Silyl tether

The conformations of a number of silyl-tethered nucleosides typified by 3, 5 -0-(di- /t-butylsilanediyl)-adenosine 3, have been studied by NMR spectroscopy <1993MRC1039>. The conformational bias in such systems was used to determine the stereochemistry of compound 4 by NOE studies <1998NN1033>. 

Rhodium carbonyl complexes also catalyze the cascade cyclization/hydrosilylation of 6-dodecene-l,l 1-diynes to form silylated tethered 2,2 -dimethylenebicyclopentanes. For example, reaction of ( )-85 with dimethylphenylsilane catalyzed by Rh(acac)(CO)2 in toluene at 50 °G under GO (1 atm) gave 86a in 55% yield as a single diastereomer (Equation (56)). Rhodium-catalyzed caseade cyclization/hydrosilylation of enediynes was stereospecific, and reaction of (Z)-85 under the conditions noted above gave 86b in 50% yield as a single diastereomer (Equation (57)). Rhodium(i)-catalyzed cascade cyclization/hydrosilylation of 6-dodecene-1,11-diynes was proposed to occur via silyl-metallation of one of the terminal G=G bonds of the enediyne with a silyl-Rh(iii) hydride complex, followed by two sequential intramolecular carbometallations and G-H reductive elimination. ... 

Consistent with most tethered photocycloadditions, the photoproducts obtained from silicon tethered irradiations are formed with complete regiocontrol [19]. Several examples of silyl tethered groups have been reported. Scheme 16 lists the variants that have been successful. As mentioned previously, the mechanistic pathway that is most consistent with the results involves interaction between the alkenes prior to cycloaddition. The experimental observation is that cycloadducts are formed only when the alkenes have extended n systems attached. 

One silicon tethered example that is unique in its selectivity is the cinnamyl tethered silyl enol ether shown in Sch. 17. Unlike all of the other silyl tethered examples, this compound gives a photoadduct that is the result of a cross 2+2. However, it is the product expected if the cycloaddition is a stepwise process involving radical intermediates. It is also the product expected if the reaction pathway is controlled by 7i-stacking. 

Scheme 16 Silyl tethered groups that undergo cycloaddition.

The parallel synthesis of an exhaustively stereodiversified library of r-l,5-enediols by silyl-tethered RCM has also been described <20010L2157>. 

Silyl-tethered stilbazole derivatives 349 were synthesized and subjected to intramolecular photocycloaddition in benzene at room temperature to give compounds of type 350 with stereochemistry cis-trans-ris and cis-trans-trans (Equation 66). It was shown that complexation of pyridine-containing stilbazoles 349 with dicarboxylic acid or catechol enhanced both the efficiency and stereoselectivity of the photocycloaddition <2006TL7865>. 

In Shea s approach to the polyhalogenated cyclohexane 87, derived from a red marine alga, Plocamium sp., a Type II IMDA reaction utilizing a disposable (allyl)silyl tether was used as a key step [29nj. The triene cyclization precursor 88 was readily prepared and underwent Diels-Alder reaction in 74% yield with the expected, complete regiocon-trol affording exclusively bicycle 89. The rigid, bicyclic framework of the cycloadduct... 

Scheme 10-33 Preparation of the silyl tether was achieved in excellent yield.

Scheme 10-39 Varying the length of the silyl tether allows access to either endo-re or endo-si products.

Bromomethyl)dimethylsilyl chloride is the most widely investigated and important reagent for incorporating a radical precursor into a silyl tether. It is commercially available and readily introduced as a silyl ether under standard conditions. Moreover, the facile cleavage of the silicon tether under a variety of conditions after reaction yet further enhances its synthetic utility. 

Scheme 10-45 A silyl-tethered radical cyclization could be used to incorporate angular hydroxymethyl functionality at a ring junction.

In most cases the radical generated after cyclization is quenched by H-abstraction. However, another possibility is to utilize the cyclized radical in another C-C bond-forming event. Fraser-Reid and co-workers utilized a silyl-tethered radical cyclization of the (L)-rhamnal-derived silyl ether 142 to generate the anomerically. stabilized radical 143, which could be trapped in the presence of an excess of acrylonitrile to generate acetate 144 after tether cleavage and peracetylation (Scheme 10-48) [55a]. This reaction sequence occurred with complete regio- and stereoselectivity. The same group has also used an acetal tether (vide infra) to effect similar transformations [55 b, 56]. 

Koreeda and Hamann have reported the use of silyl tethers in stereocontrolled syntheses of branched-chain 1,4-diols and 1,5-diols [61]. Exposure of (bromomethyl)silyl ethers prepared from the corresponding homoallylic alcohols with Bu SnH in the presence of AIBN allowed smooth conversion to the corresponding cyclic siloxanes, from which diol products were obtained using standard, oxidative cleavage protocols. While monosubstituted olefin 149 selectively underwent 1-endo cyclization, di- and trisubsti-tuted olefins 150 and 151 preferentially reacted through the 6-exo mode with complete stereocontrol, affording the diol products 152 and 153, respectively (Scheme 10-50). 

In an example from the Curran group, a silyl tether provides a method of incorporating a radical precursor into a molecule at a site remote from where it is desired [72]. 1,5-... 

Scheme 10-60 A silyl tether provides a more readily prepared radical precursor for effecting cyclization.

Previous examples of silyl-tethered radical cyclizations have involved the incorporation of the radical precursor during the formation of the silyl ether tether. An alternative would be to incorporate the radical acceptor. A number of suitable silyl chlorides are commercially available which facilitate the preparation of such cyclization precursors. 

Scheme 10-63 The stereochemical outcome in the silyl-tethered radical cyclization of nucleosides is dictated by the configuration of the silyl ether group.

Although the (bromomethyl)silyl ether connection has been more extensively utilized in radical cyclizations, Stork also introduced, at a similar time, the use of a mixed acetal function [51a, 73b, 80], This tether differs in that a two-carbon unit is introduced on the proximal carbon atom of the olefin, whereas the silyl tether allows the incorporation of only one carbon atom. The chemistry of this tether is dominated by 5-exo-trig cyclizations onto allylic double bonds which proceed with the usual degree of high stereoselectivity. 

Silyl tethered amines are used frequently in amide-forming coupling reactions [e.g.. Fig. 16(c)] (169, 170). Isocyanate compounds are also commercially available, and have been used in the immobilization of enzymes within the sol-gel pores (171). These isocyanates can also be used to prepare silylated phen ligands that have been used in our own studies (172). Silylated isocyanates have... 

Harrison, B. A., Verdine, G. L. The synthesis of an exhaustively stereo-diversified library of cis-1,5 enediols by silyl-tethered ring-closing metathesis. Org. Lett. 2001, 3, 2157-2159. 

Sinay s group have used silicon tethering to facilitate radical addition reactions for construction of C-disaccharides. Thus, 166, prepared by reacting the constituent monosaccharide derivatives with BuLi and dichlorodimethylsilane, undergoes radical reaction (AIBN) followed by cleavage of the silyl tether (TBAF) to provide C-disaccharide 167 (see also Chapter 3) which is related to the carbon skeleton of the herbicidins." ... 

In parallel, the development of a 3,2 silyl tether allowed access to the p-linked product as demonstrated in Sinay s synthesis of methyl P-C-lactoside (68) (Scheme 11.17) [82]. Alcohols (64) and (65) were connected via... 

Water soluble p-sulfonato calbc[w]arenes (w = 8, la-lb and n=6, 2a-2b) was employed as host to control the outcome of photodimerization and photoisomerization of 4-stilbazoles [17]. Novel macrocydic and medium-size stilbenophanes tethered by silyl chains were synthesized, and their photochemical and photophysical properties were examined (Figure 5.5) [18]. Direct irradiation of macrocydic stilbenophanes stereoselectively gave intramolecular photocydoadducts, and the efficiency increased with decreasing distance between the two stilbene units. The triplet-sensitized photoreaction of stilbenophanes caused cis-trans photoisomerization. Photoreactions of as-fixed stilbenophanes under an oxygen atmosphere selectively led to phenanthrenophanes. Fluorescence quantum yields increased with the introduction of silyl substituents, and hence those of silyl-tethered stilbenophanes were larger than that of unsubstituted fraws-stilbene. Intramolecular excimer emis-... 

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