Iterative synthetic sequence

Fig. (33). Iterative synthetic sequence based on the Zincke method for the selective access to dimers and higher 3-alkylpyridinium oligomers...

More recently, the same group proposed a new methodology for the synthesis of exact graft copolymers composed of PMMA and five PS branches [231]. For this synthesis, a specially designed hving AB diblock copolymer (PS-b-PMMA), in-chain-functionahzed with a 3-tert-butyldimethylsilyloxymethylphenyl (SiOMP) group, is used as the building block unit (Scheme 5.23). In this case, three reaction steps are employed in an iterative synthetic sequence ... 

We outlined the rapid syntheses of oligo(2-alkyl-l,4-phenylene-ethynylene)s via an iterative divergent/convergent approach that needed only three sets of reaction conditions for the entire iterative synthetic sequence an iodination, a protodesilylation, and a Pd/Cu-catalyzed cross coupling. The syntheses were conducted in solution and on a polymer support. At each stage in the iteration, the length of the framework doubled. Equations were derived... 

Very recently, a series of well-defined dendrimer-like star-branched (PS)s was synthesized by a new modified methodology (Yoo et al, 2009). As illustrated in Scheme 5.14, the following three reaction steps are employed in the iterative synthetic sequence (1) a linking reaction of a-chain-end 3-( eri-butyldimethylsilyloxy)propyl (SiOP)-functionalized PSLi end capped with 1,1-diphenylethylene (DPE) with either a core substituted with four BnBr functions or a chain-end (BnBr)2-functionalized PS connected to the core, (2) a transformation reaction... 

The history of dendrimer chemistry can be traced to the foundations laid down by Flory [34] over fifty years ago, particularly his studies concerning macro-molecular networks and branched polymers. More than two decades after Flory s initial groundwork (1978) Vogtle et al. [28] reported the synthesis and characterization of the first example of a cascade molecule. Michael-type addition of a primary amine to acrylonitrile (the linear monomer) afforded a tertiary amine with two arms. Subsequent reduction of the nitriles afforded a new diamine, which, upon repetition of this simple synthetic sequence, provided the desired tetraamine (1, Fig. 2) thus the advent of the iterative synthetic process and the construction of branched macromolecular architectures was at hand. Further growth of Vogtle s original dendrimer was impeded due to difficulties associated with nitrile reduction, which was later circumvented [35, 36]. This procedure eventually led to DSM s commercially available polypropylene imine) dendrimers. 

Scheme 5.50 Synthetic route to oligo-(2,8)-3-deoxy-a-D-manno-2-octulosonic acid derivatives via iterative iodoalkoxylation sequence.

In the simplest case, reaction of a primary monoamine via a two-fold Michael reaction with acrylonitrile (bis-cyanoethylation) led to the dinitrile (Fig. 1.1). Subsequent reduction of the two nitrile functions - by hydrogenation with sodium borohydride in the presence of cobalt(II) ions - afforded the corresponding terminal diamine. Repetition (iteration) of this synthetic sequence, consisting in Michael addition followed by reduction, provided the first - structurally variable - access to regularly branched, many-armed molecules. 

In an initial assembly step, trichlorothiophosphorus is allowed to react with the sodium salt of 4-hydroxybenzaldehyde. Subsequent activation by addition of a hydrazine derivative yields a first-generation phospho-dendrimer (Fig. 4.54). Iteration of this synthetic sequence ultimately leads to the fourth generation (molar mass 11 269 Da). 

Heathcock and Walker" previously developed an extremely efficient iterative coupling sequence to similar peptides as part of their synthetic efforts leading to mirbazoles. In addition, these same authors described an elegant TiCl4-mediated cyclization of such peptides for preparing the polythiazoline rings of mirbazoles simultaneously. 

Since all p-star polymers still possess several DPE functions, the synthetic sequence may possibly further continue to synthesize higher armed and compositional star-branched polymers. It should be mentioned that styrene derivatives were generally used herein both for facile synthesis of highly reactive living anionic polymers and for easy characterization of the resulting stars by H NMR, but living anionic polymers of 1,3-butadiene, isoprene, and certain functional styrene and 1,3-dienes can also be employed in the iterative methodology. 

DPE moiety was converted to a reactive DPE anion by treatment with cc-BuLi, the coupling step was repeated between the star-branched anion and 7 in the second iteration. An 8-arm A4B4 star was obtained in 60% yield, but not quantitatively. The yield was not improved after several attempts under various conditions. A subsequent repetition of the same synthetic sequence resulted in a 16-arm AgBg star. The reaction yield was significantly reduced to less than 20%. 

As seen in Scheme 5.1, preparation of the IG polymer in this synthesis involved the ROP of cCL and subsequent chain-end modification. Conversion of the terminal hydroxyl group to two hydroxyl functions enabled further ROP to the 2G polymer. The IG polymer synthesized by this procedure was a 6-arm star-branched PcCL. The target dendrimer-like star-branched polymer was obtained as a 2G polymer by the second iteration and possessed a minimum architectural unit. One more repetition of the synthetic sequence involving the two reaction steps resulted in a 3G dendrimer-like star-branched PaCL. The 3G polymer possessed six branches at the core and two branches at the junctions in both the 2G- and 3G-based layers, composed of 42 arm segments (6 (IG) + 12 (2G) + 24 (3G) = 42). The observed M value was 96 000 g/mol, close to the theoretical value, and the molecular-weight distribution was not narrow, but an acceptable value of 1.14. 

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