The [4+2]‐Cycloaddition of α‐Nitrosoalkenes with Thiochalcones as a Prototype of Periselective Hetero‐Diels–Alder Reactions—Experimental and Computational Studies

• Published in: Chemistry : a European journal 2020-01, Vol.26 (1), p.237-248
• Main Authors: Mlostoń, Grzegorz, Urbaniak, Katarzyna, Jasiński, Marcin, Würthwein, Ernst‐Ulrich, Heimgartner, Heinz, Zimmer, Reinhold, Reissig, Hans‐Ulrich
• Format: Article
• Language: English
• Subjects: Adducts; Chemistry; Computer applications; Cycloaddition; DFT calculations; Diels-Alder reactions; Dimerization; Dimers; hetero-Diels–Alder reactions; Isomers; Mathematical analysis; Nitroso compounds; organic synthesis; periselectivity; Prototypes; Selectivity; thiochalcone
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201903385

The [4+2]‐cycloadditions of α‐nitrosoalkenes with thiochalcones occur with high selectivity at the thioketone moiety of the dienophile providing styryl‐substituted 4H‐1,5,2‐oxathiazines in moderate to good yields. Of the eight conceivable hetero‐Diels–Alder adducts only this isomer was observed, thus a prototype of a highly periselective and regioselective cycloaddition has been identified. Analysis of crude product mixtures revealed that the α‐nitrosoalkene also adds competitively to the thioketone moiety of the thiochalcone dimer affording bis‐heterocyclic [4+2]‐cycloadducts. The experiments are supported by high‐level DFT calculations that were also extended to related hetero‐Diels–Alder reactions of other nitroso compounds and thioketones. These calculations reveal that the title cycloadditions are kinetically controlled processes confirming the role of thioketones as superdienophiles. The computational study was also applied to the experimentally studied thiochalcone dimerization, and showed that the 1,2‐dithiin and 2H‐thiopyran isomers are in equilibrium with the monomer. Again, the DFT calculations indicate kinetic control of this process. Superdienophiles select one of eight conceivable pathways! The hetero‐Diels–Alder reactions of α‐nitrosoalkenes with thiochalcones are highly periselective and regioselective processes, providing only one of eight possible constitutional isomers. The thiochalcones undergo a regioselective, but reversible dimerization. High‐level DFT calculations reveal that these processes are kinetically controlled.