Thiazolium salts esters

The conjugate addition of carbonyl anions catalysed by thiazolium salts (via umpol-ung) that is fully operative under neutral aqueous conditions has been accomplished. The combination of a-keto carboxylates (157) and thiazolium-derived zwitterions (e.g. 160) in a buffered protic environment (pH 7.2) generates reactive carbonyl anions that readily undergo conjugate additions to substituted o /3-unsaturated 2-acylimidazoles (158) to produce (159). The scope of the reaction has been examined and found to accommodate various a-keto carboxylates and /3-aryl-substituted unsaturated 2-acylimidazoles. The optimum precatalyst for this process is the commercially available thiazolium salt (160), a simple analogue of thiamine diphosphate. In this process, no benzoin products from carbonyl anion dimerization were observed. The resulting 1,4-dicarbonyl compounds (159) can be efficiently converted into esters and amides by way of activation of the A-methylimidazole ring via alkylation.181... 

The broad scope of the catalytic generation of activated carboxylates was demonstrated by Bode et al. in the diastereoselective synthesis of / -hydroxy esters 79 from a,/ -epoxy aldehydes 80 employing achiral thiazolium salts 81 as precatalysts (Scheme 9.24) [67]. The incorporation of a reducible functionality into the aldehyde substrate is the premise for a catalyst-induced intramolecular redox reaction generating the activated carboxylate 82. 

In the early 1970s Stetter and co-workers succeeded in transferring the concept of the thiazolium catalyzed nucleophilic acylation to the substrate class of Michael acceptors (Stetter 1976 Stetter and Schreck-enberg 1973). Since then, the catalytic 1,4-addition of aldehydes 6 to an acceptor bearing an activated double bond 131 carries his name. The Stetter reaction enables a new catalytic pathway for the synthesis of 1,4-bifunctional molecules 132, such as 1,4-diketones, 4-ketoesters and 4-ketonitriles (Stetter and Kuhlmann 1991 for a short review, see Christmann 2005). The reaction can be catalyzed by a broad range of thiazolium salts. Stetter and co-workers found the benzyl-substituted thiazolium salt 86a to give the best results for the addition of aliphatic aldehydes, whereas 86b and 86c were chosen for the addition of aromatic aldehydes. Any one of these three was found to be suitable for additions with heterocyclic aldehydes. Salt 86d was utilized with a, )-unsaturated esters (Fig. 15). 

The thiazolium-catalyzed addition of an aldehyde-derived acyl anion with a Michael acceptor (Stetter reaction) is a well-known synthetic tool leading to the synthesis of highly funtionalized products. Recent developments in this area include the thiazolylalanine-derived catalyst 191 for asymmetric intramolecular Stetter reaction of a,P-unsaturated esters <05CC195>. However, these cyclizations proceed only in moderate enantioselectivities and yields even under optimized conditions. Thiazolium salt 191 has been used successfully for enantioselective intermolecular aldehyde-imine cross coupling reactions <05JA1654>. Treatment of tosylamides 194 with aryl aldehydes in the presence of 15 mol% of 191 and 2... 

Addition of aldehydes to activated double bonds. Aldehydes add to a,j3-unsaturated ketones, esters, and nitriles in the presence of triethylamine and catalytic amounts of this salt. Other thiazolium salts are effective. 

Reactions of Thiazolium Salts. The thiazolium salt (45 R = benzyl, X = OH, Y = Cl) catalyses the addition of aldehydes to activated double-bonds, e.g. a/S-unsaturated acids, esters, and nitriles. A novel route to 4-alkyl-2H-l,4-thiazin-3-ones (46 R = alkyl or benzyl) involves the quaternization of 2-methylthiazole with RI, iodination with I2 and NEta, and treatment of the 2-(iodomethyl)thiazolium iodides with potassium hydroxide. ... 

Review. In the classical benzoin condensation cyanide ion is used as the catalyst. However, in the case of aliphatic aldehydes, thiazolium salts such as (1) and (2) are usually superior catalysts. The salts catalyze 1,4-addition of aldehydes to a,/3-unsaturated ketones, esters, and nitriles. 

The original benzoin condensation catalyzed by cyanide ion has been modified to use thiamin and a related thiazolium salt, diamine, or enzyme as a catalyst. In addition, the aldehyde group can be replaced by a bisulfite group or converted to silyl-ester to undergo the benzoin condensation. 

Novak et a 1. prepared the synthon (82 R = Me) by application of the thiazolium salt catalysed addition of the aldehyde (92) to methyl acrylate. The desired keto-ester (93) was obtained together with the dimer (94) of the starting aldehyde. The ester (93) was readily transformed into the eyelopentenone (82 R =Me)... 

In 1973, Stetter and Schreckenberg found that the reaction of aromatic aldehydes with a,(3-unsaturated nitriles or ketones gave y-oxo nitriles or y-diketones, respectively, in the presence of catalytic amounts of sodium cyanide. Later on, Stetter demonstrated that thiazolium salt could also be the catalyst for the addition of generated acyl anions to a,(3-unsaturated ketones, esters, and nitriles (Scheme 7.20). 

N-Substituted thioamides cyclocondense with (a-halogeno) carbonyl compounds to give N-substituted thiazolium salts 21, salts (or esters) of dithiocarbamic acid yield 2-sulfanylthiazoles 22, and thiourea affords 2-aminothiazoles 23 ... 

Alkynyltrialkylborates are versatile intermediates to 1,4-dikelones and y-oxo-esters, -nitriles, and -alkynes, as well as substituted ketones. A route from a -unsaturated cycloalkenones to 1,4-diketones is available wherein an aldehyde undergoes photoaddition to the alkene unit, and a variety of 1,4-diones is obtained by thiazolium salt-catalysed addition of aldehydes to but-2-enone. Monoacetalized 1,4-diketones and y-keto-aldehydes are formed on reaction of acyl chlorides with the Grignard reagents (13) and (14), respectively. 

Stetter and his co-workers have extended their investigations of the thiazolium salt-catalysed condensation of aldehydes with activated olefins cf. 1, 191) to include a synthesis of dioxo-esters (Scheme 31) ° Although yields are not always... 

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