Dendrimers accelerated synthesis

Unfortunately, the presence of the benzylic alcohol moiety at the focal point of the dendrimer, along with the catalyst (used in the urethane formation) led to the formation of undesired side products, presumably due to carbamate interchange. These side reactions were avoided by switching to monomer 19, methyl-3,5-dihydroxybenzoate. While the carbamate linkages of dendrons 53 and 54 were too unstable under the alkylation conditions required to afford larger dendrons, the merits of the concept was adequately demonstrated for this accelerated synthesis of [G-3] dendrons. 

Scheme 4. Accelerated synthesis of dendrimers using two types of AB2 monomers...

Accelerated Synthesis. Dendrimer chemistry requires usually tedious and time-consuming reaction protocols with high production costs and is, therefore, a major obstacle to their potential use in commercial applications. Consequently, some new strategies have been introduced to facilitate and accelerate dendrimer synthesis. 

Scheme 30.18 Accelerated synthesis of a fourth-generation bis-MPA dendrimer using CuAAC click coupling reactions in combination with esterification chemistry by the divergent growth approach. Reproduced with permission from Ref [132] 2007, The Royal Society of Chemistry.

Figure 23 The accelerated synthesis of PMMH dendrimers using AB2+ CD2 growth approach. Reproduced with permission from Brauge, L. Magro, G. Caminade, A. M. Majoral, J. P. J. Am. Chem. Soc. 2001,123, 8446." Copyright 2001 American Chemical Society.

Figure 8.2 General scheme for the divergent synthesis of bis(MPA)-type dendrimers using a combination of CuAAC and traditional esterification reactions, as synthesized by Malkoch et al (Antoni et ah, 2007). (Reproduced from P. Antoni, D. Nystrom, C.J. Hawker et ah, A chemoselective approach for the accelerated synthesis of well-defined dendritic architectures, Chemical Communications, 22, 2249-2251, 2007, by permission of the Royal Society of Chemistry.)...

Malkoch recently reported the accelerated synthesis of a new class of degradable polyester dendrimers that were decorated with internal and surface acetylenic moieties (Fig. 5) [66]. The G2 dendrimer 64 was then cross-linked with 1 equiv. of Ns-PEOgooo-Na to give a hydrogel. Due to the acid- and base-labile ester linkages, the hydrogel could be degraded within 1 h at pH 11 or 4 days at pH 4 in aqueous solutions. 

While the convergent strategy, as described above, has been exceptionally successful, a considerable amount of effort has been devoted to improving its speed and synthetic efficiency. The remainder of this chapter reviews the major methodological developments and improvements in the accelerated, covalent, convergent synthesis of dendrimers. Dendrimers constructed via self-assembly and noncovalent interactions, as well as inorganic dendrimers [25], are beyond the scope of this brief chapter. 

Since the first report of the synthesis of dendrimers twenty years ago [1], there has been a remarkable increase in interest in these fascinating materials. For example, the number of publications relating to dendrimers was about 15 in 1990, but this number increased to 150 in 1995, and 420 in 1997. Until very recently emphasis in this field was placed on the synthesis of new families of dendrimers having novel architectures, but more recently there has been interest in finding technological applications for these materials [2-5]. The pursuit of applications has been greatly accelerated by the recent commercial availability of dendrimers through Dendritech, Inc. (Midland, MI), Dutch State Mines (DSM, The Netherlands), and the Aldrich Chemical Co. (Milwaukee, WI). 

Moore et al.[104 106a reported a double exponential dendrimer growth , which is an accelerated convergent process for the synthesis of monodendrons by means of a bidirectional procedure, where the degree of polymerization follows Equation (5.1). 

The other accelerated approach for dendrimer synthesis, the orthogonal approach, involves convergent growth with two different monomers. The monomers, an AB2 and a CD2 must be carefully selected such that the focal functionalities of each individual monomer will only react with the periphery of the other monomer (B couples only with C and D only with A) thus removing the need for activation reactions. As... 

Dendrimer synthesis is constantly progressing with the emergence/development of new accelerated routes toward higher-generation dendrimers. There are, however, several criteria that must be identified in order to accelerate dendrimer synthesis ... 

Today, several methodologies are available for the acceleration of dendrimer synthesis (i) An acceleration of the reaction steps towards a higher number of generations (ii) an acceleration of the number of branches and (iii) an acceleration of the functional groups. 

P., Caminade, A.M., and Majoral, ).P. (2005) Accelerated methods of synthesis of phosphorus-containing dendrimers. ]. Organomet. Chem., 690, 2458 2471. 

Antoni, P., Hed, Y., Nordberg, A., Nystrom, D., von Holst, H., Hult, A., and Malkoch, M. (2009) Bifunctional dendrimers from robust synthesis and accelerated one-pot postfunctionalization strategy to potential applications. Angew. Chem. Int Ed., 48, 2126-2130. 

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