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Carbon-carbon bond-forming processes that involve the deprotonation of a weakly acidic C-H pro-nucleophile using a strong Brønsted base are central to synthetic methodology. Enzymes also catalyze C-C bond formation from weakly C-H acidic substrates; however, they accomplish this at pH 7 using only collections of noncovalent interactions. Here, we show that a simple, bioinspired synthetic cage catalyzes Michael addition reactions using only Coulombic and other weak interactions to activate various pro-nucleophiles and electrophiles. The ani