Traceless Linker Units

Sulfur-based linker units have been developed that utilize the reactivity of sulfur in a multitude of different forms and oxidation states. i ° The simplest linker units are the thioether-based linkers, and initially conditions for traceless cleavage of aliphatic... 

Finally, homolytic cleavage via a radical mechanism has also proven a powerful cleavage technique. Such cleavage is traceless and can be mediated by AIBN and tributyltin hydride (Table 1.14, Entry 14) or AlBN/tils(trimethylsilyl)silane (Table 1.14, Entry 15). Tellurium linker units are cleavable via the same mechanisms (Table 1.14, Entry... 

Alkoxyaniline units have been used as traceless linkers for the solid-phase combinatorial synthesis of 2-arylbenzoxazoles, 2-arylbenzothioazoles, and 2-arylbenzimidazoles [40] (Scheme 18). This method has an added advantage as the products can be released from the solid support only by exposing it to an air atmosphere without any kinds of oxidants under neutral conditions. The solid support could be easily recovered and recycled after cleavage. 

The synthetic route developed by Craig et al. examines a traceless cleavage model for resin-bound o-quinodimethane (753) and the transformation into naphthalene-derivative 759,2,3-naphthoquinone (755) and 3-(trichloro-methyl)-isoquinoline (757) (Scheme 112). The linker unit synthesized via a three-step procedure contains no visible dien structure to undergo Diels-Alder reactions but can be seen as a precursor for a solid-supported dien. 

Related isoflavones have been prepared, using SPOS, by Harikrishnan and Showalter. Resin-bound salicyl aldehyde derivatives 336, immobilized via a traceless silyl linker unit, were prepared and treated with a Grignard reagent to introduce the first point of diversity. Subsequent re-oxidation with 2-iodoxybenzoic acid (IBX), and deprotection of the methoxymethyl (MOM) group provided ketone 338. Treatment of ketone 338 with amide acetals promoted an unusual cyclization, which concurrently installed R to give 339. Final traceless cleavage with CsF or TBAF releases isoflavones 340 (Scheme 3.59). 

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