Regio- and Stereoselective Synthesis of Sulfur-Bearing Four-Membered Heterocycles: Direct Access to 2,4-Disubstituted Thietane 1-Oxides

Abstract

Starting from readily available C2-substituted thietane 1-oxides, a straightforward synthesis of new C2,C4-disubstituted thietane 1-oxides has been developed by using a lithiation/electrophilic trapping sequence. The chemical and configurational stability of lithiated C2-substituted thietane 1-oxides has been investigated as well as the stereochemical implications for this process. The results demonstrate that a stereoselective functionalization at the C2, C4 positions of a thietane is feasible, leaving intact the four-membered ring.

Transfer of Electrophilic NH Using Convenient Sources of Ammonia: Direct Synthesis of NH Sulfoximines from Sulfoxides

“…Zuschriften suitable substrates. [27,28] Theb enzyl-substituted example 1r was obtained from the corresponding sulfoxide in very good yields by using reaction conditions i. Diastereomerically pure tertiary-alcohol-containing thietane oxides led stereospecifically to the sulfoximines 1s-u.Avery good yield was obtained for the benzothiazole-substituted sulfoximine 1v.F urthermore,protected methionine sulfoxide gave the derivative 1w in af ormal synthesis of MSO (see Figure 1). [29] As ulfoxide bearing the electron-withdrawing trifluoromethyl group appeared to be at the limit of reactivity for this methodology, thus affording a9 %y ield of the p-bromophenyl trifluoromethyl sulfoximine 1x.O xfendazole,abenzimidazole-containing anthelmintic,g ave the corresponding sulfoximine 1y in 70 %u nder am odified set of reaction conditions,w hich were required because of the low solubility of the sulfoxide.…”

“…The thietanesulfoximine 1 q was prepared on an 11 mmol scale in similarly good yield (81 %). Several unusual substituted thietane oxides were also suitable substrates 27, 28. The benzyl‐substituted example 1 r was obtained from the corresponding sulfoxide in very good yields by using reaction conditions i. Diastereomerically pure tertiary‐alcohol‐containing thietane oxides led stereospecifically to the sulfoximines 1 s – u .…”

Computational NMR as Useful Tool for Predicting Structure and Stereochemistry of Four‐Membered Sulfur Heterocycles

“…Calculations allowed to solve an intriguing stereochemical scenario and to propose a model based on a deprotonative dynamic resolution . The same approach has been employed to demonstrated preferential conformations kept in four membered heterocycles (FMHs) such as azetidines 3a and 3b , and thietanes of the kind 4a and 4b …”

Thia‐Michael Addition: An Emerging Strategy in Organic Synthesis

“…Likewise, they represent ak ey pharmacophore in artificial sweeteners, such as alitame. [90][91][92] The reported synthesis utilized Baylis-Hillman alcohols 62 and O,O-diethyl hydrogen phosphorodithioates 64 as substrates and involved the concomitant generation of an ucleophile,f ollowed by thia-Michael addition and intramolecular cyclization to access the resultant 2,3-disubstituted thietanes (65). Furthermore, to enhance the generality of this method, the authors performed the oxidation of Baylis-Hillman alcohols 62 into the corresponding aldehydes 63 by using oxidant IBX and subsequent thia-Michael addition with O,O-diethyl hydrogen phosphorodithioates 64,f ollowed by anion-induced cyclization with at ask-specific ionic liquid [bmim][XÀY],a fforded 2,3,4-trisubstituted thietanes 66 in excellent yields.…”