1.2.3.4- Tetrahydroquinoline synthesis, asymmetric transfer

Scheme 10.24 Asymmetric synthesis of tetrahydroquinoline alkaloids by asymmetric transfer hydrogenation methods.

In 2009, Seidel and co-workers reported a Lewis acid-catalyzed [l,5]-hydride transfer reaction for the synthesis of polycyclic tetrahydroquinolines. It was found that the gadolinium triflate could efficiently accelerate the reaction (Scheme 4.4a). Preliminary attempts to realize asymmetric catalysis revealed that when a chiral magnesium bisoxazoline was utilized as the catalyst, the desired product 6a could be obtained in 74% yield and 30% ee, which was the first example of a catalytic asymmetric [l,5]-hydride transfer reaction by a chiral Lewis acid (Scheme 4.4b). The reason for the relatively low enanti-oselectivity was attributed to the reversibility of the ring-closure step in the presence of a strong Lewis acid catalyst. 

The Kim group envisioned that the saturated aldehydes 19 might also be used as viable substrates for asymmetrie [l,5]-hydride transfer/cyelization reactions by coupling the in situ generation of the o,p-unsaturated imin-ium intermediate 22 by oxidation (Seheme 4.11a). IBX (2.0 equiv.) was found to be the suitable organie oxidant compatible with the established catalytic system (20 mol% of C3 and 20 mol% of DNBS) for the asymmetric [l,5]-hydride transfer reactions. This novel cascade reaction also allows the efficient synthesis of ring-fused tetrahydroquinoline products with high enantioseleetivity. 

By combining regioselective Au(l)-catalyzed enamine synthesis with enantiose-lective transfer hydrogenation, the asymmetric synthesis of tetrahydroquinolines from simple 2-(2-propynyl)aniline derivatives has been achieved (Scheme 15.94). Here, a chiral Bronsted acid is used in combination with the Hantzsch ester to install the chiral center with up to 99% ee [316]. 

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