Improvements in the Synthesis of Phenylacetylene Monodendrons Including a Solid-Phase Convergent Method

A new scheme for the synthesis of phenylacetylene dendritic macromolecules is described which greatly facilitates the large-scale production of high molecular weight monodendrons. Simply by inverting the monomer protecting group scheme from B₂A_p to A₂B_p (where A = ArC≡CH; B = ArI; A_p and B_p are protected versions of these groups), we show that the repetitive synthesis can be propagated through at least one higher generation on reaction scales 2 orders of magnitude greater than previously possible. Using this new scheme, we have prepared gram quantities of phenylacetylene monodendrons through generation four (I-M₆₃-(t-Bu)₆₄), in high yields. Possible reasons for the improvements are discussed. We furthermore show that the new route is amenable to a solid-phase convergent dendrimer synthesis which involves tethering the focal point monomer to an insoluble support. Preparation of phenylacetylene monodendrons by the solid-phase method is demonstrated through generation four, yielding monodendron products identical to those synthesized by solution methods. However, at generation four, coupling reactions using polymer supports can only be driven to completion with light loading of the focal point monomer. The solid-phase convergent method offers several advantages, especially in the synthesis of early generation monodendrons.