Progressive Endergonic Synthesis of Diels–Alder Adducts Driven by Chemical Energy

The overwhelming majority of artificial chemical reaction networks respond to stimuli by relaxing towards an equilibrium state. The opposite response—moving away from equilibrium—can afford the endergonic synthesis of molecules, of which only rare examples have been reported. Here, we report six examples of Diels–Alder adducts formed in an endergonic process and use this strategy to realize their stepwise accumulation. Indeed, systems respond to repeated occurrences of the same stimulus by increasing the amount of adduct formed, with the final network distribution depending on the number of stimuli received. Our findings indicate how endergonic processes can contribute to the transition from responsive to adaptive systems. Going uphill. While most chemical reactions proceed towards equilibrium, we describe herein how to drive Diels–Alder reactions away from equilibrium (ΔG >0) using the hydration energy of carbodiimides. Our strategy yielded products up to 400 % of what thermodynamics would allow at equilibrium. Progressive accumulation upon repeated fueling cycles unlocks adaptive behaviors in chemical reaction networks.