Pyridyl Tags as Phase Labels in Organic Synthesis: Fluorous and Non‐Fluorous Approaches

Abstract

Pyridyl tags represent very attractive phase labels for reactants and reagents. Pyridyl tags are the prototypical example of "masked phase tags" which require an activation step to modify the natural phase affinity of the tagged compound. The activation is carried out by either protonation or coordination to a metal ion, whereas deactivation is achieved by basification or addition of competitive ligands. By such simple operations the tagged compounds can be reversibly switched between a liquid-organic phase and other liquid phases (aqueous or fluorous) or between a liquid-organic phase and a solid phase. The purification of reaction products can thus be achieved by straightforward liquid/liquid or solid/liquid separation procedures. Additionally, the pyridyl tags may function both as a phase label and directing tags by accelerating reactions and/or increasing their selectivity.

Liquid–Liquid Equilibria for the Ternary Systems of Perfluorohexane or Perfluamine + Hydrofluoroether + Tetrahydrofuran at 298.15 K or 273.15 K

“…One of the common solvents used with the fluorinated solvents is tetrahydrofuran (THF) since it can dissolve a wide range of nonpolar and polar chemical compounds. Rhodium catalyzed hydroboration of alkenes and alkynes, , palladium catalyzed alkylation reactions of allylic substrates, the protonation/deprotonation reaction, , rhodium catalyzed hydrogenation of 1-octene, preparation of fluoroacrylate bound hydrogenation catalyst, and pyridyl tags were studied as phase labels for the rapid purification of reaction products using the fluorinated solvent/THF biphasic system.…”

Comprehensive Survey of Chemical Libraries for Drug Discovery and Chemical Biology: 2006

“…Publications appeared in 2006 on new polymer supports, – solid-phase trapping for compound isolation, pyridyl tags as phase labels, NMR functional libraries, a molecular building kit for spirocycles, target-family privileged substructures, and in silico identification of biologically active heterocyclic scaffolds . Selected high throughput chemistry reviews published in 2006 include topics on fluorous chemistry, – multicomponent condensations, , enantioselective synthesis on the solid phase, automated synthesis of heterocycles on the solid phase, fragment-based lead discovery, DNA-encoded chemical libraries, , dynamic combinatorial chemistry, in situ click chemistry, approaches to preparing discovery libraries, defining the medicinal chemistry diversity space, chemical genomics, DOS, structure-based design and library synthesis, SPOT synthesis, resin-bound reagents and catalysts, and parallel medicinal chemistry …”

“…52 The remaining selections describe new biselectrophilic annulation reagents to prepare piperazines and diazacycles, 250 the simultaneous processing of two heterocycles, 196 novel variants on multicomponent condensation reactions, 109,159,398,350,363 DOS and natural product-based libraries 19,200,217,240,262 and libraries/new methodology generated using fluorous technology. 98,185,282,419,420 Publicationsappearedin2006onnewpolymersupports, [430][431][432] solid-phase trapping for compound isolation, 433 pyridyl tags as phase labels, 434 NMR functional libraries, 435 a molecular building kit for spirocycles, 436 target-family privileged substructures, 437 and in silico identification of biologically active heterocyclic scaffolds. 438 Selected high throughput chemistry reviews published in 2006 include topics on fluorous chemistry, [439][440][441][442][443][444][445] multicomponent condensations, 447,448 enantioselective synthesis on the solid phase, 449 automated synthesis of heterocycles on the solid phase, 450 fragmentbased lead discovery, 451 DNA-encoded chemical libraries, 452,…”