High fidelity Suzuki-Miyaura coupling for the synthesis of DNA encoded libraries enabled by micelle forming surfactants.

DNA encoded chemical libraries provide a highly efficient means of screening vast numbers of small molecules against an immobilised protein target. Their potential is currently restricted by the constraints of carrying out library synthe-sis in the presence of attached DNA tags, for which a limited number of reactions and substrates can be used. Even established reactions, such as Suzuki-Miyaura couplings, do not give efficient coupling reactions across a wide range of substrates and can lead to significant DNA degradation. We developed an efficient protocol for carrying out Suzu-ki-Miyaura couplings on DNA tagged substrates that proceeds with unprecedented efficiency to the desired biaryl products (>98% on average with no detectable DNA degradation) across a wide range of drug-like substrates using a micellar promoted process with commercial TPGS-750-M surfactant. We have demonstrated the applicability of this method in DEL synthesis by preparing a prototypical 2-dimensional 36-membered library employing...