Stereocontrolled IMDA reaction of styrene derivatives. A way to enantiopure 3a,4,9,9a-tetrahydrobenz[f]isoindolines

IMDA reactions on chiral perhydro-1,3-benzoxazines, derived from (-)-8-amino menthol, bearing a styrene substituent at C-2 acting as diene and an acryl amide acting as dienophile occur with high stereoselection and excellent chemical yields. After elimination of the chiral appendage, enantiopure 3a,4,9,9a-tetrahydrobenz[f]isoindolines are prepared in this way. The effect of the substituents at both diene and dienophile are studied, showing that a methyl group at C-1 in the diene inhibited the reaction, while the ene adduct, instead of the IMDA product, was obtained when a methyl group was at C-2.     

Enantioselective Diels-Alder reactions of 3-(acyloxy)acrylates

Diels-Alder reactions with 3-(acyloxy)acrylates using chiral Lewis acid catalysts have been successfully carried out. These reactions proceed with high enantioselectivity when a chiral Lewis acid derived from Cu(OTf)₂ and a bisoxazoline is used. The facility of the reaction is dependent on the nature of the acyloxy group in the dienophile.     

Experimental and theoretical insights regarding the cycloaddition reaction of carbohydrate-based 1,2-diaza-1,3-butadienes and acrylonitrile. A model case for the behavior of chiral azoalkenes and unsymmetric olefins

A series of carbohydrate-based tetrahydropyridazines are prepared by the hetero-Diels-Alder reaction of the chiral 1,2-diaza-1,3-butadienes 1 and 2 with acrylonitrile. Reactions are regiospecific, and the observed diastereoselection is consistent with a preferred attack to the Re face of the heterodiene unit, as the chiral sugar placed at C4 does largely protect the opposite Si face. The stereochemistry of the major cycloadduct 4 has been firmly established by an X-ray crystallographic study that, in addition, reveals a conformation placing the cyano group in axial orientation. Cycloadducts such as 9 and 11, in which the axial cyano group and the carbohydrate moiety exhibit a cis relationship, undergo a facile E2 elimination that relieves the steric congestion. A detailed computational study is reported to provide better insight into the factors that influence this asymmetric cycloaddition. A DFT study (B3LYP/6-31G) on a reduced model does correctly predict the regiochemistry observed experimentally, while the facial diastereoselection is modeled at a semiempirical (PM3) level on the parent reagents, thereby accounting for the steric factor provided by the chiral substituent. The calculations also indicate that the axial orientation of the cyano group can be rationalized in terms of a stabilizing anomeric effect.     

Studies of some monocyclic and bicyclic arylacetonitriles

The high-resolution (1)H, (13)C, (1)H-(1)H COSY and (1)H-(13)C COSY NMR spectra have been recorded in CDCl(3) for arylacetonitriles 1-12 and analyzed. The arylacetonitriles 3-7 exist in two isomeric forms E (methyl group is anti to cyano group) and Z (the methyl group is syn to cyano group) in solution. Normal chair conformation with equatorial orientations of phenyl rings at C-2 and C-6 for monocyclic nitriles 1 and 2, epimeric chair structure EC (axial configuration of methyl group at C-3) for both the E and Z isomers of arylacetonitrile derivatives (3-7) and a distorted boat form, B(3), for the N-acylacetonitrile derivatives (8-10) have been proposed based on NMR data. The bicyclic nitriles 11 and 12 exist in twin chair conformations in solution. DFT calculations and chemical shifts also support these conformations. Geometry optimizations for 1-12 were carried out according to density functional theory using B3LYP/6-31G(d,p) basis set and for 1 and 8 the theoretical geometrical parameters have been compared with those of single crystal measurements.     

Asymmetric Diels-Alder Reaction of 1-Methoxybuta-1,3-diene with (2R)-N-Glyoxyloylbornane-10,2-sultam

Starting from sultam 1 , the chiral dienophile (2R)-N-glyoxyloylbornane-10,2-sultam ( 4 ) was readily prepared. Non-catalyzed atmospheric- and high-pressure as well as [Eu(fod)₃]-promoted [4 + 2] cycloadditions of 1-methoxy-buta-1,3-diene ( 5 ) to chiral dienophile 4 , leading with high asymmetric induction to 6-methoxy-3,6-dihydro-2H-pyran-2-yl derivatives 6 – 9 , are described. The extent and direction of asymmetric induction in these reactions were established by ¹H-NMR analysis and chemical correlation, respectively. Stereochemical models for both non-catalyzed and [Eu(fod)₃]-promoted reactions are proposed.     

Gas-phase protonation and deprotonation of acrylonitrile derivatives N[triple chemical bond]C--CH==CH--X (X=CH(3), NH(2), PH(2), SiH(3))

A combined experimental and theoretical study on the gas-phase basicity and acidity of a series of cyanovinyl derivatives is presented. The gas-phase basicities and acidities of (N[triple chemical bond]C--CH==CH--X, X=CH(3), NH(2)) were obtained by means of Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry techniques. The corresponding calculated values were obtained at the G3B3 level of theory. The effects of exchanging CH(3) for SiH(3), and NH(2) for PH(2), were analyzed at the same level of theory. For the neutral molecules, the Z isomer is always the dominant species under standard gas-phase conditions at 298 K. The loss of the proton from the substituent X was found systematically to be much more favorable than deprotonation of the HC==CH linking group. The corresponding isomeric E ion is much more stable than the Z ion, so that only the former should be found in the gas phase. The most significant structural changes upon deprotonation occur for the methyl and amino derivatives because, in both cases, deprotonation of X leads to a significant charge delocalization in the corresponding anion. Protonation takes place systematically at the cyano group, whereby the isomeric E ion is again more stable than the Z ion. Push-pull effects explain the preference of aminoacrylonitrile to be protonated at the cyano group, which also explains the high basicity of this derivative relative to other members of the analyzed series that present rather similar gas-phase basicities, GB approximately 780 kJ mol(-1), indicating that the different nature of the substituents has only a weak effect on the intrinsic basicity of the cyano group. The cyanovinyl derivatives have a significantly stronger gas-phase acidity than that of the corresponding vinyl compounds CH(2)==CH--X. This acidity-strengthening effect of the cyano group is attributed to the greater stabilization of the anion with respect to the corresponding neutral compound.     

Responsive Supramolecular Polymers Based on the Bis[alkynylplatinum(II)] Terpyridine Molecular Tweezer/Arene Recognition Motif

Supramolecular polymers are constructed based on the novel bis[alkynylplatinum(II)] terpyridine molecular tweezer/pyrene recognition motif. Successive addition of anthracene as the diene and cyano‐functionalized dienophile triggers the reversible supramolecular polymerization process, thus advancing the concept of utilizing Diels–Alder chemistry to access stimuli‐responsive materials in compartmentalized systems.     

Synthesis and properties of chiral stilbene diacrylates

Two chiral and isomerizable liquid crystalline diacrylates were synthesized. The purpose of these compounds was to tune the helical twisting power of cholesteric materials containing these compounds by means of an E - Z photoisomerization of the photoactive group derived from stilbene. The photochemical behaviour of these compounds was studied with the aid of two model compounds containing the same isomerizable mesogenic group. The mesogenic group derived from 4-(4-hydroxybenzoyloxy)-4'-hydroxystilbene decomposes upon irradiation. Its isomer, derived from 4-(4-hydroxyphenoxycarbonyl)-4'-hydroxystilbene, shows a clean E - Z isomerization. The HTP of the chiral diacrylate derived from the latter mesogenic group changes from 7 to 3 µm -1 in dilute nematic solution. Colour changes in a cholesteric material containing this compound were observed. The effect was very dependent on temperature and concentration due to the strong smectic character of this diacrylate.     

On the total synthesis and determination of the absolute configuration of rishirilide B: exploitation of subtle effects to control the sense of cycloaddition of o-quinodimethides

The total synthesis of racemic rishirilide B has been accomplished. The synthesis serves to define the relative relationships of its stereogenic centers. Also, starting with readily available chiral pool, ent-rishirilide B was synthesized, thereby demonstrating that natural configuration of rishirilide B. The defining step in our total synthesis is the facile cycloreversion of the bis(siloxy)benzocyclobutane and the intermolecular o-quinodimethide Diels-Alder cycloaddition. We believe that the tight regiochemical guidance in this step arises from a meshing of the electron-donating effects of the symmetry-perturbing aromatic OTBS group of the o-quinodimethide diene with the reactivity differential of the dienophile (enedione), modulated by the hydroxyl group at the alpha-position. The validity of the hypothesis of hydroxy-directed activation of its vicinal ketone function in the context of the enedione dienophile warrants further study. This type of activation may find broader applications in distinguishing reactivity profiles of key closely related functional groups in organic substrates.     

5-L-孟氧基4-苄氨基丁烯内酯的不对称合成和晶体结构研究

温和条件下,苄胺与手性合成子5-(L)-孟氧基3-溴-2(5)呋喃酮通过串联的不对称迈克尔加成/分子内消除反应合成了一种新手性化合物:5-L-孟氧基-4-苄胺基丁烯内酯。产物经过IR、1H-NMR、MS谱学表征,并经X-ray单晶衍射测定了其结构。新化合物属于正交晶系,P212121空间群,a=5.2945(4),b=14.2829(10),c=26.0769(18),Mr=343.45,Z=4,V=1972.0(2)3,Dc=1.157g/cm3,μ(MoKα)=0.076mm-1,F(000)=744,R=0.0387,wR=0.0880。     

Synthesis and Crystal Structure of （R）-4-Hydroxymethyl-2-thioxo Thiazolidine and Its Asymmetric Catalysis

(R)-4-Hydroxymethyl-2-thioxo thiazolidine as a new chiral catalyst in the asymmetric addition of diethyl-zinc to benzaldehyde was synthesized from (R)-4-hydroxymethyl-2-thioxo thiazolidine carboxylic acid and its crystal structure was determined by X-ray diffraction method. The compound was crystallized in the orthorhombic system, space group P212121 with unit cell dimensions a=0.67253(12) nm; b=0.89164(17) rim; c=1.06146(19) nm, volume 0.6365(2) nm3; Z=4, calculated denisity 1.557 Mg/m3; absorption coefficient 0.733 mm-1; F(000)=312. The X-ray crystal structure analysis reveals that the compound has a thione group.     

Dienophile twisting and substituent effects influence reaction rates of intramolecular Diels-Alder cycloadditions: a DFT study

Intramolecular cycloadditions of 5-vinyl-1,3-cyclohexadienes were studied with B3LYP/6-31G(d) density functional calculations. The one-atom tether dictates that the Z substituent becomes exo and the E substituent becomes endo in the TS. The geometry of the cycloaddition TS is typical of a pericyclic transformation except unusual twisting of the dienophile places the endo substituent in a relatively steric-free position and the exo substituent in a highly crowded position. The experimental rate differences between isomeric pairs of vinylcyclohexadienes can be explained by comparing reactant destabilization when a bulky group occupies the Z position of the starting alkene and transition state stabilization when a bulky group is endo in the cycloaddition TS.     

A test for the coexistence of reactive intermediates with different molecular composition in chiral Lewis acid-catalysed reactions: the case of Ti-TADDOLate-catalysed Diels–Alder reactions

The Diels–Alder reactions between cyclopentadiene 2 and (E)-3-butenoyl-1,3-oxazolidin-2-one 1 catalysed by several TADDOL-TiCl₂ complexes have been studied with different [dienophile]/[catalyst] ratios and different concentrations of reagents and catalyst. The enantioselectivity of some of the reactions depends on these factors, which indicates the participation of intermediate complexes with different catalyst and dienophile compositions (1:1, 1:2 and 2:1). The best results are obtained under conditions that favour the formation of an equimolecular intermediate, whereas the conditions favouring the formation of intermediates containing two molecules of dienophile and one of catalyst give rise to lower enantiomeric excesses (e.e.s). In one case the asymmetric induction was not dependent on the above factors, meaning that the effect described strongly depends on the structure of the chiral ligand. The results described show that this kind of mechanistic study complements those carried out on the influence of the enantiomeric composition of the chiral ligand on the enantioselectivity.     

Conformational model for asymmetric Diels-Alder reactions with chiral dienes

1-(O-methylmandeloxy)dienes have significant advantages for asymmetric Diels-Alder reactions, and we now show that high (90%) diastereofacial selectivities can be obtained with these dienes, permitting considerable choice as to dienophile and the presence of additional functionality. We present experimental support, including X-ray structures showing the conformations of three Diels-Alder adducts, for a transition state model which explains the origin of these selectivities. The distinctive characteristics of this model are that the phenyl group is nearly perpendicular to the ester CO, i.e., the PhCCO dihedral angle is near 90°, and that the methoxy group is close to the carbonyl oxygen. These features may have wider applications for chiral control by α-chiral ester groups in other types of reactions. Our results should renew interest in the use of chiral 1-acyloxydienes.     

Enlargement of blue-phase stability for rod-like low-molecular-weight chiral nematic liquid crystal mixtures

In this study, we investigated the enlargement of liquid crystal (LC) blue-phase (BP) temperature range using the rod-like low-molecular-weight cyano phenyl-type chiral nematic LC with various core group and chiral dopant concentrations. Also, the electro-optic response time was investigated for them. We found that the BP temperature range was strongly dependent upon the core structure and the chiral dopant concentration for the chiral nematic LC mixtures having the same terminal group. Also, we found a stable BP with a wide temperature range (more than 6 K), including a BP-isotropic coexistence state over 13.5 K upon heating and cooling processes and very fast response time (less than 1 ms), by using the cyano phenyl-type chiral nematic LC mixture with a high molecular aspect ratio and a high chiral dopant concentration.     

Spectroscopic investigations of bis(sulfoximine) copper(II) complexes and their relevance in asymmetric catalysis

The structure of Cu(II) complex 3 formed within the course of a stereoselective Diels-Alder reaction was investigated by EXAFS, CW-EPR at X- and W-band, HYSCORE, pulsed ENDOR, and UV-vis spectroscopy. The experimental techniques indicate that the chiral bis(sulfoximine) ligand (S,S)-1 and the dienophile form a tetragonally distorted complex in CH(2)Cl(2). The ligand binds to the Cu(II) center via the imine nitrogens, whereas the dienophile interacts via the carbonyl oxygen atoms. The additional sites of the first coordination sphere are occupied by counterions and, presumably, solvent molecules. At the axial position, a triflate anion binds via an oxygen atom.     

A practical new chiral controller for asymmetric Diels-Alder and alkylation reactions

[formula: see text] The enantiomerically pure hydroxy sulfones (+)- and (-)-2 have been prepared from 1,2-epoxycyclohexane by a simple and practical procedure. The acrylate esters of these alcohols undergo BCl3-catalyzed Diels-Alder reactions with a variety of dienes at -78 to -55 degrees C in CH2Cl2 or C7H8 with high dienophile face selectivity (Table 1). The chiral esters so formed are readily cleaved with recovery of the controllers (+)- or (-)-2. Esters of (+)- and (-)-2 can be converted to Z-potassium enolates and alkylated with high face selectivity.     

松毛虫性信息素共轭双键定位方法的研究

亲二烯体试剂4-甲基-1,2,4-三唑啉-3,5-二酮(MTAD)与共轭二烯成分形成衍生物,经气相色谱-质谱分析,衍生物质谱图中各种特征碎片离子简单、明显,可用于确定共轭双键在碳链中的位置。以鉴定云南松毛虫性信息素腺体成分的共轭双键位置为例,进一步探讨了反-5-,顺-7-十二碳二烯醇及相应的醛和乙酸酯与MTAD形成衍生物的化学反应特点及色谱分析中应注意的问题。     

Synthesis and Facile One-pot Aldol/Elimination/Diels-Alder Reaction of ß-Keto-Z-Dienylamides as Cytochalasin C Intermediates1

The coupling of chiral dienylamine 1ZE with ß-ketoesters and subsequent one-pot aldol reaction with derivatives of glyoxylic acid, acetylation of the hydroxyester thus produced, and intramolecular Diels-Alder reaction of the diene portion of the molecule with the incipient dienophile is described. The entire sequence generates all of the requisite chiral centers in the isoindolone skeleton of cytochalasin C simultaneously, in an overall yield of approximately 85%.     

Tandem transesterification and intramolecular cycloaddition of alpha-methoxycarbonylnitrones with chiral acyclic allyl alcohols: systematic studies on the factors affecting diastereofacial selectivity of the cycloaddition

Factors affecting the stereochemical course of the intramolecular cycloaddition of intermediary alpha-allyloxycarbonylnitrone resulting from transesterification of alpha-methoxycarbonylnitrones 1a-d with chiral allyl alcohols 5 or 6 were investigated systematically. It was found that the factors of diastereofacial selection are highly dependent on the geometries of the allyl alcohols. In the cases where primary or secondary chiral (Z)-allyl alcohols are used, A(1,3)-strain arising from the chiralities in the (Z)-nitrone transition states of the intramolecular cycloaddtion is the most important factor. In contrast, in the case of the reaction using chiral nitrones 1c,d and (E)-allyl alcohols, steric interaction between the chiral N-substituent and the trans substituent of the olefin moiety in the intermediate is dominant. These aspects were applied to geometry-differentiated cycloaddition using a mixture of (E)-5 and (Z)-5. As a typical example, treatment of bulky 1b with a 1:1 mixture of (E)-5 and (Z)-5 in the presence of a catalytic amount of TiCl(4) and MS 4A gave 7b as the predominant product among four possible products.