One-pot Cascade Reaction Research Articles

Sophisticated Design of Covalent Organic Frameworks with Controllable Bimetallic Docking for a Cascade Reaction.

Precise control of the number and position of the catalytic metal ions in heterogeneous catalysts remains a big challenge. Here we synthesized a series of two-dimensional (2D) covalent organic frameworks (COFs) containing two different types of nitrogen ligands, namely imine and bipyridine, with controllable contents. For the first time, the selective coordination of the two nitrogen ligands of the 2D COFs to two different metal complexes, chloro(1,5-cyclooctadiene)rhodium(I) (Rh(COD)Cl) and palladium(II) acetate (Pd(OAc)2 ), has been realized using a programmed synthetic procedure. The bimetallically docked COFs showed excellent catalytic activity in a one-pot addition-oxidation cascade reaction. The high surface area, controllable metal-loading content, and predesigned active sites make them ideal candidates for their use as heterogeneous catalysts in a wide range of chemical reactions.

Sequence-defined bioactive macrocycles via an acid-catalysed cascade reaction.

Synthetic macrocycles derived from sequence-defined oligomers are a unique structural class whose ring size, sequence and structure can be tuned via precise organization of the primary sequence. Similar to peptides and other peptidomimetics, these well-defined synthetic macromolecules become pharmacologically relevant when bioactive side chains are incorporated into their primary sequence. In this article, we report the synthesis of oligothioetheramide (oligoTEA) macrocycles via a one-pot acid-catalysed cascade reaction. The versatility of the cyclization chemistry and modularity of the assembly process was demonstrated via the synthesis of >20 diverse oligoTEA macrocycles. Structural characterization via NMR spectroscopy revealed the presence of conformational isomers, which enabled the determination of local chain dynamics within the macromolecular structure. Finally, we demonstrate the biological activity of oligoTEA macrocycles designed to mimic facially amphiphilic antimicrobial peptides. The preliminary results indicate that macrocyclic oligoTEAs with just two-to-three cationic charge centres can elicit potent antibacterial activity against Gram-positive and Gram-negative bacteria.

ChemInform Abstract: Iodine‐Induced Efficient Construction of a Chromone‐Linked Furo‐[3,2‐c]chromene Scaffold by a One‐Pot 3‐Component Cascade Reaction.

Abstract A novel and efficient method for the construction of 4-(3-chromonyl)furo[3,2- c ]-1-benzopyran scaffold by molecular iodine-induced cascade reaction between 3-(1-alkynyl)chromone and 1-(2-hydroxyphenyl)-3- N , N -dimethylaminoprop-2-ene-1-one is described. Two new C–O, one C–C, and one C–I bonds are formed in this one-pot cascade reaction. This tandem process involves Michael addition and double annulation under mild conditions without using transition metal, inert atmosphere, or dry solvent. Deiodination of the product was also accomplished.

Copper-Catalyzed Cascade Reaction via Intramolecular Hydroamination Cyclization of Homopropargylic Amines and Intermolecular Povarov Reaction with Imines.

A new one-pot cascade reaction of homopropargylic amines with simple imines is developed in the presence of Cu(OTf)2 and affords a series of hexahydro-1H-pyrrolo[3,2-c]quinoline derivatives in good to high yields. This reaction proceeds through an intramolecular hydroamination cyclization of homopropargylic amine to generate a highly reactive dihydropyrrole intermediate in situ. It subsequently reacts with imine via an intermolecular inverse-electron-demand aza-Diels-Alder reaction and a 1,3-H shift to give the fused pyrroloquinoline structures, forming two new C-C bonds and one C-N bond and one N-H bond.

Rh(II)-catalyzed intramolecular annulation of N-sulfonyl 1,2,3-triazoles with indole derivatives: a new method for synthesis pyranoindoles

A direct and highly stereoselective approach for the synthesis of Z-alkenyl-pyranoindoles had been developed by utilizing Rh(II)-catalyzed intramolecular cyclization of N-sulfonyl-1,2,3-triazoles with indole derivatives. A variety of pyranoindoles were obtained in 44–93% yields. Moreover, a more convenient synthesis of pyranoindoles starting from terminal alkyne was realized via a Cu–Rh sequentially catalyzed one-pot cascade reaction.

Exfoliated Pd/HNb3O8 nanosheet as highly efficient bifunctional catalyst for one-pot cascade reaction

Ultrathin two-dimensional metal oxide nanosheets have drawn attention as potential solid acid catalysts owing to their strong acidity, attributed to the bridged OH groups formed on the nanosheets. In this study, a new class of bifunctional acid–metal catalyst was realized by the deposition of Pd on layered niobium oxide (KNb3O8 and HNb3O8) or its exfoliated nanosheet (Pd/HNb3O8-NS) and applied to one-pot cascade deacetalization and hydrogenation. It was found that the acid strength of the support exerted a large influence not only on the promotion of the first deacetalization step, but also on the acceleration of the subsequent hydrogenation step. Comparative experiments using a series of Pd/HZSM-5 catalysts with different acidities reconfirmed the crucial role of acid strength on hydrogenation. However, the superior catalytic activity of Pd/HNb3O8-NS for hydrogenation compared to that of Pd/HZSM-5 of similar acidity suggests a more efficient ensemble effect of the strong acid sites with the nearby metal sites on the nanosheet surface. Among the catalysts used, Pd/HNb3O8-NS showed the best catalytic performance for one-pot cascade reaction affording the desired product (benzyl alcohol) in approximately 92% yield, which was 7.1 and 1.2 times higher than that of layered Pd/KNb3O8 or Pd/HNb3O8, respectively. The excellent catalytic performance of Pd/HNb3O8-NS may result from the characteristic features of nanosheets: (i) the synergistic cooperation between the bifunctional active sites and (ii) the two-dimensional open surface offering easier access of the reactants to the active sites. Although the use of NaBH4 as hydrogen source was effective in improving the initial reaction performance, the basic nature of NaBH4 adversely resulted in weakening the acid strength of the catalyst, and consequently led to a reduction in catalytic activity.

Nickel and molybdenum containing mesoporous catalysts for ethylene oligomerization and metathesis

Ethylene is converted into propylene by one-pot cascade reactions over catalysts prepared using a commercial mesoporous non-ordered silica as a support.

Microporous organic nanotube network supported acid and base catalyst system for one-pot cascade reactions

Acid/base functionalized microporous organic nanotube networks with excellent catalytic performance for one-pot cascade reactions were successfully prepared.

Synthesis of 2-BMIDA 6,5-bicyclic heterocycles by Cu(i)/Pd(0)/Cu(ii) cascade catalysis of 2-iodoaniline/phenols.

A one-pot cascade reaction for the synthesis of 2-BMIDA 6,5-bicyclic heterocycles has been developed using Cu(i)/Pd(0)/Cu(ii) catalysis. 2-Iodoanilines and phenols undergo a Cu(i)/Pd(0)-catalyzed Sonogashira reaction with ethynyl BMIDA followed by in situ Cu(ii)-catalyzed 5-endo-dig cyclization to generate heterocyclic scaffolds with a BMIDA functional group in the 2-position. The method provides efficient access to borylated indoles, benzofurans, and aza-derivatives, which can be difficult to access through alternative methods.

Yolk–shell-structured mesoporous silica: a bifunctional catalyst for nitroaldol–Michael one-pot cascade reaction

A site-isolated yolk–shell-structured mesoporous silica for the nitroaldol–Michael one-pot enantio-relay reaction to convert aldehydes, nitromethane and acetylacetone to chiral diones is developed.

ChemInform Abstract: Synthesis of Pyrazolo[5,1‐a]isoindoles and Pyrazolo[5,1‐a]isoindole‐3‐carboxamides Through One‐Pot Cascade Reactions of 1‐(2‐Bromophenyl)buta‐2,3‐dien‐1‐ones with Isocyanide and Hydrazine or Acetohydrazide.

A novel and efficient method for the construction of the pyrazolo[5,1-a]isoindole scaffold via a one-pot three-component cascade reaction of 1-(2-bromophenyl)buta-2,3-dien-1-one with hydrazine and isocyanide promoted by a Pd catalyst is described. This cascade process proceeds through initial condensation of the allenic ketone with hydrazine followed by Pd-catalyzed isocyanide insertion into the C–Br bond and intramolecular C–N bond formation. Interestingly, when acetohydrazide was used in place of hydrazine, a more sophisticated procedure involving condensation, isocyanide insertion into C–H and C–Br bonds, deacetylation, and formation of C–C, C–O, and C–N bonds occurred to afford pyrazolo[5,1-a]isoindole-3-carboxamides with good efficiency.

Iodine-induced efficient construction of a chromone-linked furo-[3,2-c]chromene scaffold by a one-pot 3-component cascade reaction

A novel and efficient method for the construction of 4-(3-chromonyl)furo[3,2-c]-1-benzopyran scaffold by molecular iodine-induced cascade reaction between 3-(1-alkynyl)chromone and 1-(2-hydroxyphenyl)-3-N,N-dimethylaminoprop-2-ene-1-one is described. Two new C–O, one C–C, and one C–I bonds are formed in this one-pot cascade reaction. This tandem process involves Michael addition and double annulation under mild conditions without using transition metal, inert atmosphere, or dry solvent. Deiodination of the product was also accomplished.

One-pot Enantioselective Multi-component Cascade Reactions for Synthesis of Chiral Functionalized Hydro-epoxyisochromenes: A Rapid Access toMolecular Complexity

设计、研究了一种重氮、4-羟基丙烯酸乙酯和呋喃衍生物参与的三组分串联反应,在Rh2（OAc）4/Zr-3-I-联二萘酚共催化下,该反应能快速高效地一锅构建复杂O-杂并环化合物.利用该方法,可从简单起始原料高立体选择性地合成含有八个连续手性中心的氢化环氧异色烯衍生物,非对映选择性和高对映选择性分别高达99/1 dr和99%ee.结合理论计算对反应的高立体选择性进行了探讨.可能的反应机理为羟基叶立德捕捉的多组分反应后发生分子内的Diels-Alder反应,再发生双键环氧化反应.该方法为复杂O-并杂环化合物的高效合成提供了一种新途径,同时也为高效构建分子复杂性提供了一种新思路,在基于表型筛选的新药发现中具有重要潜在应用.

Regioselective Synthesis of Indolo[1,2-c]quinazolines and 11H-Indolo[3,2-c]quinolines via Copper-Catalyzed Cascade Reactions of 2-(2-Bromoaryl)-1H-indoles with Aldehydes and Aqueous Ammonia.

Highly selective and convenient synthesis of indolo[1,2-c]quinazolines and 11H-indolo[3,2-c]quinolines through copper-catalyzed one-pot cascade reactions of 2-(2-bromoaryl)-1H-indoles with aldehydes and aqueous ammonia has been achieved. Notably, the regioselectivity was easily controlled by tuning the reaction conditions. Compared with literature methods, the present protocol features easily controlled selectivity, readily available starting materials, good functional group tolerance, and simple operation procedures.

ChemInform Abstract: The Long Underestimated Carbonyl Function of Carbohydrates — An Organocatalyzed Shot into Carbohydrate Chemistry

AbstractReview: [38 refs.

Two-Component Domino Reactions Initiated from Ketenes: Serendipitous Synthesis of Quinolizidinones Analogous to Chelated Lobeline's Conformation.

An original and efficient synthesis of quinolizidinones through a one-pot two-component cascade reaction of norlobelanine with in situ generated ketenes is reported. Functionalized fused azabicyclic scaffolds bearing multiple stereogenic centers were prepared with excellent diastereoselectivities. Mild optimized conditions involving a key "shuttle base" deprotonation strategy was applied to the synthesis, in a short sequence, of a constrained mimetic of the privileged H-bonded conformation of (-)-lobeline.

A cascade synthetic route to new bioactive spiroindolinepyrido[1,2-a]indolediones from indirubin

The allylation of indirubin produced the expected indolic N′-allylindirubin and N,N′-diallylindirubin derivatives in moderate yields, together with the corresponding N-substituted isatin products. At higher temperatures, the base-initiated reaction with allylic halides yielded spiroindolinepyrido[1,2-a]indolediones in a one-pot cascade reaction sequence with yields of up to 70%. These readily accessed, new spiro compounds represent the first reported examples of indirubin participating in cascade reactions. Preliminary in vitro biological testing of some of the products indicated promising activity against some cancer cell lines and against Plasmodium falciparum for two spiro derivatives. Computational methods were used to gain a greater understanding of the UV/Vis spectroscopic data for the N′-substituted and N,N′-disubstituted indirubin derivatives.

Synthesis of Pyrazolo[5,1-a]isoindoles and Pyrazolo[5,1-a]isoindole-3-carboxamides through One-Pot Cascade Reactions of 1-(2-Bromophenyl)buta-2,3-dien-1-ones with Isocyanide and Hydrazine or Acetohydrazide

A novel and efficient method for the construction of the pyrazolo[5,1-a]isoindole scaffold via a one-pot three-component cascade reaction of 1-(2-bromophenyl)buta-2,3-dien-1-one with hydrazine and isocyanide promoted by a Pd catalyst is described. This cascade process proceeds through initial condensation of the allenic ketone with hydrazine followed by Pd-catalyzed isocyanide insertion into the C-Br bond and intramolecular C-N bond formation. Interestingly, when acetohydrazide was used in place of hydrazine, a more sophisticated procedure involving condensation, isocyanide insertion into C-H and C-Br bonds, deacetylation, and formation of C-C, C-O, and C-N bonds occurred to afford pyrazolo[5,1-a]isoindole-3-carboxamides with good efficiency.

Facile Synthesis of Spirocyclic Lactams from β-Keto Carboxylic Acids.

A facile synthesis of spirocyclic lactams starting from β-keto carboxylic acids via a one-pot cascade reaction involving a Curtius rearrangement and an intramolecular nucleophilic addition of the enol carbon to the isocyanate intermediate is reported. The same conditions have also been used for the generation of fused cyclic lactams with similar good yields. The synthetic value of this method has been demonstrated by efficient synthesis of tetracyclic spirolactam 8 and pentacyclic spirolactam 9.

Iodine catalyzed mild 4CR protocol for synthesis of Tetrahydroimidazo[1,2-a]pyridines: cascade construction of multiple C–C and C–Hetero bonds

A highly convergent and straight forward synthesis of N-fused heterocycles, including 1,2,3,7-tetrahydroimidazo[1,2-a]pyridine-5-carboxylic acids is successfully achieved via a one-pot four-component cascade reaction utilizing pyruvic acid, aldehydes, diamines and 1,1-bis(methylthio)-2-nitroethylene (BMTNE) in the presence of a catalytic amount of molecular iodine in acetonitrile. The new efficient domino protocol generates two rings by the concomitant formation of C–N (three) and C–C (two) multiple bonds presumably involving a sequence of N,N-acetal formation, Knoevenagel reaction, aza–ene reaction, imine–enamine/keto–enol tautomerization, and N-cyclization as key steps. The merit of this protocol is highlighted by its easily available and economical starting materials, operational simplicity, efficient utilization of all the reactants, clean reaction profile, simple workup procedure, and tolerance of a wide variety of functional groups.