Catalysis, in principle, should offer an infinite turnover number for a desired chemical transformation by regenerating the catalyst without altering its molecular-level structure and physicochemical properties. However, limitations arise from different deactivation mechanisms and catalyst poisoning by chemical impurities and/or side products, lowering the lifetime of catalytically active species.
The field of organocatalysis has blossomed over the past few decades, becoming an alternative to transition-metal catalysis or even replacing the realm of transition-metal catalysis. However, a truly powerful organocatalyst with a high turnover number and turnover frequency while retaining high enantioselectivity is yet to be discovered. Despite many efforts, the current limit of catalyst loading for asymmetric organocatalysis is usually in the range of 0.1–1 mol% for overriding of the non-selective background pathway. Similar to metal catalysis, thus, extremely low catalyst loading (ppm or ppb levels) is the ultimate goal of the organocatalysis community.
Quite recently, we developed ppm-level loading asymmetric hydrogen-bond catalysis by designing an in-situ repairable catalyst system.1 For example, in the presence of catalyst healing agents (e.g., KF and Amberlite CG-50), 1 ppm loading of our chiral oligoethylene glycol catalyst was enough to achieve highly enantioselective silylation of functionally unbiased alcohols.

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