Light-enabled scalable synthesis of bicyclo[1.1.1]pentane halides and their functionalizations
Vasyl Ripenko, Vadym Sham, Vitalina Levchenko, Serhii Holovchuk, Daniil Vysochyn, Ivan Klymov, Dmytro Kyslyi, Stanislav Y. Veselovych, Serhii Zhersh, Yurii V. Dmytriv, Andrey A. Tolmachev, Iryna V. Sadkova, Iryna Pishel, Kateryna Horbatok, Viktoria Kosach, Yelyzaveta Nikandrova, Pavel K. Mykhailiuk
Abstract
In 2012, bicyclo[1.1.1]pentanes were demonstrated to be bioisosteres of the benzene ring. Here, we report a general scalable reaction between alkyl iodides and propellane that provides bicyclo[1.1.1]pentane iodides in milligram, gram and even kilogram quantities. The reaction is performed in flow and requires just light; no catalysts, initiators or additives are needed. The reaction is clean enough that, in many cases, evaporation of the reaction mixture provides products in around 90% purity that can be directly used in further transformations without any purification. Combined with the subsequent functionalization, >300 bicyclo[1.1.1]pentanes for medicinal chemistry have been prepared. So far, this is the most general and scalable approach towards functionalized bicyclo[1.1.1]pentanes. A general and scalable approach to prepare functionalized bicyclo[1.1.1]pentanes is reported. The key reaction between alkyl iodides and propellane is performed in flow and requires just light; no catalysts, initiators or additives are needed. Combined with the subsequent functionalization, >300 bicyclo[1.1.1]pentanes for medicinal chemistry have been prepared.