Molecular Insights on Chirality Transfer from Double Axially Chiral Phosphoric Acid in a Synergistic Enantioselective Intramolecular Amination

In the most general practice of asymmetric catalysis, a chiral catalyst, typically bearing a center or an axis of chirality, is employed as the chiral source for imparting enantiocontrol over...

Transferrable Selectivity Profiles Enable Prediction in Synergistic Catalyst Space

Organometallic intermediates participate in many multi-catalytic enantioselective transformations directed by a chiral catalyst, but the requirement of optimizing two catalyst components is a significant barrier to widely adopting this approach for chiral molecule synthesis. Algorithms can potentially accelerate the screening process by developing quantitative structure-function relationships from large experimental datasets. However, the chemical data available in this catalyst space is limited. We report a data-driven strategy that effectively translates selectivity relationships trained on enantioselectivity outcomes derived from one catalyst reaction systems where an abundance of data exists, to synergistic catalyst space. We describe three case studies involving different modes of catalysis (Brønsted acid, chiral anion, and secondary amine) that substantiate the prospect of this approach to predict and elucidate selectivity in reactions where more than one catalyst is involved. Ultimately, the success in applying our approach to diverse areas of asymmetric catalysis implies that this general workflow should find broad use in the study and development of new enantioselective, multi-catalytic processes.

Recent Advances in Selected Asymmetric Reactions Promoted by Chiral Catalysts: Cyclopropanations, Friedel–Crafts, Mannich, Michael and Other Zinc-Mediated Processes—An Update

The main purpose of this review article is to present selected asymmetric synthesis reactions in which chemical and stereochemical outcomes are dependent on the use of an appropriate chiral catalyst. Optically pure or enantiomerically enriched products of such transformations may find further applications in various fields. Among an extremely wide variety of asymmetric reactions catalyzed by chiral systems, we are interested in: asymmetric cyclopropanation, Friedel–Crafts reaction, Mannich and Michael reaction, and other stereoselective processes conducted in the presence of zinc ions. This paper describes the achievements of the above-mentioned asymmetric transformations in the last three years. The choice of reactions is related to the research that has been carried out in our laboratory for many years.

Asymmetric Synthesis of Stereogenic Phosphorus P(V) Centers Using Chiral Nucleophilic Catalysis

Organophosphates have been widely used in agrochemistry, as reagents for organic synthesis, and in biochemistry. Phosphate mimics possessing four unique substituents, and thereby a chirality center, are useful in transition metal catalysis and as nucleotide therapeutics. The catalytic, stereocontrolled synthesis of phosphorus-stereogenic centers is challenging and traditionally depends on a resolution or use of stochiometric auxiliaries. Herein, enantioenriched phosphorus centers have been synthesized using chiral nucleophilic catalysis. Racemic H-phosphinate species were coupled with nucleophilic alcohols under halogenating conditions. Chiral phosphonate products were synthesized in acceptable yields (33–95%) and modest enantioselectivity (up to 62% ee) was observed after identification of an appropriate chiral catalyst and optimization of the solvent, base, and temperature. Nucleophilic catalysis has a tremendous potential to produce enantioenriched phosphate mimics that could be used as prodrugs or chemical biology probes.

Stereoselective organocascades: from fundamentals to recent developments

Reaction sequences where more bonds are sequentially formed (cascade reactions) may be started either by a stoichiometric or by a catalytic reagent, and proceed in an enantio- diastereo- or non-stereo- selective manner. A wide variety of such strategies has been developed, including both stoichiometric and catalytic ones. Within the widely developed cascade reactions field, this chapter is not meant to be omni-comprehensive, but to offer an as much as possible complete overview on organocatalytic stereoselective methods. We embrace the more general definitions by Tietze and Denmark, considering as cascade reactions all those one-pot processes that involve two or more bond formations, where each subsequent step is enabled by a structural change caused by the previous one. We will include both two- and multi-component reactions where one or more organocatalysts may be responsible either for all or just some of the occurring transformations. Organocascades will be reported according to the number of involved catalytic cycles. In the following paragraphs, only cascade reactions that are stereoselective by means of a chiral catalyst will be considered. It will be shown that multiple possibilities, relying on different catalysis modes, are available to achieve the same reaction sequence.

Brucine Diol-Catalyzed Enantioselective Morita-Baylis-Hillman Reaction in the Presence of Brucine N-Oxide

Brucine diol (BD) catalyzed asymmetric Morita–Baylis–Hillman (MBH) reaction is observed for the first time. Brucine N-oxide (BNO) was found to not have an effective chiral catalyst. Faster reaction rate was obtained using unsaturated ester or aromatic aldehydes in the presence of BNO. 4-Nitrobenzaldehyde and α,β-unsaturated ketone/ester were converted to the MBH adduct in moderate yields (up to 74%) with 70% ee value by this catalytic system. The mechanism of BD catalysis is probably initiated by conjugating the vicinal diol of BD to the carbonyl group of the aromatic aldehyde through hydrogen bonding. The tertiary amine of BD acts as a nucleophile to activate vinyl ketone for coupling with the carbonyl of aldehyde through an intramolecular carbonylated reaction. Finally, the breakdown of the complex caused the formation of the MBH adduct (a benzyl-allyl alcohol). The chirality of the benzyl-allyl alcohol is likely affected by the interaction of the bulky asymmetric plane of BD.

Fast Multipoint Immobilization of Lipase through Chiral L-Proline on MOF as Chiral Bioreactor

In this paper, we describe the facile preparation of a chiral catalyst by the combination of the amino acid, L-proline (Pro), and the enzyme, porcine pancreas lipase (PPL), immobilized on...

Ru-Tethered (R,R)-TsDPEN with DMAB as an efficient catalytic system for high enantioselective one-pot synthesis of chiral β-aminol via asymmetric transfer hydrogenation

This work reflects Ru-tethered-TsDPEN as an active chiral catalyst for one pot selective synthesis of optically active α-substituted alcohols and its derivatives from α-bromo ketones in the presence of dimethylamine borane (DMAB) as the hydrogen source.