(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• candidates in development. Bioisosteres of para-benzenes, such as those based on bicyclo[1.1.1]pentane, are now very common and can be used to increase aqueous solubility and improve metabolic stability, among other benefits. Bioisosteres of ortho- and meta-benzenes were for a long time severely

• benzenes are by now relatively well established. Cubanes [16][17], alkynes [18], and bicyclo[2.2.2]octanes [19] can all replicate the linear geometry of the para-substituents, but arguably the most well-investigated para-benzene bioisostere is bicyclo[1.1.1]pentane (BCP) [20][21][22][23] (Figure 1). The

• parent compounds over a wide range of concentrations. Nevertheless, the data indicates that the 3-oxa-1,5-BCH scaffold can be used as a bioisostere of an ortho-benzene. 1,2-Disubstituted bicyclo[3.1.1]heptanes Apart from the previously discussed isosteric replacements based on the bicyclo[1.1.1]pentane

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• chemoselective in the presence of other oxidisable moieties such as in the cases of 2i and 2j. Additionally, the stereoconfiguration of the styryl moiety was maintained as confirmed via the X-ray structure of 2j (Scheme 3). As a potential application of our previously reported synthesis of useful bicyclo[1.1.1

• ]pentane (BCP) building blocks [36], we investigated their use in the oxadiazole-forming reaction. The BCP acid chloride 5 was synthesised from [1.1.1]propellane (3) via the photochemical reaction with isopropyl 2-chloro-2-oxoacetate (Scheme 4). The corresponding BCP acyl hydrazone was then obtained

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• some cases can be undesirable. Recent studies from our group have been carried out on the use of halogens as a binding motif in cubanes [15], bicyclo[1.1.1]pentane [16], and nonplanar porphyrins [17]. Another reason to investigate the effect of meso-halogenation of porphyrins is due to the potential of

Insertion of [1.1.1]propellane into aromatic disulfides

• Robin M. Bär,
• Gregor Heinrich,
• Martin Nieger,
• Olaf Fuhr and
• Stefan Bräse

Beilstein J. Org. Chem. 2019, 15, 1172–1180, doi:10.3762/bjoc.15.114

• in most cases. Single crystal X-ray diffraction analysis confirms the rod-like structure of the [2]staffanes that is often required in material applications. Keywords: bicyclo[1.1.1]pentane; bioisosteres; disulfides; linkers; [1.1.1]propellane; Introduction Rigid structures are emerging in both

• , which was opened with free radicals in most cases. The reaction with diacetyl and subsequent oxidation leads to the important intermediate bicyclo[1.1.1]pentane-1,3-dicarboxylic acid which provides access to unsymmetrically substituted BCPs (not shown) [13]. It is assumed that the reaction of 1 with