RESUMEN

An efficient cascade cyclization strategy was developed to synthesize aminobenzofuran spiroindanone and spirobarbituric acid derivatives utilizing 2-bromo-1,3-indandione, 5-bromo-1,3-dimethylbarbituric acid, and ortho-hydroxy α-aminosulfones as substrates. Under the optimized reaction conditions, the corresponding products were obtained with high efficiency, exceeding 95% and 85% yields for the respective derivatives. This protocol demonstrates exceptional substrate versatility and robust scalability up to the Gram scale, establishing a stable platform for the synthesis of 3-aminobenzofuran derivative. The successful synthesis paves the way for further biological evaluations with potential implications in scientific research.

RESUMEN

An efficient and practical organocatalyzed asymmetric Mannich/cyclization tandem reaction strategy of 2-benzothiazolimines and 2-isothiocyanato-1-indanones was developed, and novel spirocyclic compounds containing benzothiazolimine and indanone scaffolds were obtained. This chiral thiourea-catalyzed Mannich/cyclization tandem reaction offers chiral spirocyclic compounds with continuous tertiary and quaternary stereocenters in good to high yields (up to 90%) with excellent diastereoselectivities (up to >20:1 dr) and enantioselectivities (up to 98% ee) at -18 °C. Additionally, the scaled-up synthesis was also performed with retained yield and stereoselectivity, and a reaction mechanism was also proposed.

RESUMEN

The sulfa-Michael addition reaction is a crucial subset of the Michael addition reaction, and aroused the interest of numerous synthetic biologists and chemists. In particular, sulfa-Michael addition triggered cascade reaction has developed quickly in recent years because it offers an efficient method to construct C-S bonds and other bonds in one approach, which is widely applicable for building chiral pharmaceuticals, their intermediates, and natural compounds. This review emphasizes the recent advancements in sulfa-Michael addition-triggered cascade reactions for the stereoselective synthesis of sulfur-containing compounds, including sulfa-Michael/aldol, sulfa-Michael/Henry, sulfa-Michael/Michael, sulfa-Michael/Mannich and some sulfa-Michael triggered multi-step processes. Moreover, some reaction mechanisms and derivatization experiments are introduced appropriately.

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RESUMEN

In this paper, the organocatalytic asymmetric Michael addition/hemiketalization cascade reactions between hydroxymaleimides and 2-hydroxynitrostyrenes were developed, which provided a new protocol for building a chiral ring-fused chroman skeleton. This squaramide-catalyzed cascade reaction provided chiral chroman-fused pyrrolidinediones with three contiguous stereocenters in good to high yields (up to 88%), with excellent diastereoselectivities (up to >20:1 dr) and enantioselectivities (up to 96% ee) at −16 °C. Moreover, a scale-up synthesis was also carried out, and a possible reaction mechanism was proposed.

Asunto(s)

RESUMEN

A class of o-sulfonylaminostyryl isoxazole synthons were designed and demonstrated to be useful building blocks in asymmetric cascade aza-Michael/Michael reaction with 3-olefinic oxindoles. This squaramide-catalysed cascade reaction afforded structurally complex isoxazole-containing spirooxindole tetrahydroquinolines bearing three contiguous stereocenters in good to excellent yields (up to 99%) with high diastereoselectivities (up to >20 : 1 dr) and enantioselectivities (up to 88% ee). Moreover, the gram-scale synthesis and synthetic transformations were also demonstrated.

Asunto(s)

RESUMEN

A highly efficient squaramide-catalysed asymmetric domino Michael/Mannich [3 + 2] cycloaddition of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles and N-2,2,2-trifluoroethylisatin ketimines was developed. A new class of complex and diverse-skeleton isoxazole and trifluoromethyl-containing 3,2'-pyrrolidinyl dispirooxindoles bearing four contiguous stereogenic centers including two adjacent spiro quaternary stereocentres were obtained in good to excellent yields (up to 99%) with excellent diastereoselectivities (>20 : 1 dr, in all cases) and enantioselectivities (up to 96% ee). Moreover, the potential utilities of the protocol have been demonstrated by gram-scale synthesis and further transformation experiments.

RESUMEN

An efficient and practical organocatalytic asymmetric strategy was developed using unsaturated benzothiophenones and α-nitroketones catalysed by bifunctional squaramide via Michael addition and acyl transfer steps. A broad range of chiral acyloxybenzothiophene derivatives were obtained in good yields (up to 97%) with excellent enantioselectivities (up to 98% ee). What's more, employing different chiral squaramide catalysts and unsaturated benzothiophenones can deliver the acyloxy unit at the 2-position or 3-position of benzothiophene.

RESUMEN

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins have been developed to afford chiral dispiro[indene-pyrrolidine-pyrimidine]s. Through this strategy, the target products could be obtained in good to excellent yields with excellent stereoselectivities. In addition, the synthetic utility was verified through a gram-scale synthesis, one-pot three-component reactions and further transformation experiments of the products.

RESUMEN

An effective strategy for the stereoselective synthesis of spiro isoxazolone-cyclohexenimines was developed using a bifunctional squaramide-catalysed vinylogous Michael addition/cyclization cascade reaction of 4-unsaturated isoxazol-5-ones and α,α-dicyanoalkenes. The atom-economical cascade process can proceed smoothly under extremely low catalyst loading (1 mol%) and mild conditions, and the corresponding products were obtained in moderate to good yields (45% to 90%) and enantioselectivitites (51% to 96% ee). Meanwhile, the scale-up reaction and transformation of the products were also demonstrated.

RESUMEN

In this paper, the organocatalytic asymmetric 1,4-Michael addition reaction of azadienes and α-thiocyanoindanones was investigated. A series of chiral benzofuran compounds containing thiocyano group and quaternary carbon center were synthesized in moderate yields with good enantioselectivities (up to 90:10 er) and high diastereoselectivities (up to >95:5 dr). This is the first case of 1,4-Michael addition reaction using α-thiocyanoindanones to obtain a series of chiral thiocyano compounds and further broaden the scope of application of azadiene substrates. In addition, a possible reaction mechanism is also described in the article.

RESUMEN

A highly efficient cinchona alkaloid-derived squaramide catalysed asymmetric Michael/cyclization cascade reaction of 4-arylmethylidene-2,3-dioxopyrrolidines with 2-isothiocyanato-1-indanones was successfully developed. This protocol provides an efficient and mild access to indanone-derived spiropyrrolidone scaffolds containing three contiguous stereocenters with two spiroquaternary stereocenters in excellent yields (up to 99%) with high enantio- and diastereoselectivities (up to 99% ee and up to >20 : 1 dr). This method provides an economical and practical approach for the asymmetric synthesis of medicinally relevant molecules.

RESUMEN

A highly enantioselective [3+2] annulation of 3-((2-oxoindolin-3-yl)oxy)acrylates with isoxazol-5(4H)-ones has been accomplished by squaramide-catalyzed cascade Michael/Michael addition reactions under mild conditions. The corresponding isoxazolone-spirooxindoles with four continuous stereocenters were obtained in moderate to high yields with excellent stereoselectivities (up to >20:1 dr, 97% ee). The synthetic practicality of this methodology was illustrated by performing the reaction on a gram scale with the same efficiency and stereoselectivity. Meanwhile, the isoxazol-5(4H)-one ring could be opened by the reaction with iron powder and ammonium chloride, and the corresponding acyl derivative can be obtained with a maintained yield and stereoselectivity.

RESUMEN

We herein report a highly efficient strategy for the stereoselective synthesis of structurally complex bispiro[oxindole-thiazolidinone-hexahydroxanthone]s. This squaramide-catalyzed domino Michael addition afforded these products in good to excellent yields with excellent stereoselectivities bearing five contiguous stereocenters with two spiroquaternary stereocenters. Meanwhile, both gram-scale synthesis and further transformation experiments have been also demonstrated.

RESUMEN

Thiazolones as a class of five-membered heterocyclic compounds containing both nitrogen and sulfur, have been proved to possess important biological activities. Because thiazolone molecules have many reaction sites, they can carry out a series of modification reactions, which makes them good reaction substrates for various molecular syntheses. In recent years, research on the use of asymmetric organocatalysis to construct thiazolone derivatives has attracted a lot of attention. Among these, some breakthrough results have been achieved in the asymmetric synthesis of thiazolone derivatives. This review highlights recent developments in thiazolone derivatives in asymmetric reactions, including Michael additions, Mannich reactions as well as various cascade reactions.

RESUMEN

A highly efficient method for the enantioselective construction of dispirocyclic compounds has been developed by the squaramide-catalysed asymmetric Michael addition/cyclization cascade reaction of 2,3-dioxopyrrolidines with 3-chlorooxindoles. The corresponding chiral dispiro[indoline-3,1'-cyclopropane-2',3''-pyrrolidine]-2,4'',5''-triones were obtained in high yields with excellent stereoselectivities (up to 94% yield, >25 : 1 dr and >99% ee). Furthermore, a gram-scale experiment confirmed the reliability of the current reaction and further effective transformation of the product has been realized.

RESUMEN

3-Fluorooxindoles and the dibenzo[b,f][1,4]oxazepane scaffolds are important pharmacophores that have important application in medicinal chemistry. An organocatalyzed asymmetric Mannich reaction of 3-fluorooxindoles with dibenzo[b,f][1,4]oxazepines affording various seven-member cyclic amines containing chiral tetrasubstituted C-F stereocenters was developed. These reactions which were catalyzed by a bifunctional Cinchona alkaloid-derived thiourea catalyst afforded a wide range of substrates in moderate to high yields with excellent diastereo- and enantioselectivities (up to 88% yield, >20:1 dr and >99% ee). A feasible reaction mechanism was also proposed.

RESUMEN

The present paper reports a highly stereoselective synthesis of spirooxindole-fused spiropyrazolones through the asymmetric [3 + 2] cyclization reaction of 2-(1-methyl-2-oxoindolin-3-yl)malononitriles with unsaturated pyrazolones under mild conditions. With only a 1 mol % bifunctional squaramide catalyst, a series of chiral dispirocyclic pyrazolone derivatives were attained in high yields (85-97%) with excellent stereoselectivities (up to >99% ee and in all cases >20:1 dr). Moreover, gram-scale synthesis and further transformation of the products were also demonstrated.

RESUMEN

An enantioselective Mannich reaction between 3-fluorooxindoles and pyrazolinone ketimines has been developed for the construction of amino-pyrazolone-oxindoles containing stereogenic C-F units. Based on this new protocol that allows for the generation of two adjacent tetrasubstituted stereocenters, a variety of structurally diverse fluorinated amino-pyrazolone-oxindoles were obtained in good to excellent yields with excellent diastereoselectivities and enantioselectivities (up to 98% yield, >20 : 1 dr and >99% ee). What's more, good yield and high stereoselectivities were obtained in the gram-scale reaction.

RESUMEN

An efficient and practical organocatalyzed asymmetric formal [2 + 1] cycloaddition of 3-chlorooxindoles with 5-alkenyl thiazolones by using hydroquinine-derived squaramide as the catalyst has been developed. Under mild conditions, a broad range of spirooxindole-fused spirothiazolones bearing three adjacent stereogenic centers including two vicinal spiro quaternary chiral centers were obtained in high yields (up to 99% yield) with excellent diastereoselectivities (up to >99 : 1 dr) and enantioselectivities (up to 99% ee).

RESUMEN

A bifunctional squaramide-catalyzed asymmetric cascade aza-Michael/Michael addition reaction for the synthesis of chiral spirothiazolidinone tetrahydroquinolines with three contiguous stereocenters has been developed. This cascade reaction proceeded well under mild conditions, and afforded the desired products in high to excellent yields (up to >99% yield) with excellent diastereoselectivities (>25 : 1 dr) and high enantioselectivities (up to 96% ee). More importantly, both the amplification and the derivation experiments do not affect the stereoselectivity.