Alkene/Alkyne Chemistry #1

A mechanism and a synthesis problem related to alkene and alkyne chemistryTwo problems related to alkene and alkyne chemistr

Mechanism, reactivity, and selectivity of nickel-catalyzed [4 + 4 + 2] cycloadditions of dienes and alkynes.

Density functional theory (DFT) calculations with B3LYP and M06 functionals elucidated the reactivities of alkynes and Z/E selectivity of cyclodecatriene products in the Ni-catalyzed [4 + 4 + 2] cycloadditions of dienes and alkynes. The Ni-mediated oxidative cyclization of butadienes determines the Z/E selectivity. Only the oxidative cyclization of one s-cis to one s-trans butadiene is facile and exergonic, leading to the observed 1Z,4Z,8E-cyclodecatriene product. The same step with two s-cis or s-trans butadienes is either kinetically or thermodynamically unfavorable, and the 1Z,4E,8E- and 1Z,4Z,8Z-cyclodecatriene isomers are not observed in experiments. In addition, the competition between the desired cooligomerization and [2 + 2 + 2] cycloadditions of alkynes depends on the coordination of alkynes. With either electron-deficient alkynes or alkynes with free hydroxyl groups, the coordination of alkynes is stronger than that of dienes, and alkyne trimerization prevails. With alkyl-substituted alkynes, the generation of alkyne-coordinated nickel complex is much less favorable, and the [4 + 4 + 2] cycloaddition occurs

A Simple Nickel Catalyst Enabling an E‐Selective Alkyne Semihydrogenation

Stereoselective alkyne semihydrogenations are attractive approaches to alkenes, which are key building blocks for synthesis. With regards to the most atom economic reducing agent dihydrogen (H 2 ), only few catalysts for the challenging E ‐selective alkyne semihydrogenation have been disclosed, each with a unique substrate scope profile. Here, we show that a commercially available nickel catalyst facilitates the E ‐selective alkyne semihydrogenation of a wide variety of substituted internal alkynes. This results in a simple and broadly applicable overall protocol to stereoselectively access E ‐alkenes employing H 2 which could serve as a general method for synthesis.DFG, 352364740, Diwasserstoff-vermittelte nachhaltige BindungsknüpfungsreaktionenTU Berlin, Open-Access-Mittel - 201

Orthogonal, metal-free surface modification by strain-promoted azide–alkyne and nitrile oxide–alkene/alkyne cycloadditions

In this article we present a fast and efficient methodology for biochemical surface patterning under extremely mild conditions. Micropatterned azide/benzaldoxime-surfaces were prepared by microcontact printing of a heterobifunctional cyclooctyne oxime linker on azide-terminated self-assembled monolayers (SAMs). Strain-promoted azide–alkyne cycloaddition (SPAAC) in combination with microcontact printing allows fast and effective surface patterning. The resulting bifunctional azide/oxime substrates could successfully be used for metal-free, orthogonal immobilization of various biomolecules by 1,3-dipolar cycloadditions at room temperature. Azide-decorated areas were modified by reaction with a cyclooctyne-conjugate using SPAAC, while benzaldoxime-decorated areas were activated by in situ oxidation to the reactive nitrile oxides and subsequent nitrile oxide cycloaddition with alkene- and alkyne-functionalized bioconjugates. In addition, orthogonal double immobilization was achieved by consecutive and independent SPAAC and nitrile oxide cycloadditions

Electrochemically modified Corey-Fuchs reaction for the synthesis of arylalkynes. the case of 2-(2,2-dibromovinyl)naphthalene

The electrochemical reduction of 2-(2,2-dibromovinyl)naphthalene in a DMF solution (Pt cathode) yields selectively 2-ethynylnaphthalene or 2-(bromoethynyl)naphthalene in high yields, depending on the electrolysis conditions. In particular, by simply changing the working potential and the supporting electrolyte, the reaction can be directed towards the synthesis of the terminal alkyne (Et4NBF4) or the bromoalkyne (NaClO4). This study allowed to establish that 2-(bromoethynyl)naphthalene can be converted into 2-ethynylnaphthalene by cathodic reduction

Discovery of TUG-770: a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes

Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing

Cyclooctyne-based reagents for uncatalyzed click chemistry: A computational survey

With the goal of identifying alkyne-like reagents for use in click chemistry, but without Cu catalysts, we used B3LYP density function theory (DFT) to investigate the trends in activation barriers for the 1,3-dipolar cycloadditions of azides with various cyclooctyne, dibenzocyclooctyne, and azacyclooctyne compounds. Based on these trends, we find monobenzocyclooctyne-based reagents that are predicted to have dramatically improved reactivity over currently employed reagents