A fluorous-tagged linker from which small molecules are released by ring-closing metathesis.
A fluorous-tagged linker for the parallel synthesis of small- and medium-ring and macrocyclic nitrogen heterocycles using ring-closing metathesis is described. The linker was designed such that "cyclization-release" of the cyclic heterocyclic products was coupled with liberation of the active catalyst. The design of the linker was validated using a non-fluorous-tagged model. A wide range of unsaturated alcohols were used as reagents to functionalize a fluorous-tagged sulfonamide, (Z)-{N-[4-(2-(N'-3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)-4-methylsulfonamido)methylallyloxy]but-2-enyl}-2-nitrobenzenesulfonamide, using Fukuyama-Mitsunobu reactions; in each case, fluorous-solid-phase extraction (F-SPE) was used to purify the functionalized linker from the excess reagents. In general, the "cyclization-release" of cyclic products was triggered using a light-fluorous tagged derivative of the Grubbs-Hoveyda second-generation catalyst. After the metathesis step, F-SPE was used to purify released cyclic compounds from the fluorous-tagged linker and the fluorous-tagged catalyst. The scope and limitations of the approach were determined using a range of substrates which probed different aspects of the functionalization and metathesis steps. In the study as a whole, a wide range of small- and medium-ring and macrocyclic nitrogen heterocycles were prepared using polyene and polyenyne metathesis cascades.
Leach
Stuart G
SG
School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
Cordier
Christopher J
CJ
Morton
Daniel
D
McKiernan
Gordon J
GJ
Warriner
Stuart
S
Nelson
Adam
A
D003500:Cyclization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D008970:Molecular Weight; D009584:Nitrogen / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry; D013237:Stereoisomerism
D006571:Heterocyclic Compounds; D006845:Hydrocarbons, Fluorinated; D047028:Macrocyclic Compounds; D009942:Organometallic Compounds; D012428:Ruthenium; D009584:Nitrogen