“Goldilocks Effect” of Water in Lewis-Brønsted Acid and Base Catalysis

Different catalytic protocols were
evaluated in the enantioselective
Pd-catalyzed aza-Michael reaction involving monoprotected
phenylenediamine (PDA) derivatives. The use of these nucleophilic
amines leads to the poisoning of the (monomeric) Lewis acidic catalyst,
and significant competitive formation of side products were observed.
In contrast, good yields and enantioselectivities can be attained
by employing the Brønsted basic–Lewis acidic dimeric Pd
catalyst, in combination with PDA derivatives protonated by triflic
acid. In this case, the presence of the right amount of water was
found to be critical for success (“Goldilocks effect”).
The results were rationalized on the basis of delicately balanced
acid–base equilibria, dependent upon the nature of the catalyst
and the amine.