1.2- Thiazetidine 1,1-dioxides

Thermolysis of the thiadiazabicyclo[3.1.0]hexene 30, obtained from reaction of an azide with an isothiazole dioxide affords the 1,2-thiazetidine-1,1-dioxide 31, but in poor yield and as part of a three-component mixture <96T7183>. Isocyanates 32 are available in moderate yield <94ZOR1700>. 

Alkylidene sulfenes (75), generally prepared by the dehydrohalogenation of alkylsulfonyl chlorides, add readily to electron-rich multiple bonds. For example, with enamines, the thietane dioxide (e.g., 76) is formed diazoalkanes yield thiirane dioxides (episulfones) and imines (Schiff bases) afford 1,2-thiazetidine 1,1-dioxides. There are available numerous reviews of sulfenes, including cycloaddition reactions.102... 

A stereoselective one-pot synthesis of substituted 1,2-thiazetidine 1,1-dioxides (P-sultams) 55 started from heterocyclic pentafluorophenyl (PFP) sulfonates <06OL5513>. 

Thiazetidine 1,1,-dioxides ((3-sultams) 67 were directly synthesised from pentafluorophenyl (PFP) isoxazolidine-4-sulfonates 66 under mild reducing conditions [Mo(CO)6, MeCN, H20, reflux]. The process is stereoselective and goes through N-O bond cleavage followed by intramolecular displacement of the PFP group by the amine <06OL5513>. 

There are two reports describing the preparation of derivatives of 1,2-thiazetidine-1,1-dioxide. The sulfur atom in L-cystine diethyl ester was oxidized and the corresponding sulfonyl chloride was cyclized with ammonia (Scheme 3) (60CB784). A similar transformation used protected )3-homocysteine as starting material (94LA251). 

Simple saltams, 1,2-thiazetidine 1,1-dioxides, are known to polymerize thermally (73MI51500), although in one case the alkene product was reported to be formed with retention of stereochemistry (Scheme 11) (75BCJ480). 

Reaction of 1,2-thiazetidine 1,1 -dioxides with nucleophiles by S-N bond cleavage 731... 

Saturated rings such as 1,2-thiazetidines 5, 1,2-thiazetidine A-oxides 6, 1,2-thiazetidine 1,1 -dioxides, commonly named /3-sultams 7 and 1,3-thiazetidines 8 ... 

Experimental reactivity and mechanistic studies on the solvolysis of /3-sultams have shown that opening of the S-N bond produced a sulfonic acid or sulfonate ester and that there was no evidence of C-S fission. Alcoholysis of A-methyl-1,2-thiazetidine 1,1-dioxide 11 was investigated using ab initio calculations and density functional theory... 

Reaction of the 1,2-thiazetidine 1,1 -dioxide 68 with the weaker Lewis acid, tin(iv) chloride, gives the CM-aziridine as a major product together with benzophenone (Equation 2). However, when the reaction is carried out on the /raor-isomer, it affords essentially benzophenone accompanied by a trace amount of the /ra r-aziridine <1998T8941>. 

Reactivity of Substituents Attached to Ring Heteroatoms 2.15.7.1 1,2-Thiazetidine 1,1 -Dioxides... 

A synthetic approach to /3-sultams containing a direct bond between a tri- or tetracoordinated phosphorus atom and the nitrogen atom of the 1,2-thiazetidine 1,1-dioxide ring has been realized by direct phosphitylation or phosphorylation at nitrogen. Unfortunately, attempts to synthesize N-phosphorylated /3-sultams by reaction with diethyl phosphorochloridate and diethyl phosphorobromidate, generated in situ from diethyl phosphate and carbon tetrachloride or carbon tetrabromide, failed. However, when the /3-sultam is treated with freshly distilled diethyl phosphorochloridite or tetramethylphosphorodiamidous chloride in the presence of triethylamine, the expected AHliethy I phosphite and iV-phosphorodiamidous /3-sultams 150 are obtained (Equation 10). /3-Sultams unsubstituted... 

The synthesis of 3-alkyl-substituted 1,2-thiazetidine 1,1-dioxides starts by transformation of the amino acids L-Val, L-Leu, L-Ile, and L-Phe into amino alcohols. These ate converted via the bromides to the corresponding thiols 161. Immediate oxidative chlorination affords either sulfonyl chloride hydrochlorides or sulfonic acids 162 which are transformed into the parent /3-sultams 163 <2004HCA90>. Similarly, L-cystine derivatives 164 have also been transformed into the parent /3-sultams 165 by oxidative chlorination followed by cyclization (Scheme 50) C1997LA1261, 2004HCA90>. 

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