Regioselective unusual formation of spirocyclic 4-{2'-benzo(2',3'-dihydro)furo}- 9-methyl-2,3,9-trihydrothiopyrano[2,3-b]indole by 4-exo-trig aryl radical cyclization and rearrangement

4-(2'-Bromoaryloxymethylene)-9-methyl-2,3,9-trihydrothiopyrano[2,3-b]indoles under tri-n-butyltin hydride mediated aryl radical cyclization furnished exclusively the 4-{2'-benzo(2',3'-dihydro)furo}-9-methyl-2,3,9-trihydrothiopyrano[2,3-b]indoles in excellent yield (75-80%) via 4-exo-trig cyclization, opening of the oxetene ring, and 5-endo-trig cyclization.     

Novel diastereoselective synthesis of bicyclic beta-lactams through radical cyclization and their reduction toward 2-(1-alkoxy-2-hydroxyethyl)piperidines and 2-(1-alkoxy-2-hydroxyethyl)azepanes

1-Allyl- and 1-(3-phenylallyl)-substituted 4-(2-bromo-1,1-dimethylethyl)azetidin-2-ones were transformed into 3-substituted 7-alkoxy-5,5-dimethyl-1-azabicyclo[4.2.0]octane-8-ones through radical cyclization by means of n-tributyltin hydride and AIBN in toluene with excellent diastereocontrol (>or=99%). The radical cyclization of 4-(2-bromo-1,1-dimethylethyl)-1-(2-methylallyl)azetidin-2-ones afforded 8-alkoxy-3,6,6-trimethyl-1-azabicyclo[5.2.0]nonan-9-ones in good diastereomeric excess (75-78%). The reductive ring opening of 1-azabicyclo[4.2.0]octane-8-ones and 1-azabicyclo[5.2.0]nonan-9-ones with lithium aluminum hydride resulted in novel 2-(1-alkoxy-2-hydroxyethyl)piperidines and -azepanes, which were isolated as single isomers.     

Gold(I)-catalyzed intramolecular [4+2] cycloadditions of arylalkynes or 1,3-enynes with alkenes: scope and mechanism

The cyclizations of enynes substituted at the alkyne gives products of formal [4+2] cyclization with Au(I) catalysts. 1,8-Dien-3-ynes cyclize by a 5-exo-dig pathway to form hydrindanes. 1,6-Enynes with an aryl ring at the alkyne give 2,3,9,9a-tetrahydro-1H-cyclopenta[b]naphthalenes by a 5-exo-dig cyclization followed by a Friedel-Crafts-type ring expansion. A 6-endo-dig cyclization is also observed in some cases as a minor process, although in a few cases, this is the major cyclization pathway. In addition to cationic gold complexes bearing bulky biphenyl phosphines, a gold complex with tris(2,6-di-tert-butylphenyl)phosphite is exceptionally reactive as a catalyst for this reaction. This cyclization can also be carried out very efficiently with heating under microwave irradiation. DFT calculations support a stepwise mechanism for the cycloaddition by the initial formation of an anti-cyclopropyl gold(I)-carbene, followed by its opening to form a carbocation stabilized by a pi interaction with the aryl ring, which undergoes a Friedel-Crafts-type reaction.     

Intramolecular carbolithiation reactions for the preparation of Azabicyclo

Tin-lithium exchange and intramolecular carbolithiation (anionic cyclization) have been used to construct the three nitrogen-positional isomers of the azabicyclo[2.2.1]heptane ring system. The 7-azabicyclo[2.2.1]heptane ring system is accessed from either diastereomer of a 2,5-disubstituted pyrrolidine, via a chiral organolithium intermediate. The 2-azabicyclo[2.2.1]heptane ring system is formed stereoselectively in low yield by a tandem cyclization, together with the product from monocyclization. Better yields of the 2-aza ring system can be obtained using an alternative approach from a 2-tributylstannyl-4-allylpyrrolidine, despite the trans arrangement of the tin (and, hence, lithium) atom and the allyl unit. The 1-azabicyclo[2.2.1]heptane ring system is accessed in just three steps from 4-piperidone.     

Synthesis of 2-phenylthieno[3,2-d]oxazole and 2-phenylthieno[3,2-d]thiazole

2-Phenylthieno[3,2-d]oxazole and 2-phenylthieno[3,2-d]thiazole were obtained by cyclization of the corresponding 2-phenyloxazole and 2-phenylthiazole derivatives. Their spectra and chemical properties were studied, and the pK_a values of carboxylic acids with other two-ring systems with a condensed thiophene ring were also compared.See [1] for our preceding communications.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 474–476, April, 1979.     

Synthesis of some fused β‐carbolines including the first example of the pyrrolo[3,2‐c]‐β‐carboline system

Condensation of 1‐methyl‐β‐carboline‐3‐carbaldehyde with ethyl azidoacetate and subsequent thermolysis of the resulting azidopropenoate was used to [c] annulate a pyrrole ring onto the β‐carboline moiety, thus producing the first example of the pyrrolo[3,2‐c]‐β‐carboline ring system. The latter ring system results from cyclization at the C‐4 carbon, whereas cyclization at the N‐2 nitrogen atom also occurs to form a pyrazolo[3,2‐c]‐β‐carboline ring system. Condensation of β‐carboline‐1‐carbaldehyde with ethyl azidoacetate produced a non‐isolable intermediate, which immediately underwent cyclization, however in this case cyclization occurred via attack at the ester and the azide remained intact. The resulting 5‐azidocanthin‐6‐one was transformed to the first examples of 5‐aminocanthin‐6‐ones. β‐Carboline‐1,3‐dicarbaldehyde failed to give an acceptable reaction with ethyl azidoacetate, but did undergo selective condensation with dimethyl acetylene dicarboxylate at the C‐1 carbaldehyde with concomitant cyclization to form a highly functionalized 2‐formyl‐canthine derivative.     

Base‐Catalyzed Formation of Isoxazoles from Dialkyl Acetylenedicarboxylates and 2‐Nitroacetophenones

The reaction of dialkyl acetylenedicarboxylates with 1‐aryl‐2‐nitroethanones in the presence of pyridine leads to dialkyl 5‐aryloyl‐isoxazole‐3,4‐dicarboxylates through a novel mechanism, which involves a [2+2] cycloaddition/ring opening/cyclization sequence.     

N-Alkenyl-2-aziridinylmethyl radicals and N-alkenylaminyl radicals in cascade cyclizations to pyrrolizidines and indolizidines

[reaction: see text] The radical cascade cyclizations of N-alkenyl-2-aziridinylmethyl radicals to pyrrolizidines and indolizidines were examined using density functional theory (DFT) calculations. A large preference for cyclization to pyrrolizidines was found. These predictions corroborated very well with experimental results, leading to an efficient synthesis of pyrrolizidines. No radical cascade cyclization to indolizidines could be performed in practice as only ring opening of N-alkenyl-2-aziridinylmethyl radicals to N-allyl-N-alkenylamines occurred.     

Synthesis and Characterization of Two [2]Catenanes Based on Phenylene-diacetylene Crown Ethers

Two charged donor-acceptor [2]catenanes were synthesized by the cyclization of the π-acceptor 1,1 ＇-[1, 4-phenylenebis-（methylene）]bis（4,4＇-bipyridinium）bis（hexafluorophosphate）（2） and bis（bromomethyl）benzene with the templates of the π-donor phenylene-diacetylene crown ethers la and lb in the yields of 31%, 35%, respectively. The mass spectra, 1H and 13C NMR spectra confirm that the phenylene-diacetylene crown ethers, with a nonaromatic ~r-system, successfully template the cyclization of CBPQT4＋. The X-ray crystallography analysis shows that the CBPQT4＋ ring encircles around the phenylene motif of the crown ethers, leaving the 1,3-butadiyne fragment out of the cavity of CBPQT4＋ ring. The mechanically interlocked structure of [2]catenanes was stabilized by the cooperative effects of π-stacking and hydrogen bonding interactions.     

Synthesis and reactivity of 4-(2-chloro-5-nitrophenyl)-1,2,3-thiadiazole. A novel one-pot synthesis of N-substituted indole-2-thiols

4-(2-Chloro-5-nitrophenyl)-1,2,3-thiadiazole undergoes ring opening to produce a thioketene intermediate that reacts with an O- or N-nucleophile, forming an ester or an amide of the aryl-substituted thioacetic acid. Intermolecular cyclization of the thioacetic acid derivative via nucleophilic substitution of halogen in the aromatic ring gives an N-substituted indole-2-thiol (in case of an N-nucleophile) or a 2-alkoxy-substituted benzo[b]thiophene (in case of an O-nucleophile). The reaction is also applicable to the synthesis of heterocyclic analogues of N-substituted indole-2-thiols: 1-butyl-1,3-dihydropyrrolo[2,3-b]pyridine-2-thione was synthesized as an example. In the presence of potassium thioacetate (an S-nucleophile) 4-nitro-2-(1,2,3-thiadiazol-4-yl)benzenethiol is formed more quickly than thiadiazole ring opening occurs, making the heterocyclic ring tolerant toward the base.     

Synthesis and Properties of Derivatives of the new Heterocyclic System Benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine

Derivatives of a new heterocyclic system - benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine have been obtained by successive reactions in three stages - alkylation of 3-cyanopyridine-2(1H)-thiones with 2-chloromethylbenzylimidazole to give 2-benzimidazolylmethylthio-3-cyanopyridines, closing the thiophene ring in the latter to form 3-amino-2-(benzimidazolyl-2)thieno[2,3-b]pyridines, and cyclization of the pyrimidine ring by acylation with carboxylic acid anhydrides or chlorides.     

Revisit of the Dessy-White intramolecular acetylene-acetylene [2 + 2] cycloadditions

In this experiment, a series of thermal reactions of 4,4'-disubstituted 2,2'-bis(phenylethynyl)biphenyls with 2,3,4,5-tetraphenylcyclopenta-2,4-dienone were carried out under neat conditions and in diphenyl ether at temperatures between 260 and 270 degrees C to give rise to 9,10,11,12,13,14-hexaphenylcycloocta[l]phenanthrenes as the adducts in 12-23% yields. We traced these results to the intramolecular [2 + 2] thermal cyclization of 2,2'-bis(phenylethynyl)biphenyls to form 1,2-diphenylcyclobuta[l]phenanthrenes, which were further trapped as bridged-ketone Diels-Alder adducts, followed by thermal decarbonylative ring opening, which gave rise to the products.     

Anion templated double cyclization assembly of a chloride selective [2]catenane

The interweaving of two identical acyclic positively charged anion recognizing units around a chloride anion template leads to the formation of an orthogonal supramolecular ensemble which upon subsequent double ring cyclization gives a chloride selective [2]catenane in very high yield.     

Bischler-Napieralski Reaction of 2-(3,4-Dimethoxy-2-nitrophenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]-N-[(S)-1-phenylethyl] acetamide Accompanied by Elimination of Chiral Auxiliary

Chiral 1-benzyltetrahydroisoquinoline alkaloids can be asymmetrically synthesized via Bischler-Napieralski (B-N) cyclization followed by stereoselective NaBH4 reduction (Polniaszek抯 method) of the N- (2-phenylethyl)-2-phenylacetamides bearing chiral auxiliary such as (S)-1-phenylethyl group on the nitrogen atom1-4. Recently Y. Ohishi and co-workers found an unusual B-N reaction on the carbon at 2-position of the A ring, which bears a bromine atom5, 6. They indicated that the steric ef…     

Expeditious construction of a carbobicyclic skeleton via sp3-C-H functionalization: hydride shift from an aliphatic tertiary position in an internal redox process

Described herein is the first example of an aliphatic, nonbenzylic hydride shift/cyclization sequence that contains two types of novel sp(3)-C-H functionalization: (1) construction of a tetraline skeleton via [1,5]-hydride shift/cyclization and (2) [1,6]-hydride shift/cyclization to form a five-membered ring (indane derivatives).     

Mode selectivity in the intramolecular cyclization of ketenimines bearing N-acylimino units: a computational and experimental study

[reaction: see text] The mode selectivity in the intramolecular cyclization of a particular class of ketenimines bearing N-acylimino units has been studied by ab initio and DFT calculations. In the model compounds the carbonyl carbon atom and the keteniminic nitrogen atom are linked either by a vinylic or an o-phenylene tether. Two cyclization modes have been analyzed: the [2+2] cycloaddition furnishing compounds with an azeto[2,1-b]pyrimidinone moiety and a 6pi-electrocyclic ring closure leading to compounds enclosing a 1,3-oxazine ring. The [2+2] cycloaddition reaction takes place via a two-step process with formation of a zwitterionic intermediate, which has been characterized as a cross-conjugated mesomeric betaine. The 6pi-electrocyclic ring closure occurs via a transition state whose pseudopericyclic character has been established on the basis of its magnetic properties, geometry, and NBO analysis. The 6pi-electrocyclic ring closure is energetically favored over the [2+2] cycloaddition, although the [2+2] cycloadducts are the thermodynamically controlled products. A quantitative kinetic analysis predicts that 1,3-oxazines would be the kinetically controlled products, but they should transform rapidly and totally into the [2+2] cycloadducts at room temperature. In the experimental study, a number of N-acylimino-ketenimines, in which both reactive functions are supported on an o-phenylene scaffold, have been successfully synthesized in three steps starting from 2-azidobenzoyl chloride. These compounds rapidly convert into azeto[2,1-b]quinazolin-8-ones in moderate to good yields as a result of a formal [2+2] cycloaddition.     

The synthesis of substituted pyrido[1′,2′:1,5]pyrazolo[3,4-d]pyrimidines

A convenient synthesis of derivatives of the pyrido[1′,2′:1,5]pyrazolo[3,4-d]pyrimidine ring system from readily available 2-amino-3-cyano-5,7-diphenylpyrazolo[1,5-a]pyridine I and carbon disulfide, aryl isothiocyanates or nitriles is described. Derivatives of compound I undergo cyclization to the titled ring system by action of dimethylformamide dimethylacetal or hydrogen sulfide followed by treatment with triethylamine.     

A new cyclization to fused pyrazoles tunable for pericyclic or pseudopericyclic route: an experimental and theoretical study

2-Pyrazinyl (2) and 3-pyridazinylketone arylhydrazones (6) and their benzologues undergo a ring closure reaction to yield pyrazolo[3,4- b]pyrazines (4) and pyrazolo[4,3- c]pyridazines (7), respectively, in acceptable to good yields. The reaction was found to be accelerated by using acidic or basic conditions. Quantum chemical calculations suggest the key step of the mechanism to be a direct cyclization; analysis of aromaticity based on computed magnetic properties revealed its medium-dependent pericyclic or pseudopericyclic character. The cyclization reaction has also been extended for the synthesis of related ring systems ( 9, 12, 14).     

Potential ambifunctionality of 2-azidopyrido[1,2-a] pyrimidin-4-one

2-Azidopyrido[1,2-a]pyrimidin-4-one can exit only in the azido form and undergoes cyclo-addition reaction with 1,3-dicarbonyl compounds to form 1,2,3-triazole derivatives. Under the influence of bases or hydrochloric acid the carbonyl group is attacked with subsequent opening of the pyrimidine ring. This causes an immediate cyclization of the azide group to give a tetrazolo derivative. In a similar way a triazole ring can be formed from the appropriate hydrazino derivatives of pyrido[1,2-a]pyrimidin-4-one.     

Synthesis of 4-membered ring alkaloid analogues via intramolecular [2+2] cycloaddition involving keteniminium salt intermediates

We have developed a very straightforward method for the synthesis of 4-membered ring alkaloid analogues via intramolecular [2+2] cycloadditions. This involves the cyclization of a keteniminium salt in which an alkene is linked by the nitrogen atom, and where, the resulting cyclobutane iminium is reduced in a diastereoselective manner. Competition reactions have been performed to fully understand the features of this sequence. Moreover, DFT calculations have verified that the [2+2] cycloaddition step is driven by kinetic and not thermodynamic factors confirming all the experimental observations.