Nucleophilic substitution at an sp carbon of vinyl halides with an intramolecular thiolate moiety: synthesis of 2-alkylidenethietanes

Various 2-alkylidenethietanes were synthesized by intramolecular nucleophilic substitution reactions at an sp² carbon of vinyl halides with thiolate moieties. The reaction pathway of the substitution reactions was confirmed as a very rare S_NVπ mechanism by theoretical and experimental studies.     

Effects of stereochemistry and β-substituents on the rates of vinylic SN2 reaction of hypervalent vinyl(phenyl)-λ-iodanes with tetrabutylammonium halides

Both stereoisomers of β-(2-phenylethoxy)vinyl-λ³-iodane and (Z)-β-aroyloxyvinyl-λ³-iodane were prepared stereoselectively. These substituted vinyl-λ³-iodanes undergo nucleophilic vinylic substitutions with n-Bu₄NX (X=Cl, Br, I) under mild conditions, yielding vinyl halides. The observed inversion of configuration at the ipso vinylic carbon atom is compatible with a concerted vinylic S_N2 mechanism. Kinetic measurements indicated that the rates for vinylic S_N2 reaction of (Z)-vinyl-λ³-iodane are greater than those of the E-isomer, probably because of the higher ground state energy of the Z-isomer. Electronic effects of β-substituents of vinyl-λ³-iodanes in the vinylic S_N2 reaction are also discussed.     

Nucleophilic substitution at phosphorus: stereochemistry and mechanisms

This review is devoted to the stereochemistry of nucleophilic substitution reactions at phosphorus. The study of the reactions of phosphoryl group transfer is important for biological and molecular chemistry. The stereochemistry and mechanisms of S_N1(P) monomolecular and S_N2(P) bimolecular nucleophilic substitution reactions of organophosphorus compounds are discussed. It has been shown that hydrolysis of many natural phosphates proceeds according to the monomolecular S_N1(P) mechanism via the formation of metaphosphate intermediate (PO₃^?). S_N2(P) nucleophilic substitution at chiral trivalent or pentavalent phosphorus compounds proceeds via the formation of penta-coordinated transition state or pentacoordinate intermediate.     

Efficient synthesis of α-alkylidene-β-lactams via NaOH-promoted intramolecular aza-Michael addition of α-carbamoyl ketene-S,S-acetals in aqueous media

A facile and efficient synthesis of substituted α-alkylidene-β-lactams have been developed via a NaOH-promoted intramolecular aza-Michael addition of α-carbamoyl, α-(1-chlorovinyl) ketene-S,S-acetals and subsequent nucleophilic vinylic substitution (S_NV) reaction in alcoholic aqueous media.     

Defluorosilylation of Industrially Relevant Fluoroolefins Using Nucleophilic Silicon Reagents

A number of new magnesium and lithium silyl reagents were prepared and shown to be outstanding nucleophiles in reactions with industrially relevant fluoroolefins. These reactions result in a net transformation of either sp² or sp³ C?F bonds into C?Si bonds by two modes of nucleophilic attack (S_NV or S_N2′). The methods are mild, proceeding with high chemo‐ and regioselectivity. Mechanistic pathways are described that lead to new substitution patterns from HFO‐1234yf, HFO‐1234ze, and HFO‐1336mzz, previously inaccessible by transition metal catalyzed difluorosilylation routes.     

Do the solvolysis reactions of secondary substrates occur by the S<Subscript>N</Subscript>1 or S<Subscript>N</Subscript>2 mechanism: or something else?

Primary and methyl aliphatic halides and tosylates undergo substitution reactions with nucleophiles in one step by the classic S_N2 mechanism, which is characterized by second-order kinetics and inversion of configuration at the reaction center. Tertiary aliphatic halides and tosylates undergo substitution reactions with nucleophiles in two (or more) steps by the classic S_N1 mechanism, which is characterized by first-order kinetics and incomplete inversion of configuration at the reaction center due to the presence of ion pairs. When the nucleophile is also the solvent, the substitution reaction is called a solvolysis, and both the S_N2 and S_N1 reactions now obey first-order kinetics. Schleyer and Bentley have provided solid, but not conclusive, evidence that secondary substrates undergo solvolysis by a merged mechanism, one that blends characteristics of both the S_N2 and S_N1 mechanisms. The following paper presents the history of their sustained pursuit of a merged mechanism and subsequent rebuttals to this claim. Several issues related to the philosophy and sociology of science are also discussed.     

Mild and Copper‐Free Stereoselective Cyanation of gem‐Difluoroalkenes by Using Benzyl Nitrile as a Cyanating Reagent

A novel copper‐free highly stereoselective cyanation of gem‐difluoroalkenes by using benzyl nitrile as a cyanating reagent with the assistance of tBuOLi under air atmosphere at room temperature was developed. A variety of versatile fluorinated alkenyl nitriles were obtained. The proposed mechanism involved the C?H bond oxidation, C?CN bond cleavage, and then nucleophilic vinylic substitution (S_NV).     

Mechanistic study of multi-step nucleophilic substitution for trifluoromethylated styrenes

The key steps of the reactions of nitrogen nucleophiles with β-halogen-β-trifluoromethylstyrenes have been studied by ¹⁹F and ¹H NMR monitoring and quantum-chemical calculations. In contrast to the mechanism proposed earlier for nucleophilic vinylic substitution of captodative carbonyl-bearing haloalkenes, this reaction proceeds via either E–Ad or Ad–E sequence depending on the nature of aromatic substituents of the parent styrenes.     

An alternate approach to quinoline architecture via Baylis-Hillman chemistry: SnCl2-mediated tandem reaction toward synthesis of 4-(substituted vinyl)-quinolines

An alternate approach to densely substituted quinolines from the products of S_N2 nucleophilic substitution reaction between the acetyl derivatives of the Baylis-Hillman adducts obtained from 2-nitrobenzaldehydes and the carbonyl group containing carbon nucleophiles is described. Treatment of these compounds with SnCl₂, triggers a tandem reaction wherein reduction of the nitro group is followed by a remarkably regioselective intramolecular cyclization and subsequent dehydrogenation to afford 4-(substituted vinyl)-quinolines.     

SILICON-PHOSPHORUS ANALOGIES THE MECHANISM OF NUCLEOPHILIC SUBSTITUTION AT SILICON AND PHOSPHORUS ACTIVATED BY EXTERNAL NUCLEOPHILES EXTENSION OF COORDINATION OF THE REACTIVE SPECIES

Abstract

A comparison is made concerning the mechanism of S_N2 reactions of silicon and phosphorus compounds, catalyzed by nucleophiles. The rate-law of the catalyzed solvolysis of halogenophosphorus esters corresponds to a mechanism with extension of coordination of the reactive species. The overall inversion observed with chlorophosphonates affords a distinction between a nucleophilic activated substitution S_NA (P) and a nucleophilic double displacement at phosphorus.     

A novel synthesis of functionalized 1,1-difluoro-1-alkenes via isolable 2,2-difluorovinylsilanes

Various 1,1-difluoro-1-alkenes such as monosubstituted 1,1-difluoro-1-alkenes, 2-bromo-1,1-difluoro-1-alkenes, and 1,1-difluoro-3-hydroxy-1-alkenes are prepared in two simple steps from 1-trifluoromethylvinylsilane: (i) its S_N2′ reaction with nucleophiles to construct 2,2-difluorovinylsilanes and (ii) the subsequent substitution of electrophiles for the vinylic silyl group.     

Transition-Metal-Free Coupling of Polyfluorinated Arenes and Functionalized,Masked Aryl Nucleophiles

A chemoselective C(sp²)−C(sp²) coupling of sufficiently electron-deficient fluorinated arenes and functionalized N-aryl-N’-silyldiazenes as masked aryl nucleophiles is reported. The fluoride-promoted transformation involves the in situ generation of the aryl nucleophile decorated with various sensitive functional groups followed by a stepwise nucleophilic aromatic substitution (S_NAr). These reactions typically proceed at room temperature within minutes. This catalytic process allows for the functionalization of both coupling partners, furnishing highly fluorinated biaryls in good yields.     

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.     

Activation Strain Analyses of Counterion and Solvent Effects on the Ion-Pair SN2 Reaction of and CH3Cl

We have computationally studied the bimolecular nucleophilic substitution (S_N2) reactions of M_nNH₂⁽ⁿ⁻¹⁾ + CH₃Cl (M⁺ = Li⁺, Na⁺, K⁺, and MgCl⁺; n = 0, 1) in the gas phase and in tetrahydrofuran solution at OLYP/6-31++G(d,p) using polarizable continuum model implicit solvation. We wish to explore and understand the effect of the metal counterion M⁺ and of solvation on the reaction profile and the stereochemical preference, that is, backside (S_N2-b) versus frontside attack (S_N2-f). The results were compared to the corresponding ion-pair S_N2 reactions involving F⁻ and OH⁻ nucleophiles. Our analyses with an extended activation strain model of chemical reactivity uncover and explain various trends in S_N2 reactivity along the nucleophiles F⁻, OH⁻, and , including solvent and counterion effects. © 2019 Wiley Periodicals, Inc.     

Kinetics of the reaction of the potassium salt of trinitromethane with normal primary alkyl iodides in acetone

Conclusions The kinetics of the reaction of the potassium salt of trinitromethane with normal primary alkyl iodides was studied. The reaction proceeds according to a mechanism of bimolecular nucleophilic substitution (S_N2) and represents alkylation of the trinitromethane anion at the carbon atom.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 720–725, April, 1970.     

1,3‐Difunctionalization of Aminocyclopropanes via Dielectrophilic Intermediates

We report an oxidative ring‐opening strategy to transform acyl, sulfonyl or carbamate protected aminocyclopropanes into 1,3‐dielectrophilic carbon intermediates bearing a halide atom (Br, I) and a N,O‐acetal. Replacing the alkoxy group of the N,O‐acetal can be achieved under acidic conditions through an elimination–addition pathway, while substitution of the halides by nucleophiles can be done under basic conditions through a S_N2 pathway, generating a wide range of 1,3‐difunctionalized propylamines. A proof of concept for asymmetric induction was realized using a chiral phosphoric acid (CPA) as catalyst, highlighting the potential of the method in enantioselective synthesis of important building blocks.     

Nucleophilic and organometallic displacement reactions of allylic compounds: stereo-and regiochemistry

Allylic alcohols, esters, halides and related compounds have been of mechanistic and synthetic interest for years. This Report focuses on the stereo- and regiochemical aspects of three reaction types: the S_N2' reaction (bimolecular nucleophilic substitution with allylic rearrangement); displacement reactions effected by organometallic reagents; the conversion of allylic alcohols into halides.     

Special features of the nucleophilic substitution of halogen in alkyl and benzyl halides with anions generated from 4-hydroxy-2-mercapto-6-methylpyrimidine

The nucleophilic substitution of halogen (chlorine, bromine, and iodine) in alkyl and benzyl halides has been effected in aqueous dioxane media with S-and O-anions generated from 4-hydroxy-2-mercapto-6-methylpyrimidine. Under these conditions replacement of halogen proceeds by an S_N2 mechanism and the reactivity of S-anions is 10 times greater than that of O-anions, which is in agreement with the results of ab initio quantum-chemical calculations of the electronic structure and total energy of transition states, carried out within the framework of the restricted Hartree-Fock method, basis 6-31G**. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 874–883, June, 2008.     

Chlor-fluor-austauschreaktionen mit antimonhalogeniden

The kinetics and mechanism of Cl-F exchange between C-Cl-containing compounds and antimony(V) halides are discussed. The reaction proceeds via the formation of fluorine bridges through an S_N mechanism. This contradicts the mechanism proposed by Booth and Swineheart [1]. Complex formation of different antimony halides in the system influences and sometimes inhibits the exchange. The role of other fluorinating agents together with antimony halides is described.     

Nucleophilic vinylic substitutions of (Z)-(2-aroyloxyvinyl)phenyl-λ-iodanes with tetrabutylammonium halides: vinylic SN2 reactions and ligand coupling on iodine(III)

Treatment of (Z)-(β-benzoyloxyvinyl)phenyl-λ³-iodanes, readily prepared from ethynyl(phenyl)(tetrafluoroborato)-λ³-iodane via stereoselective Michael-type addition of benzoic acids in methanol in the presence of sodium benzoates, with tetrabutylammonium halides in THF at 65 °C results in a vinylic S_N2 reaction to give the inverted (E)-β-benzoyloxyvinyl halides in high yields.