Traceless link

Van der Eycken and coworkers have presented a study describing the microwave-assisted solid-phase Diels-Alder cycloaddition reaction of 2(lH)-pyrazinones with dienophiles [69]. After fragmentation of the resin-bound primary cydoadduct formed by Diels-Alder reaction of the 2(lH)-pyrazinone with an acetylenic dieno-phile, separation of the resulting pyridines from the pyridinone by-products was achieved by applying a traceless linking concept, whereby the pyridinones remained on the solid support with concomitant release of the pyridine products into solution (Scheme 7.58). 

Phosphonium salts can be dealkylated by treatment with alkoxides to yield alkanes. Although the hydrolytic cleavage of phosphonium salts in solution has been well investigated, the solid-phase variant of this reaction has not yet found broad application. One example, in which traceless linking was based on the alkoxide-induced dealkylation of a resin-bound phosphonium salt, is given in Table 3.48 (Entry 1). 

Scheme 7.43 General reaction sequence for microwave assisted traceless-linking concept for 2(liT)-pyrazinone Diels-Alder cycloadditions with acetylenic dienophiles.

An anchor for traceless linking might also have a safety-catch function or be suitable for multifunctional cleavage. Linker systems enable the introduction of certain atoms or molecule fragments and will play an important role in the development of diverse organic substance libraries. It is important to point out that the final diversity is achieved on cleavage, and not in an additional solution phase re-... 

The development of suitable linkers is a continuous area of interest in solid-supported synthesis. Based on their previously explored traceless linking strategy using HASC (a-heteroatom-substituted carbonyl) linkers employing Smb, Procter and coworkers have demonstrated the use of a novel sulfur-based linker for the synthesis of the tetra-... 

Piscopio AD, Miller JF, Koch K. Solid phase heterocyclic synthesis via ring closing metathesis traceless linking and cyclative cleavage through a carhon-carbon double bond. Tetrahedron Lett. 1997 38 7143-7146. 

In this synthesis, a traceless linking concept was applied and the products (pyri-dines) were separated from the by products (pyridinones), which remained on the solid support, where as pyridine was released in the solution. It was observed that the rate of reaction was accelerated from hours or days to minutes, when carried out under high temperature microwave conditions. 

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