Michael addition Quinones

The most extensive mechanistic studies of quinone Michael addition chemistry involve the arylsufinic acids, which yield reduced product (50,51). The sulfones produced in such reactions have been examined electrochemicaHy (48) and kineticaHy (52). The influence of substitutents in the quinone has... 

At least two pathways have been proposed for the Nenitzescu reaction. The mechanism outlined below is generally accepted." Illustrated here is the indolization of the 1,4-benzoquinone (4) with ethyl 3-aminocrotonate (5). The mechanism consists of four stages (I) Michael addition of the carbon terminal of the enamine 5 to quinone 4 (II) Oxidation of the resulting hydroquinone 10 to the quinone 11 either by the starting quinone 4 or the quinonimmonium intermediate 13, which is generated at a later stage (HI) Cyclization of the quinone adduct 11, if in the cw-configuration, to the carbinolamine 12 or quinonimmonium intermediate 13 (IV) Reduction of the intermediates 12 or 13 to the 5-hydroxyindole 6 by the initial hydroquinone adduct 7 (or 8, 9,10). 

The best yields of 5-hydroxyindoles are obtained when equimolar amounts of the quinone and enamine are used. An excess of enamine gives rise to non-indolic products derived from reaction of two enamine units and one quinone unit or the product which results from the initial Michael addition of the enamine to the quinone. Use of excess quinone has been reported less frequently, but limited studies indicate no advantage. When 2,5-dichloro-l,4-benzoquinone (32) was treated with a 50% excess of ethyl 3-... 

The mercaptol alcohol rac-14 undergoes facile Michael addition reaction with quinone ketal 13 which is commercially available or can be readily prepared. 

Mercapto-l,2,4-triazole 67 reacted in a standard coulometric cell with the ortho-quinone generated electroche-mically from 1,2-dihydroxybenzene to give 4-(l//-l,2,4-triazole-3-ylsulfanyl)-l,2-benzenediol 68 via a Michael addition (Equation 23) <2005MI68>. 

Michael addition of di- and tri-hydric phenols to /V-cinnamoylimidazoles followed by a lactonisation offers a route to 4-aryI-3,4-dihydrocoumarins and their [/]-benzologues <00S123>. The lactonisation of the naphthoquinone derivative 66 is sensitive to the acidic cyclising medium and it is possible to obtain the thermodynamically less stable o-quinone derivative exclusively (Scheme 44) <00TL3007>. Some related quinones have been obtained from 1-benzylisoquinolines via an arylnaphthoquinone <00T6O23>. 

Michael additions to quinones. In the presence of TrC104, enol silyl ethers undergo 1,4-addition to benzoquinone to give adducts that cyclize to benzofurans.1 A similar reaction with diimidoquinones produces indole derivatives. 

Quinone dyes, 9 503 Quinone ketals, anodic oxidation of hydroquinone ethers to, 21 264 Quinone methides, 2 209-211 Quinone Michael addition chemistry, 21 248-249, 250, 252 Quinone monoacetals, 21 251 Quinone monoimine (QMI), 19 246 Quinone oximes, formation of,... 

Substituted quinone ketals, prepared in this manner, serve nicely in annelation strategies leading to natural products. Two are illustrated, one in Scheme 20 leading to (+)-4-demethoxydaunomycinone (87) and (+)-daunomycinone (88) [46-48], the other in Scheme 21 serving as a pathway to a-citromycinone (94). The first calls for a Michael addition of (84) to quinone ketal (83) followed by capture of the intermediate enolate, and leads to annelated... 

The first step of the enzymatic process is the transaldimination of the Schiff base lysine-PLP by the amino acid. The pulling out of the proton in a of the fluorinated amino acid is accompanied by elimination of a fluorine atom of the CX2F group, thus affording a very reactive quinonic species. This latter one can further react with a nucleophilic entity of the enzyme (e.g., the lysine of the active site) ( Michael addition inactivation process ) (Figure 7.47). ... 

In the presence of a protic acid, triazolium thiolates underwent 1,4-Michael addition to p-quinones, and formed the corresponding thioether-substituted hydroquinone salts, which could be oxidized to quinones (85JA6987 85JOC433). This addition is also possible with o-quinones. Since they are... 

Addition of water to quinones. The yields of the known Michael addition of water or an alcohol to a 1,4-naphthoquinone such as 5,8-dimethoxy-l,4-naphtho-qninonc arc improved by addition of an oxidant such as Fe2(S04)3 to convert the initial 2-hydroxynuphlhohydroquinone to the corresponding quinone. The presence til ll 1 rcc pert-hydroxy group interferes with the reaction. 

Nucleophilic Substitution Reactions. Many of the transformations realized through Michael additions to quinones can also be achieved using nucleophilic substitution chemistry. In some instances die stereoselectivity can be markedly improved in this fashion, e.g., in the reaction of benzenethiol with esters (R = CH3C=0> and ethers (RJ = CH,) of 1,4-naphthoquinones. 2-Bromo-5-acetyloxy-1,4-naphthoquinone, R1 — Hr, yields 75% of 2-thiophenyl-5-acetyloxy-1,4-naphdloquinone. R1 = SCr.Hv 3-Bronio-5-methoxy-l,4-naplitlioquinone, R2 = Br, yields 82% of 3-thiophenyl-5-methoxy-1,4-naphthoquinone R2 = SCr.IIs. 

Aziridines can add to carbon—carbon multiple bonds. Elevated temperature and alkali metal catalysis are required in the case of nonpolarized double bonds (193—195). On the other hand, the addition of aziridines onto the conjugated polarized double or triple bonds of a,p-unsaturated nitriles (196—199), ketones (197,200), esters (201—205), amides (197), sulfones (206—209), or quinones (210—212) in a Michael addition-type reaction frequendy proceeds even at room temperature without a catalyst. The adducts obtained from the reaction of aziridines with a,p-unsaturated ketones, eg, 4-aziridinyl-2-butanone [503-12-8] from 3-buten-2-one, can be converted to 1,3-substituted pyrrolidines by subsequent ring opening with acyl chlorides and alkaline cyclization (213). 

Diels-Alder reactions leading to polycyclic addition products in good yields. Some of such quinone oxidation products have also been used in Michael additions [80,81] or in Diels-Alder reactions [82,83]. 

Nucleophile addition to a quinone methide is formally a Michael addition reaction.153 However, an important difference between 1,6-addition of nucleophiles to / -quinone methides and conventional Michael addition reactions is the aromatization of the cyclohexadiene ring that accompanies this addition. The effect of aromatic ring formation on the thermodynamic driving force for 1,6-addition of water to p-1 has been evaluated by comparing the thermodynamics... 

Treatment of the ot/ o-quinones 687 with 2equiv of carbethoxymethylenetriphenylphosphorane 688 affords coumarins in good yield. The reaction proceeds via Wittig olefination of the C-6 carbonyl to form the intermediate ort o-quinone methanides 689. Michael addition of a second equivalent of the phosphorane 688 followed by a Hoffmann type elimination of triphenylphosphine affords the intermediate 690. Intramolecular lactonization then forms the desired coumarins (Scheme 167) <2002J(P1)1455>. 

The Addition of the NH-Gtroup ofPyrazoles to Activated Double Bonds Pyrazoles undergo Michael addition to a,j3-unsaturated acids and esters,618,736,737,737 acrylonitrile,104,483,738 maleic anhydride, acetylene dicarboxylic ester,282,737 a,j8-unsaturated ketones,736 and quinones.104 Alkaline catalysts667 are not essential in this reaction,104 at least for addition to unsaturated nitriles, maleic anhydride, and quinones. The reaction is reversible, and V-pyrazolyl propionic... 

Baylis-Hillman adducts such as 55 and 56 derived from 2-nitrobenzaldehydes were shown to function as useful precursors to functionalized (1H)-quinol-2-ones and quinolines. Treatment of 55 and 56 with iron and acetic acid at 110 °C afforded 57 and 58, respectively <02T3693>. A variety of other cyclization reactions utilized in the preparation of the quinoline scaffold were also reported. An iridium-catalyzed oxidative cyclization of 3-(2-aminophenyl)propanols afforded 1,2,3,4-tetrahydroquinolines <02OL2691>. The intramolecular cyclization of aryl radicals to prepare pyrrolo[3,2-c]quinolines was studied <02T1453>. Additionally, photocyclization reactions of /rans-o-aminocinnamoyl derivatives were reported to provide 2-quinolones and quinolines <02JHC61>. Enolizable quinone and mono- and diimide intermediates were shown to provide quinolines via a thermal 6jt-electrocyclization <02OL4265>. Quinoline derivatives were also prepared from nitrogen-tethered 2-methoxyphenols. The corresponding 2-methoxyphenols were subjected to a iodine(III)-mediated acetoxylation which was followed by an intramolecular Michael addition to afford the quinoline OAc O... 

In the presence of bulky groups, such as in 3,5-di-ferf-butylquinone, the quinone is stable and can be isolated, but in most cases, it easily undergoes other reactions, such as Michael addition by nucleophiles present in solution, including the catechol itself. On the other hand, in some cases, the substrate oxidation can be driven to selected products [44], as in the synthesis of neurotrophic americanol A and isoamericanol by HRP-catalyzed oxidative coupling of caffeic acid [45] (Fig. 6.3b). 

The first step in the reaction of aminocycloalkenones with quinones is a normal Michael addition to yield hydroquinone adducts, as is known from the Nenitzescu reaction with / -ketoenamines. However, the consecutive cyclization is quite different, and the structure of the heterocycles formed depends on the substitution at the nitrogen and the size of the cycloalkane ring. 

An oxidatively induced ring closure occurs during the oxidation of various catecholamines (33)72 at a carbon paste electrode. Whereas the oxidation in 1 M H2SO4 yielded the 1,2-benzoquinone (34), sufficient free amine of 34 was present at pH 3 to allow an internal Michael addition of the adrenaline quinone. As would be expected, the resulting catechol (35) is more easily oxidizable than adrenaline and is converted into the quinone adrenochrome (36) by chemical oxidation by adrenaline quinone. 

A two-electron oxidation of N-acetyltyrosine ethyl ester with mushroom tyrosinase, or with periodate, afforded the N-acetyIdopa ester 142, together with the (Z)-enamide 145 and the 6-acetoxydopa amide 146 (Fig. 40) (284). It is assumed that 145 originates from dopaquinone 143 via 144 by tautomerization. Michael addition of acetate to quinone 143 is believed to be the origin of 146. The formation of quinone methide 144 from dopa ester 142 by tyrosinase is reminiscent of the formation of iminochromes and quinone methides catalyzed by this enzyme in their formation from a-methyl dopa ester (285), and such reactions may well occur in mammalian systems. 

Most examples of quinone dehydrogenations adjacoit to have been earned out on steroidal ketones and are essentially limited to readily enolizable species. Reactions on esters and amides (Table 8) are far less common and, because of their relatively low ease of enolization, require hanh conditions. Thus, unless stabilization of the intermediate carbonium ion is possible, - elevated temperatures and prolonged reaction times are required (Table 8), which increases the incidence of unwanted side reactions. Frequent by-products are those arising as a result of Diels-Alder reactions or Michael addition to the quinone." Allylic alcohols may be rapidly oxidized to aldehydes or ketones under these conditions and requite prior protection. 

Oxidative demethylation A new approach to indoloquinones such as 5 involves Michael addition of ethyl acetoacetate to the quinone monoimide 1 to give 2, which is dehydrated to the indole 3 in 73% overall yield. The latent quinone ring is then modified to give the p-methoxyaniline 4. The final step involves the oxidative demethylation reaction of Rapoport (4, 431-432) to give an intermediate quinone imine, which is hydrolyzed to 5. 

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