Thioesters acrylates

The mechanism of these reactions was proposed to take place by initial electron transfer to the carbonyl group of the thioester, generating a ketyl-like radical anion such as 103 (Scheme 7.43). Subsequent radical addition to the electron-deficient alkene (acrylamide or acrylate), possibly guided by pre-complexation to a Sm(III) metal ion, generates a new radical centre, which is reduced to the corresponding Sm(III) enolate by a second equivalent of Sml2. Protonation of this enolate and hydrolysis of the hemithioacetal upon work-up then lead to the y-ketoamide or ester. 

Regioselective acylations of polyhydroxylated compounds such as carbohydrates, glycerols, steroids, or alkaloids have been carried out with lipases, esterases, and proteases [13, 20]. One example is the Candida antartica lipase (immobilized on acrylic resin) catalyzed monoacylation of the signalling steroid ectysone (1) giving selectively the 2-C)-acetate 2 (eq. (1)). Using vinyl acetate for this transesterification the reaction was irreversibly pushed to the product side, since the liberated enol instantaneously isomerizes to acetaldehyde [21]. The sometimes unfavorable aldehyde is avoided when 1-ethoxyvinyl acetates [22], trichloro- or -fluoroethyl esters [23 a, b], oxime esters [23 c] or thioesters [23 d] are employed for the quasi-irreversible reaction courses. 

Hydrocarbonylation of alkynes. 2-Substituted acrylic thioesters are obtained from 1-alkynes under CO in the presence of the Pt complex and thiols, in contrast to the generation of the regioisomeric products when using (Ph3P)jRhH(CO). The Pt-catalyzed reaction on 5-hydroxy-l-pentyne yields a-thiomethyl-8-lactones. ... 

In a similar study by Dixon [19], acrylic esters, thioesters, and N-acryloyl pyrrole were also identified as effective acceptors in the Michael addition with [3-ketoesters catalyzed by 64b. Enantiomeric excesses of up to 98% and yields of up to 96% were reported (Scheme 9.22). 

Abeles and co-workers extended the work of Buckel on the properties and mechanism of the reductive dehydration of lactate to propionate in C. propionicum (234, 235). Studies by Abeles concluded that acrylate is indeed an intermediate in lactate dehydration, based on the observation of a primary kinetic isotope effect of 1.8 on the conversion of [3- H3]lactate to propionate, indicating that -hydrogen abstraction is at least partially rate limiting. The true substrates for the reaction were determined to be the CoA thioesters of lactate and acrylate, hence the enzyme has been aptly named lactyl-CoA dehydratase (234). The reaction was found to be mediated by two proteins, El and E2, and like the (R)-2-hydroxyglutarate-dehydrating enzyme from A. fermentans, both El and E2 from... 

Neither El nor E2, together or alone, mediated the formation of acrylyl- or lactyl-CoA from the respective acid plus CoA and acetyl phosphate or acetyl-CoA. However, a CoA transferase that catalyzes the formation of the CoA thioesters of lactate, acrylate, and propionate from acetyl-CoA has been isolated from C. propionicum (233). It is curious that acrylyl-CoA could not be isolated as a product with the crude or purified enzyme system, although acrylyl-CoA is readily converted to lactyl-CoA in the purified system. Abeles suggested that perhaps acrylyl-CoA exists as an enzyme-bound intermediate that requires the presence of a reductase for release as propionate. In this manner the organism is protected from buildup of toxic amounts of any acrylyl intermediates, which are known to undergo Michael addition reactions with biological nucleophiles. 

As mentioned above, although some examples of intramolecular MBH reactions have been reported in the literature, this aspect is still in its infancy. Most known reports are based on the cyclizations of combinations of enone-enone, enone-acrylate, enone-aldehyde, unsaturated thioester-aldehyde, enone-allylic carbonate frameworks, etc. More recently, Krafft et al. have developed a novel, entirely organo-mediated intramolecular MBH reaction by using allyl chloride 277 as an alternative electrophile to afford densely functionalized cyclic enones 278. This reaction tolerates modification of the enone and the use of primary and secondary allylic chlorides and generates both five-and six-membered rings in excellent yields. Both mono- and disubstituted alkenes are formed with excellent selectivity in the absence of a transition metal catalyst (Scheme 1.100). ... 

Diunsubstituted coumarins are available from the palladium(II)-catalyzed intermolecular annulation reaction of phenols with methyl acrylate (13AGE12669) and from an organocatalytic cascade reaction of salicylalde-hydes with malonic acid half-thioesters mediated by a combination of ben-zylamine and triethylamine (Scheme 60) (13EJ04499). 

Acrylic esters, thioesters and A-acryloyl pyrrole have been identified by Dixon and Rigby as elfective electrophiles in the enantioselective Michael addition reaction with p-keto esters catalysed by a cinchona alkaloid bearing a bulky phenanthrene group (Scheme 1.27). High yields combined with excellent enantioselectivities of up to 96% ee were obtained in almost all cases of substrates. 

Scheme 1.27 Michael additions of P-keto esters to acrylic esters, thioesters and N-acryloyl pyrrole catalysed by cinchona alkaloid.

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