Nitrones reaction with silyl ketene acetals

Theoretical calculations at DFT level agree that the reactions of nitrones with silyl ketene acetal proceeds via 1,3-dipolar cycloaddition followed by the transfer of the silyl group, yielding an open-chain product (641). 

However, C,C-coupling reactions of sterically less hindered alkyl nitronates derived from secondary AN with silyl ketene acetal were successfully performed (Eq. 3). These reactions produced the target mixed nitroso acetals in moderate yields. 

It should be noted that specially purified individual stereoisomers of six-membered cyclic nitronates were used in coupling with silyl ketene acetal. Hence, the mechanistic model of the C,C-coupling reaction can be discussed on the basis of the configurations of the stereocenters of the starting nitronates of intermediate cations (357) (see Section 3.5.2.1), and the resulting tetrahydro-oxazines (358) (for more details, see below). It should be noted that most of C,C-coupling reactions of six-membered cyclic nitronates with silyl ketene acetal are characterized by a very high diastereoselectivity. 

The matched double stereoselective reaction between the chiral C-phenyl A -( 1-phenylethyl) nitrone and the chiral silyl ketene acetals 558 in acetonitrile/dichloromethane at 20 °C under zinc iodide-catalyzed conditions resulted in only the single diastereomer 559 in 98% yield. Exposure of 559 to acid afforded the isoxazolidinone 560 in 74% yield, together with the chiral auxiliary (li ,2 S )-2-phenylcyclohexanol (Scheme 135) <1997JOC6672>. 

The TiCU-mediated reaction of enol silanes with imines was first introduced by Ojima and coworkers in 1977. The reaction was then extended to several similar substrates, i.e. nitrones, ot-methoxycarba-mates, aminals, 4-acetoxyazetidin-2-one, 40 anj to different Lewis acids, i.e. SnCU, TiCU-(0PH)2, catalytic ZnX2, catalytic TMSOTf, ° to give good yields of the addition products with low levels ( 80 20) or a complete lack of simple stereoselection. Moderate to good anti selectivities were reported in the addition of silyl ketene acetals to imines under particular reaction conditions (equation 9) significant results are summarized in Table 4. 

The use of oxygen-containing dienophiles such as enol ethers, silyl enol ethers, or ketene acetals has received considerable attention. Yoshikoshi and coworkers have developed the simple addition of silyl enol ethers to nitroalkenes. Many Lewis acids are effective in promoting the reaction, and the products are converted into 1,4-dicarbonyl compounds after hydrolysis of the adducts (see Section 4.1.3 Michael addition).156 The trimethylsilyl enol ether of cyclohexanone reacts with nitrostyrenes in the presence of titanium dichloride diisopropoxide [Ti(Oi-Pr)2Cl2], as shown in Eq. 8.99.157 Endo approach (with respect to the carbocyclic ring) is favored in the presence of Ti(Oi-Pr)2Cl2. Titanium tetrachloride affords the nitronates nonselectively. 

Addition of Ketene Acetals and Enoles In recent years, much attention has been given to the synthesis of optically active nitrogen-containing compounds, with the key step being the highly stereoselective nucleophilic addition of ketene silyl acetals to nitrones (Scheme 2.174). Similar to nitrone cyanations, in ketene silyl acetal reactions one observes an accelerating effect with thiourea derivatives (633). 

The reactions of nitroalkenes (42) with various enols (43b) (vinyl ethers, silyl, and acyl enolates, ketene acetals) have been studied in most detail (110, 111, 125—154). As a mle, these reactions proceed smoothly to give the corresponding nitronates (35f) in yields from high to moderate. As in the reactions with enamines, the formation of compounds (44b) is attributed to the ambident character of the anionic centers in zwitterionic intermediates analogous to those shown in Scheme 3.43. 

Conjugate addition of allylsilanes to enones results in regiospe-cific introduction of the allyl group (eq 34). The reaction can be intramolecular (eq 35). TiCU or SnCU activates nitro alkenes for Michael addition with silyl enol ethers or ketene silyl acetals. The silyl nitronate product is hydrolyzed to a 1,4-diketone or -y-keto ester (eq 36). ... 

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). 

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). 

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