Beilstein J. Org. Chem.2021,17, 2585–2610, doi:10.3762/bjoc.17.173
subsequently deprotonates pyrrole to provide the stronger nucleophilic pyrrolide anion [27].
Similarly, Liu et al. accomplished an asymmetric intramolecular aza-Michael addition of various enone carbamates 10 using a chiral cinchona-based primary-tertiarydiamine as catalyst to obtain 2-substituted piperidines
appears that in this case, both activation mechanisms, namely through hydrogen bonding and iminium ion formation are operating.
Using the same chiral cinchona-based primary-tertiarydiamine as catalyst (cat. 11), Zhai et al. developed a highly efficient intramolecular enantioselective aza-Michael addition
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Graphical Abstract
Scheme 1:
Asymmetric aza-Michael addition catalyzed by cinchona alkaloid derivatives.
Beilstein J. Org. Chem.2014,10, 929–935, doi:10.3762/bjoc.10.91
in Michael addition reactions via an iminium–enamine catalysis [31][32][33][34][35][36][37]. A few applications of primary-tertiarydiamine in aldol reactions have been published [39][40][41][42][43]. To the best of our knowledge, however, the catalytic potential of amino acids derived primary
-tertiarydiamine organocatalysts for Michael reaction via enamine activation has not been investigated so far [38]. With readily available and inexpensive natural amino acids as a chiral source, we developed very simple primary-tertiarydiamine organocatalysts (Figure 2) for asymmetric aldol reactions [44
% ee after a reaction time of 24 hours (Table 3, entry 6) [46].
Even though an excellent level of enantioselectivity of the product was observed with catalyst 1a we screened different diamine catalysts in our quest for a superior catalyst. L-Isoleucine derived primary-tertiarydiamine catalysts having