Javier Mazuela

Pyranoside phosphite-oxazoline ligands for the highly versatile and enantioselective ir-catalyzed hydrogenation of minimally functionalized olefins. A combined theoretical and experimental study.

A modular set of phosphite-oxazoline (P,N) ligands has been applied to the title reaction. Excellent ligands have been identified for a range of substrates, including previously challenging terminally disubstituted olefins, where we now have reached enantioselectivities of 99% for a range of substrates. The selectivity is best for minimally functionalized substrates with at least a moderate size difference between geminal groups. A DFT study has allowed identification of the preferred pathway. Computational prediction of enantioselectivities gave very good accuracy.

Chiral Pyranoside Phosphite-Oxazolines : A New Class of Ligand for Asymmetric Catalytic Hydrogenation of Alkenes

We have described the first successful application of a phosphite-oxazoline ligand library in the asymmetric Ir-catalyzed hydrogenation of several unfunctionalized olefins. The introduction of a bulky biaryl phosphite moiety in the ligand design is highly adventitious in the product outcome. By carefully selecting the ligand components, we obtained high activities (TOFs up to >1500 mol x (mol x h)(-1) at 1 bar of H2) and enantioselectivities (ee values up to >99%) and, at the same time, show a broad scope for different substrate types. So, this is an exceptional ligand class that competes favorably with a few other ligand series that also provide high ee values for tri- and disubstituted substrate types.

Iridium Phosphite−Oxazoline Catalysts for the Highly Enantioselective Hydrogenation of Terminal Alkenes

A modular library of readily available phosphite-oxazoline ligands (L1-L16a-f) has been successfully applied for the first time in the Ir-catalyzed asymmetric hydrogenation of a broad range of highly unfunctionalized 1,1,-disubstituted terminal alkenes. Enantioselectivities up to >99% and full conversions were obtained in several 1,1-disubstituted alkenes, including substrate classes that have never been asymmetrically hydrogenated before (i.e., 1,1-heteoraryl-alkyl, 1,1-diaryl, trifluoromethyl, etc.). The results indicated that these catalytic systems have high tolerance to the steric and electronic requirements of the substrate and also to the presence of a neighboring polar group. The asymmetric hydrogenations were also performed using propylene carbonate as solvent, which allowed the Ir catalyst to be reused and maintained the excellent enantioselectivities.

Biaryl phosphite-oxazolines from hydroxyl aminoacid derivatives: highly efficient modular ligands for Ir-catalyzed hydrogenation of alkenes

High enantioselectivities and activities are achieved in the Ir-catalyzed hydrogenation of several unfunctionalized olefins using modular biaryl phosphite-oxazoline ligands from hydroxyl aminoacid derivatives; the presence of a biaryl phosphite group is crucial to this success.

Biaryl Phosphite–Oxazoline Ligands from the Chiral Pool: Highly Efficient Modular Ligands for the Asymmetric Pd-Catalyzed Heck Reaction

A highly modular library of readily available phosphite-oxazoline ligands L1-L21a-g was successfully applied in the asymmetric Pd-catalyzed Heck reactions of several substrates and triflates under thermal and microwave conditions. This ligand library contains three main ligand structures that have been designed by systematic modification of one of the most successful ligand families developed for this process. As well as studying the effect of these three ligand structures on the catalytic performance, we also evaluated the effect of modifying several ligand parameters in these ligand structures. The effectiveness of these ligands at transferring the chiral information into the product can be tuned by correctly choosing the ligand components. Both enantiomers of the Heck coupling products were obtained in excellent activities (conversion: >100% in 10 min), regioselectivities (>99%) and enantioselectivities (>99% ee). Under microwave-irradiation conditions, the reaction times were considerably shorter (full conversion was achieved in a few minutes) and the regio- and enantioselectivities were still excellent.

Adaptative Biaryl Phosphite–Oxazole and Phosphite–Thiazole Ligands for Asymmetric Ir-Catalyzed Hydrogenation of Alkenes

A library of readily available phosphite-oxazole/thiazole ligands (L1 a-g-L7 a-g) was applied in the Ir-catalyzed asymmetric hydrogenation of several largely unfunctionalized E- and Z-trisubstituted and 1,1-disubstituted terminal alkenes. The ability of the catalysts to transfer chiral information to the product could be tuned by choosing suitable ligand components (bridge length, the substituents in the heterocyclic ring and the alkyl backbone chain, the configuration of the ligand backbone, and the substituents/configurations in the biaryl phosphite moiety), so that enantioselectivities could be maximized for each substrate as required. Enantioselectivities were therefore excellent (enantiomeric excess (ee) values up to >99 %) for a wide range of E- and Z-trisubstituted and 1,1-disubstituted terminal alkenes. The biaryl phosphite moiety was a very advantageous ligand component in terms of substrate versatility.

Palladium(II)/Brønsted Acid-Catalyzed Enantioselective Oxidative Carbocyclization–Borylation of Enallenes†

An enantioselective oxidative carbocyclization–borylation of enallenes that is catalyzed by palladium(II) and a Brønsted acid was developed. Biphenol-type chiral phosphoric acids were superior co-catalysts for inducing the enantioselective cyclization. A number of chiral borylated carbocycles were synthesized in high enantiomeric excess.

Rh-catalyzed asymmetric hydroformylation of heterocyclic olefins using chiral diphosphite ligands. Scope and limitations.

We used a series of diphosphite ligands to study the effect of the ligand backbone, the length of the bridge, and the substituents of the biphenyl moieties and determine the scope of this type of ligand in the Rh-catalyzed asymmetric hydroformylation of several hetereocylic olefins. By carefully selecting the ligand components, we achieved high chemo-, regio-, and enantioselectivities in different substrate types. Unprecedentedly high enantioselectivities for five-membered heterocyclic olefins were therefore obtained. Note that both enantiomers of the hydroformylation products can be synthesized using the same ligand by a simple substrate change. For the seven-membered heterocyclic dioxepines, our results are among the best obtained. Also, both enantiomers of the hydroformylation products can be obtained by using pseudoenantiomer ligands or by carefully tuning the ligand parameters.

A New Modular Phosphite-Pyridine Ligand Library for Asymmetric Pd-Catalyzed Allylic Substitution Reactions: A Study of the Key Pd-π-Allyl Intermediates

A library of phosphite-pyridine ligands L1-L12 a-g has been successfully applied for the first time in the Pd-catalyzed allylic substitution reactions of several di- and trisubstituted substrates by using a wide range of C, N and O nucleophiles, among which are the little studied α-substituted malonates, β-diketones, and alkyl alcohols. The highly modular nature of this ligand library enables the substituents/configuration at the ligand backbone, and the substituents/configurations at the biaryl phosphite moiety to be easily and systematically varied. We found that the introduction of an enantiopure biaryl phosphite moiety played an essential role in increasing the versatility of the Pd-catalytic systems. Enantioselectivities were therefore high for several hindered and unhindered di- and trisubstituted substrates by using a wide range of C, N and O nucleophiles. Of particular note were the high enantioselectivities (up to>99% ee) and high activities obtained for the trisubstituted substrates S6 and S7, which compare favorably with the best that have been reported in the literature. We have also extended the use of these new catalytic systems in alternative environmentally friendly solvents such as propylene carbonate and ionic liquids. Studies on the Pd-π-allyl intermediates provide a deeper understanding of the effect of ligand parameters on the origin of enantioselectivity.

A New Class of Modular P,N‐Ligand Library for Asymmetric Pd‐Catalyzed Allylic Substitution Reactions: A Study of the Key Pd–π‐Allyl Intermediates

A new class of modular P,N-ligand library has been synthesized and screened in the Pd-catalyzed allylic substitution reactions of several substrate types. These series of ligands can be prepared efficiently from easily accessible hydroxyl-oxazole/thiazole derivatives. Their modular nature enables the bridge length, the substituents at the heterocyclic ring and in the alkyl backbone chain, the configuration of the ligand backbone, and the substituents/configurations in the biaryl phosphite moiety to be easily and systematically varied. By carefully selecting the ligand components, therefore, high regio- and enantioselectivities (ee values up to 96 %) and good activities are achieved in a broad range of mono-, di-, and trisubstituted linear hindered and unhindered substrates and cyclic substrates. The NMR spectroscopic and DFT studies on the Pd-pi-allyl intermediates provide a deeper understanding of the effect of ligand parameters on the origin of enantioselectivity.