Second‐Generation Trifluoromethyl‐Substituted Chiral Dendrimers Containing Triply Branched Building Blocks: CF3 as sensitive NMR probe for ‘remote’ diastereotopicity

Abstract

Abstract(S)‐4,4,4‐Trifluoro‐3‐hydroxybutanoic acid was used as a starting material for the synthesis of dendritic branches (16–21, 30–32) which were attached to a chiral triol (6 or ent‐6), derived from (R)‐3‐hydroxybutanoic acid, to give CF3‐substituted dendrimers (33–36, 38–40) and dendritic compounds (37) of 1st and 2nd generation. The key steps in these syntheses are diastereoselective aldol additions of dioxanone enolates (building blocks and intermediates 6–15, 22, 23, and 25–28) and Williamson etherifications of benzylic‐branch bromides with triols (intermediates and products 16–21, 28, and 30–40). The surfaces of the dendrimers are covered with MeO (33–35, 38–40) or allyloxy groups (36 and 37). The new dendrimers are characterized by NMR and mass spectroscopy. 19F‐NMR Signals of the CF3 groups reveal constitutional heterotopicities caused by substituents which are separated from the F‐nuclei by up to 15 bonds (through a 1,1′‐biphenyl‐4,4′‐diyl spacer!) (Fig. 6).