Silyl reaction with oxygen

As inert as the C-25 lactone carbonyl has been during the course of this synthesis, it can serve the role of electrophile in a reaction with a nucleophile. For example, addition of benzyloxymethyl-lithium29 to a cold (-78 °C) solution of 41 in THF, followed by treatment of the intermediate hemiketal with methyl orthoformate under acidic conditions, provides intermediate 42 in 80% overall yield. Reduction of the carbon-bromine bond in 42 with concomitant -elimination of the C-9 ether oxygen is achieved with Zn-Cu couple and sodium iodide at 60 °C in DMF. Under these reaction conditions, it is conceivable that the bromine substituent in 42 is replaced by iodine, after which event reductive elimination occurs. Silylation of the newly formed tertiary hydroxyl group at C-12 with triethylsilyl perchlorate, followed by oxidative cleavage of the olefin with ozone, results in the formation of key intermediate 3 in 85 % yield from 42. 

Ketones and carboxylic esters can be a hydroxylated by treatment of their enolate forms (prepared by adding the ketone or ester to LDA) with a molybdenum peroxide reagent (MoOs-pyridine-HMPA) in THF-hexane at -70°C. The enolate forms of amides and estersand the enamine derivatives of ketones can similarly be converted to their a hydroxy derivatives by reaction with molecular oxygen. The M0O5 method can also be applied to certain nitriles. Ketones have also been Qc hydroxylated by treating the corresponding silyl enol ethers with /n-chloroperoxy-... 

As with other reactions, silyl esters of phosphorus acids constitute an important and useful category of reagents for conjugate addition reactions. With aldehydes, ketones, and esters, the silyl ester linkage is transferred to the carbonyl oxygen, facilitating the completion of the reaction, generating the free carbonyl or ester upon workup with a protic solvent (Equation 3.25). 

Pyrrolo[l,2-c][l,3]oxazin-l-one 248 has been obtained by reaction of allylsilanes with a pyrrolidine-lV-acyliminium ion 247 (Scheme 32), formed by addition of a Lewis acid on compound 244. The /3-silyl carbocation formed by the reaction with allylsilane 246 reacted with the oxygen of the N-15OC group followed by the loss of 2-methylpropene. The reaction was not very stereoselective when trimethylsilane was used, whereas with larger group on the silicon the selectivity was increased <1997J(P1)2163>. 

The addition of carbonyl compounds towards lithiated 1-siloxy-substituted allenes does not proceed in the manner described above for alkoxyallenes. Tius and co-work-ers found that treatment of 1-siloxy-substituted allene 67 with tert-butyllithium and subsequent addition of aldehydes or ketones led to the formation of ,/i-unsaturated acyl silanes 70 (Scheme 8.19) [66]. This simple and convenient method starts with the usual lithiation of allene 67 at C-l but is followed by a migration of the silyl group from oxygen to C-l, thus forming the lithium enolate 69, which finally adds to the carbonyl species. Transmetalation of the lithiated intermediate 69 to the corresponding zinc enolate provided better access to acylsilanes derived from enolizable aldehydes. For reactions of 69 with ketones, transmetalation to a magnesium species seems to afford optimal results. 

The reaction of acylsilanes with acid chlorides in the presence of A1C13 leads to furans (Table 9.41) [45]. In these reactions an acyl cation initiates the addition with ensuing silyl migration yielding an intermediate vinyl cation. Attack of the carbonyl oxygen followed by proton loss affords the observed products (Scheme 9.16). An analogous reaction with nitrosyl fluoroborate provides a route to oxazoles (Table 9.42) [65]. The nitrosyl cation serves as the electrophile in this application. 

From singlet oxygen reaction with silyl enol ethers. 779... 

From singlet oxygen reaction with silyl enol ethers When a carbon tetrachloride solution of 1-methoxy-l-trimethylsiloxy-l-alkene in the presence of tetraphenylporphyrin and bubbling oxygen is irradiated with a 400-W Na lamp, a-trimethylsilyl peroxyesters were obtained in good yield (equation 11) . ... 

The isolation of the sily lacetal ketene is required when the reaction is catalyzed by a chiral Lewis acid. However, due to its instability, isolation yields of the compounds are very low. Reaction of difluoroketene silylacetal with electrophiles affords adducts with excellent ee (Figure 2.28). ° The instability of these difluoroketene silylacetals is due to the facile migration of the silyl group from oxygen to carbon, affording... 

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