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.     

Asymmetric Photochemical Synthesis of Chiral 5‐(R)‐(l)‐Menthyloxy‐4‐Cycloaminobutyrolactones

Through photocatalysed regiospecific and stereoselective additions of cycloamines to 5‐(R)‐(l)‐menthyloxy‐2 (5H)‐furanone (3), chiral 5‐(R)‐(l)‐menthyloxy‐4‐cycloaminobutyrolactones were synthesized. In the new asymmetric photoaddition of compound 3, the N‐methyl cyclic amines (4) gave novel chiral C? C photoadducts (5) in 24–50% isolated yields with d. e. ≥ 98%. However, the secondary cyclic amines (6) afforded optically active N? C photoadducts (7) in 34–58% isolated yields with d. e. ≥ 98% under the same condition. All the synthesized optically active compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]₅₈₉²⁰, IR, ¹H NMR, ¹³C NMR, MS and elementary analysis. The photosynthesis of chiral butyrolactones and its mechanism were discussed in detail.     

A Mild and Highly Efficient Synthesis of Chiral N‐Dichloroacetyl‐4‐ethyl‐1,3‐oxazolidines

Chiral 2‐amino‐butanols ( 4 and 5 ) were obtained via the isolation of diastereomeric salt. Then, chiral compounds ( 6 – 9) were synthesized by a sequential procedure involving condensation of chiral 2‐amino‐butanol with ketone and dichloroacetyl chloride. All the compounds were characterized by IR, ¹H NMR, ¹³C NMR, and element analysis. The absolute configurations of ( S )‐ 8 was determined by X‐ray crystallography.     

(R)‐2,3‐Cyclohexylideneglyceraldehyde,a Chiral Pool Synthon for the Synthesis of 2‐Azido‐1,3‐diols

A new approach was proposed for the synthesis of 2‐azido‐1,3‐diols from easily available and inexpensive chiral pool synthon (R)‐2,3‐O‐cyclohexylidene‐D ‐glyceraldehyde, through Mitsunobu azidation of 1,2‐diols. Both C(2) and C(1) azides in variable ratios were obtained in alkyl substituted diols with C(2) as the major one.     

Conjugate Addition of Lithiated (S)‐4‐Isopropyl‐3‐ [(methylthio)methyl]‐5,5‐diphenyloxazolidin‐2‐one to Cinnamoyl Derivatives: Preparation of Enantiomerically Pure 1,4‐Diols

The Li derivative of (S)‐4‐isopropyl‐3‐[(methylthio)methyl]‐5,5‐diphenyloxazolidin‐2‐one (Li‐ 2 ; synthetically equivalent to a chiral formyl anion) adds to enones and enoates in a 1,4‐fashion. Best results are obtained with 1,3‐diarylpropenones (chalcones; Scheme 2), trityl enones, and 2,6‐di(tert‐butyl)‐4‐methoxyphenyl cinnamates (Scheme 3), with yields up to 80% and diastereoselectivities up to and above 99 : 1 of the products ( 5a – f and 8a , b , e ) containing three stereogenic centers! X‐Ray crystal‐structure analysis reveals that the C,C‐bond formation occurs preferentially with relative topicity ul (Re/Si; Fig. 2). The MeS group of the 1,4‐adducts can be replaced by RO groups in Hg²⁺‐assisted substitutions, with subsequent removal and facile recovery of the chiral auxiliary (Schemes 4–6). 4‐Hydroxycarbonyl derivatives (‘homoaldols') and mono‐, di‐, and trisubstituted 1,4‐diols are, thus, accessible in enantiomerically pure forms (cf. 15, 16 , and 18 – 20 ).     

Weak C—H...O and C—H...π hydrogen bonds and π–π stacking interactions in a series of four N′‐[(E)‐(aryl)methylidene]‐N‐methyl‐2‐oxo‐1,3‐oxazolidine‐4‐carbohydrazides

Oxazolidin‐2‐ones are widely used as protective groups for 1,2‐amino alcohols and chiral derivatives are employed as chiral auxiliaries. The crystal structures of four differently substituted oxazolidinecarbohydrazides, namely N′‐[(E)‐benzylidene]‐N‐methyl‐2‐oxo‐1,3‐oxazolidine‐4‐carbohydrazide, C₁₂H₁₂N₃O₃, (I), N′‐[(E)‐2‐chlorobenzylidene]‐N‐methyl‐2‐oxo‐1,3‐oxazolidine‐4‐carbohydrazide, C₁₂H₁₂ClN₃O₃, (II), (4S)‐N′‐[(E)‐4‐chlorobenzylidene]‐N‐methyl‐2‐oxo‐1,3‐oxazolidine‐4‐carbohydrazide, C₁₂H₁₂ClN₃O₃, (III), and (4S)‐N′‐[(E)‐2,6‐dichlorobenzylidene]‐N,3‐dimethyl‐2‐oxo‐1,3‐oxazolidine‐4‐carbohydrazide, C₁₃H₁₃Cl₂N₃O₃, (IV), show that an unexpected mild‐condition racemization from the chiral starting materials has occurred in (I) and (II). In the extended structures, the centrosymmetric phases, which each crystallize with two molecules (A and B) in the asymmetric unit, form A+B dimers linked by pairs of N—H...O hydrogen bonds, albeit with different O‐atom acceptors. One dimer is composed of one molecule with an S configuration for its stereogenic centre and the other with an R configuration, and possesses approximate local inversion symmetry. The other dimer consists of either R,R or S,S pairs and possesses approximate local twofold symmetry. In the chiral structure, N—H...O hydrogen bonds link the molecules into C(5) chains, with adjacent molecules related by a 2₁ screw axis. A wide variety of weak interactions, including C—H...O, C—H...Cl, C—H...π and π–π stacking interactions, occur in these structures, but there is little conformity between them.     

Lipase‐Catalyzed Dynamic Kinetic Resolution of C1‐ and C2‐Symmetric Racemic Axially Chiral 2,2′‐Dihydroxy‐1,1′‐biaryls

We have discovered that the racemization of configurationally stable, axially chiral 2,2′‐dihydroxy‐1,1′‐biaryls proceeds with a catalytic amount of a cyclopentadienylruthenium(II) complex at 35–50 °C. Combining this racemization procedure with lipase‐catalyzed kinetic resolution led to the first lipase/metal‐integrated dynamic kinetic resolution of racemic axially chiral biaryl compounds. The method was applied to the synthesis of various enantio‐enriched C₁‐ and C₂‐symmetric biaryl diols in yields of up to 98 % and enantiomeric excesses of up to 98 %, which paves the way for new developments in the field of asymmetric synthesis.     

Organocatalytic Asymmetric Annulation of ortho‐Alkynylanilines: Synthesis of Axially Chiral Naphthyl‐C2‐indoles

A chiral Brønsted base catalyzed asymmetric annulation of ortho‐alkynylanilines has been developed to access axially chiral naphthyl‐C2‐indoles via vinylidene ortho‐quinone methide (VQM) intermediates. This strategy provides a unique organocatalytic atroposelective route to axially chiral aryl‐C2‐indole skeletons with excellent enantioselectivity and functional‐group tolerance. This transformation was applicable to decagram‐scale preparation (50.0 g) with perfect enantioselectivity through simple recrystallization. Moreover, the utility of this reaction was demonstrated by a variety of transformations towards chiral naphthyl‐C2‐indoles for a series of carbon–heteroatom bond formations. Furthermore, the prepared axially chiral naphthyl‐C2‐indoles were applied as a chiral skeleton for organocatalytic aza‐Baylis–Hillman reaction and asymmetric formal [4+2] tandem cyclization to give the corresponding adducts in high yields with improved enantioselectivity and diastereoselectivity.     

Synthesis of New Chiral Derivatives of N,N′‐Dimethylpropyleneurea (DMPU) and Examination of Their Influence on the Regio‐ and Enantioselectivity of Addition of 2‐(1,3‐Dithianyl)lithium to Cyclohex‐2‐en‐1‐one

The preparation of three new chiral derivatives of DMPU (N,N′‐dimethylpropyleneurea) is described (Schemes 2–4); one type of derivative carries 1‐phenylethyl or 1‐cyclohexylethyl groups at the N‐atoms of the tetrahydropyrimidin‐2(1H)‐one ring ( 2 and 4 ), another type of derivative is substituted at C(4) and C(6) of the heterocyclic ring ( 7 ). The potential of these chiral Lewis bases as promoters in the regio‐ and/or enantioselective addition of 2‐(1,3‐dithianyl)lithium to cyclohex‐2‐en‐1‐one was explored; they are all unable to effect enantioselective addition; the derivatives with branched substituents at the N‐atoms do not shift the addition mode from 1,2 to 1,4, while the 3,4,5,6‐tetrahydro‐1,3,4,6‐tetramethylpyrimidin‐2(1H)‐one does (Scheme 5). The results provide useful information regarding the nature of the nucleophilic organolithium reagent: obviously, the steric hindrance to Li complexation on the CO O‐atom of the tetrahydropyrimidin‐2(1H)‐one by branched substituents at N‐atoms (cf. X‐ray crystal structure of 2 in the Fig.) prevents solvent‐separated‐ion‐pair (SSIP) formation; this was confirmed by PM3 and B3LYP/3‐21‐G(d)//PM3 calculations (Scheme 6).     

Two pseudo‐enantiomeric forms of N‐benzyl‐4‐hydroxy‐1‐methyl‐2,2‐dioxo‐1H‐2λ6,1‐benzothiazine‐3‐carboxamide and their analgesic properties

The fact that molecular crystals exist as different polymorphic modifications and the identification of as many polymorphs as possible are important considerations for the pharmaceutic industry. The molecule of N‐benzyl‐4‐hydroxy‐1‐methyl‐2,2‐dioxo‐1H‐2λ⁶,1‐benzothiazine‐3‐carboxamide, C₁₇H₁₆N₂O₄S, does not contain a stereogenic atom, but intramolecular hydrogen‐bonding interactions engender enantiomeric chiral conformations as a labile racemic mixture. The title compound crystallized in a solvent‐dependent single chiral conformation within one of two conformationally polymorphic P2₁2₁2₁ orthorhombic chiral crystals (denoted forms A and B). Each of these pseudo‐enantiomorphic crystals contains one of two pseudo‐enantiomeric diastereomers. Form A was obtained from methylene chloride and form B can be crystallized from N,N‐dimethylformamide, ethanol, ethyl acetate or xylene. Pharmacological studies with solid–particulate suspensions have shown that crystalline form A exhibits an almost fourfold higher antinociceptive activity compared to form B.     

Chiral crystals from an achiral molecule: 4,6‐di‐O‐benzyl‐1,3‐O‐benzylidene‐2‐O‐(4‐methoxybenzyl)‐myo‐5‐inosose

The title achiral compound, C₃₅H₃₄O₇, crystallizes in the chiral monoclinic space group P2₁. The molecules are densely packed to form a helical assembly along the crystallographic twofold screw axis via C—H...O and C—H...π interactions. Interestingly, the unit‐translated helical chains are loosely connected via a rather uncommon edge‐to‐edge Ph—H...H—Ph short contact (H...H = 2.33 Å).     

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.     

New chiral α‐diimine nickel(II) complexes bearing ortho‐sec‐phenethyl groups for ethylene polymerization

A series of new α‐diimine nickel(II) catalysts bearing bulky chiral sec‐phenethyl groups have been synthesized and characterized. The molecular structure of representative chiral ligand, bis[N,N′‐(4‐methyl‐2,6‐di‐sec‐phenethylphenyl)imino]‐1,2‐dimethylethane rac‐1c and chiral complexes, {bis[N,N′‐(4‐methyl‐2‐sec‐phenethylphenyl)imino]‐2,3‐butadiene}dibromidonickel rac‐2a and bis{bis[N,N′‐(4‐methyl‐2‐sec‐phenethylphenyl)imino]‐2,3‐butadiene}dibromidonickel rac‐2b, were confirmed by X‐ray crystallographic analysis. Complex rac‐2c bearing two chiral sec‐phenethyl groups in the ortho‐aryl position and a methyl group in the para‐aryl position, activated by diethylaluminum chloride (DEAC), showed highly catalytic activity for the polymerization of ethylene [4.12 × 10⁶ g PE (mol Ni.h.bar)^?1], and produced highly branched polyethylenes under low ethylene pressure (branching degree: 104, 118 and 126 branches/1000 C at 20, 40 and 60°C, respectively). Chiral 20‐electron bis‐α‐diimine Ni(II) complex rac‐2b also exhibited high activity toward ethylene polymerization [1.71 × 10⁶ g PE (mol Ni · h · bar)^?1]. The type and amount of branches of the polyethylenes obtained were determined by ¹H and ¹³C NMR. Copyright © 2013 John Wiley & Sons, Ltd.     

A Novel Asymmetric Synthesis of 3‐(1H‐Pyrrol‐1‐yl)‐Substituted β‐Lactams via a Bismuth Nitrate‐Catalyzed Reaction

The reaction of racemic α‐keto β‐lactams 5a – 5c with the commercially available chiral compound trans‐4‐hydroxy‐L ‐proline ( 6 ) in the presence of a catalytic amount of Bi(NO₃)₃?5 H₂O in EtOH gave a diastereoisomer mixture of β‐lactams with a pyrrole ring at C(3) ( 7 to 12 ). This is the first enantioselective synthesis of optically active β‐lactams (=azetidin‐2‐ones) that possess a pyrrolyl residue at C(3), in a single step.     

(3aS,7aS)‐1‐{2‐Oxo‐1,3‐bis­[(S)‐1‐phen­ylethyl]­per­hydro‐1,3,2λ5‐benzodi­aza­phosphol‐2‐yl}‐1‐phenylmethanol: a mixture of dia­stereoiso­mers in a disordered crystal

In the title compound, C₂₉H₃₅N₂O₂P, the stereogenic C center α to the P atom, formed during the Pudovik condensation reaction between a deprotonated chiral diaza­phosphole and benz­aldehyde, has disordered substituents, giving a mixture of Cα‐R and Cα‐S diastereoisomers. Moreover, this compound crystallizes with two independent mol­ecules in the asymmetric unit. The observed configuration at the Cα atom is 0.741 (6)‐S mixed with 0.259 (6)‐R, indicating diastereoisomeric enrichment during crystallization. Data from solution and solid‐state studies consistently point to an epimerization process at the Cα atom.     

trans‐Dichloridobis(4,8‐dimethyl‐2‐phenyl‐2‐phosphabicyclo[3.3.1]nonane‐κP)platinum(II)

The crystal structure of the title compound, trans‐[PtCl₂(C₁₆H₂₃P)₂], has been determined at 100 K. The Pt atom is located on a twofold axis and adopts a distorted square‐planar coordination geometry. The structure is only the second example of a coordination complex containing a derivative of the 4,8‐dimethyl‐2‐phosphabicyclo[3.3.1]nonane (Lim) phosphine ligand family. The ligand contains four chiral C atoms, with the stereochemistry at three of these fixed during synthesis, therefore resulting in two possible ligand stereoisomers. The compound crystallizes in the chiral space group P4₃2₁2 but is racemic, comprising an equimolar mixture of both stereoisomers disordered on a single ligand site. The effective cone angles for both isomers are the same at 146°.     

Crystallographic report: [N,N′‐Bis‐(6‐methylpyrid‐2‐ylium)‐(1R,2R)‐1,2‐diaminocyclohexane] bis‐[(p‐cymene)‐ trichlororuthenate(II)]

The chiral compound (H₂cydiampy)[RuCl₃(p‐cymene)]₂ has been obtained in high yield by treating [RuCl₂(p‐cymene)]₂ with an excess of hydrochloric acid in the presence of one equivalent of N,N′‐bis‐(6‐methylpyrid‐2‐yl)‐(1R,2R)‐1,2‐diaminocyclohexane (cydiampy). It crystallizes in the chiral tetragonal space group P4₃2₁2, with half of the atoms of the dication related to the other half by a crystallographic C₂ axis that also makes equivalent the two anionic metal moieties. Copyright © 2005 John Wiley & Sons, Ltd.     

A Flexible Approach to Azasugars: Asymmetric Total Syntheses of (+)‐Castanospermine, (+)‐7‐Deoxy‐6‐epi‐castanospermine,and (+)‐1‐epi‐Castanospermine

The asymmetric total synthesis of natural azasugars (+)‐castanospermine, (+)‐7‐deoxy‐6‐epi‐castanospermine, and synthetic (+)‐1‐epi‐castanospermine has been accomplished in nine to ten steps from a common chiral building block (S)‐ 8 . The method features a powerful chiral relay strategy consisting of a highly diastereoselective vinylogous Mukaiyama‐type reaction with either chiral or achiral aldehydes (≥95 % de; de=diastereomeric excess) and a diastereodivergent reduction of tetramic acids, which allows formation of three continuous stereogenic centers with high diastereoselectivities. The method also provides a flexible access to structural arrays of 5‐(α‐hydroxyalkyl)tetramic acids, such as 17/34 , and 5‐(α‐hydroxyalkyl)‐4‐hydroxyl‐2‐pyrrolidinones, such as 18 and 25/35 a . The method constitutes the first realization of the challenging chiral synthons A and D and thus of the conceptually attractive retrosynthetic analysis shown in Scheme 1 in a highly enantioselective manner.     

基于(R)-1,1’-联萘硫脲的手性荧光受体: 合成与手性识别

Two chiral fluorescent receptors 1 and 2 based on (R)-1,1‘-binaphthylene-2,2‘-bisthiourea were synthesized, and their chiral recognition properties for enantiomeric mandelate anions were studied by fluorescence spectra and molecular modeling. Addition of the L- and D-mandelate anions caused considerable fluorescent increases in the fluorescent intensity of the host solution. The L-enantiomer can enhance the fluorescence intensity of 1 much more than the D-enantiomer can do, and 1 shows a better enantioselective recognition ability than 2.     

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.