Phosphoric acid derivatives Friedel-Crafts alkylation

Subsequently, the chiral phosphoric acid catalyzed Friedel-Crafts alkylation attracted much attention and became the subject of comprehensive investigations. In particular, the reaction with indole was investigated extensively because it provided pharmacologically important 3-substituted indole derivatives in enantio-merically enriched forms. The groups of You [35], Terada [36], and AntUla [37] almost simultaneously developed a highly enantioselective Friedel-Crafts reaction of indoles 75 with aromatic imines 74 (Scheme 11.20). Interestingly, their reactions... 

This phosphoric acid derived from (i )-BINOL was also applied by Akiyama et al. as an organocatalyst to promote the highly enantioselective Friedel-Crafts alkylation of indoles with nitroalkenes, generating the corresponding Friedel-Crafts adducts with high yields and excellent enantioselectivities of up to 94% ee for a broad range of substrates in the presence of 3-A molecular sieves (Scheme 10.2). ... 

As mentioned above, a range of enantioselective transformations have been established using chiral phosphoric acids via the activation of imines and related nitrogen-substituted substrates. In contrast, the activation of carbonyl compounds, including a,P-unsaturated carbonyl compounds, by chiral phosphoric acids has been limited. In 2008, Zhou, He, and coworkers achieved the asymmetric Friedel-Crafts alkylation reaction of indole derivatives with 1,3-diaryl a,p-unsaturated... 

Scheme 22.35 Phosphonium ion-tagged chiral phosphoric acids 117 and 118 and their use in enantioselective Friedel-Crafts alkylations of indole derivatives.

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