A new electronically deficient atropisomeric diphosphine ligand (S)-CF3O-BiPhep and its application in asymmetric hydrogenation

A new electronically deficient atropisomeric diphosphine ligand (S)-CF₃O-BiPhep was synthesized from 1-bromo-3-(trifluoromethoxy)benzene in high yield. The key steps included oxidative coupling with anhydrous ferric chloride and optical resolution by (+)-DMTA. The ligand afforded high performance for Ir-catalyzed asymmetric hydrogenation of quinolines with ee up to 92% and TON up to 25,000. It was also successfully applied to the Pd-catalyzed asymmetric hydrogenation of simple indoles with ee up to 87% and Rh-catalyzed asymmetric 1,4-addition of phenylboronic acid to 2-cyclohexenone with 97% ee.     

手性的H‘4-NOBIN衍生物在不对称加成和取代反应中的应用

以手性 H’4-NOBIN为原料合成了新型手性氨基酚2和N,P配体5, 并将化合物2应用于催化二乙基锌对醛的不对称加成反应, 产率达90%, 对映体过量最高为45.9% ee. 化合物5用于钯催化的1,3-二苯基-2-烯丙基乙酸酯的不对称烯丙基烷基化反应, 产率为89%, 对映体过量最高为81.6% ee. 结果表明氨基酚2手性诱导作用弱于未氢化的NOBIN, 但却高于其八氢衍生物, 而N,P配体5给出相反的结果.     

New chiral diamino-bis(tert-thiophene): an effective ligand for Pd- and Zn-catalyzed asymmetric transformations

Enantiomerically pure diamino-bis(tert-thiophene) proved to be a valuable and flexible chiral ligand for Pd- and Zn-catalyzed transformations, allowing for high levels of stereocontrol in asymmetric allylic alkylation (ee up to 99%) and hydrosilylations of prochiral carbonyls (ee up to 97%).     

Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated ketones with DIFLUORPHOS and SYNPHOS analogues

Applications of electron-deficient DIFLUORPHOS and SYNPHOS analogues in the rhodium-catalyzed asymmetric conjugate addition of boronic acids to α,β-unsaturated ketones afford the 1,4-addition adducts in yields up to 92% and with 99% ee. Particularly, a Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to nonsubstituted maleimide substrates using the (R)-3,5-diCF(3)-SYNPHOS ligand is also reported. This protocol provides access to various enantioenriched 3-substituted succinimide units of biological interest, in high yields and good to excellent ee up to 93%, which could be upgraded up to 99% ee, after a single crystallization.     

A P-chiral bisdiamidophosphite ligand with a 1,4:3,6-dianhydro-d-mannite backbone and its application in asymmetric catalysis

A novel readily available P,P-bidentate diamidophosphite ligand with P^∗-stereocentres is prepared from an inexpensive C₂-symmetric 1,4:3,6-dianhydro-d-mannite. By using this efficient ligand, up to 98% ee is achieved in Pd-catalysed asymmetric allylic alkylation, up to 92% ee in Pd-catalysed asymmetric allylic amination and up to 87% ee in Rh-catalysed asymmetric hydrogenation. The influence of the precatalyst, substrate and solvent on the enantioselectivity is discussed.     

Complementing Pyridine‐2,6‐bis(oxazoline) with Cyclometalated N‐Heterocyclic Carbene for Asymmetric Ruthenium Catalysis

A strategy for expanding the utility of chiral pyridine‐2,6‐bis(oxazoline) (pybox) ligands for asymmetric transition metal catalysis is introduced by adding a bidentate ligand to modulate the electronic properties and asymmetric induction. Specifically, a ruthenium(II) pybox fragment is combined with a cyclometalated N‐heterocyclic carbene (NHC) ligand to generate catalysts for enantioselective transition metal nitrenoid chemistry, including ring contraction to chiral 2H‐azirines (up to 97 % ee with 2000 TON) and enantioselective C(sp³)?H aminations (up to 97 % ee with 50 TON).     

Highly enantioselective phenyl transfer to aryl aldehydes catalyzed by easily accessible chiral tertiary aminonaphthol

A new chiral tertiary aminonaphthol ligand 3b served as a highly efficient ligand for the asymmetric catalytic phenyl transfer to aromatic aldehydes and a variety of chiral diarylmethanols was prepared in high ee values (ee up to 99%) and chemical yields. The straightforward syntheses of both 3b and its enantiomer provide an excellent opportunity for large-scale applications.     

Highly enantioselective conjugate additions of potassium organotrifluoroborates to enones by use of monodentate phosphoramidite ligands

The use of phosphoramidite ligands in the rhodium-catalyzed asymmetric conjugate addition of potassium organotrifluoroborates to various enones in the absence of water is described. A systematic search for effective catalysts has been performed by use of high-throughput screening methods. Initially, we have screened reaction conditions, catalyst precursors, and focused ligand libraries. In the next stage we have used the monodentate ligand combination approach, and finally we have made a library of 96 different phosphoramidites by parallel synthesis in the robot (instant ligand libraries) and have tested these in the vinylation of cyclohexenone (up to 88% enantiomeric excess, ee) and 4-phenyl-3-buten-2-one (up to 42% ee). Arylation of cyclohexenone by use of potassium phenyltrifluoroborate gave 3-phenylcyclohexanone with 99% ee.     

Template-induced formation of heterobidentate ligands and their application in the asymmetric hydroformylation of styrene

We report the template-induced formation of chelating heterobidentate ligands by the selective self-assembly of two different monodentate ligands on a rigid bis-zinc(II)-salphen template with two identical binding sites; these templated heterobidentate ligands induce much higher enantioselectivities (up to 72% ee) in the rhodium-catalyzed asymmetric hydroformylation of styrene than any of the corresponding homobidentate ligands or non-templated mixed ligand combinations (up to 13% ee).     

Asymmetric hydrogenation of quinolines with high substrate/catalyst ratio

The chiral diphosphinite ligand derived from (R)-1,1'-spirobiindane-7,7'-diol has been found to be highly effective in the Ir-catalyzed asymmetric hydrogenation of quinolines with high substrate/catalyst ratio (up to 5000) and high enantioselectivity (up to 94% ee).     

Asymmetric Henry reactions catalyzed by copper(II) complexes of chiral 1,2,4-triazine-oxazoline ligands: the impact of substitution in the oxazoline ring on ligand activity

An enantiomerically pure 1,2,4-triazine-oxazoline ligand with an indanol-derived substituent in the oxazoline ring has been synthesized using Buchwald–Hartwig amination of 3-bromo-1,2,4-triazine. The catalytic efficiency of the ligand was estimated in the asymmetric nitroaldol (Henry) reaction of nitromethane with several aromatic and aliphatic aldehydes. The appropriate nitroaldol products were formed in good yields (up to 91%) and with up to 92% ee. In order to investigate the influence of the conformational rigidity and the additional stereocenter in the oxazoline ring on the catalytic activity of the ligand, a 1,2,4-triazine-oxazoline ligand with two phenyl substituents in the oxazoline ring was synthesized and tested in the asymmetric nitroaldol reaction.     

Asymmetric allylic oxidation reactions catalyzed by a chiral nonracemic and C2-symmetric 2,2'-bipyridyl copper(I) complex

The evaluation of a chiral, nonracemic and C2-symmetric 2,2'-bipyridyl ligand in copper(I)-catalyzed asymmetric allylic oxidation reactions of a series of cyclic alkenes with tert-butyl peroxybenzoate is reported (up to 91% ee, the highest reported enantioselectivity for a bipyridyl ligand copper(I) complex to date).     

Asymmetric Rh-catalyzed hydrogenation using a furanoside phosphite-phosphoroamidite and diphosphoroamidite ligand library

A furanoside phosphite-phosphoroamidite and diphosphoroamidite ligand library L1-L5a-f was tested in the asymmetric Rh-catalyzed hydrogenation of α,β-unsaturated carboxylic acid derivatives and enamides. Enantioselectivity depended strongly on the ligand parameters. High enantioselectivities were obtained in the reduction of dimethyl itaconate (up to >99% ee), α-dehydroamino acid esters (up to 99% ee) and several enamides (up to 92% ee). Kinetic and NMR studies on the intermediates of the catalytic cycle of the reaction indicate that the [Rh(P(1)-P(2))(substrate)](+) species is the resting state of the reaction and that the rate dependence is first order in rhodium and hydrogen pressure and zeroth order in the substrate.     

Design and synthesis of chiral 1,10-phenanthroline ligand,and application in palladium catalyzed asymmetric 1,4-addition reactions

Pd-catalyzed asymmetric 1,4-addition of phenylboronic acid to α,β-unsaturated carbonyl compounds was developed using chiral 1,10-phenanthroline derivative as ligand. Good yields (up to 97%), and high enantioselectivities (up to 97% ee) were achieved.     

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.     

Synthesis of a new chiral nonracemic C(2)-symmetric 2,2'-bipyridyl ligand and its application in copper(I)-catalyzed enantioselective cyclopropanation reactions

An efficient synthesis of a low molecular weight, chiral nonracemic and C(2)-symmetric bipyridyl ligand is reported. The ligand was prepared using a catalytic asymmetric dihydroxylation reaction of a pyrindine as a key step. The ligand was evaluated in the asymmetric copper(I)-catalyzed cyclopropanation reactions of a series of alkenes and diazoesters. Very high diastereoselectivities and enantioselectivities were observed (>95:5 dr and up to 99% ee). These are the highest reported stereoselectivities for a chiral bipyridyl ligand. [structure: see text]     

Asymmetric synthesis of alpha-aminoamides by Pd-catalyzed double carbohydroamination

Tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3] catalyzed asymmetric double carbohydroamination of iodoarenes in the presence of a chiral ligand (Trost ligand and Me-DuPHOS are most effective) is an excellent method for the chiral synthesis of alpha-aminoamides in up to 99% ee.     

Rhodium-catalysed asymmetric hydrosilylation of ketones using HETPHOX ligands

The HETPHOX ligand class was applied to the rhodium-catalysed asymmetric hydrosilylation of a range of substituted acetophenones. Enantioselective hydrosilylation of acetophenone with the tert-butyl substituted HETPHOX ligand gave (R)-phenylethanol in excellent enantioselectivity (84% ee) and in good conversion (80%). When applied to the hydrosilylation of other ketones conversions up to 93% and enantioselectivities up to 88% were observed.     

A new type of bis(sulfonamide)-diamine ligand for a Cu(OTf)2-catalyzed asymmetric Friedel-Crafts alkylation reaction of indoles with nitroalkenes

Chiral bis(sulfonamide)-diamine served as new type of ligand for a Cu(OTf)(2)-catalyzed asymmetric Friedel-Crafts alkylation reaction of indoles with nitroalkenes. The desired products were obtained with up to 99% yield and 97% ee.     

Nickel-catalyzed 1,2-addition of arylboroxines to aromatic aldehydes

Development of Ni-Et-Duphos-catalyzed 1,2-addition of arylboroxines to aromatic aldehydes is described. The dramatic effect of boron reagent and phosphine ligand is observed. This method with a phosphine ligand allows asymmetric arylation of aromatic aldehydes (up to 78% ee).