Friedel-Crafts additions

In 2006, Xu and Xia et al. revealed the catalytic activity of commercially available D-camphorsulfonic acid (CS A) in the enantioselective Michael-type Friedel-Crafts addition of indoles 29 to chalcones 180 attaining moderate enantiomeric excess (75-96%, 0-37% ee) for the corresponding p-indolyl ketones 181 (Scheme 76) [95], This constitutes the first report on the stereoselectivity of o-CSA-mediated transformations. In the course of their studies, the authors discovered a synergistic effect between the ionic liquid BmimBr (l-butyl-3-methyl-l/f-imidazohum bromide) and d-CSA. For a range of indoles 29 and chalcone derivatives 180, the preformed BmimBr-CSA complex (24 mol%) gave improved asymmetric induction compared to d-CSA (5 mol%) alone, along with similar or slightly better yields of P-indolyl ketones 181 (74-96%, 13-58% ee). The authors attribute the beneficial effect of the BmimBr-D-CSA combination to the catalytic Lewis acid activation of Brpnsted acids (LBA). Notably, the direct addition of BmimBr to the reaction mixture of indole, chalcone, d-CSA in acetonitrile did not influence the catalytic efficiency. 

Scheme 76 Michael-type Friedel-Crafts addition of indoles to chalcones...

Later, the same group reported the Friedel-Crafts addition of unprotected indoles to enecarbamates containing aliphatic substituents (Scheme 5.6) [13]. Use... 

Borane polymers were prepared by the Rohm and Haas Corp. by using the Friedel-Crafts addition to an olefinic linkage followed by a typical silicone hydrolytic polymerization. 

Besides the addition of such reagents as halogens, hydrogen halides, or the hypohalous acids, there are other reactions which appear to proceed through addition mechanisms, but the exact course of the process is sometimes considerably obscured. The Friedel-Crafts addition of alkyl halides to olefins (p. 145), the self-condensation of olefins, and the alkylation of isoparaffins are examples in which attack at the double bond seems to be led by a carbonium ion. 

The preparation and use of two new experimental resins was described by Morris and Fritz [16]. Both resins were prepared by simple Friedel-Crafts addition reactions. One has the carboxyl group attached to the benzene ring of a spherical polystyrene-divinylbenzene (PS-DVB) resin via a spacer arm of three carbon atoms. The carboxyl group is attached directly to the benzene ring in the other resin. Excellent ion chromatographic separations of metal ions are possible using these resins in conjunction with any of several complexing eluents. 

Scheme 2.113 Asymmetric conjugate Friedel-Crafts addition of pyrrols to enals...

Asymmetric Friedel-Crafts additions of indole (19) to N-sulfonyl aldimines (31) are also possible. Bn-BOX (32)/Cu(OTf)2 provides chiral 3-indolylmethanamine derivatives (33) in moderate to good yields and excellent enantioselectivities (Scheme 17.6) [11]. 

A gold(I)-catalyzed tandem heterocyclization/Friedel-Crafts addition (aryl C(sp )-H functionalization) between enynes 105 and electron-rich arenes 106... 

Fig. 8.24 ln(OTf)3 catalyzed Friedel-Crafts addition of aromatic ring to methyl trifluoropyruvate. 

SCHEME 11.12. Friedel-Crafts addition for the concise synthesis of frondosin. 

SCHEME 31.33. Friedel-Crafts addition of pyrroles followed by enantioselective protonation. 

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