Half-thioesters

Dicarbonyl donors bearing a thioester has been applied in the Mannich reaction to A -tosyl imines. Ricci presented an enantioselective decarboxylative addition of malonic half thioester 37 to imine 38. In the Mannich-type addition, catalyst 36 deprotonates the malonic acid thioester followed by decarboxylation to generate a stabilized thioacetate enolate. This stabilized anion reacts with facial selectivity to the imine due to steric-tuning from 36 [47] (Scheme 8). 

A new thioester aldol reaction which uses a half-thioester (PhS0C- CHMe-C02H) of methylmalonic acid and a copper-bis(oxazoline) catalyst is highly enantio- and diastereo-selective, while also being mild and tolerant of protic functional groups and enolizable aldehydes.136... 

The reactions use thiol esters rather than ordinary esters. The esterifying group is a thiol called coenzyme A, and we shall just represent this molecule as R (you can find its full structure on p. 1386). The first reaction is between a malonate half-thioester and an acetate thioester of coenzyme A Look at the mechanism and you will see how similar it is to the Claisen ester condensation. 

Ricci, Pettersen, and coworkers reported that P-isocupreidine (P-ICD) derived from quinidine (69,20 mol%) promotes the enantioselective decarboxylative addition of the malonic half thioesters 70 to the imines 71 to afford the protected P-amino thioesters 72, which act as precursors for the preparation of P-amino acids [32] (Scheme 8.23). However, only low to moderate ee values (4—79% ee) were obtained. 

The epi-quinine urea 81b was also found by Wennemers to promote an asymmetric decarboxylation/Michael addition between thioester 143 and 124 to afford the product 144 in good yield and high enantioselectivity (up to 90% ee) (Scheme 9.49). Here, malonic acid half-thioesters serve as a thioester enolate (i.e., enolate Michael donors). This reaction mimics the polyketide synthase-catalyzed decarboxylative acylation reactions of CoA-bound malonic acid half-thiesters in the biosynthesis of fatty adds and polyketides. The authors suggested, analogously with the enzyme system, that the urea moiety is responsible for activating the deprotonated malonic add half-thioesters that, upon decarboxylation, read with the nitroolefin electrophile simultaneously activated by the protonated quinuclidine moiety (Figure 9.5) [42]. 

Scheme 4.11 Enantioselective Michael addition of malonic acid half-thioesters to nitroalkenes catalyzed by 70b.

Fortner, K. C., Shair, M. D. (2007). Stereoelectronic Effects Dictate Mechanistic Dichotomy between Cu(II)-Catalyzed and Enzyme-Catalyzed Reactions of Malonic Acid Half Thioesters. Journal of the American Chemical Society, 129, 1032-1033. 

Some interesting applications of the conjugate addition of malonates to nitroolefins are the stereoselective synthesis of the antispastic agent (/ )-Baclofen [238b], and the antidepressant drug (/ )-rolipram, the latter obtained via highly stereoselective conjugate addition of a malonic acid half-thioester to a nitrostyrene derivative catalyzed by urea 154 [242],... 

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). 

Malonic acid half thioesters, H02C-CH(R )-C0-SR (R =H/Me), undergo an enantioselective decarboxylative aldol reaction with aldehydes, using a chiral catalyst bearing a hydrogen-bond donor and acceptor. In situ ESI-MS evidence supports a complex between the conjugate base of the substrate and the conjugate acid of the... 

Song and coworkers compared the squaramide 31 with the sulfonamide 28 and the related C9 thiourea derivative as catalyst for the conjugate addition of 1,3-dicarbonyls to [i-nitroalkenes in brine [89] and the conjugate addition of malonic acid half thioester to various nitro alkenes [90]. In the latter reaction (Scheme 6.41), 31 afforded the best results with respect to enantioselectivity that is, the ee was 93% for 31 but only 63% for thiourea and 23% for the sulfonamide analog. 

Hajos-Parrish-Eder-Sauer-Wiechert reaction 51,1373,1374 half-thioesters 263... 

Fortner KC, Shair MD. Stereoelectronic effects dictate mechanistic dichotomy between Cu(II)-catalyzed and enzyme-catalyzed reactions of malonic acid half thioesters. J.Am. Chem. Soc. 2007 129 1032-1033. 

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