Catalytic and Stereoselective Transformations with Easily Accessible and Purchasable Allyl and Alkenyl Fluorides

Abstract

Stereochemically defined organofluorine compounds are vital to drug discovery and many applicable catalytic strategies have been introduced for accessing these entities stereoselectively. One approach entails incorporation of a fluorine atom (CÀ F bond formation) or an organofluorine moiety (e.g., CF 3 or CF 2 H), and another exploits commercially available compounds with one or more fluorine atoms. Here, we present the state-of-the-art regarding the use of alkenyl and allylic fluorides in preparation of stereochemically defined fluoro-organic molecules. Allylic and alkenyl fluorides may be purchased or generated from a commercially available acid, carboxylate salt, ester, aldehyde hydrate, or ketone bearing several fluorine atoms next to a carbonyl group. We underscore the untapped potential of purchasable organofluorine compounds, many allylic and alkenyl fluorides, as launching points for development of stereoselective processes that are of value to therapeutic science."In sciences like chemistry, …experience demonstrates at every step that the work of the past has availed much, and that, without it, it would be impossible to advance 'into the ocean of the unknown.' We are compelled to value their history … and to engage in a work which not only gives mental satisfaction but is also useful."

Synthetic Advantages of Defluorinative C−F Bond Functionalization

“…These products can serve as amide bioisosteres, as previously discussed in the Vinyl C−F section [101a] . The scope of nucleophilic coupling partners can be expanded through metal‐catalyzed addition/β‐fluoride elimination reactions [168] . This reactivity and its utility are illustrated in Scheme 32c in an example reported by Taguchi, Yanai and co‐workers for the assembly of peptide isosteres via Cu‐catalyzed defluoroarylation with PhMgBr [169] .…”

“…[101a] The scope of nucleophilic coupling partners can be expanded through metal-catalyzed addition/β-fluoride elimination reactions. [168] This reactivity and its utility are illustrated in Scheme 32c in an example reported by Taguchi, Yanai and co-workers for the assembly of peptide isosteres via Cu-catalyzed defluoroarylation with PhMgBr. [169] Hoveyda, Ito and co-workers developed an enantioselective Cu-catalyzed defluoroborylation protocol that generates chiral allylic boronates (Scheme 32d).…”

“…[179] Metal-catalyzed addition/β-fluoride elimination sequences are widely developed for 1,1-difluoroalkene synthesis, with a survey of accessible products shown in Scheme 35. [168,180] Importantly, catalytic protocols for the enantioselective addition of aryl and alkyl groups provide access to difluoroalkene isosteres that map onto α-chiral carbonyl fragments. Furthermore, defluoroborylation and -silylation provide synthetically versatile chiral products.…”

Photocatalytic redox-neutral selective single C(sp3)–F bond activation of perfluoroalkyl iminosulfides with alkenes and water

“…[1][2][3][4][5][6][7][8] In particular, the preparation of compounds containing a tetrasubstituted tertiary carbon center with a triuoromethyl group and a uorine atom has recently drawn increasing attention due to their unusual reactivity proles to corresponding host compounds. [9][10][11][12][13][14] The primary methods for synthesizing these molecules largely rely on specialized uorinated functional groups and/or the stoichiometric use of uorinating reagents. [15][16][17][18][19][20][21][22][23] Although selective C-F bond functionalization of easily accessible multiuorinated compounds has shown massive potential for atom-and stepeconomic access to complex uorine-containing molecules, [24][25][26][27][28][29][30] the concise synthesis of compounds containing a tetrasubstituted tertiary carbon center with a triuoromethyl group and a uorine atom using deuoroalkylation strategies remains underdeveloped (Fig.…”

Visible-Light-Promoted C(sp3)–C(sp3) Cross-Coupling of Amino Acids and Aryl Trifluoromethyl Ketones Through Simultaneous Decarboxylation and Defluorination

“…This can enhance the compound’s biological activity and metabolic stability. Specifically, difluoroketones, which have a CF 2 moiety adjacent to the carbonyl group, can exhibit increased electrophilicity, making them effective enzyme inhibitors . There have been significant advancements lately in the synthesis of difluoroketones, with some notable examples shown in Scheme .…”