Keto Ethers

Reaction with alcohols is general for diazo compounds, but it is most often performed with diazomethane to produce methyl ethers or with diazo ketones to produce ot-keto ethers, since these kinds of diazo compounds are most readily available. With diazomethane the method is expensive and requires great caution. It is used chiefly to methylate alcohols and phenols that are expensive or available in small amounts, since the conditions are mild and high yields are obtained. Hydroxy compounds react better as their acidity increases ordinary alcohols do not react at... 

Certain ketoximes can be converted to nitriles by the action of proton or Lewis acids. Among these are oximes of a-diketones (illustrated above), a-keto acids, a-dialkylamino ketones, a-hydroxy ketones, p-keto ethers, and similar compounds. These are fragmentation reactions, analogous to 17-25 and 17-26. For example, ot-dialkylamino ketoximes also give amines and aldehydes or ketones besides nitriles. 

Epoxide ring-opening of functionalised norbomanes can be achieved with RuClj/aq. Na(IO )/CCl -CH3CN/60°C to give diketones or keto-ethers (Fig. 4.5)... 

Monomers 111 (a -d), were prepared from the common starting material 15 by a potassium phenate displacement of the aromatic nitro group. The yields of the keto-ether amine products ranged from 90 to 100% and were of sufficient purity after extractive work up to be utilized directly in the synthesis of the various maleimide monomers. Imidization of the aminobenzocyclobutenes was accomplished using standard reaction conditions (maleic anhydride to form the amic acid followed by cyclodehydration with acetic anhydride and triethyla-mine) and provided the maleimide products in yields ranging from 60 to 90%. 

Fig. 14. A comparison of influenza virus sialidase inhibition by C-6 diethylcarboxamide 107 with related C-6-keto, -ether, and -hydroxy derivatives 108-110.

The photoalkylation reactions of lactones, lactams and keto-ethers seem to be free radical reactions. It would be too early to draw a final conclusion about the detailed mechanism of these reactions however, the fact that they can also be induced with peroxides at elevated temperatures provides a good indication as far as the nature of these reactions is concerned. 

Substituted aliphatic and aromatic a-keto ethers (Scheme 18.5) are also amenable to enantioselective hydrogenation catalyzed by cinchona-modified Pt catalysts.25 However, as opposed to the prochiral ketones discussed earlier, kinetic resolution is observed for these chiral substrates. At conversions of 20A2%, ee s of 91-98% were obtained when starting with a racemic substrate (see Table 18.5). It is somewhat surprising that a-keto ethers without substituent in the a-position, such as methoxy acetone, reacted very slowly or not at all and led to very low enantioselectivities,6 and from the results described earlier for a-ketoacetals, the same is expected if 2 substituents are present. 

FIGURE 18.5 Reaction pathways, rates, and product isomers for the hydrogenation of cyclic a-keto ether 27b.25... 

Significant progress in the substrate scope of the Pt-cinchona systems has been made in the last 5 years. Besides a-keto acids and esters, a-keto acetals, a-keto ethers, and some trifluoromethyl ketones have been shown to give high ee s. It is now possible to classify ketones concerning their suitability as substrates for the Pt-cinchona catalyst system, as depicted in Figure 18.6. Nevertheless, for the synthetic chemist, the substrate scope is still relatively narrow, and it is not expected that new important substrate classes will be found in the near future. However, the chemoselectivity of this system has not yet been exploited to its full value, and this might be a potential for future synthetically useful applications. 

New TPI AURUM NASA Mitsui Toatsu Poly(keto-ether-imide)... 

The starting material for the present synthesis was Wieland-Miescher ketone (24), which was converted to the known alcohol (25) by the published procedure [10], Tetrahydropyranylation of alcohol (25) followed by hydroboration-oxidation afforded the alcohol (26), which on oxidation produced ketone (27). Reduction of (27) with metal hydride gave the alcohol (28) (56%). This in cyclohexane solution on irradiation with lead tetraacetate and iodine produced the cyclic ether that was oxidized to obtain the keto-ether (29). Subjection of the keto-ether (29) to three sequential reactions (formylation, Michael addition with methyl vinyl ketone and intramolecular aldol condensation) provided tricyclic ether (30) whose NMR spectrum showed it to be a mixture of C-10 epimers. The completion of the synthesis of pisiferic acid (1) did not require the separation of epimers and thus the tricyclic ether (30) was used for the next step. The conversion of (30) to tricyclic phenol (31) was... 

Unsymmetrical dialkylacetaldehydes may be obtained by starting with an a-keto ether. ... 

Acylation of aromatic ethers yields the corresponding keto ethers. Typical examples are found in the conversion of anisole with aluminum chloride and appropriate acyl halide to p-methoxybutyrophenone (85%) and p-methoxyphenyl benzyl ketone (84%). Mild catalysts like iodine and phosphorus pentoxide are also effective. 

An important method for the preparation of keto ethers is the reaction of cyano ethers with Grignard reagents. In this manner, a large number of a-alkojty aliphatic ketones have been made (30-70%). ° Likewise, phenoxymethyl alkyl ketones have been prepared (20-64%).When the Grignard reagent contains an i)-alkoxy group, 0)-alkoxy ketones are formed, ... 

The reaction has been extended to other pinacols however, their preparation may involve lengthy procedures. Certain benzoins on reduction with metals and acids yield diols which are then converted to desoxybenzoins. These conversions involve the migration of a hydrogen atom rather than an alkyl group. Similarly, aromatic keto ethers and amino ketones have been prepared. 

Ether cleavage. Treatment of the keto ether (1,9-oxatricyclo[4.3.3.0]doUecane-3-one) with acetic anhydride and pyridine hydrochloride (reflux 5,5 hr.) yields the diacetatc (2, 4-acctoxy-l-(2-acetoxyethyl)bicyclo[4,3.0]nonadiene-4,6) in 93% yield. 

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