Exploiting Heavier Organochalcogen Compounds in Donor-Acceptor Cyclopropane Chemistry

Donor-acceptor (D-A) cyclopropanes have gained increased momentum over the past two decades. The use of these highly strained three-membered entities paved the way to innovative and original transformations yielding complex cyclic and acyclic architectures that otherwise might be difficult to address. Since the fundamentals were laid by Wenkert and Reissig in the late 1970s, the field has flourished impressively including asymmetric transformations as well as elegant synthetic applications in the construction of natural occurring products. In this Account, we aim to highlight especially our efforts in the context of an efficient access to sulfur- and selenium-containing compounds, of either cyclic or open-chain nature, by exploiting D-A cyclopropane chemistry. Light will be shed on the three fundamental transformations: ring-opening reactions, cycloadditions, and rearrangements.Our synthetic endeavors started back in 2011 guided by quantum chemical studies to obtain 3,3'-linked bisthiophenes along with an unprecedented rearrangement delivering sulfur- and selenium-containing cagelike scaffolds. Inspired by these surprising results, we further deepened our efforts to the construction of new sulfur-carbon and selenium-carbon bonds within the context of D-A cyclopropane chemistry. In the first instance, we capitalized on the great versatility of organosulfur and organoselenium compounds regarding their amphiphilic character to act either as nucleophilic or as electrophilic species. By such an approach, ring-openings via a nucleophilic attack of sulfenyl and selenyl halides furnished 1,3-bishalochalcogenated products. A similar protocol led us to a desymmetrization reaction of meso-cyclopropyl carbaldehydes employing novel chiral imidazolidinone organocatalysts. In contrast, electrophilic sulfur was supplied by N-(arylthio)succinimide substrates to access thiolated γ-amino acid derivatives and their selenium equivalents.Combining the highly reactive thiocarbonyl compounds and vicinal donor-acceptor substituted cyclopropanes opened new vistas in the field of atom-economic cycloaddition reactions to build up sulfur-containing heterocycles of various sizes. The first systematic study of such transformations was made by our group in 2017 leading to highly decorated thiolanes, whereas an intramolecular approach furnished thia-[n.2.1]bicyclic ring systems. Our investigations were then successfully extended to the synthesis of tetrahydroselenophenes by using capricious selenoketones. Recently, we were able to yield the unsaturated analogues, selenophenes, by a (3 + 2)-cycloaddition of D-A cyclopropanes with ammonium selenocyanates followed by oxidation. The formal insertion of thioketenes was realized by employing 3-thioxocyclobutanones as surrogates for disubstituted thioketenes to obtain 2-substituted tetrahydrothiophenes bearing a semicyclic double bond via a (3 + 2) spiroannulation/(2 + 2) cycloreversion sequence. Even the formation of seven-membered S-heterocycles was realized by (4 + 3)-cycloaddition processes. In 2016, we demonstrated the synthesis of benzo-fused dithiepines from in situ generated ortho-bisthioquinones, whereas the utilization of thia-Michael systems as a hetero-4π-component delivered tetrahydrothiepine derivatives containing just one sulfur atom embedded in the ring system.