P-Stereogenic Ir-MaxPHOX: A Step toward Privileged Catalysts for Asymmetric Hydrogenation of Nonchelating Olefins.

The Ir-MaxPHOX-type catalysts demonstrated high catalytic performance in the hydrogenation of a wide range of nonchelating olefins with different geometries, substitution patterns, and degrees of functionalization. These air-stable and readily available catalysts have been successfully applied in the asymmetric hydrogenation of di-, tri-, and tetrasubstituted olefins (ee's up to 99%). The combination of theoretical calculations and deuterium labeling experiments led to the uncovering of the factors responsible for the enantioselectivity observed in the reaction, allowing the rationalization of the most suitable substrates for these Ir-catalysts.

Proofreading experimentally assigned stereochemistry through Q2MM predictions in Pd-catalyzed allylic aminations.

The palladium-catalyzed enantioselective allylic substitution by carbon or nitrogen nucleophiles is a key transformation that is particularly useful for the synthesis of bioactive compounds. Unfortunately, the selection of a suitable ligand/substrate combination often requires significant screening effort. Here, we show that a transition state force field (TSFF) derived by the quantum-guided molecular mechanics (Q2MM) method can be used to rapidly screen ligand/substrate combinations.

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications.

This Review compiles the evolution, mechanistic understanding, and more recent advances in enantioselective Pd-catalyzed allylic substitution and decarboxylative and oxidative allylic substitutions. For each reaction, the catalytic data, as well as examples of their application to the synthesis of more complex molecules, are collected. Sections in which we discuss key mechanistic aspects for high selectivity and a comparison with other metals (with advantages and disadvantages) are also included.

Assessing Methodologies to Synthesize α-Sulfenylated Carbonyl Compounds by Green Chemistry Metrics.

α-Sulfenylated carbonyl compounds are important both as active pharmaceutical ingredients and as intermediates in organic synthesis. Owing to their relevance in synthetic organic chemistry, this Minireview focuses on assessing the most relevant synthetic procedures based on green chemistry metrics. The Minireview starts with the traditional routes and then focuses on more recently developed methodologies.

Rh-Catalyzed Asymmetric Hydroaminomethylation of α-Substituted Acrylamides: Application in the Synthesis of RWAY.

The successful rhodium-catalyzed asymmetric hydroformylation and hydroaminomethylation of α-substituted acrylamides is described using 1,3-phosphite-phosphoramidite ligands based on a sugar backbone. A broad scope of chiral aldehydes and amines were afforded in high yields and excellent enantioselectivities (up to 99%). Furthermore, the synthetic potential of this method is demonstrated by the single-step synthesis of the brain imaging molecule RWAY.

Effect of Ligand Chelation and Sacrificial Oxidant on the Integrity of Triazole-Based Carbene Iridium Water Oxidation Catalysts.

We report the effect of replacing the pyridine group in the chelating trz Ir-water oxidation catalysts by a benzoxazole and a thiazole moiety. We have also evaluated if the presence of bidentate ligands is crucial for high activities and to avoid the decomposition into undesired heterogeneous layers. The catalytic performance of these benzoxazole/thiazole-triazolidene Ir-complexes in water oxidation was studied at variable pH using either CAN (pH = 1) or NaIO (pH = 5.

Evolution of phosphorus-thioether ligands for asymmetric catalysis.

In the early 1990s chiral P-thiother ligands emerged as promising ligands in the field of asymmetric catalysis, with the development of many P-thioether ligand families. However, only a few of them have shown a broad reaction and substrate scope. So, compared with other heterodonor ligands such as the widely studied P-N ligands, their impact in asymmetric catalysis was not realised until recently.

Intramolecular substitutions of secondary and tertiary alcohols with chirality transfer by an iron(III) catalyst.

Optically pure alcohols are abundant in nature and attractive as feedstock for organic synthesis but challenging for further transformation using atom efficient and sustainable methodologies, particularly when there is a desire to conserve the chirality. Usually, substitution of the OH group of stereogenic alcohols with conservation of chirality requires derivatization as part of a complex, stoichiometric procedure. We herein demonstrate that a simple, inexpensive, and environmentally benign iron(III) catalyst promotes the direct intramolecular substitution of enantiomerically enriched secondary and tertiary alcohols with O-, N-, and S-centered nucleophiles to generate valuable 5-membered, 6-membered and aryl-fused 6-membered heterocyclic compounds with chirality transfer and water as the only byproduct.

High-Atom Economic Approach To Prepare Chiral α-Sulfenylated Ketones.

Chiral α-sulfenylated ketones are versatile building blocks, although there are still several limitations with their preparation. Here we report a new two-step procedure, consisting of Pd-catalyzed hydrothiolation of propargylic alcohols followed by an enantioselective Rh isomerization of allylic alcohols. The isomerization reaction is the key step for obtaining the ketones in their enantioenriched form.

A readily accessible and modular carbohydrate-derived thioether/selenoether-phosphite ligand library for Pd-catalyzed asymmetric allylic substitutions.

A large library of thioether/selenoether-phosphite ligands have been tested in the Pd-catalyzed asymmetric allylic substitution reaction. The presented ligands are derived from cheap and available carbohydrates and they are air-stable solids and easy to handle. Their highly modular nature has made it possible to achieve excellent enantioselectivities in the substitution of a range of hindered and unhindered substrates (ees up to 99% and 91%, respectively).

Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling Reaction of Naphthyl and Quinolyl Alcohols with Boronic Acids.

A nickel-catalyzed C(sp)-C(sp) Suzuki cross-coupling of arylboronic acids and (hetero)naphthyl alcohols has been developed. A Ni(dppp)Cl complex showed the highest efficiency and broadest substrate scope. High functional group tolerance has been achieved where 35  compounds could be generated in good to excellent yields, including both primary and secondary benzylic alcohols.

Phosphite-Thiother Ligands Derived from Carbohydrates allow the Enantioswitchable Hydrogenation of Cyclic β-Enamides by using either Rh or Ir Catalysts.

Phosphite-thioether ligands with a simple modular architecture, derived from inexpensive l-(+)-tartaric acid and d-mannitol, have been for the first time successfully applied (ee values up to 99 %) in the synthesis of 2-aminotetralines and 3-aminochromanes by metal-catalyzed asymmetric hydrogenation of cyclic β-enamides. The ligands have the advantages of the robustness of the thioether/phosphite moieties and the extra control provided by the flexibility of the chiral pocket through the presence of a biaryl phosphite group and a modular carbohydrate-derived backbone. Moreover, they are solid and stable to air and they are therefore easy to handle, manipulate, and store.

A theoretically-guided optimization of a new family of modular P,S-ligands for iridium-catalyzed hydrogenation of minimally functionalized olefins.

A library of modular iridium complexes derived from thioether-phosphite/phosphinite ligands has been evaluated in the asymmetric iridium-catalyzed hydrogenation of minimally functionalized olefins. The modular ligand design has been shown to be crucial in finding highly selective catalysts for each substrate. A DFT study of the transition state responsible for the enantiocontrol in the Ir-catalyzed hydrogenation is also described and used for further optimization of the crucial stereodefining moieties.