Acyclic 1,4-dicarbonyl compounds

In the Diels-Alder reaction with inverse electron demand, the overlap of the LUMO of the 1-oxa-l,3-butadiene with the HOMO of the dienophile is dominant. Since the electron-withdrawing group at the oxabutadiene at the 3-position lowers its LUMO dramatically, the cycloaddition as well as the condensation usually take place at room or slightly elevated temperature. There is actually no restriction for the aldehydes. Thus, aromatic, heteroaromatic, saturated aliphatic and unsaturated aliphatic aldehydes may be used. For example, a-oxocarbocylic esters or 1,2-dike-tones for instance have been employed as ketones. Furthermore, 1,3-dicarbonyl compounds cyclic and acyclic substances such as Meldmm s acid, barbituric acid and derivates, coumarins, any type of cycloalkane-1,3-dione, (1-ketoesters, and 1,3-diones as well as their phosphorus, nitrogen and sulfur analogues, can also be ap-... 

In a similar way, carbocycles having a quaternary center could be obtained from acyclic unsaturated 1,3-dicarbonyl compounds [206]. Other combinations are the domino hydroformylation/Wittig olefmation/hydrogenation described by Breit and coworkers [207]. The same group also developed the useful domino hydroformyla-tion/Knoevenagel/hydrogenation/decarboxylation process (Scheme 6/2.14) [208] a typical example is the reaction of 6/2-66 in the presence of a monoester of malonic acid to give 6/2-67 in 41 % yield in a syn anti-ratio of 96 4. Compounds 6/2-68 and 6/2-69 can be assumed as intermediates. 

The reaction is applicable to acyclic and cyclic enol ethers and to various (3-dicarbonyl compounds, but fails with silyl enol ethers and simple 1,2-disubstituted alkenes. When applicable, this route to furans is useful because the yields and regioselectivity are consistently satisfactory. The paper includes a preparation of the reagent by reaction of Mn(NO,)3 with Ac20 at 100° to give Mn,0(0Ac)7 H0Ac in 60% yield. 

Similar oxidative cyclization reactions involving the direct oxidation of acyclic 1,3-dicarbonyl compounds have not been reported. However, the generation of radical intermediates by the direct oxidation of cyclic 1,3-dicarbonyl compounds at an anode surface has been reported. Yoshida and coworkers have shown that the anodic oxidation of cyclic 1,3-dicarbonyl compounds in the presence of olefin trapping groups gives rise to a net cycloaddition reaction (Scheme 10) [23]. These cycloaddition reactions proceeded by initial oxidation of the 1,3-dicarbonyl compound at the anode followed by a radical addition to the second olefin. Following a second oxidation reaction, the material then... 

Although cyclizations from the direct anodic oxidation of acyclic 1,3-dicarbonyl compounds have not been reported, the analogous mediated reactions have been studied [24]. Snider and McCarthy compared oxidative cyclization reactions using a stoichiometric amount of Mn(OAc)3 with oxidations using a catalytic amount of Mn(OAc)3 that was recycled at an anode surface (Scheme 11). In the best case, the anodic oxidation procedure led to a 59% yield of the desired bridged bicyclic product with the use of only 0.2 equivalents (10% of the theoretical amount needed) of Mn(OAc)3- Evidence that the reaction was initiated by the presence of the mediator was obtained by examining the electrolysis reaction without the added Mn(OAc)3. In this case, none of the cyclized product was obtained. For comparison, the oxidation using... 

The asymmetric allylic C-H activation of cyclic and acyclic silyl enol ethers furnishes 1,5-dicarbonyl compounds and represents a surrogate of the Michael reaction [136]. When sufficient size discrimination is possible the C-H insertion is highly diastereoselective, as in the case of acyclic silyl enol ether 193 (Eq. 22). Reaction of aryldia-zoacetate 192 with 193 catalyzed by Rh2(S-DOSP)4 gives the C-H insertion product 194 (>90% de) in 84% enantiomeric excess. A second example is the reaction of the silyl enol ether 195 with 192 to form 196, a product that could not be formed from the usual Michael addition because the necessary enone would be in its tautomeric naphthol form (Eq. 23). 

In classical Hantzsch procedure, an enaminocarbonyl is formed in sim by condensation of ammonia source onto the 1,3-dicarbonyl substrate. But many groups have used a three-component modified-Hantzsch protocol in which the preformed enamine is introduced as a partner. Thus, utilization of cyclic or acyclic 1,3-dicarbonyl compounds, aldehydes, and acyclic or cyclic enamines has been reported, leading regioselectively to diversely substituted 1,4-DHP derivatives (Scheme 7). The sequence involving such starting materials was performed in numerous efficient systems, and more particularly in the following (1) microwave-assisted reaction in acetic acid [50], DMF [51], or an acetic acid/DMF system [52] (2) sonification in ethylene glycol [53] and (3) use of ionic liquids such as [bmim]BF4 [54]. 

Ozonolysis of acyclic ketoximes 43 in the presence of ketones resulted in the formation of tetrasubstituted cross-ozonolides (1,2,4-trioxolanes) 44 in yields up to 73% (equation 20). Ozonolysis of 0-methylated monooximes of 1,4-, 1,5- and 1,6-dicarbonyl compounds afforded bicyclic oxonides . ... 

Nitrosation of the 2-acylamino-1,3-dicarbonyl compound (126) affords an intermediate (127), which is spontaneously hydrolyzed to an A-acylamidoxime. Elimination of water produces the oxadiazole (128) (Scheme 57) <58CB1123>. Similar results have been obtained for some acyclic... 

Aromatic aldehydes react very easily with tetramic acid under acidic conditions to give 3-benzylidene compounds (41). The yields are moderate, because often there are subsequent reactions. As a,/3-unsaturated carbonyl compounds, (41) react in a Michael addition with excess tetramic acid to form (67), but it can also react with other acyclic and cyclic 1,3-dicarbonyl compounds. In these reactions the aryl substituents may vary over a wide range. Thus, (67) and (68) can be cyclized with ammonium acetate to afford pharmacologically interesting compounds (70) and (71) (90TH1). The latter are dihydropyridines. Curiously, (69) does not cyclize under these conditions. (See Fig. 32.)... 

The oxygen Hantzsch-like synthesis involving acyclic /1-dicarbonyl compounds requires ZnCl2 catalysis and yields 30 to 50% of 4//-pyrans 87a-d, which exhibit somewhat lower stabilities in comparison to 86.86... 

Several syntheses of 2//-pyrans are based on the preparation of the acyclic precursors (157b) in the hope that the dienone zZ 2//-pyran equilibrium will favor the heterocycle (157a). Often the product will contain both valence isomers. Such dienone precursors can be obtained by Knoevenagel condensation of 1,3-dicarbonyl compounds with a,(3-unsaturated aldehydes (Scheme 57). Simple 1,3-diketones yield the 2//-pyran directly (88IZV1815) and cyclohexan-l,3-diones afford fused pyrans (82S683, 84JHC913, 87JOC1972>. 

Cerium-catalyzed, direct a-hydroxylation of a variety of cyclic and acyclic /3-dicarbonyl compounds with molecular oxygen is described <2003EJ0425>. 3-Acetyloxepan-2-one is among the studied substrates (Equation 5). 

A novel hypervalent iodine-induced direct intramolecular cyclization of a-(aryl)alkyl-jS-dicarbonyl compounds 33 has been recently reported (Scheme 15) [30]. Both meta- and para-substituted phenol ether derivatives containing acyclic or cyclic 1,3-dicarbonyl moieties at the side chain undergo this reaction in a facile manner affording spirobenzannulated compounds 34 that are of biological importance. 

Using a chiral 4-dimethylaminopyridine-ferrocenyl catalyst, acyclic silyl ketene acetals react with anhydrides to furnish 1,3-dicarbonyl compounds containing allcarbon quaternary stereocentres in good yield and ee.144 Evidence for dual activation (anhydride -> acylpyridinium, and acetal -> enolate) is presented. 

Hwu et al. have examined the dependence of the metal oxidant on the mode of reactivity in silicon-controlled allylation of 1,3-dioxo compounds [95JOC856]. The use of manganese(III) acetate furnished the dihydrofuran product 22 only. On the other hand, use of cerium(IV) nitrate resulted in the formation of both acyclic (23) as well as the cyclized compound, with the product distribution dependent on the nature of the allylsilane. Facile synthesis of dihydrofurans by the cerium(IV) mediated oxidative addition of 1,3-dicarbonyl compounds to cyclic and acyclic alkenes has also been reported [95JCS(P1)187]. 

Iodonium ylides of type 6 cannot be isolated, unless the carbanion center is substantially stabilized (83MI1, 92MI1, 97MI1, 02MI1). For example, although iodonium enolates 22 can be prepared by base-catalyzed condensations of DAIB or iodosylbenzene with /J-dicarbonyl compounds, they are not similarly available from unactivated ketones and esters. Indeed, cyclic and acyclic mono-ketones are converted to a-hydroxy dimethylketals 23 with DAIB (or 13) in KOH/MeOH (86ACR244, 99QR273). Other... 

Initial attempts at the direct fluorination of carbonyl compounds such as acetone, bulan-2-one, and butyric acid with elemental fluorine resulted in the formation of complex mixtures, with only low yields of a-monofluorinated carbonyl compounds formed. However, more recently, methyl 3-phenylpyruvate. and other pyruvate derivatives, e.g. 1," are reported to be selectively monofluorinated with dilute elemental fluorine at — lO C in moderate yield. The success of this reaction is attributed to the fact that the substrate predominantly exists in the enol form and not the keto form." Direct fluorination of acyclic 1,3-dicarbonyl compounds in formic acid or acetonitrile at room temperatures results in the formation of 2-fluoro-... 

Ketones are converted into ot-fluoro ketones in excellent yield by treatment with l-fluoro-4-hydroxy-l,4-diazoniabicyclo[2.2,2]octane bis(tetrafluoroborate) in acetonitrile at 80 C. 1,3-Dicarbonyl compounds, for example, acyclic and cyclic 1,3-dikctones, f)-oxo esters and /i-oxo amides, upon treatment with l-(chloromcthyl)-4-fluoro-l,4-diazoniabicyclof2.2.2]octane tetra-fluoroborate in acetonitrile at room temperature, give the corresponding a-monofluorinated compounds in good yield. Although similar results are obtained with (V-fluorobis(perfluoroal-kyljsulfonamides (Table the synthetic utility of this reaction is limited by the lack of... 

The. splitting of a-glycol groups by periodate was discovered by Malapradc in 1928, and the reaction has since found wide application. From an acyclic glycol, the products of the reaction are two carbonyl compounds an a,w-dicarbonyl compound results from a cyclic glycol. The... 

The carbenoid reaction between a-diazo ketones and simple alkenes or styrenes leads to acylcyclopropanes. (For the enantioselective cyclopropanation of styrene with 2-diazo-5,5-dimethylcyclohexane-l,3-dione, see Section 1.2.1.2.4.2.6.3.2.). With ketene acetals, 2,3-dihyd-rofurans are obtained. In contrast, l-acyl-2-oxycyclopropanes or 2-oxy-2,3-dihydrofurans can be formed in reactions with enol ethers and enol acetates the result depends strongly on the substitution pattern of both reaction partners.Whereas simple diazo ketones usually lead to cyclopropanes (Table 15), 3-diazo-2-oxopropanoates and 2-diazo-l,3-dicarbonyl compounds, such as 2-diazoacetoacetates, 3-diazopentane-2,4-dione, and 2-diazo-5,5-dimethylcy-clohexane-1,3-dione, yield 2,3-dihydrofurans and occasionally acyclic structural isomers thereof when reacted with these electron-rich oxy-substituted alkenes. 

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