Towards Macrocyclic Assemblies Of Alternating pi-Excessive and pi-Deficient
Heterocycles: Long Linear Assemblies Containing Alternating 2,6-Fused
Otto Meth-Cohn[*], Yan Zegui and Jiang Hui
Chemistry Department, Sunderland University, Sunderland SR13SD, UK
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.
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
- The Basic Building Blocks
- The Intermediate Building Block
- The Synthesis of Long Linear Assemblies
- The Synthesis of Linear Pyridine-Thiophene Assemblies
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- T. Kauffmann, Angew. Chem. Int. Edn., 1979, 18, 1.
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- A. Minato, K. Suzuki J. Chem. Soc., Chem. Comm., 1984, 511.
- S. W. Wright, D. L. Hageman and L. D. McClure, J. Org. Chem., 1994, 59,