Properties and Reactions of Substituted 1,2‐Thiazetidine 1,1‐Dioxides: Fluoride Catalyzed Reactions of Silylated β‐Sultams with Electrophiles

Abstract

N-Silylated 8-sultams 1 and 4 react with ketones and aldehydes in the presence of fluoride ions to 0-silylated carbinolsulfonamides 3. Under similar conditions, N-aminoalkylated 4-silylated p-sultams react to O-silylated C-4 aldol adducts 7, which are deprotected and desilylated to 8 and 10. The (a-hydroxyu-methylethyl)-substituted p-sultam 1 ,ZThiazetidine 1 ,I-dioxides (psultams) can be regarded as attractive sulfonyl analogues of the biological important P-lactams. Usually, they show much higher reactivity, as the rc-bond overlap which causes the stability of p-lactams is not available to psultams. Therefore, it is of great interest to know their chemistry, and eventually to synthesize sulfonyl analogues of p-lactam antibiotics '). In the preceding paper *) we have described the silylation of 1 ,Zthiazetidine 1,l-dioxides resulting in the preparation of all possible Nand/or C-4 substituted p-sultams. These silylated p-sultams enable us to introduce different types of substituents especially to the C-4 position. In some examples, a sub5titution at C-4 is possible without silylation, but deprotonation at C-4 usually results in dimerisaition and rearrangement 3, to dithiazine tetroxides 4). Here, we report about the fluoride catalyzed reactions of silylated p-sultams with ketones and aldehydes.When 1 reacts with an excess of 4-nitrobenzaldehyde in THF at room temp. in the presence of small amounts of caesium fluoride the aldehyde is inserted into the nitrogensilicon bond without substitution at C-4 yielding the O-silylated N-aldol 2. However, when the reactions occurs with tetrabutyl-ammonium fluoride (TBAF) on silica gel, both carbon-silicon bonds at C-4 are cleaved leading to the 0-silylated product 3a. Using 4-methoxybenzaldehyde, we isolated 3b. The 0-silylated N-aldols 3a-e were also obtained from 4 reacting with the appropriate carbonyl compound and TBAF on silica gel in THF at room temp. (Table 1). AsMeyle 5, has shown, 1,Zthiazetidine 1,l-dioxide reacts with n-BuLi and aldehydes to the N-aldol adducts (carbinolsulfonamides), which can be stabilized by 0-acylation (reaction with acyl halides). Therefore, it is not surprising that even structures 3 are stable compounds, which can be stored in vucuo for several months (3a-d). However, 3e exposed to air decomposes at room temp. within 1 h yielding acetaldehyde, unsubstituted psultam, and taurine.The IR-spectra of 3 do not show any unexpected absorptions. However, we highlight the characteristic absorption >3000 cm-', which is caused by the strained 4-membered ring ' ), and which is clearly detected in the spectra of 3d and 3e. In the spectra of 3a-c, this absorption is superposed by the absorption of the aromatic increments. In contrast to other N-substituted p-sultams 'I, the protons 3-H and 3'-H are diastereotop (except in 3d) as the N-substituent contains an asymmetriccally substituted carbon atom. The effect is seen in the 'H-NMR spectra of 3a-c, where the corresponding signals show differences in the shifts up to 0.43 ppm. The effect is much smaller in...