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We described a copper(I)‐catalyzed atom economic and selective hydroamination‐cyclization of alkynyl‐tethered quinazolinones to prepare a variety of indole‐fused pyrazino[1,2‐a]quinazolinones in good to excellent yields ranging from 39 %–99 % under mild reaction conditions. Control experiments revealed that coordination‐directed method of quinazolinone moiety with copper(I) was important for the selective hydroamination‐cyclization of alkynes at the N1‐atom instead of N3‐atom of quinazolinone. The reaction could be easily performed at gram scales and some prepared indole‐fused pyrazino[1,2‐a]quinazolinones with donating groups on the indole moiety showed a distinct fluorescence emission wavelength with blue shift under the acid conditions. [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]

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 base-catalyzed and DMSO-promoted atom economic intramolecular hydroalkoxylation was developed to prepare a variety of pentacyclic chromeno[4,3-b]indolines in good yields with high regioselectivity and diastereoselectivity. Mechanistic studies revealed that DMSO played important roles as a green solvent and an activator of unactivated alkenes via hydrogen-bonding and ion pairing to facilitate a 5-exo-trig cyclization. The present method highlights mild reaction conditions, short reaction time, broad substrate scope, a new application of DMSO, and gram-scalable preparation without column chromatography. [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 pseudorutaecarpine derivatives were prepared in good to excellent yields through a gold(I)‐catalyzed selective cyclization and 1,2‐shift of N‐alkynyl quinazolinone‐tethered indoles. Mechanistic study revealed that spiroindolenines generated in situ by cyclization at the the indole C3 position underwent an alkenyl 1,2‐shift to generate pseudorutaecarpine. The reaction proceeds under mild reaction conditions, has a broad substrate scope, good functional group tolerance, and gram‐scalable application. Furthermore, biological evaluation showed that most of the pseudorutaecarpine scaffolds prepared exhibit anti‐inflammatory activity. [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]

We report a relay catalysis for the highly stereoselective synthesis of densely substituted oxazonine-fused endoperoxides in good yields. This domino reaction is based on an Yb(OTf)3 and visible light promoted [3 + 2] cycloaddition/[3,3]-rearrangement, and in situ [4 + 2] cycloaddition with air in one pot under mild reaction conditions from N-vinyl-α,β-unsaturated nitrones and methylenecyclopropanes, leading to a practical assembly of densely substituted oxazonine-fused endoperoxides containing five stereocenters with a wide substrate scope and excellent diastereoselectivity. Mechanistic studies reveal that the O–O bond of the endoperoxide ring is derived from singlet oxygen (1O2) generated by air under a white LED. Moreover, such an asymmetric relay catalyst has also been realized to afford chiral endoperoxides in good enantioselectivity. Biological tests show that the designed oxazonine-fused endoperoxides significantly inhibited nitric oxide (NO) generation in LPS-stimulated RAW264.7 cells and exhibited their bioactivity as good anti-inflammatory agents. [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 general protocol for the construction of novel densely functionalized γ-lactones was developed in good to excellent yields with high diastereoselectivity from easily available N-vinyl-α,β-unsaturated nitrones and ketenes. The reaction involves copper-catalyzed [5 + 2] cycloaddition, N–O bond cleavage, 6π electron cyclization, and aromatization to afford various γ-(pyridin-2-yl)lactones over four step transformations in a single flask. The present method features mild reaction conditions, high atom economy, high regio- and diastereoselectivity, diversity of γ-lactones, and a new application of the O-transfer reaction. [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]

Various polycyclic furo[2,3‐b]indolines containing a cyclopropane ring have been prepared in moderate yields with high diastereoselectivity from N‐aryl isatin nitrones and methylenecyclopropanes using a copper‐catalyzed [3+2] cycloaddition and subsequent interrupted Fischer indolization strategy under mild reaction conditions. The obtained furo[2,3‐b]indolines were easily converted to piperidinone‐fused furo[2,3‐b]indolines by selective [1,3]‐rearrangement through N−O bond cleavage. Finally, two chiral polycyclic furo[2,3‐b]indolines were obtained by chiral auxiliary control. [ABSTRACT FROM AUTHOR]

An iron(iii)-catalyst controlled cyclization and selective N–O bond cleavage of N-vinyl-α,β-unsaturated nitrones has been achieved under mild conditions to access tetrasubstituted pyridines and 3,5-disubstituted isoxazolines in moderate to good yields. The tetrasubstituted pyridines were afforded with FeCl3 as a catalyst while using FeCl3·6H2O combined with 1,10-phenanthroline delivered isoxazolines. The regioselectivity for cyclization of styrenyl groups in N-vinyl-α,β-unsaturated nitrones was completely different during the formation of pyridines and isoxazolines. A rational mechanism for the formation of pyridines and isoxazolines was proposed based on the further control experimental studies. The isoxazolines can be converted to a novel bidentate N-ligand over four steps and an epoxypyridine scaffold was obtained from N-vinyl nitrone when copper(ii) acetate in combination with the prepared bidentate N-ligand was used. [ABSTRACT FROM AUTHOR]

A variety of 2,3-quaternary fused indolines could be prepared in good yields with high diastereoselectivity from alkynyl tethered oximes and diaryliodonium salts under mild metal-free conditions. The reaction initially goes through a selective N-arylation to provide alkynyl tethered nitrones and regioselectively undergoes an intramolecular (3 + 2) cycloaddition followed by a [3,3]-sigmatropic rearrangement to afford 2,3-quaternary fused indolines in a one-pot fashion. The method features easily available cheap materials, multiple bond formation, gram scalable preparation and diversity of fused indoline scaffolds. [ABSTRACT FROM AUTHOR]

A variety of functionalized 2-substituted benzoxazoles can be prepared in good yields from amidoximes and diaryliodonium salts by selective O-arylation and sequential [3,3]-rearrangement under metal-free conditions. O-arylation of amidoximes was promoted by 3 Å molecule sieves in the absence of a base and a sequential TFA-mediated [3,3]-rearrangement was used to synthesize 2-substituted benzoxazoles. Both of the O-aryl products and rearrangement products were compatible with a broad range of sensitive functional groups such as ester, aldehyde, nitro, vinyl, amine, and amide groups in addition to halides. A bidentate N-ligand with double benzoxazoles was prepared at gram-scale in two steps. [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 synthetic strategy to access polysubstituted furans regiospecifically has been developed using simple bicyclic alkenes and terminal ynones as starting materials with palladacycles as unique active catalysts. A rational mechanism has also been proposed. This reaction features mild reaction conditions, easily available starting materials and palladacycle catalysts, a wide substrate scope, and high regiospecificity. [ABSTRACT FROM AUTHOR]

A new method for the synthesis of N-styrenyl amidines is described. The synthetic utility of the formed amidines is shown in the cycloaddition of (XI) with dimethylacetylene dicarboxylate. [ABSTRACT FROM AUTHOR]