A new germanium-based linker for solid phase synthesis of aromatics: Synthesis of a pyrazole library

An efficient synthesis of chlorogermane linker 12 is described. Economic in troduction of germanium into this linker is accomplished by insertion of di chlorogermylene [from germanium(IV) chloride] into the homobenzylic C-Cl bo nd of 4-(2-chloroethyl)phenol 1. Using linker 12, transmetalation with lith iated 4-acetophenone, 3-acetophenone, and 4-(4'methoxy)biphenyl followed by Mitsunobutype coupling to Argogel gives functionalized resins 14, 16, and 18, respectively. Treatment of resin 18 with TFA, ICl, Br-2, or NCS effects clean ipso-degermylation releasing biphenyls 19-22, respectively. Resins 1 4 and 16 are employed for the parallel synthesis of a library of pyrazoles by enaminone formation (using Bredereck's reagent), condensative ring-closu re (using a series of monosubstituted hydrazines), and cleavage (using TFA and Br2) Analysis of this library reveals the influence of the hydrazine su bstituent on both the regioselectivity of ring-closure and the propensity f or electrophilic substitution at the 4-position of the pyrazoles during ips o-degermylative cleavage.