Halogen bonds, anilines

Fig. 4 Halogen-bonded adducts are pre-reactive complexes, which, under convenient conditions, can lead to covalent bonds breaking and forming. Perfluoroalkylation occurs when the complexes between iodoperfluoroalkanes and anilines are heated or irradiated in certain solvents...

Finally, we briefly report another interaction not very different from the hydrogen bonding interaction, involving amines and in particular anilines the halogen bond interaction. 

Copper(I)-catalyzed amination of iodobenzene with aniline in the presence of KO-t-Bu as base was described by Don and co-workers [56] (Scheme 22.12). They reported the use of the [Cu2(p-I)2(L)2] (L = l,2-bis(diphenylphosphino)-c/oi 0-carborane(12) (1)) catalyst, which showed a conversion of the amine of 58%, compared to no significant conversion without ligand 1. The conversion is in the range of the reaction of copper(I) iodide in the presence of 2,2 -dithiobis(5-nitropyridine) but lower than that of the 2,2 -bipyridine ligand [57]. It was postulated that the reaction proceeds via an insertion of the copper(I) species into the carbon-halogen bond as the initial step. 

Category Ic cyclizations involve formation of the C3-C3a bond and require aniline derivatives with a nitrogen substituent appropriate for such reaction. Some, but not all, such cyclizations also require an o-substituent, frequently halogen. The rctrosynthetic transformations corresponding to the most important of this group of syntheses are shown in Scheme 4.1... 

An alternative method for preparing phosphinous amides makes a profit on the high affinity between silicon and halogen atoms. This is the driving force of the reactions between halophosphanes and Ar-(trimethylsilyl)anilines, AT-(tri-methylsilyl)amides or AT-(trimethylsilyl)ureas and thioureas, as represented in the Scheme 6. In these processes the desired P-N bond and an halosilane are simultaneously formed [53,58-60]. 

Duong and Gaudemer studied the alkylation of (presumably) [Co -(DMG)2X], where X is pyridine, aniline, or water, by the cis and trans isomers of )S-bromostyrene (PhCH=CHBr) and the methyl ester of )3-chloroacrylic acid (CHCl=CHCOOMe) in 50% aqueous methanol, and found that the configuration of the double bond remained unchanged, i.e., the halogen had simply been replaced by cobalt. They suggested that the reaction involved the addition of cobalt, followed by the elimination of the halide ion (apparently without rotation around the C—C bond), i.e.. 

There are numerous other syntheses of indoles, and a modern example is the Wender synthesis. Here a 2-bromo-iV-(trifluoroacetyl)aniline in THF is deprotonated by butyllithium and then, in the same pot, reacted with fert-butyllithium to effect halogen-metal exchange to give the dilithiated derivative. To this intermediate is added an a-bromo ketone. A carbon-carbon bond is established first between the reactants, and then cyclization occurs to form a hydroxyindoline. Finally, dehydration generates the indole (Scheme 7.16). 

Recently, the arylation of several specific primary amines have been studied because of the potential biological relevance of the products or products further downstream in a synthetic sequence. For example, cyclopropylamine was shown to be a viable substrate for the coupling under standard conditions [203]. Reactions of 7-azabicyclo[2.2.1]heptane have also been conducted [204] under relatively standard conditions, but with bis(imidazol-2-ylidene) as ligand. Complexes of this ligand and DPPF showed similar catalytic activities, which proved to be superior to those of most bis(phosphine)s. ortfio-Halo anilines were also studied, in this case to provide access to carbolines after use of the halogen as a means of effecting cycliza-tions by an electrophilic or reductive C-C bond formation with the other N-aryl group [205]. 

When chlorobenzene is heated with sodamide, aniline is formed. However, a direct replacement of the halogen does not occur. The reaction proceeds through a highly reactive benzyne formed by elimination in which the cleavage of the C-H bond is the rate-determining step. The amide anion may then attack the symmetrical benzyne at either end of the benzyne triple bond (Scheme 4.9). 

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