Phenylacetylene Dendrimers by the Divergent, Convergent, and Double-Stage Convergent Methods

The divergent, convergent, and double-stage convergent methods for synthesizing phenylacetylene dendritic macromolecules are examined. Syntheses based on the divergent or double-stage convergent approaches are severely hampered by poor solubility of the growing macromolecules. The double-stage method is nonetheless successfully used in attaining a high molecular weight and apparently monodisperse dendrimer. Using the convergent approach, high molecular weight mono- and tridendrons are prepared. The repetitive chemistry employed for monodendron preparation includes palladium-catalyzed coupling of terminal acetylenes to an aromatic dibromide containing a trimethylsilyl (TMS) masked terminal acetylene. The synthetic cycle is completed by removing the TMS group under mildly basic conditions. These monodendrons can be coupled around a trifunctional core, such as triiodobenzene, yielding tridendrons. Solubility of both the mono- and the tridendrons is strongly dependent on the nature of the peripheral group. Qualitatively, solubility tends to plummet in the early stages of growth. Provided that growth can be sustained, however, this trend tends to reverse as the synthesis progresses. The best peripheral group of those examined thus far for maintaining adequate solubility of both mono- and tridendrons over this critical solubility minimum is di-tert-butylphenylacetylene. For dendrimers containing this peripheral group, solubility is high even in aliphatic hydrocarbon solvents at room temperature. When poor solubility does not hamper the synthesis, the limiting factors to sustaining growth become as much dependent on the ability to purify and characterize the product of the coupling reaction as on the chemistry of the coupling reaction itself. Size-exlusion chromatography is shown to be inadequate for differentiating partially coupled products from fully coupled tridendrons. This problem is believed to be especially severe for stiff dendritic macromolecules, since their molecular cross section is essentially constant once two of the three monodendrons have coupled to the central core. Unequivocal proof of structure for mono- and tridendrons through generation four (C_1134H1146, mol wt 14 776) has been obtained using a combination of chromatographic techniques, isotope labeling studies, mass spectrometry, and multidimensional NMR experiments.