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The magnesium-mediated addition of bromoform to conjugated electron-deficient alkenes and imines, such as para -quinone methides (p -QMs) and aurone-derived azadienes, respectively, is reported here for the first time. While p -QMs undergo exclusive and hitherto unreported 1,6-addition of bromoform to afford benzylic tribromomethylated diarylmethanes, aurone-derived azadienes undergo both 1,2- and 1,4-additions to furnish α- and γ-tribromomethylamines. A mechanism involving the intermediacy of the tribromomethyl radical has been proposed based on control experiments and EPR studies. Representative synthetic transformations have also been carried out. [ABSTRACT FROM AUTHOR]

The chemoselective [4+2] annulation/aromatization reactions between benzofuran‐derived azadienes and N−Ts cyanamides are developed, affording a convenient method for synthesizing benzofuro[3,2‐d]pyrimidin‐2‐amines under mild conditions. Herein, N−Ts cyanamides participated in reactions selectively via carbodiimide anion intermediates and the corresponding cyanamide anion intermediates derived products were not observed. The proposed chemoselective stepwise reaction mechanism was well supported by DFT calculations. [ABSTRACT FROM AUTHOR]

A highly diastereo‐ and enantioselective organocatalytic Michael addition of α‐aryl isocyanoacetates to aurone‐derived azadienes under mild conditions has been developed. This efficient methodology enables access to chiral α,α‐disubstituted α‐amino ester derivatives with two adjacent stereocenters, one of them quaternary, bearing a benzofuran scaffold in their structure in high yields and stereocontrol. Furthermore, the reaction product can be readily converted into an α,α‐disubstituted α‐amino acid in high yield via hydrolysis of the isocyano group without compromising enantioselectivity. [ABSTRACT FROM AUTHOR]

We describe herein the additive‐controlled divergent [4+2] cycloaddition and 1,4‐Michael addition reaction of benzofuran‐derived azadienes (BDAs) with enamides. An unprecedented [4+2] cycloaddition reaction of BDAs and enamide compounds was developed in the presence of 4 Å MS, providing a variety of structurally complex decahydrobenzofuro[3,2‐b]quinolines (13 examples) in moderate to excellent yields (59–98 % yields) with single diastereoisomer obtained. While employing MgSO4 as desiccant, the chemoselectivity was switched to the 1,4‐addition reactions, leading to a wide range of highly functionalized hybrids of benzofurans and enamide compounds (25 examples) in 25–94 % yields under mild conditions. [ABSTRACT FROM AUTHOR]

A divergent reaction of indoline‐derived azadienes with α‐bromohydroxamates for the selective synthesis of spiro‐indolinepyrrolidinones and indoline‐fused diazepinones was disclosed. This reaction sequence involved an initial formation of five‐membered spirocyclic products followed by an intramolecular ring‐opening and ring expansion to produce seven‐membered diazepinones. We demonstrated that controlling the reaction time could modulate the reaction pathway for formation of different molecular frameworks for the same set of substrates. Based on the experimental results, the reaction mechanism was also discussed and proposed to explain the phenomena observed in the process. [ABSTRACT FROM AUTHOR]

Copper‐catalyzed 1,4‐addition of a silicon nucleophile to azadienes is reported. This method facilely provided a wide variety of dibenzylic silane derivatives in good to excellent yields. The important practical features are the use of a cheap catalytic system, mild reaction conditions, and broad substrate scope. [ABSTRACT FROM AUTHOR]

A Lewis acid-promoted annulation of azadienes and cyclobutamines was developed. This reaction proceeded through Michael addition and ring-expansion cascade, affording the corresponding nitrogen-containing medium-sized rings with a broad scope in moderate to high yields. The catalytic asymmetric version of this reaction has also been explored using a chiral base. [ABSTRACT FROM AUTHOR]

Cationic polycyclic aromatic compounds containing one or more nitrogen atom(s), also known as azonia polycyclic aromatic compounds, form a valuable class of molecules because of their fluorescent and/or medicinal properties. N -Arylated hydroisoquinoline derivatives were synthesized through an aryne aza-Diels–Alder cycloaddition/ N -arylation sequence. A subsequent two-electron oxidation allowed the synthesis of some axially chiral cationic benzo[ c ]phenanthridinium derivatives. The structural and optical properties of some of these molecules were determined. Their chirality was evidenced experimentally by single-crystal X-ray diffraction and1 H NMR spectroscopy, and their conformational behavior was examined by computational DFT methods. [ABSTRACT FROM AUTHOR]

Conjugated azapolyenes (azabuta-1,3-dienes, aza-/diaza-/oxaza-/oxadiazahexa-1,3,5-trienes) are highly reactive in electrocyclization reactions, which makes them convenient precursors for the synthesis of a wide range of four-, five-, and six-membered nitrogen heterocycles that are of relevance for medicinal chemistry. Ring opening reactions of 2H-azirines and azoles containing an N–N or N–O bond, initiated by a transition metal carbene, have become increasingly important in recent years, since they easily allow the generation of azapolyenes with different numbers of double bonds and heteroatoms in various positions. This review summarizes the literature, published mainly in the last decade, on the synthetic and mechanistic aspects of electrocyclizations of azapolyenes generated by the carbene method.

Abstract Brønsted acid‐catalyzed inverse‐electron demand (IED) aza‐Diels‐Alder reactions between 2‐aza‐dienes and ethylene were studied using quantum chemical calculations. The computed activation energy systematically decreases as the basic sites of the diene progressively become protonated. Our activation strain and Kohn‐Sham molecular orbital analyses traced the origin of this enhanced reactivity to i) “Pauli‐lowering catalysis” for mono‐protonated 2‐aza‐dienes due to the induction of an asynchronous, but still concerted, reaction pathway that reduces the Pauli repulsion between the reactants; and ii) “LUMO‐lowering catalysis” for multi‐protonated 2‐aza‐dienes due to their highly stabilized LUMO(s) and more concerted synchronous reaction path that facilitates more efficient orbital overlaps in IED interactions. In all, we illustrate how the novel concept of “Pauli‐lowering catalysis” can be overruled by the traditional concept of “LUMO‐lowering catalysis” when the degree of LUMO stabilization is extreme as in the case of multi‐protonated 2‐aza‐dienes.

Azepanes are important seven‐membered heterocycles, which are present in numerous natural and synthetic compounds. However, the development of convergent synthetic methods to access them remains challenging. Herein, we report the Lewis acid catalyzed (4+3) annulative addition of aryl and amino donor‐acceptor cyclopropanes with 2‐aza‐1,3‐dienes. Densely substituted azepane derivatives were obtained in good to excellent yields and with high diastereoselectivity. The reaction occurred under mild conditions with ytterbium triflate as the catalyst. The use of copper triflate with a trisoxazoline (Tox) ligand led to an enantioselective transformation. The obtained cycloadducts were convenient substrates for a series of further modifications, showing the synthetic utility of these compounds. [ABSTRACT FROM AUTHOR]

The reactions of donor‐acceptor cyclopropanes (DACs) and isomeric β‐styrylmalonates with conformationally non‐rigid α,β‐unsaturated imines in the presence of Lewis acids were studied. The effect of the structural features of starting compounds on the process course was determined. The main attention was focused to discover the reaction conditions for the formal (4+2)‐cycloaddition pathway with the possibility of variation of the α‐substituent in azadiene instead of known (3+2)‐cycloaddition synthetic methodology. Based on the results obtained, a method for the diastereoselective synthesis of substituted trans,trans‐tetrahydropyridines was developed. Three substrate‐sensitive diverse Lewis acid catalytic systems have been employed based on Sc(OTf)3, Sn(OTf)2, and GaCl3. The use of GaCl3 as a Lewis acid allows to obtain a minor product of the formal (2+2+2)‐cycloaddition, which represents a fully 1,2,3,4,5,6‐hexasubstituted cyclohexane derivative produced with diastereoselectivity >30:1. Appropriate mechanistic and stereochemical models have been suggested. [ABSTRACT FROM AUTHOR]

Brønsted acid‐catalyzed inverse‐electron demand (IED) aza‐Diels‐Alder reactions between 2‐aza‐dienes and ethylene were studied using quantum chemical calculations. The computed activation energy systematically decreases as the basic sites of the diene progressively become protonated. Our activation strain and Kohn‐Sham molecular orbital analyses traced the origin of this enhanced reactivity to i) "Pauli‐lowering catalysis" for mono‐protonated 2‐aza‐dienes due to the induction of an asynchronous, but still concerted, reaction pathway that reduces the Pauli repulsion between the reactants; and ii) "LUMO‐lowering catalysis" for multi‐protonated 2‐aza‐dienes due to their highly stabilized LUMO(s) and more concerted synchronous reaction path that facilitates more efficient orbital overlaps in IED interactions. In all, we illustrate how the novel concept of "Pauli‐lowering catalysis" can be overruled by the traditional concept of "LUMO‐lowering catalysis" when the degree of LUMO stabilization is extreme as in the case of multi‐protonated 2‐aza‐dienes. [ABSTRACT FROM AUTHOR]

A Pd-catalyzed oxa-(4+4)-cycloaddition between 1-azadienes and (2-hydroxymethyl)allyl carbonates is described. Aurone-derived azadienes furnished polycyclic 1,5-oxazocines in good yields. Interestingly, linear azadienes have also been involved and yielded monocyclic heterocycles with complete regioselectivity. DFT calculations were carried out to gain insight on this observation. [ABSTRACT FROM AUTHOR]

The squaramide catalyzed enantioselective Michael addition of rhodanines to 2‐arylidene‐N‐tosylbenzofuran‐3(2H)‐imines has been established, which enables the formation of benzofurans bearing both rhodanine and sulfur‐containing tetrasubstituted stereocenter structural motif in good to high yields with good to excellent enantio‐ and diastereoselectivities. [ABSTRACT FROM AUTHOR]

An efficient bifunctional squaramide‐catalyzed Michael addition/cyclization of azadienes with malononitrile has been successfully developed, providing a facile access to chiral benzofuran‐fused 1,4‐dihydropyridines with excellent yields, wide substrate scope and up to 99% ee. Additionally, this formal [4+2] cycloaddition can be performed in gram scale without noticeable loss of yield and enantioselectivity. An efficient bifunctional squaramide‐catalyzed Michael addition/cyclization of azadienes with malononitrile has been successfully developed, providing a facile access to chiral benzofuran‐fused 1,4‐dihydropyridines with excellent yields, wide substrate scope and up to 99% ee. Additionally, this formal [4+2] cycloaddition can be performed in gram scale without noticeable loss of yield and enantioselectivity. [ABSTRACT FROM AUTHOR]

Abstract: A highly enantioselective sulfa‐Michael addition of tritylthiol to azadienes catalyzed by a bifunctional squaramide organocatalyst is described, giving the chiral aminothioethers bearing benzofuran motif with high yields and up to 94 % of enantioselectivity. Notably, the aromatization to form the benzofuran is the driving force. [ABSTRACT FROM AUTHOR]

An enantioselective Michael addition of 3-methylbenzofuran-2(3H)-ones to azadienes catalyzed by an L - tert - leucine derived squaramide catalyst was developed, by which a variety of benzofuranones bearing adjacent quaternary and tertiary carbon centers were obtained in high yields (up to 98%) with moderate to excellent diastereoselectivities (up to 97:3) and enantioselectivities (up to 97%). [Display omitted] [ABSTRACT FROM AUTHOR]

The active complexes of chiral N,N′-dioxide ligands with dysprosium and magnesium salts catalyze the hetero-Diels-Alder reaction between 2-aza-3-silyloxy-butadienes and alkylidene oxindoles to selectively form 3,3′- and 3,4′-piperidinoyl spirooxindoles, respectively, in very high yields and with excellent enantioselectivities. The exo-selective asymmetric cycloaddition successfully regaled the construction of sp3-rich and highly substituted natural-product-based spirooxindoles supporting many chiral centers, including contiguous all-carbon quaternary centers. [ABSTRACT FROM AUTHOR]

Oxidative addition of N-aminophthalimide to 1,2,4-triaryl-1-azabuta-1,3-dienes leads, in most cases, to the regio-defined formation of 1,3,5-triarylpyrazoles in moderate to good yields through [4+1] annulation. This transformation is supposed to proceed by nitrenoid attack onto a lone pair of electrons of the imine nitrogen atom to give the vinylazomethine imine, followed by its 1,5-electrocyclization into pyrazoline and further aromatization into pyrazole. Rare examples of 2-imidoyl-1-phthalimidoaziridines that are formed by competitive [2+1] cycloaddition onto the C=C bond were isolated in low yields for 1-azadienes with electron-deficient aryl substituents at the imine nitrogen atom. [ABSTRACT FROM AUTHOR]

Thermal reactions of 3-( N -aryliminomethyl)chromones ( 4a – d ) with ethyl 2,3-butadienoate ( 5a ) and ethyl 4-phenyl-2,3-butadienoate ( 5b ), on refluxing in dry benzene, afford novel compounds 6a – e , apparently, derived from tandem reorganization of initially formed [2+2] cycloadducts. However, reaction of 4a , d with ethyl 2,3-pentadienoate ( 5c , R = CH 3 ) under similar condition follows a different course yielding novel molecules 7a , d and 8a , d . Plausible mechanistic rationale for the formation of new molecules is proffered. [ABSTRACT FROM AUTHOR]

Abstract: Substituted-3-formylchromones (4a–e) on reaction with 1,3-bis-dimethylaminomethylene-thiourea (5) in refluxing toluene solution give novel substituted 5-(o-hydroxyaroyl)pyrimidines (6a–e) in high yields. A mechanistic rationalization of the formation of products (6a–e) is proffered. Antimicrobial activities of all the synthesized compounds (6a–e) were evaluated against various fungal and bacterial strains. Compound 6d display significant antifungal activity (MIC 15) against Geotrichum candidum in comparison fluconazole used as positive control. Some of the compounds also display good antibacterial activity. Cytotoxic profile of compound 6d against HeLa cells indicates that at concentration (20μM) no significant cell death (∼2%) was observed. [Copyright &y& Elsevier]

Information on the development of a valuable synthetic methodology based on inverse electron-demand Diels-Alder reaction in the series of π-deficient azadienes (triazines and tetrazines) is summarized and classified. By this method it is possible to obtain mono-, di-, and triazines containing functional substituents both from the initial azine and from the dienophile. Such reactions are often the simplest and even the only possible method for the synthesis of substances with properties suitable for practical applications. [ABSTRACT FROM AUTHOR]

The synthesis of aryl-substituted 1,4-dihydroquinolines can be achieved using a [4+2] cycloaddition between benzyne and various aryl-substituted 1-azadienes. The conditions are tolerated by N-aryl-, alkyl-, tosyl-, and tert-butoxycarbonyl-protected 1-azadienes. A short synthesis of the fungal metabolite 3-O-methylviridicatin is reported. [ABSTRACT FROM AUTHOR]

Abstract: N-Vinyl 2,2-bisphosphonoaziridines are formed by treatment of 1,1-bisphosphono-2-aza-1,3-dienes with diazomethane. Depending on the substituents at the 4-position of the 1,1-bisphosphono-2-aza-1,3-dienes, exclusively 1-(ethenylamino)-2-phosphonoethenylphosphonates or mixtures of 1-(ethenylamino)-2-phosphonoethenylphosphonates and 2-imino-2-phosphonoethylphosphonates are obtained as side products. [Copyright &y& Elsevier]

Several 2-azadienes were prepared by treatment of im�ines derived from diphenylmethanamine and ketones with sodium hydride in DMF under an air atmosphere. [ABSTRACT FROM AUTHOR]

Abstract: The comparative account of the reactivities of N′-[(5-benzoyl and ethoxycarbonyl)thiazol-2-yl]-N,N-dimethylformamidines ( 1a and 1b ), tremendously influenced by the electronic nature of the substituents on C-5 of the thiazolic ring with various monosubstituted and conjugated ketenes is reported herein. The DA cycloadditions of the dienyl pyrimidinone 3h with both symmetrical as well as unsymmetrical dienophiles leading to the formation of various thiazolic pyrimidinone derivatives are also reported. [Copyright &y& Elsevier]

Simple and functionalized N-phosphorylalkyl imines and N-phosphorylalkyl-N′-phenyl-carbodiimides are obtained by aza-Wittig reaction of phosphazenes derived from aminophosphonates with carbonyl compounds and phenyl isocyanate. The reaction with dimethylformamide diethyl acetal (DMF–DEA) of these functionalized imines leads to the synthesis of 4-amino-3-phosphoryl-2-azadienes. N-Phosphorylmethyl imine derived from benzaldehyde can be used for the preparation of substituted pyrrole-phosphonates, while acid treatment of 4-dimethylamino-3-diethylphosphoryl-1-phenyl-2-azadiene gives diethyl 5-diethylphosphorylpyrazin-2-ylphosphonate. [Copyright &y& Elsevier]

Irradiation of 3-(9-fluorenyliden)-2,2-dimethylpropenal oxime acetate, using 9,10-dicyanoanthracene (DCA) as electron transfer sensitizer and biphenyl as cosensitizer, yields an unexpected product that was identified by single-crystal structure analysis as 3,3-dimethyl-4-(9-fluorenyl)-5-(9-fluorenylidene)-1-aza-1-pentenyl-acetate. The formation of this product is surprising, since related β,γ-unsaturated oxime acetates yield the corresponding products resulting from aza-di-π-methane rearrangements, under the same reaction conditions. A possible mechanism is proposed to justify the formation of this new compound. [Copyright &y& Elsevier]

Unusual cascade cycloaddition reactions with dimethylhydrazones of α-trimethylsilyloxyalkylacroleins acting as azadienes were found. Depending on the nature of the dienophile, the reactions give either fused heterocyclic compounds (when two consecutive Diels—Alder reactions take place) or azabicyclic compounds, resulting from the [2+4]- and [2+3]-cycloaddition cascade. [ABSTRACT FROM AUTHOR]

5167 5167 1 12/09/21 20211207 NES 211207 B The front cover picture b , designed by Pavel G. Sergeev and Daria I. Filina, illustrates the comparison between reactivities of donor-acceptor cyclopropanes and styrylmalonates in the Lewis acid-catalyzed formal cycloadditions with conformationally non-rigid azadienes. EN Styrylmalonates Donor-acceptor cyclopropanes Azadienes Tetrahydropyridines Formal (4+2)-cycloaddition Formal (2+2+2)-cycloaddition Lewis acid catalysis. Keywords: Styrylmalonates; Donor-acceptor cyclopropanes; Azadienes; Tetrahydropyridines; Formal (4+2)-cycloaddition; Formal (2+2+2)-cycloaddition; Lewis acid catalysis. [Extracted from the article]