Arylamines, hetero

In the original method, the Bischler synthesis, harsh acidic treatment of a-arylaminoketones (produced from the 2-haloketone and an arylamine) was used to bring about electrophilic cyclisation onto the aromatic ring these conditions often resulted in mixtures of products via rearrangements. It is now known that N-acylated-Q-arylaminoketones can be cyclised under much more controlled conditions, and in contrast to early work, this approach to indoles can even be used to produce hetero-ring-unsubstituted indoles. ... 

B/s-enaminones 52 with primary (hetero)arylamines were employed in a parallel solution-phase synthesis of a library of 22 1,4-dihydropyr-idine derivatives 53, while mono-enaminone 2 with amines produced substitution products 84. Two methods for 53 were developed (a) a one-step s5mthesis of DHPs 53 from fws-enaminones 52 (Method A) and (b) a two-step synthesis of DHPs 53 from the mono-enaminone 2 (Method B). 

Due to the ubiquity of (hetero)arylamines in biologically active compounds, natural products, and organic functional materials, the aromatic C-N formation has been widely explored over the last two decades [44, 45]. Among them, the... 

See, for instances (a) S. Santra, R R. Andreana, Org. Lett. 2007, 9, 5035-5038. A one-pot, microwave-influenced synthesis of diverse small molecules by multicomponent reaction cascades, (b) M. Presset, Y. Coquerel, J. Rodriguez, Org. Lett. 2009, 11, 5706-5709. Microwave-assisted domino and multi-component reactions with cyclic acyUcetenes expeditious syntheses of oxazinones and oxazindiones. (c) W.-J. Hao, B. Jiang, S.-J. Tu, X.-D. Cao, S.-S. Wu, S. Yan, X.-H. Zhang, Z.-G. Han, F. Shi, Org. Biomol. Chem. 2009, 7,1410-1414. A new mild base-catalyzed Mannich reaction of hetero-arylamines in water highly efficient stereoselective synthesis of 3-aminoketones under microwave heating, (d) P. Nun, J. Martinez, F. Lamaty, Synthesis 2010, 2063-2068. Microwave-assisted neat procedure for the Petasis reaction. 

In 2012, Martin-Matute and co-workers [83] reported another pincer ruthe-nium(II) complex-catalyzed selective A -alkylation of (hetero)arylamines with primary alcohols. When the method was extended to aliphatic amines, the authors found that the aliphatic amine moiety could not be oxidized or alkylated. Inspired by this finding, aminoalcohols were later used as the alkyl source for iV-alkylation of (hetero)aromatic amines. iV-Arylated diamines were selectively obtained in excellent yield (Eq. 10). 

By using certain ligands to improve the activity of the metal catalyst, the N-alkylation reactions could also be performed under milder conditions. In 2009, Kempe and co-workers reported that a [Ir(cod)Cl]2/P,N-ligand complex could enable the A -alkylation of (hetero)arylamines with alcohols under mild conditions of only 70 °C with a catalyst loading as low as 0.1 mol% (Eq. 23) [110]. In 2010, the same group designed a new P,N-ligand stabilized iridium complex 12 (Scheme 22) for efficient alkylation of anilines with alcohols under mild conditions... 

In 2015, Kempe and co-workers reported the first cobalt-catalyzed A-alkylation of (hetero)arylamines with alcohols under mild conditions (80 °C) with a relatively low catalyst loading (2 mol%) (Elq. 32) [133]. In 2016, Zhang and co-workers developed another pincer cobalt complex 19, which is an active catalyst for both imination and A-alkylation reactions of aromatic and aliphatic amines with alcohols under base-free conditions [134]. By using complex 19, monoalkylated amine products rather than the imines can be selectively achieved by simply adding 4 A molecular sieves to the reaction mixture (Eq. 33). 

Queiroz and her team 2dso reported the synthesis of aminodi(hetero)arylamines in 2012, using this reaction (Figure 2.6) [33]. 

Figure 2.6 Pharmaceutically attractive aminodi(hetero)arylamines prepared using the Buchwald-Hartwig reaction as reported by Queiroz and coworkers [33].

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