Activated imine direct asymmetric hydrogenation

The presence of a heteroatom directly connected to the nitrogen atom of the imine activates it toward hydrogenation, while creating a second coordination site for the catalyst. Indeed, some successful results have been achieved for the hydrogenation of N-acylhydrazone, sulfonimide, and N-diphenylphosphinyl ketimines. The Et-DuPhos-Rh complex is an efficient catalyst for the asymmetric hydrogenation of a variety of N-acyl- ... 

All of the above mentioned W,X-acetalizations are based on the well-established ability of phosphoric acids and their derivatives to catalyze asymmetric additions of nucleophiles to imines. Imines are readily activated by Brpnsted acids due to their relatively high basicity, and the intermediate iminium ion possesses strong hydrogen bonding to the chiral anion (Scheme 7). This makes the ion pair reasonably well organized enabling an efficient enantiocontrol. The crucial step in the direct N,N- and 77,0-acetalizations of aldehydes is the intramolecular asymmetric addition to an iminium ion intermediate, which is formed after the condensation of the amide or amine moiety with the aldehyde (Scheme 7). 

Au(l)/Br0nsted Acid System Han et al. developed an unprecedented protocol to synthesize tetrahydroquinolines 332 directly from 2-(2-propynyl)aniline derivatives 365 in one pot under relay catalysis of an achiral Au complex 368 and a chiral phosphoric acid 5j [131]. The Au -catalyzed intramolecular hydroamination of 2-(2-propynyl)aniline provided the 1,4-dihydroquinolines 366, followed by isomerization into imine-like 3,4-dihydroquinoliniums 367 with 5j. This active intermediate then underwent asymmetric transfer hydrogenation with Hantzsch ester to produce enantioenriched tetrahydroquinoUne products (Scheme 2.97). 

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