Au(I)-catalyzed tandem [3,3]-sigmatropic rearrangement-cycloisomerization cascade as a route to spirocyclic furans

Gold-catalyzed reaction of 1-(3-hydroxypropynyl)cycloalkanol derivatives was studied. The reaction profile was highly dependent on the ring size, migrating group, as well as reaction conditions. An efficient route to spirocyclic furans via tandem [3,3]-sigmatropic rearrangement-cycloisomerization is reported.     

In Situ Monitoring of Selective Catalysts on Urethane Formation by FT-IR Spectroscopy

A number of tertiary amines and organotin catalysts for the phenyl isocyanate- 1,2-propylene glycol reaction were investigated by using in situ FT-IR. The reaction rate of each hydroxyl group, which is defined as the ratio between the rate constant of the secondary hydroxyl group and the rate constant of the primary hydroxyl group, is described with a second-order equation. The influence of different catalyst concentrations as well as the reaction temperature is discussed. It is observed that the selectivity depends on temperature but not on concentration, and stannous octoate is the most effective catalyst. The thermodynamic parameters were determined for the catalyzed reactions, primary and secondary hydroxyl groups being differentiated.     

Synthesis of 1,3,5-trisubstituted hydantoins by regiospecific domino condensation/aza-Michael/O-->N acyl migration of carbodiimides with activated alpha,beta-unsaturated carboxylic acids

[reaction: see text] Carbodiimides and suitably activated alpha,beta-unsaturated carboxylic acids react effectively to afford a vast array of 1,3,5-trisubstituted hydantoins by means of a regiospecific domino condensation/aza-Michael/N-->O acyl migration. The reaction works well in very mild conditions (20 degrees C, dichloromethane) with fumaric acid derivatives bearing an electron-withdrawing group in the beta position. Good results have been obtained also with less activated substrates bearing only one electron-withdrawing group in the beta position, using more polar solvents (acetonitrile, DMF), and in the presence of a base (2,4,6-trimethylpyridine). Reactions with asymmetric carbodiimides are generally highly chemo- and regioselective, giving rise to the formation of a single regioisomeric hydantoin. However, asymmetric carbodiimides bearing one alkyl group and one aryl group can produce variable amounts of N-acylurea byproducts. The latter could be easily recovered and transformed into the corresponding hydantoins. A detailed study of the influence of key reaction parameters such as solvent, base, and structure of the reactants on the reaction outcome and mechanism is presented. This methodology is particularly convenient for the synthesis of trifluoromethyl-substituted hydantoins, which could be interesting as bioactive compounds in medicinal chemistry, as well as precursors of the corresponding alpha-amino acids.     

Organo‐Iodine(III)‐Catalyzed Oxidative Phenol–Arene and Phenol–Phenol Cross‐Coupling Reaction

The direct oxidative coupling reaction has been an attractive tool for environmentally benign chemistry. Reported herein is that the hypervalent iodine catalyzed oxidative metal‐free cross‐coupling reaction of phenols can be achieved using Oxone as a terminal oxidant in 1,1,1,3,3,3‐hexafluoropropan‐2‐ol (HFIP). This method features a high efficiency and regioselectivity, as well as functional‐group tolerance under very mild reaction conditions without using metal catalysts.     

Synthetic utility of stannyl enolates as radical alkylating agents

[reaction: see text] The radical-initiated beta-ketoalkylation of haloalkanes with tributylstannyl enolates is described. Stannyl enolates derived from aromatic ketones are reactive toward the homolytic beta-ketoalkylation of simple haloalkanes as well as those activated by an electron-withdrawing group. The reactivity of stannyl enolates as radical alkylating agents can be utilized for an efficient three-component coupling reaction among stannyl enolates, haloalkanes, and electron-deficient alkenes.     

Seven-dimensional quantum dynamics study of the O(3P)+CH4 reaction

The initial state selected time-dependent wave packet calculations have been carried out to study the title reaction with seven degrees of freedom included by restricting the nonreacting CH(3) group under C(3V) symmetry and the CH bond length in the group. Total reaction probabilities as well as integral cross sections were calculated for the ground and four vibrationally excited reagent states. Our calculation shows that the reactivity is very small for the reaction for collision energy up to 1.0 eV for all the initial states. Initial vibration excitation of CH(4), in particular, the CH stretch excitation, enhances the reactivity, but only part of the excitation energy deposited can be used to reduce the reaction threshold. The rate constant for the ground initial state agrees rather well with that from a recent quasiclassical trajectory study and is larger than that from the semirigid vibrating rotor target calculations, in particular, in the low temperature region. On the other hand, the thermal rate constant calculated from the integral cross sections for these five vibrational states is about a factor of 20 smaller than that from the multiconfiguration time-dependent Hartree study.     

Vinyl quinones as Diels-Alder dienes: concise synthesis of (-)-halenaquinone

A concise asymmetric synthesis of (-)-halenaquinone is described. The synthesis features a diastereoselective Heck cyclization to set a quaternary center as well as a novel intramolecular inverse-electron-demand Diels-Alder reaction involving a vinyl quinone. The synthesis is highly convergent and features a minimal amount of protecting group manipulations.     

A palladium complex with a new hemilabile amino- and sulfur-containing phosphinite ligand as an efficient catalyst for the Heck reaction of aryl bromides with styrene. The effect of the amino group

A palladium complex with a new hemilabile amino- and sulfur-containing phosphinite ligand has been synthesised and its crystal structure determined. This system efficiently catalyses the Heck reaction of aryl bromides with styrene at 130°C after 24 h, with turnover numbers of up to 100000 and with a selectivity towards trans-stilbenes ranging from 91.5 to 96.3%. The analogous sulfur-containing phosphinite without the amino group has also been synthesised and subjected to the Heck reaction. The constructive role of the amino group on the formation of the P,S-chelate palladium complex as well as in the Heck reaction is discussed.     

DFT study on the reaction mechanism and regioselectivity for the [1,2]-anionic rearrangement of 2-benzyloxypyridine derivatives

The reaction mechanism of the [1,2]-anionic rearrangement of 2-benzyloxypyridines has been investigated using DFT calculations. Calculated results indicate that: the deprotonation step is relatively fast and the rearrangement step is the rate-determining step; electron-donating group on the benzene ring decreases the activation energy of the rearrangement, which correlates with an increase in reaction yield, while electron-withdrawing groups show the opposite effect. The rearrangement is calculated to proceed by way of an oxirane-like transition state that had previously been postulated as a transient intermediate. Furthermore, the mechanism for the rearrangement of 2-(benzyloxy)nicotinonitrile was discussed. The quick formation of the five membered ring intermediate leads to the predominant formation of 2-phenylfuro[2,3-b]pyridin-3-amine. The calculation results indicate the possibilities of derivatizing the starting pyridyl ether as well as facilitating the rearrangement reaction by adding an appropriate electron-donating group on the benzene ring or electron-withdrawing group on the pyridine ring for future studies.     

Synthesis of polyhydroxylated bicyclic tetrahydrofurans and tetrahydropyrans via a stereoselective domino cyclization/reduction reaction

A novel reaction cascade involving a Lewis acid-induced migration of an isopropylidene protecting group followed by the formation of a pyranose or furanose ring and subsequent reduction of the hemiacetal is described. Depending on the reaction conditions, as well as, the stereochemistry of the substrate, polyhydroxylated tetrahydrofurans or tetrahydropyrans can be obtained in reasonable yields. The synthons used in this transformation were prepared via a highly stereoselective one-pot tandem reaction, consisting of a 1,4-Michael addition of vinylmagnesium bromide to d-glucose-derived cyclohexenone followed by aldol reaction with 2,3-O-isopropylidene-d-glyceraldehyde.     

Destabilized carbenium ions. Secondary and tertiary α-acetylbenzyl cations and α-benzoylbenzyl cations

The secondary α-acetylbenzyl and α-benzoylbenzyl cations, as well as their tertiary analogues, have been generated in a mass spectrometer by electron impact induced fragmentation of the corresponding α-bromoketones. These ions belong to the interesting family of destabilized α-acylcarbenium ions. While primary α-acylcarbenium ions appear to be unstable, the secondary and tertiaiy ions exhibit the usual behaviour of stable entities in a potential energy well. This can be attributed to a ‘push-pull’ substitution at the carbenium ion centre by an electron-releasing phenyl group and an electron-withdrawing acyl substituent. The characteristic unimolecular reaction of the metastaible secondary and tertiary α-acylbenzyl cations is the elimination of CO by a rearrangement reaction involving a 1,2-shift of a methyl group and a phenyl group, respectively. The loss of CO is accompanied by a very large kinetic energy release, which gives rise to broad and dish-topped peaks for this process in the mass-analysed ion kinetic energy spectra of the corresponding ions. This behaviour is attributed to the rigid critical configuration of a corner-protonatei cyclopropanone derivative and a bridged phenonium ion derivative, respectively, for this reaction. For the tertiary α-acetyl-α-methylbenzyl cations, it has been shown by deuterium labelling and by comparison of collisional activation spectra that these ions equilibrate prior to decomposition with their ‘protomer’ derivatives formed by proton migration from the α-methyl substituent to the carbonyl group and to the benzene ring.     

Computational study of the transamination reaction in vinylogous acyls: Paving the way to design vitrimers with controlled exchange kinetics

One of the key points in the design of vitrimers is controlling the associative exchange kinetics. One common chemistry used in vitrimers is based on the dynamic amine exchange reaction of vinylogous acyl compounds in presence of free amine. Understanding the reaction mechanism is essential to assist the optimization of the reaction conditions as well as the molecular structure of the reactant compounds in the pursuit of new materials. In this work, a computational study has been performed to explore different reaction mechanisms in neutral, acidic and in basic conditions or in the presence of Lewis acids, as well as the effect of chemical modifications in the exchange reaction. The results reveal that the formation of hydrogen bonds are a key feature and that the vinylogous urea improves the transamination compared to vinylogous urethane. The esteric hindrance of the amino group in the vinylogous compound also plays an important role. Finally, the nature of the free amine can improve the reactivity by equilibrating two contrary effects: the basicity favors the nucleophilic attack and the conjugated acidity favors the protonation. The findings of this theoretical work shed light in the design of new vitrimers with controlled exchange kinetics by chemical modifications.     

2,3-Bis(phenylsulfonyl)-1,3-butadiene: Substrate for Michael Donor/Acceptors in a Novel Synthesis of Fused Cyclopentenes

The reaction of 2,3-bis(phenylsulfonyl)-1,3-butadiene with the anion of various 1-substituted dimethyl 1-pentenedioates has been investigated with the purpose of devising a tandem conjugate addition-[3 + 2]-anionic cyclization route for the synthesis of bicyclo[3.3.0]octenes. The reaction proceeds with complete stereospecificity as was evidenced by treating (E)- and (Z)-dimethyl (3-cyano-2-propenyl)propanedioate with NaH in the presence of the bis(phenylsulfonyl)diene. In both cases only a single cycloadduct was obtained with no detectable signs of the other diastereomer. The overall process involves a series of three sequential conjugate additions followed by benzenesulfinate ion ejection. The success of the method is dependent on the electrophilicity of the proximal pi-bond. When 2-((5-oxo-2,5-dihydrofuranyl)methyl)malonic acid dimethyl ester was used, a mixture of the tricyclic adduct as well as an allene was obtained. In this case, elimination of the benzenesulfinate group from the initially formed sulfone-stabilized carbanion is competitive with the intramolecular [3 + 2]-annulation process. The base-induced reaction of dimethyl 2-(methoxycarbonyl)-2-pentenedioate with the bis(phenylsulfonyl)diene was also studied. Even though the position of the acceptor moiety on the pi-bond was altered, the tandem Michael reaction sequence still occurs. The course of the reaction is dependent upon the length of the tether as well as the relative placement of the electron-withdrawing group on the olefin. Reaction with gamma-substituted beta,gamma-alkenyl derivatives leads to bicyclo[3.3.0]octenes, whereas beta-substituted beta,gamma-alkenyl reagents provide bicyclo[3.3.0]octenes derived from a novel alpha-elimination reaction.     

Solid-phase synthesis of 1,2,5-trisubstituted 4-imidazolidinones

An efficient method for the preparation of 1,2,5-trisubstituted 4-imidazolidinones is presented. The synthetic approach is based on the formation of an N-[1-(benzotriazol-1-yl)alkyl] moiety on the amino group of a MBHA resin-bound amino acid. The nucleophilic substitution of the benzotriazole group with an amidic nitrogen results in the formation of a five-membered imidazolidinone ring. The reaction is nonstereospecific and produces diastereomers in ratios that vary depending on the substituents on the ring. A variety of N-alpha-alkylated amino acids were cyclized with aromatic, aliphatic, and heterocyclic aldehydes to determine optimal reaction conditions and to select building blocks for the future preparation of a large, diverse range of individual trisubstituted imidazolidinones as well as a mixture-based combinatorial library.     

Stereocontrolled 1,3-phosphatyloxy and 1,3-halogen migration relay toward highly functionalized 1,3-dienes

A double migratory cascade reaction of α-halogen-substituted propargylic phosphates to produce highly functionalized 1,3-dienes has been developed. This transformation features 1,3-phosphatyloxy group migration followed by 1,3-shifts of bromine and chlorine as well as the unprecedented 1,3-migration of iodine. The reaction is stereodivergent: (Z)-1,3-dienes are formed in the presence of a copper catalyst, whereas gold-catalyzed reactions exhibit inverted stereoselectivity, producing the corresponding E products.     

9-(4-Bromophenyl)-9-fluorenyl as a safety-catch nitrogen protecting group

[reaction: see text] The 9-(4-bromophenyl)-9-fluorenyl (BrPhF) group has been developed as a novel safety-catch amine protection. This relatively acid-stable protecting group can be successfully activated by palladium-catalyzed cross-coupling reaction of the aryl bromide with morpholine and then cleaved effectively under mild conditions using dichloroacetic acid and triethylsilane. Complementary conditions are reported for selective removal of the BrPhF group in the presence of tert-butyl esters and carbamates as well as deprotection of tert-butyl esters and carbamates in the presence of BrPhF amines.     

Rhodium-Catalyzed C8-Alkenylation of Isoquinolones with Maleimides

An efficient Rh(III)-catalyzed C−H alkenylation of N-protected isoquinolone with maleimides is reported. The carbonyl group of isoquinolone acts as an inherent directing group. Various N-substituents in the maleimide, including alkyl, aryl, and even H and −OH, were well tolerated under the developed reaction condition. This protocol showed broad substrate scope, good selectivity, and excellent yields. Hammett plot is also drawn to check the effect of substituents on the reaction progress.     

Regioselective 2-alkylation of indoles with α-bromo esters catalyzed by Pd/P,P=O system

A palladium-catalyzed 2-alkylation of indoles with α-bromo esters is developed by employing a P,P=O ligand. The method features excellent regioselectivities, mild reaction conditions, and good functional group compatibility. The employment of the P,P=O ligand as well as 4 A molecular sieves were crucial for the success of the transformation. Mechanistic studies indicate the reaction proceed through a radical pathway.     

Novel synthesis of 3-pyrrole substituted β-lactams via microwave-induced bismuth nitrate-catalyzed reaction

Highly stereoselective synthesis of 3-pyrrole substituted β-lactams is accomplished. The first step involves the synthesis of 3-phthalimido substituted β-lactams following Staudinger cycloaddition reaction of acid chloride equivalent with imines. Synthesis of 3-amino β-lactams is achieved via the deprotection of phthalimido group with ethylenediamine. These 3-amino β-lactams are converted to a new series of N-substituted pyrroles at room temperature as well as using microwave-induced bismuth nitrate-catalyzed reaction with an excellent yield. Exclusive formation of trans pyrrole-substituted β-lactams is observed with N-chrysenyl system. The method is equally efficient for the synthesis of racemic as well as optically pure 3-pyrrole substituted β-lactams.     

The electrophilic thionation and chlorination of polyfluorinated α-Keto esters

The methyl ester of trifluoropyruvic acid reacts with phosphorus pentachloride at the keto carbonyl as well as at the ester carbonyl group. The reaction of polyfluorinated α-keto esters with Davy's reagent occurs regioselectively at the keto carbonyl and is accompanied by reduction and thiomethylation.