Tether dimethylsilyl

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]. 

Curran and co-workers have explored the use of silicon tethers to carry out these reactions. They have successfully demonstrated the 1,5 and 1,6 translocation of a radical that goes on to do intramolecular cyclization reactions. This method was used to synthesize natural product such as crinipellin A22 and 2-(o)-(2-bromoaryl)dimethylsilyl-a-methyl-D-mannopyranoside.24 One of the nice benefits to the use of silicon tethers is that they serve as a hydroxyl-protecting group before and after the reaction is performed. 

In the cases of dimethylsilyl IMDA precursors, the exolendo selectivity was poor. However, this ratio could be readily and quite dramatically influenced by varying the alkyl substituents on the silicon template [12]. Thus with dienol 24, tether formation with dimethylvinylsilyl chloride and subsequent IMDA reaction afforded a 4 1 mixture of exolendo products (Scheme 10-7). The ratio could be further improved to 10 1 by using a diphenylsilyl tether, and when bulky Bu groups were used, a single stereoisomer, resulting from exo addition, was observed. This example once more illustrates the potential for tuning the stereoselectivity of the reaction by varying the steric interactions with the tether. 

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. 

Controlled radical cyclization directly onto a ring junction is less easy. Lejeune and Lallemand envisaged that a tethered radical cyclization of a (bromomethyl)dimethylsilyl ether onto an allylic double bond could be used to incorporate a hydroxymethyl functionality into an angular position at the ring junction of a decalin system [53]. This would then provide an interesting entry into a variety of natural products containing this skeletal functionality, such as the insect antifeedant clerodin 132 (Scheme 10-45). 

Tamao et al. have investigated (dichloromethyl)dimethylsilyl ethers as radical cyclization precursors [69]. Silyl ether 174 was readily prepared from the commercially available silyl chloride and isophorol. 5- xo-trig cyclization could be effected under high-dilution conditions, affording the bicycle 175 as a 6 4 mixture of stereoisomers. Subsequent oxidative tether cleavage afforded 2-formyl alcohols 176 and 177 where unfortunately, the presence of base caused partial epimerization of the center a to the formyl group (Scheme 10-56). 

Tanaka s strategy for the preparation of F-C-hydroxymethyl uridine derivatives related to angustmycin antibiotics relied on radical cyclizations from (bromomethyl)dimethylsilyl-tethered L,2 -unsaturated uridines. The best yield was obtained with a carbomethoxy substituent (eq 12), but the reaction also worked with a phenoxy substituent, giving access to the 2 -epimer in the angustmycin family, and thus to analogues for S AR examinations. 

Olefins andAlkynes. The increased scope of the silicon tether in radical chemistry, which is still the most important reactivity allowed by the (bromomethyl)dimethylsilane moiety, has been reviewed. Some authors have again illustrated the synthetic interest of Nishiyama-Stork radical cyclizations of allylic (bromomethyl)dimethylsilyl ethers. Jenkins achieved stereoselective cyclizations on a fused cyclopentanol, while Herdewijn prepared pyranosyl nucleosides. Starting from /-substituted... 

Removable Silicon Tethers. Cox and coworkers have explored the use of removable silicon tethers as a method of controlling the relative stereochemistry of the addition of allylsilane to aldehydes.This strategy relies on the construction of un-symmetrical bis(silyl)propenes with a pendant aldehyde (eq 13). When the dimethylsilyl ether was used as the tether only the corresponding diene was observed, but by increasing the steric bulk of the silane to the diethylsilyl ether the construction of the oxasilacycle was possible. Use of the diisopropyl tether completely suppressed formation of the diene by-product however, the 1,3-stereoinduction was eroded as four diastereomers were observed instead of two. Tamao-Fleming oxidation of the two diastereomers (2.7 1-9.7 1 dr) derived from the diethylsilyl ether tether yielded the stereodefined 1,2,4-triol in the case of the major... 

Scheme 7. Dimethylsilyl-tethered glycosidalion in the synthesis of p-mannopyranosides.

Scheme 8. Side-reaction in dimethylsilyl-tethered glycosidation.

Scheme 9. Dimethylsilyl-tethered glycosidation in the synthesis of a-glucopyranosides.

Scheme 11. Dimethylsilyl-tethered glycosidation with tethering to the 3 position of the donor.

The stereoselective branching of L-rhamnal at C-1 and C-2 via a silicon tethered radical cyclization is illustrated in Scheme 7, and allyl alcohol groups which are protected as their (bromomethyl)dimethylsilyl ethers undergo a radical-induced cyclization to give branched-chain sugars as shown in Scheme ZP... 

---