Silaketal

A regio- and stereospecific INOC reaction of unsymmetrical silaketals 114, synthesized in one pot from unsaturated alcohols, nitro ethanol, and dichloro-silanes, via the nitrile oxide 115 to isoxazolines 116 has been described (Scheme 14) [37a]. The intermolecular version of the cycloaddition, under similar conditions, proceeds with poor regio and stereoselectivity. 

A high level of diastereoselectivity was reported despite the length of the tether in the INOC reaction of silaketals (e.g., 118) possessing an allylic substituent (Eq. 12) [37b]. 

The total syntheses of the potent glycosidase inhibitors (+)-castanospermine, (+)-6-epicas-tanosperimine, (+)-australine, and (+)-3-epiaustraline have been reported. These four natural products are derived from a single common intermediate, the nitroso acetal (as shown in Scheme 8.43), which is created in the key step by the asymmetric tandem [4+2]/[3+2] cycloaddition between silaketal nitroolefin and chiral vinyl ether.182 The strategy of the synthesis is outlined in Scheme 8.43. Scheme 8.44 presents a total synthesis of (+)-castanosperimine and (+)-6-epi-castanosperimine from the common intermediate prepared by tandem [4+2]/[3+2] cycloaddition. 

This strategy was later refined by Stork and co-workers142 who used silicon (e.g. 164) as the tethering atom [Scheme 55a)]. The latter strategy was adapted by Sinay and co-workers143 for the synthesis of C-disaccharides (e.g. 169) by employing 8- and 9-endo radical cyclizations with the readily prepared silaketal connectors [Scheme 55b)]. 

Table 3 shows the application of these intramolecular biaryl-forming conditions to the indirect synthesis of acyclic biaryls using a temporary tether strategy (Scheme 9). Silaketal tethers (Y = SiR2 and X = O, 31a-f) react efficiently to give the biaryl unit. A sulfide derivative (Y — S, X = CH2, 31g) led to many oxidized products, but sulfoxides (Y = SO,... 

Silaketals constitute another group of convenient starting materials for silicon-tethered syntheses involving RCM [134-136]. The example in Eq. (81) [134] illustrates the synthetic potential of the reaction. For more examples see Ref. [136],... 

Unsymmetrical silaketals 201 having a 1,2-disubstituted double bond and a nitro group were prepared and transformed upon treatment with phenyl isocyanate in the presence of Et3N under mild reaction conditions into 2-oxazoline derivatives 202 by a regiospecific intramolecular 1,3-dipolar cycloaddition, as shown in Scheme 36 <1997SL1208>. The /ra r-stereochemistry of the alkene 201 was transported to the 2-isoxazoline product 202, which was confirmed by the H NMR spectroscopic data. 

Diphenyl silaketals 196 can be readily converted to the ( -symmetrical 1,4-diol 293 by reduction with Raney-Ni, followed by desilylation with TBAF in 65% yield. Another potentially powerful application of cyclic alkoxysilanes 196 consists in dihydroxylation with catalytic amount of osmium tetraoxide in the presence of A-methylmorpholine A-oxide (NMO), followed by treatment with TBAF which gives D-altriol 294 (Scheme 51) <1998JOC6768>. 

Xin, Y C, MaUet, J M, Sinay, P, An expeditious s3mthesis of a C-disaccharide using a temporary silaketal connection, J. Chem. Soc., Chem. Commun., 864-865, 1993. 

Fairbanks, A J, Perrin, E, Sinay, P, Synthesis of the carbon skeleton of the herbicidins via a temporary silaketal tether, Synlett, 679-681, 1996. 

ZnBr2-catalyzed IMDA cycloaddition of the 2-pyrone 152 (Scheme 37), tethered with a chiral enol silaketal, provided (+)-153-exo in 74% yield, along with a small amount of (-)- 5 i-endo <95JOC1617>. In this case, the -geometry of the dienophile was not preserved during the cycloaddition, as in the cycloaddition of 3,5-dibromo-2-pyrone with dimethyl maleate (cf. entry 9, Table 2), implying a stepwise reaetion mechanism. The isolated exo product (+)-153 was used as the key intermediate for the asymmetric total synthesis of a 2-alkyl-vitamin D3 analog. 

Scheme 13. Synthesis of methyl a-C-maltoside 76 via temporary silaketal tethering...

Breau and co-workers reported diastereoselective INOC and ISOC reactions of silaketals 205 derived from allyUc alcohols and nitroethanols for the synthesis of 3,4,5-trisubstituted 2-isoxazolines 206 (Scheme 50) [152,153]. 

All glassware must be dried in an oven prior to use, since the reaction must be performed under anhydrous conditions, in an inert atmosphere. Safety glasses should be worn during the experiment, and aU manipulations should be performed in a fume cupboard. For a typical reaction, transfer the silaketal (70) (0.68 mmol) to a two-necked flask equipped with a reflux condensor. Establish inert conditions and add anhydrous toluene (34 ml). Degass the solution three times to ensure dry and oxygen free conditions. Heat the solution to reflux. Prepare a solution of BuaSnH (403 jl1, 1.5 mmol) and AIBN (11.2 mg) in anhydrous toluene (34 ml) and again... 

Domino metathesis of siloxy-tethered dienynes offers attractive opportunities for the synthesis of stereochemically defined 1,3-dienes after desilylation [21]. These reactions also allow the efficient preparation of highly substituted cycloolefins, which is illustrated in Scheme 2.43 [21b,c]. Selective double cydization of silaketal 118 via initiation at the monosubstituted alkene led to a fused 6/7-bicychc product which was subsequently desilylated to afford the triol 119 in high overall yield. 

The formation of a glycosidic bond between two sugar moieties temporarily tethered by a silaketal linkage is covered in Chapter 3. 

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