Trimethylsulfoxonium ylide

Reaction of A,A-dimcthylsullamoyl aziridines 323 and 325 with primary amines furnishes substituted 1,2,5-thiadiazolidine 1,1-dioxides 324 and 326, respectively, in a regioselective manner <06SL833>. Aziridine 325 is made from ( I /t,6,S ,Z)-bicyclo[4.2. l]non-3-en-9-one in two steps /V,/V-dimethylsulfamoyl imine formation using dimethylsulfamide and subsequent reaction with trimethylsulfoxonium ylide. The product from the reaction with 4-methoxy-benzyl amine can be subsequently manipulated (debenzylation and derivatization) to give the alternative nitrogen substitution pattern in a controlled manner. 

Treatment of wortmannin with trimethylsulfoxonium ylide gave the ring expanded product 2 (R = H). The Lilly chemists considered two possible mechanisms for the formation of 2 and preferred one of them on the basis that use of the perdeuterated sulfoxonium ylide gave exclusively the deuterated product 2 (R = D). 

The reaction of epoxides (1) with trimethylsulfoxonium ylide leads to oxetanes (2) in high yields through a nucleophilic ring opening followed by intramolecular dimethylsulfoxide elimination (Eq. (1)) (83JOC5133). This is probably the simplest homologation reaction of a three-membered heterocycle. 

Vinylaziridine 7.6 Vinyl azide 5 (20 mmol) and trimethylsulfoxonium ylide (2 equiv) in DMSO was stirred at 20°C for 12 h. The reaction mixture wad diluted with Et20 (100 mL) and washed with water (5x100 mL). Evaporation of the solvent afforded triazoline 6 in 95% yield. Pyrolysis of 6 in refluxing PhMe (3 h) gave 7 in 65% yield alternatively flash vacuum pyrolysis (FVP) afforded 7 in 93% yield. 

The mechanism is demonstrated by the reaction between trimethylsulfoxonium ylide and a general ketone, as shown here. 

Still documented another innovative case of macrocyclic stereocontrol in the synthesis of periplanone B (58), the sex excitant pheromone of the American cockroach (Scheme 1.7) [23]. The conformationally rigid ten-membered enone 55 was employed as a platform for two diastereoselective epoxidation reactions. Use of t-BuOOH under alkaline conditions effects chemoselective epoxidation of the enone, and subsequent exposure of the resulting epoxyketone 56 to trimethylsulfoxonium ylide converts the ketone into the corresponding epoxide to furnish 57. 

Corey s seminal investigations of the chemistry of trimethylsulfoxonium ylide established a powerful method for the generation of cyclopropanes from enones [19, 21, 73, 74). In a typical experiment, treatment of enones such as carvone (121) with Me3S(0)I/NaH in DMSO leads to the formation of 122 in 82% yield as a single diastereomer (Equation 19) [74]. 

The echoes of Corey s seminal discovery with sulfonium and sulfoxonium ylides have found considerable resonance in modern investigations of enan-tioselective cyclopropanation reactions. Shibasaki showed that treatment of pyrrole amides such as 126 with trimethylsulfoxonium ylide was effectively promoted by the La-Li-(biphenyldiolate) catalyst 127 to give the cyclopropane adduct 128 in 98% ee (Equation 20) [78]. Key to the success of the transformation was the use of Nal as an additive. The investigators speculated that exchange of Li for Na occurs in 127 to some extent to give an active cyclopropanation catalyst that is more enantioselective. The observation underscored the versatility of such bifunctional heterobimetallic catalysts, the properties of which can be fine-tuned in a multitude of ways by variation of the ligand and the nature of the metals employed [79]. 

Calculate the energy of proton transfer from trimethylsulfoxonium cation to its ylide, relative to that for trimethylsulfonium cation to its ylide, i.e. 

Sulfur ylides 1 and 2 are usually prepared by treatment of either trimethylsulfoxonium... 

Cyclic dinuclear ylide complexes have also been prepared with sulfur ylides. The reactions of (dppm)(AuCl)2 or (dppe)(AuCl)2 with trimethylsulfoxonium tetrafluoroborate and base under phase-transfer conditions gave the products shown in Scheme 42. Auration of the dppm ligand leads to the byproducts.27... 

With strong bases it is also possible to remove a proton from the methyl group of triarylmethylphosphonium halides, trimethylsulfonium iodide, or trimethylsulfoxonium iodide (Figure 9.1). Here, too, species are produced that are betaines of the ylide type. 

A The epoxide can be prepared from cyclohexanone by reaction with the ylide derived from trimethylsulfoxonium iodide or in a... 

Dimethyloxosulfonium Methylide " Deprotonation of trimethylsulfoxonium iodide forms a sulfur ylide that is significantly more stable than dimethylsulfonium methylide and may be prepared and used at room temperature. 

Methylation of DMSO with methyl iodide yields trimethylsulfoxonium iodide (Scheme 14). This is an unusual reaction since other sulfoxides and halides form the products of O-alkylation. By treatment with strong bases, the trimethylsulfoxonium salt is converted into the sulfoxonium ylide (25) (Scheme 14). 

The 6-keto group of naltrexone (1) is accessible to nucleophilic attack from the [5-side to provide 6ot-alcohol derivatives. Therefore, we attempted to synthesize a 6a-epoxide derivative 24 of naltrexone with a stable sulfur ylide derived from trimethylsulfoxonium iodide [24]. The 6ot-epoxide 24 was expected to convert to the objective oxabicyclo[2.2.2]octane derivative 20. Instead, the 6 3-epoxide 23 was obtained in 67% yield, but not the objective 6ot-epoxide 24 (Scheme 6). The structure of 23 was determined by X-ray crystallographic analysis (Fig. 8). 

Scheme 6 Reaction of naltrexone methyl ether (22) with a stable sulfur ylide. Reagents and conditions (a) trimethylsulfoxonium iodide, NaH, THF, 55 °C to rt, 67%...

To investigate the source of the unexpected cyclization, we combined a precursor 28 that did not have a 4-hydroxy group with the same stable ylide. This produced compound 29 with an oxabicyclo[2.2.1]heptane skeleton via the epoxide 30. Alternatively, the morphinan methyl ether 28 could also react with the stable sulfur ylide derived from trimethylsulfoxonium iodide at room temperature. The definitive intermediate, 6a-epoxide 30, was isolated, and then treated with NaH in DMF at 80 °C to produce the objective bicyclic compound 29 (Scheme 9). 

Here, both the starting material and the ylide contain hexavalent sulfur. The pA g of the starting material, the trimethylsulfoxonium cation (Me3S" 0), is about 18.2 and is expected to be lower than that of the trimethylsulfonium cation (Me3S+). Dimethylsulfoxonium methylide is thus more stable as well as a softer nucleophile than dimethylsulfonium methylide. Qualitatively, however, the two ylides react in a similar way. The most prominent difference... 

Dimethylsulfoxonium methylide 1, an ylide developed by Corey and coworker (Corey and Chaykovsky, 1965), is synthesized from trimethylsulfoxonium iodide 2 which is converted to trimethylsulfoxonium chloride 3 via ion exchange with benzyltributylammonium chloride. The ylide 1 is produced by refluxing a heterogeneous mixture of trimethylsulfoxonium chloride 3 and sodium hydride in toluene (Scheme 11.2). Homogeneous solutions of ylide 1 of approximately 0.6M can be stored at —20 °C for >3 weeks (Busch et al, 2002). 

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