Friedel-Crafts reactions through asymmetric activation

Asymmetric catalysis of Friedel-Crafts reaction with fluoral is established using chiral binaphthol-derived titanium catalysts with or without asymmetric activation to provide a practical synthetic route not only for chiral a-trifluorobenzylalcohols but so for highly enantiopure functionalized jS-trifluoroaldols through the sequential diastereoselective reactions of the resultant vinyl ethers or silyl enol ethers with electrophiles. 

We developed two highly efficient approaches toward the 5HT2b receptor antagonist LY414197. The first route utilized a Pictet-Spengler reaction to construct the racemic TH(3C derivative. Access to the most active (5)-enantiomer was then achieved in up to 70% yield through a one-pot resolu-tion-racemization process. The second approach is based on the chiral A-arenesulfonylated-1,2-diamine/ruthenium(II)-catalyzed asymmetric reduction of a 3,4-dihydro- 3-carboline precursor, obtained from a Bischler-Napieralski or related Friedel-Crafts methodology. 

Evans and coworkers [44] expanded the scope of enanti-oselective Friedel-Crafts alkylation of indoles 122 through the utilization of a series of p-snbstituted a,p-unsaturated phosphonates 123 and a,p-nnsaturated 2-acyl imidazoles 124 (Scheme 10.25). The active catalyst was proposed to be the respective complex of these enones in a bidentate fashion with bis(oxazolinyl)pyridine-scandium(III) triflate 125. Generally, this asymmetric addition reaction was found to be... 

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