Elemental Sulfur-Mediated Aromatic Halogenation.

A method for aromatic halogenation using a combination of elemental sulfur (S8) and N-halosuccinimide has been developed. A catalytic quantity of elemental sulfur (S8) with N-bromosuccinimide (NBS) and N-chlorosuccinimide (NCS) effectively halogenated less-reactive aromatic compounds, such as ester-, cyano-, and nitro-substituted anisole derivatives. No reaction occurred in the absence of S8, underscoring its crucial role in the catalytic activity. This catalytic system was also applicable to aromatic iodination with 1,3-diiodo-5,5-dimethylhydantoin.

Phosphazene Base-Catalyzed Intramolecular Hydroamidation of Alkenes with Amides.

A method for the synthesis of cyclic amides via phosphazene base-catalyzed intramolecular hydroamidation of amide alkenes was developed. The reaction using a catalytic amount of P4-base had a good functional group tolerance and a broad substrate scope and could also be used to synthesize lactam, cyclic urea, and oxazolidinone compounds. This catalytic system was expanded to a one-pot intramolecular hydroamidation and intermolecular hydroalkylation. Deuterium labeling and radical trapping experiments provided mechanistic insights into the catalytic cycle of the hydroamidation reaction.

Azido-Alkynes in Gold(I)-Catalyzed Indole Syntheses.

The exploitation of nitrogen-functionalized reactive intermediates plays an important role in the synthesis of biologically relevant scaffolds in the field of pharmaceutical sciences. Those based on gold carbenes carry a strong potential for the design of highly efficient cascade processes toward the synthesis of compounds containing a fused indole core structure. This personal account gives a detailed explanation of our contribution to this sector, and embraces the reaction development of efficient gold-catalyzed cascade processes based on diversely functionalized azido-alkynes. Challenging cyclizations and their subsequent application in the synthesis of pharmaceutically relevant scaffolds and natural products conducted in an intra- or intermolecular fashion are key features of our research.

[Total Synthesis of Dictyodendrins].

In total and formal syntheses of dictyodendrins A, B, C, D, E and F, the key step involved the direct construction of the pyrrolo[2,3-c]carbazole core by the gold-catalyzed annulation of a conjugated diyne with a pyrrole to form three bonds and two aromatic rings. The subsequent introduction of substituents at the C1 (Suzuki-Miyaura coupling), C2 (acylation), N3 (alkylation) and C5 positions (Ullmann coupling) provided divergent access to dictyodendrins. Some dictyodendrin analogues exhibited inhibitory activities toward CDK2/CycA2 and GSK3.

Total Synthesis of Dictyodendrins A-F by the Gold-Catalyzed Cascade Cyclization of Conjugated Diyne with Pyrrole.

Invited for the cover of this issue is Hiroaki Ohno and co-workers at Kyoto University and National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN). The image depicts gold catalysis which promotes the domino reaction to push the switch for the diversity-directed total synthesis. Read the full text of the article at 10.1002/chem.202001950.

Total Synthesis of Dictyodendrins A-F by the Gold-Catalyzed Cascade Cyclization of Conjugated Diyne with Pyrrole.

The total synthesis of dictyodendrins A-F was achieved by using the gold(I)-catalyzed annulation of a conjugated diyne with N-Boc-pyrrole for direct construction of the pyrrolo[2,3-c]carbazole scaffold. Late-stage functionalization of the resulting pyrrolo[2,3-c]carbazole to introduce various substituents provided divergent access to dictyodendrins. Some dictyodendrin analogues exhibited inhibitory activities toward CDK2/CycA2 and GSK3.

Construction of the Pyrrolo[2,3-d]carbazole Core of Spiroindoline Alkaloids by Gold-Catalyzed Cascade Cyclization of Ynamide.

We achieved direct construction of the common pyrrolo[2,3-d]carbazole core of aspidosperma and malagasy alkaloids by a gold-catalyzed cascade cyclization of ynamide. This reaction involves intramolecular cyclization from indole to ynamide followed by trapping of the resulting iminium intermediate. Through the use of chiral gold complexes, an enantiomerically enriched pyrrolo[2,3-d]carbazole was obtained in up to 74% ee. This methodology was successfully applied to the asymmetric formal synthesis of vindorosine.

Direct synthesis of aryl-annulated [c]carbazoles by gold(i)-catalysed cascade reaction of azide-diynes and arenes.

The gold-catalysed annulation of conjugated alkynes bearing an azido group with arenes gave annulated [c]carbazoles. Using benzene, pyrrole, and indole derivatives as the nucleophiles, benzo[c]-, pyrrolo[2,3-c]-, and indolo[2,3-c]carbazoles were produced, respectively. The reaction proceeded through pyrrole and benzene ring construction accompanied by the formation of two carbon-carbon and one carbon-nitrogen bond and the cleavage of two aromatic C-H bonds. The mechanism of the reaction with pyrrole was investigated by density functional theory calculations. N,N'-dimethylated indolo[2,3-c]carbazole showed dual ultraviolet-visible-near-infrared and fluorescence spectral changes upon electrolysis.

Total Synthesis of Dictyodendrins by the Gold-Catalyzed Cascade Cyclization of Conjugated Diynes with Pyrroles.

In total and formal syntheses of dictyodendrins B, C, E, and F, the key step involved the direct construction of the pyrrolo[2,3-c]carbazole core by the gold-catalyzed annulation of a conjugated diyne with a pyrrole to form three bonds and two aromatic rings. The subsequent introduction of substituents at the C1 (Suzuki-Miyaura coupling), C2 (addition to an aldehyde), N3 (alkylation), and C5 positions (Ullman coupling) provided divergent access to dictyodendrins.

CAr-O Rotamers in 3,3'-Disubstituted BINOL Esters.

Rotamers around the CAr-O bond were disclosed in 3,3'-disubstituted BINOL esters by NMR spectroscopy. A bulky R1 group increased the rotational barrier. The pivalate showed two rotamers at 2 °C, and broad signals were observed close to room temperature when R2 = Ph. The highest rotational barrier was recorded for the (tetracyanocyclopentadienyl)carboxylate, and C-O rotamers were present at room temperature. DFT calculations indicated the presence of repulsion between R1 and R2 during rotation of the CAr-O bond.

Synthesis of functionalized tetracyanocyclopentadienides from tetracyanothiophene and sulfones.

Tetracyanothiophene and tetracyano-1,4-dithiin react with a leaving group substituted carbon nucleophile such as ethyl benzenesulfonylacetate to afford substituted tetracyanocyclopentadienyl sodium derivatives in moderate to high yields through a putative condensation and desulfurization pathway. Subsequent functional-group transformation reactions on the Cp anion ring provided various C5R(CN)4(-) derivatives.