Silicon-tethered synthesis

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

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

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). 

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

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). 

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... 

We sought catalytic methods that would allow formation of chiral tethers that are asymmetric at the silicon center. Synthesis of the chiral tether by our method would be advantageous for the reasons we described in the Introduction. Chiral information could be transferred during an intramolecular reaction. This would be an example of substrate-controlled transformation. 

In combination with the range of standard transformations of alcohols, alkenes, and vinylsulfides, these silicon-tethered additions of functionalized radicals offer a versatile and stereoselective approach to amino alcohol synthesis. Whereas vinyl and 2-oxoethyl radicals have not yet been demonstrated as competent participants in the various intermolecular additions reported in the literature, the temporary tether approach allows such functionalized fragments to be installed in an efficient and stereoselective manner. Synthesis of the aminosugar daunosamine from achiral precursors shows how this concept, employing hydrazone radical acceptors, can be merged with asymmetric catalysis to achieve practical synthetic advances. 

Regioselective synthesis of unsymmetrical C-aryl glycosides using silicon tethers, as disposable linkers, has been developed (Scheme 55). Deprotonation of 304 with Bu Li led to the formation of an intermediate benzyne 305 that underwent cycloaddition to deliver 306. When 306 was treated with TBAF in DMF at 70°C, the tether was cleaved and 307 was obtained in 80% yield. The acid-catalyzed opening of the oxabicycloheptadiene ring afforded the glycosyl naphthols 308 in quantitative yield <2003JA12994>. 

A diastereoselective formal addition of a 7ra i-2-(phenylthio)vmyl moiety to a-hydroxyhydrazones through a radical pathway is shown in Scheme 2.29. To overcome the lack of a viable intermolecular vinyl radical addition to C=N double bonds, not to mention a reaction proceeding with stereocontrol, this procedure employs a temporary silicon tether, which is used to hold the alkyne unit in place so that the vinyl radical addition could proceed intramolecularly. Thus, intermolecular addition of PhS" to the alkyne moiety in the chiral alkyne 161 leads to vinyl radical 163, which cyclizes in a 5-exo fashion, according to the Beckwith-Houk predictions, to give aminyl radical 164 with an a 7z-arrangement between the ether and the amino group. Radical reduction and removal of the silicon tether without prior isolation of the end product of the radical cyclization cascade, 165, yields the a-amino alcohol 162. This strategy, which could also be applied to the diastereoselective synthesis of polyhydroxylated amines (not shown), can be considered as synthetic equivalent of an acetaldehyde Mannich reaction with acyclic stereocontrol. 

Our strategy for the Smij-promoted synthesis of l,2-cis-C-glycosides is illustrated in Figure 3. It was assumed that one-electron transfer to the LUMO of the aryl sulfone group in A would result in concomitant cleavage of the C1 -S bond liberating an anomeric radical intermediate, as previously observed in the reductive lithiation of glycosyl phenyl sulfones." If 5-exo cyclization onto the silicon-tethered alkene/alkyne is substantially favored over a second electron transfer from Smij, then the exocyclic carbon radical B would ultimately be formed. On the other hand, reduction of the Cl-radical by... 

Bols, M, Synthesis of koiitriose using silicon-tethered glycosidation, Acta Chem. Scand, 50, 931-937, 1996. 

In a different version of the same concept. Stork [67,68] and Bols [69-72] introduced silylene type tethering with glycosyl sulfoxide [67,68] or thioglycoside [69-72] donors. The silicon-tethered acceptor approach was also extended to the synthesis of a-D-gluco- [70,72] and a-D-galactopyranosyl linkages in oligosaccharides [70,72]. 

An efficient synthesis of adenophostin (55a) analogues (55b-f) from d-xylose has been reported." The C-glycosidic analogue of adenophostin A and its uracil congener (56a,b) have also been prepared via a temporary silicon-tethered radical coupling reaction as the key step. ... 

A highly general procedure relies on the use of a silicon tethered radical cyclization process to provide for introduction of a hydroxymethyl substituent using the Tamao conditions.33 38 Pioneered by Nishiyama39 the synthesis of regioisomeric diols, as in 33, from readily available ally silyl ethers, such as 31, was achieved via radical cyclization and oxidization. The predominance of the 5-exo cyclization is further demonstrated by the formation of 36 by this same process. 

Denmark and Cottell combined a novel silicon-tethered cycloaddition with a later oxidation for the synthesis of (+)-l-epiaustraline.42 Treatment of the nitroalkene with MAPh,... 

Scheme 12. Stereospecific synthesis of C-styryl glycosides using temporary silicon tethering...

Tebbe olefination, 441 Tebbe olefinations, 368 Tebbe s reagent, 457 Tedania ignis, 246 Tedanolide, 246 tedanolide, 256 TEMPO, 250, 301 temporary silicon tether, 103 Tennant quinoline synthesis, 7 tetra-n-butylammonium fluoride (TBAF), 214 2-(7-aza-1 H-benzotriazole-1 -yl)-1,1,3, 3-tetramethyluronium hexafluorophosphate (HATU), 25... 

Scheme 10-47 Crimmins and O Mahony used a silicon-tethered radical cyclization in a synthesis of talaromycin A.

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