A Alkoxyketones

Buu-Hoi has shown that n-alkyl methyl ketones excluding ethyl methyl ketone, yield primarily 2-monosubstituted cinchoninic acids. It has been demonstrated that the products of the condensation of isatin with aryloxyketones are the corresponding 3-aryloxy-4-quinoline carboxylic acids rather than the isomeric 2-aryloxymethylcinchoninic acids.In the case of simple a-alkoxyketones such as 1-alkoxyethyl methylketones, the preferred products are the 2-alkoxyalkylcinchoninic... 

For ketones and aldehydes in which adjacent substituents permit the possibility of chelation with a metal ion, the stereochemistry can often be interpreted in terms of the steric requirements of the chelated TS. In the case of a-alkoxyketones, for example, an assumption that both the alkoxy and carbonyl oxygens are coordinated with the metal ion and that addition occurs from the less hindered face of this chelate correctly predicts the stereochemistry of addition. The predicted product dominates by as much as 100 1 for several Grignard reagents.120 Further supporting the importance of chelation is the correlation between rate and stereoselectivity. Groups that facilitate chelation cause an increase in both rate and stereoselectivity.121 This indicates that chelation not only favors a specific TS geometry, but also lowers the reaction barrier by favoring metal ion complexation. 

Synthesis of a-alkoxyketones from a-diazocarbonyl compounds and alcohols under the influence of copper or rhodium catalysts is well established as an alternative to the Lewis or proton acid catalyzed variant of this synthetic transformation. The sole recent contribution to the aspect of general reactivity deals with the competition between O/H insertion and cyclopropanation of unsaturated alcohols 162). The results... 

The PhSiH3/Mn(dpm)3 combination nicely reduces the conjugated C=C bond in a polyfunctional ketone without affecting the trityl group or causing reaction at the a-alkoxyketone function (Eq. 273).448... 

Trost and coworkers employed a magnesate reagent in the formal synthesis of fostriecin (Scheme 18). Stereoselective addition of the corresponding alkenylmagnesium to a-alkoxyketone proceeded smoothly in 75% yield with more than 20 1 diastereoselectivity. 

Synthetic Utility. One goal of this research was to investigate new synthetic uses of organomercurials. Although the synthetic utility of this reaction has not been extensively investigated, products such as that from Reaction 16 in Table I do suggest a possible utility to organic chemists. Thus, the preparation of a-alkoxyketones should be possible by consecutive alkoxymercuration and ozonation reactions. 

Dihydrofurans. Alkylidenecarbene formation from a-alkoxyketones is followed by C-H bond insertion. 2,8-Dioxabicyclo[3.2.1]oct-6-enes can be made this way, although such compounds are unstable. 

Eliel and coworkers [94] have shown that the occurrence of chelation-control provides a corresponding rate increase in the reactions of a-alkoxyketones with Me2Mg (Figure L24). To observe chelation control and the attendant rate enhancement, the solvent should be a poor Lewis base in order not to compete with the ether substituent The ether R" substituent must not be too bulky methyl or benzyl ethers are highly reactive and selective, while trimethylsilyl ethers are less useful. Triisopropylsilyl ethers react non stereoselectively and at the lowest rate (Figure L25). 

One further insight into the coordination chemistry of these lithium enolates is obtained from the stereoselectivity observed in the reactions of chiral a-alkoxyketone enolates. For example, the... 

Reaction with carbonyl electrophiles is possible, so enantiopure stannanes are excellent precursors of enantiopure a-alkoxy tertiary alcohols [165,167], a-alkoxy acids and esters [180], and a-alkoxyketones [181], and y-alkoxyhydrazides (precur-... 

For example, a-hydroxy and a-alkoxyketones are reduced to anti 1,2-diols by Zn(6114)2 chelated TSs. This stereoselectivity is consistent with the preference for... 

Reductions. The reduction of a-alkoxyketones with Sml2 in the presence of fluorous BINOL (chiral) derivative shows that the protonation step is enantioselective. The use of fluorous tin hydrides that are highly soluble in fluorinated solvents facilitates dehalogenation. ... 

Reduction of carbonyl groups. Aldehydes and ketones are subjected to enantioselective reduction. Hydrogenation of benzaldehyde-a-d, a-alkoxyketones " or )3-ketoesters can be accomplished using either the Ru dihalide complexes or some modified forms. a-Ketoesters are also similarly reduced. 

OH and SH insertions are also known. They are used for the synthesis of a-alkoxyketones by reaction of a-diazocarbonyl compounds with alcohols, and for the synthesis of a-phenylthioketones, using thiophenol (see review of Maas, 1987, p. 204). 

Markownikoff addition. 2-Methylpent-l-ene allowed to react with tertAmiyl hydroperoxide and mercuric acetate with initial cooling and shaking, after 2 hrs. the volatiles removed by distillation in vacuo, and the residue digested repeatedly with coned, aq. NaCl -> l-diloromercuri-2-tert-butylperoxy-2-methylpentane. Y 19%. F. e., also hydroperoxymercuration with H2 2 s. E. Schmitz, A. Riedie, and O. Brede, J. pr. 312, 30 (1970) a-alkoxyketones from enolesters s. ibid. 312, 43 peroxy- and methoxy-mercuration of a,i -unsatd. ketones and esters s. A. J. Bloodworth and R. J. Bunce, Soc. (C) 1971, 1453. 

Scheme 4.3 L-Pioline aldol reaction between a-alkoxyketones and aldehydes...

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