A-Diketones monoketals

A general method for the preparation of a-cyclopropylidene-aldehydes and -ketones (26) involves reaction of cyclopropylidenetriphenylphosphorane with the requisite a-keto-aldehyde or a-diketone monoketal followed by deketalization. ... 

Aroxyacoxy compds. Bis(hemiacetals), cyclic 1-Carbalkoxyoxonium salts Diacetals, cyclic a-Diketone monoketals Enolperoxides a-Hydroxyacetals... 

Aroxyacoxy compds. a-Diketone monoketals Enolperoxides Glycidic acid esters a-Hydroxyacetals 1-Hydroxylactones a-Ketoacetals a-Keto-Y-lactones Lactolesters... 

Mono ethylene ketals of a-diketones. Yields are generally low for monoketal-ization of a-diketones. A recent expedient is outlined in equation (1). ... 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

The monoketal of some diketones is formed in reasonable yield by the statistical method. Thus (3) gives a reasonable yield of (4) after separation from (3) and the bis-ketal, 64% of (4) can be isolated. ... 

However, it does not follow that in any individual case, the same applies. The monoketal (6) of the cyclic diketone (5) is much in demand as a synthetic intermediate and in conformational studies. Mono ketalisation is unsatisfactory here - very little of (6) can be isolated. This may be simply because the right conditions have not yet been found. Various solutions to this problem have been published I shall describe two, both based on the statistical method. 

The approach to 731 developed by Dauben and Walker, outlined in Scheme LXXXII, begins with the Weiss-Cook condensation of 743 and proceeds after hydrolysis and monoketalization to furnish keto acid 744. Wolff-Kishner reduction, cycliza-tion, and methylation of this intermediate provided diketone 745 which was transformed by standard means to 746, a molecule which had previously been carried on to 731 (Scheme LXXX). 

The principle of condensation with diketones has further been extended by using 1,3-diketones to form 2,4-disubstituted quinolizines.14 In general the reaction involves the condensation of 2-picolyllithium with the enol ether or the monoketal of a /3-dicarbonyl compound followed by cyclodehydration of the resulting carbinol by means of acid. This scheme is illustrated in Eq. (5). 

If the moeity adding to the aryne carries a suitably placed electrophilic center, cyclization with the initially formed anion can occur as observed in the synthesis of dibenzothiophene (60).92 Of wider synthetic import in this context is enolate addition to arynes. Here, after the initial ring closure many types of products can be formed (Scheme ll).35 However, with some substrates, a particular reaction course can predominate 93 94 for example, reaction of cyclodecanone with bromobenzene provides an efficient method for benzo-annulation and ring expansion. Similarly, high yields of benzocyclobutenols can be obtained from the monoketals of ot-diketones.9s... 

In certain cases, the selective protection of the closely similar sites offers an opportunity to achieve a reversal in selectivity from a common precursor. Thus, the monoketal derivative 228 (Scheme 2.94) can easily be prepared from the respective diketone owing to the steric shielding of the C-17 carbonyl. The opportunity, now, to reduce the non-protected carbonyl in 228 to form alcohol 229 should not be a surprise. However, it is truly remarkable that a selective reduction can also be achieved at the C-3 protected carbonyl. This paradoxical result is due to the utilization of the reagent H2Sil2, which selectively attacks the ketal moiety and induces its removal coupled with a reduction to form the iodo derivative 230. A successful and nearly quantitative reductive conversion at either C-17 or at C-3 is achieved in this manner. In this example, the protected carbonyl functionality served as a non-conventional functional group with a pattern of reactivity sharply differing from that of the unprotected group,... 

Kuhn found that carbohydrates can be completely methylated in a single step by silver oxide and methyl iodide if dimethylformamide is used as solvent. The carbohydrate is dissolved in 10-25 times its weight of DMF and treated at room temperature with methyl iodide (3 equiv. per OH group) and silver oxide (2 equiv. per OH group). Barium oxide can also be used." 1,2-Diketones are converted by this procedure into monoketals. Thus benzil is converted into (1), phenanthrenequinone into (2), and ninhydrin into (3). ... 

Various approaches to the assembly of the 1,3-dienes that engage in the Diels-Alder cycloaddition reactions leading to substrates for DPM and ODPM processes have been reported. Thus, for example. Yen and Liao demonstrated, during the course of a total synthesis of the Lycopodium alkaloid magellanine, that oxidation of acetovanillone (109) rScheme 9.151 with diacetoxyiodobenzene (DAIB) in the presence of methanol afforded the o-benzoquinone monoketal 110. The latter conpound engaged in an in situ Diels-Alder reaction with added cyclopentadiene (111) and the resulting adduct 112 proved to be an excellent substrate for the ODPM rearrangement reaction. Thus, photolysis of 112 as a solution in acetone afforded the pivotal tetracyclic diketone 113 in 92% yield. 

The selective ketalization of a typical Of-diketone, cyclohexane-1,2-dione, has been studied in some detail [259, 260]. It appeared that the monoketal, once formed, ketalizes more rapidly than the enolic starting material, thus accounting for the low yield of the mono-dioxolan (15-18%). The mono-oxathiolan and -dithiolan were formed in somewhat h her yield. Various nucleophilic reactions could be performed on the ee ketone function in these compounds. 

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