Catalytic Asymmetric Ring‐Opening Reactions of Aziridines with 3‐Aryl‐Oxindoles

A highly enantioselective ring‐opening alkylation reaction between 3‐aryl‐oxindole and N‐(2‐picolinoyl) aziridine has been realized for the first time. The reaction is efficiently mediated by a simple in‐situ‐generated magnesium catalyst and 3,3′‐fluorinated‐BINOL (BINOL=1,1′‐binaphthalene‐2,2′‐diol) has been identified as a powerful chiral ligand. Notably, the fluorine atom on the chiral ligand plays a key role in providing the desired chiral 3‐alkyl‐3‐aryl oxindoles with excellent enantioselectivities.     

Synthesis of (+) or (-)-2-(8′-Diphenylphosphino-1′-naphthyl)oxazoline Ligands and Their Application in Pd-Catalyzed Allylic Alkylation Reaction

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Synthesis of 1,3‐thiazole and 1,2,4‐oxadiazole substituted spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐diones

Some new derivatives of spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐dione with the heterocyclic ring such as substituted thiazole and 1,2,4‐oxadiazole attached to the indolinone ring via CH₂ linkage has been synthesized in moderate yields. The synthesis have been carried out by making use of the reactivity of the NH group of the indolinone moiety present in spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐dione.     

Efficient asymmetric addition of diethylzinc to aldehydes using C2‐novel chiral pyridine β‐amino alcohols as chiral ligands

A series of novel C₂‐symmetric chiral pyridine β‐amino alcohol ligands have been synthesized from 2,6‐pyridine dicarboxaldehyde, m‐phthalaldehyde and chiral β‐amino alcohols through a two‐step reaction. All their structures were characterized by ¹H NMR, ¹³C NMR and IR. Their enantioselective induction behaviors were examined under different conditions such as the structure of the ligands, reaction temperature, solvent, reaction time and catalytic amount. The results show that the corresponding chiral secondary alcohols can be obtained with high yields and moderate to good enantiomeric excess. The best result, up to 89% ee, was obtained when the ligand 3c (2S,2′R)‐2,2′‐((pyridine‐2,6‐diylbis(methylene))bisazanediyl))bis(4‐methyl‐1,1‐diphenylpentan‐1‐ol) was used in toluene at room temperature. The ligand 3g (2S,2′R)‐2,2′‐((1,3‐phenylenebis(methylene))bis(azanediyl))bis(4‐methyl‐1,1‐diphenylpentan‐1‐ol) was prepared in which the pyridine ring was replaced by the benzene ring compared to 3c in order to illustrate the unique role of the N atom in the pyridine ring in the inductive reaction. The results indicate that the coordination of the N atom of the pyridine ring is essential in the asymmetric induction reaction. Copyright © 2014 John Wiley & Sons, Ltd.     

Solvent‐ and Temperature‐Controlled In Situ Ligand Reactions Mediated by CuII and 3′‐[(E)‐{[(1S,2S)‐2‐Aminocyclohexyl]imino}methyl]‐4′‐hydroxy‐4‐biphenylcarboxlic Acid

Three new compounds, CuL, CuL′, and Cu₂O₂L′′₂ (H₂L=3′‐[(E)‐{[(1S,2S)‐2‐aminocyclohexyl]imino}methyl]‐4′‐hydroxy‐4‐biphenylcarboxlic acid, H₂L′=3′‐[(E)‐{[(1S,2S)‐2‐aminocyclohexyl]imino}methyl]‐4′‐hydroxy‐5′‐nitro‐4‐biphenylcarboxlic acid, H₂L′′=3′‐(N,N‐dimethylamino methyl)‐4′‐hydroxy‐4‐biphenylcarboxlic acid), were selectively synthesized through a controlled in situ ligand reaction system mediated by copper(II) nitrate and H₂L. Selective nitration was achieved by using different solvent mixtures under relatively mild conditions, and an interesting and economical reductive amination system in DMF/EtOH/H₂O was also found. All crystal structures were determined by single‐crystal X‐ray diffraction analysis. Both CuL and CuL′ display chiral 1D chain structures, whereas Cu₂O₂L′′₂ possesses a structure with 13×16 Å channels and a free volume of 41.4 %. The possible mechanisms involved in this in situ ligand‐controlled reaction system are discussed in detail.     

Configurational assignments of the diastereomers of 3,3′‐(1,2‐ethanediyl)bis[2‐(3‐fluorophenyl)‐5‐methyl‐4‐thiazolidinone] derivative with four stereogenic centers

Diastereomers of antiinflammatory/analgesic and antihistaminic 3,3′[(1,2‐ethanediyl)bis(2‐aryl‐4‐thiazo‐lidinone)] derivatives possessing two stereogenic centers (indicated as BIS 2*C) have been widely investigated in recent years. The 5,5′‐dimethyl analogues (BIS 4*C), now reported, have been synthesized by reaction of (±) α‐mercaptopropionic acid and N,N'‐di(3‐fluorobenzyliden)ethylenediamine. Because the 2 and 2′carbons bear the same groups and similarly the 5 and 5′ carbons, and the latter groups are different from the former, four enantiomeric pairs and two meso forms exist in this situation. These diastereomers were identified by the concerted use of nmr spectroscopy and hplc on chiral stationary phase.     

Design and Catalytic Asymmetric Construction of Axially Chiral 3,3′‐Bisindole Skeletons

The first catalytic asymmetric construction of 3,3′‐bisindole skeletons bearing both axial and central chirality has been established by organocatalytic asymmetric addition reactions of 2‐substituted 3,3′‐bisindoles with 3‐indolylmethanols (up to 98 % yield, all >95:5 d.r., >99 % ee). This reaction also represents the first highly enantioselective construction of axially chiral 3,3′‐bisindole skeletons, and utilizes the strategy of introducing a bulky group to the ortho‐position of prochiral 3,3′‐bisindoles. This reaction not only provides a good example for simultaneously controlling axial and central chirality in one operation, but also serves as a new strategy for catalytic enantioselective construction of axially chiral 3,3′‐bisindole backbones from prochiral substrates.     

Synthesis of New Heterocyclic Compounds Using 2‐(3,3‐dimethyl‐1H‐pyrroloisoquinolin‐2(3H)‐ylidene)malonaldehydes

Isoquinolin‐5‐ylhydrazinium chloride 13 and 5‐bromoisoquinolin‐8‐ylhydrazinium chloride 14 were converted via Fischer syntheses with 3‐methylbutan‐2‐one into indolenines, 2,3,3‐trimethyl‐3H‐pyrrolo[2,3‐f]isoquinoline 15 and 5‐bromo‐2,3,3‐trimethyl‐3H‐pyrrolo[3,2‐h]isoquinoline 16 , respectively. Exposure of the indolenines to the Vilsmeier reagent produced diformyl compounds 17 and 18 , which reacted with arylhydrazines to give the corresponding pyrazoles 19a , 19b , 19c , 19d , 19e , 19f , 19g , 19h , 19i and 20a , 20b , 20c , 20d , 20e , 20f , 20g . Reaction of 17 with thiourea gave a pyrimidine‐2(1H)‐thione 23 or with hydroxylamine hydrochloride, an isoxazole 24 .     

Asymmetric Hydroformylation of 4‐Vinyl‐1,3‐dioxolan‐2‐one

A chiral cyclic carbonate, 4‐vinyl‐1,3‐dioxolan‐2‐one was used as racemic substrate in asymmetric hydroformylation. The catalysts were formed in situ from “pre‐formed” PtCl₂(diphosphine) and tin(II) chloride. (2S,4S )‐2,4‐Bis(diphenylphosphinopentane ((S,S )‐BDPP)), (S,S )‐2,3‐O‐izopropylidine‐2,3‐dihydroxy‐1,4‐bis(diphenylphosphino)butane ((S,S )‐DIOP)), and (R )‐2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl ((R )‐BINAP)) were used as optically active diphosphine ligands. The platinum‐containing catalytic systems provided surprisingly high activity. The hydroformylation selectivities of up to 97% were accompanied by perfect regioselectivity towards the dioxolane‐based linear aldehyde. The enantiomeric composition of all components in the reaction mixture was determined and followed throughout the reaction. The unreacted 4‐vinyl‐1,3‐dioxolan‐2‐one was recovered in optically active form. The kinetic resolution was rationalized using the enantiomeric composition of the substrate and the products.     

Synthesis of Chiral 2,5—Bis（oxazolinyl） thiophenes and Their Application as Chiral Shift Reagents for 1,1′—Bi—2—naphthol

A series of C2-symmetrical chiral 2,5-bis (4′-alkyloxazolin-2-yl) thiophenes (thiobox) have been synthesized from thiophene-2,5-dicarboxylic acid by sequential amidation with a chiral ethanolamine,conversion of hydroxyl to chloro group, and base-promoted oxazoline ring formation.As demonstrated by (-)-2,5-bis[4′-(S)-isopropyloxazolin-2′-yl] thiophene,these thiobox systems exhibited remarkable chirality recognition of 1,1′-bi-2-naphthol giving rise to pronounced shifts in the ^1H NMR signals of the latter axial chiral compound at the positions of C-3,C-4,C-5,and C-8.     

An Imidazoline–Aminophenol (IAP) Nickel Catalyst: Structure and Catalytic Activity in the Enantioselective 1,4‐Addition of 3′‐Indolyl‐3‐Oxindoles to Nitroethylene

The structure of a nickel complex of imidazoline–aminophenol (IAP) prepared from IAP with Ni(OAc)₂ was elucidated as cis‐bis(imidazolineaminophenoxide) [Ni(IAP)₂]. The [Ni(IAP)₂] complex smoothly promoted catalytic asymmetric 1,4‐addition of 3′‐indolyl‐3‐oxindole to nitroethylene to provide chiral mixed 3,3′‐bisindoles with high enantioselectivities. Mechanistic studies using ESI‐MS analyses suggest that one IAP ligand dissociated from [Ni(IAP)₂] to generate the Ni–enolate of 3′‐indolyl‐3‐oxindole. From the optically active 3,3′‐mixed indole adduct, biologically important 3′‐indolyl‐3‐pyrrolidinoindoline was successfully synthesized in a three‐step reaction sequence.     

Quinolone Analogs 13: Synthesis of Novel 1,1′‐(2‐Methylenepropane‐1,3‐diyl)di(4‐quinolone‐3‐carboxylate) and Related Compounds

The reaction of the 4‐hydroxyquinoline‐3‐carboxylate 6 with pentaerythritol tribromide gave the 1,1′‐(2‐methylenepropane‐1,3‐diyl)di(4‐quinolone‐3‐carboxylate) 11 , whose reaction with bromine afforded the 1,1′‐(2‐bromo‐2‐bromomethylpropane‐1,3‐diyl)di(4‐quinolone‐3‐carboxylate) 12 . Compound 12 was transformed into the (Z)‐1,1′‐(2‐acetoxymethylpropene‐1,3‐diyl)di(4‐quinolone‐3‐carboxylate) 13 or (E)‐1,1′‐[2‐(imidazol‐1‐ylmethyl)propene‐1,3‐diyl]di(4‐quinolone‐3‐carboxylate) 14 . Hydrolysis of the dimer (Z)‐ 13 or (E)‐ 14 with potassium hydroxide provided the (E)‐1,1′‐(2‐hydroxymethylpropene‐1,3‐diyl)di(4‐quinolone‐3‐carboxylic acid) 15 or (Z)‐1,1′‐[2‐(imidazol‐1‐ylmethyl)propene‐1,3‐diyl]di(4‐quinolone‐3‐carboxylic acid) 16 , respectively. The nuclear Overhauser effect (NOE) spectral data supported that those hydrolysis resulted in the geometrical conversion of (Z)‐ 13 into (E)‐ 15 or (E)‐ 14 into (Z)‐ 16 .     

Silica Hybrid Containing （ R ）-2, 2＇-Binaphtho-20-crown-6 Moieties via the Sol-Gel Process

(R)-6,6‘-Bis(triethoxysilylethen-2-yl)-2,2-‘binaphtho-20-crown-6(precursor,R-2) derived form(R)-2,2-BINOL derivative was synthesized by Pd-catelyzed Heck reaction of (R)-6-6‘-dibromo-2,2‘-binaphtoh-20-crown-6(R-1) intermediate with vinyltriethoxysilane. The hydrolysis and polycondensatlon ofthe precursor gave rise to the corresponding xerogei. Both pre cursor and xerogei were analysed by NMR, FT-IR, UV, CD spectra, fluorescent spectroscopy, polarimetry and elemental analysis. The precursor and xerogei can emit strong blue fluorescenee and are expected to have the potential appficatiou inthe separation of chiral molecules as fluorescent sensor. The precursor exhibits strong Cotton effect in its circular dichroism (CD) spectrum indicating that it is a highly rigid structure.     

The amplified circularly polarized luminescence emission response of chiral 1,1′‐binaphthol‐based polymers via Zn(II)‐coordination fluorescence enhancement

Two kinds of chiral 1,1′‐binaphthol (BINOL)‐based polymer enantiomers were designed and synthesized by the polymerization of 5,5′‐((2,2′‐bis (octyloxy)‐[1,1′‐binaphthalene]‐3,3′‐diyl)bis(ethyne‐2,1‐diyl))bis(2‐hydroxybenzaldehyde) ( M1 ) with alkyl diamine ( M2 ) via nucleophilic addition–elimination reaction. The resulting chiral polymers can exhibit mirror image cotton effects either in the absence or in the presence of Zn²⁺ ion. Almost no fluorescence or circularly polarized luminescence (CPL) emission could be observed for two chiral BINOL‐based polymer enantiomers in the absence of Zn²⁺. Interestingly, the chiral polymers can show strong fluorescence and CPL response signals upon the addition of Zn²⁺, which can be attributed to Zn²⁺‐coordination fluorescence enhancement effect. This work can develop a new strategy on the design of the novel CPL materials via metal‐coordination reaction. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1282–1288     

5‐Hydroxyalkyl derivatives of tert‐butyl 2‐oxo‐2,5‐dihydro‐1H‐pyrrole‐1‐carboxylate: diastereoselectivity of the Mukaiyama crossed‐aldol‐type reaction

The title compounds, rac‐(1′R,2R)‐tert‐butyl 2‐(1′‐hydroxyethyl)‐3‐(2‐nitrophenyl)‐5‐oxo‐2,5‐dihydro‐1H‐pyrrole‐1‐carboxylate, C₁₇H₂₀N₂O₆, (I), rac‐(1′S,2R)‐tert‐butyl 2‐[1′‐hydroxy‐3′‐(methoxycarbonyl)propyl]‐3‐(2‐nitrophenyl)‐5‐oxo‐2,5‐dihydro‐1H‐pyrrole‐1‐carboxylate, C₂₀H₂₄N₂O₈, (II), and rac‐(1′S,2R)‐tert‐butyl 2‐(4′‐bromo‐1′‐hydroxybutyl)‐5‐oxo‐2,5‐dihydro‐1H‐pyrrole‐1‐carboxylate, C₁₃H₂₀BrNO₄, (III), are 5‐hydroxyalkyl derivatives of tert‐butyl 2‐oxo‐2,5‐dihydropyrrole‐1‐carboxylate. In all three compounds, the tert‐butoxycarbonyl (Boc) unit is orientated in the same manner with respect to the mean plane through the 2‐oxo‐2,5‐dihydro‐1H‐pyrrole ring. The hydroxyl substituent at one of the newly created chiral centres, which have relative R,R stereochemistry, is trans with respect to the oxo group of the pyrrole ring in (I), synthesized using acetaldehyde. When a larger aldehyde was used, as in compounds (II) and (III), the hydroxyl substituent was found to be cis with respect to the oxo group of the pyrrole ring. Here, the relative stereochemistry of the newly created chiral centres is R,S. In compound (I), O—H...O hydrogen bonding leads to an interesting hexagonal arrangement of symmetry‐related molecules. In (II) and (III), the hydroxyl groups are involved in bifurcated O—H...O hydrogen bonds, and centrosymmetric hydrogen‐bonded dimers are formed. The Mukaiyama crossed‐aldol‐type reaction was successful when using the 2‐nitrophenyl‐substituted hydroxypyrrole, or the unsubstituted hydroxypyrrole, and boron trifluoride diethyl ether as catalyst. The synthetic procedure leads to a syn configuration of the two newly created chiral centres in all three compounds.     

Diastereo‐ and Enantioselective Intramolecular [2+2] Photocycloaddition Reactions of 3‐(ω′‐Alkenyl)‐ and 3‐(ω′‐Alkenyloxy)‐Substituted 5,6‐Dihydro‐1H‐pyridin‐2‐ones

3‐(ω′‐Alkenyl)‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones 2 – 4 were prepared as photocycloaddition precursors either by cross‐coupling from 3‐iodo‐5,6‐dihydro‐1H‐pyridin‐2‐one ( 8 ) or—more favorably—from the corresponding α‐(ω′‐alkenyl)‐substituted δ‐valerolactams 9 – 11 by a selenylation/elimination sequence (56–62 % overall yield). 3‐(ω′‐Alkenyloxy)‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones 5 and 6 were accessible in 43 and 37 % overall yield from 3‐diazopiperidin‐2‐one ( 15 ) by an α,α‐chloroselenylation reaction at the 3‐position followed by nucleophilic displacement of a chloride ion with an ω‐alkenolate and oxidative elimination of selenoxide. Upon irradiation at λ=254 nm, the precursor compounds underwent a clean intramolecular [2+2] photocycloaddition reaction. Substrates 2 and 5 , tethered by a two‐atom chain, exclusively delivered the respective crossed products 19 and 20 , and substrates 3 , 5 , and 6 , tethered by longer chains, gave the straight products 21 – 23 . The completely regio‐ and diastereoselective photocycloaddition reactions proceeded in 63–83 % yield. Irradiation in the presence of the chiral templates (?)‐ 1 and (+)‐ 31 at ?75 °C in toluene rendered the reactions enantioselective with selectivities varying between 40 and 85 % ee. Truncated template rac‐ 31 was prepared as a noranalogue of the well‐established template 1 in eight steps and 56 % yield from the Kemp triacid ( 24 ). Subsequent resolution delivered the enantiomerically pure templates (?)‐ 31 and (+)‐ 31 . The outcome of the reactions is compared to the results achieved with 4‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones and quinolones.     

New Optically Active 2H‐Azirin‐3‐amines as Synthons for Enantiomerically Pure 2,2‐Disubstituted Glycines

The synthesis of novel 2,2‐disubstituted 2H‐azirin‐3‐amines with a chiral amino group is described. Chromatographic separation of the diastereoisomer mixture yielded the pure diastereoisomers (1′R,2R)‐ 4a – e and (1′R,2S)‐ 4a – e (Scheme 1, Table 1), which are synthons for the (R)‐ and (S)‐isomers of isovaline, 2‐methylvaline, 2‐cyclopentylalanine, 2‐methylleucine, and 2‐(methyl)phenylalanine, respectively. The configuration at C(2) of the synthons was determined by X‐ray crystallography relative to the known configuration of the chiral auxiliary group. The reaction of 4 with thiobenzoic acid, benzoic acid, and the dipeptide Z‐Leu‐Aib‐OH ( 12 ) yielded the monothiodiamides 10 , the diamides 11 (Scheme 2, Table 3), and the tripeptides 13 (Scheme 3, Table 4), respectively.     

γ′‐Selective Functionalization of Cyclic Enones: Construction of a Chiral Quaternary Carbon Center by [4+2] Cycloaddition/Retro‐Mannich Reaction with 3‐Substituted Maleimides

The first example of organocatalyzed γ′‐selective functionalization of cyclic enones with 3‐substituted maleimides results in the stereoselective construction quaternary carbon center is presented. The reactions provided γ′‐functionalized cyclic enones and β‐functionalized cyclopentenones in good to excellent yields with excellent diastereo‐ and enantioselectivities. DFT calculations indicated that the reaction might proceed as a [4+2] cycloaddition/retro‐Mannich reaction which could explain the unexpected product with a chiral quaternary carbon center and the excellent stereoselectivity.     

Asymmetric anionic polymerizations of 7‐cyano‐7‐alkoxycarbonyl‐1,4‐benzoquinone methides

Asymmetric anionic polymerizations of 7‐cyano‐7‐alkoxycarbonyl‐1,4‐benzoquinone methides ( 1 ) with various alkoxy groups were performed using chiral initiators such as lithium isopropylphenoxide (ⁱPrPhOLi)/(S)‐(–)‐2,2′‐isopropylidene‐bis(4‐phenyl‐2‐oxazoline) ((–)‐PhBox) and lithium isopropylphenoxide (ⁱPrPhOLi)/(–)‐sparteine ((–)‐Sp) to investigate the effect of the alkoxy groups of alkoxycarbonyl substituent in the monomers 1 and chiral ligands of chiral initiators on the control of chiral center in the formation of polymers. Molar optical rotation values of the polymers were significantly dependent upon alkoxy groups, and the polymers with higher molar optical rotation were obtained in monomers with primary alkoxy groups. The asymmetric anionic oligomerizations of the quinone methides having methoxy( 1a ), ethoxy( 1b ), and n‐propoxy( 1c ) groups with chiral initiators were carried out. Both 1‐mers and 2‐mers were isolated and their optical resolutions were performed to determine the extent of stereocontrol. High stereoselectivity was observed at the propagation reaction, but not at the initiation reaction. The effect of the counterion on the control of chiral center in the formation of the polymer was investigated in the asymmetric anionic polymerizations of 1b with ⁱPrPhOM(M = Li, Na, K)/(–)‐Sp and ⁱPrPhOM(M = Li, Na, K)/(–)‐PhBox initiators and discussed. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Engaging Allene‐Derived Zwitterions in an Unprecedented Mode of Asymmetric [3+2]‐Annulation Reaction

Catalytic addition of chiral phosphine, that is, (R)‐ or (S)‐SITCP, to an α‐substituted allene ester generated a zwitterionic dipole. Under optimized reaction conditions, this dipole could engage isatine‐derived N‐Boc‐ketimines in a novel mode of [3+2] annulation reaction. Pyrrolinyl spirooxindoles are thus afforded in high yields and with excellent enantioselectivities. The unprecedented annulation reaction successfully facilitated the construction of sp³‐rich and highly substituted 3,2′‐pyrrolidinyl spirooxindoles supporting many chiral centers.