A New Germanium-Based Linker for Solid Phase Synthesis of Aromatics:  Synthesis of a Pyrazole Library

Abstract

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

The development of a ‘safety‐catch’ arylgermane for biaryl synthesis by palladium‐catalysed germyl‐stille cross‐coupling

“…It was expected a priori, that Ge would require additional such ligands to offset its greater electronegativity relative to Si (see above). To evaluate this, we prepared 4-tolyl and 4-anisyl, monoand dichlorogermane substrates 3, 10, 6b and 7b from trichlorogermane 1 (Scheme 2) As in our previous studies, 61 the ethoxyethyl ether in these derivatives was envisioned to act as a surrogate for the polyethyleneglycol (PEG) chain of a PEG-grafted polystyrene resin for SPS such as Tentagel  .…”

“…61 (2, 0.553 g, 1.67 mmol) was placed in an N 2 atmosphere and dissolved in 10 ml toluene immediately after purification. A solution of 4-TolMgBr in Et 2 O (6.30 ml, 6.30 mmol, 1.0 M) was added via a syringe with stirring.…”

“…In the context of a program to develop arylgermane-based linkers for phase-tagged synthesis of heterocyclic libraries 61,62 and of high purity oligothiophenes 63,64 for 'plastic electronic' applications, we required a 'safety-catch' linker that would allow cleavage from the phase-tag with concomitant C-C bond formation. 65 It was envisaged that such a method of cleavage in which the arylgermane, following 'activation' of the safety-catch, could be enticed to participate in Pd(0)-catalysed cross-coupling with aryl halides would constitute a powerful method of diversification via biaryl formation in these and other applications (Scheme 1).…”

Organic Molecular Nanotechnology

“…4-Iodo-4´-methoxy-biphenyl (MOIP2) [112,[211][212][213][214] Treatment of MOPYRP2 according to general procedure B gave 324 mg (1.05 mmol, 55%) of MOIP2. The analytical data were in agreement with those published by R.N.…”

tert-Butoxy Bis(dimethyl-amino)methane (Bredereck’s Reagent)

“…6 (F) Solid-phase synthesis: The usefulness of the Bredereck's reagent was extended to the solid-phase synthesis of a library of pyrazoles, employing a germanium-based linker, via the formation of enaminones from aromatic ketones. 7 (G) Enamine formation from active methylene compounds: 5-Acyl-6-methyl-2-pyridinones were converted to the corresponding enamines upon treatment with Bredereck's reagent. …”