Oxidation of p, y-unsaturated esters

For internal olefins, the Wacker oxidation is sometimes surprisingly regioselective. By using aqueous dioxane or THF, oxidation of P,y-unsaturated esters can be achieved selectively to generate y-keto-esters (Eq. 3.18).86 Under appropriate conditions, Wacker oxidation can be used very efficiently in transforming an olefin to a carbonyl compound. Thus, olefins become masked ketones. An example is its application in the synthesis of (+)-19-nortestosterone (3.11) carried out by Tsuji (Scheme 3.5).87... 

It is well known that n -allylpalladium complexes (86) are easily formed by the reaction of PdCh widi l. y-unsaturated esters or ketones (85). An attempted oxidation of p.y-unsaturated esters and ketones with the PdCl2/CuCl/02 catalyst system in aqueous DMF led to tr-allylpalladium complex formation as the main reaction, and the oxidation of the alkenic bond was hardly observed to a significant extent However, in aqueous dioxane or THF, the oxidation became the main reaction, giving y-keto esters and 1,4-diketones (87), respectively, with high regioselectivity (Scheme 26).Some results are shown in Table 2. In all cases, no 3-keto ester or 1,3-diketone was detected. At the end of the reaction, formation of a considerable amount of the ir-allylpalladium complex (86) was observed. y-Keto esters and 1,4-diketones are useful intermediates for die preparation of cyclopentanedione and cyclopentenone, respectively, by base-catalyzed cyclization. Tliis legioselective oxidation provides a unique and efficient synthetic method for y-keto ester and 1,4-diketone synthesis. 

For internal olefins, the Wacker oxidation is regioselective. Thus, oxidation of P,y-unsaturated esters in aqueous dioxane or THF under appropriate condition gives y-ketoester (Scheme 19). ... 

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>. 

It is well known that ir-allylpalladium complexes (86) are easily formed by the reaction of PdCh with P. y-unsaturated esters or ketones (85). An attempted oxidation of. y-unsaturated esters and ketones with the PdCl2/CuCl/02 catalyst system in aqueous DMF led to ir-allylpalladium complex formation as the main reaction, and the oxidation of the alkenic bond was hardly observed to a significant extent. However, in aqueous dioxane or THF, the oxidation became the main reaction, giving y-keto esters and... 

The reaction conditions are important for the preparation of pure ( )-p,"y-unsaturated esters. No Z isomer is found in the product when the reaction mixture is oxidized with HjOj/OAc at 0 °C. However, when the reaction mixture is oxidized with HjOj/OAc at room temperature or H Oj/OH at 0 °C, a small amount of Z isomer is formed in the product. 

Indirect allylic oxidation of x,p-unsaturated esters.3 No satisfactory method is known for effecting this oxidation directly, but it can be accomplished indirectly in three steps from a /i.y-unsaturated ester. 

In an effort to make productive use of the undesired C-13 epimer, 100-/ , a process was developed to convert it into the desired isomer 100. To this end, reaction of the lactone enolate derived from 100-) with phenylselenenyl bromide produces an a-selenated lactone which can subsequently be converted to a,) -unsaturated lactone 148 through oxidative syn elimination (91 % overall yield). Interestingly, when 148 is treated sequentially with lithium bis(trimethylsilyl)amide and methanol, the double bond of the unsaturated lactone is shifted, the lactone ring is cleaved, and ) ,y-unsaturated methyl ester alcohol 149 is formed in 94% yield. In light of the constitution of compound 149, we were hopeful that a hydroxyl-directed hydrogenation52 of the trisubstituted double bond might proceed diastereoselectively in the desired direction In the event, however, hydrogenation of 149 in the presence of [Ir(COD)(py)P(Cy)3](PF6)53 produces an equimolar mixture of C-13 epimers in 80 % yield. Sequential methyl ester saponification and lactonization reactions then furnish a separable 1 1 mixture of lactones 100 and 100-) (72% overall yield from 149). 

Asymmetric aziridination of a,P-unsaturated esters by use of N-nitrenes was studied in great detail by Atkinson and co-workers [34, 35]. Here, lead tetraacetate-mediated oxidative addition of N-aminoquinazolone 30 (Scheme 3.10) to a-methy-lene-y-butyrolactone 32 was reported to proceed with complete asymmetric indue-... 

Differences in electrophysiological and contractile properties of mammalian cardiac tissues bathed in bicarbonate- and HEPES-buffered solutions, Acto Physiol. Scand.YT, 11-18, 2003 Mash, H.E., Chin, Y.P., Sigg, L. et al., Complexation of copper by zwitterionic aminosulfonic (good) buffers. Anal. Chem. 75, 671-677, 2003 Sokolowska, M. and Bal, W., Cu(ll) complexation by non-coordinating M2-hydroxyethylpiperazine-iV -ethanesulfonic acid (HEPES buffer), J. Inorg. Biochem. 99, 1653-1660, 2005 Zhao, G. and Chasteen, N.D., Oxidation of Good s buffers by hydrogen peroxide, Anal. Biochem. 349, 262-261, 2006 Hartman, R.F. and Rose, S.D., Kinetics and mechanism of the addition of nucleophiles to alpha,beta-unsaturated thiol esters, J. Org. Chem. 71, 6342-6350, 2006. 

The alkoxy radicals so formed are the precursors of a, P-unsaturated ketones, aldehydes, carboxylic acids and alcohols. Saturation reactions, Nor-rish type I reactions of ketonic compounds and oxidation of aldehydic species occur under irradiation. This finally leads to the formation of saturated carboxylic acids as the main oxidation products accompanied by esters, y-lactones, peresters, anhydrides, alcohols and ether bridges. 

The intermediate a-sulfenyl carbonyl compounds may be alkylated prior to oxidative elimination. Phe-nylsulfenylation of the cw-fused butyrolactone (61), followed by methylation and oxidative elimination, gave the a-methylenebutyroiactone (62) because endocyclic elimination is stericaliy inhibited (Scheme 6). For the tran -fused butyrolactone (63), the alkylation was carried out first to ensure exocyclic elimination (Scheme 1). The intermediate a-sulfinylcarbonyl compounds may also be modified before elimination, the alkylation of keto sulfoxides (64) providing a useful synthesis of a,p-unsaturated -y-keto esters (65 Scheme In some cases the use of an excess of strong base provides a dimetaliated... 

The electrophile E+ can be an alkyl halide or sulfate, an aldehyde to give aldol products, or an a,P-unsatunited ester when conjugate addition is preferred. Examples from simple alkylation show that the alkyl halide can be primary alkyl, allylic 33, and even an a-bromoester or y-bromo-a,P-unsaturated ester 31. The original carbonyl compound that forms the chiral imine with SAMP or RAMP can be an aldehyde 27 or 29, a ketone (symmetrical 32 or blocked on one side 35), or an enone. Only the reagents and products are shown with oxidative [O] or hydrolytic [H20] workup. Notice that SAMP is used for the formation of either enantiomer of 28 by using different starting materials but that RAMP is used to enter the other enantiomeric series from 32. 

BINAPO (the bis-oxide of BINAP) can complex samarium and gives some stereocontrol in the formation of y-butyrolactones by reaction of ketones with a,p-unsaturated esters and Sml2 in THR Enantiomeric excesses (ee s) of up to 90% were obtained [106]. 

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