Asymmetric Synthesis of a Series of Chiral AB₂Monomers for Dendrimer Construction

Abstract

Efficient preparation of a series of four chiral, nonracemic AB2 monomers suitable for the construction of dendrimers is presented. Monomers 1−4 possess the common structural features of a diphenolic moiety and a benzylic or aliphatic hydroxyl which render these molecules suitable for convergent dendrimer synthesis. The same basic, high-yielding, five-step sequence is employed for 1−4. Stilbene derivatives 13 and 14 are prepared by a Horner−Wadsworth−Emmons modified Wittig reaction between 3,5- or 3,4-bis(benzyloxy)benzaldehyde (8 and 10) and an ester-substituted benzylphosphonate (11 or 12). Cinnamate derivatives 21 and 22 are prepared similarly from 8 and 10 and triethyl phosphonoacetate. Chirality is introduced in the form of a 1,2-diol unit by Sharpless asymmetric dihydroxylation (AD) (>97% ee in all cases). Protection of the 1,2-diols as their acetonide derivatives provides dioxolane intermediates 17, 18, 25, and 26. Reduction of the ester groups followed by hydrogenolysis of the benzyl ethers yields AB2 monomers 1−4 in 57−67% overall yield from 8 and 10.