,-Unsaturated five-and six-membered sultams are useful dipolarophiles for the [3 + 2] cycloaddition reactions with nitrones, nitrile oxides, and some azomethine ylides. Analysis of the product yields shows that -sultams are in general more reactive towards various 1,3-dipolar compounds as compared to their counterparts (Figure ). Furthermore, N-Boc protection reduces the compound's reactivity. We believe that these effects might be explained by the disruption of optimal orbital orientation for the interaction of C=C and SO2 fragments caused by six-membered ring and flattened carbamate Nitrogen atom, respectively. Since we elaborated efficient protocols for the preparation of the starting ,-unsaturated sultams on up to 100-g scale, the corresponding cycloadducts can be considered readily accessible sp -rich bicyclic systems with significant potential for early drug discovery programs (more than 30 isoxazolidine-, izoxazoline-, and piperidine-derived representatives were obtained successfully in this study). We illustrated this by the multigram synthesis of valuable bi-and trifunctional bicyclic pyrrolidinederived building blocks (including amino acid derivatives), as well as identification of compounds with (sub)micromolar activity against human polyomavirus 1. We hope that these results will inspire the scientific community towards further investigation of the proposed bicyclic sultams and other related derivatives as useful chemotypes for the discovery of biologically active compounds.