Olefinic linkers

An illustrative example of an alternative strategy (cf Fig. 11c) involving the use of a novel traceless linker is found in the multistep synthesis of 6-epi-dysidiolide (363) and several dysidiolide-derived phosphatase inhibitors by Waldmann and coworkers [153], outlined in Scheme 70. During the synthesis, the growing skeleton of 363 remained attached to a robust dienic linker. After completion of intermediate 362, the terminal olefin in 363 was liberated from the solid support by the final metathesis process with concomitant formation of a polymer-bound cyclopentene 364. Notably, during the synthesis it turned out that polymer-bound intermediate 365a, in contrast to soluble benzoate 365b, produced diene 367 only in low yield. After introduction of an additional linker (cf intermediate 366), diene 367 was released in distinctly improved yield by RCM. 

Scheme 5.13 Cleavage of an octenediol linker by olefin cross-metathesis to yield NPG63.69...

The power of the HR-MAS method for on-resin analysis has been further underscored in the development of new linkers. Without this method, only indirect analytical data after removal from the resin was available. Direct assessment of the resin-bound linker greatly facilitated the introduction of a 4,5-dibromo octane- 1,8-diol linker that was converted into an octane-1,8-diol linker cleavable by olefin metathesis at the end of the synthesis.6 The disappearance and reappearance of the olefinic protons as well as the growing oligosaccharide chain was clearly visible in the H spectrum (Fig. 8.7).7... 

The stereochemical outcome of such cycloadditions may be altered by substituents attached to the nitrile oxide-olefin linker. Hassner and co-workers (75,240,253-255) and Kurth and co-workers (256) examined the influence of a stereogenic center a to the dipole in the cycloaddition of alkene-tethered nitrile oxides that feature a sulfur or oxygen atom within the connecting chain (Table 6.13). As expected, the diastereofacial selectivity is increased in the presence of fragments with increasing steric demand. Cycloadditions of thioethers show lower... 

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. 

Linkers for Alkenes Cleavable by Olefin Metathesis and Miscellaneous Linkers for Alkenes... 

An automated solid-phase method necessitates a polymer support and a linker that are compatible with the reagents used in carbohydrate synthesis. Several strategies have been developed that address functional group compatibility and swelling of the polymer support. Of these strategies, a family of olefinic linkers has proven to be readily cleaved under neutral... 

A typical coupling cycle (Scheme 2) for glycosyl trich1oroacet.imidat.es is outlined in Table I. A polystyrene support, functionalized with an olefinic linker, is loaded into a reaction vessel in the instrument.1617 The activating reagent (trimethylsilyl trifluoromethanesulfonate (TMSOTf /... 

In addition to analogs incorporating an olefinic double bond as a linker between the macrolactone ring and different types of heterocycles, we have also studied a new family of side-chain modified structures, which are characterized by rigidifica-tion of the entire side-chain manifold (exemplified for quinoline-based analogs 30 and 31). ... 

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