P,y-unsaturated ester

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... 

Wolff rearrangement of a-diazoketones to give ketenes or subsequent products is an often used synthetic procedure the scope and limitations of which are well established 13 390), so that only a few new features of this reaction need to be considered here. Concerning its catalytic version, one knows that copper, rhodium and palladium catalysts tend to suppress the rearrangement390). A recent case to the contrary is provided by the Rh2(OAc)4-catalyzed decomposition of ethyl -2-diazo-3-oxopent-4-enoates 404 from which the p,y-unsaturated esters 405 are ultimately obtained via a Wolff rearrangement 236). The Z-5-aryl-2-diazo-3-oxopent-4-enoates undergo intramolecular insertion into an aromatic C—H bond instead (see Sect. 4.1). 

Claisen rearrangement. As for the mechanism, the reaction begins with intramolecular cyclopropanation the resulting bicyclo[2.1.0]pentan-2-one then undergoes fragmentation to a p,y-unsaturated ketene which finally is trapped by the added alcohol to afford a p,y-unsaturated ester (Scheme 41). The intermediates could be observed in selected cases. 

INAS reactions of carbonates of 3,5-dienyl alcohols (i. e., involving a conjugated diene moiety) [72] and 3,4-dienyl alcohols (i. e., having an allene moiety) [73] also proceed smoothly to furnish the corresponding (3,y-unsaturated esters. The reaction of 4-silyl- or 4-stannyl-3,4-dienyl carbonate having axial chirality proceeds with excellent chirality transfer, as exemplified in Eq. 9.39, thereby affording a novel access to optically active a-substituted p.y-unsaturated esters [73],... 

The efficient enantioselective alkylation of the P/y-unsaturated ester 39 was achieved1351 by use of the N-anthracenylmethyl catalyst 12 (R=benzyl, X=Br) together with CsOH-H20 under phase transfer conditions analogous to those in the alkylation of the O Donnell imine 23, as shown in Scheme 13. The enantioselectivity of the alkylation correlates with Hammett o constants, and the N,N-dimethylamino substituents in 39 showed the most effective enantioselectivity. The tight ion pair in which the enolate... 

P, y-Unsaturated esters (184) have been synthesized by a one-step electrochemical procedure from a-chloroesters (183) and aryl or vinyl halides (Scheme 73b) [294, 295]. This novel electroreductive cross-coupling method is based on the use of a Ni(II)(bpy) catalyst and a sacrificial aluminum anode in a one-compartment cell (Scheme 73). The whole cathodic process progresses at —1.2 V (SCE) (Scheme 73c),... 

In this case, however, double-bond migration is an advantage, because nonconjugated p,y-unsaturated esters are usually much more difficult to prepare than their a,p-unsaturated isomers. 

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. 

Deconjugation of a, fi-unsaturated esters (11, 297). This base is more effective than LDA/HMPT for isomerization of a,p-unsaturated esters to (Z)-p, y-unsaturated esters. The (Z)-selectivity is increased somewhat with increasing size of the ester group. Isobutyl esters are isomerized to (Z)-3-alkenoates almost exclusively (Z/E = 97 3). 

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... 

It is well known that ir-allylpalladium complexes (86) are easily formed by the reaction of PdCb 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 1,4-diketones (87), respectively, with high regioselectivity (Scheme 26).Some results are shown in Table 2. In all cases, no P-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 Ae preparation of cyclopentanedione and cyclopentenone, respectively, by base-catalyzed cyclization. Tliis regioselective oxidation provides a unique and efficient synthetic method for y-keto ester and 1,4-diketone synthesis. 

The phthalazide bis(cinchona) derivatives [(DHQD)2-PHAL] are the best ligands for the asymmetric dihydroxyla-tion of trans, 1,1-disubstituted, and trisubstituted alkenes, enol ethers, a,p-unsaturated ketones, and a,p- and p,y-unsaturated esters, whereas the DHQD-IND ligand turns out to be superior for c/j -alkenes (Table 1). The bis(cinchona) alkaloid-substituted pyrimidine ligand was found to be the best for monosubstituted terminal alkenes. The addition of Methanesulfonamide to enhance the rate of osmate(VI) ester hydrolysis is recommended for all nonterminal alkenes. 

In a similar manner, iminium salts derived from a, -unsaturated aldehydes and ketones are reduced by Hantzsch ester (Scheme 79). The ratio between the 1,4- and 1,2-reduction products depends upon the p/(a of the amine component. a-Keto-P,y-unsaturated esters are reduced by NAD(P)H models in the presence of Mg(Cl04)2- At room temperature 1 equiv. of the reducing agent effects 1,4-reduction of the... 

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). 

Under thermal activation conditions, ester 161 reacts with benzylamine to give a mixture of a-amino-p,y-unsaturated ester 164 and amide 165, but under 1.1 GPa pressure ester 161 gives the spiro-aziridines 162 and 163 in high yield and good diastereoselectivity. These are part of an attractive class of compounds that are formed by hetero-Michael addition of amine onto the unsaturated ester 161, followed by intramolecular nucleophilic substitution of the bromine atom (Scheme 7.41). ... 

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. ... 

Pete and coworkers [1000, 1001] have irradiated a,P-ethylenic esters of enantiopure alcohols, and the intermediate dienols that form are protonated either with AyV-dimethylethanol at -35°C in hexane [1001] or with i-PrOH or terf-BuOH [1000], The chiral auxiliaries are diacetoneglucose 1.48 or (S)-ethyl lactate 2.1 (R = Me, R = Et), or better yet the corresponding add (Figure 4.9). The cleavage of the chiral auxiliary is accomplished by treatment with PhCH20H/Ti(0/-Pr)4 or by mild hydrolysis. After the subsequent reaction with diazomethane, nonracemic benzyl or methyl a-alkylated-P.y-unsaturated esters are obtained with high enantiomeric excesses (Figure 4.9). 

Keto ester tosylhydrazones serve as a convenient source of a-functionalized p,y-unsaturated esters. Thus, the reaction of a variety of / -keto ester tosylhydrazones (containing five-, six- or seven-membered rings, i.e., n = 1-3) 122 with 3.1 equivalents of LDA in THF at — 78 °C, followed by warming to room temperature, yields a-lithio-/ ,y-unsaturated esters 125 (equation 72). When the reaction mixture of 125 was quenched with various electrophiles, a-functionalized / ,y-unsaturated esters 126 were available as shown in Table 660. 

P,y-Unsaturated esters. Ruden and Gaffney have prepared j3,7-unsaturated esters by a method based on the facile elimination of trimethylsUanol from 3-hydroxysilanes. Thus reaction of trimethylsilylacetone (1) with f-butyl lithioacetate (2) gives the hydroxy ester (3), which is converted into (4) by treatment with acid. 

Carboxylation. Homologation of allyUc halides to give P,y-unsaturated esters in a... 

Jechlorinated by j-PrMgCl, and the it.- -dienes. Treatment with CICOOR 1rd p.y-unsaturated esters. ... 

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