Ir(III) complexes of diamine ligands for asymmetric ketone hydrogenation

The use of a combination of IrCl₃ with a series of ligands derived from the C2-symmetric diamine diphenylethanediamine (DPEN) forms a catalyst capable of the asymmetric hydrogenation of ketones in up to 85% ee.     

Synthesis of new C2-symmetric bis(β-hydroxy amide) ligands and their applications in the enantioselective addition of alkynylzinc to aldehydes

A series of chiral C₂-symmetric bis(β-hydroxy amide) ligands was synthesized via the reaction of isophthaloyl dichloride and amino alcohols derived from l-amino acid. The titanium(IV) complex of C₂-symmetric chiral ligand 3b was effective for the asymmetric alkynylation of aldehydes and the propargyl alcohols were obtained in high yields (up to 94%) and high enantiomeric excesses (up to 98%) under optimized conditions. The results obtained using ligand 3h support that the two β-hydroxy amide moieties in these ligands behave as two independent ligands in the catalytic system.     

Novel chiral C2-symmetric multidentate aminophosphine ligands for use in catalytic asymmetric reduction of ketones

A series of novel chiral C₂-symmetric multidentate aminophosphine ligands have been successfully synthesized by Schiff-base condensation of bis（o-formylphenyl）phenylphosphane and easily available monoprotected（1R,2R）-diaminocyclohexane.The catalytic properties of these ligands were investigated in Ir-catalyzed asymmetric transfer hydrogenation of various aromatic ketones,giving the corresponding optical active alcohols with up to 98%conversion and good ee under mild reaction conditions.     

The synthesis of chiral amino diol tridentate ligands and their enantioselective induction during the addition of diethylzinc to aldehydes

A series of C₂-symmetric chiral amino diol tridentate ligands 3a–g were prepared from achiral bulky organolithiums, achiral bulky primary amines, and optically active epichlorohydrin (ECH). The prepared C₂-symmetric chiral amino diol tridentate ligands were capable of inducing enantioselectivity in the model reaction of aromatic and aliphatic aldehydes with diethylzinc with an ee of up to 96%. The enantioselectivity can be modulated by adjusting the steric hindrance of the achiral reagents employed in the synthesis of the chiral ligand. The configuration of the addition product depended on the configuration of the amino diol ligands, which can be simply controlled as desired by using the ECH with the desired configuration during the preparation of the ligand.     

A novel C3-symmetric prolinol-squaramide catalyst for the asymmetric reduction of ketones by borane

A novel C₃-symmetric prolinol-squaramide has been developed for the asymmetric reduction of ketones by borane. By using only 5 mol % catalyst 1a for the reaction, high yields and excellent enantioselectivities (up to 95% yield, 93% ee) were obtained. Moreover, 1a can be easily recovered by simple precipitation and re-used for four cycles without losing the selectivity.     

A new chiral sulfinyl-NH-pyridine ligand for Ir-catalyzed asymmetric transfer hydrogenation reaction

A new flexible C₁-symmetric tridentate ligand (S)-N-(2-(tert-butylsulfinyl)benzyl)-1-(pyridin-2-yl)methanamine sulfoxide (L1) was successfully prepared and utilized as a chiral ligand for Ir(I)-catalyzed ATH (asymmetric transfer hydrogenation) reactions. Without any cooperation of other chiral center, encouraging ee and conversion values have been achieved, which provide us a better understanding on these types of ligands and a new strategy to develop new high-efficiency chiral catalysts for asymmetric reaction.     

SPANamine derivatives in the catalytic asymmetric α-fluorination of β-keto esters

The use of C₂-symmetric enantiopure nitrogen ligands in the asymmetric catalytic α-fluorination of β-ketoesters is described. SPANamine 1 in the presence of nickel salts gives up to 63% ee in the fluorination of tert-butyl 2-oxocyclopentanecarboxylate with N-fluorosuccinimide (NFSI). The same enantioselectivity is obtained when SPANamine 1 is used as an organocatalyst, although the reaction is much slower.     

Chiral diphenylselenophosphoramides: a new class of chiral ligands for the titanium(IV) alkoxide-promoted addition of diethylzinc to aldehydes

Chiral C₂-symmetric diphenylselenophosphoramides 1 and 2 were prepared from the reaction of diphenylselenophosphinic chloride with (1R,2R)-(−)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylenediamine, respectively, in high yields. Another novel chiral ligand 3 was prepared from the reaction of diphenylselenophosphinic chloride with (R)-(+)-1,1′-binaphthyl-2,2′-diamine using butyllithium as the base. The ligands were used as catalytic chiral ligands in the titanium(IV) alkoxide-promoted enantioselective addition reaction of diethylzinc to aldehydes.     

Asymmetric hydrogenation of quinolines with recyclable and air-stable iridium catalyst systems

The iridium complex-catalyzed asymmetric hydrogenation of quinolines in a DMPEG/hexane biphasic system was studied. Catalysts with C₂-symmetric ligands such as Xyl-P-Phos, Cl–MeO–BIPHEP, SYNPHOS, and DifluorPhos are highly effective for this type of reaction. Most of the catalysts tested can be retained in DMPEG (M_n = 500), and the asymmetric hydrogenation of various quinoline substrates can be carried out in DMPEG/hexane biphasic system with up to 92% ee. The catalysts and the products can be separated via simple phase separation, and the reactivity/stereoselectivity of the catalysts can be retained for at least three reaction cycles.     

Asymmetric addition of diethylzinc to benzaldehyde catalyzed by novel chiral C2-symmetric tetrakis(sulfonamide)–titanium(IV) complexes

A series of chiral C₂-symmetric tetrakis(sulfonamides) 3a–f, 4a–f were prepared and employed as ligands for titanium(IV) complexes in the asymmetric addition of diethylzinc to benzaldehyde. The chiral secondary alcohols were obtained in high yields and in moderate enantioselectivities.     

Novel C2-symmetric chiral O,N,N,O-tetradentate 2,2-bipyridyldiolpropane ligands: synthesis and application in asymmetric diethylzinc addition to aldehydes

First synthesis of C₂-symmetric chiral O,N,N,O-tetradentate 2,2-bipyridyldiolpropane ligands is described. The Mukaiyama–Michael reaction was applied as an important reaction for the synthesis of 2,2-bipyridylpropane 9. Among the ligands synthesized, ligand 11 exhibits excellent chiral induction (up to 97% ee) in diethylzinc addition to various aldehydes. The use of additional Lewis acid such as Ti(OⁱPr)₄ in diethylzinc addition reaction is not required for the present catalytic system.     

Chiral diphenylthiophosphoramides: a new class of chiral ligands for the silver(I)-promoted enantioselective allylation of aldehydes

Chiral C₂-symmetric diphenylthiophosphoramides 1 and 2 were prepared in high yields from the reaction of diphenylthiophosphinic chloride with (1R,2R)-(−)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylenediamine, respectively. Another novel chiral ligand 4 was prepared from reaction of diphenylthiophosphinic chloride with (R)-(+)-1,1′-binaphthyl-2,2′-diamine using butyllithium as a base. They were used as catalytic chiral ligands in the silver(I)-promoted enantioselective allylation reaction of aldehydes with allyltributyltin.     

Asymmetric cyanosilylation of ketones catalyzed by novel chiral N,N′-dioxide titanium complexes

A novel C₂-symmetric chiral N,N′-dioxide titanium complex was described, which could efficiently catalyze the asymmetric cyanosilylation of ketones in high yields with up to 92% ee under mild conditions. In addition, the catalyst system was simple and the ligands could be easily prepared from commercially available chiral amino acid.     

New C2-symmetrical ferrocenyl diamines as ligands for ruthenium catalyzed transfer hydrogenation

The new C₂-symmetrical ferrocenyl diamines 5–7 and 13 proved to be good ligands for the ruthenium catalyzed enantioselective transfer hydrogenation of unsymmetrical ketones. The stereocontrolled and highly flexible synthetic route to the new diamines made it possible to vary the ligand structure in an efficient manner. A short trial and error process led to a very active catalytic system with diamine 6a as the ligand, which is capable of reducing ketones even at −30°C using 2-propanol as a hydrogen source. Enantioselectivities up to 90% were reached in the reduction of 1′-acetonaphthone.     

The synthesis and application of novel C2-symmetric chiral N,N,O,O bisoxazoline ligands with a ferrocene backbone

Novel C₂-symmetric bisoxazoline ligands 5 with a ferrocene backbone and a hydroxyl group at the substituent of the oxazoline ring were designed and prepared. With these ligands, up to 94% ee was obtained for the alkylation of arylaldehyde with diethylzinc.     

New C2-symmetric bis(sulfonamide)-cyclohexane-1,2-diamine-RhCp complex and its application in the asymmetric transfer hydrogenation (ATH) of ketones in water

C₂-symmetric bis(sulfonamide) ligands derived from trans-(1R,2R)-cyclohexane-1,2-diamine were synthesized and complexed with [Cp^∗RhCl₂]₂ in situ and used in the ATH of aromatic ketones with aqueous sodium formate as the hydrogen source. The chiral secondary alcohols were obtained with 90-99% enantioselectivity and in 50-100% yield. Reductions in water were faster than those in isopropanol/KOH.     

Malonate-type bis(oxazoline) ligands with sp hybridized bridge carbon: synthesis and application in Friedel-Crafts alkylation and allylic alkylation

A series of simple and new C₂-symmetric diphenylmethylidene malonate-type bis(oxazoline) ligands were synthesized and applied to the Friedel-Crafts reaction and allylic alkylation. The Cu(II) complex of ligand 4b bearing the benzyl group afforded good to excellent enantioselectivity for the F-C adducts (up to >99% ee) between indole and alkylidene malonate, and the palladium complex of ligand 4c bearing the phenyl group afforded excellent enantioselectivity (up to 94% ee) for the allylic alkylation product.     

Bifunctional pyridyl alcohols with the bicyclo[3.3.0]octane scaffold in the asymmetric addition of diethylzinc to aldehydes

Some new pyridyl alcohols with the cis-bicyclo[3.3.0]octane scaffold were synthesized and used as chiral ligands for the enantioselective addition of diethylzinc to aldehydes. Ligands 4 were found to be far superior to the C₂-symmetric ligands 2 in terms of enantioselectivities. Quantitative yields and enantiomeric excesses of up to 92% were obtained when the ligand 4 was used. The carbonyl function in 4 proved to be beneficial for the high enantioselectivities in the addition of diethylzinc to aldehydes. Conversion of the carbonyl group into oxime or oxime ether group led to a sort of more active ligands, which catalyzed the same reaction with rate acceleration.     

Axially dissymmetric binaphthyldiimine chiral salen-type ligands for copper-catalyzed asymmetric aziridination

Axially dissymmetric chiral salen-type ligands 1–4 and 7 were prepared from the reaction of (R)-(+)-1,1′-binaphthyl-2,2′-diamine with 2,6-dichlorobenzaldehyde, 2,3-dichlorobenzaldehyde, 3,4-dichlorobenzaldehyde or salicylaldehyde in high yields, respectively. The catalytic asymmetric aziridination of alkenes has been examined using these novel chiral ligands. Excellent enantioselectivity in the aziridination of cinnamates has been achieved using the C₂-symmetric chiral ligand 1.     

Axially chiral C2-symmetric N-heterocyclic carbene (NHC) palladium complexes-catalyzed asymmetric arylation of aldehydes with arylboronic acids

Chiral C₂-symmetric N-heterocyclic carbene (NHC) palladium diaquo complexes 5a–c and the chiral C₂-symmetric NHC-palladium complexes 5d and 5e prepared from (R)-BINAM or H₈-(R)-BINAM could be used as the catalysts for the enantioselective arylation of arylaldehydes with arylboronic acids in which NHC-Pd complex 5a was found to be fairly effective in this reaction to give the corresponding adducts in moderate enantioselectivities along with moderate to good yields.