The subsequent Michael addition of aminonitriles 65 to mesylsulfene 67 proceeds through the formation of (methylsulfonyl)methanesulfonamides 68, which are then transformed into C-mesylene amino sultams 66 via the common CSIC reaction. Another limitation involves the presence of bulky bridging fragments. For example, the CSIC cyclization of the sterically hindered N-mesylated aminonitrile 77 (obtained from tropinone 78 via aminonitrile 79) in attempts to synthesize spirosultam 80 also proved unsuccessful (Scheme 10). In contrast, the less rigid aminonitrile 81 (counterpart to tropinone 79 derived from piperidin-4-one 82, lacks an ethylene bridge), readily undergoes sulfonylation and subsequent cyclization. 61 The subsequent stages involved the alkylation of sulfonamide 83 with BnBr in DMF in the presence of NaH to synthesize derivative 84, which then underwent a CSIC reaction using NaH in MeCN at rt to form enaminosultam 85 (Scheme 11). Furthermore, the synthesis of β-keto-γ-sultam 86 was demonstrated through the TMSCl-mediated transformation of enamine 85. Protected pentofurano-3-ulose derivatives 87 underwent conversion to aminonitriles 88 using NH3-MeOH and Ti(OiPr)4 as Lewis acid, followed by treatment with TMSCN to introduce a nitrile group (Table ). Subsequent sulfonylation of aminonitriles 88 with mesyl chloride, ethyl or benzylsulfonyl chlorides in the presence of pyridine and DMAP proved to be an effective method for the synthesis of cyanoalkylsulfonamides 89 in high yields (80-98%). Notably, unlike intramolecular attacks of the nitrile group by carbanions of methylene-active N, N-disubstituted sulfonamides, the CSIC condensation of N-monosubstituted cyanosulfonamides 89 is possible under the action of a threefold excess of n-BuLi or lithium diisopropylamide (LDA) in THF, following N-and C-deprotonation reactions. Excess of bases are necessary in this step due to the presence of the acidic NH proton of the secondary sulfonamide fragment 89 and the formation of the N-lithium salt 90, which could be then proceed to C-deprotonation. The subsequent cyclization of the formed dianions 90 serves as a successful approach for the synthesis of 4-aminosultams 91 in 60-98% yield (Table ). As it was previously mentioned, these 4-aminosultams, i.e. АТСАО-Т and related compounds, serve as important precursors for the synthesis of various pharmaceutical agents. Alkylation reactions of cyanosulfonamides 89 are feasible, specifically with methyl iodide, benzyl bromide, or allyl bromide, by reflux in acetone in the presence of K2CO3 to give sulfonamides 92 in 25-80% yield (Table ). The subsequent cyclization of the N-substituted sulfonamides 92 into the corresponding N-substituted sultams 1.63 could be achieved using either Cs2CO3 or NaH in MeCN to give products in 25-96%. It was observed that in the case of using Cs2CO3, the yields are higher (up to 90%), compared to NaH (35-61% yield). To achieve a complete conversion of 92 into the cyclic derivatives 93, the reaction time needs to be extended to 48 h. The use of Cs2CO3 resulted in improved yields, and this method has been extended to a larger number of products (25-96% yield). A novel method for the sulfonylation of aminonitriles 52 and 53 using methyl-2-(chlorosulfonyl)acetate 94 has been developed under standard conditions. The process involves the use of a threefold excess of Et3N in CH2Cl2 at 0 °C to rt and further reflux (Scheme 12).