Fluorinating Cleavage of Solid Phase Linkers for Combinatorial Synthesis

Abstract

Multitasking: A new preparative route to fluorine‐containing compounds combines the advantages of solid‐phase synthesis with the incorporation of fluorine at the end of the synthetic route. A sulfur linker enables simultaneous fluorination of the target structures in the cleavage step. As it is stable under different reaction conditions, the linker has potential in the combinatorial synthesis of fluorinated drug structures.

A Versatile Organocatalytic Approach for the Synthesis of Enantioenriched gem‐Difluorinated Compounds

“…The 1,3‐benzodithiol group can be used to generate its anionic or cationic equivalent, and it can also be easily removed by treatment with Raney nickel, to give the corresponding methyl substituent, or transformed into a carbonyl group 17. We were inspired by the works published by Kollonitsch and Marburg,15a Katzenellenbogen,15b and Bräse,18a wherein efficient methods for the preparation of several gem ‐difluorinated compounds from CS units were reported 18. We wondered whether optically active 1,3‐benzodithiol adducts could be used similarly to access enantioenriched and valuable chiral difluorinated intermediates.…”

Supported Synthesis of Halogenated Organic Compounds

“…The cleavage of solid-phase linkers for combinatorial synthesis upon oxidative difluorination was reported by Bräse and co-workers. 33,34 In the first instance, a dithiane linker attached to an aminomethyl-functionalized polystyrene resin reacted with a series of carbonyl compounds under Lewis acidic conditions (Scheme 18).…”

“…The purity was typically lower (50-60%) for cleaved products derived from palladium-catalyzed transformations and thus was attributed to the presence of residual metal catalyst (Scheme 21). 33,34 A further modification used Horner-Wadsworth-Emmons methodology to install carbon-carbon double bonds (Scheme 22, top). The umpolung nature of the dithiane was also exploited with an alkylation preceding the fluorinating cleavage (Scheme 22, bottom).…”

(Het)aryl Difluoromethyl‐Substituted β‐Alkoxyenones: Synthesis and Heterocyclizations

“…Most known approaches rely on gem ‐difluorination reactions, i.e. deoxofluorination of diarylketones (Scheme , A ),, fluorodesulfurization of thioketones ( B ) or thioketals ( C ) . Alternative strategy implies the use of building blocks already containing the (het)aryl difluoromethyl moiety; it is represented by [4+2] or [3+2] cycloadditions of 4,4‐difluorobutynoates ( D ) …”

“…deoxofluorination of diarylketones (Scheme 1, A), [3,[26][27][28][29][30][31][32][33] fluorodesulfurization of thioketones (B) [33][34][35] or thioketals (C). [36][37][38][39][40][41][42] Alternative strategy implies the use of building blocks already containing the (het)aryl difluoromethyl moiety; it is represented Scheme 1. Known syntheses of difluorodi(het)arylmethanes.…”