Esters, conjugated, isomerization

The phosphitylation of a ketone through its enol form leads to the phosphorus(III) esters carrying a conjugated unsaturated carbonyl moiety their isomerization to the phosphonic diesters 603 (R = EtO) occurs reasonably readily, but other compounds in which, for example, R2P = (Pr 0)(Et2N)P, isomerize with greater difficulty, during distillation, or during an extended period at room temperature ". Other phosphite esters, 604, isomerize when heated at 160 or in the presence of a trace of metallic sodium at the same tem-perature. The formation of dialkyl (4-oxopentyl)phosphonates by similar means has also been reported. ... 

With a 16,17-dihalide, the initial product would be expected to be the A -olefin, which in the presence of alkali isomerizes to the conjugated ester. 

The addition of secondary amines to acetylenes is most applicable to the synthesis of conjugated acyclic enamines (50,171,172). Particularly the addition to acetylenic esters and sulfones has been investigated (173-177) and it appears that an initial trans addition is followed by isomerization to more stable products where the amine and functional group are in a trans orientation (178). Enamines have also been obtained by addition of secondary amines to allenes (179). 

Conjugated dienes can be epoxidized to provide vinylepoxides. Cyclic substrates react with Katsuki s catalyst to give vinylepoxides with high ees and moderate yields [17], whereas Jacobsen s catalyst gives good yields but moderate enantiose-lectivities [18]. Acyclic substrates were found to isomerize upon epoxidation (Z, )-conjugated dienes reacted selectively at the (Z)-alkene to give trans-vinylepoxides (Scheme 9.4a) [19]. This feature was utilized in the formal synthesis of leuko-triene A4 methyl ester (Scheme 9.4b) [19]. 

Several examples of conjugate addition of carbanions carried out under aprotic conditions are given in Scheme 2.24. The reactions are typically quenched by addition of a proton source to neutralize the enolate. It is also possible to trap the adduct by silylation or, as we will see in Section 2.6.2, to carry out a tandem alkylation. Lithium enolates preformed by reaction with LDA in THF react with enones to give 1,4-diketones (Entries 1 and 2). Entries 3 and 4 involve addition of ester enolates to enones. The reaction in Entry 3 gives the 1,2-addition product at —78°C but isomerizes to the 1,4-product at 25° C. Esters of 1,5-dicarboxylic acids are obtained by addition of ester enolates to a,(3-unsaturated esters (Entry 5). Entries 6 to 8 show cases of... 

Scheme 6.17 gives some examples of the orthoamide and imidate versions of the Claisen rearrangement. Entry 1 applied the reaction in the synthesis of a portion of the alkaloid tabersonine. The reaction in Entry 2 was used in an enantiospecific synthesis of pravastatin, one of a family of drugs used to lower cholesterol levels. The product from the reaction in Entry 3 was used in a synthesis of a portion of the antibiotic rampamycin. Entries 4 and 5 were used in the synthesis of polycyclic natural products. Note that the reaction in Entry 4 also leads to isomerization of the double bond into conjugation with the ester group. Entries 1 to 5 all involve cyclic reactants, and the concerted TS ensures that the substituent is introduced syn to the original hydroxy substituent. 

In the present case, the proportion of A2-isomer in the original dehydration mixture may be estimated to be 42% of the total unsaturated esters, while an equilibrium mixture contains about 67% of the conjugated compound.3 Thus, the amount of conjugated isomer in the mixture may be considerably increased by base-catalyzed isomerization of the unsaturated esters. For other unsaturated esters, both the composition of the dehydration mixture3 7 and the equilibrium ratio of tile two isomers 3 x vary, depending on the position and... 

The isomerization of the double bonds conjugated with the ester moiety to enol ethers can be carried out using RuCl(H)(CO)(PPh3)3 as catalyst (Scheme 42).69... 

Starting from 2,4,6-octatriene and pivaldehyde, the conjugated homoallylic alcohol 8 is obtained as the sole product. Cycloheptatriene-derived complexes react with aldehydes and C02 to afford mixtures of the isomeric 1,3- and 1,4-cycloheptadienyl carbinols or acids, respectively. Interestingly, analogous reactions with methyl chloroformate or dimethyl carbamoyl chloride produce the conjugated dienyl ester 9 or amide 10 as unique products [19,20]. 

Carbonylation of 4-en-2-ynyl carbonates offers a novel synthetic method for cross-conjugated 4-oxo-5-alkylidene-2-cyclopentenecarboxylates (Scheme 16.35) [38]. The primary product of the process appears to be a 2-vinyl-2,3-dienyl ester, leading to a palladacycle, which in turn follows CO insertion into the Pd-sp2 carbon, reductive elimination of Pd(0) species and isomerization, leading to the final product. 

Other functional groups tolerated in these isomerizations are ethers [65], alcohols [38, 66-69], propargylic trifluoromethyl groups [70], conjugated enones such as 36 [71] and esters [72] (Scheme 1.14). 

Whereas the Markovnikov addition of carboxylic acids to propargylic alcohols produces P-ketoesters, resulting from intramolecular transesterification [30, 31], the addition to propargylic alcohols in the presence of Ru(methallyl)2(dppe) 1 at 65 °C leads to hydroxylated alk-l-en-l-yl esters via formation of a hydroxy vinylidene intermediate [32, 33]. The stereoselectivities are lo ver than those obtained from non-hydroxylated substrates. These esters, which are protected forms of aldehydes, can easily be cleaved under thermal or acidic conditions to give conjugated enals, corresponding to the formal isomerization products of the starting alcohols (Scheme 10.6). 

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