Enones anhydride

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

Photoaddition of acetylene, 349 Photoaddition of allene, 349 Photoaddition of dichloroethylene, 349 Photoaddition of ethylene, 348 Photoaddition of hexafluoroacetone, 345 Photoaddition of maleic anhydride, 348 Photochemical addition of ethylenes and acetylenes to steroidal enones and dienones, 343... 

Use of the imonium group for protection of enones was explored. Stability to peracids, lead tetraacetate, bromine, and acetic anhydride was claimed (727). The usual resistance of enamines (but not their salts) to additions of Grignard reagents was used for selective addition to a 3,17-diketosteroid by formation of the usual 3-monoenamine 728). 

The key step in this sequence, achieved by exposure of 46 lo a mixture of sulfuric acid and acetic anhydride, involves opening of the cyclopropane ring by migration of a sigma bond from the quaternary center to one terminus of the former cyclo-l>ropane. This complex rearrangement, rather reminiscent of the i enone-phenol reaction, serves to both build the proper carbon. keleton and to provide ring C in the proper oxidation state. 

Asymmetric conjugate addition of dialkyl or diaryl zincs for the formation of all carbon quaternary chiral centres was demonstrated by the combination of the chiral 123 and Cu(OTf)2-C H (2.5 mol% each component). Yields of 94-98% and ee of up to 93% were observed in some cases. Interestingly, the reactions with dialkyl zincs proceed in the opposite enantioselective sense to the ones with diaryl zincs, which has been rationalised by coordination of the opposite enantiofaces of the prochiral enone in the alkyl- and aryl-cuprate intermediates, which precedes the C-C bond formation, and determines the configuration of the product. The copper enolate intermediates can also be trapped by TMS triflate or triflic anhydride giving directly the versatile chiral enolsilanes or enoltriflates that can be used in further transformations (Scheme 2.30) [110],... 

A Nazarov-type cyclization was exploited to prepare annelated pyrroles <06OL163>. Acylation of iV-tosylpyrrole 65 with carboxylic acid 66 promoted by trifluoroacetic anhydride gave intermediate 2-ketopyrrole 67 which underwent a Nazarov-type cyclization to give cyclopenta[fc> pyrrolc 68. Another route to cyclopenta[fc]pyrroles involved a novel cyclization involving pyrrole-substituted enones and isocyanides <06OL3975>. 

Microwave heating has also been employed for performing retro-Diels-Alder cycloaddition reactions, as exemplified in Scheme 6.94. In the context of preparing optically pure cross-conjugated cydopentadienones as precursors to arachidonic acid derivatives, Evans, Eddolls, and coworkers performed microwave-mediated Lewis acid-catalyzed retro-Diels-Alder reactions of suitable exo-cyclic enone building blocks [193, 194], The microwave-mediated transformations were performed in dichloromethane at 60-100 °C with 0.5 equivalents of methylaluminum dichloride as catalyst and 5 equivalents of maleic anhydride as cyclopentadiene trap. In most cases, the reaction was stopped after 30 min since continued irradiation eroded the product yields. The use of short bursts of microwave irradiation minimized doublebond isomerization. 

Like unsaturated ketones, a,0-unsaturated carboxylic acid derivatives, e.g. lactones and anhydrides, undergo cycloadditions to alkenes. As for the preparative conditions (direct irradiation or sensitized experiments) these compounds are situated somewhere in between enones on the one side and olefins on the other. 

Diels-Alder, imino dienophiles, 65, 2 Diels-Alder, intramolecular, 32, 1 Diels-Alder, maleic anhydride, 4, 1 [4 -h 3], 51, 3 of enones, 44, 2 of ketenes, 45, 2 of nitrones and alkenes, 36, 1 Pauson-Khand, 40, 1 photochemical, 44, 2 retro-Diels-Alder reaction, 52, 1 53, 2 [6-h4], 49, 2 [3-h2], 61, 1 Cyclobutanes, synthesis ... 

Other five-membered heterocyclic enones used in [2 + 2] photocycloadditions are 1//-pyrrole-2,3-diones86-88 and derivatives of maleic anhydride. Some cycloadducts of dimethylmaleic anhydride and unsaturated acid esters have been used as monomers for condensation polymers.89... 

Lithio-l-methoxycyclopropane can be generated by reductive lithiation of 1-methoxy-l-phenylsulfanylcyclopropane with lithium 1-dimethylaminonaphthalenide (Method A)146,147 or lithium 4,4 -di-f< r/-butylbiphenylide (Method B)148 in tetrahydrofuran at — 78 °C. 1-Lithio-l-methoxycyclopropanc reacts with enones and enals to produce 1-methoxycyclo-propanemethanols, which rearrange to vinylcyclobutanones 1 using tetrafluoroboric acid in tetrahydrofuran (Method C) 146,147 or triflic anhydride in the presence of 2,6-di-f 77-butyl-4-methylpyridine in dichloromethane (Method D).148 The latter method avoids destruction of acid-sensitive products (Table 11). 

The addition of fluorine is successfully executed on various deactivated 7t-centers as well. Fluorine was used to prepare perfluorocyclopentadiene and its anion 6 for the first time by addition of fluorine to perchlorocyclopentadiene followed by total dechlorination.68 Fluorine undergoes addition to enones 7,65 including dioxine derivatives 9,69 chloroenone 1070 and even to the very deactivated double bond in maleic anhydride (11) forming difluorosuccinic acids.71... 

Dorofeenko and his coworkers have extended this route to the synthesis of a range of cyclic analogues of pyrylium salts. Thus, cyclohexenylacetophenone affords the reduced isobenzopyrylium salt (635) on treatment with acetic anhydride (67MI22402) and 2-(indol-2-yl)cyclohexanone yields the indolo[2,3-rf]pyrylium salt (636) in the same way (69ZOB716). The yields in these reactions are much improved, a feature which may be attributable to the conformational preference for the structure shown for the enone rather than a conjugated arrangement of double bonds. 

The reaction between acetophenone and acetic anhydride alone yields 2-methyl-4,6-diphenylpyrylium (23CB1012). It seems possible that a 1,3-diketone is formed by the acetylation of acetophenone (540R(8)59), which subsequently reacts with unchanged ketone. Alternatively, an intermediate enone derived from the condensation of two moles of acetophenone (53JA626) may be acylated to the pyrylium salt. There is supporting evidence for both reaction schemes and it is not possible to discard either alternative (Scheme 255). 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

Friedel-Crafts acylation of alkenes.9 C2H5A1C12 is an effective catalyst for acylation of alkenes with acyl chlorides or anhydrides in CH2C12. The reaction proceeds in higher yield than that previously reported with other Lewis acid catalysts (such as ZnCl2). The reaction provides a useful route to /J,y-enones. 

J-ENONES Benzeneseleninic anhydride. I LAVANONES Thallium(IU) nitrate. IIYDROARENES Manganese dioxide. INDOLES Bcn/rncsclcninic anhydride. KETONES lodylhenzcne LACTONES Benzene,soloninic anhydride. 

A regioselective and highly syn-stereoselective catalyst-free intermolecular alkylation of aryl borates with aryl epoxides under mild, neutral conditions has been reported.27 The reaction of /ra .s-stilbene oxide with tri(3,5-dimethylphenyl)borate gave a 38% yield (>95% syn) of the C-alkylated product (13), easily separated from (g) the O-alkylated product(s). Triflic anhydride has been used to activate enones to nucleophilic attack by electron-rich arenes in the presence of a sterically hindered base.28 Resorcinol dimethyl ether, for example, reacted with cyclohex-2-en-l-one to... 

Triflic anhydride has been shown to activate enones (113) with an electron-rich aromatic pendant to undergo a Friedel-Crafts-like cyclization, affording the cyclic enol triflate (114).170... 

The norbelladine derivative 408, which served as the starting material for the synthesis of ( )-oxocrinine (415) (Scheme 35), may be readily prepared from the reductive animation of piperonal with tyramine followed by acylation with trifluoroacetic anhydride (191,192). When the N-acylated monophenol 408 was treated with excess thallium tris(trifluoroacetate) in methylene chloride, the di-enone 412 was obtained in 19% yield (191), whereas use of the oxidant vanadium oxyfluoride in trifluoroacetic acid/trifluoroacetic anhydride afforded 412 in 88% yield (192). Base-induced N-deacylation of 412 was accompanied by spontaneous cyclization to furnish racemic oxocrinine (415). Attempts to oxidize the free amine derived from 408 led to the formation of a number of products, some of which resulted from oxidation at nitrogen. 

Because the catalyst is usually prepared by the polymerization of amino acid N-carboxy anhydrides, induced by water or amines [66, 67], the Julia-Colonna epox-idation was soon recognized as a reaction of great practical value. In the course of exploration of the scope of the Julia-Colonna procedure many enone substrates were successfully epoxidized by use of the original three-phase conditions (Table 10.8). 

Electroreduction of conjugated enone systems is a possible route for carotenoid synthesis. The electroreduction of astaeene 88 gives 90 after passage of 2 F/mol of electricity in a CHjClj—Bu4NBF4—(Hg) system in the presence of acetic anhydride. Similar electrolysis of 88 in a C Clj/MeCN—LiC104 system (4 F/mol of electricity) provides 89 in 25% yield (Scheme 3-33)80). 

Dehydrogenation of enones. Tl(OAc)3 can be as effective as DDQ or benzene-selenenic anhydride for dehydrogenation of a, 3-enones to 1,4-dienones. However, in some cases the reaction involves dehydrogenation, acetylation, and aromatization to catechols, as in the oxidation of 1 to 2. 

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