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A set of iridium(I) and iridium(III) complexes is reported with triazolylidene ligands that contain pendant benzoxazole, thiazole, and methyl ether groups as potentially chelating donor sites. The bonding mode of these groups was identified by NMR spectroscopy and X-ray structure analysis. The complexes were evaluated as catalyst precursors in transfer hydrogenation and in acceptorless alcohol oxidation. High-valent iridium(III) complexes were identified as the most active precursors for the oxidative alcohol dehydrogenation, while a low-valent iridium(I) complex with a methyl ether functionality was most active in reductive transfer hydrogenation. This catalyst precursor is highly versatile and efficiently hydrogenates ketones, aldehydes, imines, allylic alcohols, and most notably also unpolarized olefins, a notoriously difficult substrate for transfer hydrogenation. Turnover frequencies up to 260 h–1 were recorded for olefin hydrogenation, whereas hydrogen transfer to ketones and aldehydes reached maxim...

A novel series of modular amino acid thioamide ligands functionalized with carbohydrates were introduced and employed in the rhodium-catalyzed asymmetric transfer hydrogenation (ATH) of aryl alkyl ...

We have replaced the oxazoline group with a thiazoline moiety in one of the most successful of the phosphite–oxazoline ligand families for the Ir-catalyzed hydrogenation of minimally functionalized olefins. A small but structurally important library of Ir phosphite–thiazoline precatalysts (Ir-L1–L2 a–e) has been developed by changing the substituents/configurations at the biaryl phosphite group. We found that the replacement of the oxazoline with a thiazoline moiety in the ligand design is beneficial in terms of substrate scope.

The first successful application of phosphite-pyridine ligands in the Ir-catalyzed asymmetric hydrogenation of di- and trisubstituted olefins is developed.

We have expanded the ligand design of one of the most successful phosphite-oxazoline ligands, derived from hydroxyl amino acid derivatives, in Pd-catalyzed allylic alkylation by replacing the oxazoline group with a thiazoline moiety. These phosphite-thiazoline ligands have been evaluated in the Pd-catalyzed allylic substitution of a wide range of mono-, di-, and trisubstituted substrates with several carbon nucleophiles, such as the less studied α-substituted malonates and β-diketones. For comparison we have also expanded our previous work on phosphite-oxazoline to carbon nucleophiles other than dimethyl malonate and to the alkylation of trisubstituted substrates. For hindered substrates such as disubstituted rac-1,3-diphenyl-3-acetoxyprop-1-ene and trisubstituted rac-1,1,-diphenyl-1-hepten-3-yl acetate and rac-1,3,3-triphenylprop-2-enyl acetate, enantioselectivities (ee values up to >99 %) are best obtained with phosphite-oxazoline ligands, whereas for unhindered cyclic substrates such as rac-3-acetoxycyclohexene, rac-3-acetoxycyclopentene, and rac-3-acetoxycycloheptene, enantioselectivities (ee values up to 94 %) improved considerably with phosphite-thiazoline ligands. In the case of monosubstituted substrates, the regio- and enantioselectivities obtained with both ligand types were comparable and excellent (regioselectivities up to 90 % and ee values up to 95 %). Therefore, by correctly combining substrate and ligand type (phosphite-oxazoline or phosphite-thiazoline), we have identified one of the few catalytic systems that provide high regio- and enantioselectivities in both enantiomers of the alkylation product for a wide range of hindered and unhindered mono-, di-, and trisubstituted substrates with several carbon nucleophiles. We have also discussed the synthesis and characterization of Pd-π-allyl intermediates to provide greater insight into the origin of enantioselectivity in these catalytic systems.

A highly modular furanoside thioether-phosphite/phosphinite/phosphine ligand library has been synthesized for the iridium-catalyzed asymmetric hydrogenation of minimally functionalized olefins. These ligands can be prepared efficiently from easily accessible D-(+)-xylose. We found that their effectiveness at transferring the chiral information in the product can be tuned by correctly choosing the ligand components. Enantioselectivities were therefore excellent (ees up to 99%) in a wide range of E- and Z-trisubstituted alkenes using 5-deoxyribofuranoside thioether-phosphite ligands. It should be pointed out that these catalysts are also very tolerant to the presence of a neighbouring polar group. For 1,1-disubstituted substrates, both enantiomers of the hydrogenation product can be obtained in high enantioselectivities simply by changing the configuration of the biaryl phosphite moiety. The asymmetric hydrogenation was also performed using propylene carbonate as solvent, which allowed the iridium catalysts to be reused while maintaining the excellent enantioselectivities.

A family of 12 modular ferrocenyl planar chiral phosphine-thioethers (P,S) has been studied in the asymmetric hydrogenation of minimally functionalized alkenes. These ligands differ by the substituent on sulfur or by the linker between the ferrocene moiety and the sulfur atom (no linker, methylene or methyl substituted methylene linker bearing an additional element of chirality). The cationic iridium(cod) complexes of the different P,S ligands have been efficiently synthesized. For the majority of the ligands, coordination yielded only a single diastereoisomer with full control of the absolute configuration on sulfur. The different iridium complexes have been used in the hydrogenation of various di, tri, and tetrasubstituted minimally functionalized olefins. Conversions and enantioselectivities are highly dependent on the ligand and substrate structure. Full conversions and low-to-excellent enantioselectivities could be obtained (maximum ee from 14 to 94% for 1,1-disubsituted alkenes, from 17 to 99% for trisubstituted olefins, and 34% for the tetrasubstituted alkene).

Asymmetric hydrogenation is one of the most efficient and atom-economical tools to prepare chiral molecules. However, the enantiodiscrimination of simple, minimally functionalized olefins is still challenging and requires more sophisticated ligand design. Herein, we discuss our progress in the successful development of ligand design for the iridium-catalyzed asymmetric hydrogenation of minimally functionalized olefins.

Asymmetric transfer hydrogenation (ATH) has emerged as one of the most effective and sustainable synthetic tool for synthesizing enantiopure alcohols. Since Noyori’s group successfully applied Ru-catalysts modified with chiral β-amino alcohols or diamines as ligands, a large number of catalytic systems has been successfully developed. However, further improvement in terms of substrate scope, selectivity, and turnover frequency are required to make the process competitive with conventional hydrogenations. Overcoming these limitations requires research toward the design of new ligands. Such a task becomes easier if readily modulable chiral ligands are at hand. Sugar-based ligands are particularly useful for addressing this need. They are readily available, highly functionalized, and their modular constructions are easy. Series of chiral ligands can be screened in the search for high activities and selectivities for each type of substrate. This digest paper will discuss the progress on the use of sugar-based ligands in ATH reactions.

Asymmetric hydrogenation is one of the most efficient and atom-economical tools to prepare chiral molecules. However, the enantiodiscrimination of simple, minimally functionalized olefins is still challenging and requires more sophisticated ligand design. Herein, we discuss our progress in the successful development of ligand design for the iridium-catalyzed asymmetric hydrogenation of minimally functionalized olefins.

DOI: 10.1002/adsc.201600903 URL: http://onlinelibrary.wiley.com/doi/10.1002/adsc.201600903/abstract Filiació URV: SI Inclòs a la memòria: SI A modular ligand library of α-amino acid hydroxyamides and thioamides was prepared from 10 different N-tert-butyloxycarbonyl-protected α-amino acids and three different amino alcohols derived from 2,3-O-isopropylidene-α-d-mannofuranoside. The ligand library was evaluated in the half-sandwich ruthenium- and rhodium-catalyzed asymmetric transfer hydrogenation of a wide array of ketone substrates, including simple as well as sterically demanding aryl alkyl ketones, aryl fluoroalkyl ketones, heteroaromatic alkyl ketones, aliphatic, conjugated and propargylic ketones. Under the optimized reaction conditions, secondary alcohols were obtained in high yields and in enantioselectivities up to >99%. The choice of ligand/catalyst allowed for the generation of both enantiomers of the secondary alcohols, where the ruthenium-hydroxyamide and the rhodium-thioamide catalysts act complementarily towards each other. The catalytic systems were also evaluated in the tandem isomerization/asymmetric transfer hydrogenation of racemic allylic alcohols to yield enantiomerically enriched saturated secondary alcohols in up to 98% ee. Furthermore, the catalytic tandem α-alkylation/asymmetric transfer hydrogenation of acetophenones and 3-acetylpyridine with primary alcohols as alkylating and reducing agents was studied. Secondary alcohols containing an elongated alkyl chain were obtained in up to 92% ee.

International audience; A family of 12 modular ferrocenyl planar chiral phosphine-thioethers (P,S) has been studied in the asymmetric hydrogenation of minimally functionalized alkenes. These ligands differ by the substituent on sulfur or by the linker between the ferrocene moiety and the sulfur atom (no linker, methylene or methyl substituted methylene linker bearing an additional element of chirality). The cationic iridium(cod) complexes of the different P,S ligands have been efficiently synthesized. For the majority of the ligands, coordination yielded only a single diastereoisomer with full control of the absolute configuration on sulfur. The different iridium complexes have been used in the hydrogenation of various di, tri, and tetrasubstituted minimally functionalized olefins. Conversions and enantioselectivities are highly dependent on the ligand and substrate structure. Full conversions and low-to-excellent enantioselectivities could be obtained (maximum ee from 14 to 94% for 1,1-disubsituted alkenes, from 17 to 99% for trisubstituted olefins, and 34% for the tetrasubstituted alkene).

Eight (biaryl)phosphite/pyridine ligands 1–2a–d have been prepared by the modular functionalization of positions C-2 and C-3 of two d -glucopyranoside backbones. The chiral ligands were examined in the iridium-catalyzed asymmetric hydrogenation of poorly functionalized alkenes, as a function of the relative position of the coordinating groups and the geometric properties of the biaryl phosphite moieties. Enantiomeric excesses of up to 90% were achieved in the hydrogenation of E-2-(4-methoxyphenyl)-2-butene by using 1a and 1c, which seemingly combine the beneficial effect of the phosphite at the 2-position with the matching (Rax)-configuration of their encumbered biaryl substituents. The results of the hydrogenation of more challenging substrates, such as Z-trisubstituted alkenes, alkenes with a neighboring polar group or demanding 1,1-di-substituted alkenes, generally confirmed this trend, and in some significant cases, the chiral hydrogenated products were isolated with ees of 65–79%.

This review discusses the latest developments in ligand design for the Pd-catalyzed asymmetric intermolecular Mizoroki-Heck reaction, from the successful phosphine/phosphinite-nitrogen ligands to the recently reported phosphite-nitrogen ligands. The presence of a biaryl phosphite group offers several advantages as a ligand scaffold for this process.

Two new highly modular carbohydrate-based, pseudodipeptide and thioamide ligand libraries have been synthesized for the rhodium- and ruthenium-catalyzed asymmetric transfer hydrogenation (ATH) of prochiral ketones. These series of ligands can be prepared efficiently from easily accessible D-xylose and D-glucose. The ligand libraries contain two main ligand structures (pseudodipeptide and thioamide) that have been designed by making systematic modifications to one of the most successful ligand families developed for the ATH. As well as studying the effect of these two ligand structures on the catalytic performance, we also evaluated the effect of modifying several of the ligand parameters. We found that the effectiveness of the ligands at transferring the chiral information in the product can be tuned by correctly choosing the ligand components (ligand structure and ligand parameters). Excellent enantioselectivities (ees up to 99%) were therefore obtained in both enantiomers of the alcohol products using a wide range of substrates.

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.

A series of readily available sugar-based phosphite ligands were applied to the Ni-catalyzed asymmetric trialkylaluminum additions to aldehydes. The ability of the catalysts to transfer chiral information to the product could be tuned by choosing suitable ligand components (configuration at C-3 of the furanoside backbone; the steric hindrance of the substituent at C-3 and the substituents/configuration of the biaryl phosphite moieties). Good enantioselectivities (ee’s up to 84%) were obtained for several aryl aldehydes using several organoaluminum sources.

We describe the application of a new class of ligands –the phosphite-oxazole/imidazole (L1–L5a–g) – in asymmetric intermolecular Pd-catalyzed Heck reactions under thermal and microwave conditions. These ligands combine the advantages of the oxazole/imidazole moiety with those of the phosphite moiety: they are more stable than their oxazoline counterparts, less sensitive to air and other oxidizing agents than phosphines and phosphinites, and easy to synthesize from readily available alcohols. The results indicate that activities, regio- and enantioselectivities, are highly influenced by the type of nitrogen donor group (oxazole or imidazole), the oxazole and biaryl-phosphite substituents and the axial chirality of the biaryl moiety of the ligand. By carefully selecting the ligand components, we achieved high activities, regio- (up to 99%) and enantioselectivities (up to 99%) using several triflate sources. Under microwave-irradiation conditions, reaction times were considerably shorter (from 24 h to 30 min) and regio- and enantioselectivities were still excellent.

This review describes recent development in the use of sugar-derived ligands in the selective synthesis of organic molecules. Developments in the recent literature (2004–2009) are highlighted in the areas of hydrogenation, 1,2- and 1,4-additions of nucleophiles to C O and C NR based substrates, cross-coupling, hydroformylation, oxidation and other reactions. Connections to earlier studies are also noted were relevant. Some suggestions as to the underlying features that make sugar-based ligands highly useful modular ligands in selective catalysis are given. Finally, advice is presented (for the non-specialist) on optimal entry points and basic starting materials for sugar-ligand synthesis.

A biaryl-based monophosphoroamidite L1–L4a–f and aminophosphine L5–L7a–f ligand library was screened in the Rh-catalyzed asymmetric hydroformylation of several vinylarenes and heterocyclic olefins. Our results indicate that the selectivity is strongly dependent on the ligand parameters and on the substrate type. Enantioselectivities (up to 46%) were moderate in the hydroformylation of several vinylarenes S1–S5 and promising (up to 58%) for the more challenging heterocyclic olefins S6–S9.

We have screened a library of modular phosphite-oxazoline ligands for asymmetric allylic substitution reactions. The library is efficiently prepared from the commercially available and cheap D -glucosamine. The introduction of a phosphite moiety into the ligand design is highly advantageous for the product outcome. Therefore, this ligand library affords good-to-excellent reaction rates [TOFs up to 600 mol substrate x (mol Pd x h) -1 ] and enantioselectivities (ees up to 99%) and, at the same time, shows a broad scope for mono-, di- and trisubstituted linear hindered and unhindered substrates and cyclic substrates. The NMR studies on the palladium allyl intermediates provide a deeper understanding about the effect of the ligand parameters on the origin of enantioselectivity.

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 ligand's 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 catalyst's 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.

A modular sugar-based phosphoroamidite L1–L5a–g and phosphite L6–L9a–g ligand library was tested in the asymmetric Cu-catalyzed 1,4-conjugate addition reactions of β-substituted (cyclic and linear) and β,β′-disubstituted (cyclic) enones. The selectivity depended strongly on the configuration of carbon atom C-3, the size of the sugar backbone ring, the flexibility of the ligand backbone, the substituents and configurations in the biaryl phosphoroamidite moieties a–g, the type of functional group attached to the ligand backbone and the substrate structure. Therefore, by carefully selecting the ligand parameters, enantioselectivities of up to 60% for cyclic substrates and 72% for linear ones were achieved.

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.

A sugar-based phosphite–phosphoroamidite and diphosphoroamidite ligand library L1–L5a–g was tested in the asymmetric Cu-catalyzed 1,4-conjugate addition reactions of β-substituted and β,β′-disubstituted enones. Our results indicated that the selectivity was strongly dependent on the ligand parameters and on the substrate structure. Moderate-to-good enantioselectivities (ees up to 84%) were obtained in the 1,4-addition of several types of β-substituted cyclic and linear substrates. Of particular note is the high enantioselectivity (ees up to 90%) obtained for the more challenging β,β′-disubstituted 3-methyl-cyclohexenone.

A library of furanoside phosphite-phosphoroamidite ligands has been synthesized and screened in the palladium-catalyzed allylic substitution reactions of several substrate types. These series of ligands can be prepared efficiently from easily accessible D -xylose and D -glucose. Their modular nature enables the position of the phosphoroamidite group, configuration of C-3 of the furanoside backbone and the substituents/configurations in the biaryl phosphite/phosphoroamidite moieties to be easily and systematically varied. By carefully selecting the ligand components, therefore, high regio- and enantioselectivities (ees up to 98%) and good activities have been achieved in a broad range of mono- and disubstituted hindered and unhindered linear and cyclic substrates. The NMR studies on the palladium-π-allyl intermediates provide a deeper understanding about the effect of the ligand parameters on the origin of enantioselectivity. They also indicate that the nucleophilic attack takes place predominantly at the allylic terminal carbon atom located trans to the phosphoroamidite moiety.

A modular sugar-based phosphoroamidite ligand library for the Ni-catalyzed trialkylaluminium addition to aldehydes has been synthesized and screened. After systematic variation of the sugar backbone, the substituents at the phosphoroamidite moieties and the flexibility of the ligand backbone, the monophosphoroamidite ligand 3-amine-3-deoxy-1,2:5,6-di- O -isopropylidene-((3,3′-di-trimethylsilyl-1,1′-biphenyl-2,2′-diyl)phosphite)-α- d -glucofuranose 1d were found to be optimal. Activities were high and enantioselectivities were good (ees up to 78%) for several aryl aldehydes.

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

Modular sugar phosphite-oxazoline L1–L5a–c and phosphite-phosphoroamidite L6a–c ligand libraries were screened in the asymmetric Ni-catalyzed 1,2-addition reactions to aldehydes. Systematically varying the electronic and steric properties of the oxazoline and biaryl phosphite substituents and the functional groups attached to the basic sugar-backbone, we found a strong influence of the oxazoline and the functional groups of the sugar-backbone on the catalytic performance. Enantioselectivity (ee values up to 59%) was best with the catalysts precursor containing the phosphite-oxazoline ligand L3a, that contains a sterically hindered tert-butyl oxazoline group.

This review describes the use of the most representative carbohydrate derivative ligands in asymmetric catalysis between 1972 and 2006 (approximately). Particular emphasis is placed on the latest results published in the most active period of this area of research (1998 to January 2007). In the first sections we cover the results obtained using homodonor ligands, such as phosphanes, phosphinites, phosphites and dithioethers. In the next sections, we present the results of using heterodonor ligands, such as P–P′, P–S, P–N and N–S ligands. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

A sugar-based monophosphite ligand library L1 – L5 was screened in the Cu-catalyzed asymmetric 1,4-addition to cyclic and aliphatic linear enones. These ligands are derived from d -glucose, d -galactose and d -fructose, which lead to a wide range of sugar backbones, and contain several substituents/configurations in the biaryl moiety, with different steric and electronic properties. Systematic variation of the ligand parameters indicates that the catalytic performance (activities and enantioselectivities) is highly affected by the configuration of C-4 of the carbohydrate backbone, the size of the ring of the sugar backbone and the cooperative effect between configurations of C-3 and of the binaphthyl phosphite moiety. Good activities and enantioselectivities up to 57% and 51% were achieved for cyclic and aliphatic linear enones, respectively.

Sugar–phosphite–oxazoline L1 – L5a – g and phosphite–phosphoroamidite L6a – c ligand libraries were tested in the asymmetric Cu-catalyzed 1,4-conjugate addition reactions of cyclic and acyclic enones. Systematically varying the electronic and steric properties of the oxazoline and biaryl phosphite substituents and the functional groups attached to the basic sugar-backbone had a strong effect on the catalytic performance. In general, good activities and enantioselectivities were obtained. The enantioselectivity (up to 80%) was optimized with catalyst precursors containing the phosphite–oxazoline ligands L1c and L1f that contain encumbered biaryl phosphite moieties and a phenyl oxazoline group.

We have designed a new family of readily available highly-modular phosphite-phosphoramidite ligands for asymmetric allylic alkylation reactions. The introduction of a phosphoramidite moiety in the ligand design is highly advantageous in the product outcome. Thus, this ligand series affords high reaction rates and enantioselectivities and, at the same time, shows a broad scope for disubstituted hindered and unhindered substrate types.

A library of novel modular iridium complexes derived from thioether-phosphite/phosphinite ligands are synthesized and evaluated in the asymmetric hydrogenation of minimally functionalized olefins.

The stereospecific hydrolysis of bulky aminophosphine boranes is reported for the first time. The resulting phosphinous acid boranes, upon activation, undergo stereospecific nucleophilic substitution reaction at the phosphorous center with amine nucleophiles. The combination of these two processes provides a novel access to bulky P*-ligands.

[reaction: see text] A series of phosphite-phosphoroamidite ligands, derived from readily available d-xylose, has been successfully applied for the first time in the Pd-catalyzed allylic substitution of several substrates with different steric and electronic properties, with high enantioselectivities (ee's up to 98) and activities in standard conditions.

We have designed and synthesized a new family of readily available phosphite–phosphoroamidite ligands for Pd-catalyzed allylic substitution reactions of several substrates with different steric and electronic properties. These ligands are derived from d -glucosamine and contain several substituents in the biphenyl moieties, with different steric and electronic properties. Systematic variation of the ligand parameters indicates that enantioselectivities are mainly affected by the substituents at the para-positions of the biphenyl moieties. Enantiomeric excesses of up to 89% with high activities were obtained for rac-1,3-diphenyl-3-acetoxyprop-1-ene S1, rac-(E)-ethyl-2,5-dimethyl-3-hex-4-enylcarbonate S2 and rac-3-acetoxycycloheptene S5.

A series of readily available thioether–phosphinite ligands has been tested in the Pd-catalyzed allylic substitution reactions of several acyclic and cyclic allylic substrates ( S1 – S7 ). This series of ligands have been designed to uncover their important structural features and to determine the scope of the thioether–phosphinite ligands in these catalytic reactions. Systematic variation of the electronic and steric properties at the thioether moiety provide useful information about the ligand parameters that control the enantiodiscrimination. By carefully selecting the ligand parameters, good enantioselectivities with high activities were obtained for hindered linear substrates S1 and S2 (ee’s up to 95%) and for unhindered cyclic substrates S4 and S5 (ee’s up to 91%).

A series of phosphite–oxazoline ligands was tested in the Rh-catalyzed hydrosilylation of ketones. Systematic variation of the electronic and steric properties at the biphenyl phosphite moiety and at the oxazoline moiety provide useful information about the ligand parameters that control the enantiodiscrimination. The results show that the enantiomeric excesses are dependent on the properties on both the phosphite and oxazoline moieties of the ligand and on steric and electronic properties of the substrate. Low-to-moderate enantiomeric excesses (up to 62%) were obtained in the hydrosilylation of several aryl ketones.

The syntheses of ligands (I) and numerous derivatives thereof are described allowing the enantioselective reduction of arylalkyl and hetarylalkyl ketones to both enantiomers of the corresponding alcohols in high yields.

We have designed and synthesized a new family of readily available phosphite-oxazoline ligands for Pd-catalyzed asymmetric allylic substitution reactions. These ligands can be tuned in two regions to explore their effect on catalytic performance. By carefully selecting the ligand components, we obtained high enantioselectivities in the Pd-catalyzed allylic substitution in.substrates with different steric properties.

We have synthesized a library of furanoside diphosphite ligands for the Pd-catalyzed allylic substitution reactions of acyclic and cyclic allylic esters. The library has been designed to rapidly screen the ligands to uncover their important structural features and to determine the scope of diphosphite ligands in these catalytic reactions. After the systematic variation of the sugar backbone, the substituent at C-5 and the phosphite moieties, the diphosphite ligand 4c was found to be optimal in the Pd-catalyzed asymmetric allylic substitution of hindered (S1) and unhindered (S2-S5) substrates, yielding high activities [TOFs up to > 3000 mol x (mol x h) - 1 ] and enantioselectivities (ees up to 99%). In addition, the screening of the library enabled us to find other suitable ligands for hindered disubstituted linear substrate S1 (ligands 1b-d, g and 4b, d, g) and for unhindered cyclic substrates S3-S5 (ligands 6c and 7c).