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1. Chemo- and enantioselective intramolecular silver-catalyzed aziridinations of carbamimidates

   https://doi.org/10.1039/D3CC05670H  

   Trinh, Tuan Anh; Fu, Yue; Hu, Derek B.; Zappia, Soren A.; Guzei, Ilia A.; Liu, Peng; Schomaker, Jennifer M. (December 2023, Chemical Communications)

   Transition metal-catalyzed asymmetric nitrene transfer is a powerful method to generate enantioenriched amines found in natural products and bioactive molecules. 

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2. Palladium-catalyzed enantioselective (2-naphthyl)methylation of azaarylmethyl amines

   https://doi.org/10.1039/D2QO00273F  

   Chen, Shuguang; Tan, Jiahong; Xiong, Dan; Shang, Yongjia; Mao, Jianyou; Walsh, Patrick J. (May 2022, Organic Chemistry Frontiers)

   Enantioenriched azaarylmethyl amine derivatives are useful building blocks in synthetic and medicinal chemistry. To access these valuable motifs, an enantioselective palladium-catalyzed benzylation of azaarylmethyl amine pronucleophiles is introduced. Of note, this is a rare application of asymmetric (2-naphthyl)methylation of pro-nucleophiles with high p K a values (p K a ≈ 34 in DMSO). Control experiments support the notion that the coordination of Li + to the azaaryl nitrogen plays a critical role in the substitution process. With this procedure, enantioenriched (2-naphthyl)methylene azaarylmethyl amines with a variety of azaaryl groups (pyridyl, pyrazine, quinoxaline and isoquinoline) and cyclic and acyclic amines are readily obtained with good yields and enantioselectivities up to 99%. 

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3. Direct Observation of Diastereomeric α-C-Bound Enolates during Enantioselective α-Arylations: Synthesis, Characterization, and Reactivity of Arylpalladium Fluorooxindole Complexes

   https://doi.org/10.1021/jacs.1c05346  

   Kalkman, Eric D.; Hartwig, John F. (July 2021, Journal of the American Chemical Society)

   The Pd-catalyzed asymmetric α-arylation of carbonyl compounds is a valuable strategy to form benzylic stereocenters. However, the origin of the stereoselectivity of these reactions is poorly understood, and little is known about the reactivity of the putative diastereomeric arylpalladium enolate intermediates. To this end, we report the synthesis and characterization of a series of diphosphine-ligated arylpalladium fluoroenolate complexes, including complexes bearing a metal-bound, stereogenic carbon and an enantioenriched chiral diphosphine ligand. These complexes reductively eliminate to form chiral α-aryl-α-fluorooxindoles with enantioselectivities and rates that are relevant to those of the catalytic process with SEGPHOS as the ancillary ligand. Kinetic studies showed that the rate of reductive elimination is slightly slower than the rate of epimerization of the intermediate, causing the reductive elimination step to impart the greatest influence on the enantioselectivity. DFT calculations of these processes are consistent with these experimental rates and suggest that the minor diastereomer forms the major enantiomer of the product. The rates of reductive elimination from complexes containing a variety of electronically varied aryl ligands revealed the unusual trend that complexes bearing more electron-rich aryl ligands react faster than those bearing more electron-poor aryl ligands. Noncovalent Interaction (NCI) and Natural Bond Orbital (NBO) analyses of the transition-state structures for reductive elimination from the SEGPHOS-ligated complexes revealed key donor-acceptor interactions between the Pd center and the fluoroenolate fragment. These interactions stabilize the pathway to the major product enantiomer more strongly than they stabilize that to the minor enantiomer. 

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4. Sequential Iron-Catalyzed C(sp2)–C(sp3) Cross-Coupling of Chlorobenzamides/Chemoselective Amide Reduction and Reductive Deuteration to Benzylic Alcohols

   https://doi.org/10.3390/molecules28010223  

   Bisz, Elwira; Podchorodecka, Pamela; Li, Hengzhao; Ochędzan-Siodłak, Wioletta; An, Jie; Szostak, Michal (January 2023, Molecules)

   Benzylic alcohols are among the most important intermediates in organic synthesis. Recently, the use of abundant metals has attracted significant attention due to the issues with the scarcity of platinum group metals. Herein, we report a sequential method for the synthesis of benzylic alcohols by a merger of iron catalyzed cross-coupling and highly chemoselective reduction of benzamides promoted by sodium dispersion in the presence of alcoholic donors. The method has been further extended to the synthesis of deuterated benzylic alcohols. The iron-catalyzed Kumada cross-coupling exploits the high stability of benzamide bonds, enabling challenging C(sp2)–C(sp3) cross-coupling with alkyl Grignard reagents that are prone to dimerization and β-hydride elimination. The subsequent sodium dispersion promoted reduction of carboxamides proceeds with full chemoselectivity for the C–N bond cleavage of the carbinolamine intermediate. The method provides access to valuable benzylic alcohols, including deuterium-labelled benzylic alcohols, which are widely used as synthetic intermediates and pharmacokinetic probes in organic synthesis and medicinal chemistry. The combination of two benign metals by complementary reaction mechanisms enables to exploit underexplored avenues for organic synthesis. 

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5. Sulfenate Anion Catalyzed Enantio- and Diastereoselective Aziridination

   https://doi.org/10.1039/D5SC05077D  

   Pu, Youge; Smaldone, Anthony M; Adrio, Javier; Walsh, Patrick J (September 2025, Chemical Science)

   The synthesis of enantioenriched aziridines is important for drug development due to their prevalence in bioactive molecules. Previous methods often use expensive catalysts, activated substrates, or show poor stereoselectivity. Herein,... 

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