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Reactions of 2‐Aryl‐1,3‐Dithianes and [1.1.1]Propellane
Author(s) -
Trongsiriwat Nisalak,
Pu Youge,
NievesQuis Yexenia,
Shelp Russell A.,
Kozlowski Marisa C.,
Walsh Patrick J.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201905531
Subject(s) - propellane , chemistry , aryl , combinatorial chemistry , bioisostere , bicyclic molecule , stereochemistry , chemical synthesis , organic chemistry , biochemistry , alkyl , in vitro
Bicyclo[1.1.1]pentanes (BCPs) have sparked the interest of medicinal chemists due to their recent discovery as bioisosteres of aromatic rings. To study the biological activity of this relatively new class of bioisosteres, reliable methods to incorporate BCPs into target molecules are in high demand, as reflected by a flurry of methods for BCP synthesis in recent years. In this work, we disclose a general method for the synthesis of BCP‐containing dithianes which, upon deprotection, provide access to BCP analogues of medicinally abundant diarylketones. A broad scope of 2‐aryl‐1,3‐dithianes, including several heterocyclic derivatives, react with [1.1.1]propellane to afford 26 new derivatives in good to excellent yields. Further transformation of the dithiane portion into a variety of functional groups demonstrates the robustness of the products. A computational study indicates that the reaction of 2‐aryl‐1,3‐dithianes and [1.1.1]propellane proceeds via a two‐electron pathway.