Results and Discussion
Continuing our efforts to develop efficient asymmetric hydrogenations of challenging substrates, we are conviced that the additional coordination of a directing group to the metal and attractions between the ligand and substrate play a crucial role for both high reactivity and stereoselectivity.[5,7] Typically, catalyzed by a bisphosphine-Rh complex bearing a large bite angle (SKP[8] or SDP[9]) and assisted by a directing group (amide or ester) present in substrates,β -branched enamides or enols have been hydrogenated to produceβ -chirogenic amines or alcohols in quantitative yields and with excellent enantioselectivities.[5,7f] Inspired by these results, we are wondering whether the challenging asymmetric hydrogenation of γ -branched allylamines bearing a remote directing group, which is considered to form a larger and more unstable coordinating ring, can be realized by adopting a similar strategy. The experimental studies in this work will provide an unprecedented protocol for the efficient synthesis of γ -chirogenic amines, while the computational results will give a reasonable explanation for the catalytic mechanism and stereocontrol.
Initially, the model substrate (E)-1a was tested in the Rh-catalyzed asymmetric hydrogenation (Table 1). (R )-BINAP (the P-Rh-P angle of its RhI-complex: 92°),[10] (R )-DTBM-SegPHOS, (R ,R )-Me-DuPhos (85°)[11] and (R ,R )-QuinoxP* (86°)[12] showed almost no reactivity. The desired product could be obtained in good conversion, but poor enantioselectivity by using (R ,R )-BenzP* (85°).[13](R )-PhanePhos, (R ,R )-Me-FcPhos (the P-Rh-P angle of an analogous RhI-complex: 99°)[14] and (R ,Sp )-JosiPhos (the P-Rh-P angle of an analogous RhI-complex: 95°)[15] promoted the hydrogenation with complete conversions, however unsatisfactory enantioselectivities were still observed. Similar to the trend observed for the asymmetric hydrogenation of β -branched enol esters and β -branched enamides,[5,7f] the ligands (R )-SDP and (R )-SKP, bearing a large bite angle in their RhI-complexes (97° according to the XRD of [Rh((R )-SKP)(cod)]SbF6 shown in Table 1), showed high activities and enantioselectivities. To our delight, the rhodium complex of (R )-SKP showed the most promising results, giving the desired product with both excellent conversion and a high enantioselectivity of 91% ee. After the screening of different solvents (entries 1-8), the enantioselectivity could be further increased to 92% ee by using ethyl acetate (EtOAc, entry 2). When the hydrogenation is carried out at lower hydrogenation pressures, the reactivity is reduced (entry 9). The substrate (Z)-1a gives the corresponding product with a better enantioselectivity of 97% ee but with the opposite configuration (entry 10). The substrate(E)-1a-Bz in which the phthaloyl group is replaced by a benzoyl group shows low reactivity and enantioselectivity (entry 11). Under the optimized reaction conditions, the substrate(E)-1a-H without phthaloyl group shows no reactivity (entry 12). The δ -branched substrate (E)-1a-δ , which possesses a longer distance between phthaloyl and vinyl groups, also shows no reactivity (entry 13). These results reveal that the presence of the phthaloyl group at a suitable position is important for the hydrogenation.