A fluorous-tagged linker from which small molecules are released by ring-closing metathesis

J Org Chem. 2008 Apr 4;73(7):2753-9. doi: 10.1021/jo7026273. Epub 2008 Mar 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclization
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Hydrocarbons, Fluorinated / chemistry*
  • Macrocyclic Compounds / chemical synthesis*
  • Macrocyclic Compounds / chemistry
  • Molecular Structure
  • Molecular Weight
  • Nitrogen / chemistry*
  • Organometallic Compounds / chemistry
  • Ruthenium / chemistry
  • Stereoisomerism

Substances

  • Heterocyclic Compounds
  • Hydrocarbons, Fluorinated
  • Macrocyclic Compounds
  • Organometallic Compounds
  • Ruthenium
  • Nitrogen