4, 4‐Difluorospiro[2.2]pentan‐1‐yl – A Fluorinated Substituent To Expand the Synthetic and Medicinal Chemists' Toolbox. Issue 40 (12th September 2022)

• Record Type: Journal Article
• Authors: Melnykov, Kostiantyn P.; Voloshyna, Olena V.; Vashchenko, Bohdan V.; Demchuk, Oleksandr P.; Hryshchuk, Oleksandr V.; Grygorenko, Oleksandr O.
• Is Part Of: European journal of organic chemistry. Volume 2022:Issue 40(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-12
• Subjects: Bicyclic compounds -- Building blocks -- Fluorine -- gem-Difluorocyclopropanation -- Spiro compounds; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202200863
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: Functionalized 4, 4‐difluorospiro[2.2]pentan‐1‐yl derivatives are proposed as promising building blocks for synthetic and medicinal chemistry. Scalable, efficient, and diastereoselective approach to their preparation via the difluorocyclopropanation of (2‐methylenecyclopropyl)methanol is developed. Stability of the title scaffolds towards common reaction conditions is confirmed by a series of typical functional group transformations. Physicochemical characteristics (p K a, log P, and aqueous solubility) and structural features of the key 4, 4‐difluorospiro[2.2]pentan‐2‐yl derivatives are established and compared with those of non‐fluorinated analog, 2, 2‐difluorinated isomer, as well as monocyclic gem ‐difluorinated counterparts. Abstract : Scalable and diastereoselective synthetic approach to 4, 4‐difluorospiro[2.2]pentan‐1‐yl derivatives by the difluorocyclopropanation of (2‐methylenecyclopropyl)methanol and further chemical modifications were disclosed. Structural features, p K a, log P, and aqueous solubility of the products were established and compared with those of non‐fluorinated and 2, 2‐difluorinated analogs, as well as monocyclic gem ‐difluorinated counterparts.