Various polar tripeptides as asymmetric organocatalyst in direct aldol reactions in aqueous media

A series of tripeptide organocatalysts containing a secondary amine group and two amino acids with polar side chain units were developed and evaluated in the direct asymmetric intermolecular aldol reaction of 4-nitrobenzaldehyde and cyclohexanone. The effectiveness of short polar peptides as asymmetric catalysts in aldol reactions to attain high yields of enantio- and diastereoselective isomers were investigated. In a comparison, glutamic acid and histidine produced higher % ee and yields when they were applied as the second amino acid in short trimeric peptides. These short polar peptides were found to be efficient organocatalysts for the asymmetric aldol addition reaction in aqueous media. Chirality 25:726-734, 2013

Validation of a hemiacetal intermediate during absolute Soai autocatalytic amplification under heterogenous phase

Absolute asymmetric synthesis produces chiral molecules without any chiral polarization and is an interesting rational for the origin of homochirality. Remarkably, in the Soai reaction absolute asymmetric amplification of alkanol product is observed under heterogenous conditions. Reaction of iPr2Zn vapor on solid carbaldehyde produced corresponding alkanol with up to 96% ee. In a parallel amplification process, a chiral ester is produced with 98% ee. The latter is attributed to disproportionation of starting aldehyde into hemiacetal followed by a subsequent Claisen-Tishchenko mechanism. This observation provide evidence for the debated transient intermediate, and opens new perspectives in the elucidation of the mechanism of amplification of chirality in the Soai reaction

Absolute Autocatalytic Amplification Under Heterogenous Conditions Involving Subsequent Hydride Transfer and Hemiacetal Intermediate.

Absolute asymmetric amplification is observed for pyridine alkanol by reaction with iPr2Zn vapor under heterogenous conditions. Beside the chiral alkanol, formation of a chiral ester is observed and identified as a subsequent Claisen-Tishchenko product of a hemiacetal intermediate during a Soai absolute amplification

Kinetic relationship in parallel autocatalytic amplifications of pyridyl alkanol and chiral trigger pyrimidyl alkanol

Experimental and kinetic analysis of a chemical system combines autocatalytic amplification of 2‐alkynyl‐5‐pyrimidyl alkanol 2 and 6‐alkynyl‐3‐pyridyl akanol 4 in which 2 acts as a chiral trigger and 4 being the subsequent autocatalyst. Starting from a very low initial ee, both alkanols are produced with high enantiopurity in one single cycle. This provides insight into a dual nonlinear amplification of chirality observed with amplifying trigger 2 and accelerated amplification of autocatalyst 4. These kinetic studies reveal a five‐fold magnitude superior amplification rates of 4 associated with trigger's enantiopurity at the outset

A DFT Perspective on Diels-Alder Organocatalysts Based on Substituted Phosphoramides

Phosphoramides are an interesting alternative to the thiourea motif that has long been used in organocatalysis. In the R1N(H)-P(O)(R3)-N(H)R2 formulation, phosphoramides give the advantage of having a third variable substituent, R3, compared to the two available in thioureas, and the possibility of introducing chirality with an asymmetric phosphorous center. In this work, we present a systematic computational study on the catalytic properties of these underexplored compounds. These studies show the catalytic potential of a series of substituted phosphoramides in Diels-Alder reactions, including the asymmetric [4+2] cycloaddition of pro-chiral substrates. The nature of the phosphorous-bound R3 substituent has a significant impact both on catalytic activity and enantioselectivity. Remarkably, several of the phosphoramides studied are predicted to be more active than the Schreiner’s thiourea organocatalyst