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Enzymes catalyze organic transformations with exquisite levels of selectivity, including chemoselectivity, stereoselectivity, and substrate selectivity, but the types of reactions catalyzed by enzymes are more limited than those of chemical catalysts. Thus, the convergence of chemical catalysis and biocatalysis can enable enzymatic systems to catalyze abiological reactions with high selectivity. Recently, we disclosed artificial enzymes constructed from the apo form of heme proteins and iridium porphyrins that catalyze the insertion of carbenes into a C-H bond. We postulated that the same type of Ir(Me)-PIX enzymes could catalyze the cyclopropanation of a broad range of alkenes with control of multiple modes of selectivity. Here, we report the evolution of artificial enzymes that are highly active and highly stereoselective for the addition of carbenes to a wide range of alkenes. These enzymes catalyze the cyclopropanation of terminal and internal, activated and unactivated, electron-rich and electron-deficient, conjugated and nonconjugated alkenes. In particular, Ir(Me)-PIX enzymes derived from CYP119 catalyze highly enantio- and diastereoselective cyclopropanations of styrene with ±98% ee, >70:1 dr, >75% yield, and ∼10,000 turnovers (TON), as well as 1,2-disubstituted styrenes with up to 99% ee, 35:1 dr, and 54% yield. Moreover, Ir(Me)-PIX enzymes catalyze cyclopropanation of internal, unactivated alkenes with up to 99% stereoselectivity, 76% yield, and 1300 TON. They also catalyze cyclopropanation of natural products with diastereoselectivities that are complementary to those attained with standard transition metal catalysts. Finally, Ir(Me)-PIX P450 variants react with substrate selectivity that is reminiscent of natural enzymes; they react preferentially with less reactive internal alkenes in the presence of more reactive terminal alkenes. Together, the studies reveal the suitability of Ir-containing P450s to combine the broad reactivity and substrate scope of transition metal catalysts with the exquisite selectivity of enzymes, generating catalysts that enable reactions to occur with levels and modes of activity and selectivity previously unattainable with natural enzymes or transition metal complexes alone.

Given that (hetero)aryl carboxylic acids are inexpensive materials available in a great variety from commercial and natural resources or synthesis, the strategies enabling their use as starting materials for preparing fine chemicals are highly sought after. Here we report a photoinduced Cu(II)‐mediated protocol converting (hetero)aryl carboxylic acids into (hetero)aryl thianthrenium salts, high value‐added building blocks that can undergo various subsequent transformations, creating an attractive two‐step pathway for the divergent functionalization of these ubiquitous starting materials. The excellent compatibility of the method is shown by preparing a broad range of sterically and electronically varied (hetero)aryl thianthrenium salts, including derivatives of pharmaceuticals, such as ataluren, celecoxib, flavoxate, probenecid, repaglinide, and tamibarotene. The syntheses of 13 C‐labeled probenecid and bioisosteres of ataluren as well as the unconventional modifications of celecoxib and flavoxate, illustrate the synthetic potential of the strategy. Mechanistic studies are in line with a reaction occurring through a photoinduced ligand‐to‐metal charge transfer (LMCT) of Cu(II)‐arylcarboxylates, enabling radical decarboxylative carbometallation to form arylcopper(II) intermediates that in turn react with thianthrene to form the product. Noteworthy, the susceptibility of aryl thianthrenium salts to photodegradation is overcome by a Cu(I)‐driven salvage loop, which continuously intercepts the transiently formed radicals and regenerates the products. [ABSTRACT FROM AUTHOR]

Given her unrivalled proficiency in the synthesis of all molecules of life, nature has been an endless source of inspiration for developing new strategies in organic chemistry and catalysis. However, one feature that remains thus far beyond chemists' grasp is her unique ability to adapt the productivity of metabolic processes in response to triggers that indicate the temporary need for specific metabolites. To demonstrate the remarkable potential of such stimuli‐responsive systems, we present a metabolism‐inspired network of multicatalytic processes capable of selectively synthesising a range of products from simple starting materials. Specifically, the network is built of four classes of distinct catalytic reactions—cross‐couplings, substitutions, additions, and reductions, involving three organic starting materials—terminal alkyne, aryl iodide, and hydrosilane. All starting materials are either introduced sequentially or added to the system at the same time, with no continuous influx of reagents or efflux of products. All processes in the system are catalysed by a multifunctional heteronuclear PdII/PtII complex, whose performance can be controlled by specific additives and external stimuli. The reaction network exhibits a substantial degree of orthogonality between different pathways, enabling the controllable synthesis of ten distinct products with high efficiency and selectivity through simultaneous triggering and suppression mechanisms. [ABSTRACT FROM AUTHOR]

The conceptual merger of relay catalysis with dynamic kinetic resolution strategy is reported to enable regio‐ and enantioselective C(sp3)‐H bond arylation of aliphatic alcohols, forming enantioenriched β‐aryl alcohols typically with >90 : 10 enantiomeric ratios (up to 98 : 2 er) and 36–74 % yields. The starting materials bearing neighbouring stereogenic centres can be converted to either diastereomer of the β‐aryl alcohol products, with >85 : 15 diastereomeric ratios determined by the catalysts. The reactions occur under mild conditions, ensuring broad compatibility, and involve readily available aryl bromides, an inorganic base, and commercial Ru‐ and Pd‐complexes. Mechanistic experiments support the envisioned mechanism of the transformation occurring through a network of regio‐ and stereoselective processes operated by a coherent Ru/Pd‐dual catalytic system. [ABSTRACT FROM AUTHOR]

Keywords: hydroformylation; selectivity; palladium; transition metal; aldehydes; hydrocarbons; isobutanal EN hydroformylation selectivity palladium transition metal aldehydes hydrocarbons isobutanal 1185 1194 10 06/19/23 20230704 NES 230704 1 Introduction Hydroformylation, often referred to as the oxo process, [1] is a transition-metal-catalyzed reaction of olefines with syngas - a mixture of CO and H SB 2 sb - to produce aldehydes. The key question remained whether the iodide-dependent hydroformylation activity would be pronounced in the reactions with Pd complexes that favor the formation of iso-Pd-acyl intermediates and whether the isoselectivity would be maintained throughout the release of the isoaldehyde product. We reasoned that the regioselectivity in Pd-catalyzed hydroalkoxycarbonylation of alkenes, which occurs through Pd-acyl intermediates as the hydroformylation reactions do, can be steered between I n i - and iso-products depending on the phosphine ligand used (Scheme 12). [29] (4) Most importantly, the rate- and selectivity-determining step involves the unusual iodide-assisted binuclear reductive elimination occurring between the Pd-acyl and Pd-hydride species, which releases the aldehyde product and forms a Pd(I)-Pd(I) intermediate. [Extracted from the article]

Keywords: Bürgenstock Conference; Catalysis; Chemical Biology; Organic Chemistry; Stereochemistry EN Bürgenstock Conference Catalysis Chemical Biology Organic Chemistry Stereochemistry 1 10 10 12/16/22 20221223 NES 221223 The 55th edition of the Bürgenstock Conference took place in Brunnen (Switzerland) from May 1 to May 5, 2022. Chem. 2022, 87, 1934 - 1940; 28 D. Xu, N. Rivas-Bascón, N. M. Padial, K. W. Knouse, B. Zheng, J. C. Vantourout, M. A. Schmidt, M. D. Eastgate, P. S. Baran, J. Am. Chem. Soc. 2020, 142, 5785 - 5792; 29 J. C. Vantourout, S. R. Adusumalli, K. W. Knouse, D. T. Flood, A. Ramirez, N. M. Padial, A. Istrate, K. Maziarz, J. N. deGruyter, R. R. Merchant, J. X. Qiao, M. A. Schmidt, M. J. Deery, M. D. Eastgate, P. E. Dawson, G. J. L. Bernardes, P. S. Baran, J. Am. Chem. Soc. 2020, 142, 17236 - 17242. 51 D. C. Behenna, B. M. Stoltz, J. Am. Chem. Soc. 2004, 126, 15044 - 15045; 52 A. Q. Cusumano, B. M. Stoltz, W. A. Goddard, J. Am. Chem. Soc. 2020, 142, 13917 - 13933. 86 D. Parmar, H. Matsubara, K. Price, M. Spain, D. J. Procter, J. Am. Chem. Soc. 2012, 134, 12751 - 12757; 87 D. Parmar, K. Price, M. Spain, H. Matsubara, P. A. Bradley, D. J. Procter, J. Am. Chem. Soc. 2011, 133, 2418 - 2420. [Extracted from the article]

Organoboron compounds continue contributing substantially to advances in organic chemistry with their increasing role as both synthetic intermediates and target compounds for medicinal chemistry. Particularly attractive methods for their synthesis are based on the direct borylation of C–H bonds of available starting materials since no additional pre-functionalization steps are required. However, due to the high abundance of C–H bonds with similar reactivity in organic molecules, synthetically useful C–H borylation protocols demand sophisticated strategies to achieve high regio- and stereoselectivity. For this purpose, selective transition-metal-based catalysts have been developed, with group 9 centered catalysts being among the most commonly utilized. Recently, a multitude of diverse strategies has been developed to push the boundaries of C–H borylation reactions with respect to their regio- and enantioselectivity. Herein, we provide an overview of approaches for the C–H borylation of arenes, alkenes, and alkanes based on group 9 centered catalysts with a focus on the recent literature. Lastly, an outlook is given to assess the future potential of the field. 1 Introduction 1.1 Mechanistic Considerations 1.2 Selectivity Issues in C–H Borylation 1.3 Different Modes of Action Employing Directing Group Strategies in C–H Borylation 1.4 Scope and Aim of this Short Review 2 Trends in C–H Borylation Reactions 2.1 Photoinduced Catalysis 2.2 Transfer C–H Borylation 2.3 Lewis Acid Mediated C–H Borylation 2.4 Directed Metalation 2.5 Miscellaneous C–H Borylation Reactions 2.6 Electrostatic Interactions 2.7 Hydrogen Bonding 3 Conclusion and Outlook [ABSTRACT FROM AUTHOR]