Tethers silicon

The use of silicon as a temporary tether in intramolecular reactions has found widespread application in organic chemistry [17]. This concept was first described by Stork et al. in 1992 for intramolecular stereocontrolled glycosidation reactions. With a silyl group connected to the 0-2 position of a P-mannosyl donor it was demonstrated that the glycosyl acceptors could contain primary and secondary hydroxyl groups [18, 19]. 

A similar observation was made when silyl acetal 21f was activated, producing the expected glycoside 23f in 54% yield and 41% of a debenzylated compound [19]. 

It has recently been demonstrated that treatment of disaccharide 31 with NIS produces the debenzylated compound 32, probably via a benzylidene intermediate and without participation of silicon [24], 

Higher yields and better selectivity were obtained when the silyl group was anchored to the 0-4 position of thioglucoside derivative 37, giving exclusively the a- 

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Intramolecular reactions of temporarily silicon-tethered molecules in synthesis of 0,Si-heterocycles 97S813. 

Another strategy to control the regio- and stereochemistry of cycloaddidon is a silicon-tethered reacdon, as discussed in the secdon of nitronates fSecdon 8.2.3 fEq. 8.65. ... 

Keywords regio- and stereoselective silicon-tethered Diels-Alder cycloadditions, synthesis of branched sugars and linear and polycyclic hydrocarbons... 

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]. 

Recently, silicon-tethered diastereoselective ISOC reactions have been reported, in which effective control of remote acyclic asymmetry can be achieved (Eq. 8.91).144 Whereas ISOC occur stereoselectively, INOC proceeds with significantly lower levels of diastereoselection. The reaction pathways presented in Scheme 8.28 suggest a plausible hypo thesis for the observed difference of stereocontrol. The enhanced selectivity in reactions of silyl nitronates may he due to 1,3-allylie strain. The near-linear geometry of nitrile oxides precludes such differentiating elements (Scheme 8.28). 

Type I and II silicon-tethered carbonyl-ene reactions were first performed by Robertson.4,4a,4b One particularly striking application of this method is the conversion of isoserine derivative 3 (Scheme 1) into amino triol 4 via a carbonyl-ene reaction followed by Tamao-Fleming oxidation.5... 

In this approach, the glycosyl donor and the glycosyl acceptor are linked by the 2-OH of the donor and the free OH of the acceptor. It is one of the most predictable and reliable methods for achieving 1,2-cis stereocontrol. Acetals, mixed p-methoxybenzylacetals and silicon tethering have been widely used as well as iodonium mediated tethering acetals derived from vinyl, allyl and allenyl ethers. These methodologies have been revised.6,76... 

Skrydstrup, Beau and co-workers122 have adapted Stork s method to the SmI2-reduction of glycosyl pyridyl sulfones bearing a silicon-tethered unsaturated group at HO-C(2). An example is shown with the synthesis of methyl a-C-zso-maltoside 172 from alkyne 170 via the 5-exo-dig radical cyclization of 171 (Scheme 56).144... 

In a similar manner, Brummond et al. demonstrated the first total synthesis of 15-deoxy-A12,14-prostaglandin J2 (162) that was completed using a silicon-tethered allenic Pauson-Khand reaction to obtain the highly unsaturated cyclopentenone substructure [36]. Treatment of alkynylallene 160 with molybdenum hexacarbonyl and dimethyl sulfoxide affords the desired cycloadduct 161 in 43% yield (Scheme 19.30). Trienone 161 was obtained as a 2 1 Z E mixture of isomers in which the Z-isomer could be isomerized to the desired E-isomer. The silicon tether was cleaved and the resulting product converted to 15-deoxy-A12,14-prostaglandin J2 (162). 

The Ir-catalyzed [2+2+2] cycloaddihon of diynes and monoalkyne advocates a new synthehc approach to silafluorenes [13]. The Ir-PPh3-complex-catalyzed reac-hon of benzene and silicon-tethered 1,6-diynes with disubstituted alkynes gave tetra-subshtuted silafluorenes (Scheme 11.3). The consecutive [2+2+2] cycloaddihon of two types of tehayne provided a ladder-type silafluorene and a spirosilabi-fluorene (Schemes 11.4 and 11.5). 

For the synthesis of C2-symmetric 1,4-diol, Evans planned temporary silicon-tethered ring-closing metathesis, and asymmetric synthesis of D-altritol was... 

Cyclic alkyl nitronates may be used in tandem [4+2]/[3+2] cycloadditions of nitroalkanes, and this reaction has been extensively studied by Denmark et al. (64,333-335). In recent work, they developed the silicon-tethered heterodiene-alkene 219 (Scheme 12.63). Steric hindrance and the fact that both the nitroalkene and the a,p-unsaturated ester in 219 are electron deficient renders the possibility of self-condensation. Instead, 219 reacts with the electron-rich chiral vinyl ether 220 in the presence of the catalyst 224 to form the intermediate chiral nitronate 221. The tandem reaction proceeds from 221 with an intramolecular 1,3-dipolar cycloaddition to form 222 with 93% de. Further synthetic steps led to the formation of ( )-detoxinine 223 (333). A similar type of tandem reaction has also been applied by Chattopadhyaya and co-workers (336), using 2, 3 -dideoxy-3 -nitro-2, 3 -didehydrothymidine as the starting material (336). 

An intermolecular coupling reaction between three organonitrile molecules and a silicon-tethered diyne is reported to give good yields of pyrrolo[3,2-f]pyridine derivatives <2004JA7172>. The reaction is promoted by a low-valent zirconocene species (Equation 13). 

A highly functionalized conjugated diene has been synthesized through sequential silicon-tethered ring-closing enyne metathesis by ruthenium-carbene catalyst Ic followed by Tamao oxidation (Equation (9)). ... 

An alternative approach involves the use of a silicon atom as a removable tether. Since silicon is more versatile in further functionalization like photodesilylation and Tamao-Eleming oxidation, much effort has been directed to realize PKR of silicon-tethered substrates. However, the outcome in the beginning was far from the expected. 

J. C. Lopez, A. M. Gomez, and B. Fraser-Reid, Silicon-tethered radical cyclization and intramolecular Diels-Alder strategies are combined to provide a ready route to highly functionalized decalins, J. Chem. Soc. Chem. Comtmm. p. 762 (1993). 

Z. Xi, J. Rong, and J. Chattopadhyaya, Diastereospecific synthesis of 2 - or 3 -C-branched nucleosides through intramolecular free-radical capture by silicon-tethered acetylene, Tetrahedron 50 5255 (1994). 

Intramolecular anodic olefin coupling reactions involving allyl- (equation 18) and vinyl-silanes (equation 19) can lead to good yields of quaternary carbons with control of the relative stereochemistry19,20. This is the first example of an electrochemical reaction that makes use of a temporary silicon tether. 

A silicon-tethered [5+2] intramolecular cycloaddition of vinylsilane moiety to apyrone ring to 220 has been executed in regio- and stereoselective manners (equation 181)326. 

Silicon-tethered intramolecular carbonyl-ene reactions of vinylsilanes have been shown to generate methylene silacyclohexanols 232 stereoselectively in good yield (equation 190)340. 

In the final synthesis a silicon tethered olefin was used as a protecting group that facilitates a RCM-ROM-RCM sequence. An alternative strategy was to carry out ROM-RCM with TBS protected alcohol (Scheme 20) and subsequent CM, but this strategy was low yielding. 

Fraser-Reid s stereocontrolled synthesis of the Woodward reserpine precursor 195 relied upon a tandem 5-exol6-exo radical cyclization of pyranose-derived dienes [76-77]. As outlined in Scheme 36, a,P-unsaturated ester 188 was prepared by free radical coupling of iodide 187 with a tin acrylate. After hydrolysis of 188 (MeONa, MeOH, 100%) to give primary alcohol 189, the silicon tethered diene 190 was installed by silylation. Treatment of 190 with n-BujSnH led to the desired cage molecule 192 in high yield via a 5-exo-trig cyclization to intermediate 191 followed by a 6-exo cyclization. Tamao oxidation of tricycle 192 led to diol... 

Blakemore and Gilbert found that the SiMe2 unit induces high selectivity in the meta photocycloaddition [241], Irradiation (254 nm) of the silicon-tethered bichromophore 186 gives only one photoisomer 187 in 60% yield (Scheme 56). The ability of silicon to stabilize a (3-positive center acts to stabilize the developing positive charge in the ipso carbon hence, the photocycloaddition directs to the 2,6-position of the benzene ring rather than the 1,3-addition. 

Amey et al. proposed the Si-F interaction in the photocycloaddition of silicon-tethered bichromophore 188 by the fact that 189 was the sole product and 190 was not obtained [242,243] (Scheme 57). On the contrary, similar irradiation of siloxy derivative (191) gave only an ortho adduct (192). Moreover, removal of the trifluoromethyl substituent gave rise to the formation of the meta cycloadduct (193) as the major product [244],... 

Eq. 3.21 shows the introduction of a hydroxymethyl group at the (3-position of allylic alcohol with the silicon-tethered radical approach developed by Stork [78-83]. Allyl silyl ether (64) was first prepared by the treatment of allylic alcohol (63) with dimethylbromomethylsiliyl chloride, and subsequently treated with Bu3SnH/AIBN, and finally treated with hydrogen peroxide in the presence of KF, to give a 1,3-diol derivative (66), as shown in eq. 3.21. 

Scheme 18. Examples of silicon tethered intramolecular reactions.

Silicon tethers based on bis-alkoxysilanes (silyl ketals) are commonly prepared from the dichlorosilanes by reaction with an alcohol in the presence of base. These conditions are not compatible with some base labile compounds. To make unsymmetrical bis-alkoxysilanes requires a method for breaking the symmetry of the dichlorosilane. Without such a method, one must accept a statistically determined mixture of mono-alkoxy and bis-alkoxy products. This may be acceptable for inexpensive readily available alcohols, but it precludes the use of bis-alkoxysilane tethers for high-value synthetic intermediates. To overcome these limitations to... 

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. 

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