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A highly efficient and flexible protocol for intramolecular annulation of exocyclic β-enaminones has been disclosed for the synthesis of carbazolones and imidazo[1,2-a]pyridines through a counter-anion-controlled free-radical mechanism promoted by hypervalent iodine(III). The cooperative behavior of HTIB and AgSbF6 plays a crucial role in the intramolecular annulation process through C-C and C-N bond formation to give the desired products. The mechanistic insights suggest that the two competitive reactions involved in the system are guided by the nature of the counteranion, which determines the formation of the final products. A wide variety of carbazolones and imidazo[1,2-a]pyridine molecules have been prepared and isolated in good to excellent yields.

A novel and efficient L-proline catalyzed Michael reaction of several 4-aryl/heteroaryl-substituted cyclic sulfamidate imines with a variety of β-styryl/aryl/alkyl-substituted acroleins, followed by in situ elimination-iminocyclization-dehydration sequence process in the presence of DABCO as a base is reported for the first time. By this unconventional one-pot sequential protocol, a number of 2-aryl/heteroaryl-4-styrylpyridines and 2,4-diarylpyridines have been prepared in good to high yields under metal-free conditions. Besides, the synthesized 4-styrylpyridine derivatives were also further utilized for the synthesis of commercially as well as pharmaceutically important 2-arylisonicotinic acids.

Microwave irradiation of 2-carbethoxyacetamidine and an ethynyl ketone under acidic or basic conditions in ethanol at 150 °C for 1.5 hours facilitated Bohlmann–Rahtz pyridine synthesis to give highly substituted ethyl 2-aminonicotinates with total regiocontrol and in reasonable to excellent yield, following purification by immobilization upon an acidic resin.

The kinetics of vapour phase aminocylisation of acetaldehyde, formaldehyde, and ammonia over deactivating HZSM-5 catalyst is studied. A series-parallel reaction scheme has been employed in which coke formation from its precursors has been lumped. Applying the concept of separable kinetics, the catalyst deactivation and reaction kinetics unconstrained and constrained by it are studied independently. Employing experimental time on stream studies, the rate of catalyst decay has been computed from the latter. A catalyst deactivation function based on experimental decay of its activity has been evaluated separately. Its magnitude and trajectory matched well with that of the computed catalyst decay function. It facilitated to obtain a direct relationship between coke formation and product distribution as a function of time on stream for aminocyclisation. An attempt has also been made to study the regeneration characteristics of the catalyst. On a etudie la cinetique de l'aminocyclisation en phase gazeuse de l'acetaldehyde, du formaldehyde et de l'ammoniaque, avec desactivation du catalyseur HZSM-5. Un schema de reactions serie-parallele a ete utilise, schema dans lequel la formation de coke a partir de ses precurseurs a ete consideree en bloc. En appliquant le concept de cinetiques separees, la desactivation du catalyseur et la cinetique des reactions freinees ou non par cette desactivation sont etudiees independamment. En utilisant le temps experimental pour les etudes des differents circuits, le taux de decomposition du catalyseur a ete calcule par ordinateur. Une fonction de desactivation du catalyseur base sur la degradation experimentale de son activite a ete evaluee separement. Son amplitude et sa trajectoire correspondaient bien avec la fonction calculee par ordinateur de la degradation du catalyseur. Il etait utile d'obtenir une relation directe entre la formation de coke et la distribution de produits comme une fonction du temps pour les circuits d'aminocyclisation. Une tentative d'etude des caracteristiques de regeneration du catalyseur a egalement ete faite.

Recent advances in pyridine synthesis are described. Modification of traditional condensation strategies continues to be a recurrent theme in contemporary literature. Advancements in transition-metal-catalyzed cyclization and cross-coupling procedures offer new routes to functionalized pyridine derivatives. These recently developed methodologies are a valuable addition to azaheterocycle synthesis.

The scope of a novel alkoxyallene-based pyridine synthesis was expanded to enantiopure carboxylic acids and nitriles as starting materials. The enantiomeric purity of the chiral α-secondary carboxylic acids and nitriles was completely preserved during this reaction sequence thus allowing the one-pot preparation of a whole range of 4-hydroxy-pyridines or their 4-pyridinone tautomers in good yields.

Redox activity of copper is combined with the iminium activation strategy to construct various pyridine derivatives, including polysubstituted pyridines.

A new methodology has been developed for the synthesis of pyridines from allyl amines and alkynes, which involves sequential Cu(II)-promoted dehydrogenation of the allylamine and Rh(III)-catalyzed N-annulation of the resulting α,β-unsaturated imine and alkyne.

The synthesis of pyridines, e.g. (III)/(IV) from readily available α,β-unsaturated oximes such as (I) and alkynes (II) under mild conditions using Rh(III) catalysis is developed.

Recent advances in pyridine synthesis are described. Modification of traditional condensation strategies continues to be a recurrent theme in contemporary literature. Advancements in transition-metal-catalyzed cyclization and cross-coupling procedures offer new routes to functionalized pyridine derivatives. These recently developed methodologies are a valuable addition to azaheterocycle synthesis.

An activation of the pyridine nucleus has been achieved via 1,5-electrocyclization of vinyl pyridinium ylides generated from bromo isomerized Morita-Baylis-Hillman adducts of isatin and pyridine under basic conditions. The method has been successfully applied for an efficient synthesis of a number of 3-spirodihydroindolizine-2-oxindoles, which have been found as core structure of secoyohimbane and heteroyohimbane alkaloid natural products.

If sodium methoxide was present as an electrolyte and nacleophile,the 1-acylpyridinium salt intermediate would be deacylated and converted to the free base pyridine.

[reaction: see text] The formal synthesis of the ocular age pigment A2-E was achieved by the efficient one-pot preparation of the substituted pyridine, which involves the aza-6pi-electrocyclization of the Schiff base derived from (E)-3-carbonyl-2,4,6-trienal followed by oxidation.

A novel and useful method for the synthesis of 2-arylpyridines with a high efficiency and generality was achieved by utilizing the one-pot 6π-azaelectrocyclization followed by a base treatment. This is the first example of applying a sulfonamide to the azaelectrocyclization for efficient substituted pyridine synthesis.

The results of our research into the Bohlmann-Rahtz -pyridine synthesis are summarized. The historic discovery of this reaction and its mechanism are discussed; followed by recent improvements in methodology, such as Bronsted and Lewis acid catalysis, microwave assistance, process in a continuous flow reactor, and incorporation into multicomponent and tandem reactions. -Applications of these methods in the synthesis of pyrido[2,3- D]pyr-imidines, combinatorial pyridine libraries, heterocyclic α- and γ-amino acids, α-helix mimetics, and complex natural products are discussed, along with a consideration of future perspectives. 1 Discovery 2 Recent Improvements in Methodology 2.1 Catalyst and Solvent Effects 2.2 Tandem Bohlmann-Rahtz Processes 2.3 Microwave Dielectric Heating 2.3.1 Batch Reactors 2.3.2 Continuous-Flow Reactors 3 Recent Applications 3.1 Pyridine Libraries and Scaffolds 3.2 Fused Heterocycles 3.3 Natural Product Chemistry 4 Conclusion and Perspectives

Reaction of 1-(cyanoacetyl)-3,5-dimethylpyrazole with (E)-2-cyano-3-(het)arylprop-2-enethioamides was used for the synthesis of N-methylmorpholinium 3,5-dicyano-4-(het)aryl-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates for the first time. The latter were also obtained in a multicomponent one-pot mode via the condensation of cyanothioacetamide with corresponding aldehydes and above 1-cyanoacetylpyrazole in the presence of N-methylmorpholine under mild conditions. Thiolates 1 exist as a pair of cis/trans-diastereomers in different ratios (from 3:4 to 2:1).

The α-Chloro-α-acetoxy-β-keto-esters were prepared from β-keto-esters in good overall yields. These compounds reacted as α,β-diketo-ester equivalents with amidrazones yielding triazines, generally in good yields, or with an amidrazone and 2,5-norbornadiene in a one-pot aza Diels–Alder reaction to give the corresponding pyridines.

Recently, we found that (E)-3-carbonyltrienal compounds irreversibly reacted with the specific Lys of phospholipase A2 (PLA2) to produce 1, 2-dihydropyridine via facile 6π-azaelectrocyclization leading to inactivation of the enzyme. The smooth azaelectrocyclization was due to the presence of both the C 4-carbonyl group and the C 6-alkenyl group in 1-azatriene: this attractive discovery prompted us to investigate the substituent effects on azaelectrocyclization and to develop it as a method of natural products synthesis. The paper describes our efforts on (i) establishing the new synthesis of 3-cis-1-azatrienes as the precursors of azaelectrocyclization, (ii) cyclization studies, and (iii) rationale for smooth electrocyclization based on molecular orbital calculation. Then, we achieved (iv) one-pot pyridine synthesis and (v) highly stereoselective asymmetric azaelectrocyclization, which were applied to the formal syntheses of the ocular age pigment, A 2-E, and an optically active indole alkaloid, 20-epiuleine, respectively.

1-α-Pyridinium acetophenone chloride 2 on reaction with 2-cinnamoylbenzimidazoles 3 followed by alkylation yieldsl-alkyl-2-(substituted-2-pyridyl) benzimidazoles 5. The latter could also be synthesized by direct reaction of 2 with 1-alkyl-2-cinnamoylbenzimidazoles 6 in accordance with the Krohnke's pyridine synthesis.

(η3-Allyl)(η5-pentamethylcyclopentadienyl)cobalt – a Selective Catalyst for the Pyridine Synthesis (η3-Allyl)(η5-pentamethylcyclopentadienyl)cobalt (1) catalyses the synthesis of various pyridines from alkynes and nitriles under mild conditions. Only small amounts of benzenes are formed in this selective reaction.

A variety of 5-mono- and 5,6-disubstituted 1,4-dihydro-4-oxonicotinates were prepared by a novel pyridine synthesis which involves thermal cyclisation of enaminomethylenemalonates 9. The intermediates 9 were readily prepared through a few steps from commercially available starting materials.

Perehloroimidazo[1,2-a]pyridine has been prepared and it has been shown that nucleophilic substitution occurs preferentially at C5 possibly followed by substition at C7.

Recent syntheses of kainoids were reviewed with 96 references. In the syntheses, formation of the proline nucleus and stereochemical arrangement of the substituents around the proline ring were the key steps, in which ene-reactions, homo- and hetero-Diels-Alder reactions, radical ring closures, Claisen rearrangement and 1, 3-dipolar cyclo-additions were mainly employed. A new method for a pyridine synthesis was also developed for acromelic acids. The synthetic schemes were classified into the following 5 groups according to the position of C-C bond formation in the key steps. 1) C3-C4 bond formation, 2) C2-C3 and C4-C5 bond formation, 3) side chain introduction to proline moiety, 4) conversion of kainic acid to other kainoids and 5) some other synthetic approaches and syntheses of derivatives.