Combining catalysts having different or similar properties is currently an important topic in catalysis development. [1] Various catalyst combinations, such as Lewis acid/Brønsted base, [2] Lewis acid/Lewis base, [3,4] Lewis acid/Brønsted acid, [5] Lewis acid/Lewis acid, [5] and transition metal/Lewis acid [6] have been developed to provide unique catalytic activities. Herein we describe a different class of combination catalysts, in which Brønsted base catalysis is assisted by a Lewis base catalyst (Figure 1). A catalytic amount of Lewis basic bidentate phosphine oxide 1 effectively activated and modified the properties of Brønsted basic rare-earth metal aryloxide catalysts, switching the diastereoselectivity from syn to anti in the lanthanum-catalyzed direct Mannich-type reaction. The mechanistic studies, a preliminary trial in a catalytic asymmetric reaction, and the extension of the Lewis base/Brønsted base catalysis to Michael and nitroaldol reactions are also described.
We recently reported an iPr-pybox/La(OAr 1 ) 3 (Ar 1 = 4-MeO-C 6 H 4 ) complex which catalyzed the syn-selective direct asymmetric Mannich-type reactions [7] of imines 2 [8] with trichloromethyl ketone 3 a, an ester donor equivalent (Table 1, entry 1). [9,10] During the mechanistic studies of the reaction, we found that the reaction did not proceed with either La(OAr 1 ) 3 alone (Table 1, entry 2,) or iPr-pybox alone (Table 1, entry 3). In addition, an electron-donating Me 2 N group appended to iPr-pybox, which is sterically similar to the standard iPr-pybox, significantly decreased the diastereoselectivity (Table 1, entry 4). On the basis of these results, we hypothesized that the pybox acts not only as a simple chiral ligand to provide a steric bias in the transition state, but also as a Lewis base to electronically modify the properties of the Brønsted basic La(OAr) 3 . [11] To test this hypothesis involving Lewis base assisted Brønsted base catalysis, we decided to search for a new catalyst system.