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A class of novel chiral‐bridged biphenyl monophosphine ligands with a benzofuran moiety (He‐phos) has been successfully synthesized and reported. These ligands exhibited good performance in the gold‐catalyzed enantioselective cycloaddition reaction of 2‐(1‐alkynyl)‐2‐en‐1‐ones with nitrones, resulting in the successful preparation of a series of polyaryl‐substituted heterocyclic compounds with high enantioselectivities (up to 99% yield, 98% ee). The wide substrate adaptability (53 examples) and mild reaction conditions demonstrate the practicability of He‐phos in this reaction. [ABSTRACT FROM AUTHOR]

An asymmetric 1,3‐dipolar cycloaddition of β‐fluoroalkylated α,β‐unsaturated 2‐acyl imidazole with nitrones or N,N'‐cyclic azomethine imines to construct chiral α‐fluoroalkylated γ‐amino alcohols or chiral α‐fluoroalkylated 1,3‐diamino compounds has catalyzed by chiral‐at‐metal rhodium complexes is reported. The corresponding products with three contiguous tertiary stereocenters were obtained in 62%–98% yields with stereoselectivities up to >20:1 dr and 99% ee. Remarkably, as low as 0.06 mol% of chiral‐at‐metal rhodium complex can promote a gram‐scale reaction with nitrones or N,N'‐cyclic azomethine imines. [ABSTRACT FROM AUTHOR]

Complex spirocyclic isoindolines and pyrrolidines are formed in a tandem process involving Co(III)‐catalyzed dienylation of cyclic C‐aryl nitrones with 2,3‐butadien‐1‐ol carbonates, followed by intramolecular 1,3‐dipolar cycloaddition. The nitrone moiety serves both as a directing group for the C(aryl)−H activation and the dipole in the cycloaddition step. High regioselectivity of the fused vs. bridged product can be obtained by adjusting the reaction temperature. Reactions with substituted allenic substrates provide heterocycles with additional stereocenters usually with complete diastereoselectivity. The reaction products were readily transformed further into other complex nitrogen‐containing spirocyclic systems. [ABSTRACT FROM AUTHOR]

δ,ϵ‐Unsaturated oximes, on heating with O‐alkyl S‐(pyridin‐2‐yl)carbonothioates (PySCO2R) in refluxing toluene, undergo intramolecular cycloaddition to give N‐alkoxycarbonylated multi‐cyclic compounds. Mechanistic studies indicate that the reaction involves direct generation of N‐alkoxycarbonyl nitrones followed by cycloaddition, instead of intramolecular oxime‐olefin cycloaddition (IOOC) followed by alkoxycarbonylation. DFT calculation indicates that N‐alkoxycarbonylation of oxime with PySCO2R is a concerted reaction. The reaction of oxime with a chiral alkoxycarbonylation reagent exhibits a reasonably high diastereo‐face selectivity. [ABSTRACT FROM AUTHOR]

We herein disclose a simple and general method for the synthesis of chromendiones through Rh(III)‐catalyzed C−H functionalization/annulation reactions of nitrones with cyclic 2‐diazo‐1,3‐diones by using nitrone group as a traceless directing group. This method exhibits high efficiency and broad functional group compatibility. The derivatization of these chromendiones has been also demonstrated to further strengthen the synthetic utility of the transformation. [ABSTRACT FROM AUTHOR]

Gold‐catalyzed cascade reactions between 1,5‐diyn‐3‐ols and nitrones to deliver carbazole derivatives are described. Such cascade reactions are applicable to facile synthesis of polyaromatic compounds containing carbazole subunits. Notably, the reaction mechanism involves unexpected oxoarylations, rather than oxidative Mannich reactions as known for but‐1‐yn‐4‐ols. Our control experiments indicate that the presence of a second alkyne as in 1,5‐diyn‐3‐ols enables such oxoarylations due to a weak bonding between gold and this alkyne, rending the tethered alcohol less conformationally flexible. [ABSTRACT FROM AUTHOR]

A variety of functionalized 2‐pyrrolidinones bearing N‐trifluoromethylphenyl moieties were prepared in moderate to good yields with high diastereoselectivity through copper(II)‐catalyst and base co‐catalyzed formal [4+1] cycloaddition of cinnamaldehyde nitrones with 1‐ethynylnaphthalen‐2‐ols in the presence of m‐CPBA as the oxidant. The triple bond of 1‐ethynylnaphthalen‐2‐ol served as one‐carbon synthon for the pyrrolidinone ring formation. Mechanistic studies revealed that m‐CPBA played an important role to interrupt the intramolecular O‐cyclization to afford the 2‐pyrrolidinones. Moreover, the reaction could be easily performed at gram scales and the obtained products were selectively converted into diverse pyrroline scaffolds. [ABSTRACT FROM AUTHOR]

A variety of 4‐phosphinylpyrrolidin‐3‐ones was prepared via a [3+2] cycloaddition between aryl aldonitrones and phosphinylallenes. The products were isolated as unique 4,5‐trans diastereomers, in yields between 47% and 80%, over 23 examples. In the case of chiral racemic allenes, a 2:1 to 4:1 moderate 2,5‐diastereoselectivity was observed. Under the reaction conditions, the cycloadducts directly undergo a rearrangement to afford selectively the corresponding pyrrolidin‐3‐ones. DFT calculations provide some insights into the mechanism, involving the homolytic cleavage of the N−O bond of the cycloadduct. [ABSTRACT FROM AUTHOR]

We described a copper(II)‐catalyzed [3+2] cycloaddition of N‐aryl‐α,β‐unsaturated nitrones with disubstituted allenoates bifurcated to prepare various [1,3]oxazino[3,2‐a]indolines and dihydropyrido[1,2‐a]indolines in moderate to excellent yields. Mechanistic studies revealed that [1,3]oxazino[3,2‐a]indoline was a kinetically favored product and dihydropyrido[1,2‐a]indoline was thermodynamically favored product. Moreover, the reaction was easily performed at gram scales and chiral dihydropyrido[1,2‐a]indoline could be obtained by using chiral auxiliary. The present method highlights broad substrate scope, good functional group tolerance, and diversity of indoline scaffolds with high diastereoselectivity. [ABSTRACT FROM AUTHOR]

A self‐enabled electrooxidative protocol for the synthesis of nitrones from bench stable amines has been developed under constant current electrolysis at room temperature, rendering metal and external oxidant‐free protocol in an alkaline medium. The electrocatalysis steps of reported strategy involve anodic oxidation of benzyl amines followed by cathodic reduction of nitro‐functional group in an undivided cell affording functional nitrones. The robustness of the electrocatalysis was reflected by tolerant substrate scope, oxidant‐free conditions, and an operationally friendly procedure. Moreover, the cyclic voltammetry and control experiment studies also support the electrochemical process in alkaline medium. [ABSTRACT FROM AUTHOR]

We describe a DBU‐controlled 6π‐azaelectrocyclization of dibenzylideneacetone‐derived N‐vinyl‐α,β‐unsaturated nitrones to prepare 6‐alkyl pyridine N‐oxides in 24–82% yields. Mechanistic studies revealed that DBU had a great impact on the formation of 6‐alkyl pyridine N‐oxides and served as a base and the carrier of hydrogen sources to in situ reduce C=C bonds. The 6‐alkyl pyridine N‐oxide was prepared at gram‐scales and converted to estrone‐derived pyridine and pyrido[2,3‐c]carbazole 4‐oxide in 46% and 52% yields in two steps, respectively. [ABSTRACT FROM AUTHOR]

Various spirooxindole‐benzo[d]oxazoles and dihydrobenzofurans were prepared in good to excellent yields by [3+2] cycloaddition and selective rearrangement of N‐vinyl oxindole nitrones and arynes under transition metal‐free conditions. Experimental results showed that the substituent on the nitrone N‐vinyl group controlled the [1,3]‐ or [3,3]‐rearrangement of their cycloadduct owing to its steric effect. The present method features broad substrate scope, good functional group tolerance, controllable [1,3]‐ or [3,3]‐rearrangement, and diverse oxindole scaffolds. [ABSTRACT FROM AUTHOR]

A variety of chiral nine‐membered N‐heterocycles were prepared in moderate to good yields with high diastereoselectivity through a silver(I)‐catalyzed [3+2] cycloaddition and [3,3]‐rearrangement of N‐vinyl‐α, β‐unsaturated nitrones and chiral 3‐propioloyloxazolidin‐2‐ones. Experimental studies showed that silver catalyst promoted the cycloaddition and rearrangement process, and the stereochemistry of the nine‐membered N‐heterocycles was controlled via [3,3]‐rearrangement by chiral oxazolidinone‐auxiliary through a boat‐like transition state. Moreover, the obtained nine‐membered N‐heterocycle diastereomers were converted to chiral pyrrolizines with high diastereoselectivity and pyrrolizine carboxylate was obtained in 54% yield with 90% ee by the removal of chiral auxiliary. [ABSTRACT FROM AUTHOR]

A gold‐catalyzed synthesis of 1,3‐dihydrooxazolo[3,4‐a]indoles from 1‐oxo‐3‐yn‐4‐ols and nitrones is described; this new bicyclic annulation presents the first examples that internal alkynes can react with nitrones to undergo an oxoarylation route. DFT calculations indicate a [3,3]‐sigmatropic shift of initial alkenylgold intermediates to elude the intermediacy of gold carbenes. We also developed new [3+2]‐annulations of the same 1‐oxo‐3‐yn‐4‐ols with imines, yielding oxazolidin‐4‐ylidene derivatives efficiently. The tethered alcohols of these 1‐oxo‐3‐ynes allow trapping of their metastable 2‐azadienium intermediates to enable a novel annulation. Our mechanistic analysis indicates that the two products, despite their structural relevance, are produced from two independent systems. [ABSTRACT FROM AUTHOR]

Herein we report a mild and diastereoselective access to ketonitrones by reacting easily available aryl acetic acid esters and other active methylene compounds, with nitrosoarenes under catalytic loading of 2‐tert‐butylimino‐2‐diethylamino‐1,3‐dimethylperhydro‐1,3,2‐diazaphosphorine (BEMP) at room temperature. Depending on the substitution pattern and nature of the aryl moiety, a switch toward the formation of imines can be observed. The mechanistic framework is put to scrutiny by experimental and theoretical studies, pointing to the formation of a nitroso aldol intermediate, whose fate toward one of the competing pathways, namely hydride transfer or elimination, would depend upon the NOH/CHα relative acidities. [ABSTRACT FROM AUTHOR]

Nitrones are key intermediates in organic synthesis. Herein, we report the first photo‐redox synthesis of methylene nitrone intermediates from nitroarenes and arylamines. The highly reactive methylene nitrones are in situ trapped by alkenes to afford various isoxazolidines. This three‐component reaction features the use of N,N‐dimethylanilines or N‐aryl glycines as C1 building blocks, which allow for the one‐pot formal [1+2+2] cycloaddition from simple starting materials. A wide range of useful isoxazolidines can be obtained under mild conditions with moderate to good yields. Mechanistic investigations support the formation of methylene nitrone via selective N−CH3 bond cleavage and methylene transfer. [ABSTRACT FROM AUTHOR]

In this review, the versatile and rich chemistry for the electrochemical reduction of substrates involving N−O bonds is surveyed. By the cathodic treatment of nitro, nitroso and other oxygenated organic nitrogen substrates, versatile and reactive intermediates are formed which can be subsequently converted to high value‐added products. In many examples, nitrogen heterocycles are selectively formed, but, also depending on the electrolytic conditions, free oximes, nitrones, amines and other entities can be obtained as well. The recent decades have witnessed two major advances – (i) going directly to more complex target molecules and (ii) conducting the electrolyses in much simpler set‐ups. Both improvements make the cathodic access of the target compounds much more practical and scalable. [ABSTRACT FROM AUTHOR]

The review summarizes the chemistry of nitrones and nitronates in the context of the C−H reactivity of their α‐carbon atoms. Electrophilic, nucleophilic and radical reactions leading to functionalization of the α‐position are described. Examples of the application of these processes in total synthesis are outlined. [ABSTRACT FROM AUTHOR]

We report a Yb(OTf)3‐catalyzed formal [7+2] cycloaddition for the preparation of nine‐membered N‐heterocycles bearing three stereocenters in good yields with high diastereoselectivity through a [3+2] cycloaddition/[3,3]‐rearrangement cascade strategy from N‐vinyl‐α,β‐unsaturated nitrones and methylenecyclopropanes. Preliminary studies show that the Yb(OTf)3 catalyst accelerates the reaction affording kinetically controlled cis‐diastereomers as the major products. The obtained nine‐membered N‐heterocycles are easily converted to useful derivatives for late‐stage modification. [ABSTRACT FROM AUTHOR]

A variety of spirofluorenyl‐β‐lactams have been prepared in moderate yields over three steps from N‐aryl fluorenone nitrones and methylenecyclopropanes through a [3+2] cycloaddition, reduction and subsequent acid‐catalyzed ring contraction cascade strategy under mild reaction conditions. Experimental studies showed that the stereochemistry remained intact after the ring contraction step. Furthermore, the obtained spirofluorenyl‐β‐lactam was easily converted to two novel spiroazetidine and spiroquinolinone scaffolds in good yields. [ABSTRACT FROM AUTHOR]

An unprecedented gold‐catalyzed dual annulation of homopropargyl alcohols with nitrones has been developed, which provides an effective access to the 1,3,4,5‐tetrahydropyrano[4,3‐b]indole derivatives in good to high yields. Mechanistically, this one‐pot three‐step cascade reaction is initiated by a gold‐catalyzed alkyne oxoarylation, followed by an intramolecular cyclodehydration and terminated with an intermolecular cyclization with aldehyde which is a leaving species in the early stage of this cascade process. [ABSTRACT FROM AUTHOR]

An efficient organocatalytic cascade reaction for synthesising functionalized bicyclic nitrones is reported. The reaction of dielectrophilic ethyl 2‐(nitromethylene)‐4‐arylbut‐3‐ynoate and (E)‐diethyl 2‐((2‐hydroxybenzylidene)‐amino)malonates to give a unique nitrone scaffold in the presence of a catalytic amount of DABCO is described. The working mechanism was proposed to proceed with allene formation followed by intramolecular cyclization and the rearrangement of an oxygen atom in the nitro group. A broad range of substrates was accessed in this facile chemical transformation, in which the bicyclic nitrones were isolated in moderate to good yields (19% to 79%) with excellent diastereoselectivity (>20:1 dr). [ABSTRACT FROM AUTHOR]

Abstract: A reaction of nitrones with 1,2‐dibromotetrafluoroethane affording bromodifluoroethyl‐substituted hydroxylamines is described. The process is performed in the presence of a ruthenium photocatalyst and ascorbic acid as a stoichiometric reducing agent and is mediated by blue light irradiation. The fluroalkylation products can undergo chemoselective transformations involving either N−O or C−Br bonds furnishing various tetrafluorinated compounds. [ABSTRACT FROM AUTHOR]

Abstract: An effective and facile method for the synthesis of highly substituted 1,2,3,5‐tetrahydrobenzo[e][1,2,4]‐oxadiazepines is described. A formal [4+3] cycloaddition of N‐(2‐(chloromethyl) phenyl) amides with nitrones afforded benzo[e][1,2,4]‐oxadiazepine derivatives with high atom economy and excellent yields (up to 97%). [ABSTRACT FROM AUTHOR]

Abstract: An effective and facile method for the synthesis of highly substituted 1,2,3,5‐tetrahydrobenzo[e][1,2,4]‐oxadiazepines is described. A formal [4+3] cycloaddition of N‐(2‐(chloromethyl) phenyl) amides with nitrones afforded benzo[e][1,2,4]‐oxadiazepine derivatives with high atom economy and excellent yields (up to 97%). [ABSTRACT FROM AUTHOR]

Abstract: Two controllable one‐pot cascade cyclization reactions of homopropargylic amines and nitrones were developed by using different metal Cu and Ag salts. The pyrroloisoxazolidines and γ‐lactams were obtained in good to high yields, respectively. Herein, nitrones played dual roles, both as 1,3‐dipoles and oxidants, and four stereocenters were simultaneously formed in the hydroamination cyclization‐1,3‐dipolar cycloaddition cascade reaction of homopropargylic amines and nitrones in the presence of AgOAc. [ABSTRACT FROM AUTHOR]

The experimental and computational study of the mechanism of the iminium-organocatalyzed formation of N-hydroxypyrrolidines from nitrones, revealed up to three activation levels of the Schreiner's thiourea used as co-catalyst, i.e: (i) formation of the iminium ion through hydroxyl anion recognition forming a stable ion pair; (ii) enolization of the nitrone through a H-bond network and (iii) activation of the nitrone moiety towards the final ring closure. The computational model supports the mechanism and the catalytic cycle. This mechanistic rationale is supported by the lack of reactivity of preformed iminium ion with the nitrone in the absence of thiourea-hydroxyl complex and the observed reactivity when a complex thiourea-tetrabutylammonium hydroxide is added. [ABSTRACT FROM AUTHOR]

A new 4-dimethylaminopyridine (DMAP)-mediated [3+3] cycloaddition reaction of in situ- generated aza-oxyallyl cations with nitrones is reported. This simple and efficient method delivers a series of new motifs in good to excellent yields under mild conditions. [ABSTRACT FROM AUTHOR]

The enantioselective synthesis of tetralin derivatives bearing a trifluoromethylated all-carbon quaternary stereocenter has been accomplished through a synthetic sequence comprising an organocatalytic β-functionalization of ortho-1-trifluoromethylvinyl-(hetero)aromatic conjugated aldehydes followed by the intramolecular nitrone 1,3-cycloaddition reaction (INCR). Both nitromethane and N-Cbz-hydroxylamine were employed as nucleophiles in the initial organocatalytic conjugate addition step, which provided the chiral information required for the subsequent diastereoselective INCR. Although diastereoselectivity was moderate, good yields and enantioselectivities were, in general, obtained. Interestingly, an inversion of the selectivity in the intramolecular cycloaddition step was observed when either nitromethane or N-Cbz-hydroxylamine was employed. This outcome was studied by means of theoretical calculations, which were in agreement with the experimental results. In addition, the ring opening of the isoxazolidine moiety furnished the corresponding fluorinated diamino alcohols in a very efficient manner. [ABSTRACT FROM AUTHOR]

A metal-free construction of highly diastereoselective nine-membered heterocycles is described via the cycloaddition and rearrangement of N-vinyl- α,β-unsaturated ketonitrones and isocyanates. Notably, the prepared nine-membered heterocycles afforded 2,3-dihydropyrrolizines under heating conditions. Mechanistic studies showed that the nine-membered rings might undergo decarboxylation, isomerization, aza-Michael addition, and aromatization to afford 2,3-dihydropyrrolizines in a one-pot reaction. [ABSTRACT FROM AUTHOR]

A new and straightforward protocol for the synthesis of quinoline N-oxides from the annulation of arylnitrones and alkynes is described. For the first time, a [4+2] cyclization of nitrone and alkynes has been achieved by cobalt catalysis via a nitrone-assisted dual C-H cleavage under relatively mild conditions. [ABSTRACT FROM AUTHOR]

The first copper(I)-catalyzed asymmetric 1,3-dipolar [3+4] cycloaddition of nitrones with azoalkenes has been developed, affording a variety of biologically important 1,2,4,5-oxatriazepane derivatives in good yields with exclusive regioselectivities and excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

A zinc diiodide (ZnI2)-mediated direct synthesis of 2,3-dihydroisoxazoles via a [3+2] cycloaddition reaction of the nitrones and non-electron-deficient terminal alkynes has been developed. This method was applied in the formal synthesis of HPA-12 and aminoglucose. [ABSTRACT FROM AUTHOR]

In the presence of sodium carbonate, the [4+3] cycloadditions of α-halogeno hydrazones with nitrones were performed efficiently, and affording 2,3,4,7-tetrahydro-1,2,4,5-oxatriazepines in moderate to high yields. [ABSTRACT FROM AUTHOR]

Nitrone and nitroso species are versatile compounds to react with alkenes or butadienes to access five- and six-membered nitroxy (NO) containing heterocycles, to offer further access to acyclic 1,3- and 1,4-amino alcohols after facile cleavage of the NO bonds. The N- and O-functionalizations of alkynes with nitrones or nitroso species have been explored less well than the corresponding alkene reactions. In recent decades, gold catalysts have enabled the electrophilic activation of alkynes with weak nucleophiles. This review summarizes recent progress to implement N- and O-functionalizations of alkynes with common NO containing species including nitrone, nitroso, nitro and other nitroxy derivatives. Reported reactions include the following three topics: (i) 1,2-difunctionalizations, (ii) cyclizations and (iii) cycloaddition or annulation reactions. The review is organized according to the types of nucleophiles, followed by reactions of the mentioned types. Enantioselective functionalizations of alkynes with these nitroxy nucleophiles are also included. [ABSTRACT FROM AUTHOR]

By using a nitrone as the oxidizing directing group, a mild, practical and efficient rhodium(III)-catalyzed CH functionalization for the synthesis of indole derivatives has been developed. This reaction obviates the need for an external oxidant and shows good functional group tolerance. The employment of a sterically hindered Mes group on the carbon center of the nitrone is crucial to produce indoles in high yield. [ABSTRACT FROM AUTHOR]

Some readily available Boc-protected 2-(3-methoxy-1-propynyl)anilines and nitrones in platinum-catalyzed reactions deliver [1,2]oxazino[5,4- b]indoles. Twelve examples with yields of 41-95% are reported. Different substituents like nitro, trifluoromethyl, fluoro, bromo, and ester groups are tolerated. With regard to the mechanism, this reaction probably combines an initial intramolecular cyclization/elimination to vinylcarbenoid species and a subsequent stepwise intermolecular [3+3] cycloaddition with the nitrones. [ABSTRACT FROM AUTHOR]