syn-Selective Asymmetric Mannich Reaction of Sulfonyl Imines with Iminoesters Catalyzed by the N,N,N-Tridentate Bis(imidazolidine)pyridine (PyBidine)-Cu(OTf)(2) Complex

Chiral ligand: The [PyBidine-Cu(OTf)(2) ] (Tf=trifluoromethanesulfonate) complex catalyzed the asymmetric Mannich reaction of sulfonyl imines and iminoesters to give the products in a high syn-selective manner. For both 4-toluene (Ts)- and 4-nitrophenylsulfonyl (Ns)-imines, the syn-adducts were obtained in up to 99?% ee.     

Chiral 2,6-bis(oxazolinyl)pyridine-rare earth metal complexes as catalysts for highly enantioselective 1,3-dipolar cycloaddition reactions of 2-benzopyrylium-4-olates

Significant levels of enantioselectivity were obtained in 1,3-dipolar cycloadditions of 2-benzopyrylium-4-olate generated from the Rh(2)(OAc)(4)-catalyzed decomposition of o-methoxycarbonyl-alpha-diazoacetophenone. This reaction utilized chiral 2,6-bis(oxazolinyl)pyridine (Pybox)--rare earth metal triflate complexes as chiral Lewis acid catalysts. The reactions with several benzyloxyacetaldehyde derivatives catalyzed by a Sc(III)--Pybox-i-Pr complex (10 mol %) proceeded smoothly to yield endo-adducts selectively with high enantioselectivity (up to 93% ee). For the reaction with benzyl pyruvate, the Sc(III)-Pybox-i-Pr complex (10 mol %) catalyzed the reaction effectively in the presence of trifluoroacetic acid (10 mol %) to yield an exo-adduct with both high diastereo- and enantioselectivity (94% ee). This catalytic system was efficiently applied to the reactions with several other alpha-keto esters with high exo- and enantioselectivities (up to 95% ee). In contrast to the reaction with carbonyl compounds, Yb(III)--Pybox-Ph complex (10 mol %) was found to be effective to obtain high enantioselectivity (96% ee) of diastereoselectively produced exo-cycloadduct in the reaction with 3-acryloyl-2-oxazolidinone.     

Ruthenium(II) Pyrazolyl-Pyridyl-Oxazolinyl Complex Catalysts for the Asymmetric Transfer Hydrogenation of Ketones

Lowering the ketone: Ru(II) complexes containing a chiral pyridyl-based 1H-pyrazolyl-oxazolinyl NNN ligand were synthesized and structurally characterized by X-ray crystallographic studies. These complex catalysts efficiently catalyzed the asymmetric transfer hydrogenation of ketones, reaching up to 99?%?ee for the desired products.     

Enantioselective diene Cyclization/Hydrosilylation catalyzed by optically active palladium bisoxazoline and pyridine-oxazoline complexes

A 1:1 mixture of (N-N)Pd(Me)Cl ?N-N = (S,S)-4,4'-dibenzyl-4,5,4', 5'-tetrahydro-2,2'-bisoxazoline (S,S-4a) and NaBAr(4) ?Ar = 3, 5-C(6)H(3)(CF(3))(2) (5 mol %) catalyzed the asymmetric cyclization/hydrosilylation of dimethyl diallylmalonate (2) and triethylsilane at -30 degrees C for 48 h to form an 8.1:1 mixture of the silylated carbocycle (S,S)-trans-1, 1-dicarbomethoxy-4-methyl-3-?(triethylsilyl)methylcyclop ent ane (S, S-3) (95% de, 72% ee) and dimethyl 3,4-dimethylcyclopentane-1, 1-dicarboxylate (S,S-6) in 64% combined yield. In comparison, a 1:1 mixture of the palladium pyridine-oxazoline complex (N-N)Pd(Me)Cl ?N-N = (R)-(+)-4-isopropyl-2-(2-pyridinyl)-2-oxazoline (R-5b) and NaBAr(4) (5 mol %) catalyzed the asymmetric cyclization/hydrosilylation of 2 and triethylsilane at -32 degrees C for 24 h to form carbocycle S,S-3 in 82% yield (>95% de, 87% ee) as the exclusive product. Asymmetric diene cyclization catalyzed by complex R-5b was compatible with a range of functional groups and produced carbocycles with up to 91% ee. The procedure also tolerated substitution at a terminal olefinic position and at the allylic position of the diene.     

Asymmetric epoxidation of conjugated olefins with dioxygen

A complex situation: Asymmetric epoxidation of conjugated olefins was achieved at room temperature using ruthenium complex 1 as the catalyst and air as the oxidant to give epoxides in up to 95?%?ee. When the product was acid sensitive, the reaction was carried out at 0?°C under oxygen.     

Enantioselective formation of tert-alkylamines by desymmetrization of 2-substituted serinols

Novel enantioselective desymmetrization of 2-substituted 2-amino-1,3-propanediols has been established to generate asymmetric quaternary carbon centers comprising an amino group. Enantioselective as well as chemical conversion proved to be greatly dependent on the protecting group of the amino group in the substrate, desymmetrizing reagent, base, solvent, and naturally, catalyst. The highly effective desymmetrization has been implemented by using N-benzoylated substrates with benzoyl chloride and triethylamine in the presence of tetraphenylbisoxazoline (24)-CuCl(2) complex in THF at ambient temperature. An extensive survey of catalysts revealed that dimethylmalonate-bridged bisoxazoline-CuCl(2) complexes were superior. Among them, the tetraphenylbisoxazoline (24)-CuCl(2) complex turned out to work most efficiently with a wide array of the substrates. All the examined substrates, with the exception of 2-phenylserinol 36, were desymmetrized in the presence of 24-CuCl(2) complex to give high enantioselectivities ranging from 85 to 95 % ee. Complementary use of the diisopropylbisoxazoline (22)-CuCl(2) complex has remedied the mediocre desymmetrization of 36 to give a significantly improved enantioselectivity from 63 to 83 % ee.     

Copper(II) complexes of 2-(pyridine-2-yl)imidazolidine-4-thione derivatives for asymmetric Henry reactions

The preparation of a new series of 2-(pyridine-2-yl)imidazolidine-4-thione derivatives is described. Their corresponding copper(II) complexes were found to be highly enantioselective catalysts for asymmetric Henry reactions (up to 98% ee). Immobilization of these complexes by anchoring onto Merrifield? resin with respect to their use as recyclable catalysts was subsequently performed. The heterogeneous catalysts prepared in this way were tested in the asymmetric Henry reactions and showed high catalytic activity; they can be easily recycled, although their enantioselectivities were only moderate (～50% ee).     

Dicationic [(BINAP)Pd(solvent)2]2+[TfO-]2: enantioselective hydroamination catalyst for alkenoyl-N-oxazolidinones

Dicationic (BINAP)palladium(II) complex induced high enantioselectiviies in the addition of primary (and secondary) aromatic amines to alpha,beta-unsaturated oxazolidinones (up to 93% ee).     

Enantioselective Michael additions on α,β-unsaturated N-acylated oxazolidin-2-ones using mild scandium triflate catalysis

The asymmetric conjugate addition of thiophenol to (E)-3-crotonoyloxazolidin-2-one catalysed by the scandium(III) triflate complex of Ph-PYBOX gave the corresponding adduct in 66% ee. Lanthanoid triflates gave lower enantioselectivities (?28% ee).     

Isopinocampheylborane derivatives with >99% ee via the DMAP complex

The complex 8 of isopinocampheylborane and p-(dimethylamino)pyridine (DMAP) can be obtained with >99% ee starting from alpha-pinene with 80-90% ee by hydroboration using DMAP.BH3 (5) activated by 5% iodine, or by the conventional hydroboration of alpha-pinene, followed by addition of DMAP. Purification of the air-stable 8 is readily accomplished by crystallization from methanol. Conversion of 8 into the trifluoroborate adduct 1 using KHF2 occurs without erosion of ee. Generation of the derived 2 in situ with TMSCl as the fluorophile also occurs with little, if any, loss of ee, as evidenced by the preparation of the salicaldimine complex 11 and the derived amino alcohol 12 with 94% ee overall.     

A chiral phenoxyamine magnesium catalyst for the enantioselective hydroamination/cyclization of aminoalkenes and intermolecular hydroamination of vinyl arenes

If Grignard had only known! A chiral magnesium complex catalyzes the intramolecular hydroamination/cyclization of aminoalkenes with high efficiency at temperatures as low as ?20?°C and enantioselectivities as high as 93?%?ee. The high activity of this system also allows the catalytic intermolecular anti-Markovnikov addition of pyrrolidine and benzylamine to vinyl arenes.     

Direct generation of nucleophilic chiral palladium enolate from 1,3-dicarbonyl compounds: catalytic enantioselective Michael reaction with enones

Generation of chiral palladium enolates from 1,3-dicarbonyl compounds with the palladium aqua complex and its application to the highly efficient catalytic enantioselective Michael reaction with enones are described. The palladium aqua complexes are likely to supply Br?nsted base and Br?nsted acid successively during the reaction. The former activates the carbonyl compounds to give chiral palladium enolates, and the latter cooperatively activates enones. Using a catalytic amount (2-10 mol %) of the palladium complexes, the various 1,3-dicarbonyl compounds including diketones and beta-ketoesters were converted to the desired Michael adducts in good yields (69-92%) with excellent enantiomeric excesses (89-99% ee).     

Enantiocontrolled synthesis of spirooxindoles based on the [5 + 2] cycloaddition of a Tp(CO)(2)Mo(pyridinyl) scaffold (Tp = hydridotrispyrazolylborate)

[structure] A [5 + 2] cycloaddition of the pyridinyl pi-complex (-)-1 (98% ee) to methyleneoxindole 2 afforded the spirooxindole complex (-)-3 in high enantiomeric purity. Complex (-)-3 was converted to pyrrolidine (-)-8 (97% ee), which is related to potent cytotoxic analogues of the spirotryprostatins alkaloids.     

Enantioselective addition of allyltin reagents to amino aldehydes catalyzed with bis(oxazolinyl)phenylrhodium(III) aqua complexes

Bis(oxazolinyl)phenylrhodium(III) aqua complexes, (Phebox)RhX?(H?O) [X = Cl, Br], were found to be efficient Lewis acid catalysts for the enantioselective addition of allyl- and methallyltributyltin reagents to amino aldehydes. The reactions proceed smoothly in the presence of 5-10 mol % of (Phebox)RhX?(H?O) complex at ambient temperature to give the corresponding amino alcohols with modest to good enantioselectivity (up to 94% ee).     

Asymmetric cycloaddition reactions of diazoesters with 2-alkenoic acid derivatives catalyzed by binaphthyldiimine-Ni(II) complexes

The catalytic activity of chiral binaphthyldiimine (BINIM)-Ni(II) complexes for asymmetric enantioselective diazoalkane cycloadditions of ethyl diazoacetate with 3-acryloyl-2-oxazolidinone and 2-(2-alkenoyl)-3-pyrazolidinone derivatives was evaluated. The cycloadditions of 3-acryloyl-2-oxazolidinone and its 5,5-dimethyl derivative, in the presence of the BINIM-Ni(II) complex (10 mol %; prepared from (R)-BINIM-4Ph-2QN (ligand C) and Ni(ClO(4))(2)·6H(2)O) afforded 2-pyrazolines having a methine carbon substituted with an oxazolidinonyl group in moderate ratios (70:30 to 72:28), along with high enantioselectivities (90-92% ee) via 1,3-proton migration. On the basis of the investigations on the counteranions of the Ni(II) complex, the N-substituent of pyrazolidinone, and reaction temperatures, the optimal enantioselectivity (97% ee) and ratio (85:15) of 2-pyrazoline were obtained for the reaction of 2-acryloyl-1-benzyl-5,5-dimethyl-3-pyrazolidinone in the presence of (R)-BINIM-4Ph-2QN-Ni(II) ((R)-C/Ni(II)) complex prepared using Ni(BF(4))(2)·6H(2)O. In the cases of 1-benzyl-2-crotonoyl-5,5-dimethyl-3-pyrazolidinone, 1-benzyl-2-(2-butenoyl)-5,5-dimethyl-3-pyrazolidinone, and 1-benzyl-5,5-dimethyl-2-(3-ethoxycarbonyl)propenoyl-3-pyrazolidinone, the use of the (R)-BINIM-2QN-Ni(II) ((R)-A/Ni(II)) complex gave good to high enantioselectivities (85-93% ee) with the sole formation of the 2-pyrazoline having a methine carbon substituted with a pyrazolidinonyl group. Relatively good enantioselectivity (77% ee) was observed for the reaction between 2-acryloyl-5,5-dimethyl-1-naphthylmethyl-3-pyrazolidinone and an α-substituted diazo ester, ethyl 2-diazo-3-phenylpropanoate, which has yet to be employed as a diazo substrate in asymmetric cycloaddition reactions catalyzed by a chiral Lewis acid.     

C2-Symmetric 4,4′,5,5′-Tetrahydrobi(oxazoles) and 4,4′,5,5′-Tetrahydro-2,2′-methylenebis[oxazoles] as Chiral Ligands for Enantioselective Catalysis Preliminary Communication

The synthesis of a series of enantiomerically pure, C₂-symmetric 4,4′,5,5′-tetrahydro-2,2′-methylenebis[oxazoles] and 4,4′,5,5′-tetrahydro-2,2′-bi(oxazoles) is reported. Copper complexes with anionic tetrahydromethylenebis[oxazole] ligands are efficient catalysts for the enantioselective cyclopropane formation from olefins and diazo compounds (up to 96% ee in the reaction of styrene with menthyl diazoacetate). Tetrahydrobi(oxazole)iridium(I) complexes were found to catalyze transfer hydrogenations of aryl alkyl ketones with i-PrOH (up to 91% ee). Tetrahydrobi(oxazole)palladium complexes can be used as enantioselective catalysts for allylic nucleophilic substitution (up to 77% ee in the reaction of PhCH?CHCH(OAc)Ph with NaHC(COOMe)₂).     

Cu(ii)/SPDO complex catalyzed asymmetric Baeyer–Villiger oxidation of 2-arylcyclobutanones and its application for the total synthesis of eupomatilones 5 and 6

A novel classical kinetic resolution of 2-aryl-substituted or 2,3-disubstituted cyclobutanones of Baeyer–Villiger oxidation catalyzed by a Cu(ii)/SPDO complex is reported for the first time, producing normal lactones in excellent enantioselectivities (up to 96% ee) and regioselectivities (up to >20/1), along with unreacted ketones in excellent enantioselectivities (up to 99% ee). The current transformation features a wide substrate scope. Moreover, catalytic asymmetric total syntheses of natural eupomatilones 5 and 6 are achieved in nine steps from commercially available 3-methylcyclobutan-1-one.

A novel classical kinetic resolution of Baeyer–Villiger oxidation catalyzed by a Cu(ii)/SPDO complex with excellent enantioselectivity, regioselectivity and wide substrate scope is reported for the first time and explore the synthetic application.     

Iridium-catalyzed asymmetric allylation of sodium triisopropylsilanethiolate: a new way to form chiral thiols

The iridium phosphoramidite complex-promoted regio- and enantioselective reaction of allylic carbonates with sodium triisopropylsilanethiolate produced allylic sulfides in 40-77% yields with up to 97 : 3 (branched?:?linear) and 89% ee, which were readily transformed into chiral thiol in 68% yield with 87% ee or disulfides with two chiral C-S bond centers in 40-73% yields with up to 90 : 10 dr and 99% ee.     

Asymmetric iodocyclization catalyzed by salen-CrIIICl: its synthetic application to swainsonine

The previously developed enantioselective iodocyclization of gamma-hydroxy-cis-alkenes required 30 mol% of (R,R)-salen-Co(II) complex as chiral catalyst and 0.75 equivalent of N-chlorosuccinimide (NCS) as activator to produce 2-substituted tetrahydrofurans with 61 to 90% ee. Due to the considerable loading amount of the Co(II) complex, another more effective catalyst was pursued by screening (R,R)-salen-transition metal complexes. When 10 mol% of the catalysts were applied with 0.5 equivalent of NCS, a higher level of stereoselectivity was attained with the corresponding Cr(III)Cl (84% ee), Mn(II)Cl (52% ee) and Co(II) complexes (66% ee). Refinement of the conditions established a novel catalytic enantioselective iodocyclization protocol using iodine in the presence of 7 mol% of (R,R)-salen-Cr(III)Cl complex activated by 0.7 equivalent of NCS in toluene to induce 74 to 93% ee.     

Enantioselective Addition of Cyclic Enol Silyl Ethers to 2-Alkenoyl-Pyridine-N-Oxides Catalysed by Cu(II) -Bis(oxazoline) Complexes

Asymmetric reactions involving (E)-3-aryl-1-(pyridin-2-yl-N-oxide)prop-2-en-1-ones and cyclic enol silyl ethers show good yields and excellent enantioselectivities (up to 99.9?% ee) when catalysed by bis(oxazoline)-Cu(II) complexes. Different reaction pathways can be followed by different enol silyl ethers: with 2-(trimethylsilyloxy)furan, a Mukaiyama-Michael adduct is obtained, whereas a hetero Diels-Alder cycloadduct was formed by using (1,2-dihydronaphthalen-4-yloxy)trimethylsilane. In the latter reaction, the absolute configuration of the product is consistent with a reagent approach to the less hindered Re face of the coordinated substrate in the reactive complex.