Deployment of Small-Ring Azaheterocycles as Building Blocks for the Synthesis of Organofluorine Compounds

Abstract

This account describes the endeavors made by our group concerning the synthesis of aziridines and azetidin(on)es and their use as novel building blocks for the preparation of nitrogen-containing organofluorine compounds. The majority of contributions, covered in the first part, comprises the study of fluorinated small-ring substrates, focusing on both their synthesis and their synthetic applicability for further transformations. These investigations revealed a pronounced effect of fluorine on the overall reactivity of small-ring azaheterocycles, often resulting in a different behavior compared with that of their nonfluorinated counterparts. In the second part, contributions are covered dealing with the transformation of nonfluorinated small rings into fluorinated target molecules upon treatment with fluorinated reagents.

Access to 2-Fluorinated Aziridine-2-phosphonates from α,α-Halofluorinated β-Iminophosphonates—Spectroscopic and Theoretical Studies

“…The aziridine motif frequently appears in biologically active compounds [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Therefore, this heterocyclic three-membered ring motif also serves as an attractive building block for organic transformations owing to the strained ring system and its ability to undergo highly regio- and stereospecific ring-opening reactions [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

“…Among the commonly encountered substituents in aziridine systems, heteroatoms or heteroatom-based groups, such as fluorine or phosphonates are of special interest [ 8 , 14 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Incorporating electronegative fluorine atoms in organic molecules often dramatically influences the physical and biological properties of the parent compounds [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

Asymmetric synthesis of CF2-functionalized aziridines by combined strong Brønsted acid catalysis

“…Among them, the introduction of fluorine or fluoroalkyl groups into three-membered N-heterocycles has emerged as an attractive direction due to the unique fluorine effect in pharmaceuticals and biology [7][8][9][10][11]. In this context, it is not surprising that the syntheses of trifluoromethylaziridines have been pursued from versatile precursors [12][13][14][15][16][17][18][19][20][21][22][23][24][25]. However, catalytic asymmetric approaches to chiral CF 3 -functionalized aziridines have only been reported by Cahard in 2012, who utilized trifluorodiazoethane (CF 3 CHN 2 ) as the nucleophile to react with aldimines catalyzed by chiral phosphoric acid (Scheme 1a) [26].…”