1,3-dicarbonyl compounds allylation

Several 1,4-dicarbonyl compounds are prepared based on this oxidation. Typically, the 1,4-diketone 10 or the 1,4-keto aldehyde 12 can be prepared by the allylation of a ketone[24] or aldehyde[61,62], followed by oxidation. The reaction is a good annulation method for cyclopentenones (11 and 13). Syntheses of pentalenene[78], laurenene[67], descarboxyquadrone[79], muscone (14 R = Me)[80]) and the coriolin intermediate 15[71] have been carried out by using allyl group as the masked methyl ketone (facing page). 

The enol ethers of P-dicarbonyl compounds are reduced to a, 3-unsaturated ketones by LiAlH4, followed by hydrolysis.115 Reduction stops at the allylic alcohol, but subsequent acid hydrolysis of the enol ether and dehydration leads to the isolated product. This reaction is a useful method for synthesis of substituted cyclohexenones. 

Microwave-mediated transesterification of commercially available neat poly(styr-ene-co-allyl alcohol) with ethyl 3-oxobutanoate, ethyl 3-phenyl-3-oxopropanoate, and diethyl malonate provided the desired polymer-supported /i-dicarbonyl compounds (Scheme 12.18) [65]. Multigram quantities of these interesting building blocks for heterocycle synthesis were obtained simply by exposing the neat mixture of reagents to microwave irradiation in a domestic microwave oven for 10 min. 

Scheme 12.18 Derivatization of poly(styrene-co-allyl alcohol) with R = Me, Ph, OEt /7-dicarbonyl compounds.

Alkylation of P-dicarbonyl compounds and p-keto esters occurs preferentially on the carbon atom, whereas acylation produces the 0-acyl derivatives (see Chapter 3). There are indications that C- and 0-alkylated products are produced with simple haloalkanes and benzyl halides, but only C-alkylated derivatives are formed with propargyl and allyl halides [e.g. 90]. Di-C-alkylation frequently occurs and it has been reported that the use of tetra-alkylammonium 2-oxopyrrolidinyl salts are more effective catalysts (in place of aqueous sodium hydroxide and quaternary ammonium salt) for selective (-90%) mono-C-alkylation of p-dicarbonyl compounds [91]. 

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). 

Beside the Friedel-Crafts-type alkylation of arenes, the direct functionalization of 2,4-pentanediones is of great interest in Lewis acid catalysis. Although Pd-catalyzed Tsuji-Trost type allylations of 1,3-diketones are known, direct benzylation procedures catalyzed by Lewis acids are less explored [40-43]. Based on the previously described Friedel-Crafts alkylation of arenes and heteroarenes, the Rueping group developed a Bi(OTf)3-catalyzed benzylation of 2,4-pentanediones. Alcohols such as benzyl, allyl or cinnamyl alcohols were used as the electrophilic component to yield important 2-alkylated 1,3-dicarbonyl compounds. Initially, different Bi(III) salts were screened. In contrast... 

Knoevenagel condensation of aldehydes with 1,3-dicarbonyl compounds and subsequent NBS bromination yields allylic bromides, which are converted thermally to 3-acyl- or 3-alkoxycarbonyl furans (Scheme 51) (78JOC4596). 

The treatment of 1,2-diols with Dess-Martin periodinane may lead either to a 1,2-dicarbonyl compound,14 or to an oxidative breakage of a C-C bond14,72 depending on stereoelectronic factors. When a 1,2-dicarbonyl compound is obtained, very often, one of the carbonyl groups tautomerizes to the enol form. Under controlled conditions, very often, it is possible to selectively oxidize one of the alcohols in a 1,2-diol, particularly when this alcohol is an allylic one.73... 

With 1-alkoxyallenes as proelectrophiles, the palladium-catalysed asymmetric allylic alkylation proceeds with 1,3-dicarbonyl compounds as pronucleophiles with excellent regioselectivity good enantioselectivity (82-99% ee) was obtained with the Trost lig- and. The pH of the medium proved crucial for the reactivity and selectivity. By using the more acidic Meldrum s acids, the reactions required a co-catalytic amount of a Brpnsted acid, such as CF3CO2H. On the other hand, the less acidic 1,3-diketones failed to react under these conditions but the reaction proved to occur in the presence of the weaker benzoic acid, suggesting the need for general base catalysis. Indeed, a mixture of Et3N and PhCOiH proved to be optimal (93-99% ee). A mechanistic model to rationalize these results has been developed.88... 

We had to be careful in chapter 25 when we wanted to add bromoketones 4 to enolates 3 to make the 1,4-dicarbonyl compound 5. We could not use a lithium enolate because it would be too basic. No such difficulties exist in the reaction of enolates with allylic halides such as 2. Any enol(ate) equivalent will do as there are no acidic hydrogens and allylic halides are good electrophiles for the Sn2 reaction. 

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]. 

The resulting 5-methylene-2-oxa-l-silacyclohexanes are insufficiently Lewis acidic to react with a second equivalent of the carbonyl compound. However, the incipient allylsilane does react with dimethyl acetals in decent yields in the presence of external Lewis acids including BF3-Et20 or AICI3. Based on these results, double allylation of dicarbonyl compounds with 3-methylene-l,l-diphenyl-l-silacyclobutane was examined, leading to the formation of 3-methylene-oxabicyclo[3.2.1]octanes. This transformation proceeded in one pot and in the presence of BF3-Et20 (Scheme 42). 

Allylic C-H insertions have been used in key steps of the enantioselective synthesis of the pharmaceuticals (+)-ceitedil (26) [21] and (+)-indatraline (27) [22] (Scheme 11). The allylic C-H insertion reaction is an exciting alternative to the Claisen rearrangement as a rapid method for the synthesis of y,c>-unsaturated ester [23 ]. Similarly, the allylic C-H insertion with vinyl silyl ethers generates protected 1,5-dicarbonyl compounds, a complimentary reaction to the Michael addition [24]. Both types of C-H insertion can be achieved with high diastereoselectiv-ity and enantioselectivity [23, 24]. 

Morken and Lavastre used the formation of a colored side product to identify catalysts for the allylation of /i-dicarbonyl compounds [8]. The researchers employed 1-naphthyl allyl carbonate 5 as an allyl source and the diazonium salt of fast red as an indicator. Formation of the active 7z>allyl complex furnishes C02 and 1-naphthoxide which deprotonates the 1,3-dicarbonyl compounds which can, in turn, react with the 71-allyl metal complex. 1-Naphthol is the only species in the reaction mixture that can react with the diazonium salt 6 to generate the bright red azo dye fast red. Thus the red color is indicative of successful formation of the active re-allyl complex (Figure 5.4.3). 

Combinations of eight different ligands and twelve different metal salts were screened for their efficiency to catalyze the allylation of /i-dicarbonyl compounds. The assay identified not only the well known catalyst system Pd(OAc)2 combined with a phosphine ligand but also the combination [ IrCl(cod) 2] and iPr-pybox or 1,10-phenanthroline as efficient catalysts. These are the first examples of non-phosphane iridium catalysts capable of allylic alkylations. 

In the oxygenation of 5,6-dihydro- 1,4-oxathiin 116, despite the presence of allylic hydrogens and the sulfide moiety, the sole reaction product is the dicarbonyl compound 118 (isolated yield 90%) [126a] deriving from the corresponding dioxetane 117, which has been spectroscopically... 

Sulphonium ylides are in certain cases unstable and they undergo further transformation affording useful final products. In this way allylic sulphides and selenides were used to transfer an alkylthio- or alkylseleno-group onto the a-carbon of / -dicarbonyl compounds in the form of their ylides the sequence of reactions were a transylidation followed by [2,3]-sigmatropic rearrangement. 

Cyclopentadienes. Allyl chlorides that are monosubstituted at the central allylic position, such as 1, react with 1,3-dicarbonyl compounds such as acetyl-acetone (2) to form acetylcyclopentadienes (3) via an allylated dicarbonyl intermediate (a), which can be isolated from reactions of 1 with 2 at -78°. 

Tetraphenylantimony methoxide (Ph4SbOMe) reacts with 1,3-dicarbonyl compounds to generate tetraphenylantimony(v) enolates, which are readily alkylated by allyl, propargyl, and benzyl bromides as well as by ethyl bromoacetate (Equation (20)).54... 

Other Carbonyl Allylation Reactions 9.14.3.5.1 Allylation of quinones and dicarbonyl compounds... 

The coupling reaction of a-keto esters with allyl, propargyl, and allenyl halides using indium metal in aqueous solvents affords a-hydroxy-y,<5-unsaturated esters (Equation (28)).197,198 1,3-Dicarbonyl compounds undergo efficient carbonyl allylation reactions in an aqueous medium through a Barbier-type reaction (Equation (29)). The reaction is general and a variety of 1,3-dicarbonyls has been alkylated using allyl bromide or allyl chloride in conjunction with indium.199... 

Sequential nucleophilic and electrophilic alkylations of 1,3-dicarbonyl compounds with a trimethylenemethane zwitterion equivalent lead to [3 + 2]-annulation. The nucleophilic carbonyl alkylation step has been carried out via an indium-mediated allylation in water (Equation (30)).200 Indium-mediated allylation of a-chlorocarbonyl compounds with allyl bromides in aqueous media gives the corresponding homoallylic chlorohydrins, which can be transformed to allyloxiranes (Equation (31)).201 Allylation of the G3 position of the cephem nucleus has been accomplished by indium-mediated allylation reaction in aqueous media (Equation (32)).202... 

Treatment of 1,3-dicarbonyl compounds with DBP in a methoxide/methanol system affords 2-alkyl-4-[(phenylsulfonyl)methyl]furans, where reaction proceeds by Initial addition-elimination on the vinyl sulfone moiety. In contrast, silyl enol ethers in the presence of silver tetrafluoroborate resulted in products derived from Sn2 displacement at the allylic site.11 Anions derived from 1,3-dicarbonyls substituted at the C-2 position are found to induce a complete reversal in the mode of ring closure.12 The major products obtained are 3-[(phenylsulfonyl)methyl]-substituted cyclopentenones. The internal displacement reaction leading to the furan ring apparently encounters an unfavorable Ai -interaction in the transition state when a substituent group is present at the 2-position ol the dicarbonyl compound. This steric Interaction is not present in the transition state leading to the cyclopentenone ring. 

Selenium dioxide (SeOi) oxidation Selenium dioxide is an excellent oxidizing agent for the oxidation of allylic and benzylic C-H fragments to allylic or benzylic alcohol. It also oxidizes the aldehydes and ketones to 1,2-dicarbonyl compounds (i.e. oxidation of active methylene groups to carbonyl groups). 

The monoanions of /3-dicarbonyl compounds also form organometallic species, usually involving the central carbon atom in the M-C bond (14). Such species are known for a number of metals, particularly those of the platinum group. This mode of binding leaves the two carbonyl oxygen atoms free, allowing the formation of bimetalhc species (15). ry -Allylic (16) and terminal (17) carbon bonding have also been observed. 

A simple synthetic method for 1,4-dicarbonyl compounds was introduced, based on the allylation of carbonyl compounds with allyl halide as a C3 component, followed by the palladium-catalyzed oxidation of the terminal alkenes (20) to methyl ketones (21). In this method, the allyl group is a synthetic equivalent of the 2-oxopropyl group (Scheme 5). This is a good anellation method for cyclopentenones. 

The 1,5-diketone foimation by the Michael addition of allylsilane (48) to a, -unsaturated ketones was applied to the synthesis of (-i-)-nootkatone." Reaction of the keto group of keto aldehyde (58) with allyl Grignaid reagent and dehydration gave the diene aldehyde (59). The selective oxidation of the terminal double bond afforded the 1,5-dicarbonyl compound (60), which is not stable and converted directly to pyridines and phenols (Scheme 18)." ... 

In the acid-catalyzed ortho ester Claisen rearrangement of allylic alcohol (303) with trimethyl orthobutyrate, diastereomers (304), (305) and (306) were isolated in a ratio of 63 30 7 (Scheme 53). The 3,3-sigmatropic rearrangement occuned with a high degree of stereofacial selectivity from the p-face of the allylic alcohol (a >13 1 for Ht). In contrast, Qaisen rearrangement of the enol ether (307) at 135-140 C (PhH, sealed tube) provid the desired -dicarbonyl compound (308) as a single diastereomer at... 

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