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Herein we report the synthesis of bicyclo[1.1.1]pentane (BCP)‐containing sulfonamides via a transition metal‐free process of a three‐component reaction among BCP‐containing N‐tosyl hydrazones, 1,4‐diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO), and amines. Different from existing methods to synthesize BCP‐containing sulfonamides, our method avoids the usage of sulfonyl halides, which could be challenging due to chemical instabilities. We have also demonstrated that this methodology is suitable for library synthesis of such sulfonamides. As a result, we can expect future application in drug discovery. [ABSTRACT FROM AUTHOR]

Within a medicinal chemist's toolbox, one of the most effective strategies to improve the overall properties of a biologically active compound is bioisosteric replacement. Ever since the first example of replacing benzene with a bicyclo[1.1.1]pentane (BCP) group was published in the late 1990s,[1] the medicinal chemistry community has continually been expanding the scope of such phenyl bioisosteric replacements. Recent interest from academia has focused on novel synthetic strategies to access C(sp3)‐rich bicyclic hydrocarbons with expanded ring sizes. Herein, we summarize some of these transformations and reveal that most rely on strain releasing cycloadditions with bicyclo[1.1.0]butane (BCB) and bicyclo[2.1.0]pentane (housane). We have organized this review based on the mechanism of such strain release strategies, namely, carbene cycloadditions, energy transfer photocatalyzed cycloadditions, electron transfer catalyzed cycloadditions, and polar cycloadditions. [ABSTRACT FROM AUTHOR]

Bicyclo[1.1.1]pentanes (BCP's) have been applied in medicinal chemistry as bioisosteres for phenyl groups. In pursuit of novel BCP analogs, we reported the first synthesis of 2,2‐difluorobicyclo[1.1.1]pentanes (BCP–F2) in 2019. Herein, we detail the extension of our effort in the synthesis of BCP‐F2 analogs. [ABSTRACT FROM AUTHOR]

This Minireview focuses on selected topics in the syntheses of bicyclo[1.1.1]pentane (BCP) analogues. A brief historical introduction was included. The content covers various synthetic routes of 1‐substituted and 1,3‐disubstituted BCPs. Selective examples of synthetically useful building blocks are summarized for each category for synthetic organic chemists' and medicinal chemists' reference. A compare‐and‐contrast analysis is also applied to evaluate these routes and to demonstrate the progress of strategic functional group transformations using modern organic methodologies. By systematically analyzing the synthetic strategies to access these strained molecules, we also hope that this Minireview will provide inspirations for future developments in this area. [ABSTRACT FROM AUTHOR]