Ketones, conjugated from vinyl ethers

There are a wide variety of synthetic applications of this chemistry, making it one of the most powerful reactions in organic chemistry (sec. 10.5.B.vi). An example is the Birch reduction of the methoxybenzene portion of 514, which gave 515.Subsequent treatment with methanolic HCl converted the vinyl ether moiety in 515 to the ketone unit (via the enol) found in 516. Note that Birch reduction formed a trans ring juncture in 515 from the conjugated C=C unit in 514. Initial hydrolysis of 515 led to a nonconjugated ketone, but under the acidic conditions the conjugated systems found in 516 was formed. However, it is... 

Acetylketene [4 + 2] cycloaddition with vinyl n-butyl ether gave the useful dihydropyranone intermediate (32), from which various 2,6-dideoxy monosaccharides were obtained. The key steps in synthesis of racemic butyl olivoside (34) consisted of stereoselective 1,2-reduction of conjugated ketone with diisobutylaluminum hydride, followed by standard hyrobora-tion/oxidation procedure (Scheme 3) [53]. 

Organocuprates are generated from an organolithium reagent (see Chapter 15, Section 15.5) and a cuprous salt such as Cul (cuprous iodide). When two equivalents of n.-butyllithium are mixed with Cul in ether at -10°C, the product is lithium dibutylcuprate, 52. When 52 reacts with a conjugated ketone such as methyl vinyl ketone (10), the product is enolate anion 53, which gives 54... 

Acetal Condensations. The acid-catalyzed condensation of ethyl vinyl ether with acetals derived from a,p-unsaturated aldehydes and ketones is an excellent method to lengthen a carbon chain by two carbon atoms, particularly of polyenals. In an industrial process for the manufacture of the Cie aldehyde (eq 13), the C14 acetal is reacted with ethyl vinyl ether in the presence of Zinc Chloride to give an alkoxy acetal, which, without isolation, is then hydrolyzed with moist acetic acid. Longer conjugated carotenals have been synthesized by this method, and montmo-rillonite K-10 clay (see MontmoriUonite KIO) has been reported to be an excellent replacement for the Lewis acids normally used in the condensation. ... 

Conjugate addition reactions, including the Robinson annulation, which make use of reactive Michael acceptors such as methyl vinyl ketone, can suffer from low yields of the desired adduct. The basic conditions required for enolate formation can cause polymerization of the vinyl ketone. Further difficulties arise from the fact that the Michael adduct 42 and the original cyclohexanone have similar acidities and reactivities, such that competitive reaction of the product with the vinyl ketone can ensue. These problems can be minimized by the use of acidic conditions. Sulfuric acid is known to promote the conjugate addition and intramolecular aldol reaction of 2-methylcyclohexanone and methyl vinyl ketone in 55% yield. Alternatively, a silyl enol ether can be prepared from the ketone and treated with methyl vinyl ketone in the presence of a Lewis acid such as a lanthanide triflate" or boron tri fluoride etherate (BF3 OEt2) and a proton source to effect the conjugate addition (followed by base-promoted aldol closure). 

Disubstituted vinyl silanes are epoxidized in high ee s and enantiomerically enriched 1,1-disubstituted epoxides can be obtained via the desilylation of these epoxides e.g., 18). Allylic alcohols and conjugated dienes and enynes are effective substrates (e.g. 19 and 20). ° The epoxidations of enol ethers and enol esters were also studied. The resulting epoxides (e.g., 21) from enol esters can undergo stereoselective rearrangement to give optically active a-acyloxy ketones, (5)-22 or (i )-23, under different acidic conditions. 

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