Cyclobutane-Derived Diamines: Synthesis and Molecular Structure
J. Org. Chem. , 2010, 75 (17), 5941-5952
Cyclobutane diamines (i.e., cis- and trans-1,3-diaminocyclobutane, 6-amino-3-azaspiro[3.3]heptane, and 3,6-diaminospiro[3.3]heptane) are considered as promising sterically constrained diamine building blocks for drug discovery. An approach to the syntheses of their Boc-monoprotected derivatives has been developed aimed at the preparation of multigram amounts of the compounds. These novel synthetic schemes exploit classical malonate alkylation chemistry for the construction of cyclobutane rings. The conformational preferences of the cyclobutane diamine derivatives have been evaluated by X-ray diffraction and compared with the literature data on sterically constrained diamines, which are among the constituents of commercially available drugs.
Radchenko D. S.; Pavlenko S. O.; Grygorenko O. O.; Volochnyuk D. M.; Shishkina S. V.; Shishkin O. V.; Komarov I. V.
J. Org. Chem. 2010, 75 (17), 5941-5952