Asymmetric nitroaldol reaction catalyzed by a C2-symmetric bisoxazolidine ligand

A C2-symmetric bisoxazolidine was found to effectively catalyze the asymmetric Henry reaction of aliphatic and aromatic aldehydes. Beta-hydroxy nitroalkanes were produced in up to 99% yield and 95% ee. The bisoxazolidine-catalyzed nitroaldol formation requires relatively short reaction times, proceeds under mild conditions and is applicable to a wide range of substrates including sterically hindered aldehydes.     

Rhodium-catalyzed isomerization of alpha-arylpropargyl alcohols to indanones: involvement of an unexpected reaction cascade

A rhodium-catalyzed isomerization of alpha-arylpropargyl alcohols to indanones has been developed under mild conditions. Considering the ease of preparation of these propargyl alcohols (terminal alkynes + aromatic aldehydes), this method provides a new way of constructing indanones with high efficiency. By the mechanistic investigations using deuterium-labeled substrates, it has also been demonstrated that the reaction goes through an unexpected cascade, with a 1,4-hydrogen shift being the turnover-limiting step of the catalytic cycle.     

Chemoselective Schmidt reaction mediated by triflic acid: selective synthesis of nitriles from aldehydes

An excellent utility of Schmidt reaction of aldehydes to access corresponding nitriles in an instantaneous reaction is demonstrated. The reaction of aldehydes with NaN(3) and TfOH furnishes the corresponding nitriles in near quantitative yields and tolerates a variety of electron-withdrawing and electron-donating substituents on the substrates. Formanilides, a common side product in Schmidt reaction, is not observed in this reaction. Besides these advantages, the salient feature of this reaction is that it exhibits a remarkable chemoselectivity, as acid and ketone functionalities are well tolerated under the reaction conditions. The reaction is easily scalable, high yielding, and nearly instantaneous.     

Selective tryptophan modification with rhodium carbenoids in aqueous solution

A new transition metal-based reaction has been developed for the selective modification of tryptophan residues on protein substrates. After activation of vinyl-substituted diazo compounds by Rh2(OAc)4, the resulting metallocarbenoid intermediates were found to modify indoles in aqueous media despite competing reactions with water. Both N- and 2-substituted indole products were observed in the reaction. Following initial small-molecule studies, the reaction was performed on two protein substrates. Both myoglobin and subtilisin Carlsberg were modified readily in aqueous solution, and the tryptophan selectivity of the reactions was confirmed through MS analyses of trypsin digest fragments. It was also demonstrated that myoblobin concentrations as low as 10 muM still led to appreciable levels of modification. Reconstitution experiments confirmed that myoglobin retained its ability to bind heme following modification.     

Versatility of the Biginelli reaction: Synthesis of new biphenyl dihydropyrimidin-2-thiones using different ketones as building blocks

A multi-component synthesis of biphenyl dihydropyrimidin-2-thiones from 1-phenylthiourea, aldehydes and ketones or di-ketones has been demonstrated. The reaction proceeded well for aldehydes with electron donor or acceptor substituents under mild conditions.     

Rhodium-catalyzed addition of alkynes to activated ketones and aldehydes

[reaction: see text] The rhodium-catalyzed addition of alkynes to 1,2-diketones, 1,2-ketoesters, and aldehydes provides a method for the synthesis of tertiary alkynyl alcohols under mild conditions. The reaction tolerates many functional groups (such as carboxylic acids) that are incompatible with other methods. The alkyne addition reaction proceeds best using bulky phosphine ligands such as 2-(di-tert-butylphosphino)biphenyl. This method fills a void in the more common zinc-catalyzed processes, which give poor yields with enolizable 1,2-dicarbonyl substrates.     

Catalyzed selective direct α- and γ-alkylation of aldehydes with cyclic benzyl ethers by using T(+)BF4- in the presence of an inexpensive organic acid or anhydride

The cross dehydrogenative coupling (CDC) of cyclic benzyl ethers with aliphatic and α,β-unsaturated aldehydes has been developed. The mild reaction conditions, in which an N-oxoammonium salt derived from TEMPO (2,2,6,6-tetramethyl-1-piperidinoxyl) is employed as the oxidant in combination with a Cu catalyst, allow the use of relatively redox-unstable aldehydes under oxidative CDC conditions. The addition of a catalytic amount of trifluoroacetic acid (TFA) or Ac(2)O facilitates the reaction and increases the efficiency and selectivity. In contrast to the expected α-alkylation obtained with aliphatic aldehydes, α,β-unsaturated aldehydes led preferentially to the more challenging γ-alkylated products. The utility of the developed methodology was demonstrated by the synthesis of isochromane-derived bioactive compounds, such as the dopamine antagonist sonepiprazole.     

Highly selective oximation of aldehydes by reusable heterogeneous sandwich-type polyoxometalate catalyst

The selectivity of oximation of a variety of aliphatic aldehydes and polycyclic aromatic aldehydes as substrates has been greatly improved by applying a reusable heterogeneous sandwich-type polyoxometalate as catalyst under mild conditions.     

BF3-promoted reactions between aryl aldehydes and 3-diazoindolin-2-imines: Access to 2-amino-3-arylindoles

An efficient and highly regioselective synthesis of 2-amino-3-arylindoles via the BF₃-promoted reaction of 3-diazoindolin-2-imines with aryl aldehydes is described. This reaction could be carried out under mild reaction conditions with a broad scope of substrates. Moreover, the operation is of practical usage and could be scaled up.     

Enantioselective synthesis of quaternary stereocenters via a catalytic asymmetric Stetter reaction

A new electron-deficient chiral triazolium salt has been shown to catalyze the formation of quaternary stereocenters by an asymmetric intramolecular Stetter reaction. Pentafluorophenyl substitution on an aminoindanol-derived catalyst affords tertiary ether, thioether, and quaternary stereocenters in typically greater than 90% ee and very good chemical yield. Aromatic and aliphatic aldehydes are equally competent substrates for this reaction. The reaction proceeds at room temperature under mild conditions to provide quaternary stereocenters with functional group relationships that are particularly difficult to access by other methods.     

Ionic liquid [omim][PF6] as an efficient and recyclable reaction media for the cyanosilylation of aldehydes without Lewis acid or any special activation

Ionic liquid [omim][PF₆] has been demonstrated as an efficient and environmentally friendly reaction media as well as a promoter for the cyanosilylation of aldehydes under mild conditions. In addition, the recovered ionic liquid could be reused for subsequent runs with only a gradual decrease in activity.     

Synthesis of 2-phosphonopyrroles via a one-pot RCM/oxidation sequence

A four-step synthesis of 2-phosphonopyrroles is presented starting from suitable aldehydes. The key step in the synthesis involves a one-pot ring-closing metathesis/oxidation sequence of a functionalized alpha-aminoalkenyl phosphonate. Notwithstanding the presence of a nucleophilic nitrogen atom and high substitution patterns in the substrate, the results of the RCM reaction are excellent using mild reaction conditions. Furthermore, a synergism is observed between the RCM catalyst and the oxidizing agent, causing higher oxidation rates and allowing reaction for substrates that normally fail to ring close under standard RCM conditions.     

An Organocatalytic Azide–Aldehyde [3+2] Cycloaddition: High‐Yielding Regioselective Synthesis of 1,4‐Disubstituted 1,2,3‐Triazoles

An organocatalytic azide–aldehyde [3+2] cycloaddition (organo‐click) reaction of a variety of enolizable aldehydes is reported. The organo‐click reaction is characterized by a high rate and regioselectivity, mild reaction conditions, easily available substrates with simple operation, and excellent yields with a broad spectrum of substrates. It constitutes an alternative to the previously known CuAAC, RuAAC, and IrAAC click reactions.     

Rhodium-catalyzed methylenation of aldehydes

The rhodium-catalyzed methylenation of aldehydes using trimethylsilyldiazomethane and triphenylphosphine produces a variety of terminal alkenes in excellent yields. These mild and nonbasic reaction conditions allow the conversion of enolizable substrates (keto aldehydes and nonracemic alpha-substituted aldehydes) to terminal alkenes without epimerization. Optimization of the reaction conditions led to the conclusion that a variety of rhodium(I) sources can be used as catalysts. The effect of the solvent on the reaction has also been studied, and it indicates that although the THF is the best solvent, other solvents may be used. The reactivity of the system is very much dependent on the nature of the phosphine reagent. The use of an easily removable phosphine is also described. Spectroscopic studies indicate that the reaction proceeds via an unusual mechanism which leads to the in situ formation of the salt-free phosphorus ylide, methylenetriphenylphosphorane.     

Titanium tetrachloride incorporated crosslinked polystyrene copolymer as an efficient and recyclable polymeric Lewis acid catalyst for the synthesis of Β-amino carbonyl compounds at room temperature

An efficient and eco-friendly procedure for one-pot synthesis of β-amino carbonyl compounds by three-component reaction of aromatic aldehydes, acetophenone, and aromatic amines via a Mannich type reaction using a stable tightly bound complex, titanium tetrachloride incorporated crosslinked polystyrene copolymer (PS/TiCl₄), as a water tolerant, recoverable, and reusable polymeric Lewis acid catalyst in ethanol at room temperature is reported. The complex of the polystyrene and TiCl₄ provides a shelf-stable acidic, water tolerant material, and it is not easily hydrolyzed by water. Our findings thus show a novel and improved modification of the Mannich type reaction in terms of mild reaction conditions, clean reaction profiles, applicability to various substrates using a simple workup procedure which makes this reaction an interesting alternative to previously applied procedures. The recyclability of the catalyst makes this protocol environmentally benign.     

Cyclen-catalyzed Henry reaction under neutral conditions

A convenient cyclen-catalyzed Henry reaction of aldehydes with nitroalkanes under mild and neutral conditions is reported. This procedure constitutes the first cyclen-catalyzed synthesis of nitroalcohols and is adapted to the condensation of both aromatic and aliphatic aldehydes with nitromethane in THF at room temperature without addition of stoichiometric amount of the base. A wide range of substrates, β-nitroalcohols, were obtained in moderate to good yields (up to 98%) using this methodology.     

B(C6F5)3催化合成二吲哚甲烷类化合物的研究

以硼试剂B(C₆F₅)₃为催化剂, 吲哚类化合物与芳香醛为底物, 经过脱除一分子水的过程, 简洁有效地制得了一系列二吲哚基甲烷类化合物. 该方法的模板反应在最优条件下可以实现快速转化, 底物范围适用性较广泛, 可以适用一系列取代基和官能团. 该研究发展了无过渡金属参与条件下直接制备二吲哚甲烷类化合物的简单策略, 其反应副产物为水, 反应条件温和, 可以实现目标化合物的有效合成.     

Investigation of alkyl metal intermediate formation in the rhodium-catalyzed hydroformylation: Experimental and theoretical approaches

This review describes experimental results obtained for regioselectivities and diastereoselectivities in rhodium-catalyzed hydroformylations and deuterioformylations of a variety of unsaturated substrates with unmodified Rh catalysts and compares them with values computed in the density functional theory (DFT) framework. Deuterioformylation experiments pointed out that under mild reaction conditions isomeric alkyl metal intermediate formation is non-reversible; hence the selectivity for alkyls reflects the selectivity for the aldehydes. The stability of the relevant alkyl rhodium transition states (TS) has been determined with computational methods at the B3P86/6-31G* level (employing effective core potentials for Rh in the LanL2DZ valence basis set). Theoretical results turn out to be in good agreement with the experimental ones obtained under mild reaction conditions. Significant differences between theory and experiment are conversely obtained for hydroformylations of vinylidenic olefins, such as 1,1-diphenylethene, carried out at high temperature, where β-hydride elimination takes place. To clarify the reaction mechanism under those reaction conditions, it was necessary to compute the whole reaction mechanism, including zero point and thermal corrections also. The calculations, performed on the hydroformylation of 1,1-diphenylethene (yielding almost exclusively linear aldehydes), allowed us to put forward a novel explanation for that behavior: the addition of the fourth CO group to the tricarbonyl intermediate to give the tetracarbonyl one is prevented in the branched isomer, but not in the linear isomer.     

Effective syntheses of quinoline-7,8-diol, 5-amino-l-DOPA, and 3-(7,8-dihydroxyquinolin-5-yl)-l-alanine

A modification of the Baeyer-Villiger reaction allows the conversion of aromatic 2-hydroxy-3-nitroketones and aldehydes into 3-nitrocatechols, which can be reduced to 3-aminocatechols. Reaction of the latter with acrolein yields quinoline-7,8-diols under exceptionally mild conditions. This new reaction sequence was successfully applied to the synthesis of the title compounds.     

One-pot Three-component Mannich Reaction Catalyzed by 2-Hydroxylpyridine

An effcient synthetic protocol for the β-amino carbonyl compounds was developed via one-pot three-component Mannich reaction of aromatic aldehydes, aromatic amines and cyclohexanone catalyzed by 2-hydroxylpy-ridine under mild reaction conditions. β-Amino carbonyl compounds were obtained in moderate to good yields and reasonable diastereoselectivities. The effects of different solvents, catalyst amounts and the scope of different substrates on the Mannich reactions were investigated. The plausible reaction mechanism was also discussed.