Thiourea Friedel-Crafts alkylation, nitroalkenes

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). 

Ricci et al studied a series of thiourea catalysts for the Friedel-Crafts alkylation of aromatic and heteroaromatic compounds with nitroalkenes. They have succeeded in developing the Friedel-Crafts alkylation of indoles with nitroalkenes for the first time by means of a novel thiourea catalyst (13) (Scheme 2.48) [101]. The authors proposed the bifunctional nature of the thiourea catalyst, where thiourea activates the nitro group and at the same time the free alcoholic function interacts with the indole proton through a weak hydrogen bond, directing the attack of the incoming nucleophile on the Si face of the nitroalkene (Figure 2.18). 

The use of naphthols 145 as the carbon nucleophilic readion component in Friedel-Crafts type Michael addition readions was also reported in 2007 by Chen and coworkers [43], In this system, the pronucleophile is activated by the quinuclidine unit of bifundional cinchona-based thiourea catalysts such as 81a. A range of aryl-and alkyl-substituted nitroalkene derivatives 124 were applicable to this system. The corresponding adducts 146 were obtained with 85-95% ee at low temperature... 

On the other hand, 2-naphthols have been used with different success as Michael donors in conjugate Friedel Crafts reactions with nitroalkenes and related substrates (Scheme 4.53). For example, cinchonine-derived thiourea 72b was identified as an excellent promoter for the reaction of a wide variety of 2-naphthols and nitroolefins, providing excellent yields and enantioselectivities. Remarkably, the more challenging p-alkyl substituted nitroalkenes were also found to undergo the reaction in a highly stereoselective way and with comparable yields to those obtained when nitrostyrene derivatives were employed. 

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