The catalytic enantioselective synthesis of α‐chiral alkenes and alkynes represents a powerful strategy for rapid generation of molecular complexity. Herein, we report a transient directing group ...(TDG) strategy to facilitate site‐selective palladium‐catalyzed reductive Heck‐type hydroalkenylation and hydroalkynylation of alkenylaldehyes using alkenyl and alkynyl bromides, respectively, allowing for construction of a stereocenter at the δ‐position with respect to the aldehyde. Computational studies reveal the dual beneficial roles of rigid TDGs, such as L‐tert‐leucine, in promoting TDG binding and inducing high levels of enantioselectivity in alkene insertion with a variety of migrating groups.
Use of tert‐leucine as a chiral transient directing group enables the enantioselective reductive‐Heck‐type hydroalkenylation and hydroalkenylation of alkenyl benzaldehydes under palladium catalysis. The dual catalytic reaction proceeds under mild conditions and offers high enantioselectivity.
An asymmetric 1,2-dicarbofunctionalization of unactivated alkenes with aryl iodides and aryl/alkenylboronic esters under nickel/bioxazoline catalysis is disclosed. A wide array of aryl and alkenyl ...nucleophiles are tolerated, furnishing the products in good yield and with high enantioselectivity. In addition to terminal alkenes, 1,2-disubstituted internal alkenes participate in the reaction, establishing two contiguous stereocenters with high diastereoselectivity and moderate enantioselectivity. A combination of experimental and computational techniques shed light on the mechanism of the catalytic transformation, pointing to a closed-shell pathway with an enantiodetermining migratory insertion step, where stereoinduction arises from synergistic interactions between the sterically bulky achiral sulfonamide directing group and the hemilabile bidentate ligand.
Abstract
AQME, automated quantum mechanical environments, is a free and open‐source Python package for the rapid deployment of automated workflows using cheminformatics and quantum chemistry. AQME ...workflows integrate tasks performed across multiple computational chemistry packages and data formats, preserving all computational protocols, data, and metadata for machine and human users to access and reuse. AQME has a modular structure of independent modules that can be implemented in any sequence, allowing the users to use all or only the desired parts of the program. The code has been developed for researchers with basic familiarity with the Python programming language. The CSEARCH module interfaces to molecular mechanics and semi‐empirical QM (SQM) conformer generation tools (e.g., RDKit and Conformer–Rotamer Ensemble Sampling Tool, CREST) starting from various initial structure formats. The CMIN module enables geometry refinement with SQM and neural network potentials, such as ANI. The QPREP module interfaces with multiple QM programs, such as Gaussian, ORCA, and PySCF. The QCORR module processes QM results, storing structural, energetic, and property data while also enabling automated error handling (i.e., convergence errors, wrong number of imaginary frequencies, isomerization, etc.) and job resubmission. The QDESCP module provides easy access to QM ensemble‐averaged molecular descriptors and computed properties, such as NMR spectra. Overall, AQME provides automated, transparent, and reproducible workflows to produce, analyze and archive computational chemistry results. SMILES inputs can be used, and many aspects of tedious human manipulation can be avoided. Installation and execution on Windows, macOS, and Linux platforms have been tested, and the code has been developed to support access through Jupyter Notebooks, the command line, and job submission (e.g., Slurm) scripts. Examples of pre‐configured workflows are available in various formats, and hands‐on video tutorials illustrate their use.
This article is categorized under:
Data Science > Chemoinformatics
Data Science > Computer Algorithms and Programming
Software > Quantum Chemistry
The cover image is based on the Software Focus AQME: Automated quantum mechanical environments for researchers and educators by Juan V. Alegre‐Requena et al., https://doi.org/10.1002/wcms.1663.
The catalytic enantioselective synthesis of α‐chiral alkenes and alkynes represents a powerful strategy for rapid generation of molecular complexity. Herein, we report a transient directing group ...(TDG) strategy to facilitate site‐selective palladium‐catalyzed reductive Heck‐type hydroalkenylation and hydroalkynylation of alkenylaldehyes using alkenyl and alkynyl bromides, respectively, allowing for construction of a stereocenter at the δ‐position with respect to the aldehyde. Computational studies reveal the dual beneficial roles of rigid TDGs, such as L‐tert‐leucine, in promoting TDG binding and inducing high levels of enantioselectivity in alkene insertion with a variety of migrating groups.
Use of tert‐leucine as a chiral transient directing group enables the enantioselective reductive‐Heck‐type hydroalkenylation and hydroalkenylation of alkenyl benzaldehydes under palladium catalysis. The dual catalytic reaction proceeds under mild conditions and offers high enantioselectivity.
We report a redox-neutral catalytic coupling of nitroalkanes and unactivated alkenes that proceeds by a directed carbopalladation mechanism. The reaction is uniquely enabled by the combination of ...PdI2 as the precatalyst and HFIP solvent. Structurally complex nitroalkane products, including nitro-containing carbo- and heterocycles, are prepared under operationally convenient conditions without the need for toxic or corrosive reagents. Deuterium labeling experiments and isolation of a catalytically relevant intermediate shed light on the reaction mechanism. By taking advantage of different catalytic activation modes, we demonstrate orthogonal methods for site-selective functionalization of a polyfunctional nitroalkyl ketone. Density functional theory (DFT) calculations show that the carbopalladation transition state is stabilized by a Na···I interaction and H···I hydrogen bond with HFIP.
Currently, bladder cancer (BCa) evaluation depends mainly on traditional clinicopathological parameters encompassing tumor stage and grade, which will not reflect the behavior of the disease. Diverse ...molecular alterations are responsible for the heterogeneous course. The differences in molecular pathogenesis between non-invasive BCa and invasive BCa have been recognized. Molecular biomarkers are promising to predict progression and survival. The management of advanced BCa remains somewhat primitive in comparison with other more common malignancies. This topic will discuss the molecular pathways, biomarkers and potential targets that may improve the outcome in BCa.
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