Stefan Dahmen

Traceless Linkers-Only Disappearing Links in Solid-Phase Organic Synthesis?

Traceless linkers, which enable the attachment of arenes and alkanes to a polymeric support, have received increased attention in recent years. These anchoring groups allow chemical transformations on the polymer-bound molecules, which can be cleaved from the resin leaving no residual functionality to bias the library. Various approaches based on different Group 14 to Group 16 heteroatoms have been developed in the past and used in new syntheses of diverse compound libraries.

Solid-phase synthesis of substituted cinnolines by a Richter type cleavage protocol☆

Starting from triazene bound ortho-halo arenes on a solid support, palladium-catalyzed alkynylations and subsequent cleavage reactions under acidic conditions give rise to ortho-alkynylaryldiazonium salts, which in turn undergo cyclization to afford substituted 4-halo- and 4-hydroxycinnolines in moderate to good yields. The method is applicable to automated synthesis.

Hydro-dediazoniation of diazonium salts using trichlorosilane: new cleavage conditions for the T1 traceless linker

An efficient, selective cleavage of triazenes and in situ hydro-dediazoniation of the intermediately formed diazonium salts with trichlorosilane (HSiCl3) in liquid as well on solid phase is reported. Starting from anilines, attachment to solid support and subsequent cleavage gives rise to the corresponding unsubstituted arenes. This cleavage reagent is compatible with various functionalities (esters, amides, nitro groups, halides, aliphatic double and triple bonds).

Enantioselective catalytic syntheses of α-branched chiral amines

Chiral amines play a pivotal role in fine chemical and natural product syntheses and the design of novel materials.

Synthesis of alkyl sulfonates from sulfonic acids or sodium sulfonates using solid-phase bound reagents

Abstract An efficient and selective method for the synthesis of sulfonic esters from sulfonic acids or sodium sulfonates using polymer-bound primary triazenes based upon the T2* linker has been developed. The purities of the esters obtained are usually greater than 95% without any further purification steps.

Polymer-bound 1-aryl-3-alkyltriazenes as modular ligands for catalysis. Part 1: synthesis and metal coordination.

A range of di- and tri-substituted triazenes have been synthesized from a polymer-supported diazonium salt and various primary and secondary amines. The triazenes obtained were treated with transition metal salts to form polymer-supported metal complexes in firstly a general screen and then in a specific manner.

Polymer-bound 1-aryl-3-alkyltriazenes as modular ligands for catalysis. Part 2: screening immobilized metal complexes for catalytic activity.

A range of polymer-supported triazenes and their metal-bound analogues were screened for use in catalysis. Fe, Cu and Zr complexes were, together with the polymer-supported triazene ligand alone, screened in the addition of Et(2)Zn to benzaldehyde. A supported Pd triazene complex was screened for activity in Suzuki and Sonogashira reactions and a supported Ru triazene complex screened for transfer hydrogenation.

Cleavage of immobilized disubstituted triazenes with electrophiles: solid-phase synthesis of alkyl halides and esters

Abstract An efficient, selective cleavage of polymer-bound disubstituted triazenes with trimethylsilyl halides produces alkyl chlorides, bromides and iodides in good to excellent purities and yields. Similarly, alkyl esters are formed upon cleavage with carboxylic acids.

Multifunctional Linkers as an Efficient Tool for the Synthesis of Diverse Small Molecule Libraries: The Triazene Anchors

Publisher Summary Triazenes provide new possibilities for the activation of the ortho-position of arenes by coordination of metal ions and/or by lowering the electron density of the arene ring, they are also ideal synthons for diazonium salts. This chapter discusses two linkers based on the triazene chemistry, T 1 and T 2, used for the synthesis of diverse small molecule libraries. While the T 1 linker system consists of 3,3-dialkyl-1 aryl triazene bound to the support via the alkyl chain, the T 2 linker family is based on immobilized aryl diazonium salts. The triazene T 1 linker has been successfully used as a linker for arenes. While the T 1 linker involves an immobilization of a diazonium salt on an amine resin, the T 2 linker represents the reversal of this concept. The T2 linker has recently been shown to be a versatile backbone amide anchor. Immobilized disubstituted triazenes were acylated with carboxylic acid anhydrides or chlorides to give amide derivatives. These amides were cleaved under very mild conditions using trimethyl chlorosilane. This sequence thus, employs the T 2 system as backbone amine linker and was demonstrated in the automated library synthesis of substituted amide derivatives.

Preparation of planar chiral amino phenols based on the [2.2]paracyclophane backbone

Abstract The synthesis of various planar and central chiral secondary and tertiary amino phenols based on the [2.2]paracyclophane backbone is described. Planar chiral tertiary amino phenols are prepared by reductive amination of 5-formyl-4-hydroxy[2.2]paracyclophane (FHPC) with secondary amines. The reduction of imine and ketimine precursors, as well as the 1,2-addition to these compounds is also described.