Oscar Pàmies

Enantioselective copper-catalyzed conjugate addition and allylic substitution reactions

Departament of Organic Chemistry, University of Geneva, 30 Quai Ernest Ansermet, 1211 Geneve 4, Switzerland, Department of Organic Chemistry, Stockholm University, Arrhenius Laboratoriet, 106 91 Stockholm, Sweden, Organic Chemistry II, Dormund University of Technology, Otto-Hahn-Strasse 6, D-44227 Dortmund, Germany, and Departament de Quimica Fisica i Inorganica, Universitat Rovira i Virgili, C/ Marcel · li Domingo s/n, 43007 Tarragona, Spain

Phosphite-containing ligands for asymmetric catalysis.

Phosphite-Containing Ligands for Asymmetric Catalysis PietW. N.M. van Leeuwen, Paul C. J. Kamer,Carmen Claver,Oscar P amies,* andMontserrat Di eguez* Institute of Chemical Research of Catalonia, Avinguda Països Catalans 16, 43007 Tarragona, Spain University of St. Andrews, EaStCHEM, School of Chemistry, St. Andrews, Fife KY16 9ST, United Kingdom Universitat Rovira i Virgili, Departament de Química Física i Inorg anica, C/Marcel 3 lí Domingo s/n, 43007 Tarragona, Spain

Asymmetric Hydrogenation of Olefins Using Chiral Crabtree-type Catalysts : Scope and Limitations

Asymmetric Hydrogenation of Olefins Using Chiral Crabtree-type Catalysts : Scope and Limitations

Biaryl Phosphites: New Efficient Adaptative Ligands for Pd-Catalyzed Asymmetric Allylic Substitution Reactions

Pharmaceuticals, agrochemicals, fragrances, fine chemicals, and natural product chemistry all rely on the preparation of enantiomerically enriched compounds. The palladium-catalyzed asymmetric allylic substitution, which allows for the enantioselective formation of carbon-carbon and carbon-heteroatom bonds, is a potential synthetic tool for preparing these compounds. To date, most of the successful ligands reported for the Pd-catalyzed allylic substitution reactions have used three main design strategies. The first, developed by Hayashi and co-workers, used a secondary interaction of the nucleophile with a side chain of the ligand to direct the approach of the nucleophile to one of the allylic terminal carbon atoms. The second increased the ligands bite angle in order to create a chiral cavity in which the allyl system is perfectly embedded. To discriminate electronically between the two allylic terminal carbon atoms, the third strategy employed heterodonor ligands. Although many chiral ligands have been successfully applied in the substitution of several disubstituted substrates, problems generally remain with both substrate specificity and reaction rates using these methods. Other substrates, such as those that are monosubstituted, will require more active and more regio- and enantioselective Pd-catalysts. Overcoming these limitations requires research toward the development of new ligands. This Account discusses the application of homo- and heterodonor biaryl-containing phosphites as new, versatile, and highly effective ligands in the Pd-catalyzed asymmetric allylic substitution of several substrate types. We and others recently demonstrated that the inclusion of biarylphosphite moieties in ligand design is highly advantageous. In these systems, the catalysts substrate specificity decreases because the chiral pocket created (the chiral cavity with the embedded allyl ligand) is flexible enough to allow the perfect coordination of hindered and unhindered substrates. Reaction rates with these ligands increase because of the larger pi-acceptor ability of these moieties. The ability of the phosphite moiety to accept pi-electrons and enhance the S(N)1 character of the nucleophilic attack increases the regioselectivity of the reactions toward the desired branched isomer in monosubstituted linear substrates. Finally, the easy synthesis of biaryl phosphites from readily available alcohols allows for simple ligand tuning as well as systematic modifications of several important ligand parameters. Taking advantage of these features, we and others have designed highly adaptative biaryl-phosphite-containing ligands for asymmetric Pd-allylic substitution reactions. In this context, several diphosphites, phosphite-oxazolines, and phosphite-phosphoroamidites have recently emerged as extremely effective ligands for this process. Using a broad range of mono- and disubstituted hindered and unhindered linear and cyclic substrates, we have obtained high activities (turnover frequencies up to 22,000 mol substrate x (mol Pd x h)(-1)) unprecedented in the literature along with excellent regio- (up to 99%) and enantioselectivitites (up to >99%) at low catalyst loadings (turnover numbers up to 10,000 mol substrate x (mol Pd x h)(-1)). Appropriate ligand tuning allows access to both enantiomers of the substitution products.

Chiral diphosphites derived from D-glucose: new ligands for the asymmetric catalytic hydroformylation of vinyl arenes.

A series of novel diphosphite ligands derived from readily available D-(+)-glucose has been synthesized. These ligands have been applied to the Rh-catalyzed hydroformylation of vinyl arenes. Both excellent enantioselectivities (up to 91%) and regioselectivities (up to 98.8%) were achieved under mild conditions. The advantage of these ligands is that their modular natures allow facile, systematic variation in the configurations at the stereocenters [C(3), C(5)] at the ligand bridge and in the biphenyl substituents, enabling their effects on the stereoselectivity to be studied. Results show that the absolute configuration of the product is governed by the configuration at the stereogenic center C(3), while the level of the enantioselectivity is influenced by a cooperative effect between stereocenters C(3) and C(5). Replacement of the tert-butyl substituent by methoxy substituents at the para positions of the biphenyl moieties improved the enantioselectivities. We have characterized the rhodium complexes formed under CO/H2 by NMR techniques and in situ IR spectroscopy and have observed that there is a relationship between the structure of the [HRh(CO)2(PP)] species and their enantiodiscriminating performance in hydroformylation. Enantioselectivities were highest with ligands with a strong bis-equatorial coordination preference, while an equilibrium of species with bis-equatorial and equatorial-axial coordination modes considerably reduced the ees.

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.

Asymmetric Hydrogenation of Minimally Functionalised Terminal Olefins: An Alternative Sustainable and Direct Strategy for Preparing Enantioenriched Hydrocarbons

This account discusses the progress made in the asymmetric hydrogenation of minimally functionalised terminal olefins as a new, alternative, sustainable and direct strategy for preparing enantioenriched hydrocarbons. It discusses the latest development in catalyst design, from the initial discovery of lanthanide catalytic precursors, through the use of transition-metal/diphosphine-iminophosphorane precursors, to the successful iridium/P,N catalytic systems.

Modular Phosphite–Oxazoline/Oxazine Ligand Library for Asymmetric Pd‐Catalyzed Allylic Substitution Reactions: Scope and Limitations—Origin of Enantioselectivity

A library of phosphite-oxazoline/oxazine ligands L1-L15 a-h 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 amino acid derivatives. Their modular nature enables the substituents/configurations in the oxazoline/oxazine moiety, alkyl backbone chain and 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 99 %) and good activities have been achieved in a broad range of mono- and disubstituted linear hindered and unhindered liner and cyclic substrates. The NMR studies on the Pd-pi-allyl intermediates provide a deeper understanding about the effect of the ligand parameters on the origin of enantioselectivity. It also indicates that the nucleophilic attack takes place predominantly at the allylic terminal carbon atom located trans to the phosphite moiety.