Oxidations ketene silyl acetals

DDQ (2,3-dichloro-5,6-dicyano-l,4-benzoquinone) conveniently oxidizes ketene silyl acetal (15) to give a-alkoxycarbonyl iminium salt (16)63 Subsequent reaction with nucleophiles gives amino ester derivatives, Nu-CH(NBn2)-C02R. Grignards... 

Pro-chiral pyridine A-oxides have also been used as substrates in asymmetric processes. Jprgensen and co-workers explored the catalytic asymmetric Mukaiyama aldol reaction between ketene silyl acetals 61 and pyridine A-oxide carboxaldehydes 62 <06CEJ3472>. The process is catalyzed by a copper(II)-bis(oxazoline) complex 63 which gave good yields and diastereoselectivities with up to 99% enantiomeric excess. 

As demonstrated in a series of kinetic experiments by Wittkopp and Schreiner, nitrone N-benzylideneanihne N-oxide can be activated for 1,3-dipolar cycloadditions through double hydrogen-bonding 9 [Ij. Takemoto and co-workers, in 2003, published the nucleophilic addition of TMSCN and ketene silyl acetals to nitrones and aldehydes proceeding in the presence of thiourea organocatalyst 9 (Figure 6.4) [147]. 

The reaction of nitroarenes with silyl end ethers and ketene silyl acetals in MeCNATiF with 1 equiv. of TASF, followed by in situ oxidation with Br2 or DDQ, provides an easy route to a-nitroaryl carbonyl compounds (Scheme l).12 The use of these compounds as reagents for the synthesis of arylacetic acids, propionic acids, indoles, 2-indolinones and other heterocyclic compounds has recently been described.88... 

Considerable use has also been made of allyl carbonates as substrates for the allylation of Pd enolates.9 The reaction of Pd° complexes with allyl enol carbonates119,120 proceeds by initial oxidative addition into the allylic C—O bond of the carbonate followed by decarboxylation, yielding an allylpalladium enolate, which subsequently produces Pd° and the allylated ketone (equation 22). In like fashion, except now in an intermolecular sense, allyl carbonates have been found to allylate enol silyl ethers (equation 23),121 enol acetates (with MeOSnBu3 as cocatalyst) (equation 24),122 ketene silyl acetals (equation 25)123 and anions a to nitro, cyano, sulfonyl and keto groups.115,124 In these cases, the alkoxy moiety liberated from the carbonate on decarboxylation serves as the key reagent in generating the Pd enolate. 

Michael reactionsThis reagent serves as a nonacidic catalyst for Michael reactions of ketene silyl acetals with a,P-enones, and is more effective than dialkoxy-titanium oxides, (R0)2Ti=0. The reaction proceeds at -78° in various solvents, CH2C12, ether, and toluene. 

The low oxidation potentials of stannyl compounds gave us a clue to develop the selective cross-coupling reaction between the a-posi-tions of two carbonyl compounds. Generally, silyl enol ethers or ketene silyl acetals are employed for this purpose to prepare 1,4-di-... 

The carbon-carbon bond formation via photoinduced electron transfer has recently attracted considerable attention from both synthetic and mechanistic viewpoints [240-243]. In order to achieve efficient C-C bond formation via photoinduced electron transfer, the choice of an appropriate electron donor is essential. Most importantly, the donor should be sufficiently strong to attain efficient photoinduced electron transfer. Furthermore, the bond cleavage in the donor radical cation produced in the photoinduced electron transfer should occur rapidly in competition with the fast back electron transfer. Organosilanes that have been frequently used as key reagents for many synthetically important transformations [244-247] have been reported to act as good electron donors in photoinduced electron-transfer reactions [248, 249]. The one-electron oxidation potentials of ketene silyl acetals (e.g., E°o relative to the SCE = 0.90 V for Me2C=C(OMe)OSiMe3) [248] are sufficiently low to render the efficient photoinduced electron transfer to Ceo [22], which, after the addition of ketene silyl acetals, yields the fullerene with an ester functionality (Eq. 15) [250, 251]. 

The 2,5-dihydro-l,2,3-triazines 20, obtained by reaction of 1,2,3-triazines 19 with ketene silyl acetals or silyl enol ethers in the presence of 1-chloroethyl chloroformate, can be readily oxidized and hydrolyzed with ammonium cerium(lV) nitrate (CAN) in acetonitrile/water to afford 5-substituted 1,2,3-triazines 21.3 64... 

Kobayashi s group37 developed a new enantioselective synthesis of Cis phytosphingosine using catalytic asymmetric aldol reactions as a key step (Scheme 23). The key catalytic aldol reaction of acrolein with the ketene silyl acetal 148 derived from phenyl a-benzyloxyacetate was carried out by using tin(II) triflate, chiral diamine 149, and tin(II) oxide. The desired aldol product... 

L-Daunosamine (166) (R=H), (3-amino-2,3,6-trideoxy-L-/yxo-hexose), is an essential component of both natural and unnatural anthracycline antitumor agents. The 1,3-addition of ketene silyl acetal 164 to the chiral nitrone (Z)-[(4i )- ra 5-2,2,5-trimethyl-l,3-dioxolan-4-yl]methylene[(l S)-l-phenylethyl] amine 7V-oxide (163), prepared by the conversion of 141 to 103 [62] and then reaction of 103 with the hydroxylamine 162, provides the 0-silylated addition product 165 in quantitative yield with an anti relative stereochemistry at C-3 and C-4 (anti syn =>100 1). Efficient transformation of 165 to 166 (R=COPh) is achieved in three steps [63] (Scheme 39). 

The r-nucleophilicity and electron-transfer oxidation of silyl enol ethers and ketene silyl acetals has been studied by DFT, focusing on local softness and local nucle-ophilicity index as parameters for intramolecular reactivity and the corresponding group parameters for intermolecular reactivity. ... 

Oxidation of Ketene Silyl Acetals. Singlet oxygen oxidizes KSAs resulting in a cleavage of C-C bonds (eq 16),4 the reaction presumably proceeding through a silyl peroxide intermediate. Lead(IV) acetate and m-chloroperbenzoic acid" oxidize KSAs to or-acetoxy (or hydroxy) carboxylic acid derivatives. Oxidative dimerization of ketene silyl acetals by TiCU (eq 17) can be understood in terms of single-electron transfer to the Lewis acids.4 ... 

Silyl enol ethers and ketene silyl acetals add to aromatic nitro compounds in the presence of TASF(Me) to give intermediate dihydro aromatic nitronates which can be oxidized with bromine or 2,3-dichloro-5,6-dicyano-l,4-benzoquinone to give a-nitroaryl carbonyl compounds the latter are precursors for indoles and oxindoles. The reaction is widely applicable to alkyl-, halo-, and alkoxy-substituted aromatic nitro confounds, including heterocyclic and polynuclear derivatives (eq 7). 

In 2006, catalytic enantioselective Michael addition of ketene silyl acetals to cyclic and acyclic a, P-enones was devised using the chiral BLA (3a) (Scheme 1.6) [8]. Various Michael donors and ketene silyl acetals can be employed for this process. Here again, the use of triphenylphosphine oxide is crucial to trap any catalytically active silyl cation species. In addition, the combined use of triphenylphosphine oxide and a stoichiometric amount of 2,6-diisopropylphenol (which acts as a scavenger of silyl cation species) is sometimes required to get both high enantioselectivity and the chemical yield. This enantioselective methodology was applied to the asymmetric synthesis of a key intermediate of caryophyllene. 

As for the C-C bond formation with fullerene, the pho-toinduced electron transfer with ketene silyl acetal (KSA) was reported. For example, KSA derived from ethyl acetates generated fullerene-acetates quantitatively upon photoirradiation in benzene (Scheme 4) [66]. Their reactivities to form Cgg-adducts are studied on the basis of the oxidation potentials of the KSA, indicating adduct formation via electron transfer with triplet excited Cgg. Furthermore, Danishefsky s diene, which is a vinylogue of KSA, formed [4 -I- 2] cycloadducts of Qg by the Diels-Alder reaction (Scheme 5)... 

Fukuzumi, S., Fujita, M., Otera, J., and Fujita, Y, Electron-transfer oxidation of ketene silyl acetals and other organosilanes. The mechanistic insight into Lewis acid mediated electron transfer, /. Am. Chem. Soc., 114, 10271, 1992. 

In the synthesis of D-eryt/zro-sphingosine (78 without BOC protection), the key step is the asymmetric aldol reaction of trimethylsilylpropynal 75 with ke-tene silyl acetal 76 derived from a-benzyloxy acetate. The reaction was carried out with 20 mol% of tin(II) triflate chiral diamine and tin(II) oxide. Slow addition of substrates to the catalyst in propionitrile furnishes the desired aldol adduct 77 with high diastereo- and enantioselectivity (syn/anti = 97 3, 91% ee for syn). In the synthesis of protected phytosphingosine (80, OH and NH2 protected as OAc and NHAc, respectively), the asymmetric aldol reaction is again employed as the key step. As depicted in Scheme 3-27, the reaction between acrolein and ketene silyl aectal 76 proceeds smoothly, affording the desired product 80 with 96% diastereoselectivity [syn/anti = 98 2) and 96% ee for syn (Scheme 3-27).50... 

One report has indicated the potential of this mild reagent for a-oxidation of silyl ketene acetals. Once again the usefulness is restricted by competition between the required silatropic ene process and the prototropic ene reaction giving rise to the enoate. For substrates lacking p-protons the a-hydroperoxy ester is readily obtained in good yield. In one case where -protons were present (methyl group) an 80% yield of the silatropic product was obtained by carefully optimizing the reaction conditions. This may not however always be possible. 

Indirect replacement of the a-hydrogen atom of carboxylic esters by the nitroso group is remarkable. This procedure uses ketene 0-alkyl O -silyl acetals (1), generated from carboxylic esters, which are treated with nitric oxide or isopentyl nitrite in the presence of titanium(IV) chloride. In the absence of an a-hydrogen a-nitroso esters (2) are obtained. a-Nitroso esters with an a-hydrogen undergo isomerization to oximes of a-keto esters (3 equation 1). Similarly, silyl enol ethers of aldehydes or ketones can be used instead of the carbonyl compound itself for nitrosation. Thus, treatment of enol ether (4) with nitro-syl chloride gives the a-nitroso aldehyde (5 equation 2), which is quite stable at 0 C, but dimerizes at room temperature. 

Adam, W., Fell, R. T., Stegmann, V. R., Saha-Moeller, C. R. Synthesis of Opticaiiy Active a-Hydroxy Carbonyl Compounds by the Catalytic, Enantioselective Oxidation of Silyl Enol Ethers and Ketene Acetals with (Salen)manganese(lll) Complexes. J. Am. Chem. Soc. 1998,120, 708-714. 

Enol ethers are interesting substrates for epoxidations since a-hydroxy ketones or the corresponding acetals are isolated, depending on the choice of solvent. Kat-suki has used enol ethers as substrates, including the cyclic enol ether (4.67), which affords the hydroxy acetal product (4.68). ° Adam has used silyl enol ethers and silyl ketene acetals as substrates. A typical example is provided by the asymmetric oxidation of silyl enol ether (4.69), generating the oi-hydroxy ketone (4.70) after a suitable work up. ... 

Silyl enol ethers as electron-rich olefins are susceptible to one-electron oxidation by metallic oxidants [121-123]. The chemoselectivity in the oxidative transformations is controlled by the redox potentials of the reactants. VO(OEt)Cl2 induces chemose-lective homo- or cross-coupling of silyl enol ethers as shown in Scheme 2.58 to give the 1,4-diketones via regioselective carbon-carbon bond formation [124]. The more highly substituted the silyl enol ethers 68 are, the more readily they are oxidized. The silyl ketene acetals 73 are also readily oxidized and undergo cross-coupling with silyl enol ethers 69 to give the y-keto esters 74 (Scheme 2.59). 

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