Linker selenium linkers

Linkers based on sulfur, stannane and selenium chemistry are certainly some of the most flexible systems, because these elements can favorably be tailored for the use as fragile points of attachment. 

Scheme 3.2 Solid-phase semi synthesis of Vancomycin (48) based on a new selenium linker [123, 124].

The preparation of solid-supported selenium resins and their application as linkers and reagents for sohd-phase synthesis have heen described [121, 122]. These reagents have proven to be useful for applications in sohd-phase and combinatorial synthesis because of their versatility and ease of handling. 

Recently, the semi-synthesis of Vancomycin (48) on solid supports was accomplished using an allylic linker (Scheme 3.2) [123, 124]. Polymer-bound chiral electrophilic selenium reagents have been developed and applied to stereoselective se-lenylation reactions of various alkenes (Tab. 3.9) [125]. 

The selenium linker has been used as starting point for a library of natural products and medicinal relevant molecules by Nicolaou et al. (Scheme 3.29) [295,... 

Resin-bound selenium has been used as a linker for alkenes in two ways (a) as an oxidant-sensitive linker (selenoxides readily undergo [5-elimination at room temperature Entries 6-8, Table 3.43 [767-773]), or (b) as a linker cleavable by tin radicals (Figure 3.37 Entries 9 and 10, Table 3.43). The main advantages of selenides as linkers are their stability under a broad variety of (non-oxidizing) reaction conditions, including high temperatures and treatment with acids or bases, and the mild conditions required for their cleavage. 

Support-bound organoselenium compounds have mainly been used as synthetic intermediates and linkers. The use of organoselenium compounds as linkers for solid-phase synthesis has been investigated by several groups [1-4]. The selenium-carbon bond is stable under a broad variety of reaction conditions, but can be selectively cleaved by tin radicals or by oxidants (see Sections 3.15.1 and 3.16.4). 

Traceless linkers enable the solid-phase synthesis of products which were formerly only accessible by tedious, multistep solution-phase chemistry. Some of these linkers tolerate a broad range of reaction conditions, giving the chemist plenty of freedom in the design of new solid-phase synthetic sequences. Interestingly, polystyrene-bound selenium reagents can also mediate useful chemical transformations of substrates during their attachment to the support, and thereby function both as reagents and as linkers. 

Synlett 1999, 1802-1804 d) Selenium-based linker K. C. Nicolaou, H. J. Mitchell, K. C. Fylaktakidou, et al., Angew. Chem. 2000, 112, 1089-1093 e) Ether-type linker K. Fukase, Y. Nakai,... 

Cleavage reagents Benzyl- type linkers Ketal/ acetal linkers Esters/ amide linkers Silyl linkers Triazene linkers Selenium/ sulfur/ stannane linkers... 

Scheme 6.1.36. Electrophilic selenium anchors as multifunctional linkers.

The selenium linker 1.45 (103), obtained from Merrifield resin and potassium selenocyanate, was treated according to oxyselenylation conditions to give a supported selenolactone. Oxidative deseleny lation (m-CPB A, DCM, rt) produced the unsaturated lactone in good yield and purity. An expansion of this chemistry, including several SP transformations prior to the cleavage, is mentioned in the original paper (103). 

The selenium-sihcon linker 1.46 (104), obtained from hydroxy PS resin and methyl glyoxylate through a simple five-step scheme, was coupled with a steroid scaffold to give an acetal then transformed on SP and finally cleaved with TB AF/tetramethyl urea, 1 h, 100 °C to give decorated alcohols via unstable hemiacetals with good yields and purities. 

This approach may represent a novel application for recently reported multipurpose selenium-based SP linkers (21). 

Nicolaou [44-47] has pioneered the use of selenium linkers in soUd-phase synthesis. A selenium linker [44,45], cleaved under radical conditions, has been utilized in a cyclative-capture strategy for the soUd-phase synthesis of indolines (Scheme 61). Treatment of o-allylanihnes with selenenyl bromide resin in the presence of a Lewis acid results in cyclative-capture to give immobilized indoline 240. Further functionalization was then carried out prior... 

Scheme 61 Radical cleavage of a selenium linker by Nicolaou [44,45]...

Scheme 63 Selenium linker cleavage in the absence of a radical quench by Nicolaou [45]...

Scheme 64 Selenium linker cleavage in the synthesis of 2-deoxyglycosides by Nicolaou [46]...

Scheme 65 Selenium linker cleavage in an approach to everinomicin 13,384-1 by Nico-laou [47]...

Scheme 66 Selenium linker cleavage, carbonylation and cyclization by Engman [48]...

Scheme 68 Cleavage of a chiral selenium linker by Wirth [50]...

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