Catalytic enantioselective electrophilic aromatic substitutions

Dipartimento di Chimica G. Ciamician , Alma Mater Studiorum, Universitd di Bologna, Bologna, Italy 

Due to ubiquity of arenes in added value compounds, the stereochemical manipulation of aromatic species is rapidly becoming a hot spot in organic synthesis with developments both in metal-based and metal-free catalysis. 

Arene Chemistry Reaction Mechanisms and Methods for Aromatic Compounds, First Edition. Edited by Jacques Mortier. 

FIGURE 5.1 Pictorial representation of targeted benzylic stereocenters and common partners in catalytic 

From a mechanistic viewpoint, asymmetric Friedel-Crafts alkylation (AFCA) reactions are similar to the historical version, with the chiral additives responsible for triggering and controUing the overall aromatic C—H replacement. Interestingly, covalent (organocatalysis) or noncovalent (metal catalysis) interactions can take place between catalysts and electrophiles during the enantiodis-criminating step of the reaction course (Fig. 5.1). 

---

Despite the prevalence and importance of atropisomerism in organic structures, the field of asymmetric catalysis has not yet recorded extensive success in the development of catalysts, which control this stereochemical feature. Indeed, catalytic reactions of this nature are presently rare and only modest atropi-somer selectivity has been observed. In this context. Miller s group recently developed the DKR of biaryl atropisomers via peptide-catalysed asymmetric bromination. The reaction proceeded via an atropisomer-selective electrophilic aromatic substitution reaction using a simple bromination reagent such as A7-bromophthtalimide. As shown in Scheme 5.27, a series of chiral bromi-nated biaryl compounds could be prepared with excellent enantioselectivities of... 

---