Nucleophilic aromatic substitution by organostannylsodiums. A second-order reaction displaying a solvent cage effect

Abstract

Results of a study of mechanistic aspects of the reaction of triorganostannylsodiums with halobenzenes are reported. The reaction in tetraglyme, which is first order in each reactant, is unusually fast for an unactivated nucleophilic aromatic substitution, and provides high yields of arylstannanes, R3SnAr. Minor amounts of R3SnAr2 and R4Sn are also formed by a mechanism which is presumed to involve initial dissociation of R3SnNa into (RzSn) and RNa. Reduction product, ArH, is formed when effective proton donors are present in the reaction mixture. ArD is formed when 2-propanol-4 is present, indicating that aryl anions are intermediates. The initial step in the proposed mechanism of the reaction between the aryl halide and organostannylsodium results in the formation of caged species, which may react in the cage to form substitution product, ArSnR3, or diffuse from the cage as ArNa and R3SnX, which may react with each other to form more substitution product or with other species present in the bulk of the solvent. This concept of the mechanism is based on the results of proton trapping, which shows a saturation effect, and on the effect of solvent viscosity on the fractions of ArH and ArSnR3 formed in the presence of tertbutyl alcohol. Study of the course of reactions of trimethylstannylsodium with aryl bromides bearing intramolecular traps such as ketone carbonyls and hydroxyl groups provides support for the mechanism proposed. The order of reactivities of aryl halides is Arl > ArBr > ArCl > ArF.

The Reaction of the [CpFe(CO)2]− Anion with Pentafluorochlorobenzene: Nucleophilic Aromatic Substitution by Halogen-Metal Exchange

“…Thus, for the reactions of the Me 3 Sn À anion with halobenzenes the mechanism with halogen transfer in the solvent cage as a key step was established by Kuivila et al [29] The effect of MeCN, similar to that observed in our study, has been reported in the reaction of another metal-centred nucleophile, [Re(O)(R ± CC ± R) 2 ] À (R Et, Ph) with halobenzenes. [30] Instead of the s-aryl rhenium complex observed in benzene solution, when the reaction was carried out in MeCN cyanomethyl complex NCCH 2 ± [Re(O)(RCCR) 2 ] was formed with the equivalent amount of benzene.…”

Labeling monoclonal antibodies and F(ab')2 fragments with the alpha-particle-emitting nuclide astatine-211: preservation of immunoreactivity and in vivo localizing capacity.

“…Decreasing the bulk of the alkyltin substituent has been shown to increase the rate of iododestannylation (17,28) Although the astatination of mAbs has been reported (29)(30)(31), retention of immunocompetence after 211At labeling was not demonstrated. In the present study, we have shown that 81C6 IgG2b mAb and Mel-14 IgG2a F(ab')2 fragment can be labeled with 211At and retain their specific binding to human glioma homogenates in vitro.…”

Metal carbonyl anions as model metal-centered nucleophiles in aromatic and vinylic substitution reactions

“…Their ability to react with unactivated aryl and vinyl halides, which are inert towards conventional nucleophiles, forms another aspect of their exceptional nucleophilic reactivity. [6][7][8][9][10][11][12][13][14] The term "supersoftness" is used to refer to much higher affinity of metal-centred anions towards organic substrates with soft leaving groups, e.g. higher than usual k I /k OTos or k I /k Br ratios.…”

“…higher than usual k I /k OTos or k I /k Br ratios. While evident already in aliphatic S N 2 reactions, [4][5][6]15 in aromatic and vinylic substitution with metal centred anions the leaving group effect is often reversed: from F>>Cl, Br, I typical for Ad N E mechanism it changes to I>Br>Cl>F. [6][7][8]12,[14][15][16][17][18] The last but not least is the high reducing power of metal-centred nucleophiles. Their reactions with organic halides formally considered as nucleophilic are frequently accompanied by the formation of dehalogenated or homocoupled products.…”