Paternò-Büchi反应的区域选择性

Paternò-Büchi(P-B)反应,即羰基-烯的[2+2]光环化加成反应,利用其特殊的区域及立体选择性可以合成一些结构精巧的取代氧杂环丁烷。随着P-B反应在有机合成中越来越广泛的应用,人们对P-B反应的区域选择性的研究也越来越深入。在P-B反应发现之初,人们一直用“最稳定的双自由基规则”解释其区域选择性,这一规则对有些体系却不适用,近年来有人开始运用“自旋化学”理论来解释区域选择性。本论文结合作者的研究工作,评述了近年来P-B反应的区域选择性的研究进展,重点阐述了反应温度、反应物的取代基对P-B反应区域选择性的影响及其规律。     

Effect of methoxyl group position on the regioselectivity of ammonia substitution reactions involving 3,3'-dichloro-2,2'-binaphthoquinones

A series of methoxyl-substituted 3,3'-dichloro-2,2'-binaphthoquinones 2 were prepared and evaluated for regioselectivity in ammonia substitution reactions. Biquinone 2b underwent regiospecific amination at the unsubstituted chloronaphthoquinone unit whereas the isomeric biquinone, 2c, produced moderate regioselectivity (85:15). Biquinone 2d, however, showed no level of regioselectivity demonstrating that the position of the methoxyl group influences the regiochemistry. The intramolecular hydrogen bond in biquinone 5 altered the regioselectivity. Semiempirical calculations revealed comparatively larger LUMO coefficients at the chlorinated carbons that underwent preferential substitution.     

Catalytic activity of salenCo(III)OAc complex in the reaction of addition of carboxylic acids to terminal epoxides

The catalytic activity and regioselectivity were studied of the salenCo(III)OAc complex in the reaction of addition of aliphatic carboxylic acids to a series of terminal epoxides (epichlorohydrin, 1,2-epoxybutane, propylene oxide, tert-butyl glycidyl ether and 2,3-epoxypropyl phenyl ether). The reduction in the activity in the order: acetic > acrylic > methacrylic acid was found. The regioselectivity of the addition was independent on carboxylic acid nature and depended on the nature of the epoxide. The best regioselectivity for the addition to epichlorohydrin was observed. The catalytic activity and regioselectivity of salenCo(III)OAc were compared with those for chromium(III) acetate catalyst.     

Remote substituent effects on the oxymercuration of 2-substituted norbornenes: an experimental and theoretical study.

The effect of a remote substituent on regioselectivity in the oxymercuration of 2-substituted norbornenes has been investigated experimentally and theoretically using density functional theory (DFT). Regioselectivities of 1:1 to 14:1 were observed with various 2-substituted norbornenes. Exo-2-substituted norbornenes always gave greater regioselectivities compared to the corresponding endo-2-substituted norbornenes. The effects of solvents on the regioselectivity have also been examined, and ethereal solvents were found to be the best choice giving the optimal yield and regioselectivity. The relative rate of oxymercuration was estimated by competition experiments. The least reactive substrate (X = OAc) gave the highest regioselectivity. According to DFT predictions, the increased difference between the reaction barriers that results in the greater regioselectivity is correlated directly with the larger polarity of the C=C double bond, which is attacked by the mercury and oxygen. A number of stable exo and endo conformers were predicted. All exo conformers show the same polarity of the double bond, while some endo conformers have a reversal of this polarity. All the conformers except those with the OAc substituent are very close in energy and thus should react. The existence of a mixture of endo conformers with the C=C double bond of opposite polarity clearly explains a decrease in regioselectivity for the endo species. The origin of the greatest regioselectivity for the OAc-2-norbornenes lies in the fact that the conformer with the largest polarity is notably lower in energy than others due to an internal C-H-O hydrogen bond.     

(Z)-1,2-二苯基-1,3-丁二烯与单取代的乙烯衍生物区位选择性环加成反应

(Z)-1,2-二苯基-1,3-丁二烯分别与甲基乙烯基酮、丙烯酰胺、丙烯腈以及丙烯醛发生环加成反应,均生成顺式和反式的连位取代环己烯衍生物。以IR、¹HNMR和MS鉴定了产物的结构。利用CNDO/2法计算了分子轨道能量和系数,由前线分子轨道理论解释了这种环加成反应的区位选择性。     

Investigation of regioselectivity in the synthesis of spiro [pyrrolidine-2,3′-oxindoles] by use of the Huisgen reaction

The Huisgen reaction has been used to synthesize five-membered heterocyclic compounds in high yield and with high regio and stereoselectivity. In the synthesis of spiro [pyrrolidine-2,3′-oxindole] derivatives from isatin, α-amino acids, and (E)-β-phenyl nitroolefins, two regioisomers were obtained in each reaction. The regioselectivity of the major product was found to be different from that in reported work, and was investigated at the B3LYP/6-311G* level of theory. On the basis of this new finding, several conditions, for example molar ratio, solvent, and temperature, which affect the regioselectivity of this reaction were investigated; the results obtained are discussed. It was found that the regioselectivity of this reaction was affected by solvent and temperature, irrespective of the ratio of the reactants. Low temperature and high solvent polarity leads to high regioselectivity, and protic solvents result in higher yield and regioselectivity. These results are of benefit for regioselective synthesis of some compounds.     

Ligand-Regulated Regiodivergent Hydrosilylation of Isoprene under Iron Catalysis

A method for the regiodivergent and stereoselective hydrosilylation of the basic industrial feedstock isoprene with unactivated silanes has been developed using earth-abundant iron catalysts. The manipulation of regioselectivity relies on fine modification of the coordination geometry of the iron center. While a bidentate pyridine imine ligand promoted the formation of allylic silanes through 4,1-addition, selectivity for the 3,4-adduct homoallylic silanes was observed with a tridentate nitrogen ligand. Experimental studies and analysis were carried out to elucidate the reaction mechanism and the factors enabling manipulation of the regioselectivity. This study contributes to the art of regioselectivity control in alkene hydrofunctionalization.     

Theoretical calculational investigation on the regioselectivity of the ring opening of thiiranes with ammonia and amines

The course, especially the regioselectivity, of the nucleophilic ring opening of thiiranes with ammonia and amines was investigated with the density functional theory (DFT) calculation. In the ring-opening reaction, thiiranes could be attacked on either their less or more substituted carbon atoms. The analyses of the potential energy surfaces, the bond lengths, and charges of key species in both pathways indicate that alkyl-substituted thiiranes are attacked dominantly on their less substituted ring carbon atom, whereas arylthiiranes are on their more substituted one due to the existence of the p-π conjugative effect, which stabilizes the transition states generated in the reaction. Furthermore, the Lewis acid can modulate the regioselectivity. However, the steric hindrance of nucleophiles and solvents affect the regioselectivity slightly as they show similar influence on both pathways, despite the fact that they can put an impact on the energy. NBO and MO analyses also support the substituent-depended regioselectivity. This is the first DFT calculational investigation on the regioselective ring opening of thiiranes and provides a rational explanation for the experimental results. The theoretical investigation gives a general understanding and a rule for the rationale and prediction of the regioselectivity in the nucleophilic ring opening of thiiranes, even other three-membered heterocycles.     

Effect of the electronic structure of the radical anions of 4-substituted 1,2-and 1,3-dinitrobenzenes on the regioselectivity of reduction of the nitro groups

Theoretical and experimental regularities of the regioselectivity of the reduction of one of the two nitro groups in unsymmetrical dinitrobenzenes were studied. It was found that the regioselectivity of the formation of isomeric nitroanilines depends on the structure of the substrate and the nature of the reducing agent. The reduction regioselectivity model was verified, according to which radical anion protonation is the major reaction direction.     

Regioselectivity in the palladium-catalyzed addition of carbon nucleophiles to carbocyclic derivatives.

The regioselectivity of Pd-catalyzed malonate additions and arylations to cycloalkenyl esters can be predicted by completing a stereochemical analysis of the Pd-pi-allyl complex. The Pd-catalyzed malonate additions which have the greatest degree of regioselectivity are in which substituents have a steric influence in blocking the incoming nucleophile. Cyclopentenyl substrates displayed lower regioselectivity than the cyclohexyl counterparts presumably due to increased planarity of the system. Arylations using tin and hypervalent silicon reagents were compared.     

Highly enantioselective hydroformylation of aryl alkenes with diazaphospholane ligands

Asymmetric, rhodium-catalyzed hydroformylation of terminal and internal aryl alkenes with diazaphospholane ligands is reported. Under partially optimized reaction conditions, high enantioselectivity (>90% ee) and regioselectivities (up to 65:1 alpha:beta) are obtained for most substrates. For terminal alkenes, both enantioselectivity and regioselectivity are proportional to the carbon monoxide partial pressure, but independent of hydrogen pressure. Hydroformylation of para-substituted styrene derivatives gives the highest regioselectivity for substrates bearing electron-withdrawing substituents. A Hammett analysis produces a positive linear correlation for regioselectivity.     

Predicting the regioselectivity of nucleophilic addition to arynes using frontier molecular orbital contribution analysis

The regioselectivity of nucleophilic addition to substituted arynes was predicted using frontier molecular orbital contribution analysis. This model indicates that the percentage of the LUMO on the reacting terminus of the aryne is responsible for the observed regioselectivity; the nucleophile attacks the carbon possessing higher contribution of the LUMO.     

Tuning of regioselectivity in the coupling reaction involving allenic/propargylic palladium species

Two different types of coupling patterns for the Pd(0)-catalyzed coupling reaction of allenic/propargylic zinc reagents with organic halides or propargylic carbonates (acetate) with the corresponding organometallic reagents were observed. After studying the controlling factors on the regioselectivity of this reaction, we demonstrated that the steric hindrance of both reactants and the types of organic halides determine the regioselectivity of this coupling reaction. By subtle choosing of the substrates, the regioselectivity can be tuned. On the basis of these results, new methodologies for the highly regio- and stereoselective synthesis of 6-substituted hex-5-yn-2-enoates and 4,6-dialkylhexa-2,4,5-trienoates have been developed. Some of the products synthesized by the carbonate protocol cannot be prepared by the lithiation protocol because the regioselectivity of lithiation of dialkyl-substituted internal alkynes is an intrinsic problem.     

Regioselective glycosylation reactions based on computational predictions

Regioselectivity is a major issue in glycosylation reactions. Better understanding of regioselectivity of acceptors can greatly facilitate and simplify the syntheses of oligosaccharides. The reactivity of diol acceptors is often affected by stereochemistry and protecting groups, which make prediction the regioselectivity of diol acceptors extremely difficult. Quantum mechanic methods were used to study the relationship between protecting groups and reactivity of diol acceptor and a correlation between Fukui function and regioselectivity is established through series of glycosylation reactions.     

Elucidating the Mechanism and Chemoselectivity in the PBu3-Catalyzed Rauhut-Currier Reaction of Chalcone with Ethyl Acrylate

Disclosing the chemoselectivity and regioselectivity of phosphine-catalyzed Rauhut-Currier (R−C) reaction remains a challenge. Here, a comprehensive study on the possible mechanisms and origins of the chemoselectivity and regioselectivity of PBu₃-catalyzed R−C reactions between ethyl acrylate and chalcone is performed by DFT. Both cross and homo R−C reactions are investigated and compared. The computational results show that the cross R−C reaction is energetically favorable than the homo R−C reaction, with head-to-tail product being generated preferentially. Moreover, the C−C bond formation process is identified to be the regioselectivity- and chemoselectivity-determining step. The CDFT and Parr function analyses are successfully used to predict the origins of chemoselectivity and regioselectivity, respectively. This work would provide a valuable case for exploring the origins of the chemoselectivity and regioselectivity of the phosphine catalyzed reactions, which should be helpful to understand and control the selectivities by rational design.     

Indolyne experimental and computational studies: synthetic applications and origins of selectivities of nucleophilic additions

Efficient syntheses of 4,5-, 5,6-, and 6,7-indolyne precursors beginning from commercially available hydroxyindole derivatives are reported. The synthetic routes are versatile and allow access to indolyne precursors that remain unsubstituted on the pyrrole ring. Indolynes can be generated under mild fluoride-mediated conditions, trapped by a variety of nucleophilic reagents, and used to access a number of novel substituted indoles. Nucleophilic addition reactions to indolynes proceed with varying degrees of regioselectivity; distortion energies control regioselectivity and provide a simple model to predict the regioselectivity in the nucleophilic additions to indolynes and other unsymmetrical arynes. This model has led to the design of a substituted 4,5-indolyne that exhibits enhanced nucleophilic regioselectivity.     

Polar vs steric effects in the 1,3-dipolar cycloaddition reactions of acetonitrile oxide and 2-endO-acetoxy-5-halo-7-oxabicyclo[2.2.1]hept-5-en-2-exo-carbonitrile

The regioselectivity of the cycloaddition reactions between acetonitrile oxide and a number of 7-oxabicyclo[ 2.2.1]hept-5-enes is discussed. Acetonitrile oxide adds with complete regioselectivity to 2-endo-acetoxy-5-halo-7-oxabicyclo[2.2.1]hept-5-en-2-exo-carbonitriles. Kinetic measurements indicate a more polar transition state for 2a than for the unsubstituted substrate la     

Diastered and Regiochemical Control in the Functionalization of the Allylic [dbnd] of a Natural 5-(1-Alkenyl)-2-Enono-1,5-Lactone

The diastereo and regioselectivity of the bromohydrination of argentilactona [(5R)-(-)-δ-lactone of 5-hydroxydodeca-Z, Z-2,6-dienoic acid] and the regioselectivity of the aqueous acidic opening of its 65,75 and 6R,7R-epoxides were studied. Although the reactions occurred with low diasterofacial control, the regioselectivity observed in all cases was high, suggesting that the sequences could be of some synthetic value.     

Remarkable phosphine-effect on the intramolecular aldol reactions of unsaturated 1,5-diketones: highly regioselective synthesis of cross-conjugated dienones

We report a phosphine-mediated intramolecular aldol cyclization of unsaturated diketones that proceeds with extremely high levels of regioselectivity for the cross-conjugated bicyclic dienone products. The sense of regioselectivity observed in this reaction is complementary to that obtained using traditional aldol conditions. Experimental evidence that supports the involvement of a phosphine Michael adduct is described.     

Unexpected role of O-2 "protecting" groups of glycosyl donors in mediating regioselective glycosidation

Glycosidation of several vicinal diols reveals that exquisite regioselectivity can be achieved by using 2-O-benzoyl n-pentenyl glycoside donors and/or their cyclic 1,2-ortho ester counterparts. The regioselective preferences for both are the same, although ratios and yields may differ. In stark contrast, glycosidation of the diols with the corresponding 2-O-benzylated donors gives poor, if any, regioselectivity.