Mechanistic Investigation of a Synthetic Route to Biaryls by the Sigmatropic Rearrangement of Arylsulfonium Species.

A comprehensive mechanistic investigation was conducted on the coupling reaction of aryl sulfoxides with phenols by using trifluoroacetic anhydride to yield biaryls. NMR experiments revealed that our previously proposed mechanism, which consists of a cascade of an interrupted Pummerer reaction and a rate-determining [3,3] sigmatropic rearrangement, is reasonable. The electronic effects of the substrates were also evaluated to elucidate the nature of the rearrangement step. Based on experimental observations and theoretical calculations, we conclude that the rearrangement is highly asynchronous and stepwise rather than concerted when electron-rich phenols are employed for the reaction.

Asymmetric systematic synthesis, structures, and (chir)optical properties of a series of dihetero[8]helicenes.

A series of dihetero[8]helicenes have been systematically synthesized in enantiomerically enriched forms by utilizing the characteristic transformations of the organosulfur functionality. The synthetic route begins with assembling a ternaphthyl common synthetic intermediate from 2-naphthol and bissulfinylnaphthalene through an extended Pummerer reaction followed by facile multi-gram-scale resolution. The subsequent cyclization reactions into dioxa- and dithia[8]helicenes take place with excellent axial-to-helical chirality conversion. Dithia[8]helicene is further transformed into the nitrogen and the carbon analogs by replacing the two endocyclic sulfur atoms via SNAr-based skeletal reconstruction. The efficient systematic synthesis has enabled comprehensive evaluation of physical properties, which has clarified the effect of the endocyclic atoms on their structures and (chir)optical properties as well as the unexpected conformational stability of the common helical framework.

Ni-Catalyzed Carboxylation of Aziridines en Route to ß-Amino Acids.

A Ni-catalyzed reductive carboxylation of N-substituted aziridines with CO2 at atmospheric pressure is disclosed. The protocol is characterized by its mild conditions, experimental ease, and exquisite chemo- and regioselectivity pattern, thus unlocking a new catalytic blueprint to access ß-amino acids, important building blocks with considerable potential as peptidomimetics.

Generation of Organozinc Reagents from Arylsulfonium Salts Using a Nickel Catalyst and Zinc Dust.

Readily available aryldimethylsulfonium triflates react with zinc powder under nickel catalysis via the selective cleavage of the sp2-hybridized carbon-sulfur bond to produce salt-free arylzinc triflates under mild conditions. This zincation displays superb chemoselectivity and thus represents a protocol that is complementary or orthogonal to existing methods. The generated arylzinc reagents show both high reactivity and chemoselectivity in palladium-catalyzed and copper-mediated cross-coupling reactions.

Construction of Biaryls from Aryl Sulfoxides and Anilines by Means of a Sigmatropic Rearrangement.

Invited for the cover of this issue is the group of Hideki Yorimitsu and colleagues at Kyoto University. The image depicts the sigmatropic rearrangement of aryl sulfoxides and anilines to form biaryls. Read the full text of the article at 10.1002/chem.201903570.

Construction of Biaryls from Aryl Sulfoxides and Anilines by Means of a Sigmatropic Rearrangement.

An unprecedented S-N variant of the benzidine rearrangement for construction of biaryls has been developed. Aryl sulfoxides underwent dehydrogenative coupling with anilines by successive treatment with trifluoromethanesulfonic anhydride and trifluoromethanesulfonic acid to provide the corresponding 2-amino-2'-sulfanyl- and/or 4-amino-4'-sulfanylbiphenyls. Mechanistic studies indicate that the C-C-bond-forming sigmatropic rearrangement proceeds intramolecularly from dicationic S-N-tethered species.

Sigmatropic Dearomatization/Defluorination Strategy for C-F Transformation: Synthesis of Fluorinated Benzofurans from Polyfluorophenols.

Facile synthesis of fluorinated benzofurans from polyfluorophenols has been accomplished by means of a sigmatropic dearomatization/defluorination strategy composed of three processes: (1) interrupted Pummerer reaction of ketene dithioacetal monoxides with polyfluorophenols followed by [3,3] sigmatropic rearrangement, (2) Zn-mediated smooth reductive removal of fluoride from the dearomatized intermediate, and (3) acid-promoted cyclization/aromatization. Mechanistic investigations revealed important characteristic reactivity of polyfluorophenols in the present system. Some of the fluorinated benzofuran products were transformed by utilizing the 2-methylsulfanyl moieties.

Sigmatropic Rearrangements of Hypervalent-Iodine-Tethered Intermediates for the Synthesis of Biaryls.

Metal-free dehydrogenative couplings of aryliodanes with phenols to afford 2-hydroxy-2'-iodobiaryls have been developed. This reaction proceeds through ligand exchange on the hypervalent iodine atom followed by a [3,3] sigmatropic rearrangement and with complete regioselectivity. This coupling, in combination with in situ oxidation by mCPBA, enables the convenient conversion of iodoarenes into desirable biaryls. The obtained biaryls have convertible iodo and hydroxy groups in close proximity, and are thus synthetically useful, as exemplified by the controlled syntheses of π-extended furans and a substituted [5]helicene. DFT calculations clearly revealed that the rearrangement is sigmatropic, with C-C bond formation and I-O bond cleavage proceeding in a concerted manner. Acetic acid, which was found to be the best solvent for this protocol, renders the iodine atom more cationic and thus accelerates the sigmatropic rearrangement.

Regioselective C-H Sulfanylation of Aryl Sulfoxides by Means of Pummerer-Type Activation.

A regioselective C-H sulfanylation of aryl sulfoxides with alkyl aryl sulfides in the presence of acid anhydride was developed, which resulted in the formation of 1,4-disulfanylarenes after dealkylation of initially formed sulfonium salts. The reaction began with Pummerer-type activation of aryl sulfoxides followed by nucleophilic attack of alkyl aryl sulfides. The nucleophilic attack occurred exclusively at the para positions, or at specific positions in case the para position was not available, under perfect control by the dominating sulfoxide directors regardless of any other substituents. The initially formed aryl sulfonium salts were isolable and usefully served as aryl halide surrogates for palladium-catalyzed arylation with sodium tetraarylborates.

Metal-Free Approach to Biaryls from Phenols and Aryl Sulfoxides by Temporarily Sulfur-Tethered Regioselective C-H/C-H Coupling.

We have developed metal-free regiocontrolled dehydrogenative C-H/C-H cross-coupling of aryl sulfoxides with phenols by means of trifluoroacetic anhydride. Because the reaction would proceed through an interrupted Pummerer reaction followed by sulfonium-tethered [3,3]-sigmatropic rearrangement, the C-H/C-H coupling takes place exclusively between the ortho positions of both substrates. Various functional groups including carbonyl, halo, siloxy, and even boryl moieties are compatible. The biaryl products naturally possess hydroxy and sulfanyl groups, which allows the products to be useful synthetic intermediates, as evidenced by the syntheses of π-expanded heteroarenes such as unprecedented 7,12-dioxa[8]helicene.

Asymmetric Cyclization of N-Sulfonyl Alkenyl Amides Catalyzed by Iridium/Chiral Diene Complexes.

Iridium/chiral diene complexes efficiently catalyzed the asymmetric cyclization of N-sulfonyl alkenyl amides to give the corresponding 2-pyrrolidone derivatives with high enantioselectivity. A mechanistic study revealed that the reaction proceeds via nucleophilic attack of the amide on the alkene moiety.