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Angewandte Chemie (International Ed. in... Jun 2021A colorimetric indicator displacement assay (IDA) amenable to high-throughput experimentation was developed to determine the percentage of cis and trans alkenes. Using...
A colorimetric indicator displacement assay (IDA) amenable to high-throughput experimentation was developed to determine the percentage of cis and trans alkenes. Using 96-well plates two steps are performed: a reaction plate for dihydroxylation of the alkenes followed by an IDA screening plate consisting of an indicator and a boronic acid. The dihydroxylation generates either erythro or threo vicinal diols from cis or trans alkenes, depending upon their syn- or anti-addition mechanisms. Threo diols preferentially associate with the boronic acid due to the creation of more stable boronate esters, thus displacing the indicator to a greater extent. The generality of the protocol was demonstrated using seven sets of cis and trans alkenes. Blind mixtures of cis and trans alkenes were made, resulting in an average error of ±2 % in the percentage of cis or trans alkenes, and implementing E and Wittig reactions gave errors of ±3 %. Furthermore, we developed variants of the IDA for which the color may be tuned to optimize the response for the human eye.
Topics: Alkenes; Colorimetry; Molecular Structure; Stereoisomerism
PubMed: 33723888
DOI: 10.1002/anie.202101004 -
Journal of the American Chemical Society Dec 2021Allylic amines are valuable synthetic targets en route to diverse biologically active amine products. Current allylic C-H amination strategies remain limited with...
Allylic amines are valuable synthetic targets en route to diverse biologically active amine products. Current allylic C-H amination strategies remain limited with respect to the viable -substituents. Herein, we disclose a new electrochemical process to prepare aliphatic allylic amines by coupling two abundant starting materials: secondary amines and unactivated alkenes. This oxidative transformation proceeds via electrochemical generation of an electrophilic adduct between thianthrene and the alkene substrates. Treatment of these adducts with aliphatic amine nucleophiles and base provides allylic amine products in high yield. This synthetic strategy is also amenable to functionalization of feedstock gaseous alkenes at 1 atm. In the case of 1-butene, high -selective crotylation is observed. This strategy, however, is not limited to the synthesis of simple building blocks; complex biologically active molecules are suitable as both alkene and amine coupling partners. Preliminary mechanistic studies implicate vinylthianthrenium salts as key reactive intermediates.
Topics: Alkenes; Amines; Electrochemical Techniques; Models, Molecular; Molecular Structure
PubMed: 34914394
DOI: 10.1021/jacs.1c11763 -
Organic & Biomolecular Chemistry Sep 2022The hydroarylation of alkynes, alkenes, and allenes is a cost-effective and efficient way to incorporate unsaturated moieties into aromatic substrates. This review... (Review)
Review
The hydroarylation of alkynes, alkenes, and allenes is a cost-effective and efficient way to incorporate unsaturated moieties into aromatic substrates. This review focuses on gold-catalyzed hydroarylation, which produces aromatic alkenes, diaryl-alkanes, heterocycles, carbocycles, and arylbutadienes by directly functionalizing C-H bonds. Without the need for prefunctionalization, direct functionalization of aromatic C-H bonds with unsaturated moieties (alkyne, alkene, allene) provides an efficient synthetic strategy with fewer reaction steps. This review offers an overview of the recently developed hydroarylation processes catalyzed by gold. Mechanisms of hydroarylation alkyne, alkene, allene, and arene activation receive special attention.
Topics: Alkadienes; Alkanes; Alkenes; Alkynes; Catalysis; Gold
PubMed: 36069264
DOI: 10.1039/d2ob00960a -
Bioorganic & Medicinal Chemistry Letters Jan 2014A new class of CGRP receptor antagonists was identified by replacing the central amide of a previously identified anilide lead structure with ethylene, ethane, or ethyne...
A new class of CGRP receptor antagonists was identified by replacing the central amide of a previously identified anilide lead structure with ethylene, ethane, or ethyne linkers. (E)-Alkenes as well as alkynes were found to preserve the proper bioactive conformation of the amides, necessary for efficient receptor binding. Further exploration resulted in several potent compounds against CGRP-R with low susceptibility to P-gp mediated efflux.
Topics: Alkenes; Amides; Calcitonin Gene-Related Peptide Receptor Antagonists; Dose-Response Relationship, Drug; HEK293 Cells; Humans; Molecular Structure; Structure-Activity Relationship
PubMed: 24332093
DOI: 10.1016/j.bmcl.2013.11.027 -
Chemistry (Weinheim An Der Bergstrasse,... Jan 2023Recently, it was shown that the double Ca-H-Ca bridged calcium hydride cation dimer complex [LCaH CaL] (macrocyclic ligand L=NNNN-tetradentate Me TACD) exhibited...
Recently, it was shown that the double Ca-H-Ca bridged calcium hydride cation dimer complex [LCaH CaL] (macrocyclic ligand L=NNNN-tetradentate Me TACD) exhibited remarkable activity in catalyzing the hydrogenation of unactivated 1-alkenes as well as the H isotope exchange under mild conditions, tentatively via the terminal Ca-H bond of cation monomer LCaH . In this DFT mechanistic work, a novel substrate-dependent catalytic mechanism is disclosed involving cooperative Ca-H-Ca bridges for H isotope exchange, competitive Ca-H-Ca bridges and terminal Ca-H bonds for anti-Markovnikov addition of unactivated 1-alkenes, and terminal Ca-H bonds for Markovnikov addition of conjugation-activated styrene. THF-coordination plays a key role in favoring the anti-Markovnikov addition while strong cation-π interactions direct the Markovnikov addition to terminal Ca-H bonds.
Topics: Hydrogenation; Calcium; Alkenes; Catalysis; Cations
PubMed: 36214655
DOI: 10.1002/chem.202202602 -
Angewandte Chemie (International Ed. in... Nov 2020The gold-catalyzed intermolecular oxyarylation of alkenes is reported. This work employed the oxidative addition of aryl iodides to Me-DalphosAu for the formation of a...
The gold-catalyzed intermolecular oxyarylation of alkenes is reported. This work employed the oxidative addition of aryl iodides to Me-DalphosAu for the formation of a Au -Ar intermediate. The better binding ability of alkenes over O nucleophiles ensured the success of intermolecular oxyarylation, giving desired products with a broad substrate scope and high efficiency (>50 examples with up to 95 % yield). One-pot converting of methoxy groups into other nucleophiles allowed achieving alkene difunctionalization with the construction of C-N, C-S, and C-C bonds under mild conditions.
Topics: Alkenes; Catalysis; Gold; Molecular Structure; Oxidation-Reduction; Stereoisomerism
PubMed: 32748527
DOI: 10.1002/anie.202009636 -
Angewandte Chemie (International Ed. in... Oct 2015Radical changes: The applicability of alkene hydroamination has recently been significantly expanded by the development of radical variants that are based on initial...
Radical changes: The applicability of alkene hydroamination has recently been significantly expanded by the development of radical variants that are based on initial hydrogen atom transfer to the alkene. This Highlight assesses the current state of the art, focusing on an iron-catalyzed reaction that utilizes stable nitroarenes as the electrophilic N component and is based on the dual catalytic activation of both starting materials.
Topics: Alkenes; Amination; Catalysis; Hydrogen; Iron; Nitro Compounds
PubMed: 26358866
DOI: 10.1002/anie.201506885 -
Journal of the American Chemical Society Apr 2015OleT(JE), a cytochrome P450, catalyzes the conversion of fatty acids to terminal alkenes using hydrogen peroxide as a cosubstrate. Analytical studies with an eicosanoic...
OleT(JE), a cytochrome P450, catalyzes the conversion of fatty acids to terminal alkenes using hydrogen peroxide as a cosubstrate. Analytical studies with an eicosanoic acid substrate show that the enzyme predominantly generates nonadecene and that carbon dioxide is the one carbon coproduct of the reaction. The addition of hydrogen peroxide to a deuterated substrate-enzyme (E-S) complex results in the transient formation of an iron(IV) oxo π cation radical (Compound I) intermediate which is spectroscopically indistinguishable from those that perform oxygen insertion chemistries. A kinetic isotope effect for Compound I decay suggests that it abstracts a substrate hydrogen atom to initiate fatty acid decarboxylation. Together, these results indicate that the initial mechanism for alkene formation, which does not result from oxygen rebound, is similar to that widely suggested for P450 monooxygenation reactions.
Topics: Alkenes; Cytochrome P-450 Enzyme System; Decarboxylation; Fatty Acids; Molecular Structure
PubMed: 25843451
DOI: 10.1021/jacs.5b01965 -
Molecules (Basel, Switzerland) Mar 2012Fully substituted olefin generation via metathesis is presented. Catalyst development, optimization of reaction conditions and substrate screening are included. In...
Fully substituted olefin generation via metathesis is presented. Catalyst development, optimization of reaction conditions and substrate screening are included. In addition, asymmetric alkene metathesis, the cross metathesis reaction for this transformation and its application in natural products will be discussed.
Topics: Alkenes; Catalysis; Molecular Structure; Stereoisomerism
PubMed: 22421789
DOI: 10.3390/molecules17033348 -
Journal of the American Chemical Society Mar 2018An expansion of methodologies aimed at the formation of versatile organonitriles, via the intramolecular aminocyanation of unactivated alkenes, is herein reported....
An expansion of methodologies aimed at the formation of versatile organonitriles, via the intramolecular aminocyanation of unactivated alkenes, is herein reported. Importantly, the need for a rigid tether in these reactions has been obviated. The ease-of-synthesis and viability of substrates bearing flexible backbones has permitted for diastereoselective variants as well. We demonstrated the utility of this methodology with the formation of pyrrolidones, piperidinones, isoindolinones, and sultams. Furthermore, subsequent transformation of these motifs into medicinally relevant molecules is also demonstrated. A double crossover C-labeling experiment is consistent with a fully intramolecular cyclization mechanism. Deuterium labeling experiments support a mechanism involving syn-addition across the alkene.
Topics: Alkenes; Amination; Catalysis; Cyclization; Deuterium; Lewis Acids; Models, Molecular; Nitriles; Palladium; Phthalimides; Pyrrolidinones; Stereoisomerism
PubMed: 29465996
DOI: 10.1021/jacs.8b01330