Thioamides adducts

When hexafluoroacetone reacts with amides, urethanes [25], thioamides [26], amidines [27], sulfonamides [28, 29], sulfinainides [20], and f),0-dialkyl-amido-phosphates [27], the correspondmg semiamidals are formed m nearly quantitative yield The thermal stabihty of these adducts toward the retro reaction increases with the nucleophihcity of the ammo compound [5] Many polyfluonnated carbonyl compounds react likewise [22 22] On treatment of ureas [34], thioureas [34], thioamides [26], and C,77 diarylatmdmes [27, 25] first with hexa- fluoroacetone and then with dehydratmg agents, heterodienes are obtamed (equation 4)... 

With (Z)-amide enolates and (Z)-thioamide enolates a strong preference for sm-adducts is also observed. In general, boron or zirconium (Z)-enolates of ketones and amides display a higher simple diastereoselectivity in favor of syn-products than the corresponding lithium or magnesium enolates6,7. 

In the Michael addition of achiral enolates and achiral Michael acceptors the basic general problem of simple diastereoselection (see Section D.1.5.1.3.2.), as described in Section 1.5.2.3.2. is applicable. Thus, the intermolecular 1,4-addition of achiral metal enolates to enones, a.jS-unsat-urated esters, and thioamides, results in the formation of racemic syn-1,2 and/or anti-3,4 adducts. 

There are amines such as A-methylnitroamine, that are too weakly nucleophilic to be able to form covalent adducts with arenediazonium ions. The products of the latter appear to be those of salts ArNJ N(N02)CH3, as found by Baranchik et al. (1957). Amides also appear not to be sufficiently nucleophilic, but thioamides are, as is shown by the reaction of A-phenylthiourea in the presence of NaOH (Scheme 13-12 Nesynov et al., 1970). First a (probably homolytic) phenylation-de-diazoniation takes place, followed by A-coupling. Selenourea also reacts a mixture of products is formed, which indicates a reaction of the same type as with thiourea (Nesynov and Aldokhina, 1976). 

A recent total synthesis of tubulysin U and V makes use of a one-pot, three-component reaction to form 2-acyloxymethylthiazoles <06AG(E)7235>. Treatment of isonitrile 25, Boc-protected Z-homovaline aldehyde 26, and thioacetic acid with boron trifluoride etherate gives a 3 1 mixture of two diastereomers 30. The reaction pathway involves transacylation of the initial adduct 27 to give thioamide 28. This amide is in equilibrium with its mercaptoimine tautomer 29, which undergoes intramolecular Michael addition followed by elimination of dimethylamine to afford thiazole 30. The major diastereomer serves as an intermediate in the synthesis of tubulysin U and V. 

Addition to thioamides.s Alkyl- or aryllithiums add to the carbon-sulfur bond of aromatic thioamides to give adducts that are hydrolyzed to unsymmetrical ketones. Reduction of the adducts with LiAlHj before hydrolysis provides a-alkylated amines. 

A number of addition reactions to the salt (150) have been reported.140 With azide ion, the ylide (151) is formed. Diels-Alder addition of cyclopentadiene occurs to form isomeric adducts (152). With thioamides, a mixture of the salts (153) and (154) results, and with, e.g., 2-aminopyridine, the salt (155) is formed. 

Very interesting transformations were observed with dimedone 103b and arylidenethioacetamides 110 (88ZOR460). When the reaction was carried out at ambient temperature, Michael adducts 111 were formed. Compounds 111 can be converted on heating into hydrogenated pyridi-nethiones 112 (in ethanol) or to 2-aminopyran-3-thioamides 113 (in benzene). The formation of the latter ones was found to be reversible. Thus, 113 convert into 112 on heating in ethanol, and yield 2-amino-3-cyanopyr-ans 104 when heated with MN in benzene (Scheme 39). 

A -Silylmethyl-amidines and -thioamides (42) (X=NR or S) undergo alkylation at X with, for example methyl triflate, and then fluorodesilylation to give the azomethine ylides 43 (identical with 38 for the thioamides) (25,26). Cycloaddition followed by elimination of an amine or thiol, respectively, again leads to formal nitrile ylide adducts. These species again showed the opposite regioselectivity in reaction with aldehydes to that of true nitrile ylides. The thioamides were generally thought to be better for use in synthesis than the amidines and this route leads to better yields and less substituent dependence than the water-induced desilylation discussed above. 

A new tandem Michael-aldol reaction of a,ft-unsaturated compounds bearing a chalcogenide or thioamide group with electrophiles has been reviewed.163 The product o -(o -hydroxyalkyl)enones - Morita-Baylis-Hillman (MBH) adducts - can be formed with significant stereocontrol when an optically active thione is used. 

The reaction of 1,2,4-dithiazolines 22 (R = Buc, R1 = Ph) with Ph3P in the presence of EtOH in CH2C12 at room temperature afforded thioamide 102, which is the 1,4-adduct of heterodiene 101 with EtOH, together with Ph3P=S (Scheme 24) <2004TL6187>. 

Tellurium tetrachloride in combination with a strong amine base effected the mild dehydrosulfurization of thioamides to nitriles. Treatment of the thioamides (60) with tellurium tetrachloride and triethylamine in chloroform at room temperature formed nitriles (61) in excellent yield. Using selenium tetrachloride, a similar reaction also occurred in a little lower yield and accompanied by the formation of the 1,2,4-thiadiazole (63). In a plausible mechanism, some of the 1 1 adduct (61) undergoes a further addition reaction with another thioamide molecule prior to the degradation reaction to nitrile, leading to the formation of the 1,2,4-... 

Other results with unsaturated thioamides include a nice reversal [233] of the endo selectivity in favour of the exo adduct by adjustment (Table 4, entry 9) of the thermal conditions (-30 °C vs 80 °C). Unexpected dimerisa-tions of enethioamides (entries 10 and 11) were observed [234, 235]. Thiocarbonyl chemistry has already been used in fullerene chemistry Acyl thio-acrylamides react [236] with [60]fullerene to yield hetero-Diels-Adler products (Table 4, entry 12). 

Isothiocyanates react with stannyl ynamines to give adducts 65 which upon careful hydrolysis yield the still rare ynamines thioamides 66 (109) 153). 

Acyclic alkenic sulfur compounds have also been obtained via pyrolytic rDA reactions. A general route to thioacrylamides utilizing rDA reactions under FVP conditions has been developed. The rDA reaction of the appropriate adducts yields thioacrylamide, V-methylthioacrylamide and NA -dimethyl-thioacrylamide in approximately quantitative yield (equation 13). The high reactivity of these a,3-unsaturated thioamides had previously limited their availability. a,3-Unsaturated acyclic chio-ketones such as (17) were prepared via a rDA reaction using a FVP technique. These highly reactive species dimerize to 4//-l,3-dithiins (18) on warming to-60 °C (equation 14). ... 

Like thioamides and thiazolidinethiones <2002EJI1718>, the reaction of 105 with iodine in carbon disulfide as a solvent led to the formation of the thermally rather stable adduct 106, in which, as determined by X-ray crystallography, the coordination of the (C)(S)C=S thiocarbonyl group to I2 takes place. A stable polymorphic adduct was previously obtained on crystallization of a,/3-C4S6-l2 from acetonitrile <1989JOC2165>. 

Heating of P4S10 with nitriles (73) yields adducts incorporating a P4 tetrahedron hydrolytic cleavage furnishes thioamides. ... 

Adducts from Amides (Thioamides) and Acylating Reagents... 

Crystalline adducts from thioamides and aromatic acid chlorides ate well known. A very convenient synthesis of diacyl sulfides and thiocarboxylic acids - proceeds via adducts of thio-DMF with acid chlorides. 

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