Alkenes traceless linkers

The main strategies used for the preparation of alkenes by cleavage from insoluble supports are (3-elimination and olefin metathesis (Figure 3.35). Because some of these strategies enable the preparation of pure alkenes, devoid of additional functional groups, the linkers are sometimes also called traceless linkers, although the C=C double bond reveals the original point of attachment to the support. 

The first traceless linker was developed by Kamogawa and coworkers in 1983 [82]. Starting from a polymer-bound sulfonylhydrazine, sulfonylhydrazone resin 88 was formed by reaction with ketones or aldehydes. The cleavage step was conducted either by reduction with sodium borohydride or lithium aluminium hydride to yield alkanes 89 or by treatment with base to give the corresponding alkenes 90 in a Bamford-Stevens reaction (Scheme 16.20). This work was a pioneering approach in the field of traceless tinkers. 

Starting from a vinyl-substimted resin, hydroboration with 9-BBN yields a homobenzylb-orane (Scheme 9). This intermediate can be coupled with various functionalized aryl iodides as well as vinyl and alkyl iodides giving rise to resins with amide, ester, or protected hydroxy functionaUties.t Similarly, bromostyrene could be coupled with functionalized boranes for the attachment of preformed handles, for example, for the construction of the silicon traceless linker.t i The carbometaUation of certain alkenes such as tropanes and the subsequent treatment with aryl boronic acid gives rise to two new C—C bonds (Scheme 10). 

Stannaries have become prominent in multifunctional anchoring groups. A polymer-bound tin hydride 41 has been used to hydrostannylate alkynes under the action of palladium-catalysis to give polymer-bound alkenylstannanes 42. These alkenyl stannanes have been employed in intermolecular [45] and intramolecular Stille reactions [46]. Alkenylstannanes can also undergo protonation to give alkenes 44 in a traceless fashion. This linker is therefore multifunctional (Scheme 6.1.12). 

In planning fhe solid-supported total synfhesis of 6-epi-dysidiohde and other related phosphatase inhibitors, Brohm and co-workers [226] developed a robust linker, which provided the terminal alkene by means of a traceless RCM release from the resin. Thus, suitable precursor (112) was prepared, after intensive investigations, on Ellman s dihydropyran resin [227]. Subsequent RCM with the Grubbs catalyst afforded the expected triene (113) in 82% isolated yield along with the solid-supported cyclopentene derivative (114) (Scheme 26). The tetrahydro-pyran link has a great impact on the yield of the RCM a direct benzylic resin attachment resulted in much lower yields. 

A selenium linker has been used in the preparation of various nitrogen-containing heterocycles. Cycloaddition of nitrile oxides to resin-bound alkynes gave resin-bound isoxazoles (Scheme 11.41). a-AIkylation of the resin-bound cycloadducts with halides under basic conditions gave additional diversity for the products. Traceless oxidative cleavage of the isoxazoles was achieved via the elimination of the resin with hydrogen peroxide. The diversity of the products was still expanded with a second cascade of 1,3-dipolar cycloadditions to alkenes attached to the resin. 

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