Semeno, Volodymyr V. Vasylchenko, Vadym O. Vashchenko, Bohdan V. Lutsenko, Dmytro O. Iminov, Rustam T. Volovenko, Olesia B. Grygorenko, Oleksandr O. Building the Housane: Diastereoselective Synthesis and Characterization of Bicyclo[2.1.0]pentane Carboxylic Acids An approach to 1,3-disubstitued bicyclo[2.1.0]­pentane (housane) derivatives was developed. The method relied on lithium bis­(trimethylsilyl)­amide-mediated intramolecular cyclization of trisubstitued cyclopentane carboxylates bearing a leaving group (at the C-4 position) and an additional substituent (at the C-3 atom), in turn synthesized from cyclopent-3-ene carboxylate. The synthetic sequence allowed for the preparation of both <i>cis</i>- and <i>trans</i>-1,3-disubstituted housane-1-carboxylic acids in diastereoselective manner on up to 80 g scale. In particular, bicyclic γ-amino acidsγ-aminobutyric acid analogueswere synthesized. It was shown that the bicyclo[2.1.0]­pentane did not significantly affect p<i>K</i><sub>a</sub> of the corresponding derivatives and slightly increased their hydrophilicity (by 0.07–0.25 Log <i>P</i> units) as compared to cyclopentane. X-ray diffraction studies showed that <i>cis</i>- and <i>trans</i>-1,3-disubstituted housanes can be considered as flattened analogues of the corresponding cyclopentane derivatives with fixed envelope conformation of the five-membered ring. p K;analogue;X-ray diffraction studies;bicyclic γ-;tran;bicyclo;five-membered ring;acid;trisubstitued cyclopentane carboxylates;cyclopent -3-ene carboxylate;housane;ci;Diastereoselective Synthesis;envelope conformation;C -4 position;80 g scale;diastereoselective manner;cyclopentane derivatives;disubstituted 2020-01-06
    https://acs.figshare.com/articles/dataset/Building_the_Housane_Diastereoselective_Synthesis_and_Characterization_of_Bicyclo_2_1_0_pentane_Carboxylic_Acids/11523174
10.1021/acs.joc.9b03044.s003