Stille coupling amine nucleophiles

The triflate 125 is formed from the hydroxy precursor (Equation 131) and undergoes a variety of nucleophilic substitution processes <2006TL4437>, including Suzuki and Stille couplings (Equations 132 and 133, respectively). Amination of 125 with aliphatic amines occurs under thermal conditions, using either conventional or microwave heating (Equation 134), but the reactions of 125 with less reactive amines require palladium catalysis (Equation 135). 

Primary aromatic amines (e.g., aniline) and secondary aliphatic-aromatic amines (e. g., 7V-methylaniline) usually form triazenes in coupling reactions with benzenedi-azonium salts. If the nucleophilicity of the aryl residue is increased by addition of substituents or fused rings, as in 3-methylaniline and 1- and 2-naphthylamine, aminoazo formation takes place (C-coupling). However, the possibility has also been noted that in aminoazo formation the initial attack of the diazonium ion may still be at the amine N-atom, but the aN-complex might rearrange too rapidly to allow its identification (Beranek and Vecera, 1970). 

Interestingly, a first successful extension of the amination to oxygen nucleophils has been reported very recently. [19] Still at the beginning, this discovery opens the door to C-O coupling reactions for the synthesis of arylethers, including oxygen heterocycles. 

A number of nitrogen nucleophiles can be arylated by triflates, and this methodology has found application, for example, in the synthesis of nonsteroidal selective glucocorticoid modulators [91]. However, triflates are not always practical due to their sensitivity toward moisture and strong nucleophiles such as NaOtBu, which is still the most often utilized base in aminations. Buchwald et al. [92] reported the efficient coupling of nonaflates as an appealing alternative to triflates (Scheme 13.30). 

Compared with aUylic C-H bond, benzylic C-H bond has similar BDE. Under the oxidative conditions, it is still susceptible to undergo SET to form a benzyl radical or carbocation, which would like to be trapped by a series of C(sp )-H nucleophiles or electron-rich aromatic rings (Scheme 2.30). For example, active methylenic 1,3-dicarbonyl compounds [148-153], nitrogen nucleophiles (amines or amides or almidine), [154—158] IV-hydroxyamides [159], ketones [160, 161], aldehydes [162], electron-rich alkenes [163], aromatic rings [164, 165], and terminal alkynes [166] are good coupling partners in the oxidative benzylic C-H bond... 

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