Olefinic linker

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... 

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 /... 

Olefinic linker [330, 331] Cleavage Product after cleavage ... 

Alkenes can be considered as a class of protected carbonyl compounds since they can be converted into carbonyls by ozonolysis. Hall [69] demonstrated a practical strategy for solid phase synthesis of peptide aldehydes using an olefinic linker, which was constructed using Wittig chemistry. After normal peptide synthesis using the alkene linker, ozonolysis of the linker and subsequent workup with... 

Scheme 17.27 Solid phase synthesis of peptide aldehydes using an olefinic linker.

Application of purification methods has been used to improve the quality of products in a number of examples. Boger et al. have published two papers on the preparation of indexed libraries suitable for probing receptor and protein homo- and hetero-dimerisation events [8,9]. Two different linking strategies were developed either an olefinic linker introduced via olefin metathesis or a bis-amide linker (Figure 3). The work extends their previous synthesis of libraries using liquid-liquid extraction to effect purification of intermediate stages in the library preparation. 

Once we knew that CP-392,110 was the final candidate, a more efficient bond disconnection was the one across the olefin linker to provide the same quinazolinone nucleus 2 and a novel aldehyde 4 (Scheme 4). The initial starting materials for each of these were meto-fluorobenzoic acid and 2,6-dibromopyridine, which were both available in kilogram quantities at a reasonable price. This disconnection would provide a more efficient synthetic sequence and avoid the potential for "dimer" formation in the aldol addition. The major xmcertainty with this approach was finding an efficient synthesis of the aldehyde 4. 

Scheme 108 Release of terminal olefins from olefinic linker s) tems...

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 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... 

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