Experimental investigation on the mechanism of chelation-assisted, copper(II) acetate-accelerated azide-alkyne cycloaddition

A mechanistic model is formulated to account for the high reactivity of chelating azides (organic azides capable of chelation-assisted metal coordination at the alkylated azido nitrogen position) and copper(II) acetate (Cu(OAc)(2)) in copper(II)-mediated azide-alkyne cycloaddition (AAC) reactions. Fluorescence and (1)H NMR assays are developed for monitoring the reaction progress in two different solvents, methanol and acetonitrile. Solvent kinetic isotopic effect and premixing experiments give credence to the proposed different induction reactions for converting copper(II) to catalytic copper(I) species in methanol (methanol oxidation) and acetonitrile (alkyne oxidative homocoupling), respectively. The kinetic orders of individual components in a chelation-assisted, copper(II)-accelerated AAC reaction are determined in both methanol and acetonitrile. Key conclusions resulting from the kinetic studies include (1) the interaction between copper ion (either in +1 or +2 oxidation state) and a chelating azide occurs in a fast, pre-equilibrium step prior to the formation of the in-cycle copper(I)-acetylide, (2) alkyne deprotonation is involved in several kinetically significant steps, and (3) consistent with prior experimental and computational results by other groups, two copper centers are involved in the catalysis. The X-ray crystal structures of chelating azides with Cu(OAc)(2) suggest a mechanistic synergy between alkyne oxidative homocoupling and copper(II)-accelerated AAC reactions, in which both a bimetallic catalytic pathway and a base are involved. The different roles of the two copper centers (a Lewis acid to enhance the electrophilicity of the azido group and a two-electron reducing agent in oxidative metallacycle formation, respectively) in the proposed catalytic cycle suggest that a mixed valency (+2 and +1) dinuclear copper species be a highly efficient catalyst. This proposition is supported by the higher activity of the partially reduced Cu(OAc)(2) in mediating a 2-picolylazide-involved AAC reaction than the fully reduced Cu(OAc)(2). Finally, the discontinuous kinetic behavior that has been observed by us and others in copper(I/II)-mediated AAC reactions is explained by the likely catalyst disintegration during the course of a relatively slow reaction. Complementing the prior mechanistic conclusions drawn by other investigators, which primarily focus on the copper(I)/alkyne interactions, we emphasize the kinetic significance of copper(I/II)/azide interaction. This work not only provides a mechanism accounting for the fast Cu(OAc)(2)-mediated AAC reactions involving chelating azides, which has apparent practical implications, but suggests the significance of mixed-valency dinuclear copper species in catalytic reactions where two copper centers carry different functions.     

Water as a solvent for Ru‐catalyzed click reaction: Highly efficient recyclable catalytic system for triazolocoumarins synthesis

A new family of Ru (III) complexes has been synthesized, characterized and their catalytic performance has been tested for alkyne–azide cycloaddition (AAC) in water under ultrasonic irradiation conditions. These complexes are found to be effective heterogeneous catalysts for the regioselective synthesis of 1,4‐disubstituted‐1,2,3‐triazoles giving access to these products in excellent yields. The catalyst system is equally active for one‐pot multi‐component protocol of the AAC reactions. Also, successive sequencing of Huisgen reaction with Knoevenagel condensation reaction results in the effective assembly of a diversified hitherto unreported 1,2,3‐triazolyl coumarin frameworks. In present strategy, the catalyst could be easily isolated by simple filtration and reused up to eight consecutive cycles without significant drop in the reaction yields. During the leaching experiment, there is no leaching amount of the catalyst was detected, suggesting true heterogeneity in the catalytic system. The results of gram‐scale reaction and green metrics calculations also confirmed the sustainability and industrial applicability of the current catalytic protocol.     

S(N)2 ring opening of beta-lactones: an alternative to catalytic asymmetric conjugate additions

Merging catalytic asymmetric acyl halide-aldehyde cyclocondensation (AAC) reactions with ensuing Grignard-mediated ring opening of the derived enantiomerically enriched beta-lactones is presented as a generally useful asymmetric synthesis of beta-disubstituted carboxylic acids. Enantiomerically enriched beta-lactones are subject to efficient S(N)2 ring opening with a variety of copper-modified alkyl Grignard reagents, including highly branched nucleophiles. Considerable structural variation in the lactone electrophile is also tolerated. Phenyl- and vinyl-derived organometallics are not efficient nucleophiles for the ring-opening reactions.     

Catalytic Asymmetric Propionate Aldol Reactions via Acyl Halide-Aldehyde Cyclocondensations

Catalyzed asymmetric acyl halide-aldehyde cyclocondensation (AAC) reactions afford highly enantiomerically enriched 3,4-disubstituted-2-oxetanones. These reactions constitute catalytic asymmetric propionate aldol additions. An optically active Al(III)-triamine complex (10 mol %) catalyzes the di(isopropyl)ethylamine-mediated cyclocondensation of propionyl bromide and a variety of aldehydes to afford beta-lactone adducts with uniformly high enantioselection (90 --> 98% ee), diastereoselection (74 --> 98% de), and chemical yields (78-90%). Lactone ring opening reveals that the enantiomerically enriched beta-lactones act as surrogates for syn propionate aldol adducts.     

Catalytic asymmetric assembly of stereodefined propionate units: an enantioselective total synthesis of (-)-pironetin

Double diastereoselection in alkaloid-catalyzed acyl halide-aldehyde cyclocondensation (AAC) reactions provides a strategy for realizing syn- or anti-selective propionate aldol additions from a common reaction manifold. Matched AAC homologation of enantioenriched aldehydes afford cis-disubstituted beta-lactones as surrogates for syn aldols; the mismatched AAC reactions provide anti-selective aldols in the form of trans-disubstituted 2-oxetanones. The utility of this reaction technology in synthesis activities is exemplified in a catalytic asymmetric total synthesis of (-)-pironetin.     

Cinchona alkaloid-lewis acid catalyst systems for enantioselective ketene-aldehyde cycloadditions

Asymmetric cinchona alkaloid-catalyzed acid chloride-aldehyde cyclocondensation (AAC) reactions afford enantioenriched 4-substituted and 3,4-disubstituted beta-lactones with near perfect absolute and relative stereocontrol. These reactions are characterized by the operational simplicity derived from using commercially available or easily obtained (one-step) reaction catalysts and in situ ketene generation from acid chlorides. The range of aldehyde substrates that serve as effective AAC substrates include sterically hindered aldehydes such as cyclohexanecarboxaldehyde and pivaldehyde.     

Highly cis-selective Rh(I)-catalyzed cyclopropanation reactions

The performance of recently reported highly cis-diastereoselective Rh(I) cyclopropanation catalysts has been significantly improved by a systematic study of different reaction parameters (catalyst activation, solvent, temperature, stoichiometry). The catalyst efficiency and diastereoselectivity were enhanced by changing the activating agent from AgOTf to NaBArf. With this new system, the Rh(I) catalyst was shown to be a highly efficient and cis-diastereoselective cyclopropanation catalyst in reactions between α-diazoacetates and a range of different alkenes and substituted derivatives. Particularly noteworthy is the remarkable reactivity and cis-diastereoselectivity displayed in the reactions between ethyl diazoacetate and cyclopentene, 2,5-dihydrofuran, and benzofuran, with yields up to 99% and cis-selectivities greater than 99%.     

Didecyldimethylammonium bromide (DDAB): a universal, robust, and highly potent phase-transfer catalyst for diverse organic transformations

Didecyldimethylammonium bromide (DDAB) has been scrutinized in comparison with traditional phase-transfer catalysts in variety of liquid-liquid reactions. It was found to be an exceptionally comprehensive, durable, and highly efficient phase-transfer catalyst (PTC) in a number of representative organic transformations such as C- and N-alkylations, isomerization, esterification, elimination, cyanation, bromination, and oxidation under very mild conditions of temperature and mixing. It was confirmed that DDAB is an exceedingly accessible and concurrently a highly liphophilic phase-transfer catalyst. This unprecedented characteristic renders DDAB to be a multipurpose catalyst that functions effectively both in mass transfer controlled and chemically controlled phase-transfer reactions.     

Pd(0)-Schiff-base@MCM-41 as high-efficient and reusable catalyst for C–C coupling reactions

A Pd-Schiff-base grafted on functionalized mesoporous MCM-41 (Pd(0)-Schiff-base@MCM-41) was prepared using a post-grafting procedure and used as a highly efficient and reusable nanostructural catalyst for the carbon–carbon cross-coupling reactions of various aryl halides (including aryl iodide, bromide and chloride) with sodium tetraphenyl borate, phenylboronic acid and butyl acrylate. This catalyst exhibits interesting reactivity through Heck and Suzuki reactions.     

A robust hydrophilic pyridine-bridged bis-benzimidazolylidene palladium pincer complex: synthesis and its catalytic application towards Suzuki-Miyaura couplings in aqueous solvents

A novel hydrophilic pyridine-bridged bis-benzimidazolylidene palladium pincer complex (3) acted as a highly efficient robust recyclable molecular catalyst towards Suzuki-Miyaura coupling reactions in aqueous media and tolerated various functional groups (even heterocycles) with extremely low catalyst loading.     

Identification of an activated catalyst in the iridium-catalyzed allylic amination and etherification. Increased rates, scope, and selectivity

Studies were conducted to determine possible intermediates in the highly enantioselective, iridium-catalyzed amination and etherification of allylic carbonates, and these studies revealed that cyclometalation of the phosphoramidite ligand is likely to generate the active catalyst. The square-planar [Ir(COD)(L1)Cl] (L1 = P(BINOL)(bisphenethylamine)) did not react with cinnamyl carbonate, but did react with amine to generate an Ir(I) trigonal bipyramidal complex coordinated by COD, a cyclometalated kappa2-phosphoramidite, and a kappa1-phosphoramidite. This complex reacted with phosphines to generate products from replacement of the kappa1-phosphoramidite. These cyclometalated complexes were highly active catalysts for allylic amination and etherification and retained the high selectivity of the original catalyst system. In addition, these complexes combined with [Ir(cod)Cl]2 catalyzed reactions of amines with lower loadings, catalyzed reactions of alkylamines and aromatic amines that did not react with the original catalyst system, and catalyzed reactions of phenoxides under milder conditions.     

有氧条件下聚(氯乙烯)负载Pd(Ⅱ)配合物高效催化Heck和无铜Sonogashira反应(英文)

A novel poly(vinyl chloride)-supported Pd complex was found to be a highly active catalyst for the Heck and Sonogashira reactions of aryl halides under aerobic conditions.The complex is thermally stable,and can be easily recovered and reused.The catalyst was recycled for the Heck and Sonogashira reactions for five runs without appreciable loss of its catalytic activity,and with negligible metal leaching.     

Well-Defined,Versatile and Recyclable Half-Sandwich Nickelacarborane Catalyst for Selective Carbene-Transfer Reactions

Catalytic carbene-transfer reactions constitute a class of highly useful transformations in organic synthesis. Although catalysts based on a range of transition-metals have been reported, the readily accessible nickel(II)-based complexes have been rarely used. Herein, an air-stable nickel(II)-carborane complex is reported as a well-defined, versatile and recyclable catalyst for selective carbene transfer reactions with low catalyst loading under mild conditions. This catalyst is effective for several types of reactions including diastereoselective cyclopropanation, epoxidation, selective X−H insertions (X = C, N, O, S, Si), particularly for the unprotected substrates. This represents a rare example of carborane ligands in base metal catalysis.     

有氧条件下聚(氯乙烯)负载Pd(II)配合物高效催化Heck和无铜Sonogashira反应Mohammad Bakherad,Ali Keivanloo,Shahrzad Samangooei简

A novel poly(vinyl chloride)-supported Pd complex was found to be a highly active catalyst for the Heck and Sonogashira reactions of aryl halides under aerobic conditions. The complex is thermally stable, and can be easily recovered and reused. The catalyst was recycled for the Heck and Sonogashira reactions for five runs without appreciable loss of its catalytic activity, and with negligible metal leaching.     

Mizoroki–Heck and Suzuki–Miyaura reactions mediated by poly(2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid)‐stabilized magnetically separable palladium catalyst

The purpose of this work was to synthesize and characterize a new magnetic polymer nanosphere‐supported palladium(II) acetate catalyst for reactions requiring harsh conditions. In this regard, an air‐stable, moisture‐stable and highly efficient heterogenized palladium was synthesized by the coordination of palladium(II) acetate with poly(2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid)‐grafted modified magnetic nanoparticles with a core–shell structure. The structure of the newly developed catalyst was characterized using various techniques. The catalytic activity of the resultant nano‐organometallic catalyst was evaluated in Mizoroki–Heck and Suzuki–Miyaura reactions to afford the corresponding coupling products in good to excellent yields. High selectivity as well as outstanding turnover number (14 143, 4900) and turnover frequency (28 296, 7424) values were recorded for the catalyst in Suzuki–Miyaura and Mizoroki–Heck reactions, respectively. Magnetic separation and recycling of the catalyst for at least six runs became possible without any significant loss of efficiency or any detectable palladium leaching.     

Highly efficient silica gel-supported 1,2-diaminocyclohexane-Pd catalyst for Suzuki-Miyaura and Sonogashira coupling reactions

A palladium (Pd) catalyst was prepared by immobilization of a 1,2-diaminocyclohexane based Pd-complex onto amorphous silica gel and its applications as a heterogeneous catalyst for Suzuki-Miyaura and Sonogashira coupling reactions are described. The catalyst was highly efficient, reusable and air-stable. An erratum to this article is available at .     

Copper- and phosphine-free Sonogashira coupling reactions of aryl iodides catalyzed by an N,N-bis(naphthylideneimino)diethylenetriamine-functionalized polystyrene resin supported Pd(II) complex under aerobic conditions

A polymer-supported palladium(II) N,N-bis(naphthylideneimino)diethylenetriamine complex is found to be a highly active catalyst for Sonogashira coupling reactions. The reactions are performed under copper- and phosphine-free conditions in an air atmosphere. The palladium catalyst is easily separated, and can be reused several times without significant loss in catalytic activity.     

An efficient Yb(OTf)3 catalyzed alkylation of 1,3-dicarbonyl compounds using alcohols as substrates

A highly efficient and environmentally friendly method for catalytic benzylation/allylation of 1,3-dicarbonyl compounds with alcohols has been developed by using Yb(OTf)₃ as a catalyst. The reactions proceed smoothly to give the desired products in moderate to excellent yields, mostly at room temperature. The catalyst can be recovered and reused at least six times without visible loss of catalytic activity for such reactions.     

Switch in Catalyst State: Single Bifunctional Bi-state Catalyst for Two Different Reactions

Disclosed here is a molecular switch which responds to acid-base stimuli and serves as a bi-state catalyst for two different reactions. The two states of the switch serve as a highly active and poorly active catalyst for two catalytic reactions (namely a hydrogenation and a dehydrogenative coupling) but in a complementary manner. The system was used in an assisted tandem catalysis set-up involving dehydrogenative coupling of an amine and then hydrogenation of the resulting imine product by switching between the respective states of the catalyst.     

Direct asymmetric anti-Mannich-type reactions catalyzed by a designed amino acid

The development of catalysts for Mannich-type reactions that afford anti-products with excellent diastereo- and enantioselectivities under mild conditions and low catalyst loadings (1-5 mol %) is reported. Based on principles gained from the study of (S)-proline-catalyzed Mannich-type reactions that afford enantiomerically enriched syn-products, (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid (RR35) has been designed to catalyze the direct enantioselective anti-selective Mannich-type reactions. Computational studies of the above reaction using HF/6-31G* level of theory suggested that this design would be highly effective. The catalyst was subsequently synthesized and studied in organocatalytic Mannich-type reactions between unmodified aldehydes and N-PMP-protected alpha-imino esters. In accord with the design principles and in quantitative agreement with the theoretical predictions, reactions catalyzed by this catalyst afforded anti-products in good yields with excellent diastereo- and enantioselectivities (anti:syn 94:6 to 98:2, >97 to >99% ee).