This is a repository for paper "Electrochemical Direct Arene Alkenylations without Directing Groups: Selective Late-Stage Drug Diversification".
Electrooxidation has emerged as an increasingly viable platform in molecular syntheses that can avoid stoichiometric chemical redox agents. Despite major progress in electrocatalyzed C−H activations, these arene functionalizations generally require directing groups to enable the C−H activation. The installation and removal of these directing groups calls for additional synthesis steps, which jeopardizes the inherent efficacy of the electrochemical C−H activation approach, leading to undesired waste with reduced step and atom economy. In sharp contrast, herein we present palladium-electrocatalyzed C−H olefinations of simple arenes devoid of exogenous directing groups. The robust electrocatalysis protocol proved amenable to a wide range of both electron-rich and electron-deficient arenes under exceedingly mild reaction conditions, avoiding chemical oxidants. This study points to an interesting approach of two electrochemical transformations for the success of outstanding levels of position-selectivities in direct olefinations of electron-rich anisoles. Physical organic parameters-based machine learning models were developed to enable the regioselectivity prediction in electrochemical C−H olefinations. Furthermore, late-stage functionalizations set the stage for the direct C−H olefinations of structurally complex pharmaceutically relevant compounds, thereby avoiding protection and directing group manipulations.
In order to run Jupyter Notebook involved in this repository, several third-party python packages are required. The versions of these packages in our station are listed below.
matplotlib = 3.4.2
morfeus = 0.5.5
numpy = 1.22.4
pandas = 1.3.3
rdkit = 2022.03.2
scipy = 1.4.1
seaborn = 0.11.1
sklearn = 0.23.2
xgboost = 1.3.3
Notebook 1 demonstrates the prediction of sites leave-one-out.
Notebook 2 demonstrates the prediction of compounds leave-one-out.
Notebook 3 demonstrates the external prediction.
Lin, Z., Dhawa, U., Hou, X. et al. Electrochemical Direct Arene Alkenylations without Directing Groups: Selective Late-Stage Drug Diversification. Nat. Commun., 14, 4224 (2023) DOI: https://doi.org/10.1038/s41467-023-39747-0.
Email: shuwen_li@zju.edu.cn