N-Thioacylation

The most suitable synthetic method for these products is the heterocyc-lization reaction of N-thioacyl derivatives of amino acids (202) with phosphorus tribromide (378, 442-450, 559, 560) or anhydrous trifluoroacetic acid (448, 449, 451, 452) (Scheme 103). Treatment of N-thioacyl amino acids with acetic anhydride leads directly to the thiazolylacetate without isolation of an intermediate thiazolinone (365. 452). 2-Alkoxy-derivatives of A-2-thiazoline-5-one, however, can be obtained without acetylation by this method (453, 454). 

Substituted 5-hydroxythiazoles (267b), Rj = alkylmercapto, acyl-amino, and sec-amino, are prepared by cydization of N-thioacyl-amino acids (266) with phosphorus tribromide or acetic anhydride (Scheme 137) (317, 350). i en the cydization of 266, R2 = H, is carried out with acetic anhydride in the presence of benzaldehyde (317, 325) or ethylformate (317), the benzylidene (268), R2=Ph, Rj = SR or CH2Ph, or 4-ethoxymethylene (268), Rj = SR and R2 = OEt, derivative is obtained directly (Scheme 138). 

The sialic acid aldolase-catalyzed condensation of D-mannose 8 and pyruvate led, in an excellent yield, to the synthesis of KDN 9 [33], a natural deaminated neuraminic acid first isolated from rainbow trout eggs [34] and then discovered in other species. The discovery that sialic acid aldolase accepts as substrates D-mannose substituted on the 2-position, even by bulky substituents such as phenyl, azido, or bromine, opened the route to novel unnatural sialic acid derivatives [35-39]. Pentoses also are substrates. N-Substituted neuraminic acids could be prepared either directly from the corresponding Af-substituted mannosamine, such as N-thioacyl derivatives [40], or after reduction and acylation of 5-azido-KDN [41]. Recently, AT-carbobenzyloxy-D-mannosamine was converted, in a good yield, into the N-carbobenzyloxy-neurarninic acid, further used as a precursor of a derivative of castanospermine [42]. 

R. Iseke and R. Brossmer, Synthesis of 5-N- and 9-N-thioacylated sialic acids, Tetrahedron 50 7445 (1994). 

Another catalytic application of chiral ketene enolates to [4 + 2]-type cydizations was the discovery of their use in the diastereoselective and enantioselective syntheses of disubstituted thiazinone. Nelson and coworkers described the cyclocondensations of acid chlorides and a-amido sulfones as effective surrogates for asymmetric Mannich addition reactions in the presence of catalytic system composed of O-TM S quinine lc or O-TMS quinidine Id (20mol%), LiC104, and DIPEA. These reactions provided chiral Mannich adducts masked as cis-4,5 -disubstituted thiazinone heterocycles S. It was noteworthy that the in situ formation of enolizable N-thioacyl imine electrophiles, which could be trapped by the nucleophilic ketene enolates, was crucial to the success of this reaction. As summarized in Table 10.2, the cinchona-catalyzed ketene-N-thioacyl-imine cycloadditions were generally effective for a variety of alkyl-substituted ketenes and aliphatic imine electrophiles (>95%ee, >95%cis trans) [12]. 

Asymmetric Cycloadditions Catalyzed by QumucM me Tertiary Amim 303 Table 10.2 Cinchona alkaloid catalyzed ketene-N-thioacyl imine [4 + 2] cycloadditions ... 

Thia-1-aza- N-Thioacylimines butadienes x = o,s Thioacyl isocyanates and N-Thioacyl dithioimidocaibonates... 

Fur die Synthese von 1,3-Thiazolen aus Halogenmethyl-Verbindungen sind als Eddukte in breitem MaBe N-Thiocarbonyl-carbamidin-Strukturen eingesetzt worden, wobei ein Amino-Rest als Abgangsgruppe dient. Aus N-Thioacyl-carbamidinen und a-Halogen-ketonen erhalt man 5-Acyl-l,3-thiazole ... 

Die Cyclisierungen lassen sich auch Basen-katalysiert, thermisch (in der Schmelze) sowie, aus-gehend von N-Thioacyl-Derivaten, in Gegenwart von Quecksilberoxid durchfiihren z. B. ... 

In Tetrahydrofuran werden die N-Thioacyl-Dcrivate erhalten, die sich zu den Pyrido-1,3-lhiazolen kondensieren lassen... 

A wide range of 3-aza-l-thia-l,3-butadiene systems has been extensively investigated as 4ir components of Diels-Alder reactions. The work with each of these systems is summarized in Chapter 9 and includes the 4tt Diels-Alder reactions of appropriately substituted At-thioacylimines (e.g., 29, Chapter 9, Section 3)/ thioacyl isocyanates (e.g., 30, Chapter 9, Section 3), thioacyl isothiocyanates (e.g., 31, Chapter 9, Section 3), and N-thioacyl dithioimidocarbonates (e.g., Examples of... 

Nelson and co-workers reported cinchona alkaloid-catalyzed [4-1-2] cycloaddition of ketenes and N-thioacyl imine, affording the 4,5-cw-disubstituted l,3-thiazin-6-one derivatives 146 with high enantioselectivities (>95% ee) and diastereoselectivities (>95 5 cis. trans). Scheme 3.47 [63], Ketene, in situ generated from acyl halide 143 and base, followed by addition to imine which was generated in situ via basic elimination of a-amido sulfone 144, providing the ketene-imine addition pathway toward the cycloadducts. 

A Specialized synthesis used ethyl N-thioacyl urethane 7.275 in a Wittig olefin-ation 34 reaction to give 1.276. The requisite starting material (1.275) was... 

O-Metfayl thiocarboxylates are very suitable for the N-thioacylation of N-unprotected amino acids. Thus, shaking a heterogenous mixture of PhCSOMe in ether and the amino acid in aq. NaOH gives good yields of A thiobenzoylated material. Using (7-alkyI thiocarboxylates of amino acids (2 R = R NHCHR ), the approach has been extended to synthesize endothiopeptides such as (5) formaticm of imidates may interfere with the desired process. The reaction has been carried out in water/THF using NajCOs or as shown in equation (3). ... 

Thioacetals s. Mercaptals Thioacetamide as reagent 27,19 Thioacylamines s. Carboxylic acid thioamides N-Thioacylation with N-thio-acylimidazoles 26,397 selective 16,468 suppl. 28 Thioacyl disulfides... 

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