Untethering sparteine: 1,3-diamine ligand for asymmetric synthesis in water

Chiral ligands are the toolbox for asymmetric synthesis to access 3D molecular world. Enabling efficient asymmetric reaction in water is a big challenge. As moisture/air stable and strong binding moieties, amines, compared to imine and phosphine ligands, are ideal candidates to accommodate asymmetric transformations in water. Known amine ligands like Proline analogues and Cinchona alkaloids showed excellent asymmetric induction. Sparteine, an alkaloid studied originated in 1968, had never been considered as a privileged catalyst due to its structure defection which led to poor reaction compatibility and unsatisfactory stereoselectivity. Here, we report the design of a chiral diamine catalyst untethering one of the sparteine rings. The diamine catalyst was easily accessed in two steps on 100 gram-scale. This chiral ligand was proved to be efficient for addition reactions in water providing products with excellent yields and enantiomeric ratios. This pluripotent catalyst has also shown good reactivity/enantioselectivity under organocatalysis, Cu and Pd-catalysed conditions. We anticipate that the ligand would allow further development of other catalysts for important yet challenging green stereoselective transformations.

Chemoenzymatic Stereoselective Synthesis of trans-Flavan-4-ols via Lipase-Catalyzed Kinetic Resolutions

Flavan-4-ols are a subclass of flavonoids that are present in complex molecules with application in the industrial sector as pigments, antioxidants, or antimitotics, among many others. The most traditional way to achieve their synthesis is from naturally abundant flavanones, asymmetric transfer hydrogenation reactions or bioreduction being well known strategies, while their preparation from racemic flavan-4-ols has been less explored. In this article, we have focused on the synthesis of a series of trans-flavan-4-ols bearing different substitution patterns in the aromatic ring to explore later the potential of lipases as biocatalysts for stereoselective acylation reactions. Therefore, a series of flavanones have been chemically prepared, starting from the corresponding benzaldehydes by aldol condensation with 2′-hydroxyacetophenone in a strongly basic medium, and later transformed into the corresponding racemic trans-flavan-4-ols following a carbonyl reduction, Mitsunobu reaction, and ester deprotection sequence. A screening of lipases and optimization of the reaction conditions for the stereoselective acylation of racemic 2-phenylchroman-4-ol were performed before expanding the best reaction conditions to the kinetic resolution of other 2-arylchroman-4-ols. Interestingly, the combination of AK lipase from Pseudomonas fluorescens as enzyme and vinyl acetate as both acyl donor and solvent allowed the performance of highly asymmetric transformations (E > 200, 50–90% eeS and >99% eeP) under mild reaction conditions (30 °C and 250 rpm).

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.

Organocatayzed Oxa-Diels-Alder Reactions: Recent Progresses

Oxa-Diels-Alder reaction is a straightforward, atom-economical process for the construction of six membered oxa-cycle which is a privileged structure due to its omnipresence in several pharmaceuticals and natural products. Like many other asymmetric transformations, organocatalysis provides an elegant pathway to their synthesis via [4+2] annulation under mild reaction conditions. The oxa-Diels reactions either utilize α,β-unsaturated carbonyl as oxadiene with a suitable dienophile or simple carbonyl as dienophile with other dienes. A range of organocatalysts have been explored in the past decade to execute this strategy. The catalysts induce stereoselectivities via two basic reactivities: 1) Formation of chiral intermediates, 2) Selectively activating suitable reactants in transition state. The present review assembles organocatalyzed asymmetric oxa-Diels-Alder reactions published in last ten years’ time span with detailed discussion on mechanistic approaches.

Gold Catalyzed Asymmetric Transformations

In this chapter, the strategies developed to attain asymmetric reactions with gold are disclosed. Because of its preferred linear arrangement, to induce asymmetry, gold(I) needs to fulfill one of the following requirements: a) the use of bulky chiral ligands, that create a chiral pocket around the active site, b) the coordination to bifunctional ligands capable to establish secondary interactions with substrates, or c) tight ion pairing with chiral counteranions. On the other hand, gold(III) profits of a square-planar coordination mode, which approaches chiral ligands to substrates. However, its tendency to be reduced leads to difficulties for its applications in catalytic asymmetric transformations. Pioneering works using cyclometaled structures, have found the balance between stability and activity, showing its potential in asymmetric transformations.

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

Cinchona alkaloid-derived organocatalysts are widely employed in various asymmetric transformations, yielding products with high enantiopurity. In this respect, a bifunctional quinine-derived sulfonamide organocatalyst was developed to catalyze the asymmetric sulfa-Michael reaction of naphthalene-1-thiol with trans-chalcone derivatives. The target sulfa-Michael adducts were obtained with up to 96% ee under mild conditions and with a low (1 mol %) catalyst loading. Selected enantiomerically enriched sulfa-Michael addition products were subjected to oxidation to obtain the corresponding sulfones.

Alkylzirconocenes in Organic Synthesis: An Overview

Organozirconium chemistry has found extensive applications in organic synthesis since its discovery in the last century. Alkyl­zirconocenes, which are easily generated by the hydrozirconation of alkenes with the Schwartz reagent, are widely utilized for carbon–carbon­ and carbon–heteroatom bond formation. This short review summarizes the progress to date on the applications alkylzirconocenes in organic synthesis.1 Introduction2 General Methods for Generating Alkylzirconocenes3 Transformations of Alkylzirconocenes by Heteroatoms4 Insertion of Unsaturated Groups into Alkylzirconocenes5 Transmetalations6 Cross-Coupling Reactions of Alkylzirconocenes7 Photochemistry of Alkylzirconocenes8 Bimetallic Reagents of Zirconium9 Asymmetric Transformations10 Applications of Alkylzirconocenes Generated from the Negishi Reagent11 Conclusions and Outlook