Catalytic Asymmetric Total Synthesis of (−)-Actinophyllic Acid

Described herein is a catalytic asymmetric total synthesis of (−)-actinophyllic acid, with the key step being a chiral phosphine-catalyzed [3 + 2] annulation between an imine and an allenoate to form a pyrroline intermediate in 99% yield and 94% ee. The synthesis also features CuI-catalyzed coupling between a ketoester and a 2-iodoindole to shape the tetrahydroazocine ring; intramolecular alkylative lactonization; SmI₂-mediated intramolecular pinacol coupling between ketone and lactone subunits to assemble the complex skeleton of (−)-actinophyllic acid; and an unprecedented regioselective dehydroxylation

Phosphine-Catalyzed Intramolecular Cyclizations of α‑Nitroethyl­allenoates Forming (<i>Z</i>)‑Furanone Oximes

A novel and efficient phosphine-catalyzed intramolecular cyclization of α-nitroethyl­allenic esters is reported. This process appears to be practical for the stereoselective syntheses of (<i>Z</i>)-furan-2­(3<i>H</i>)-one oxime derivatives in excellent yields. Mechanistically, the reaction involves a phosphine-catalyzed Michael addition of an alkylideneazinate and rearrangement of the cyclic nitronate to the α-nitroso­dihydrofuran

Phosphine-Catalyzed Intramolecular Cyclizations of α‑Nitroethyl­allenoates Forming (<i>Z</i>)‑Furanone Oximes

A novel and efficient phosphine-catalyzed intramolecular cyclization of α-nitroethyl­allenic esters is reported. This process appears to be practical for the stereoselective syntheses of (<i>Z</i>)-furan-2­(3<i>H</i>)-one oxime derivatives in excellent yields. Mechanistically, the reaction involves a phosphine-catalyzed Michael addition of an alkylideneazinate and rearrangement of the cyclic nitronate to the α-nitroso­dihydrofuran

TFE-Facilitated Synthesis of Tetrahydropyridino[2,3‑<i>d</i>]pyrimidine via Cascade [1,5]-Hydride Transfer/Cyclization

An efficient fluorinated alcohol-driven cascade [1,5]-hydride transfer/cyclization between o-amino pyridyl aldehydes and primary amines has been developed. This unique transformation enabled an array of tetrahydropyridino[2,3-d]pyrimidine construction. Furthermore, the encouraging antifungal activity of Thanatephorus cucumeris was demonstrated by this tetrahydropyridino[2,3-d]pyrimidine core structure

Phosphine-Mediated Iterative Arene Homologation Using Allenes

A PPh₃-mediated multicomponent reaction between <i>o</i>-phthalaldehydes, nucleophiles, and monosubstituted allenes furnishes functionalized non-<i>C</i>₂-symmetric naphthalenes in synthetically useful yields. When the <i>o</i>-phthalaldehydes were reacted with 1,3-disubstituted allenes in the presence of PPh₂Et, naphthalene derivatives were also obtained in up to quantitative yields. The mechanism of the latter transformation is straightforward: aldol addition followed by Wittig olefination and dehydration. The mechanism of the former is a tandem γ-umpolung/aldol/Wittig/dehydration process, as established by preparation of putative reaction intermediates and mass spectrometric analysis. This transformation can be applied iteratively to prepare anthracenes and tetracenes using carboxylic acids as pronucleophiles

In Situ Generation of Fluorescent Amino Acids and Peptides via Double C–H Activation/Annulation

Unnatural fluorescent amino acids have been synthesized to obtain better emission wavelengths, fluorescence lifetime, and quantum yields. Despite major advances, most of them face inherent restrictions as fluorophores and are limited to the methods from coupling between amino acids and fluorophores. Herein, we develop a Rh­(III)-catalyzed double C–H activation/annulation reaction of diverse benzamides with alkynes for the synthesis of tricyclic-fused aromatic hydrocarbon carbocations. The robustness of this strategy is demonstrated by the diversification of Lys-based amino acids and peptides, in situ generating tricyclic fluorophores. This method features broad substrate scope and high atom and step economy as well as high chemo- and site selectivity. Unsymmetrical double C–H activation/annulation employing two different alkynes is well tolerated to produce the unnatural fluorescent amino acids in high yields. These tricyclic fluorophores display tunable fluorescence emission, low cytotoxicity, and the potential for specifically targeting lysosomes

Oxidation-Induced Protein Cross-Linking in Mammalian Cells

A proximity-enabled protein cross-linking strategy with additional spatiotemporal control is highly desirable. Here, we report an oxidation-induced protein cross-linking strategy involving the incorporation of a vinyl thioether group into proteins in both Escherichia coli and mammalian cells via genetic code expansion. We demonstrated that vinyl thioether can be selectively induced by exogenously added oxidant or by reactive oxygen species from the cellular environment, as well as by photocatalysts, and converted into a Michael acceptor, enabling fluorescence labeling and protein cross-linking