3 substituted quinolines transfer hydrogenation

Scheme 3.46 Transfer hydrogenation of 2 substituted quinolines to tetrahydroquinolines.

Though efforts to reduce the environmental impacts of asymmetric imine hydro genation and transfer hydrogenation have been made, more progress is desirable in this field. The development of reusable catalysts that perform well in less toxic solvents would be particularly useful. Success in this area has been achieved in the hydrogenation of 2 substituted quinolines. 

Then, the same group extended this strategy to transfer hydrogenation of 3 substituted quinolines with up to 86% ee (Scheme 10.25) [27]. They thought the transfer hydrogenation of 3 substituted quinolines was also a cascade reaction involving 1,4 hydride addition, enantioselective isomerization, and... 

In 2008, Du and coworkers designed and synthesized novel double axially chiral phosphoric acid catalysts based on BINOL [28]. Subsequently, these catalysts have been successfully applied in asymmetric transfer hydrogenation of 2 substitued (Table 10.8) and 2,3 disubstitued quinolines (Scheme 10.26). They found that ether was the best solvent. For 2 substitued quinolines, up to 98% ee was obtained when the substitutent of catalyst was cyclohexanyl. 

Recently, an interesting principle of formation for 2-substituted quinoline derivatives was realized in the Pd-catalysed transfer hydrogenation/heterocyclization of (o-aminophenyl)ynones 60 in the presence of tertiary amin/formic acid to give 61 [96] ... 

The transfer hydrogenation of 3-substituted quinolines was also studied, with the particularity that the stereogenic center was generated in this case during the conjugate addition step (Scheme 4.60). ° The reaction needed for a more sterically demanding catalyst such as partially hydrogenated derivative 60f and, in addition, the nature of the Hantzsch ester required further optimization in order to achieve the best enantioselectivities, which still remained in values around 80% ee. In this case, the scope of the reaction was limited to the use of quinolines with aromatic or heteroaromatic substituents at the 3-position. 

N. Shindoh, H. Tokuyama, Y. Takemoto, K. Takasu, J. Org. Chem. 2008,73, 7451-7456. Auto-tandem catalysis in the synthesis of substituted quinolines from aldimines and electron-rich olefins cascade Povarov-hydrogen-transfer reaction. 

Mechanistically, the Brpnsted acid-catalyzed cascade hydrogenation of quinolines presumably proceeds via the formation of quinolinium ion 56 and subsequent 1,4-hydride addition (step 1) to afford enamine 57. Protonation (step 2) of the latter (57) followed by 1,2-hydride addition (step 3) to the intermediate iminium ion 58 yields tetrahydroquinolines 59 (Scheme 21). In the case of 2-substituted precursors enantioselectivity is induced by an asymmetric hydride transfer (step 3), whereas for 3-substituted ones asymmetric induction is achieved by an enantioselective proton transfer (step 2). 

Rather complex fragmentation is often observed with alkoxy-substituted azines, especially with quinolines and isoquinolines, and intramolecular transfer of a hydrogen atom from the ether alkyl group to a ring carbon atom appears... 

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