Chalcones Friedel-Crafts alkylation

The synthesis of 2,4-diarylchromen-2-ols through the reaction of phenols with an excess of a chalcone in TFA involves sequential Friedel-Crafts alkylation, cyclisation to a 4/7-1-benzo-pyran, an intermolecular hydrogen transfer generates the 4-arylflavylium ion which is hydrated to give the final product (Scheme 12) <07JOC9383>. 

Scheme 4.57 Enantioselective conjugate Friedel-Crafts alkylation of indoles with chalcones.

To end this section, it has to be mentioned that there is a single example of a conjugate Friedel Crafts alkylation involving enones as Michael acceptors. In particular, a camphor-based sulfonic acid (94) has been used as catalyst in the reaction of indoles with chalcones (Scheme 4.57). It has also to be noted that the best conditions involved the use of catalyst 94 together with an ionic liquid (l-butyl-3-methyl-l//-imidazolium bromide BmimBr). However, although excellent yields were obtained for a set of different substrates tested, the enantioselectivities remained in rather low values. 

Polysubstituted 3,4-dihydro-3-nitro-2ff-chromans are obtained from the enantioselective Michael—Michael cascade reaction of chalcone enolates and nitromethane catalyzed by bifunctional thiourea 19 (Scheme 31) (13JOC6488) and tandem Friedel—Crafts alkylation—Michael addition reaction of nitroolefin enoates and 1-methylindole promoted by Zn(OTf)2 (13S601).A squaramide-tertiary amine catalyst promotes the asymmetric sulfa-Michael—Michael cascade reaction of thiosalicylates with nitroalkene enoates which leads to polysubstituted chromans in high yields with excellent stereoselectivities (13OL1190). 

Kobayashi et al. also reported asymmetric Friedel-Crafts-type alkylation reactions of an indole with a chalcone (Scheme 5) [49]. A chiral calcium complex... 

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