A,p-Unsaturated thioesters

Certain CoA thioester using enzymes catalyze reactions at the fS-carbon or other carbons of the acyl group more distant from the thioester functionality. The fatty acid fi-oxidation cycle provides some examples (Fig. 3). Fatty acids 7 enter the cycle by initial conversion to the CoA ester 8, which is then oxidized to the a,P-unsaturated thioester 9 by a flavin-dependent enzyme. Addition of water to the double bond to form the fi-hydroxy thioester 10 is catalyzed by the enzyme crotonase, which is the centerpiece of the crotonase superfamily of enzymes that catalyze related reactions (37), which is followed by oxidation of the alcohol to form the fi-keto thioester 11. A retro-Claisen reaction catalyzed by thiolase forms acetyl-CoA 12 along with a new acyl-CoA 13 having a carbon chain two carbons shorter than in the initial or previous cycle. 

Yoshimatsu, M., Naito, M., Kawahigashi, M., Shimizu, H., Kataoka, T. Meyer-Schuster Rearrangement of y-Sulfur-Substituted Propargyl Alcohols A Convenient Synthesis of a,P-Unsaturated Thioesters. J. Org. Chem. 1995, 60,4798-4802. 

S Kobayashi, R Akiyama, M Moriwaki. Three-component or four-component coupling reactions leading to 8-lactams. Facile synthesis of y-acyl-8 lactams from silyl enolates, a,P-unsaturated thioesters, and imines or amines and aldehydes via tandem Michael-imino aldol reactions. Tetrahedron Lett 38 4819-4822, 1997. 

Fig. 19 Representative examples for the copper-NHC-catalysed ECB of acyclic p,p-disubstituted a,P-unsaturated thioesters by Hoveyda [111] (all reactions carried out at —50 °C for 18 h)...

Scheme 5 The ACA of MeMgBr to a,p-unsaturated thioesters in the synthesis of the deoxypropionate motif present in many natural products...

The procedure involves copper(I)-catalysed conjugate addition of MeMgBr to an a,p-unsaturated thioester 4, followed by reduction to the corresponding aldehyde and subsequent olefination to elongate the chain. This yields anew a,p-unsaturated thioester 6, which, in turn, can be subjected to the next catalytic reaction (Scheme 5). 

More recent studies have shown that the regioselectivity of alkyne thiocarbonylation depends on both the metal-ligand combination and the solvent with Pd(0 Ac)2/dppb in THF affording the linear a, P-unsaturated thioester 4 as the dominant product, whereas Pd(OAc)2/dppp in CH2CI2 was highly regioselective for the branched isomer S (Equation 10.3) [11]. 

Other catalytic applications of HBF4 include alkene isomerizations, alkylation of alcohols with diazoalkanes, preparations of substituted pyridines, hydrolysis of a-hydroxyketene or a-(methylthio)ketene thioacetals to a,p-unsaturated thioesters, and terpene formation from isoprenic precursors. ... 

Another enzyme that bears a close resemblance to bifunctional acid-base catalysts is enoyl-CoA hydratase (ECH). This enzyme is discussed here as an example of an enolate-stabilizing enzyme. The mechanism of ECH involves an enolate intermediate that is formed upon addition of a nucleophile, water molecule, to an a,p-unsaturated thioester. This reaction is the second step in the metabolic oxidation of fatty acids. The X-ray structures of enoyl hydratase enzymes complexed with various substrates analogs are available [29, 30]. A simplified view of the mechanism of ECH is presented in Scheme 6.14. The lifetime of the enolate intermediate is not... 

The method was extended to a,p-unsaturated thioesters [ 149]. The catalysts 137, 160 and 161 were employed in 10 mol% (Scheme 7.24) [150]. In this reaction some hydrogen chloride adduct was formed as byproduct or intermediate. 

Scheme 7.24 MBH reaction with a,p-unsaturated thioesters catalyzed by chalcogenides...

The latter carbonylation involves the formation of PtH(SR)(PPh3)2 by the oxidative addition of RSH to the zero-valent platinum complex. A possible pathway may include the CO insertion into the S-Pt bond of PtH(SR)(PPh3)2. Then, acylplatination of alkynes generates p-thiocarbonyl-substituted vinylplatinum intermediate, which undergoes reductive elimination to give the a,p-unsaturated thioesters with regeneration of the catalyst. 

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