Ethers 1.3-dicarbonyl compound

Butyl vinyl ether reacts with aroyl chlorides using Pd(OAc)2 without a ligand to give the unsaturated ketone 839, which is a precursor of a 1-aryl-1,3-dicarbonyl compound. The reaction is regioselective /3-attack. Addition of PhjP inhibits the reaction[718]. 

Vinyl ethers and a,P unsaturated carbonyl compounds cyclize in a hetero-Diels-Alder reaction when heated together in an autoclave with small amounts of hydroquinone added to inhibit polymerisation. Acrolein gives 3,4-dihydro-2-methoxy-2JT-pyran (234,235), which can easily be hydrolysed to glutaraldehyde (236) or hydrogenated to 1,5-pentanediol (237). With 2-meth5lene-l,3-dicarbonyl compounds the reaction is nearly quantitative (238). 

Formation o( oleltns by coupling or cross coupling of ketones, mediated by low valent titanium Also coupling ol enol ethers of 1,3-dicarbonyl compounds. 

The carbonyl group forms a number of other very stable derivatives. They are less used as protective groups because of the greater difficulty involved in their removal. Such derivatives include cyanohydrins, hydrazones, imines, oximes, and semicarbazones. Enol ethers are used to protect one carbonyl group in a 1,2- or 1,3-dicarbonyl compound. 

The procedure described illustrates a general method for the preparation of o ,j3-unsaturated aldehydes and ketones from the enol ethers of 3-dicarbonyl compounds. 

The reaction of tnfluoromethyl-substituted A -acyl umnes toward nucleophiles in many aspects parallels that of the parent polyfluoro ketones Heteronucleophiles and carbon nucleophiles, such as enarmnes [37, 38], enol ethers [38, 39, 40], hydrogen cyanide [34], tnmethylsilylcarbomlnle [2,47], alkynes [42], electron-nch heterocycles [43], 1,3-dicarbonyl compounds [44], organolithium compounds [45, 46, 47, 48], and Gngnard compounds [49,50], readily undergo hydroxyalkylation with hexafluoroace-tone and amidoalkylation with acyl imines denved from hexafluoroacetone... 

The rhodium-mediated reaction of 69 with 2,3-dihydrofuran (a formal dipolar cycloaddition of a cyclic diazo dicarbonyl compound with a vinyl ether) yields 70. Corrqiound 70 can be transformed in a number of steps to 71 a,b <96TL2391>. 

Normal yS-dicarbonyl compounds such as ethyl acetoacetate 723 a or acetylace-tone 723 b are converted, as the free yS-dicarbonyl compounds or as their sodium salts, by TCS 14, 14/pyridine, or HMDS 2/TCS 14 into their enol silyl ethers 724a [216, 217, 219] and 724b [218]. Yet treatment of / -triketones such as 2-acetyl-dimedone 725 with HMDS 2 results, via the corresponding 2-enol trimethylsilyl... 

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. 

As the name implies, the first step of this domino process consists of a Knoevenagel condensation of an aldehyde or a ketone 2-742 with a 1,3-dicarbonyl compound 2-743 in the presence of catalytic amounts of a weak base such as ethylene diammonium diacetate (EDDA) or piperidinium acetate (Scheme 2.163). In the reaction, a 1,3-oxabutadiene 2-744 is formed as intermediate, which undergoes an inter- or an intramolecular hetero-Diels-Alder reaction either with an enol ether or an alkene to give a dihydropyran 2-745. 

Today, multi-parallel synthesis lies at the forefront of organic and medicinal chemistry, and plays a major role in lead discovery and lead optimization programs in the pharmaceutical industry. The first solid-phase domino reactions were developed by Tietze and coworkers [6] using a domino Knoevenagel/hetero-Diels-Alder and a domino Knoevenagel/ene protocol. Reaction of solid-phase bound 1,3-dicarbonyl compounds such as 10-22 with aldehydes and enol ethers in the presence of piperidinium acetate led to the 1-oxa-1,3-butadiene 10-23, which underwent an intermolecular hetero-Diels-Alder reaction with the enol ethers to give the resin-bound products 10-24. Solvolysis with NaOMe afforded the desired dihydro-pyranes, 10-25 with over 90 % purity. Ene reactions have also been performed in a similar manner [7]. 

The use of oxygen-containing dienophiles such as enol ethers, silyl enol ethers, or ketene acetals has received considerable attention. Yoshikoshi and coworkers have developed the simple addition of silyl enol ethers to nitroalkenes. Many Lewis acids are effective in promoting the reaction, and the products are converted into 1,4-dicarbonyl compounds after hydrolysis of the adducts (see Section 4.1.3 Michael addition).156 The trimethylsilyl enol ether of cyclohexanone reacts with nitrostyrenes in the presence of titanium dichloride diisopropoxide [Ti(Oi-Pr)2Cl2], as shown in Eq. 8.99.157 Endo approach (with respect to the carbocyclic ring) is favored in the presence of Ti(Oi-Pr)2Cl2. Titanium tetrachloride affords the nitronates nonselectively. 

The pyranocoumarin 105 can be prepared via a three-component Diels-Alder reaction between 4-hydroxycoumarin, ethyl vinyl ether and an a-dicarbonyl compound. Similarly to the above, upon treatment of 105 with sulfuric acid in THF, hydrolysis and rearrangement occur to give the furofurochromenone 106. The hemiacetal functionality in 106 may then be oxidized with pyridinium chlorochromate (PCC) to give the lactone 107 <2001EJ03711> (Scheme 28). 

Diazomalonic esters, in their behavior towards enol ethers, fit neither into the general reactivity pattern of 2-diazo-l,3-dicarbonyl compounds nor into that of alkyl diazoacetates. With the enol ethers in Scheme 17, no dihydrofurans are obtained as was the case with 2-diazo-l,3-dicarbonyl compounds. Rather, copper-induced cyclo-propanation yielding 70 occurs with ethoxymethylene cyclohexane u4). However,... 

Schreiber and his coworkers have published extensively over the past decade on the use of this photocycloaddition for the synthesis of complex molecules730 81. Schreiber was the first to recognize that the bicyclic adducts formed in these reactions could be unmasked under acidic conditions to afford threo aldol products of 1,4-dicarbonyl compounds (175 to 176) (Scheme 40). The c -bicyclic system also offers excellent stereocontrol in the addition of various electrophilic reagents (E—X) to the enol ether of these photoadducts on its convex face (175 to 177). This strategy has been exploited in the synthesis of a variety of architecturally novel natural products. 

Cyclopentenones. 1,3-Dicarbonyl compounds add to enol ethers or esters (terminal) in the presence of Mn30(OAc)7 (excess) to form l-alkoxy-l,2-dihydro-furans. These can be converted to a 1,4-diketone, which undergoes aldol cyclization to fused (or spiro) cyclopentenones.1... 

Furans.2 Enol ethers, p-dicarbonyl compounds, and Mn(III) acetate (2 equiv.) react in acetic acid (25°) to form l-aIkoxy-l,2-dihydrofurans, which form furans readily on acid-catalyzed elimination of ROH. 

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. 

On the other hand, the use of [Rh(CO)2Cl]2 as a catalyst results in ring opening of the siloxycyclopropanes 13 to the silyl enol ethers 14 with high stereoselectivity [10]. The 2-siloxyrhodacyclobutane 15a is proposed to undergo j8-elimination to give jr-allylrhodium 16a followed by reductive elimination to the silyl enol ether 14a. 1-Trimethylsiloxybicyclo[n.l.0]alkanes serve as / -metallo-carbonyl compounds via desilylation with a variety of transition metals [11]. The palladium-catalyzed reaction of the siloxycyclopropanes 17 under carbon monoxide in chloroform provides a route to the 4-keto pimelates 18. In the presence of aryl triflates, the 1,4-dicarbonyl compounds 19 are... 

Silyl enol ethers (Scheme 2, Y = OSi ( 113)3) can be dimerized to 1,4-dicarbonyl compounds in good yields. To suppress the methanolysis of the silyl enol ethers, MeCN-5% MeOH is used as solvent and the electrolysis is conducted within one hour by the use of a capillary gap cell, which allows high currents (Table 7, numbers 6 and 7) [59]. 

In the oxidation of anionized 1,3-dicarbonyl compounds (Table 8, numbers 1-7) at potentials between 0.6 and 1.4 V (see) and in the presence of butadiene, mainly the additive dimer (24) is obtained in the presence of ethyl vinyl ether chiefly the disubstituted monomers (28) or (29) arise. 

Scheme 44 Anodic addition of the anion of a 1,3-dicarbonyl compound to vinyl ethyl ether.

Selective formation of 1,5-dicarbonyl compounds by 1,4-addition (Michael addition) of enolates to enones is facilitated by the use of enol silyl ethers as enolate equivalents [37]. The reaction is catalyzed by... 

The cationic iridium complex [Ir(cod)(PPh3)2]OTf, when activated by H2, catalyzes the aldol reaction of aldehydes 141 or acetal with silyl enol ethers 142 to afford 143 (Equation 10.37) [63]. The same Ir complex catalyzes the coupling of a, 5-enones with silyl enol ethers to give 1,5-dicarbonyl compounds [64]. Furthermore, the alkylation of propargylic esters 144 with silyl enol ethers 145 catalyzed by [Ir(cod)[P(OPh)3]2]OTf gives alkylated products 146 in high yields (Equation 10.38) [65]. An iridium-catalyzed enantioselective reductive aldol reaction has also been reported [66]. 

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). 

Nifedipin Nifedipine, dimethyl ether l,4-dihydro-2,6-dimethyl-4-(2 -nitrophenyl)-3,5-piridindicarboxylic acid (19.3.16), is synthesized by a Hantsch synthesis from two molecules of a j3-dicarbonyl compound—methyl acetoacetate, using as the aldehyde component—2-nitrobenzaldehyde and ammonia. The sequence of the intermediate stages of synthesis has not been completely established [20-23]. 

The preparation of (128) (Scheme 34) highlights the use of the trifluoromethyl group to increase the dipolarophilicity of a ketone. This activating effect of electron withdrawing groups is also taken advantage of in the preparation of 3-carbonyl substituted 1,2,4-trioxolanes (131) via the ozonolysis of a vinyl ethers in the presence of a 1,2-dicarbonyl compound (Scheme 36) <9iJOC659l>. 

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