Recyclable fluorous organocatalysts promoted three-component reactions of pyruvate,aldehyde and amine at room temperature

A new fluorous imine carbothioate has been prepared as an organocatalyst for the synthesis of pyrrol-2-ones via the cyclo-condensation reaction of aldehydes, amines, and pyruvate at room temperature. The fluorous catalyst can be easily recovered from the reaction mixture by simple fluorous solid-phase extraction (F-SPE) and used for next run reaction without further purification.     

Direct, pyrrolidine sulfonamide promoted enantioselective aldol reactions of α,α-dialkyl aldehydes: synthesis of quaternary carbon-containing β-hydroxy carbonyl compounds

A procedure has been developed for direct, asymmetric aldol reactions of α,α-dialkyl aldehydes with aromatic aldehydes, which produces quaternary carbon-containing β-hydroxy carbonyl compounds. The processes, promoted by the organocatalyst (S) pyrrolidine sulfonamide, take place in high yields with exceptionally high levels of enantioselectivities.     

Catalyzed cycloaddition reactions of α-silyloxy-α,β-unsaturated ketone and aldehyde

The reactions of α-silyloxy-ga,β-unsaturated ketone and aldehyde with diene afforded [4+2] and [4+3] cycloadducts respectively in the presence of a catalyst.     

Highly diastereo- and enantioselective direct aldol reactions promoted by water-compatible organocatalysts bearing a pyrrolidinyl-camphor structural scaffold

Efficient synthetic routes have been developed for the synthesis of a series of pyrrolidinyl-camphor containing organocatalysts (1-10). Structural modifications were made by varying the stereo- and electronic properties of the camphor scaffold and the aromatic substituents. These readily tunable and amphiphilic organocatalysts were evaluated for the direct asymmetric aldol reaction of various aromatic aldehydes and cyclohexanone either in organic solvents or in the presence of water. The aldol reaction proceeded smoothly with excellent chemical yields (up to 99%), enantioselectivities (up to 99% ee), and anti-diastereoselectivities (up to 99:1) with a catalytical amount of the bifunctional organocatalysts (20 mol %) under optimal reaction conditions. Mechanistic transition models are proposed and the stereochemical bias of the asymmetric aldol reaction is presented.     

Highly enantioselective aldol reactions catalyzed by a recyclable fluorous (S) pyrrolidine sulfonamide on water

Fluorous (S) pyrrolidine sulfonamide serves as an efficient promoter for highly enantioselective aldol reactions of ketones and aldehydes with aromatic aldehydes on water. A notable feature of the organocatalyst is that it can be recovered from the reaction mixtures by simple fluorous solid-phase extraction and subsequently reused (up to seven cycles) without a significant loss of catalytic activity and stereoselectivity.     

Enantio- and diastereoselective Michael addition reactions of unmodified aldehydes and ketones with nitroolefins catalyzed by a pyrrolidine sulfonamide

Chiral (S)-pyrrolidine trifluoromethanesulfonamide has been shown to serve as an effective catalyst for direct Michael addition reactions of aldehydes and ketones with nitroolefins. A wide range of aldehydes and ketones as Michael donors and nitroolefins as acceptors participate in the process, which proceeds with high levels of enantioselectivity (up to 99 % ee) and diastereoselectivity (up to 50:1 d.r.). The methodology has been employed successfully in an efficient synthesis of the potent H(3) agonist Sch 50917. In addition, a practical three-step procedure for the preparation of (S)-pyrrolidine trifluoromethanesulfonamide has been developed. The high levels of stereochemical control attending Michael addition reactions catalyzed by this pyrrolidine sulfonamide, have been investigated by using ab initio and density functional methods. Transition state structures for the rate-limiting C--C bond-forming step, corresponding to re- and si-face addition to the reactive conformation of the key enamine intermediates have been calculated. Analysis of these structures indicates that hydrogen bonding plays an important role in catalysis and that the energy barrier for si-face attack in reactions of aldehydes to form 2R,3S products is lower than that for the re-face attack leading to 2S,3R products. In contrast, the energy barrier for re-face addition is lower than that for si-face addition in reactions of ketones. The computational results, which are in good agreement with the experimental observations, are discussed in the context of the stereochemical course of these Michael addition reactions.     

Bisoxazoline-Lewis acid-catalyzed direct-electron demand oxo-hetero-Diels-Alder reactions of N-oxy-pyridine aldehyde and ketone derivatives

A general catalytic oxo-hetero-Diels-Alder reaction for pro-chiral aldehyde and ketone N-oxy-pyridines is presented. The catalytic and asymmetric oxo-hetero-Diels-Alder reaction of electron-rich dienes with N-oxy-pyridine-2-carbaldehyde and ketone derivatives, catalyzed by chiral copper(II)-bisoxazoline complexes, gives optically active six-membered oxygen heterocycles in moderate to good yields and with excellent enantioselectivities.     

Effect of additives on the proline-catalyzed ketone–aldehyde aldol reactions

The effect of bases, acids, and water as additives in proline-catalyzed ketone–aldehyde aldol reactions has been studied. While the reaction appears to be relatively tolerant to small amounts of tertiary amine bases or weak acids, it stops completely with strong acids. The use of water as an additive had a highly beneficial effect on reactions that were conducted with a stoichiometric ratio of ketone to aldehyde, especially with cyclic ketones. This allows the efficient use of more precious ketones such as 4-thianone as donors in the direct enantioselective aldol and facilitates purification.     

Cooperativity in the counterion catalysis of Morita/Baylis/Hillman reactions promoted by enantioselective trifunctional organocatalysts

New trifunctional organocatalysts with a NHTs Brønsted acid were prepared and tested in their ability to promote the counterion catalysis of generic and aza-Morita/Baylis/Hillman reactions. The cooperativity between the counterion and the NHTs Brønsted acid of the trifunctional catalyst was required for good enantioselectivity and rate enhancement. Better enantioselectivity was observed for aza-MBH reactions at relatively low catalyst loading (2-5 mol %) under facile conditions.     

Chiral bifunctional organocatalysts in asymmetric aza-Morita-Baylis-Hillman reactions of ethyl (arylimino)acetates with methyl vinyl ketone and ethyl vinyl ketone

The bifunctional chiral phosphine Lewis base (R)-2'-diphenylphosphino-[1,1'-binaphthalene]-2-ol is an effective organocatalyst in the asymmetric aza-MBH reaction of ethyl (arylimino)acetates 1 with MVK and EVK to give the corresponding adducts in moderate to good yields and good to high enantiomeric excesses under mild conditions.     

Direct asymmetric aldol reactions in brine using novel sulfonamide catalyst

Direct asymmetric aldol reactions of aldehydes with ketones in the presence of a catalytic amount of sulfonamide 4 and trifluoroacetic acid afforded the corresponding anti-aldol products in moderate to excellent yields with 85-93% ee.     

The chlorine evolution reaction promoted by organocatalysts with amide functional groups

<正>Since the nineteenth century, the chlor-alkali process entails the electrochemical oxidation of sodium chloride solutions to Cl₂ by the chlorine evolution reaction(CER) and the simultaneous production of sodium hydroxide and H₂ at the cathode, of which sodium hydroxide and Cl₂ are widely used as important chemicals [1]. Currently, Cl₂ production relies heavily on the chlor-alkali process, which is implemented on an industrial scale worldwide,     

Asymmetric Michael reaction between aldehydes and nitroalkanes promoted by pyrrolidine-containing C2-symmetric organocatalysts

Russian Chemical Bulletin - Bifunctional C2-symmetric organocatalysts derived from chiral 1,2-diaminoethanes and (S)-2-aminomethylpyrrolidine were fi rst used for promoting the asymmetric Michael...     

Direct asymmetric aldol reactions inspired by two types of natural aldolases: water-compatible organocatalysts and Zn(II) complexes

In this article the utility of water-compatible amino-acid-based catalysts was explored in the development of diastereo- and enantioselective direct aldol reactions of a broad range of substrates. Chiral C(2)-symmetrical proline- and valine-based amides and their Zn(II) complexes were designed for use as efficient and flexible chiral catalysts for enantioselective aldol reactions in water, on water, and in the presence of water. The presence of 5 mol % of the prolinamide-based catalyst affords asymmetric intermolecular aldol reactions between unmodified ketones and various aldehydes to give anti products with excellent enantioselectivities. We also demonstrate aldol reactions of more demanding substrates with high affinity to water (i.e., acetone and formaldehyde). Newly designed serine-based organocatalyst promoted aldol reaction of hydroxyacetone leading to syn-diols. For presented catalytic systems organic solvent-free conditions are also acceptable, making the elaborated methodology interesting from a green chemistry perspectives.     

New mixed phosphonate esters by transesterification of pinacol phosphonates and their use in aldehyde and ketone coupling reactions with nonstabilized phosphonates

Alkylpinacol phosphonates were prepared by rhodium-catalyzed olefin hydrophosphorylation, and attempted alpha-deprotonation of the pinacol derived alkyl phosphonates resulted in ring cleavage. The propensity of the alkylpinacol phosphonates to undergo ring opening was exploited to prepare phosphonic acid monomethyl esters in high yield by transesterification in acidulated methanol. Esterification and alkylation with aldehydes or ketones gave beta-hydroxy mixed phosphonate esters. tert-Butyl and benzylic phosphonate ester protective groups were introduced to improve the efficiency and functional group compatibility of beta-hydroxy phosphonate saponification. The beta-hydroxy phosphonic acid monomethyl esters were dehydrated with diisopropylcarbodiimide, which gave oxaphosphetane intermediates that collapse to an olefin. The overall reaction sequence complements the arsenal of Horner-Wadsworth-Emmons-type coupling reactions.     

Allylation of aldehydes and imines: promoted by reuseable polymer-supported sulfonamide of N-glycine

[reaction: see text] A allylation of aldehydes and imines (generated in situ from aldehydes and amines) with allyltributyltin promoted by recoverable and reusable the polymer-supported sulfonamide of N-glycine has been developed. Good to high yields were obtained in various cases. Most of the SnBu(3) residue can be recovered as Bu(3)SnCl. Highly stereoselective synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenylpiperidine 7 was achieved by using the P4a-mediated allylation of Boc-l-phenylglycinal as a key step.     

Tandem conjugate addition-elimination reaction promoted by chiral pyrrolidinyl sulfonamide (CPS)

Chiral pyrrolidinyl sulfonamides have been found to promote the conjugate addition-elimination reaction between activated allylic bromides and 1,3-dicarbonyl compounds with high enantioselectivities and the highly functionalised products can be used to generate a variety of interesting enantiomerically pure compounds via simple transformations.     

Direct ionic liquid promoted organocatalyzed diazo-transfer reactions: diversity-oriented synthesis of diazo-compounds

A practical and novel ionic liquid promoted organocatalytic selective diazo-transfer process for the synthesis of highly substituted diazo-compounds in high yields is reported. The ionic liquid can be reused without affecting the reaction rates or yields over five runs.     

UPS on Weinreb resin: a facile solid-phase route to aldehyde and ketone derivatives of "unnatural" amino acids and peptides

The solid-phase synthesis of "unnatural" amino aldehydes, amino ketones, peptide aldehydes, and peptide ketones was accomplished from commercially available resin in a series of room temperature reactions. The initial step involved addition of an "unnatural" side chain to the N-terminus of a benzophenone imine-activated Weinreb resin-bound amino acid or peptide derivative. The alkylated imine was hydrolyzed, and the amine was converted to the Boc-, Cbz-, or naphthoyl derivative. The resin-bound substrate was then cleaved with DIBAL-H or a Grignard reagent to give the amino aldehyde, amino ketone, peptide aldehyde, or peptide ketone products. Twenty-four reactions were carried out simultaneously using a "Billboard" reaction apparatus to give products in 27-87% (59% average) isolated yield.