Liu Yanyao, Tranin Somanea, Chang Yu-Che, Piper Evan B, Fessard Thomas, Van Hoveln Ryan, Salome Christophe, Brown M Kevin
Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405, United States.
SpiroChem AG, 22 Mattenstrasse, 4058 Basel, Switzerland.
J Am Chem Soc. 2025 Feb 26;147(8):6318-6325. doi: 10.1021/jacs.4c13298. Epub 2025 Feb 17.
Rigid bicyclic hydrocarbons have emerged as important building blocks in the drug discovery industry. Despite progress in this general area, bicyclo[2.1.0]pentanes (housanes) are an understudied class of molecules. Herein we report an unconventional synthesis of borylated housanes. Our method features a broad scope and high diastereoselectivities in the synthesis of versatile intermediates. The route involves a strain-release diboration of bicyclo[1.1.0]butane and intramolecular deborylative alkylation. The versatility of the bridgehead boronic ester was demonstrated in several functionalizations. Lastly, the mechanism of the reaction was investigated, and an unusual stereospecific and diastereoselective ring expansion was uncovered.
刚性双环烃已成为药物发现行业中的重要构建模块。尽管在这一总体领域取得了进展，但双环[2.1.0]戊烷（屋烷）是一类研究较少的分子。在此，我们报道了一种硼化屋烷的非常规合成方法。我们的方法在合成通用中间体时具有广泛的适用范围和高非对映选择性。该路线涉及双环[1.1.0]丁烷的应变释放双硼化和分子内脱硼烷基化。桥头硼酸酯的多功能性在几种官能化反应中得到了证明。最后，对反应机理进行了研究，发现了一种不寻常的立体专一性和非对映选择性环扩张。
