A colorimetric competitive displacement assay for the evaluation of catalytic peptides

An assay based on competitive dye displacement was adapted to detect the formation of aldol product in crude reaction mixtures, and was used to evaluate minimal peptide aldol catalysts.</p

Tandem zinc-carbenoid mediated chain extension-aldol chemistry of beta-carbonyl imides

Synthetic sequences to prepare gamma-methoxy beta-keto imides and malonyl diimides were investigated in an effort to expand the scope of the tandem zinc-mediated chain extension aldol reaction. The chain extension-aldol reaction of the gamma-methoxy beta-keto imide proceded smoothly, although low stereoselectivity of the reaction was observed. The chain extension of malonyl diimides were slow when compared to traditional substrates. The chain extension-aldol reaction of malonyl diimides provided gamma-lactones with moderate yield and selectivity in a one-pot reaction sequence. Due to the extended chain extension reaction times, reduction of aldehydes was observed during attempted aldol reactions. A chain extension aldol protocol, specific for the application to malonyl diimides, was developed to reduce the appearance of products resulting from the reduction of the respective aldehyde

The First Direct and Enantioselective Cross-Aldol Reaction of Aldehydes

The first enantioselective catalytic direct cross-aldol reaction that employs nonequivalent aldehydes has been accomplished using proline as the reaction catalyst. Structural variation in both the aldol donor (R_1 = Me, n-Bu, Bn, 91 to >99%) and aldol acceptor (R_2 = I-Pr, I-Bu, c-C6H11, Et, Ph, 97−99% ee) are possible while maintaining high reaction efficiency (75−88% yield). Significantly, this new aldol variant allows facile enantioselective access to a broad range of β-hydroxy aldehydes which are valuable intermediates in polyketide syntheses

One-pot Synthesis of Lactams Using Domino Reactions: Combination of Schmidt Reaction with Sakuri and Aldol Reaction

A series of domino reactions in which the intramolecular Schmidt reaction is combined with either a Sakurai reaction, an aldol reaction, or both is reported. The Sakurai reaction of an allylsilane with an azido-containing enone under Lewis acidic conditions followed by protonation of the resulting titanium enolate species allowed for a subsequent intramolecular Schmidt reaction. Alternatively, the intermediate titanium enolate could undergo an aldol reaction, followed by the intramolecular Schmidt reaction to form lactam products with multiple stereogenic centers. The stereochemical features of the titanium enolate aldol reaction with several 3-azidoaldehyde substrates during this domino process is discussed

Design and Synthesis of Oxazoline-Based Scaffolds for Hybrid Lewis Acid/Lewis Base Catalysis of Carbon–Carbon Bond Formation

A new class of hybrid Lewis acid/Lewis base catalysts has been designed and prepared with an initial objective of promoting stereoselective direct aldol reactions. Several scaffolds were synthesized that contain amine moieties capable of enamine catalysis, connected to heterocyclic metal-chelating sections composed of an oxazole–oxazoline or thiazole–oxazoline. Early screening results have identified oxa­zole–oxazoline-based systems capable of promoting a highly diastereo- and enantioselective direct aldol reaction of propionaldehyde with 4-nitrobenzaldehyde, when combined with Lewis acids such as zinc triflate

Intraparticle Diffusional Effects vs. Site Effects on Reaction Pathways in Liquid-Phase Cross Aldol Reactions

Chemo- and regioselectivity in a heterogeneously catalyzed cross aldol reaction were directed by tuning the nature of the sites, textural properties and reaction conditions. Catalysts included sulfonic-acid functionalized resins or SBA-15 with varying particle size or pore diameter, H-BEA zeolites, and Sn-BEA zeotype; conditions were 25 °C to 170 °C in organic media. Benzaldehyde and 2-butanone yielded branched (reaction at -CH2- of butanone) and linear (reaction at -CH3) addition and condensation products; and fission of the branched aldol led to β-methyl styrene and acetic acid. Strong acids promoted the dehydration step, and regioselectivity originated from preferred formation of the branched aldol. Both, resins and functionalized SBA-15 materials yielded predominantly the branched condensation product, unless particle morphology or temperature moved the reaction into the diffusion-limited regime, in which case more fission products were formed, corresponding to Wheeler Type II selectivity. For Hform zeolites, fission of the branched aldol competed with dehydration of the linear aldol, possibly because weaker acidity or steric restrictions prevented dehydration of the branched aldol

The reaction of O-silylated cyanohydrin anions with epoxides as an alternative for the enantio- and diastereoselective preparation of aldols

The aldol addition is one of the most important and most utilized carbon-carbon bond forming reactions in chemical synthesis. This reaction, between an aldehyde or ketone and a second, enolized aldehyde or ketone, results in the formation of a -hydroxycarbonyl (often referred to as an “aldol product” or “aldol”). Modern variations of the aldol reaction have allowed for enantio- and diastereoselectivity in the reaction; however, many of these methods have undesirable drawbacks such as the use of expensive chiral auxiliaries. The chiral auxiliaries require additional synthesis steps for their introduction and removal and cannot be completely recovered after the reaction is complete. Methods for the preparation of aldol products that do not involve enolate chemistry have also been developed. Here we propose the reaction of O-silylated cyanohydrin anions with epoxides as an alternative to the aldol addition for the preparation of β-hydroxycarbonyls. By taking advantage of excellent, established asymmetric epoxidations, this method allows for high degrees of enantio- and diastereoselectivity in a highly atom economical way. We report here the optimization of the reaction conditions and the initial scope and limitations of the epoxide electrophiles

Activity coefficients for liquid organic reactions : towards a better understanding of true kinetics with the synthesis of jasmin aldehyde as showcase

The aldol condensation of benzaldehyde and heptanal is taken as an example of reversible liquid phase organic reactions to show that inclusion of activity coefficients reveal distinct differences in conversion and product distribution when different solvents methanol, ethanol, n-propanol, or n-butanol are used. The purpose of this work is to show a pronounced solvent effect for a given set of identical kinetic parameters, i.e., the same liquid phase kinetics can result in different conversion and yield values, depending on the choice of solvent. It was shown that subsequent parameter estimation without inclusion of the activity coefficients resulted in a pronounced deviation from the true' kinetics, up to a factor of 30. It is proposed that the usage of average activity coefficients gives already a significant improvement, resulting in acceptable parameter estimates

Silylation of Carbohydrate Syrups

Introduction Carbohydrates are usually difficult to analyze in solutions. Gas chromatography provides a suitable means for analysis. However most carbohydrate compounds are not volatile enough for use by this method. Suitable deriviatives are the aldol acetates and the silylated carbohydrates. Aldol acetates are difficult to prepare and require long time periods for their formation. Silylation is the most suitable means for preparing volatile deriviatives. However most silyl compounds are water sensitive. This paper discusses silylating agents, their reaction mechanisms and a solution to the problem of water sensitivity