Selective Construction of C-S/S-N Bonds from N-Substituted O-Thiocarbamates and Indoles under Transition-Metal-Free Conditions.

A method for the selective construction of S-N/C(sp2)-S bonds using N-substituted O-thiocarbamates and indoles as substrates is reported. This protocol features good atom utilization, mild conditions, short reaction time, and wide substrate scope, which can provide a convenient path for the functionalization of indoles. In addition, the reaction could be scaled up on gram scale, showing potential application value in industry synthesis.

C(sp2)-H Functionalization of Imidazole at the C2- and C4-Position via Palladium-Catalyzed Isocyanide Insertion Leading to Indeno[1,2-d]imidazole and Imidazo[1,2-a]indole Derivatives.

An efficient strategy for the construction of fused imidazole derivatives through a palladium-catalyzed isocyanide insertion reaction has been accomplished. The methodology provides an operationally simple and versatile route for the synthesis of indeno[1,2-d]imidazole and imidazo[1,2-a]indole skeletons which are rarely reported. The key features of the protocol are construction of sequential C-C/C-C/C-N bonds via C(sp2)-H functionalization of imidazole at the C2- and C4-position, respectively. The compounds can be synthesized with diverse scaffolds, easily accessible starting materials, and moderate to good yields.

Isocyano(triphenylphosphoranylidene)acetates: Key to the One-Pot Synthesis of Oxazolo[4,5-c]quinoline Derivatives via a Sequential Ugi/Wittig/aza-Wittig Cyclization Process.

A one-pot novel strategy is described for the construction of various oxazolo[4,5-c]quinoline derivatives starting from the isocyano(triphenylphosphoranylidene)acetates, aldehydes, amines, and 2-azidobenzoic acids. The reactions generated the target products directly in moderate to good yields via a sequential Ugi/Wittig/aza-Wittig cyclization process. The salient features of the method are that all three groups of the multifunctional isocyanides were involved in the reaction with broad substituent scopes and mild reaction conditions, making the protocol a useful contribution to the synthesis of oxazolo[4,5-c]quinoline heterocycles.

Synthesis of iminoisoindolinones via a cascade of the three-component Ugi reaction, palladium catalyzed isocyanide insertion, hydroxylation and an unexpected rearrangement reaction.

A robust ligand-free palladium-catalyzed cascade reaction for the synthesis of diversely substituted iminoisoindolinones has been developed. The cascade reaction involves isocyanide insertion into Ugi-3CR adducts, accompanied by unexpected hydroxylation and rearrangement.

Synthesis of 2,3-Dihydro-1H-2-benzazepin-1-ones and 3H-2-Benzoxepin-1-ones by Isocyanide-Based Multicomponent Reaction/Wittig Sequence Starting from Phosphonium Salt Precursors.

A one-pot synthesis of multisubstituted 2,3-dihydro-1H-2-benzazepin-1-ones and 3H-2-benzoxepin-1-ones by an I-MCR/Wittig sequence was developed. The reaction of phosphonium salt 3, arylglyoxals 4, amine 5 (or without), and isocyanide 6 produced the 2,3-dihydro-1H-2-benzazepin-1-ones 8 or 3H-2-benzoxepin-1-ones 10 in good yields via a sequential Ugi or Passerini condensation and intramolecular Wittig reaction in the presence of NEt3.

Characterization of two novel knock-in mouse models of syndromic retinal ciliopathy carrying hypomorphic Sdccag8 mutations.

Mutations in serologically defined colon cancer autoantigen protein 8 ( SDCCAG8) were first identified in retinal ciliopathy families a decade ago with unknown function. To investigate the pathogenesis of SDCCAG8-associated retinal ciliopathies in vivo, we employed CRISPR/Cas9-mediated homology-directed recombination (HDR) to generate two knock-in mouse models, Sdccag8Y236X/Y236X and Sdccag8E451GfsX467/E451GfsX467 , which carry truncating mutations of the mouse Sdccag8, corresponding to mutations that cause Bardet-Biedl syndrome (BBS) and Senior-Løken syndrome (SLS) (c.696T>G p.Y232X and c.1339-1340insG p.E447GfsX463) in humans, respectively. The two mutant Sdccag8 knock-in mice faithfully recapitulated human SDCCAG8-associated BBS phenotypes such as rod-cone dystrophy, cystic renal disorder, polydactyly, infertility, and growth retardation, with varied age of onset and severity depending on the hypomorphic strength of the Sdccag8 mutations. To the best of our knowledge, these knock-in mouse lines are the first BBS mouse models to present with the polydactyly phenotype. Major phototransduction protein mislocalization was also observed outside the outer segment after initiation of photoreceptor degeneration. Impaired cilia were observed in the mutant photoreceptors, renal epithelial cells, and mouse embryonic fibroblasts derived from the knock-in mouse embryos, suggesting that SDCCAG8 plays an essential role in ciliogenesis, and cilium defects are a primary driving force of SDCCAG8-associated retinal ciliopathies.

Divergent Conversion of Double Isocyanides with Alkenyl Bromide to Polysubstituted Pyrroles and 4-Imino-4,5-dihydropyrrolo[3,4-b]pyrrol-6(1H)-one Derivatives by Pd-Catalyzed Tandem Cyclization Reactions.

Herein a novel and concise approach to pyrrole skeletons via Pd-catalyzed tandem cyclization reactions is investigated. The substrates for the transformation could be readily prepared by phosphoric acid-catalyzed Ugi reactions with available starting materials. In this strategy, two isocyanides participate in sequential isocyanide insertion reactions, and the chemoselectivity of the products is regulated by the steric hindrance of the isocyanide. A plausible mechanism for the formation of the corresponding adducts is proposed.