Towards Macrocyclic Assemblies Of Alternating pi-Excessive and pi-Deficient Heterocycles: Long Linear Assemblies Containing Alternating 2,6-Fused Pyridines.

Otto Meth-Cohn[*], Yan Zegui and Jiang Hui

Chemistry Department, Sunderland University, Sunderland SR13SD, UK

Introduction:

The goal of this work is to generate macrocycles containing two different types of ligands based on a pi-deficient system (pyridine) and a pi-excessive system. Our initial goal outlined herein is to explore routes to two typical linear assemblies as precursors to such macrocycles - those containing alternating pyridine-imidazolidinone units and those containing alternating pyridine-thiophene units. Modelling suggests that macrocycles based on both of these systems would be of particular interest with 4 pairs of such units.

Pyridine-imidazolidinone assemblies:

The key to the first of these assemblies lies in a remarkably effective coupling of N-(dimethylthexylsilyl)-protected imidazolidinone unit with a fluoropyridine catalysed by cesium fluoride. This protecting/activating group(ref 1) is stable to heat, water, alkali and chromatography and generates beautifully crystalline derivatives in high yield - unlike all other amide-protected groups that we have examined. In this way we have made linear assemblies with up to 11 units.

Pyridine-thiophene assemblies:

Early attempts to create such assemblies by, for example, Kauffmann (ref 2) were very limited. However powerful new methods for aryl-aryl' coupling are now available. We have examined Suzuki coupling (ref 3) (via boronic acids), Stille coupling (via organotin derivatives) and palladium-catalysed Grignard coupling methods (ref 4) and by a combination of the first and last achieved efficient synthesis of such assemblies of any desired length. Particularly noteworthy in view of the poor yields in the literature of coupling thiopheneboronic acids (due to base-catalysed deboronation) is the use of KF as the base (cf. ref .5) when very high yields are available. The stage is now set for examining the macrocyclisation of these linear assemblies and an examination of their intriguing ligand properties.

Results and Discussion

  1. The Basic Building Blocks
  2. The Intermediate Building Block
  3. The Synthesis of Long Linear Assemblies
  4. The Synthesis of Linear Pyridine-Thiophene Assemblies

References:

  1. H. Wetter and K. Oertle, Tetrahedron Lett., 1985, 26, 5515.
  2. T. Kauffmann, Angew. Chem. Int. Edn., 1979, 18, 1.
  3. A. Suzuki, Acc. Chem. Res., 1982, 15, 178.
  4. A. Minato, K. Suzuki J. Chem. Soc., Chem. Comm., 1984, 511.
  5. S. W. Wright, D. L. Hageman and L. D. McClure, J. Org. Chem., 1994, 59, 6095.
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