Tethered reagents

Polymer-supported reagents differ from polymer-supported substrates in that the former mediate a reaction rather than becoming an integral part of the product. A major attribute of tethered reagents is that both the reagent and the reagent byproduct can be directly filtered away from solution-phase products. 

Figure 1.28. Resin tethered reagents used in combichem.

Figure 1.29. Illustration of tethered reagents in preparing propranoloL...

The first example in which a temporarily tethered reagent was directed to attack unactivated C-H bonds remote from the tether point was a study of the products from photolysis of esters of benzophenone-4-carboxylic acid 1 carrying long-chain alkyl groups (Scheme 6-1) [31]. The n-tetradecyl ester was attacked over carbons 8-13, with half the... 

Scheme 6-4 Examples of free-radical halogenations of steroids by tethered reagents.

In both epoxidation examples, the stereoselectivity is due to the cyclic nature of the transition state the fact that there is a hydrogen bond or O-metal bond delivering the reagent to one face of the alkene. Effectively we have moved on from the tethered nucleophiles of the last section to (transiently) tethered reagents. This is a very important concept, and we revisit it in the next chapter cyclic transition states are the key to getting good stereoselectivity in reactions of acyclic compounds. 

Reaction on the more hindered face can be encouraged by (1) tethered nucleophiles or (2) cyclic transition states (tethered reagents). 

This work has been developed to incorporate a range of substrates [83], and alternative tethering reagents [84], whilst maintaining the initial, excellent stereochemical control. 

Synthetic chiral adsorbents are usually prepared by tethering a chiral molecule to a silica surface. The attachment to the silica is through alkylsiloxy bonds. A study which demonstrates the technique reports the resolution of a number of aromatic compoimds on a 1- to 8-g scale. The adsorbent is a silica that has been derivatized with a chiral reagent. Specifically, hydroxyl groups on the silica surface are covalently boimd to a derivative of f -phenylglycine. A medium-pressure chromatography apparatus is used. The racemic mixture is passed through the column, and, when resolution is successful, the separated enantiomers are isolated as completely resolved fiactions. Scheme 2.5 shows some other examples of chiral stationary phases. 

Intramolecular [3-1-2] cycloadditions, i.e., having the TMM moiety and the acceptor linked by a tether, have great synthetic utility in polycarbocycle construction. The construction of 5.5, 6.5, and 7.5 ring systems has been demonstrated with this methodology [21-25]. A number of efficient routes to acyclic precursors were developed (Scheme 2.11). The organometallic reagent (31), generated from 2-bro-mo-3-(trimethylsilyl)propene (32) [26], is a key component in the construction of... 

Taxus baccata 656 Taxus brevifolia 655 Tebbe reagent 703 telomerization 354 ff. a-terpineol 5 tertiary radicals 409, 413 tether, disposable 664 tetrahedrane 12... 

Among special chemical methods that facilitate the Diels-Alder reaction can be included the temporary metal connection strategy [101] that is illustrated in Table 4.27. Si, Mg and A1 are used as temporary connectors of diene and dienophile moieties. The cycloaddition occurs easily due to its intramolecular nature and because the dienophilic component of reagent is now formally a vinyl carbon ion (i.e. a vinyl carbanion in 154 with M = AlEt ). Thus the metal-tethered 154, prepared from lithium alkoxide of 153 with the suitable metal vinyl halide, gives, by heating, the cycloadducts 156 and 157, through the... 

Difunctional reagents, for example the very cheap dimethyldichlorosilane 48, which is produced on a large technical scale, and the much more reactive and expensive dimethylsilyl bis(O-triflate) 49 [65-67] (Scheme 2.8) convert alcohols or phenols 11 in the presence of bases, for example triethylamine or DBU, into the silylated compounds 50. Thus 48 and 49 and other bifunctional reagents such as di-tert-butyldichlorosilane [68] or di(tert-butylsilyl)-bis(0-triflate) [69] and the subsequently described 51 and 52 combine two alcohols to silicon-tethered molecules 50, which can undergo interesting intramolecular reactions [70-74]. 

Traviglia, S.L., Datwyler, S.A., and Meares, C.F. (1999) Mapping protein-protein interactions with a library of tethered cutting reagents The binding site of sigma (70) on Escherichia coli RNA polymerase. Biochemistry 38, 4259-4265. 

Recently, the silane-mediated reductive cyclization of activated alkynes with tethered ketones using Stryker s reagent as a catalyst was reported.112,90b Alkynyl ketone substrate 84a was treated with a catalytic amount of Stryker s reagent in the presence of polymethylhydrosiloxane (PMHS) to afford the cA-fused hydrindane 84b as a single diastereomer. This method is applicable to both five- and six-membered ring formation, but often suffers from competitive over-reduction of the reaction products (Scheme 59). 

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