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.     

A novel,C2-symmetric,chiral bis-cyclosulfinamide-olefin tridentate ligand in Rh-catalyzed asymmetric 1,4-additions

A C₂-symmetric, chiral bis-cyclosulfinamide-olefin ligand composed of two 1-oxo-2,3-dihydro-1,2-benzisothiazole moieties with rigid skeletons and a conformationally flexible butenylene chain is disclosed for the first time. HRMS and ¹H NMR analyses verify that the in situ-generated complex of the ligand and [Rh(C₂H₄)₂Cl]₂ possesses a rhodium (I) center coordinated to the tridentate ligand via two sulfinyl moieties and a CdbndC bond. The chiral ligand provided extremely high enantioselectivity (up to >99%ee) in the Rh-catalyzed asymmetric 1,4-additions of arylboronic acids to cyclohexenone and cyclopentenone. The tridentate ligand gave much higher enantioselectivity than the analogous chiral bidentate ligands.     

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.     

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.     

Exploiting the Chiral Ligands of Bis(imidazolinyl)- and Bis(oxazolinyl)thiophenes—Synthesis and Application in Cu-Catalyzed Friedel–Crafts Asymmetric Alkylation

Five new C₂-symmetric chiral ligands of 2,5-bis(imidazolinyl)thiophene (L1–L3) and 2,5-bis(oxazolinyl)thiophene (L4 and L5) were synthesized from thiophene-2,5-dicarboxylic acid (1) with enantiopure amino alcohols (4a–c) in excellent optical purity and chemical yield. The utility of these new chiral ligands for Friedel–Crafts asymmetric alkylation was explored. Subsequently, the optimized tridentate ligand L5 and Cu(OTf)₂ catalyst (15 mol%) in toluene for 48 h promoted Friedel–Crafts asymmetric alkylation in moderate to good yields (up to 76%) and with good enantioselectivity (up to 81% ee). The bis(oxazolinyl)thiophene ligands were more potent than bis(imidazolinyl)thiophene analogues for the asymmetric induction of the Friedel–Crafts asymmetric alkylation.     

1,1′-Spirobiindane-7,7′-diol: a novel,C2-symmetric chiral ligand

A novel, C₂-symmetric chiral diol (16) was prepared in six steps from m-anisaldehyde and resolved via its bis-l-menthoxycarboxylate.     

Highly enantioselective copper-catalyzed conjugate addition of diethylzinc to cyclic enones with spirocyclic phosphoramidite ligands

A series of spirocyclic phosphoramidite ligands 6-9 with different substituents on the amine moiety were synthesized from the chiral spirocyclic diol (R)-5. These monodentate ligands have been applied in copper-catalyzed conjugate addition of diethylzinc to cyclic enones. Excellent enantioselectivities (up to 99% ee) can be achieved by the use of ligand (R,S,S)-9 bearing stereochemically matched structure derived from the C₂-symmetric (S,S)-bis(α-methylbenzyl)amine.     

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.     

Chiral C2-symmetric ligands containing two binaphthyl units linked by 2,2′-bipyridyl bridge in asymmetric catalysis

The catalytic activities of new chiral C₂-symmetric ligands 1–4 in the asymmetric alkylation of aromatic aldehydes with diethylzinc to give 1-arylpropanols are studied. In most cases, the yields were good and enantioselectivities up to 87% were observed. Copper-catalyzed cyclopropanation proceeded with ⩽51% enantioselectivity and ∼3:1 trans/cis-diastereoselectivity.     

Chiral thiophosphoramide and selenophosphoramide ligands in the Cu(I)-promoted catalytic enantioselective 1,3-dipolar cycloaddition reactions of azomethine ylides and pyrrole-2,5-dione derivatives

Chiral C₂-symmetric diphenylthiophosphoramide ligand L1 prepared from C₂-symmetric (1S,2S)-(−)-1,2-diphenylethylenediamine was found to be a fairly effective chiral ligand for Cu(I)-promoted 1,3-dipolar cycloaddition of imines and pyrrole-2,5-dione derivatives to give the corresponding adducts in moderate enantioselectivities and good yields.     

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.     

Chiroptical and conformational properties of (R)-1-phenylethylamine derivatives of persubstituted benzene

Chiral derivatives of 2,4,5,6-tetrachloro-1,3-dicyanobenzene 1 with one, two and three (R)-1-phenylethylamino ((R)-PEA) units 2–4 are prepared and their chiroptical and conformational properties discussed on the bases of the UV/CD, NMR and MM2 data. High polarity of the persubstituted benzene ring leads to peculiar UV and IR spectra of achiral model compounds 5–7, whereas relatively rigid conformations of the chiral analogues 2–4 are reflected in the CD spectra. Strong exciton coupling (EC) appears in the CD spectrum of pseudo-C₃-symmetric 4; this type of interaction seems not to be present in the C₁-symmetric 2 and C₂-symmetric 3. The absence of a molecular cleft in the chiral structures 2–4 could explain their inability to recognise the enantiomers of some racemates in the NMR experiment.     

Reactivity of 2-methylene-1,3-dicarbonyl compounds: catalytic enantioselective Diels–Alder reaction

The catalytic enantioselective Diels–Alder reaction of 1,1-dicarbonylethenes 3 with cyclopentadiene in the presence of Ti-TADDOLs, Mg–Ph-box and Mg–Ph-mox complexes was investigated. Although both exo- and enantioselectivity with Ti-TADDOL catalysts were poor, they were much improved using Mg–Ph-box or Mg–Ph-mox complexes as chiral catalysts. Thus, 3 was an efficient two-point binding dienophile and the non-C₂-symmetric Ph-mox 8 could be used as a chiral ligand.     

Induction of reversal chirality by C2-symmetric diamide linked-diphosphine ligands in catalytic asymmetric allylations

Bridging parts X between two amide skeletons of C₂-symmetric diphosphine ligands 1 were varied using various kinds of diacyl chlorides. The ligand 1c derived from phthaloyl chloride, which was remarkably effective in the asymmetric induction on palladium-catalyzed asymmetric allylic substitutions of 2-cyclohexenyl pivalate or acetate, exhibited a moderate level of enantioselectivity, 72% ee, in the transformations of 1,3-diphenyl-2-propenyl pivalate. The newly developed ligands 1g–i having one carbon spacers X demonstrated higher degrees of enantiomeric excess up to 93% ee. Interestingly, the present reactions catalyzed by Pd–1c–e,g–j complexes afforded the product 4 with the opposite absolute configuration S compared with the reactions using VALAP, which has the same chiral source as that of 1. The ligands 1a,b,f exhibited the induction of R configuration although the yields were very low. The production of S-4 was discussed on the basis of the Pr/Mr chirality model.     

Asymmetric Diels–Alder and ene reactions promoted by a Ti(IV) complex bearing a C2-symmetric tridentate ligand

A new Ti(IV) complex obtained from the C₂-symmetric amino diol (1R,5R)-3-aza-3-benzyl-1,5-diphenyl pentan-1,5-diol, (1R,5R)-1, is used effectively as a Lewis acid promoter in asymmetric Diels–Alder reactions. Using various Evans' oxazolidinones as dienophiles and cyclopentadiene as the diene high yields of the adducts with moderate enantioselectivity, under different reaction conditions are achieved. The effects of solvent, temperature and ligand on the enantioselectivity of the Diels–Alder products are reported. Molecular modelling studies provide an understanding of the diastereofacial selectivity of the Diels–Alder reactions. Asymmetric carbonyl-ene reactions between various glyoxylate esters and α-methyl styrene are also described.     

A new class of C2-symmetric diphosphine ligands derived from valine: remarkably diverse behavior in catalytic asymmetric transformations

A new C₂-symmetric diphosphine ligand 8a was readily prepared in one step by treatment of the synthetic precursor of VALAP, 7, with phthaloyl chloride. Remarkably high levels of asymmetric induction, over 99% ee, were achieved using 8a in palladium-catalyzed asymmetric allylic transformations of sterically less demanding cyclohexenyl substrates 9. The ligand system was easily extended to the development of analogous chiral auxiliaries 8b,c by the identical procedure but using isophthaloyl chloride and succinyl chloride. However, the ligands 8b,c exhibited much lower catalytic activity. In contrast to the asymmetric allylic substitutions, 8c demonstrated significant improvement of enantioselectivity, up to 64% ee, in rhodium-catalyzed asymmetric hydrosilylations of acetophenone 11a compared to 35% ee using 8a. In this way, the versatility of the present ligand system played an important role in variations of substrates and reaction types.     

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.     

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.     

Chiral C2-symmetric bisferrocenyldiamines as ligands for transition metal catalyzed asymmetric cyclopropanation and aziridination

A new series of chiral C₂-symmetric bisferrocenyldiimine 1 and bisferrocenyldiamines 2 and 3 proved to be efficient ligands for the copper(I)-catalyzed asymmetric cyclopropanation, cyclopropenation, and aziridination of alkenes and alkynes to give high diastereo- and enantioselectivity as well as high chemical yields. In some instances the enantiomeric excesses of cyclopropanated products are among the highest (>97% ee) ever reported. Comparative studies show that stereoselectivity depends highly on the steric variation both in the ligand and the substrate. Other transition metal complexes incorporating some of these ligands such as Ru(3c)Cl₂, [(NBD)Rh(2)]ClO₄, [Cu(2)(MeCN)₂]PF₆, and Pd(2)Cl₂ also demonstrated high enantioselectivity in cyclopropanation reactions.     

Enantioselective addition of organolithium reagents to imines mediated by C2-symmetric bis(aziridine) ligands

The C₂-symmetric bis(aziridine) ligands 1–5 have been screened in the enantioselective addition of organolithium reagents to imines. Ligand 1 (used in stoichiometric amounts) was found to be superior in terms of chemical yield and enantioselectivity, the best result being 90% yield and 89% e.e. in the addition of vinyllithium to imine 6a. Use of ligand 1 in substoichiometric amounts gave poorer yield and lower enantioselectivity. The enantioselectivity of the reaction was investigated as a function of substrate, reagent, stoichiometry and temperature, but no firm mechanistic conclusions could be drawn. Preliminary results with deuterium-labelled methyllithium indicate complexation/exchange processes involving ligand, reagent and substrate.