Hydroxy second-generation synthesis

Hydroxyl-terminated polyamine dendrons of the first and second generations were obtained on macroporous polystyrene by Qu and coworkers. The authors used diethanolamine monomer for the divergent synthesis of the dendrons. This was immobilized by nucleophilic substitution, while the terminal hydroxy groups were activated by the chlorodehydroxylation reaction (Scheme 15.23). The elemental analysis, used for quantification of the dendrimer loading, revealed 80-90% yield for each generation assembly. 

As an extension of this reaction, the selective intramolecular nucleophilic addition of a hydroxy group at Cy of a ruthenium allenylidene species generated by activation of propargylic alcohol by RuCl(Cp)(PPh3)2/NH4PF6 provides a ruthenium-vinylidene intermediate. The latter compound reacts with allylic alcohol via a second nucleophilic addition (Scheme 8.13) [27]. This unprecedented tandem reaction makes possible the construction of tetrahydrofuran derivatives in good yields, and has been used in the multistep synthesis of (-)calyculin A [28]. 

Extension of this woik to the synthesis of ot-hydroxy aldehydes with substituents other than phenyl cian be carried out by using the methyl ester (79 Scheme 7) as precursor. Grignard additions afford a vair-iety of ketoaminals (80) in good yield aldehydes (R = H) are available via diisobutylaluminum hydri(de reaction. A second Grignard addition, followed by hydrolysis, generates a-hydroxy aldehydes (82) in... 

An interesting example of the application of NHPI is the synthesis of lactones with the in situ generation of HP. Ishii et al. [31g] have reported that in the oxidation of the KA Oil mixture with air, in the presence of both NHPI and small amounts of initiator AIBN, the alcohol was converted into a mixture of cyclohexanone and HP via the intermediate formation of 1-hydroxy-1-hydroperoxycyclohexane the reaction was performed in an acetonitrile solvent at 70°C. The addition of catalytic amounts of InCla in the second step led to the reaction between cyclohexanone and HP, with the formation of 8-caprolactone, at 25 °C. The conversion was 23%, and the selectivity to the lactone was 57% (Scheme 7.8). 

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