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.