Thioimides, cycloaddition

Oxathiazolidin-3-imine (93) possesses a thioimidate moiety similar to 4-methyl-5-phenyl-imino-l,2,3,4-thiatriazoline (70) and is capable of undergoing cycloaddition-elimination reactions with isothiocyanates to give identical products, however at a much higher rate. Acetone can therefore be used as solvent to catalyze this kind of reaction of thiatriazolines. 

Azomethine ylides undergo a formal [3 + 2] cycloaddition with carbonyl compounds to provide oxazolines. Thioimidates, in particular, are effective as ylide precursors. For example, Kohra and co-workers reported that the thioimidate 260, upon activation with cesium fluoride, reacts with aromatic aldehydes and diaryl-ketones to provide oxazolines 261 in modest to good yields. Aliphatic aldehydes and simple ketones are unreactive (Scheme 8.72). 

Reaction kinetics for the interaction of 5-alkyliminothiatriazoles 52 or 58 with heterocumulenes, nitriles, ketones, imines, or other dipolarophiles a=b show that the decomposition of the thiatriazole is bimolecular, and new heterocyclic five-membered rings 71 are formed (Scheme 15). The term masked 1,3-dipolar cycloaddition was used by L abbe and co-workers for this type of reaction <1978JOC4951>, the thioimidate function being the masked 1,3-dipole. The reaction is thought to involve a thiapentalenic intermediate 70 with hypervalent sulfur. The product 71 is itself a masked dipole and often further reactions take place. 

Like imidates, thioimidates were shown to be the precursors of azomethine ylids which lead to the formation of pyrroline and pyrrole derivatives through cycloaddition with dipolarophiles.454... 

Aroyl fluorides promote dipolar cycloaddition of thioimide with dimethyl fumarate.162... 

Cyclic amidinium salts (71) are obtained by [2 + 2] cycloaddition of ketenimmonium compounds (69) to Schiff bases (70 R = H, Ph, MeOaC) or thioimidates (70 R = SBn) their thiolysis provides an elegant access to 3-thiolactams (72 equation 32). ... 

Photochemical reactions of nitrogen-containing thiocarbonyl compounds ([2 + 2] cycloaddition to alkenes with formation of thietanes, transformations of thioimides to lactams and cyclic amines, cyclizations of thioamides) 03H(59)399. 

Cycloadditions. It was found recently that N-tosyl imines of a variety of aldehydes react with alkynyl sulfides in the presence of a Lewis acid catalyst to afford a, /J- unsaturated thioimidates [100]. Thus alkynyl sulfide 291 combines with an N-sulfonyl imine in the presence of a catalyst such as BF3 etherate, Yb(OTf)3, Sc(OTf)3 or Ln(OTf)3to give an imidate 293 [Eq. (70)]. It is believed that this transformation occurs through an initial [2 + 2]-cycloaddition of the reactants to form an azetine 292. Other types of N-substituted imines were found to react with alkynyl sulfides under these conditions to provide different sorts of products and not a, /3-unsaturated imidates like 293. 

A recently developed method is the cycloaddition of 1,2,4,5-tctrazincs with imidatcs or thioimidates which includes the formation of one C-N and one C —C bond. 

For a cycloaddition reaction of a 1,2,4,5-tetrazine 1 with a heterodienophile to proceed successfully, the latter must be activated with an electron-donating group. In this sense, thioimidates, imidates, and amidines 335 proved to be reactive heterodienophiles in the inverse Diels-Alder reactions with 1,2,4,5-tetrazines 1. The reaction proceeds via the initial formation of the bicyclic adduct 336, followed by the loss of a nitrogen molecule to form the dihydro cycloadduct 337, and final aromatization by the loss of a thioalkoxy, alkoxy, or amino group to form the final 1,2,4-triazines 338 (Scheme 82). 

Other isolated examples of cycloaddition reactions of different 1,2,4,5-tetrazines 1 with activated thioimidates, imidates, and amidines can be found in <2003JOC3593> and <1998JOC6329>. 

Several methods for making pyrroles involve in situ generation of azomethine ylides and anions. In the presence of electrophilic acetylenes these can be trapped and converted to pyrroles. One source of azomethine ylides are A -(a-trimethylsilylmethyl) derivatives of imidates and thioimidates. Azomethine ylides are generated by desilylation with fluoride ion. The salts are obtained by N-alkylation of imidate esters <83TL4303> or S-alkylation of thioacetamides <86JOCi997>. The alkoxy or alkylthio groups are eliminated after cycloaddition. Electrophilic alkenes such as dimethyl maleate, dimethyl fumarate, maleonitrile and methyl acrylate give A -pyrrolenines (Scheme 80). 

In the presence of a catalytic amount of Sc(OTf)3, imines and alkynyl sulfides undergo [2 + 2] cycloaddition and successive fragmentation to afford a, -unsaturated thioimidates (eq 21)/ Alkynyl selenides or alkynyl silyl ethers undergo similar reactions in the presence of Sc(OTf)3. 

A similar cycloaddition is the stereospeciflc /3-lactam synthesis from an acid chloride—base—thioimidate system [57]. This method has been employed successfully for the synthesis of closer analogues of cephalosporins than the previously-mentioned 1-azaoctams [58]. 

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