Saturated bioisosteres of benzene: where to go next?

Abstract

Saturated bioisosteres for ortho- and meta-substituted benzenes remain a current challenge for chemists.

Bicyclo[1.1.1]pentyl Sulfoximines: Synthesis and Functionalizations

“…The conditions for the N ‐arylation were optimized in this work and a good scope could be shown. For future applications C2‐substituted BCPs would be highly desirable . The combination with sulfoximines leads to a great extension of the accessible chemical space.…”

“…For future applications C2-substituted BCPs would be highly desirable. [26] The combination with sulfoximines leads to a great extension of the accessible chemical space.…”

Quaternary Centers by Nickel‐Catalyzed Cross‐Coupling of Tertiary Carboxylic Acids and (Hetero)Aryl Zinc Reagents

“…Simple acyclic acids as well as three-, four-, five-, six-, and seven-membered rings can also be enlisted. [13] Thestructures of products 8, 23,a nd 41 were confirmed by X-ray crystallographic analysis. Theu tility of the transformation was also demonstrated by the synthesis of product 28 derived from Gemfibrozil.…”

Cubane Electrochemistry: Direct Conversion of Cubane Carboxylic Acids to Alkoxy Cubanes Using the Hofer–Moest Reaction under Flow Conditions

“…[6] To date, the only practical large-scale synthesis of cubane leads to 1,4-cubanedicarboxylic acid, [1,7] and while cubane functionalisation has been extensively investigated, [8] in practice it has relied heavily on interconversions of the carboxylic acid functional group or indirect decarboxylative functionalisation reactions (Scheme 1). To the best of our knowledge, the only direct decarboxylative cubane CÀC bond formation is a single example of Pb(OAc) 4 -mediated Kochi coupling reported by Moriarty (Scheme 1). [9] More generally, redox-active esters (RAEs), such as the N-phthalimido ester 3, have proven to be useful intermediates in Fe-catalysed cubyl-aryl coupling to give 4.…”

“…First synthesised in the 1960s [1] and originally proposed as 3D benzene bioisostere in the 1990s, [2] it is only in the past decade that cubanes have gained real traction in medicinal chemistry. [3,4] Substituting a phenyl ring by a cubyl unit can lead to improved physical and biological properties. [5] In addition, 1,4-disubstituted cubanes have applications as non-aromatic rigid spacers in organic materials and polymers.…”