Yuto Sumida

Palladium-catalyzed regio- and stereoselective hydrosilylation of electron-deficient alkynes.

Highly regio- and stereoselective hydrosilylation applicable to a broad range of electron-deficient alkynes has been established using palladium catalysis. The synthetic utility of the method has been demonstrated by further transformations of α-silylalkenes, particularly Hiyama coupling and stereoinverting iododesilylation followed by Suzuki-Miyaura coupling, which enables stereodivergent syntheses of α-arylenoates.

Generation of Arynes via Ate Complexes of Arylboronic Esters with an ortho-Leaving Group

An efficient method of generating aryne has been achieved by treating ortho-(trifluoromethanesulfonyloxy)arylboronic acid pinacol ester with tert- or sec-butyllithium. Monitoring the reaction by (11)B NMR has indicated that a boron-ate complex formed in situ is the eventual precursor that converts into aryne near room temperature. The prior formation of the ate complex at a low temperature has enabled us to use various arynophiles, including those bearing base-sensitive groups. The ready availability of the aryne precursors and mutual orthogonality in aryne generation with widely used ortho-silylaryl triflate have enhanced the utility of the method.

Nickel-Catalyzed Borylative Ring-Opening Reaction of Vinylcyclopropanes with Bis(pinacolato)diboron Yielding Allylic Boronates

Vinylcyclopropanes bearing one or two electron-withdrawing groups on the cyclopropane ring undergo nickel-catalyzed borylative ring opening with bis(pinacolato)diboron to yield allylic boronates. The reaction proceeded with high E selectivity.

Boron-Selective Biaryl Coupling Approach to Versatile Dibenzoxaborins and Application to Concise Synthesis of Defucogilvocarcin M

An efficient synthetic method for versatile dibenzoxaborins based on boron-selective Suzuki-Miyaura cross-coupling between o-borylphenols and aryl halides or triflates bearing a 1,8-diaminonaphthalene-protected o-boryl group is reported. A short synthesis of defucogilvocarcin M was achieved using the proposed method in combination with several other boron-mediated transformations.

Nickel-Catalyzed Allylation of Allyl Carbonates with Homoallyl Alcohols via Retro-Allylation Providing 1,5-Hexadienes

A highly efficient and mild method for the synthesis of 1,5-hexadienes, nickel-catalyzed reactions of Boc-protected allyl alcohols with homoallyl alcohols, has been developed. Nickel-mediated retro-allylation allows for the use of homoallyl alcohols as allylmetal equivalents in the synthesis of 1,5-hexadienes.

Palladium-Catalyzed Preparation of Silyl Enolates from α,β-Unsaturated Ketones or Cyclopropyl Ketones with Hydrosilanes

Alpha,beta-unsaturated ketones and cyclopropyl ketones undergo palladium-catalyzed hydrosilylation with hydrosilanes to yield (Z)-silyl enolates.

Nickel-Catalyzed Borylation of Aryl Cyclopropyl Ketones with Bis(pinacolato)diboron to Synthesize 4-Oxoalkylboronates

Aryl cyclopropyl ketones undergo nickel-catalyzed borylative ring opening with bis(pinacolato)diboron to yield 4-oxoalkylboronates.

An Alternative Method for Generating Arynes from ortho-Silylaryl Triflates: Activation by Cesium Carbonate in the Presence of a Crown Ether

An alternative method for generating arynes from ortho-silylaryl triflates using cesium carbonate and 18-crown-6 is reported. The method was efficiently applied to a variety of reactions between several arynes and arynophiles. We also demonstrated that the efficiency of aryne generation is significantly affected by the alkali metal countercation of the carbonate.

Selective inhibition of the kinase DYRK1A by targeting its folding process

Autophosphorylation of amino-acid residues is part of the folding process of various protein kinases. Conventional chemical screening of mature kinases has missed inhibitors that selectively interfere with the folding process. Here we report a cell-based assay that evaluates inhibition of a kinase at a transitional state during the folding process and identify a folding intermediate-selective inhibitor of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), which we refer to as FINDY. FINDY suppresses intramolecular autophosphorylation of Ser97 in DYRK1A in cultured cells, leading to its degradation, but does not inhibit substrate phosphorylation catalysed by the mature kinase. FINDY also suppresses Ser97 autophosphorylation of recombinant DYRK1A, suggesting direct inhibition, and shows high selectivity for DYRK1A over other DYRK family members. In addition, FINDY rescues DYRK1A-induced developmental malformations in Xenopus laevis embryos. Our study demonstrates that transitional folding intermediates of protein kinases can be targeted by small molecules, and paves the way for developing novel types of kinase inhibitors.

Nickel-Catalyzed Arylative Ring-Opening of 3-Methylenecycloalkane-1,1-dicarboxylates

An arylative ring-opening reaction of cyclic allylmalonates with arylzinc reagents under nickel catalysis has been developed. Upon the ring-opening sp(3)C-sp(3)C bond cleavage, the allylic moiety serves as an allylic electrophile to react with arylzinc reagents. Simultaneously, the malonate moiety is converted to the corresponding zinc enolate, which can react further with electrophiles. The overall process increases molecular complexity and diversity starting from readily available substrates and is useful in organic synthesis.