Silyl enolates chemical oxidation

Enantioselective deprotonation can also be successfully extended to 4,4-disubstituted cyclohexanones. 4-Methyl-4-phenylcyclohexanone (3) gives, upon reaction with various chiral lithium amides in THF under internal quenching with chlorotrimethylsilane, the silyl enol ether 4 having a quaternary stereogenic carbon atom. Not surprisingly, enantioselectivities are lower than in the case of 4-tm-butylcyclohexanone. Oxidation of 4 with palladium acetate furnishes the a./i-unsaturated ketone 5 whose ee value can be determined by HPLC using the chiral column Chiralcel OJ (Diacel Chemical Industries, Ltd.)59c... 

Silyl enolates are a class of electron-rich, non aromatic compounds which can be described as masked enols or enolates since hydrolysis following their reaction yields ketones they can be purified by distillation or chromatography, and then converted back to the enolate anion. The electron-rich character of these species can be used for oxidation reactions and examples have been described in the preceding sections. In this section, additional examples of chemical, PET and electrochemical redox reactions involving silyl enolates will be discussed, for a better appreciation of these interesting species in organic synthesis. 

Chemical oxidation of silyl enolates has been performed with a variety of inorganic and organic oxidants such as ozone, copper(II) salts, Pb(OAc)4, Ag20, hypervalent iodine compounds such as iodosobenzene in methanol, (NH4)2[Ce(N03)6], xenon difluoride, tetranitromethane, halogens, nitronium-, diazonium- and triphenylmethyl salts, chloranil and ddq. 

The corresponding silyl enol ethers are likewise readily available carbonyl umpolmg substrates which can be oxidized by a variety of chemical oxidants and also by cathodic oxidation. If not trapped by nucleophiles, the radical cations can dimerize and subsequently hydrolyze to give 1,4-dicarbonyl (homo)coupling products [195]. 

The protocols for the utilization of ketone-derived silyl enol ethers in Tsuji-Trost reactions were preceded by a report of Morimoto and coworkers on the enantioselective allylation of sUyl ketene acetals 88. Without external activation, they reacted with the allylic substrate 19d in the presence of the palladium complex derived from the amidine ligand 89 to give y,5-unsaturated esters 90 in moderate chemical yield but high enantiomeric excess (Scheme 5.29) [46]. Presumably, the pivalate anion hberated during the oxidative addition functions as an activator of the silyl ketene acetal. The protocol is remarkable in view of the fact that asymmetric allylic alkylations of carboxylic esters are rare. Interestingly, the asymmetric induction originates from a ligand with an uncomplicated structure. The protocol seems however rather restricted with respect to the substitution pattern of allylic component and sUyl ketene acetal. 

Various catalytic enantioselective procedures for cx-hydroxylation of ketones rely on silicon enolates. In view of the relative nonpolar character of silyl enol ethers and silyl ketene acetals and taking into account similarities in the chemical behavior with electron-rich alkenes like enol, ethers, or enamines, it was an obvious idea trying to apply the classical protocols for olefin oxidation - like Sharpless dihydroxylation [248] and epoxidation procedures of Jacobsen [249] and Shi [250] - to silicon enolates. 

Sequential Diastereoselective Reactions of Resultant Silyl Enol Ethen. Next, our attention was focused on the sequential diai ereoselective reactions with electrophiles (Scheme 6). The oxidation reaction of the F-C product ((Z)-10b) by m-CPBA proceeded to give the 5y -diastereomer in its unprotected form in hl chemical yield and hi diastereoselectivity through die above transition state (Figure 2). These products arc of synthetic importance because of similar skeletal features to Merck L-784512 (66) with cyclooxygcnase-2 selective inhibitory activity. The protodesilylation reaction of die F-C product ((Z)-10c) by TBAF also proceeded stereoi lectively to give the a ft -diastcreomer in quantitative yield in a similar manner to that by m-CPBA oxidation. ITie diastereomeric excess of 5c was determined by HPLC analysis Daicel, CHIRALPAK AS, n-hexane i-PrOH = 95 5,0.8 ml/min, 254 nm, t = 16 min syn yj min (anti). 

The success of this transformation depends upon the oxidation potential of the ESE group (Eox 1.5 V), which is lower than that of the alkyl silyl ether group (Eax 2.5 V). Recently, Schmittel et al.35 showed (by product studies) that the enol derivatives of sterically hindered ketones (e.g., 2,2-dimesityl-1-phenyletha-none) can indeed be readily oxidized to the corresponding cation radicals, radicals and a-carbonyl cations either chemically with standard one-electron oxidants (such as tris(/>-bromophenyl)aminium hexachloroantimonate or ceric ammonium nitrate) or electrochemically (equation 10). 

Single electron oxidation of the non-activated carbonyl group, e.g. in aliphatic or aromatic aldehydes, ketones and carboxylic acid derivatives, is, on the other hand, much less feasible and only a handful of methods and synthetic applications are known. Useful methods for synthetic applications are chemical modifications to lower the oxidation potentials by peripheral donor substitution and a-silylation, or redox umpolung via oxidation of the corresponding carbonyl enols or enol ethers. 

---