Stereospecific Nucleophilic Substitution with Arylboronic Acids as Nucleophiles in the Presence of a CONH Group

Stereospecific nucleophilic substitution was achieved for the first time with arylboronic acids as nucleophiles. This transition‐metal‐free coupling between chiral α‐aryl‐α‐mesylated acetamides and arylboronic acids provided access to a series of chiral α,α‐diaryl acetamides with excellent enantioselectivity and moderate to good yields. The CONH functionality proved to be crucial for bridging the reactants and promoting the reaction. Efficient syntheses of a cannabinoid CB₁ receptor ligand, the antidepressant (S)‐diclofensine, and a key chiral building block of the inhibitor implitapide were successfully accomplished by using this method.     

Intermolecular Stereospecific Substitution of Underivatized Enantioenriched Secondary Alcohols by Organocatalysis

The stereospecific substitution of non‐derivatized and non‐allylic enantioenriched alcohols with only water as a by‐product would enable the use of readily available alcohols as substrates for green and sustainable transformations. However, the poor leaving group ability of the OH group has hampered the development of such a process. Denton and co‐workers recently described the use of (2‐hydroxybenzyl)diphenylphosphine oxide as a catalyst of a redox‐neutral and zero‐waste‐generating Mitsunobu reaction. This innovative process constitutes the first intermolecular stereospecific substitution of non‐allylic alcohols, and might find industrial applications.     

Vinylic Substitution of Chlorine in the Reaction of 2,3,5,6-Tetrachloro-1,4-Benzoquinone with Cyclohexylamine in Acetonitrile Solvent

The reaction of 2,3,5,6-tetrachloro-1,4-benzoquinone with cyclohexylamine in acetonitrile has been studied spectrophotometrically. The mechanism of the reaction is a concerted vinylic substitution of Cl atoms. Kinetics and activation parameters are reported. This revised version was published online in June 2006 with corrections to the Cover Date.     

十八醇亲核取代反应修饰溴代多壁碳纳米管

Octadecanol modified multiple-walled carbon nanotubes, with octadecanol covalently bound to the nanotube surface, have been synthesized by bromination of the carbon nanotubes followed by nucleophilic substitution using octadecanol and sodium hydride. Scanning electron microscopy and transmission electron microscopy images show that the morphologies of the nanotubes are largely intact after functionalization. The brominated carbon nanotubes and octadecanol modified carbon nanotubes were characterized using energy-dispersive X-ray spectroscopy, Raman spectroscopy and Fourier transform infrared spectroscopy. The mechanism of nucleophilic substitution was discussed, and it is believed that the reaction occurs with an SN1 mechanism.     

硫原子上亲核取代反应的密度泛函理论研究

在B3LYP/6-311 G(2df,p)的水平上,对反应X- CH3SCl(X=F,Cl,Br,I)进行了理论研究.计算结果表明:X-(X=Cl,Br,I)与CH3SCl作用时,实际发生的是在硫原子上而不是在碳原子上的亲核取代反应,而且属于加成-消去机理.但是F-与CH3SCl作用则容易发生脱质子反应.     

Syntheses of Atypically Fluorinated Peptidyl Macrocycles through Sequential Vinylic Substitutions

Small peptides containing combinations of cysteine, tyrosine, histidine, and serine residues react with octafluorocyclopentene (OFCP) to afford atypically structured macrocycles through successive vinylic substitutions. The reactions proceed rapidly in air at 0 °C and are tolerant of spectating tryptophan, asparagine, glutamine, and threonine residues. Hexapeptides of consensus sequence YXCXXC displace four fluorine atoms from OFCP to generate fluorinated macrobicyclic compounds that display dual‐turn surfaces. The method provides facile access to a wide range of previously unknown heterocyclic structures.     

Nucleophilic Substitution of Halogenonitrobenzenes by Electrogenerated O2- on Carbon Gas-diffusion-electrode

Introduction The electrochemical reduction of O_2 was investigated widely during the past two decades. O_2~- can react with various organic compounds. O_2~- as a new synthesis reagent has been being explored.     

New Syntheses of Naphthostyryl Derivatives via Nucleophilic Vinylic Substitution

New substituted naphthostyryl derivatives have been synthesized by nucleophilic vinylic substitution reactions and converted to the corresponding N-alkyl derivatives by treatment with alkyl halides.     

Preparation and reactivity of phenyltelluroalkylphosphine oxides. Vinylic tellurides

Phenyltelluromethyldiphenylphosphine oxide was prepared by the reaction of methyldiphenylphosphine oxide with base and PhTeBr. The telluromethylphosphine oxide reacts with aldehydes and ketones to give the corresponding vinylic tellurides, with preferential E stereochemistry for aryl aldehydes and Z for alkyl aldehydes.     

Stereospecific Construction of Chiral Tertiary and Quaternary Carbon by Nucleophilic Cyclopropanation with Bis(iodozincio)methane

The reaction of a ketone having a leaving group at the α‐position, such as α,β‐epoxy ketone or α‐sulfonyloxy ketone, with bis(iodozincio)methane affords a zinc alkoxide of cyclopropanol. The reaction proceeds by nucleophilic addition of the dizinc to the carbonyl group and a sequential intramolecular nucleophilic substitution of the introduced iodozinciomethyl group to the adjacent electrophilic carbon that has a leaving group. When an optically active α,β‐epoxy ketone or α‐sulfonyloxy ketone is treated with the dizinc, a zinc alkoxide of cyclopropanol having a chiral tertiary or quaternary carbon in the cyclopropane ring is obtained, and the obtained zinc alkoxide of cyclopropanol acts as a chiral homoenolate. When it is treated with an electrophile in the presence of copper cyanide, it gives an optically active α‐tertiary or ‐quaternary ketone that retains high optical purity.     

Nucleophilic Substitution Reactions in the [B3H8]− Anion in the Presence of Lewis Acids

As a result of our study on the interaction between the octahydrotriborate anion with nucleophiles (Nu = THF, Ph₃P, Ph₂P-(CH₂)₂-PPh₂ (dppe), Ph₃As, Et₃N, PhNH₂, C₅H₅N, CH₃CN, Ph₂CHCN)) in the presence of a wide range of Lewis acids (Ti(IV), Hf(IV), Zr(IV), Al, Cu(I), Zn, Mn(II), Co(II) halides and iodine), a number of substituted derivatives of the octahydrotriborate anion [B₃H₇Nu] are obtained. It is found that the use of TiCl₄, AlCl₃, ZrCl₄, HfCl₄, CuCl and iodine leads to the highest product yields. In this case, it is most likely that the reaction proceeds through the formation of an intermediate [B₃H₇-HMXn_x], which was detected by NMR spectroscopy. The structures of [Ph₃P·B₃H₇] and [PhNH₂·B₃H₇] were determined by X-ray diffraction.     

Silyldefluorination of Fluoroarenes by Concerted Nucleophilic Aromatic Substitution

The reaction of readily generated silyl lithium reagents with various aryl fluorides to provide the corresponding aryl silanes is reported. DFT calculations reveal that the nucleophilic aromatic substitution of the fluoride anion by the silyl lithium reagent proceeds through concerted ipso substitution. In contrast to the classical nucleophilic aromatic substitution, this concerted ionic silyldefluorination also occurs on more electron‐rich aryl fluorides.     

Synthesis and Reaction of Vinylic Tellurides

Vinylic tellurides were synthesized by the addition of diorganyl tellurides to acetylenes in the presence of a radical initiator or by visible light irradiation. Vinylic tellurides underwent transmetalation by the reaction with triethylaluminium or diethylzinc to form the corresponding vinylmetal reagents with retention of the double bond configuration. Oxidation of vinylic tellurides formed by carbotelluration reactions followed by pyrolysis gave internal acetylenes in good yields.     

Nucleophilic Substitution at Phosphorus Centers (SN2@P)

We have studied the characteristics of archetypal model systems for bimolecular nucleophilic substitution at phosphorus (S_N2@P) and, for comparison, at carbon (S_N2@C) and silicon (S_N2@Si) centers. In our studies, we applied the generalized gradient approximation (GGA) of density functional theory (DFT) at the OLYP/TZ2P level. Our model systems cover nucleophilic substitution at carbon in X^?+CH₃Y (S_N2@C), at silicon in X^?+SiH₃Y (S_N2@Si), at tricoordinate phosphorus in X^?+PH₂Y (S_N2@P3), and at tetracoordinate phosphorus in X^?+POH₂Y (S_N2@P4). The main feature of going from S_N2@C to S_N2@P is the loss of the characteristic double‐well potential energy surface (PES) involving a transition state [X? CH₃? Y]^? and the occurrence of a single‐well PES with a stable transition complex, namely, [X? PH₂? Y]^? or [X? POH₂? Y]^?. The differences between S_N2@P3 and S_N2@P4 are relatively small. We explored both the symmetric and asymmetric (i.e. X, Y=Cl, OH) S_N2 reactions in our model systems, the competition between backside and frontside pathways, and the dependence of the reactions on the conformation of the reactants. Furthermore, we studied the effect, on the symmetric and asymmetric S_N2@P3 and S_N2@P4 reactions, of replacing hydrogen substituents at the phosphorus centers by chlorine and fluorine in the model systems X^?+PR₂Y and X^?+POR₂Y, with R=Cl, F. An interesting phenomenon is the occurrence of a triple‐well PES not only in the symmetric, but also in the asymmetric S_N2@P4 reactions of X^?+POCl₂? Y.     

Preparation of N-Arylated Heterocycles by Nucleophilic Aromatic Substitution

Nucleophilic aromatic substitution of fluorobenzoates and fluorophenylnitriles with weakly basic heterocycles readily occur. This synthetic methodology is utillized to produce potent angiotensin-II antagonists.     

Concerted Nucleophilic Aromatic Substitution Reactions

Recent developments in experimental and computational chemistry have identified a rapidly growing class of nucleophilic aromatic substitutions that proceed by concerted (cS_NAr) rather than classical, two‐step, S_NAr mechanisms. Whereas traditional S_NAr reactions require substantial activation of the aromatic ring by electron‐withdrawing substituents, such activating groups are not mandatory in the concerted pathways.     

分子内氮原子上亲核取代反应的理论研究

Using the -CHR-(CH2)3-NFCH3(R=H, CH3, CH2CF3, CHO, COCH3) as the computational model, the two possible intramolecular reactions, nucleophilic substitution on nitrogen and elimination reaction, were studied at the theoretical level of MP2(full)/6-31+G(d,p). The results indicate that the elimination mechanism, when the -CHR radical is more basic (R=H, CH3, CH2CF3) leading to linear products R-CH2-(CH2)3N=CH2 is preferred. In contrast, electro-withdrawing groups CHO and COCH3 on the attacking site will favor the intramolecular nucleophilic substitution of nitrogen and form 5-membered heterocyclic compounds. These theoretical predictions agree with the available experiments.