Linker substitution transformations

To examine the second way of binding the chloro ester 1-Me to a polymer as in 268 (Fig. 12), the TentaGel-S-COOH resin 279 which contains a succinyl linker, was esterified with the 2 -(4-hydroxybutyl)-substituted chloro ester 280 (prepared by debenzylation of compound 2l-Me) (Scheme 81) [11b]. Only the Michael addition of secondary amines onto 281 and the removal of the adducts 283 from the resin has been probed so far, any further transformations of polymer-bound compounds 281 need yet to be developed. 

The sulfide-based linker 1.32 (89), obtained from commercial thio-PEG-PS resin and chloropyrimidine, is activated to nucleophilic substitution via oxidation with perbenzoic acid after multistep SP transformations treatment with amines then releases pure 2-aminopyrimidines in solution. Other nucleophiles should be suitable for the modular release of this and other heterocyclic S-supported nuclei. 

Naturally, it is possible to synthesise a similar ligand system without central chirality and in fact without the unnecessary methylene linker unit. A suitable synthesis starts with planar chiral ferrocenyl aldehyde acetal (see Figure 5.30). Hydrolysis and oxidation of the acetal yields the corresponding carboxylic acid that is transformed into the azide and subsequently turned into the respective primary amine functionalised planar chiral ferrocene. A rather complex reaction sequence involving 5-triazine, bromoacetal-dehyde diethylacetal and boron trifluoride etherate eventually yields the desired doubly ferrocenyl substituted imidazolium salt that can be deprotonated with the usual potassium tert-butylate to the free carbene. The ligand was used to form a variety of palladium(II) carbene complexes with pyridine or a phosphane as coligand. 

Only a few examples of substrate-controlled diastereoselective intramolecular oxidative dearomatization have appeared. These transformations are analogous to the reaction shown in Scheme 15.20 in that stereogenic centers present on the linker connecting the carbon nucleophile to the arene substrate are responsible for diastereoselectivity [69, 70]. A rare example of a true metal-catalyzed oxidative dearomatization of substituted 2-naphthols is shown in Scheme 15.25. Treatment of naphthol 67 with Fe(salen) catalyst 68 in the presence of nitromethane (as a carbon nucleophile) and air (O as stoichiometric oxidant) gave naphthone 69 possessing a quaternary carbon center in 90% ee [71]. 

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