Iterative reactions

In three reaction steps the ditosylate 29 leads to the bistosylate of the mono-spiro[3.3]heptane 32, which can be converted in successive iteration steps to polyspiranes of any length. Starting from the tetratosylate of the cyclobutane compound 33 the application of two iterative reaction sequences at the same time is possible. Nonaspiro compound 34 was thus synthesized in only twelve reaction steps [56]. 

L. Jones II, J. S. Schumm, J. M. Tour, Rapid Solution and Solid Phase Syntheses of Oiigo(l,4-phenylene-ethynylene)s With Thioester Termini Molecular Scale Wires With Alligator Clips. Derivation of Iterative Reaction Efficiencies on a Polymer Support, J. Org. Chem. 1997, 62,1388-1410. 

The starting cyanothioethyl thiolate molecule (a) is converted to the thione (b) and coupling of (b) with (c) yields the fundamental TTF-derivative brick (d). Reaction with (e) renders (f) and the iterative reaction of (f) with (d) gives larger molecules such as (g). Indeed the correct experimental conditions have to be met for each step. As pointed out above, it is mandatory in order to proceed with the dendrimerization to preserve the cyanoethyl hook. 

Divergent synthesis of POPAM dendrimers is based on the concept developed by Vogtle et al. in 1978 (see Section 1.1) [4]. Acrylonitrile is added to a primary mono- or oligo-diamine in a Michael reaction (Fig. 4.2). Suitable reducing agents are Co(II)-borohydride complexes or diisobutylaluminium hydride [5]. Subsequent iterative reaction cycles permit repeated addition of acrylonitrile followed by reduction until the limiting generation is reached. 

The development of fast, reliable and convenient chemical processes is important for the whole field of organic chemistry. In fact, in many cases even a slight drop in chemical yield is acceptable when compensated for by large gains in reaction time or improved ease of handling [12-15]. These features apply in particular to iterative reaction optimization in commercial situations where the reaction time is an important parameter [16]. In particular, the pharmaceutical industry is continuously on the look-out for new rapid synthetic methods and strategies for the discovery and development of new drugs. 

Liu HY, Lu ZY, Cisneros GA, Yang WT (2004) Parallel iterative reaction path optimization in ab initio quantum mechanical/molecular mechanical modeling of enzyme reactions. J Chem Phys 121 697... 

Figure 1. Generalized oligosaccharide synthesis. Iterative reactions consisting of protection, de-protection, and glycosylation reaction are performed to obtain oligosaccharides. L = leaving group ...

The synthesis of high generation dendritic branches from building blocks 7 and 11 was found to be difficult due to steric hindrance problems. This prompted Nierengarten and coworkers to further explore the development of new fullero-dendrons starting from a less hindered fullerene derivative (Schemes 10.3 and 10.4) [19]. The iterative reaction sequence used for the synthesis of the successive dendrimer generations is the same as that described for the preparation of dendrons 4-7. 

---