Three- and Four-Membered Rings from Cycloadditions of 1,3-Thiazolium-4-olates and Aldehydes

Abstract

2-Aminothioisomünchnones, a well-known family of masked dipoles, react with aromatic aldehydes in a domino cascade reaction that produces episulfides (thiiranes) or beta-lactams (2-azetidinones). This sequence is initiated by a [3+2] dipolar cycloaddition followed by ring opening of cycloadducts and intramolecular rearrangement to afford these unusual ring contractions. The nature of the reaction products depends on the structural characteristics of the starting dipole and the experimental conditions. Episulfides are obtained selectively as cis isomers with respect to both aryl groups, whereas beta-lactams are produced as cis/trans mixtures. These structural features were determined unequivocally by X-ray crystallographic analysis. The beta-lactams still possessed a flexible acyclic chain containing sulfur, a salient lead modification of the bioactive cyclic penems and cephems. The preferential production of exo transition structures was rationalized with the aid of computational calculations at the B3LYP/6-31G* level.

Multicomponent Synthesisof Highly Substituted Imidazolines via a Silicon Mediated 1,3-DipolarCycloaddition

“…It has been well documented that azalactones undergo a Staudinger-type reaction when heated with imines in toluene, yielding b-lactams. [29][30][31] The azalactone, which is in equilibrium with valence tautomeric ketene intermediate, undergoes a [2+2]-cycloaddition reaction with the imine (Scheme 3). It can be concluded that either mesoionic oxazolium oxide, which has the nitrogen atom unsubstituted, is not in reasonable concentration and/or the imine nitrogen is not nucleophilic enough.…”

“…Hence formation of ketene is predominant, which reacts readily with the imines to afford the b-lactam. [29][30][31] We envisioned that a Lewis acid coordination to nitrogen of the azalactone, would increase the equilibrium concentration of münchnone intermediate and mediate the azomethine ylide-imine cycloaddition reaction (Scheme 3).…”

Dirhodium(ii) tetraacetate catalysed reactions of diazo thioamides: isolation and cycloaddition of anhydro-4-hydroxy-1,3-thiazolium hydroxides (thioisomünchnones), an approach to analogues of dehydrogliotoxin

“…The organic layer was separated and dried by extraction with saturated brine (2 × 5 ml) and standing over anhydrous sodium sulfate. Subsequent filtration and removal of the solvent in vacuo gave a pale yellow gum which was purified by chromatography on silica eluting with light petroleum-ethyl acetate (4 : 1) to give the title compound (24 4), 297 (6), 279 (3), 257 (9), 218 (17), 192 (42), 168 (17), 140 (100).…”

“…Ethereal diazomethane (∼0.4 mmol ml Ϫ1 ; 3 ml) was added in one portion and the reaction mixture stirred to room temperature over 0.5 h and then heated to 50 ЊC for 0.1 h. The solvents were removed in vacuo and the resulting solid purified by chromatography on silica eluting with light petroleum-ethyl acetate (9 : 1) to give the title compound (126 mg, 45%) as colourless needles, mp 159-161 ЊC (from ethyl acetate-light petroleum); (Found: C, 57.9; H, 5. (27), 344 (50), 330 (16), 314 (9), 298 (17), 284 (26), 270 (39), 258 (21), 218 (100), 146 (50).…”

“…Potts and co-workers, 4-9 and more recently the Padwa group, 10-15 have extensively investigated the cycloaddition reactions of thioisomünchnones, generating the mesoionic system by the reaction of a thioamide with an α-halo acid halide followed by treatment with triethyl- amine to generate the 1,3-dipole. 16,17 However, by analogy with the oxygen analogues, isomünchnones, which are efficiently obtained by the dirhodium() catalysed reaction of diazo imides, 18, 19 one would expect thioisomünchnones to be similarly prepared from the corresponding diazo thioamide. Although there are isolated examples of this approach, 9,10,12,14 the formation of thioisomünchnones by the interaction of rhodium carbenoids derived from diazo thioamides has not been extensively studied, and therefore we decided to investigate the synthesis of 1,3-dipoles 5 from the corresponding diazo thioamides 6 (Scheme 1).…”