P,y-Unsaturated acetals

P,Y Unsaturated acetals Reaction of ethyl diazoacetate with dimethyl acetals of a,p-unsaturated aldehydes catalyzed by BF3 etherate gives as the main product acetals of p,y-unsaturated aldehydes by a carbon-carbon insertion. A similar reaction with ketals gives a complex mixture. The reaction is less selective with diethyl acetals. 

The titanium(IV) chloride-promoted reactions of enol silyl ethers with aldehydes, ketones, and acetals, known as Mukaiyama reaction, are useful as aldol type reactions which proceed under acidic conditions (eq (23)) [20], Enol silyl ethers also undergo the Michael type reactions with enones or p.y-unsaturated acetals (eq (24)) [21]. Under similar reaction conditions, enol silyl ethers are alkylated with reactive alkyl halides such as tertiary halides or chloromethyl sulfides (eq (25)) [22], and acylated with acid halides to give 1,3-diketones (eq (26)) [23]. 

Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a, (3-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol 333 . The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a p,y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopen-tene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place 334 ). 

The benzotriazolyl derivative of acrolein acetal, compound 882, is lithiated, treated with chlorodiphenylphosphine, and the obtained intermediate is oxidized with hydrogen peroxide to phosphine oxide 883 (Scheme 145). The relatively acidic proton in derivative 883 is easily removed by a base, and the obtained anion adds to a carbonyl group of aldehyde or ketone. Subsequent rearrangement and elimination of the phosphorane group generates diene 884. For the derivatives of aldehydes (884, R2 = H), (E)-(E) stereoselectivity of the elimination is observed. Acidic alcoholysis of dienes 884 affords esters of P,y-unsaturated carboxylic acids 885 < 1997JOC4131>. 

In the Pd-catalyzed cross-coupling reactions of acylzirconocene chlorides with allylic halides and/or acetates (Section 5.4.4.4), the isolation of the expected p,y-unsaturated ketone is hampered by the formation of the a, P-un saturated ketone, which arises from isomerization of the p,y-double bond. This undesirable formation of the unsaturated ketone can be avoided by the use of a Cu(I) catalyst instead of a Pd catalyst [35], Most Cu(I) salts, with the exception of CuBr - SMe2, can be used as efficient catalysts Thus the reactions of acylzirconocene chlorides with allyl compounds (Table 5 8 and Scheme 5 30) or propargyl halides (Table 5.9) in the presence of a catalytic amount (10 mol%) of Cu(I) in DMF or THF are completed within 1 h at 0°C to give ffie acyl--allyl or acyl-allenyl coupled products, respectively, in good yields. ill... 

The synthesis of compounds 39, 41, and 43 by the ODPM rearrangement opens a novel photochemical route to chrysanthemic acid and other cyclopropane carboxylic acids present in pyrethrins and pyrethroids [52]. In fact, aldehyde 43 can be transformed to tran -chrysanthemic acid by simple oxidation. This new synthetic route to ecologically benign insecticides competes with the one previously described by us using the 1-ADPM rearrangement of p,y-unsaturated oxime acetates [30,53]. 

Steric and electronic effects on the photochemical reactivity of oxime acetates of p/y-unsaturated aldehydes. Journal of the Chemical Society, Perkin Transactions 1, 163-169 (b) Armesto, D., Horspool, W.M., Mancheno, M.J., and Ortiz, M.J. (1990) The aza-di-jt-methane rearrangement of stable derivatives of 2,2-dimethyl-4,4-diphenylbut-3-enal. Journal of the Chemical Society, Perkin Transactions... 

Carbonylation of allylic acetates. This reaction is effected by catalysis with this and a few other Pd(0) complexes, but requires bromide ion as a cocatalyst. It provides a route to (E)-p,y-unsaturated esters in generally high yield from primary allylic acetates. 

Reductive decarboxylation. The reaction of y-carbamoyloxy-a.p-unsaturated esters with a lithium dialkyl cuprate (10 equiv.) in cther-HMPT results in loss of CO, and formation of a p,y-unsaturated ester. Zinc-acetic acid has been used for this reaction," but yields are lower. 

Not surprisingly, if the ketone in the starting material is flanked by an unsaturated functional group i.e. C02Me or NO ), dehydration gives exclusively the a,P-unsaturated product (the p,y-unsaturated regioisomer is available via other methods, discussed below). While the methods described above involve direct dehydration of the alcohol, a number of reduction-dehydration sequences have been conducted by initial reduction of the ketone and subsequent derivatization of the resultant alcohol (as the phenyl methanesulfonate, methyl p-toluenesulfonate, xanthate, acetate, methyl ether, etc.). This type of reduction-dehydration sequence is discussed in detail in Volume 6, Chapter 5.1. 

An important application of the Reformatsky reaction is the conversion of P-hydroxy esters to a, P-unsaturated esters. Acid-catalyzed dehydration usually leads to a mixture of a, P- and P, y-unsaturated esters. However, conversion of the initially formed p-hydroxy esters to their corresponding acetates by treatment with acetyl chloride, followed by base-catalyzed dehydration with NaOEt, produces conjugated esters in high purity. This sequence of reactions provides an alternative route to the Homer-Wads worth-Emmons olefmation of ketones (see Chapter 8). 

Allylic ethers of cyanohydrins are easily prepared through phase transfer allylation. Deprotonation of these ethers with LDA in THF at -78 °C effects 2,3-rearrangement to transient p. y-unsaturated ketone cyanohydrins, which are transformed during work-up to the ketones (Table 16). In an extension of this work, the mixed acetal cyanohydrin ethers (187), prepared by mild acid treatment of the cyanohydrins with 2-methoxy-1,3-butadiene or 1-f-butoxyallene, rearranged to the keto enol ethers (189 equation 40). Hydrolysis of the enol ethers (189) leads to 1,4-dicarbonyl compounds, which can be cyclized to cyclopentenones. 

Taylor, E.C., and Davies, H.M.L., Rhodium(II) acetate-catalyzed reaction of ethyl 2-diazo-3-oxopent-4-enoates. Simple routes to 4-aryl-2-hydroxy-l-naphthoates and P,Y-unsaturated esters. The dianion of ethyl 4-(diethylphosphono)acetoacetate as a propionate homoenolate equivalenfi Tetrahedron Lett., 24, 5453, 1983. 

The success of the Claisen-Cope rearrangement need not be limited to the production of aldehydes via enol ethers. Allylic alcohol (58) is successively transposed into a mixture of allylic isomers (59 Scheme 4), and is subjected to an orfhoester Claisen rearrangement at 150 C to provide ester (61). The moderate temperature of the Claisen step permits the isolation of an intermediate (c/. Scheme 3) prior to the final Cope rearrangement (195 C) to p, y-unsaturated esters (60). The esters (W) are a 55 45 mixture of ( )- and (Z)-double bond isomers owing to the near equal steric bulk of the methyl and acetic acid residues in Ae transition state for the Cope rearrangement. ... 

Related condensations involving the replacement of the anhydride component with succinic acid (Fit-tig synthesis)27 or with malonic acid (Knoevenagel condensation, see Volume 2, Chapter 1.11) provide complementary preparative methods which are useful for both aromatic and aliphatic systems. The Fittig extension of the Peikin transformation involves heating an aliphatic or aromatic aldehyde with sodium succinate and acetic anhydride to give the condensation products (17), which lose carbon dioxide to afford p.y-unsaturated carboxylic acids (18), accompanied by small amounts of the corresponding y-buty-rolactones (19 Scheme 7).27... 

Fittig (Fittig synthesis) discovered that aromatic and aliphatic aldehydes (i.e., 1) react readily with sodium succinate 23 and acetic anhydride at 100 °C, to give y-phenyl and y-alkyl paraconic acid (i.e., 24) in satisfactory yield. The acid loses carbon dioxide upon heating to form a p,y-unsaturated acid 25.2... 

Oxidation of p,y-unsaturated acids. Either butenolides or degraded allylic acetates are formed. 

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