Nucleophilic vinylic substitutions on unactivated substrates. : The behaviour of styryl alkyl sulphides and selenides towards sulphur and selenium nucleophiles.

Sodium alkanethiolates or lithium methyl selenide react with styryl alkyl sulphides and selenides, in DMF at 100°C, to give the products of vinylic or aliphatic substitution. The two nucleophilic reagents are extremely selective. In the case of RSNa the attack at the vinylic carbon atom is much faster than that at the aliphatic carbon atom and the (Z)- or (E)- styryl alkyl sulphides are obtained as the result of a stereospecific vinylic substitution which occurs with retention of configuration. On the contrary, in the case of MeSeLi, under the same experimental conditions, the only reaction occurring is the aliphatic substitution which affords the vinyl thiolate anions, as an equilibrium mixture of the (E)- and (Z)- isomers, or the vinyl selenide anions which retain the configuration of the starting styryl alkyl selenides.     

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.     

Weakly nucleophilic conjugate bases of superacids as powerful nucleophiles in vinylic bimolecular nucleophilic substitutions of simple β-alkylvinyl(aryl)-λ3-bromanes

We report herein, for the first time, the stereoselective synthesis of simple (E)-β-alkylvinyl(aryl)-λ(3)-bromanes via a boron-λ(3)-bromane exchange reaction and their unique bimolecular nucleophilic substitutions at the vinylic ipso carbon atom under mild conditions. Interestingly, even weakly nucleophilic anions such as conjugate bases of superacids (HBF(4), TfOH, Tf(2)CH(2), Tf(3)CH, Tf(2)NH, etc.) function as nucleophiles toward the vinyl-λ(3)-bromanes. For instance, the vinylic S(N)2 reaction of (E)-vinyl-λ(3)-bromanes with potassium bis(triflyl)methanide stereoselectively produced (Z)-vinyloxy oxosulfonium ylides with exclusive inversion of configuration via oxygen attack, while that with potassium bis(triflyl)imide afforded predominantly (Z)-vinyloxysulfoximines. In marked contrast, (E)-β-alkylvinyl-λ(3)-iodanes do not undergo the vinylic S(N)2 reaction with these conjugate bases of superacids. The differences between the nucleofugalities of aryl-λ(3)-iodanyl and aryl-λ(3)-bromanyl groups (the latter being greater) probably play a pivotal role in these unique reactions.     

Stereoselective synthesis of (Z)-enethiols and their derivatives: vinylic S(N)2 reaction of (E)-alkenyl(phenyl)-lambda3-iodanes with thioamides

[reaction: see text]. Exposure of (E)-beta-alkylvinyl(phenyl)-lambda3-iodanes to thioamides in dichloromethane at room temperature was found to result in a bimolecular nucleophilic substitution (S(N)2) at the vinylic carbon atom to give inverted (Z)-enethiols and/or (Z)-S-vinylthioimidonium salts. Vinylic S(N)2 reactions with thioureas are also discussed.     

Reaction of perfluoro-2-methylpent-2-ene with azoles

Perfluoro-2-methylpent-2-ene reacts with pyrazole, imidazole, 1,2,4-triazole, and benzotriazole to give products of the replacement of the vinylic fluorine atom. In the case of imidazole, the product of allylic fluorine substitution, 1,3-bisimidazolylperfluoro-2-methylpent-2-ene, is also formed. The structures of the products were confirmed by spectral data. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 835–837, April, 1997.     

Michael addition-elimination mechanism for nucleophilic substitution reaction of cycloalkenyl iodonium salts and selectivity of 1,2-hydrogen shift in cycloalkylidene intermediate

Reactions of cyclohexenyl and cyclopentenyl iodonium salts with cyanide ion in chloroform give cyanide substitution products of allylic and vinylic forms. Deuterium-labeling experiments show that the allylic product is formed via the Michael addition of cyanide to the vinylic iodonium salt, followed by elimination of the iodonio group and 1,2-hydrogen shift in the 2-cyanocycloalkylidene intermediate. The hydrogen shift preferentially occurs from the methylene rather than the methine beta-position of the carbene, and the selectivity is rationalized by the DFT calculations. The Michael reaction was also observed in the reaction of cyclopentenyliodonium salt with acetate ion in chloroform. The vinylic substitution products are ascribed to the ligand-coupling (via lambda3-iodane) and elimination-addition (via cyclohexyne) pathways.     

Synthesis of 2-nitrogenous derivatives of methyl (2E)-(2,3-dichloro-4-oxocyclopent-2-en-1-ylidene)acetate

Methyl (2E)-(2,3-dichloro-4-oxocyclopent-2-en-1-ylidene)acetate reacted with N-nucleophiles to give the corresponding 2-substituted derivatives via replacement of the vinylic chlorine atom according to the AdNE scheme.     

Reactions of (Me2N)3P with functionalized di- and trichlorocyclopentenones

2,3-Dichloro-4,4-ethylenedioxycyclopent-2-enone, its 5-chloroderivative, and 5-allyl-2,3,5-trichloro-4,4-dimethoxycyclopent-2-enone react with (Me₂N)₃P to give the corresponding products of substitution of the NMe₂ group for the vinylic Cl atom at C(3). Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2555–2556, December, 1998.     

Photostimulated reactions of vinyl phosphate esters with triorganostannides. evidence for an SRN1 vinylic mechanism

Ketones are converted into vinyl diethyl phosphate esters (VinDEP), which under photostimulation reacted with sodium trimethylstannide (1) or sodium triphenylstannide (2) in liquid ammonia affording vinylstannanes via a vinylic S(RN)1 mechanism. Thus, (1-phenylvinyl)DEP (3), (3,4-dihydro-1-naphthyl)DEP (7), (3,4-dihydro-2-naphthyl)DEP (9), (E)-(1,2-diphenylvinyl)DEP (12), (E/Z)-(1-methyl-2-phenylvinyl)DEP (14) and (E)-(1-phenyl-2-methylvinyl)DEP (16) react with 1 and 2, under photostimulation, leading to the corresponding substitution products in good to excellent yields (45-89%). On the other hand, there is no reaction between (1-cyclohexenyl)DEP (5) or (1-benzylvinyl)DEP (18) with either 1 or 2, under similar conditions. These reactions appear to be strongly dependent on structural features of the vinyl phosphate since only conjugated vinyl phosphates afforded substitution products. These substitution reactions are completely regioselective and stereoconvergent. It seems to be the first example of a vinylic S(RN)1 process involving organotin anions as nucleophiles.     

Inversion versus retention of configuration for nucleophilic substitution at vinylic carbon

A high-level computational study using CCSD, CCSD(T), and G2(+) levels of theory has shown that unactivated vinyl substrates such as vinyl chloride would afford gas phase, single-step halide exchange by a pure in-plane sigma-approach of the nucleophile to the backside of the C--Cl sigma bond. Geometry optimization by CCSD/6-31+G* and CCSD(T)/6-31+G* confirms the earlier findings of Glukhovtsev, Pross, and Radom that the S(N)2 reaction of Cl(-) with unactivated vinyl chloride in the gas phase occurs by a sigma attack. Complexation of vinyl chloride with Na(+) does not alter this in-plane sigma preference. However, moderately activated dihaloethylenes such as 1-chloro-1-fluoroethylene undergo gas-phase S(N)2 attack by the accepted pi-route where the nucleophile approaches perpendicular to the plane of the C==C. In the latter case a single-step pi pathway is preferred for the Cl(-) + H(2)C==CFCl reaction. This is the first definitive example at a high level of theory where a single-step pi nucleophilic vinylic substitution is preferred over a multistep mechanism in the gas phase. The activation barriers for these gas-phase single-step sigma- and pi-processes involving both naked anions and Na(+) complexes are, however, prohibitively high. Solvation and the presence of a counterion must play a dominant role in nucleophilic vinylic substitution reactions that proceed so readily in the condensed phase. In solution, nucleophilic vinylic substitution reactions involving electron-withdrawing groups on the carbon--carbon double bond (e.g., -CN, -CHO, and -NO(2)) would almost certainly proceed via a free discrete carbanionic intermediate in accord with experiment.     

A mechanistic and synthetic study of organocopper substitution reactions with some homoallylic and cyclopropylcarbinyl substrates : Application to isoprenoid synthesis

The double bond of cholesteryl and 5-norbornen-2-yl tosylates and the cyclopropane ring of cyclopropylmethylcarbinyl tosylate participate in organocuprate substitution reactions; retention of configuration at the nucleofugal sp³-C atom and skeletal reorganizations are observed. A plausible mechanism for these reactions is discussed. Coupling of homogeranyl iodide with a four-carbon, functionalized, vinylic cuprate reagent is applied to stereospecific synthesis of trans, trans-farnesol.     

Specificity of the reaction of 2,3-dichloro-4,4-dimethoxy-5-(2-methylfuran-3-yl)cyclopent-2-en-1-one with amines

2,3-Dichloro-4,4-dimethoxy-5-(2-methylfuran-3-yl)cyclopent-2-en-1-one reacted with diethyl-and dipropylamines to give products of Ad_NE replacement of the chlorine atom at the vinylic C³ atom and substitutive opening of the furan ring with simultaneous deprotection of the dimethyl acetal moiety in the 2,3-dichlorocyclopentenone fragment.     

Vicarious nucleophilic substitution of hydrogen versus vinylic substitution of halogen in the reactions of carbanions of halomethyl aryl sulfones with dialkyl halofumarates and halomaleates

Reaction of halomethyl aryl sulfone carbanions with dialkyl halofumarates and halomaleates results in nucleophilic substitution of hydrogen and/or of the halogen. The reaction with halofumarates proceeds via addition of the carbanions to the vinylic carbon atom connected with hydrogen, followed by base promoted β-elimination of hydrogen halide in which the halogen originates from the carbanion moiety or from the alkene. In the case of halomaleates the reaction proceeds via an elimination-addition sequence.     

Synthesis of hetero- and carbocycles by nucleophilic substitution at sp carbon

Vinylic halides having alcohol, sulfonamide, active methine, and thiol moieties as nucleophiles cyclize to hetero- and carbocycles by intramolecular nucleophilic substitution at the sp² carbon centers. The density functional theory calculations suggest that the cyclization proceeds through S_N2-type substitution (the in-plane vinylic nucleophilic substitution, S_NVσ), when vinyl halides are substituted with oxygen, nitrogen, and carbon nucleophiles. The substitution with sulfur nucleophiles, in contrast, proceeds through both routes of S_NVσ and out-of-plane vinylic nucleophilic substitution (S_NVπ).     

A simple and general preparation of vinylic sulfides, selenides and tellurides

A general method for the synthesis of vinylic chalcogenides by nucleophilic and Ni-catalyzed vinylic substitution on vinylic halides by phenyl chalcogenolates is described. The reactions were regio and stereoselective for the nickel catalyzed substitution, and mixture of isomers was observed for some examples in the thermal process in DMF.     

Competition between vinylic substitution and conjugate addition in the reactions of vinyl selenoxides and vinyl selenones with nucleophiles in DMF

Vinyl selenoxides and vinyl selenones present a different reactivity towards thiolate or alkoxide anions in DMF. In the case of selenoxides the addition of the nucleophiles regioselectively occurs at the α-carbon leading to the formation of the vinylic substitution products with complete retention of configuration. These reactions occur under very mild conditions indicating that the seleninyl group markedly enhances nucleophilic vinylic substitution rates. The results obtained with vinyl selenones are consistent with competitive nucleophilic attack at the α- and at the β-carbon. The former yields irreversibly the vinylic substitution products, whereas attack at the β-carbon leads to the reversible formation of selenonyl stabilized carbanions. The fate of these intermediates depends upon the nucleophilic reagent employed. With thiolate anions the vinyl selenones are rapidly subtracted from the equilibrium and the carbanion does not give any other product. With methoxide anions, on the contrary, the vinylic substitution is a slow process and the carbanion can give rise to conjugate addition products also. Malonate anions react only at the β-carbon of vinyl selenones and the resulting carbanions suffer proton transfer and intramolecular displacement of the selenonyl group to afford cyclopropane derivatives.     

Intramolecular Homolytic Substitution of Sulfinates and Sulfinamides

A general and efficient method for the synthesis of cyclic sulfinates and sulfinamides based on intramolecular homolytic substitution (S_Hi) at the sulfur atom by aryl or alkyl radicals is described. Both alkyl and benzofused compounds can be accessed directly from easily prepared acyclic precursors. Enantiomerically enriched sulfur‐based heterocycles were formed through an S_Hi process with inversion of configuration at the sulfur atom. Cyclization of prochiral radicals proceeded with varying stereochemical outcomes, depending on the size of the incoming radical. 2‐Pyridyl and 2‐quinolyl radicals led to biaryl compounds, which result from attack onto the ortho position of the arylsulfinate rather than a thiophilic substitution.     

Intramolecular cyclization of beta,beta-difluorostyrenes bearing an iminomethyl or a diazenyl group at the ortho position: synthesis of 3-fluorinated isoquinoline and cinnoline derivatives

o-Formyl-substituted beta,beta-difluorostyrenes readily react with NH(2)OH.HCl or NH(4)OAc to afford 3-fluoroisoquinoline derivatives in good yield via (i) the formation of the corresponding oximes or imines and (ii) subsequent intramolecular replacement of a vinylic fluorine by the sp(2) nitrogen of the iminomethyl group (HON=CH- or HN=CH-). Beta,beta-Difluorostyrenes bearing an o-diazenyl group (HN=N-), generated by reduction of the corresponding diazonium ions, undergo a similar substitution to afford 3-fluorinated cinnolines.     

5-Substituted 3-Nitro-1-vinyl-1,2,4-triazoles

A series of 5-substituted 3-nitro-1-vinyl-1,2,4-triazoles were synthesized by alkaline treatment of the corresponding 1-(2-haloethyl- or 2-nitroxyethyl)-3-nitro-1,2,4-triazoles and by transvinylation of NH acids of the same series with vinyl acetate. The scope of applicability of the transvinylation procedure was established with respect to the azole pK _a value. The vinylic double bond on the nitrogen was shown to be inactive toward both nucleophilic and electrophilic reagents, whereas the halogen atom in position 5 exhibits enhanced reactivity. The latter factor provides the possibility for versatile structural modification via nucleophilic replacement of the 5-halogen atom by various groups, including triazolate ion.     

Vinylic nucleophilic substitution in functionalized 2-vinylpyrroles: a route to a new family of stable enols

2-(2-Cyano-1-ethylthioethenyl)pyrroles easy exchange their ethylthio group for hydroxyl (NaOH, H₂O-methanol, 40-45 °C, 1 h) to give 2-(2-cyano-1-hydroxyethenyl)pyrroles, a new family of stable enols, in 50-94% yields. The vinylic nucleophilic substitution proceeds at the double bond of both the starting pyrroles and their cyclic isomers, 3-iminopyrrolizines. X-ray structure analysis and NMR spectra show the enols to be stabilized by exceptionally strong intramolecular H-bonding.