract: A general one-pot synthesis of pyridines 4a−t from the reaction of dialkyl acyclic/cyclic ketones 1a−i, methyl, aryl/heteroaryl ketones 1m−r, and aldehydes bearing α-hydrogens 1s,t with propargylamine 2 is described. Gold and copper salts are efficient catalysts for the reaction of ketones with 2. The formation of the pyridines 4 is suggested to proceed through the sequential amination of carbonyl compounds followed by regioselective 6-endo-dig cyclization of the N-propargylenamine (N-propargyldienamine) intermediate 3(5) and aromatization reaction. Whereas the preparation of linear polycyclic pyridine 4i can be carried out by reacting cholestan-3-one 1i with 2, the angular polycyclic pyridine 4j has been obtained starting from cholest-5-en-3-one 1j. Selectivity of the reaction of polycyclic dicarbonyls 1k,l with 2 has also been investigated.
127 citations
TL;DR: Indanones and 2-cyclopentenones have been successfully prepared in good to excellent yields by the palladium-catalyzed carbonylative cyclization of unsaturated aryl iodides and dienyl triflates, iodides, and bromides, respectively.
Abstract: Indanones and 2-cyclopentenones have been successfully prepared in good to excellent yields by the palladium-catalyzed carbonylative cyclization of unsaturated aryl iodides and dienyl triflates, iodides, and bromides, respectively. The best results are obtained by employing 10 mol % of Pd(OAc)(2), 2 equiv of pyridine, 1 equiv of n-Bu(4)NCl, 1 atm of CO, a reaction temperature of 100 degrees C, and DMF as the solvent. This carbonylative cyclization is particularly effective on substrates that contain a terminal olefin. The proposed mechanism for this annulation includes (1) Pd(OAc)(2) reduction to the active palladium(0) catalyst, (2) oxidative addition of the organic halide or triflate to Pd(0), (3) coordination and insertion of carbon monoxide to produce an acylpalladium intermediate, (4) acylpalladation of the neighboring carbon-carbon double bond, (5) reversible palladium beta-hydride elimination and re-addition to form a palladium enolate, and (6) protonation by H(2)O to produce the indanone or 2-cyclopentenone.
111 citations
TL;DR: In this article, a TTF unit was applied directly to the porphyrin chromophore to produce an almost non-fluorescent species which can be transformed into a fluorescent species by oxidation of the unit.
111 citations
TL;DR: P-tert-butyl-phenol from Aldrich Chemical Company, Inc. as mentioned in this paper is a product of ptert butyl-calix, which is used for carbocyclic synthesis.
Abstract: p-tert-Butylcalix[4]arene
reactant: p-tert-Butylphenol from Aldrich Chemical Company, Inc.
product: p-tert-butylcalix[4]arene
Keywords:
annulation, carbocyclic-[>6];
cyclization, condensation
105 citations
TL;DR: This strategy has the potential for producing phakellstatin derivatives, derived from (R,R)-cyclo (Pro, Pro), necessary for biological studies and is expected to be applicable to the synthesis of palau'amine.
Abstract: The first enantioselective total synthesis of (+)-phakellstatin and (+)-dibromophakellstatin was achieved. Key steps in the synthesis were a desymmetrization of the diketopiperazine (S,S)-cyclo (Pro, Pro) via a diastereoselective acylation, an intramolecular Mitsunobu reaction to introduce the C6 aminal, and a tandem Hofmann rearrangement/cyclization to simultaneously introduce the C10 quaternary aminal center and deliver the cyclic urea. The synthesis also demonstrates the unusual stability of pyrrolo aminals. Importantly, this strategy has the potential for producing phakellstatin derivatives, derived from (R,R)-cyclo (Pro, Pro), necessary for biological studies. A similar annulation protocol is also expected to be applicable to the synthesis of palau'amine.
99 citations
TL;DR: Macrocyclization via rhodium-catalyzed intramolecular [2 + 2 + 2] annulation of triynes has been explored in an aqueous-organic biphasic system and achieves selective cross-annulation between hydrophobic diynes and hydrophilic alkynes.
Abstract: Macrocyclization via rhodium-catalyzed intramolecular [2 + 2 + 2] annulation of triynes has been explored in an aqueous−organic biphasic system. The biphasic system controls the concentration of hy...
TL;DR: Free-radical mediated stannylcarbonylation of azaenynes provides a general [n + 1]-type annulation approach leading to alpha-stannylmethylene lactams.
Abstract: Free-radical mediated stannylcarbonylation of azaenynes provides a general [n + 1]-type annulation approach leading to α-stannylmethylene lactams. The cyclization is unusual in its breadth, covering 4-exo, 5-exo, 6-exo, 7-exo, and 8-exo modes.
TL;DR: The palladium-catalyzed annulation of internal alkynes by o-iodophenols in the presence of CO results in exclusive formation of coumarins, the first example of intermolecular insertion of an alkyne occurring in preference to CO insertion.
Abstract: The palladium-catalyzed annulation of internal alkynes by o-iodophenols in the presence of CO results in exclusive formation of coumarins. No isomeric chromones have been observed. The best reaction conditions utilize the 2-iodophenol, 5 equiv of alkyne, 1 atm of CO, 5 mol % Pd(OAc)2, 2 equiv of pyridine, and 1 equiv of n-Bu4NCl in DMF at 120 °C. The use of a sterically unhindered pyridine base is essential to achieve high yields. A wide variety of 3,4-disubstituted coumarins containing alkyl, aryl, silyl, alkoxy, acyl, and ester groups have been prepared in moderate to good yields. Mixtures of regioisomers have been obtained when unsymmetrical alkynes are employed. 2-Iodophenols with electron-withdrawing and electron-donating substituents and 3-iodo-2-pyridone are effective in this annulation process. The reaction is believed to proceed via (1) oxidative addition of the 2-iodophenol to Pd(0), (2) insertion of the alkyne triple bond into the aryl−palladium bond, (3) CO insertion into the resulting vinylic...
TL;DR: The reaction of alpha-aryl-substituted carbonyl compounds with terminal or internal alkynes in the presence of TiCl4 regioselectively generates substituted naphthalene derivatives in good to excellent yields.
Abstract: A new straightforward procedure has been developed for the synthesis of polysubstituted naphthalene derivatives. The reaction of α-aryl-substituted carbonyl compounds with terminal or internal alkynes in the presence of TiCl4 regioselectively generates substituted naphthalene derivatives in good to excellent yields.
TL;DR: In this paper, a formal cycloaddition method using 4-hydroxy-2-pyrones and 1,3-diketones is described, and experimental evidence is provided to support the mechanism of this reaction that involves a sequential Knoevenagel condensation and a reversible 6π-electron electrocyclic ring closure of 1-oxatrienes.
Abstract: A detailed account regarding a formal [3 + 3] cycloaddition method using 4-hydroxy-2-pyrones and 1,3-diketones is described here. This formal cycloaddition reaction or annulation reaction is synthetically useful for constructing 2H-pyranyl heterocycles. The usage of α,β-unsaturated iminium salts is significant in controlling competing reaction pathways to give exclusively 2H-pyrans. Most significantly, experimental evidence is provided to support the mechanism of this reaction that involves a sequential Knoevenagel condensation and a reversible 6π-electron electrocyclic ring-closure of 1-oxatrienes.
TL;DR: The synthetic potential of the designated Clemmensen-Clemo-Prelog-Leonard reductive rearrangement was demonstrated for the first time in a facile synthesis of the benzazepine subunit of CET.
TL;DR: In this article, the authors showed that terminal alkynes bearing alkyl, aryl, silyl, hydroxyl, ester and cyano substituents are effective in these processes affording the desired products in moderate yields.
TL;DR: An efficient synthesis of highly substituted naphthalenes has been developed by the palladium-catalyzed annulation of a variety of internal alkynes, in which two new carbon-carbon bonds are formed in a single step under relatively mild reaction conditions.
Abstract: An efficient synthesis of highly substituted naphthalenes has been developed by the palladium-catalyzed annulation of a variety of internal alkynes, in which two new carbon-carbon bonds are formed in a single step under relatively mild reaction conditions. This method has also been used to synthesize carbazoles, although a higher reaction temperature is necessary. The process involves arylpalladation of the alkyne, followed by intramolecular Heck olefination and double-bond isomerization. This method accommodates a variety of functional groups and affords the anticipated highly substituted naphthalenes and carbazoles in good to excellent yields.
TL;DR: Theoretical calculations suggest that rearrangement onto the sulfur atom of the [4 + 1] intermediate does not occur via a sulfuranyl radical but rather through either a transition state or a sulfur-centered (thioamidyl) radical; the latter is possibly the preferred route in the presence of an o-methylsulfanyl moiety that can act as a leaving group in the final ipso-cyclization process.
Abstract: Aryl radicals react with 2-(2-phenylethynyl)phenyl isothiocyanate through a novel radical cascade reaction entailing formation of α-(arylsulfanyl)imidoyl radicals and affording a new class of compounds, i.e. thiochromeno[2,3-b]indoles. These derivatives are formed as mixtures of substituted analogues arising from competitive [4 + 2] and [4 + 1] radical annulations. The isomer ratio is strongly dependent on the aryl substituent and is correlated to its capability to delocalize spin density. The presence of a methylsulfanyl group in the ortho-position of the initial aryl radical results in complete regioselectivity and better yields, as the consequence of both strong spin-delocalization effect, which promotes exclusive [4 + 1] annulation, and good radical leaving-group ability, which facilitates aromatization of the final cyclohexadienyl radical. Theoretical calculations support the hypothesis of competitive, independent [4 + 2] and [4 + 1] annulation pathways. They also suggest that rearrangement onto the ...
TL;DR: A variety of N-substituted 2-bromo-1H-indole-3-carboxaldehydes incorporating an alkyne-containing tether on the indole nitrogen have been converted to the corresponding tert-butylimines, subjected to palladium-catalyzed intramolecular iminoannulation, affording various gamma-carboline derivatives with an additional ring fused across the 4- and 5-positions in good to excellent yields.
Abstract: A variety of N-substituted 2-bromo-1H-indole-3-carboxaldehydes incorporating an alkyne-containing tether on the indole nitrogen have been converted to the corresponding tert-butylimines, which have been subjected to palladium-catalyzed intramolecular iminoannulation, affording various gamma-carboline derivatives with an additional ring fused across the 4- and 5-positions in good to excellent yields. When the tethered carbon-carbon triple bond is terminal or substituted with a triethylsilyl group, the iminoannulation generates a tert-butyl-gamma-carbolinium salt as the major product. The palladium-catalyzed intramolecular annulations of N-substituted 2-bromo-1H-indole-3-carboxaldehyde, methyl 2-iodo-1H-indole-3-carboxylate, and 2-iodo-3-phenyl-1H-indole containing a phenylpentynyl tether produce the corresponding heteropolycycles in moderate to good yields.
TL;DR: A proposed mechanism for the synthesis of 1,3-benzoxazine derivatives involves the formation of the expected 2-amino-3-(1-hydroxyalkyl)naphthalenes, followed by their condensation with an iminium ion species formed from the trialkylamine base used in the reaction.
Abstract: Intramolecular carbopalladation of the cyano group has been employed for the synthesis of 3,4-disubstituted 2-aminonaphthalenes. (2-Iodophenyl)acetonitrile reacts with a variety of internal alkynes to afford 2-aminonaphthalenes in high yields with good regioselectivity. The scope and limitations of this process, which proceeds by the intramolecular addition of a vinylpalladium species to the triple bond of the cyano group, have been studied. The annulation of certain hindered propargylic alcohols affords 1,3-benzoxazine derivatives, rather than the expected 2-aminonaphthalenes. The involvement of trialkylamine bases in the formation of these heterocyclic compounds has been established. A proposed mechanism for the synthesis of 1,3-benzoxazine derivatives involves the formation of the expected 2-amino-3-(1-hydroxyalkyl)naphthalenes, followed by their condensation with an iminium ion species formed from the trialkylamine base used in the reaction.
TL;DR: In this paper, a simple and flexible general procedure for the regiospecific annulation of the trifluoromethylpyridine ring to electron-rich amino heterocycles was proposed.
Abstract: The reaction of 4,4,4-trifluoro-3-oxobutanoates with the corresponding electron-rich amino heterocycles was investigated. A simple and flexible general procedure for the regiospecific annulation of the trifluoromethylpyridine ring to electron-rich amino heterocycles was proposed. A set of CF 3 -containing fused pyridines in almost quantitative yield was obtained.
TL;DR: Methyl-l-callipeltose, the carbohydrate associated with callipeltoside A, has been synthesized in eight steps and 23% overall yield from enantioenriched allylsilane 6 and acetaldehyde.
TL;DR: In this paper, a chiral pyridine-type N -oxides 5a was synthesized from (+)-α-pinene (+)- 6 in four steps including photochemical oxidation, followed by Krohnke annulation, α-alkylation, and N-oxidation.
Abstract: New chiral pyridine-type N -oxides 5a – e have been synthesized from (+)-α-pinene (+)- 6 in four steps including photochemical oxidation, followed by Krohnke annulation, α-alkylation, and N -oxidation. The methoxy derivative (+)- 5d exhibited the highest enantioselectivity as a catalyst in the title reaction, producing ( S )-(–)- 3 of 68% e.e.
TL;DR: The dianion 2A derived from 2-methylbenzimidazole has been shown to undergo regioselective 1,2-addition with various alpha-oxoketene dithioacetals derived from acyclic and cyclic ketones to afford various carbinol acetals in high yields.
Abstract: A highly efficient and regioselective annulation protocol for a series of linearly 2,3- and angularly 1,2-substituted and annulated pyrido[1,2-a]benzimidazoles involving [3 + 3] cyclocondensation of the dianions generated from 2-methyl (2A) and 2-cyanomethyl (3A) benzimidazoles with a variety of α-oxoketene dithioacetals has been reported. Thus the dianion 2A derived from 2-methylbenzimidazole has been shown to undergo regioselective 1,2-addition with various α-oxoketene dithioacetals derived from acyclic (4a-d) and cyclic ketones (13a,b, 20, 29 and 32) to afford various carbinol acetals which on intramolecular cyclocondensation in the presence of phosphoric acid furnish the corresponding 1-methylthio-2,3-substituted (5a-c) and 2,3-fused linear polycyclic (14a,b, 21, 30, and 33) pyrido[1,2-a]benzimidazoles in high yields. Similarly the dianion 3A from 2-cyanomethylbenzimidazole undergoes one-pot conjugate addition-elimination and cyclocondensation with these α-oxoketene dithioacetals to give 4-cyano-3-(methylthio)-1(or 1,2-)-substituted (6a-d) and the corresponding angularly 1,2-fused (16a,b, 23, 31, and 34) polycylic analogues of pyrido[1,2-a]benzimidazoles in execellent yields.
TL;DR: The key transformation features a Smiles rearrangement of the initial O-alkylation product and subsequent cyclization of the N-substituted-2-chloroacetamides with use of cesium carbonate in refluxing acetonitrile.
Abstract: Pyrido[2,3-b][1,4]oxazin-2-ones are conveniently prepared in excellent yields by a one-pot annulation of N-substituted-2-chloroacetamides with 2-halo-3-hydroxypyridines with use of cesium carbonate in refluxing acetonitrile. The key transformation features a Smiles rearrangement of the initial O-alkylation product and subsequent cyclization.
TL;DR: A radical annulation reaction among N,N-dichlorosulfonamide, 1,3-dienes, and alkenes has been developed and N-chloro-N-allylamides thus obtained react with a variety ofAlkenes to furnish pyrrolidine derivatives in good yields.
Abstract: A highly regioselective radical addition of N,N-dichlorobenzenesulfonamide (dichloramine-B) to 1-alkenes is achieved at −78 °C by the use of triethylborane as a radical initiator. The reaction of 1,3-dienes with N,N-dichlorosulfonamide in the presence of Et3B regioselectively provides N-chloro-N-allylamide derivatives. N-Chloro-N-allylamides thus obtained react with a variety of alkenes to furnish pyrrolidine derivatives in good yields. A radical annulation reaction among N,N-dichlorosulfonamide, 1,3-dienes, and alkenes has been developed.
TL;DR: The [3 + 2] annulation reactions of allylic silanes can be utilized to achieve acyclic stereocontrol and were employed as a key step in an enantioselective total synthesis of (9S)-dihydroerythronolide A.
Abstract: The [3 + 2] annulation reactions of allylic silanes can be utilized to achieve acyclic stereocontrol. This method was employed as a key step in an enantioselective total synthesis of (9S)-dihydroerythronolide A. The key annulation reaction served to establish most of the stereochemistry of the target, including the two tetrasubstituted carbon stereocenters. The symmetry of the target molecule allowed it to be disconnected into two equally sized fragments, both of which were generated from the same annulation reaction. The two fragments were coupled using a tin(II)-mediated chelation-controlled aldol reaction of an α-benzyloxy ethyl ketone. This convergent total synthesis of (9S)-dihydroerythronolide A was accomplished with the longest linear sequence of 29 steps and in 5.4% overall yield.
TL;DR: Theoretical calculations showed that the most favored intramolecular path for cycloaromatization of 1,2,4-cyclohexatriene 4 and its benzoannulated derivative 14, strained cyclic allenes, consists of a pair of successive[1,2] H shifts rather than a [1,5] shift.
Abstract: A comprehensive theoretical and experimental investigation of dehydro Diels-Alder reactions examining the evolution of the cyclic allene intermediates under conditions for intramolecular and ionic and radical intermolecular cycloaromatization processes is reported. Theoretical calculations showed that the most favored intramolecular path for cycloaromatization of 1,2,4-cyclohexatriene 4 and its benzoannulated derivative 14, strained cyclic allenes, consists of a pair of successive [1,2] H shifts rather than a [1,5] shift. Cycloaromatization of cyclic allenes may follow both inter- and intramolecular pathways, depending on the experimental conditions (use of protic or aprotic solvents). For synthetic purposes, the best procedure is to use a protic solvent to promote the ionic intermolecular route, the fastest and highest yielding. When the reaction is carried out in CCl4, intermolecular radical addition of chlorine to the cyclic allene competes with intramolecular aromatization paths. Theoretical calculations predict a low barrier for the reaction of cyclic allenes with carbon tetrachloride, and that the cyclic allenes act as nucleophiles in this reaction.
TL;DR: Indoles from 2-Methylnitrobenzenes by Condensation with Formamide Acetals Followed by Reduction: 4-Benzyloxyindole.
Abstract: Indoles from 2-Methylnitrobenzenes by Condensation with Formamide Acetals Followed by Reduction: 4-Benzyloxyindole
intermediate: 6-benzyloxy-2-nitrotoluene
intermediate: (E)-6-benzyloxy-2-nitro-β-pyrrolidinostyrene and (E)-6-benzyloxy-β-dimethylamino-2-nitrostyrene
product: 4-benzyloxyindole
intermediate: pyrrolidine enamine, mp 108–110° (MeOH), and N,N-dimethylenamine
Keywords:
alkenylation, C-alkenylation;
alkylation, O-alkylation;
aminomethylenation;
annulation, heterocyclic-[5];
cyclization, reductive cyclization;
reduction, miscellaneous