Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GPhos Ligand Enables Production of Chiral N-Arylamines in a Telescoped Transaminase-Buchwald-Hartwig Amination Cascade in the Presence of Excess Amine Donor.

ABSTRACT: The combination of biocatalysis and chemocatalysis can be more powerful than either technique alone. However, combining the two is challenging due to typically very different reaction conditions. Herein, chiral N-aryl amines, key features of many active pharmaceutical ingredients, are accessed in excellent enantioselectivity (typically>99.5 % ee) by combining transaminases with the Buchwald-Hartwig amination. By employing a bi-phasic buffer-toluene system as well as the ligand GPhos, the telescoped cascade proceeded with up to 89 % overall conversion in the presence of excess alanine. No coupling to alanine was observed.

SUBMITTER: Heckmann CM

PROVIDER: S-EPMC9292530 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

GPhos Ligand Enables Production of Chiral N-Arylamines in a Telescoped Transaminase-Buchwald-Hartwig Amination Cascade in the Presence of Excess Amine Donor.

Heckmann Christian M CM Paradisi Francesca F

Chemistry (Weinheim an der Bergstrasse, Germany) 20211008 67

The combination of biocatalysis and chemocatalysis can be more powerful than either technique alone. However, combining the two is challenging due to typically very different reaction conditions. Herein, chiral N-aryl amines, key features of many active pharmaceutical ingredients, are accessed in excellent enantioselectivity (typically>99.5 % ee) by combining transaminases with the Buchwald-Hartwig amination. By employing a bi-phasic buffer-toluene system as well as the ligand GPhos, the telesco ...[more]

PMID: 34585789

Similar Datasets

One-Pot Synthesis of Chiral N-Arylamines by Combining Biocatalytic Aminations with Buchwald-Hartwig N-Arylation.

Project description:The combination of biocatalysis and chemo-catalysis increasingly offers chemists access to more diverse chemical architectures. Here, we describe the combination of a toolbox of chiral-amine-producing biocatalysts with a Buchwald-Hartwig cross-coupling reaction, affording a variety of α-chiral aniline derivatives. The use of a surfactant allowed reactions to be performed sequentially in the same flask, preventing the palladium catalyst from being inhibited by the high concentrations of ammonia, salts, or buffers present in the aqueous media in most cases. The methodology was further extended by combining with a dual-enzyme biocatalytic hydrogen-borrowing cascade in one pot to allow for the conversion of a racemic alcohol to a chiral aniline.

| S-EPMC7590080 | biostudies-literature

Single Step Synthesis of Non-symmetric Azoarenes Using Buchwald–Hartwig Amination

Project description: Not available

| S-EPMC11603238 | biostudies-literature

Phenylboronic Ester-Activated Aryl Iodide-Selective Buchwald-Hartwig-Type Amination toward Bioactivity Assay.

Project description:In this study, a phenylboronic ester-activated aryl iodide-selective Buchwald-Hartwig-type amination was developed. When the reaction of aryl iodides and aryl/aliphatic amines using Ni(acac)2 is carried out in the presence of phenylboronic ester, the Buchwald-Hartwig-type amination proceeds smoothly to afford the corresponding amines in high yields. This reaction does not proceed in the absence of phenylboronic ester. A wide variety of aryl iodides can be applied in the presence of aryl chlorides and bromides, which remain intact during the reaction. The mechanistic studies of this reaction suggest that the phenylboronic ester acts as an activator for the amines to form the ″ate complex″. Chemical kinetics studies show that the reaction of aryl iodides, base, and Ni(acac)2 follows first-order kinetics, while that of amines and phenylboronic ester follows zero-order kinetics. The bioactivity screening of the corresponding products showed that some amination products exhibit antifungal activity.

| S-EPMC9301730 | biostudies-literature

Lithium sensors based on photophysical changes of 1-aza-12-crown-4 naphthalene derivatives synthesized <i>via</i> Buchwald-Hartwig amination.

Project description:Lithium detection is of great significance in many applications. Lithium-sensing compounds with high selectivity are scarce and, if any, complicated to synthesize. We herein report a novel yet simple compound that can detect lithium ions in an organic solvent through changes in absorbance and fluorescence. Naphthalene functionalized with 1-aza-12-crown-4 (1) was synthesized via one step from commercially available 1-bromonaphthalene through Buchwald-Hartwig amination. In order to obtain a structure-property relationship, we also synthesized two other compounds that are structurally similar to 1, wherein the compounds 2 and 3 include an imide moiety (an electron acceptor) and do not include a 1-aza-12-crown-4 unit, respectively. Upon the addition of lithium ions, compound 1 displayed a clear isosbestic point in the absorption spectra and a new peak in the fluorescence spectra, whereas the compounds 2 and 3 indicated miniscule and no spectroscopic changes, respectively. 1H NMR titration studies and the calculated optimized geometry from density functional theory (DFT) indicated the lithium binding on the aza-crown. The calculated limit of detection (LOD) was 21 μM. The lithium detection with 1 is selective among other alkali metals (Na+, K+, and Cs+). DFT calculation indicated that the lone pair electrons in the nitrogen atom of 1 is delocalized yet available to bind lithium, whereas the nitrogen lone pair electrons of 2 showed significant intramolecular charge transfer to the imide acceptor, resulting in a high dipole moment, and thus were unavailable to bind lithium. This work elucidates the key design parameters for future lithium sensors.

| S-EPMC9641676 | biostudies-literature

Rapid Evaluation of the Mechanism of Buchwald-Hartwig Amination and Aldol Reactions Using Intramolecular <sup>13</sup>C Kinetic Isotope Effects.

Project description:A practical approach is introduced for the rapid determination of 13C kinetic isotope effects that utilizes a "designed" reactant with two identical reaction sites. The mechanism of the Buchwald-Hartwig amination of tert-butylbromobenzene with primary and secondary amines is investigated under synthetically relevant catalytic conditions using traditional intermolecular 13C NMR methodology at natural abundance. Switching to 1,4-dibromobenzene, a symmetric bromoarene as the designed reactant, the same experimental 13C KIEs are determined using an intramolecular KIE approach. This rapid methodology for KIE determination requires substantially less material and time compared to traditional approaches. Details of the Buchwald-Hartwig amination mechanism are investigated under varying synthetic conditions, namely a variety of halides and bases. The enantioselectivity-determining step of the l-proline catalyzed aldol reaction is also evaluated using this approach. We expect this mechanistic methodology to gain traction among synthetic chemists as a practical technique to rapidly obtain high-resolution information regarding the transition structure of synthetically relevant reactions under catalytic conditions.

| S-EPMC8516138 | biostudies-literature

A new nanomagnetic Pd-Co bimetallic alloy as catalyst in the Mizoroki-Heck and Buchwald-Hartwig amination reactions in aqueous media.

Project description:A Pd-Co bimetallic alloy encapsulated in melamine-based dendrimer supported on magnetic nanoparticles denoted as γ-Fe2O3@MBD/Pd-Co was synthesized by a facile co-complexation-reduction method and characterized sufficiently. The catalytic evaluation of γ-Fe2O3@MBD/Pd-Co showed promising results in the Mizoroki-Heck and Buchwald-Hartwig amination reactions of various iodo-, bromo- and challenging chloroarenes in aqueous media. The synergetic cooperative effect of both Pd and Co and dispersion of the catalyst in water due to the encapsulation of γ-Fe2O3 by melamine-based dendrimer lead to high catalytic performance compared with the monometallic counterparts. The dispersion of the magnetic catalyst also facilitates the recovery and reuse of the catalyst by ten consecutive extraction and final magnetic isolation with no loss of catalytic activity, keeping its structure unaltered.

| S-EPMC8382703 | biostudies-literature

Buchwald-Hartwig Amination of Aryl Halides with Heterocyclic Amines in the Synthesis of Highly Fluorescent Benzodifuran-Based Star-Shaped Organic Semiconductors.

Project description:The study of palladium-catalyzed amination of bromobenzene with aromatic and heterocyclic amines, widely used in the synthesis of organic semiconductors, was performed. The best conditions for the coupling of aryl bromides with carbazole, diphenylamine, phenoxazine, phenothiazine, 9,9-dimethyl-9,10-dihydroacridine, and their derivatives have been developed. Based on the results, nine new star-shaped organic semiconductors, exhibiting up to 100% fluorescent quantum yield in the 400-550 nm range, have been synthesized in good yields. The TDDFT calculations of the absorption spectra revealed a good correlation with experimental results and slight solvatochromic effects with a change in the polarity of the solvent.

| S-EPMC8689646 | biostudies-literature

Prediction of the Chemical Context for Buchwald-Hartwig Coupling Reactions.

Project description:We present machine learning models for predicting the chemical context for Buchwald-Hartwig coupling reactions, i. e., what chemicals to add to the reactants to give a productive reaction. Using reaction data from in-house electronic lab notebooks, we train two models: one based on single-label data and one based on multi-label data. Both models show excellent top-3 accuracy of approximately 90 %, which suggests strong predictivity. Furthermore, there seems to be an advantage of including multi-label data because the multi-label model shows higher accuracy and better sensitivity for the individual contexts than the single-label model. Although the models are performant, we also show that such models need to be re-trained periodically as there is a strong temporal characteristic to the usage of different contexts. Therefore, a model trained on historical data will decrease in usefulness with time as newer and better contexts emerge and replace older ones. We hypothesize that such significant transitions in the context-usage will likely affect any model predicting chemical contexts trained on historical data. Consequently, training context prediction models warrants careful planning of what data is used for training and how often the model needs to be re-trained.

| S-EPMC9540548 | biostudies-literature

What can reaction databases teach us about Buchwald-Hartwig cross-couplings?

Project description:Despite the widespread and increasing usage of Pd-catalyzed C-N cross couplings, finding good conditions for these reactions can be challenging. Practitioners mostly rely on few methodology studies or anecdotal experience. This is surprising, since the advent of data-driven experimentation and the large amount of knowledge in databases allow for data-driven insight. In this work, we address this by analyzing more than 62 000 Buchwald-Hartwig couplings gathered from CAS, Reaxys and the USPTO. Our meta-analysis of the reaction performance generates data-driven cheatsheets for reaction condition recommendation. It also provides an interactive tool to find rarer ligands with optimal performance regarding user-selected substrate properties. With this we give practitioners promising starting points. Furthermore, we study bias and diversity in the literature and summarize the current state of the reaction data, including its pitfalls. Hence, this work will also be useful for future data-driven developments such as the optimization of reaction conditions via machine learning.

| S-EPMC8378852 | biostudies-literature

Concatenating Suzuki Arylation and Buchwald-Hartwig Amination by A Sequentially Pd-Catalyzed One-Pot Process-Consecutive Three-Component Synthesis of C,N-Diarylated Heterocycles.

Project description:The concatenation of Suzuki coupling and Buchwald-Hartwig amination in a consecutive multicomponent reaction opens a concise, modular and efficient one-pot approach to diversely functionalized heterocycles, as exemplified for 3,10-diaryl 10H-phenothiazines, 3,9-diaryl 9H-carbazoles, and 1,5-diaryl 1H-indoles, in high yields starting from simple staring materials. Moreover, this one-pot reaction is a sequentially palladium-catalyzed process that does not require additional catalyst loading after the first coupling step.

| S-EPMC7756286 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data