Robert Pollice#RobSelects paper of the week #J_A_C_S: Asymmetric Sm-catalyzed carbon-carbon coupling between alkenes and ketones forming tertiary alcohols. #catalysis https://doi.org/10.1021/jacs.5c20884
#RobSelects paper of the week #J_A_C_S: Excited-state triplet thiazole-2-thione biradicals as radical covalent catalysts for skeletal reorganization of N-sulfonyl vinylaziridines. #catalysis https://doi.org/10.1021/jacs.5c20284
#RobSelects paper of the week #J_A_C_S: Iridium-catalyzed reduction of beta-boryl amides triggers stereospecific cyclization to form aminocyclopropanes. #catalysis https://doi.org/10.1021/jacs.5c21144
Catalytic Stereospecific Construction of Aminocyclopropanes from β-Boryl Amides
Iridium-catalyzed reduction of β-boryl amides with tetramethyldisiloxane affords iminium ions in situ. These reactive iminium ions are directly trapped by stereospecific (invertive) reaction with the boronate, delivering aminocyclopropanes (ACPs) in excellent yield, diastereoselectivity, and enantiospecificity. The reaction applies to both secondary and tertiary benzylic boronates, allylic boronates, and α-substituted boronates, giving access to many multiply substituted ACPs.
#RobSelects paper of the week #J_A_C_S: Comprehensive investigation of regio- and stereoselectivity of iridium-catalyzed carbon-hydrogen borylation of small substituted aliphatic carbocycles. #catalysis https://doi.org/10.1021/jacs.5c18839
#RobSelects paper of the week #J_A_C_S: Enantioselective cycloaddition of cyclopropanes across alkynes via diamine phosphine oxide-ligated nickel-aluminum bimetallic catalysts. #catalysis https://doi.org/10.1021/jacs.5c18087
Enantioselective Ni–Al Bimetal-Catalyzed Cycloaddition of Cyclopropyl Ketones with Alkynes under Mild Conditions
Transition metal-catalyzed enantioselective intermolecular cycloaddition of cyclopropyl ketones and π-unsaturated compounds represents a long-standing challenge in the asymmetric C–C bond activation of cyclopropanes. Developed strategies rely on substrate modifications to mitigate racemization or to stabilize radical intermediates. In contrast, an efficient approach governed by transition-metal catalysts for general cyclopropyl ketones remains an elusive challenge. Herein, we report a highly active chiral diamine–phosphine oxide-ligated Ni–Al bimetallic catalyst that promotes enantioselective C–C cycloaddition under mild conditions. This system effectively suppresses product racemization and affords a diverse range of cyclopentyl ketones bearing a chiral α-tertiary carbon center in up to 99% yield and 99% ee.
#RobSelects paper of the week #J_A_C_S: Pd-Catalyzed Buchwald-Hartwig amination with a mild and solube potassium alkyl carboxylate salt and a phosphorinane ligand. #catalysis https://doi.org/10.1021/jacs.5c07790
Unleashing the Power of Potassium 2-Ethylhexanoate as a Mild and Soluble Base for Pd-Catalyzed C–N Cross-Coupling
The formation of C–N bonds by Pd-catalyzed cross-coupling is one of the most widely practiced reactions in chemical synthesis. Typical reaction conditions involve either a strong base, which limits the scope of substrates, or an insoluble, inorganic base, which complicates running reactions on a large scale. Reaction conditions for C–N couplings with a base that is both mild and soluble are needed. We report the discovery of a combination of a phosphorinane ligand (L147) and a soluble carboxylate base, potassium 2-ethylhexanoate (K-2-EH), which leads to the coupling of a wide range of base-sensitive coupling partners. To explore the enhanced substrate scope of the reaction with this base and catalyst, we evaluated the scope using representative reactants selected from published partners, using chemical descriptors and clustering to ensure their chemical diversity. These results show that the combination of this phosphorinane ligand and K-2-EH can couple primary aliphatic amines, amides, sulfonamides, and heteroaromatic nucleophiles as well as acidic secondary nitrogen nucleophiles, such as arylamines, heteroarylamines, and amides, with a range of electrophiles. A side-by-side comparison to form selected coupling products in the presence of a range of previously reported bases and ligands showed that the products that decomposed under standard reaction conditions were stable with K-2-EH as a base. Finally, models of quantitative structure–reactivity relationships, trained on ligand screening data, were developed to help reveal the structural features that engender reactivity.
#RobSelects paper of the week #J_A_C_S: Synthesis of substituted cycloheptatrienes through insertion of a chromium fluorocarbyne into the adduct of a nucleophile and benzene. #inorgchem https://doi.org/10.1021/jacs.5c16875
Fluorocarbyne Insertion into Benzene Skeletons
Innovative fluorinated synthons essentially advance the organofluorine chemistry. However, the fundamental fluorocarbon synthon, metal-fluorocarbyne, remains largely unexplored, in contrast to its well-established trifluoromethyl and difluorocarbene counterparts. Here, we report a fluorocarbyne-promoted skeletal editing that transforms simple benzenes into precious monofluorinated cycloheptatrienes. This fluorocarbyne insertion features broad functional-group tolerance, exclusive meta-insertion selectivity, and compatibility with arene substrates ranging from benzene to per-substituted derivatives. The selective benzene activation within polyaromatics and successful applications to late-stage drug modifications further demonstrate its utility. Pharmaceutical application to the antiviral agent tecovirimat yielded a fluorinated derivative with an approximately 3-fold increase in aqueous solubility. Mechanistic studies involving intermediate capture and DFT calculations support the fluorocarbyne intermediate and elucidate the origin of meta-insertion and the ring expansion pathway. This work presents the first application of metal-fluorocarbyne in organic synthesis, enabling concurrent fluorine incorporation and scaffold editing.
#RobSelects paper of the week #J_A_C_S: Frustrated Lewis pair catalyst for coupling formate esters with vinyl and aryl organoboranes. #catalysis https://doi.org/10.1021/jacs.5c17878
Metal-Free Catalytic Cross-Coupling of Esters and Boranes
Over the last 50 years, palladium-catalyzed cross-coupling has become ubiquitous in chemical synthesis from laboratory to commercial scale. Due to the great importance of these reactions, extensive research efforts have been devoted to improving the sustainability, cost, and diversity of the catalysts and coupling partners. Herein, we report the rational design and experimental validation of a metal-free catalyst for the cross-coupling of formate esters with organoboranes, forming aldehydes under mild, additive-free conditions. The novel mechanism establishes a model for direct C(acyl)–C(sp2) bond formation, a motif previously inaccessible via metal-free or radical-free cross-coupling pathways. Overall, this boron-/nitrogen-based system is found to even outperform the efficacy of state-of-the-art nickel catalysts for ester cross-coupling, demonstrating the utility of main-group catalysts in efficiently activating challenging bonds.
#RobSelects paper of the week #J_A_C_S: Photochemical generation of carbon radicals from organoboron starting materials enabled via catalyst-borate complexes. #catalysis https://doi.org/10.1021/jacs.5c17266
Deep-Red to Near-Infrared Light-Driven Radical Generation from Organoboron Compounds via Ligand-Induced Direct Excitation Catalysis
We report a catalytic strategy for generating carbon-centered radicals from organoboron compounds under deep-red to near-infrared (DR to NIR) light irradiation via direct excitation of substrate–catalyst complexes. Aza-dipyrromethene (ADP) catalysts form photoactive borate intermediates that enable C–B bond cleavage through ligand-induced photochemical activation. Mechanistic studies support the role of direct excitation. This method allows diverse transformations, including Giese addition, C-heteroatom bond formation, radical–radical coupling, and nickel-catalyzed cross-coupling reactions.
#RobSelects paper of the week #J_A_C_S: Deriving a model for estimating rates of C-X reductive elimination from palladium(II) derived via causal inference. #catalysis https://doi.org/10.1021/jacs.5c06124