Intercepted Decarboxylative Allylations of Nitroalkanoates

Using palladium-catalyzed decarboxylation, several cascade reactions of allyl and prenyl nitroalkanoates that lead to nitro-containing chemical building blocks are described. A nitronate Michael addition/Tsuji-Trost allylation cascade was developed, leading to functionally dense chemical building blocks. Likewise, a Tsuji-Trost/decarboxylative protonation sequence was developed for the synthesis of orthogonally functionalized 2° nitroalkanes. The latter method provides rapid access to the indolizidine core.     

Palladium-catalyzed allylic substitution with (η6-arene-CH2Z)Cr(CO)(3)-based nucleophiles

Although the palladium-catalyzed Tsuji-Trost allylic substitution reaction has been intensively studied, there is a lack of general methods to employ simple benzylic nucleophiles. Such a method would facilitate access to "α-2-propenyl benzyl" motifs, which are common structural motifs in bioactive compounds and natural products. We report herein the palladium-catalyzed allylation reaction of toluene-derived pronucleophiles activated by tricarbonylchromium. A variety of cyclic and acyclic allylic electrophiles can be employed with in situ generated (η(6)-C(6)H(5)CHLiR)Cr(CO)(3) nucleophiles. Catalyst identification was performed by high throughput experimentation (HTE) and led to the Xantphos/palladium hit, which proved to be a general catalyst for this class of reactions. In addition to η(6)-toluene complexes, benzyl amine and ether derivatives (η(6)-C(6)H(5)CH(2)Z)Cr(CO)(3) (Z = NR(2), OR) are also viable pronucleophiles, allowing C-C bond-formation α to heteroatoms with excellent yields. Finally, a tandem allylic substitution/demetalation procedure is described that affords the corresponding metal-free allylic substitution products. This method will be a valuable complement to the existing arsenal of nucleophiles with applications in allylic substitution reactions.     

Petasis Borono-Mannich reaction and allylation of carbonyl compounds via transient allyl boronates generated by palladium-catalyzed substitution of allyl alcohols. an efficient one-pot route to stereodefined alpha-amino acids and homoallyl alcohols

An efficient one-pot procedure was designed by integration of the pincer-complex-catalyzed borylation of allyl alcohols in the Petasis borono-Mannich reaction and in allylation of aldehydes and ketones. These procedures are suitable for one-pot synthesis of alpha-amino acids and homoallyl alcohols from easily available allyl alcohol, amine, aldehyde, or ketone substrates. In the presented transformations, the active allylating agents are in situ generated allyl boronic acid derivatives. These transient intermediates are proved to be reasonably acid-, base-, alcohol-, water-, and air-stable species, which allows a high level of compatibility with the reaction conditions of the allylation of various aldehyde/ketone and imine electrophiles. The boronate source of the reaction is diboronic acid or in situ hydrolyzed diboronate ester ensuring that the waste product of the reaction is nontoxic boric acid. The regio- and stereoselectivity of the reaction is excellent, as almost all products form as single regio- and stereoisomers. The described procedure is suitable to create quaternary carbon centers in branched allylic products without formation of the corresponding linear allylic isomers. Furthermore, products comprising three stereocenters were formed as single products without formation of other diastereomers. Because of the highly disciplined consecutive processes, up to four-step, four-component transformations could be performed selectively as a one-pot sequence. For example, stereodefined pyroglutamic acid could be prepared from a simple allyl alcohol, a commercially available amine, and glyoxylic acid in a one-step procedure. The presented method also grants an easy access to stereodefined 1,7-dienes that are useful substrates for Grubbs ring-closing metathesis.     

Palladium-catalyzed substitution and cross-coupling of benzylic fluorides

Benzylic fluorides are suitable substrates for Pd(0)-catalyzed Tsuji-Trost substitution using carbon, nitrogen, oxygen, and sulfur nucleophiles and for cross-coupling with phenylboronic acid. For the bifunctional substrate 4-chlorobenzyl fluoride, fine-tuning of the reaction conditions allows for the regioselective displacement of either the chlorine or fluorine substituent. The leaving group ability of fluoride vs other groups displaced in substitution is CF(3)CO(2) ≈ p-NO(2)C(6)H(4)CO(2) ≈ OCO(2)CH(3) > F > CH(3)CO(2), a ranking similar to allylic fluorides under Pd catalysis.     

Synthesis,characterization, and thermal properties of anhydride terminated and allyl terminated oligoimides

This study concerns the synthesis of anhydride terminated oligoimides (ANTOI) and allyl terminated oligoimides (ALTOI), in acetic acid medium, which allows a very fast reaction and an easy working out. For the preparation of ALTOIs, two methods are compared: the first one consists of adding the monofunctional compound (allyl amine) to the ANTOI already formed during a first step by reaction of a dianhydride (excess) and a diamine. The second method consists of a “one pot” reaction between the dianhydride, the diamine, and the monofunctional allyl–amine compounds, at the beginning of the reaction. The experimental results show that the best control of the molecular weights is obtained with the first method. If the amount of allyl amine is higher than the amount necessary to end cap the ANTOI, a transimidization reaction occurs. Thermal analyses of oligoimides terminated by anhydride or allyl groups have been performed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Transition and thermoresistance properties make ANTOI and ALTOI derivatives interesting as precursors for block polyimide copolymers. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2993–3003, 2000     

A TCF-Based Carbon Monoxide NIR-Probe without the Interference of BSA and Its Application in Living Cells

As toxic gaseous pollution, carbon monoxide (CO) plays an essential role in many pathological and physiological processes, well-known as the third gasotransmitter. Owning to the reducibility of CO, the Pd⁰-mediated Tsuji-Trost reaction has drawn much attention in CO detection in vitro and in vivo, using allyl ester and allyl ether caged fluorophores as probes and PdCl₂ as co-probes. Because of its higher decaging reactivity than allyl ether in the Pd⁰-mediated Tsuji-Trost reaction, the allyl ester group is more popular in CO probe design. However, during the application of allyl ester caged probes, it was found that bovine serum albumin (BSA) in the fetal bovine serum (FBS), an irreplaceable nutrient in cell culture media, could hydrolyze the allyl ester bond, and thus give erroneous imaging results. In this work, dicyanomethylenedihydrofuran (TCF) and dicyanoisophorone (DCI) were selected as electron acceptors for constructing near-infrared-emission fluorophores with electron donor phenolic OH. An allyl ester and allyl ether group were installed onto TCF-OH and DCI-OH, constructing four potential CO fluorescent probes, TCF-ester, TCF-ether, DCI-ester, and DCI-ether. Our data revealed that ester bonds of TCF-ester and DCI-ester could completely hydrolyze in 20 min, but ether bonds in TCF-ether and DCI-ether tolerate the hydrolysis of BSA and no released fluorescence was observed even up to 2 h. Moreover, passing through the screen, it was concluded that TCF-ether is superior to DCI-ether due to its higher reactivity in a Pd⁰-mediated Tsuji-Trost reaction. Also, the large stokes shift of TCF-OH, absorption and emission at 408 nm and 618 nm respectively, make TCF-ether desirable for fluorescent imaging because of differentiating signals from the excitation light source. Lastly, TCF-ether has been successfully applied to the detection of CO in H9C2 cells.     

Water enables direct use of allyl alcohol for Tsuji-Trost reaction without activators

[reaction: see text] An aqueous biphasic reaction system enables the direct use of allyl alcohol in the Tsuji-Trost reaction without the help of any activating reagents for allyl alcohol. The reaction conditions are neutral to basic, allowing the use of amines as the nucleophile. Theoretical calculations have elucidated the importance of hydration of the hydroxy group for the smooth generation of pi-allylpalladium species.     

Platinum-catalyzed diastereoselective intramolecular coupling of allyl halides and hydrazones

Nucleophilic allyl platinum addition to hydrazones under platinum-catalyzed conditions was studied. To generate nucleophilic allyl platinum complexes, allyl halides were employed with platinum complexes, SnCl(2), and H(2). The allyl platinum(IV) intermediates reacted with the hydrazone to give the corresponding cyclic amine derivatives in good yield and with excellent diastereoselectivity. The cis selectivity of N-tethered substrates was attributed to a tight interaction of allyl platinum species with the hydrazone, on the basis of the results of solvent screening and acid/base addition experiments.     

Fuel-driven macromolecular coacervation in complex coacervate core micelles

Fuel-driven macromolecular coacervation is an entry into the transient formation of highly charged, responsive material phases. In this work, we used a chemical reaction network (CRN) to drive the coacervation of macromolecular species readily produced using radical polymerisation methods. The CRN enables transient quaternization of tertiary amine substrates, driven by the conversion of electron deficient allyl acetates and thiol or amine nucleophiles. By incorporating tertiary amine functionality into block copolymers, we demonstrate chemical triggered complex coacervate core micelle (C3M) assembly and disassembly. In contrast to most dynamic coacervate systems, this CRN operates at constant physiological pH without the need for complex biomolecules. By varying the allyl acetate fuel, deactivating nucleophile and reagent ratios, we achieved both sequential signal-induced C3M (dis)assembly, as well as transient non-equilibrium (dis)assembly. We expect that timed and signal-responsive control over coacervate phase formation at physiological pH will find application in nucleic acid delivery, nano reactors and protocell research.

We apply an allyl acetate fuelled chemical reaction network (CRN) to control the coacervation of macromolecular species at constant physiological pH without the need for complex biomolecules.     

One-pot organocatalytic domino Michael/alpha-alkylation reactions: direct catalytic enantioselective cyclopropanation and cyclopentanation reactions

The development of one-pot organocatalytic domino Michael/alpha-alkylation reactions between bromomalonates or bromoacetoacetate esters and alpha,beta-unsaturated aldehydes is presented. The chiral-amine-catalyzed reactions with bromomalonates as substrates give access to the corresponding 2-formylcyclopropane derivatives in high yields with excellent diastereoselectivity and up to 99 % ee. The catalytic domino Michael/alpha-alkylation reactions between 4-bromo-acetoacetate and enals provide a route for the synthesis of functionalized cyclopentanones in good to high yields with 93-99 % ee. The products from the organocatalytic reactions were also reduced with high diastereoselectivity to the corresponding cyclopropanols and cyclopentanols, respectively. Moreover, one-pot combinations of amine and heterocyclic carbene catalysis (AHCC) enabled the highly enantioselective synthesis of beta-malonate esters (91-97 % ee) from the reaction between bromomalonates and enals. The tandem catalysis included the catalytic domino reaction followed by catalytic in situ chemoselective ring-opening of the 2-formylcyclopropane intermediates.     

The silicon effect on the regioselectivity of the Tsuji-Trost reaction. Experimental and theoretical approaches

Regioselectivity of the Tsuji-Trost reaction on allyl acetates and carbonates substituted with silyl groups at the olefinic moiety has been analyzed. Silicon atom in the central carbon atom increases the stability of the intermediate π-allylpalladium cation with respect to the isomeric π-allylpalladium cation featuring the silicon in a terminal carbon atom.     

Multicomponent reactions of allenes, diaryl diselenides, and nucleophiles in the presence of iodosobenzene diacetate: direct synthesis of 3-functionalized-2-arylselenyl substituted allyl derivatives

A multicomponent reaction of allenes, diaryl diselenides, and nucleophiles in the presence of iodosobenzene diacetate has been developed, providing a novel method for the preparation of synthetically useful 3-functionalized-2-arylselenyl substituted allyl derivatives.     

Asymmetric Synthesis of 2,3‐Dihydropyrroles by Ring‐Opening/Cyclization of Cyclopropyl Ketones Using Primary Amines

The asymmetric ring‐opening/cyclization of cyclopropyl ketones with primary amine nucleophiles was catalyzed by a chiral N,N′‐dioxide/scandium(III) complex through a kinetic resolution process. A broad range of cyclopropyl ketones and primary amines are suitable substrates of this reaction. The corresponding products were afforded in excellent enantioselectivities and yields (up to 97 % ee and 98 % yield) under mild reaction conditions. This method provides a promising access to chiral 2,3‐dihydropyrroles as well as an effective procedure for the kinetic resolution of 2‐substituted cyclopropyl ketones.     

Palladium‐Catalyzed Three‐Component Cascade Reaction: Facial Access to Densely Functionalized Indolizines

A palladium‐catalyzed three‐component cascade reaction of 2‐(2‐enynyl)pyridines with nucleophiles and allyl halides has been developed, enabling the synthesis of densely functionalized indolizines in moderate to good yields. The newly developed methodology offers several practical advantages, including operational simplicity, ready availability of starting materials, and mild reaction conditions.     

An efficient ultrasonic synthetic approach,DFT study,and molecular docking of 6a-hydroxy-9-nitro-6,6a-dihydro-isoindolo[2,1-a] quinazoline-5,11-dione derivatives as algaecides for refining wastewater

In the present work, reaction of 3-nitrophthalic anhydride with anthranilic acid to afford the corresponding anthranil that is treated with acetic anhydride that yielded the 2-benzoxazinonyl-5-nitrobenzoic acid (BNBA) could be isomerized to the stereogenic 9-nitrobenzoxazinone[2,3-a]isoindolinone acetate (NBIA) via basic reaction conditions. A reaction of the BNBA→NBIA was allowed with series of nitrogen nucleophiles such as formamide and hydrazine derivatives, for example, hydrazine hydrate, hydroxyl amine, acetic hydrazide, thiosemicarbazide, thiocarboihydrazide, and some amino acid, for example, glycine, alanine, and some aliphatic amine, for example, octyl amine, decyl amine, and aromatic amine, for example, aniline, o-toluidine, 4-aminobenzoic acid, and carbon nucleophiles such as malononitrile and diethylmalonate. The basicity of previous nucleophiles and thermal stability of the products can be controlled on the course of reaction. The chemical structure of the synthesized compounds can be confirmed by micro-analytical, spectral data, and they are optimized by quantum chemical parameters (DFT study) to identify the thermal stability of the products. The data obtained from the molecular modeling were correlated with those obtained from the biological screening. A novel sequence of quinazoline derivatives were synthesized, evaluated for their algaecides activity against compounds 1 , 2b , and 6 that showed the highest algaecides activities of this series with relatively low toxicity in the median lethal dose test. The obtained results proved that the most active compounds could be useful models for future design, adaptation, and investigation to construct more active analogs.     

Highly Stereoselective Intermolecular Haloetherification and Haloesterification of Allyl Amides

An organocatalytic and highly regio‐, diastereo‐, and enantioselective intermolecular haloetherification and haloesterification reaction of allyl amides is reported. A variety of alkene substituents and substitution patterns are compatible with this chemistry. Notably, electronically unbiased alkene substrates exhibit exquisite regio‐ and diastereoselectivity for the title transformation. We also demonstrate that the same catalytic system can be used in both chlorination and bromination reactions of allyl amides with a variety of nucleophiles with little or no modification.     

Zirconium-catalyzed chemoselective methylalumination of ethers, amines, and sulfides bearing two terminal alkenyl groups

Chemoselectivity in the methylalumination reaction of unsymmetrical ethers, amines, and sulfides bearing two different terminal alkenyl groups, a 13-tetradecenyl group and an allyl, 4-pentenyl or 6-heptenyl group was examined. The methylalumination of the allyl derivatives proceeded with complete chemoselectivity to afford only the 13-tetradecenyl-monomethylated products. In the methylalumination reactions of the 4-pentenyl and the 6-heptenyl derivatives, in addition to the 13-tetradecenyl-monomethylated products, and dimethylated products were also obtained. However, as in the case of the allyl derivatives, monomethylation to the shorter 4-pentenyl or 6-heptenyl group was not observed, except in the case of 6-heptenyl 13-tetradecenyl amine. The unique selectivity was rationalized upon how readily the intramolecular ligand exchange reaction between intermediate zirconocenium-alkene and zirconocenium-heteroatom complexes could occur.     

Synthesis of Novel Quinazoline Derivatives as Antimicrobial Agents

Quinazoline isothiocyanate 1 reacts with various nucleophiles(nitrogen nucleophiles,oxygen nucleophiles and sulphur nucleophiles)to afford heterocyclic systemes 2-13,Also,the [4 2] cycloaddition reaction of 1 with phenyl isocyanate,benzylidene aryl amine and cinnamic acid derivatives gave novel heterocyclic compounds 14-16,Moreover,the reaction of 1 with active methylene compounds under Michael reaction conditions also was investigated to yield 17 and 18 and it was found that all these reactions proceede via isothiocyanate heterocyclization to furnish non-condensed heterocyclic compoundes,Some of the newly synthesized compounds were tested for their antimicrobial activities.     

Silver versus gold catalysis in tandem reactions of carbonyl functions onto alkynes: a versatile access to furoquinoline and pyranoquinoline cores

An efficient and versatile tandem process of acetalization and cycloisomerization reactions has been developed for the reactions of 1-alkynyl-2-carbonylquinoline substrates. The reaction occurs thanks to Au(I) and Ag(I) catalysis. Silver(I) catalysis has been extensively studied (11 different silver species) on a broad range of quinoline derivatives (variation of alkyne substituent, of carbonyl function and of nucleophiles), leading to a variety of furoquinoline and pyranoquinoline moieties. An insight is given for the presumed mechanism along with DFT-B3 LYP/6-31G** calculations to address the 6-endo and 5-exo regioselectivities observed.     

Selective Si−C(sp3) Bond Cleavage in (Aminomethyl)silanes by Carbanionic Nucleophiles and Its Stereochemical Course

Selective cleavage of a silicon–carbon bond in tetraorganosilanes is still a great challenge. A new type of Si−C(sp³) bond cleavage in bench-stable (aminomethyl)silanes with common organolithium reagents as nucleophiles has now been identified. Suitable leaving groups are benzyl, allyl, and phenylthiomethyl groups. A β-donor function and polar solvents are essential for the reaction. Simple switching between α-deprotonation and substitution is possible through slight modifications of the reaction conditions. The stereochemical course of the reaction was elucidated by using a silicon-chiral benzylsilane. The new transformation proceeds stereospecifically with inversion of configuration and can be used for the targeted synthesis of enantiomerically pure tetraorganosilanes, which are otherwise difficult to access. Quantum chemical calculations provided insight into the mechanism of the new substitution.