Convergent Syntheses

The convergent synthesis strategy proceeds in the opposite direction, from the periphery to the core, that is from the outside inwards. (Functionalised) dendri-mer components ( dendrons ) are bonded to the reactive terminal groups linked to a focal point of a multifunctional core unit. The CFP symbolism is again used to illustrate the principle of the synthesis (Fig. 2.2). 

The dimensions of dendrimer growth are subject to limitations set by steric hindrance during reaction of the dendrons at the periphery. This is the reason 

The convergent synthetic strategy is well suited for the production of macro-molecular architectures such as segmented-block dendrimers, which bear either the same or different generations of dendrons, but with different molecular scaffolds linked to a core unit. This type of dendrimer is of interest owing to its multifunctionality. 

In the case of surface-block dendrimers, the dendrimer periphery exhibits different functionalities in specific molecular segments. They are formed by coupling of dendrons differing in the nature of their terminal functionalities to a common core unit (cf. Section 3.2.1) [6, 10]. 

Having shown that the construction of dendrimers containing multiple Cgo subunits is successful, the next challenge was to prepare fuUerene-rich 

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If the yield of each step is again 90%, what is the overall yield of this five step convergent synthesis ... 

Pentacyclosqualene, the symmetrical hydropicene corresponding to squalene, has not been made by acid-induced cation-olefin cyclization of squalene, despite considerable experimental study. A simple, convergent synthesis of pentacyclosqualene using cation-olefin cyclization to generate ring C was developed. The Cjo-framework was constructed by radical coupling to a tetracyclic intermediate that was also used for the synthesis of onoceradiene. 

This highly convergent synthesis amply demonstrates the utility of Evans s asymmetric aldol and alkylation methodology for the synthesis of polypropionate-derived natural products. By virtue of the molecular complexity and pronounced lability of cytovaricin, this synthesis ranks among the most outstanding synthetic achievements in the macrolide field. 

Examples of a desulphonylation procedure on complex molecules are provided by Fuchs and coworkers199 who reported on a triply convergent synthesis of L-( —)-prostaglandin E2. The molecules can be classified as homoallylic sulphones and reductive desulphonylation was best achieved with a mixture of sodium methoxide and sodium borohydride in methanol, with yields being better than 90%, despite the complexity of the molecules involved (equation 87). 

Co-ordination chemistry is not the only possible approach to the successful preparation of supramolecular dendrimers. Other examples include hydrogen-bonded dendrimers, which have been prepared using tetracar-boxylic acid moieties as the linking species, and others have been prepared where the hydrogen bonds were developed using melamine and cyanuric acid at the focal point (i.e. the point towards which convergent synthesis is directed). 

Ionic interactions have been used to prepare lanthanide-core dendrimers. This has been achieved using a convergent synthesis, in which polyether den-drons with a carboxylic acid group at the focal point were assembled around a lanathanide cation. This involved a metathetical reaction with compounds such as Er(OAc)3, Tb(OAc)3 or Eu(OAc)3 to introduce the appropriate lanthanide ion. 

This is clearly a linear approach. Disconnection on the other side of the carbonyl group leads to a convergent synthesis. 

Where would you make the first disconnection to devise a convergent synthesis for (14), whose epoxide is the cecropia juvenile hormone What reaction and what starting materials might you use ... 

Scheme 10. Convergent synthesis of first-generation platinum-acetylide dendrimer 31...

Fig. 6. Tetranuclear platinum-acetylide complex 35 used as the core for convergent synthesis...

Fig. 19. (a) Divergent and (b) convergent synthesis of dendritic polyrotaxanes with mechanical branching units... 

Scheme 4.8 Convergent synthesis plan fortriclosan. Reaction conditions (i) acetyl chloride, AICI3 catalyst (ei = 94.3%) (i) 2CI2 (ef = 81 %) (ii) I/2K2CO3, CuCI catalyst, xylenes (s2 = 48.3%) (iii) 62.5% H2O2, 1/2 maleic anhydride, CH2CI2 ( 3 = 91.3%) (iv) MeOH, 35% HCI catalyst ( 4 = 94.5%). Molecular weights in g/mol are given in parentheses.

We first note the following fundamental relationships for linear and convergent synthesis plans with the following designations I = number of reactant inputs, M = number of reactions, N = number of reaction stages, L = number of parallel reactions, G = number of stages with parallel reactions. 

A second convergent synthesis of haliclamine A (64) was achieved in a stepwise sequence from cyclopropyl(thiophen-2-yl)methanone (76) (Scheme 7) [37]. The protected thiophene 77 was condensed with formyl-piperidine to give 78, suitable for a Wittig olefination with 79. After desulfurization of the product 80, the deprotected alcohol 82 was subjected to homoallylic rearrangement using MesSiBr in the presence of ZnBr2. The re-... 

This catalytic process has been used for the key step of a convergent synthesis of ( )-monomorine [298] and for a stereoselective total synthesis of (+)-preussin [299]. 

Simplifying the synthesis of the catalysts (e.g., the highly optimized convergent synthesis of monometallic series 2 metalloporphyrins required between 14 and 17 steps [Collman et al., 2002d]—FeAc (Fig. 18.21a) is available in 7 steps). 

Schemes 10.1 and 10.4 of Part A, respectively, give the structure of a number of typical dienophiles and show representative D-A reactions involving relatively simple reactants. The D-A reaction is frequently used in synthesis and can either be utilized early in a process to construct basic ring structures or to bring together two subunits in a convergent synthesis. The intramolecular version, which will be discussed in section 6.1.7, can be used to construct two new rings.

Hydroxymethylation (formaldehyde) of nitro-imidazole 76 affords 77, which is oxidized to aldehyde 78. To prepare the other fragment for this convergent synthesis, reaction of epichlorohydrin with morpholine leads to the aminoepoxide 79, which is reacted with hydrazine to afford 80. Reaction of this substituted hydrazine with dimethyl carbonate affords oxazolinone 81 by sequential ester interchange reactions. Condensation of 81 with aldehyde 78 affords the antitricho-... 

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