Aromatic Aminocatalysis

Abstract

Aromatic aminocatalysis refers to transformations that employ aromatica mines, such as anilineso ra minopyridines, as catalysts. Owing to the conjugation of the amine moiety with the aromatic ring, aromatic amines demonstrate distinctive features in aminocatalysis compared with their aliphatic counterparts. For example, aromatic aminocatalysis typically proceeds with slower turnover,b ut is more active and conformationally rigid as ar esult of the stabilized aromatic imine or iminiums pecies. In fact, the advent of aromatic aminocatalysis can be traced back to before the renaissance of organocatalysis in the early 2000s. So far,aromatic aminocatalysis has been widely applied in bioconjugation reactions through transamination;i na symmetrico rganocatalysis through imine/enamine tautomerization;and in cooperative catalysis with transition metals through CÀH/CÀCa ctivation and functionalization. This Focus Review summarizes the advent of and major advances in the use of aromatic aminocatalysisi nb ioconjugation reactions and organic synthesis.

Organocatalysis in aqueous media

“…A commonly applied primary amine organocatalyst is aniline 32 (see ref. 133 for review). 32 catalyses the popular bioconjugation strategies of hydrazone and oxime formation through a transamination mechanism (Fig.4, Table 1 -reaction 16).…”

“…The bioconjugation enables amongst others functionalization of polymers 134 and biomolecules for in vitro and in vivo studies. 133,135 The nucleophilic catalytic mechanism of 32 was elucidated by Cordes and Jencks back in 1962 (FIG. 4a).…”

Unlocking Iminium Catalysis in Artificial Enzymes to Create a Friedel–Crafts Alkylase

“…Aniline and its derivatives are rather limited in their catalytic capabilities 64 − 66 which include hydrazone formation previously demonstrated with LmrR_pAF 33 , 42 but not the full breadth of iminium-based transformations catalyzed by other amine catalysts. 19 Here we have demonstrated that the microenvironment provided by the LmrR scaffold greatly improves the catalytic properties of the pAF aniline side chain, facilitating catalysis that is normally only achieved efficiently with secondary amine catalysts.…”

Unlocking Iminium Catalysis in Artificial Enzymes to Create a Friedel-Crafts Alkylase

“…Aniline and its derivatives are rather limited in their catalytic capabilities [63][64][65] which include hydrazone formation previously demonstrated with LmrR_pAF 32,41 but not the full breadth of iminium-based transformations catalysed by other amine catalysts. 19 Here we have demonstrated that the microenvironment provided by the LmrR scaffold expands the catalytic properties of the pAF residue beyond those inherent to the sidechain by itself, achieving catalysis normally associated with secondary amines.…”