Braca

Publication date: Available online 16 October 2024

Source: Chem

Author(s): Jose M. Carceller, Bhumika Jayee, Claire G. Page, Daniel G. Oblinsky, Gustavo Mondragón-Solórzano, Nithin Chintala, Jingzhe Cao, Zayed Alassad, Zheyu Zhang, Nathaniel White, Danny J. Diaz, Andrew D. Ellington, Gregory D. Scholes, Sijia S. Dong, Todd K. Hyster

Nature Catalysis, Published online: 17 October 2024; doi:10.1038/s41929-024-01234-0

The replacement of palladium with other metal catalysts in C–C bond-forming reactions is attractive in terms of costs and sustainability. Now an iron-based catalyst is successfully employed in the Suzuki cross-coupling of aryl chlorides with aryl boronic esters activated with tert-butyl lithium.

Nitrogen-heterocycles are privileged structures in both marketed drugs and natural products. On the other hand, C–H amination reactions furnish unconventional and straightforward approaches for the construction of C–N bonds. Yet, most of the known methods rely on precious metal catalysts. Herein we report a site-selective intermolecular C(sp3)–H amination of N-heterocycles, catalyzed by inexpensive FeCl2, which allows the functionalization of a wide range of pharmaceutically relevant cyclic amines. The C–H amination occurs site-selectively in α-position to the nitrogen atom, even when weaker C–H bonds are present, and furnishes Troc-protected aminals or amidines. The method employs the N-heterocycle as limiting reagent and is applicable to the late-stage functionalization of complex molecules. Its synthetic potential was further illustrated through the derivatization of α-aminated products and the application to a concise total synthesis of the reported structure for senobtusin. Mechanistic studies allowed to propose a plausible reaction mechanism involving a turnover-limiting Fe-nitrene generation followed by fast H atom transfer and radical rebound.

Synlett
DOI: 10.1055/a-2417-1070

This account describes the latest developments on 3d-metal-catalyzed single-electron-transfer (SET)-induced strategies that use carboxylic acids and their synthetic equivalents as substrates. In general, 3d-metal-promoted SET-mediated transformations of free carboxylic acids proceed readily via the formation of carboxylate radicals, whilst those of carboxylic acid equivalents, bearing an N-donor substituent, proceed via the formation of α-carbo radicals. The advantages of these strategies combine the low-cost of carboxylic acid starting materials and 3d metal catalysts with the possibility of realizing structurally diverse ranges of compounds in an atom- and step-economic manner. Developments primarily achieved by our group and a few by other researchers on this topic are discussed in this account.1 Introduction2 Mechanistic Considerations of 3d-Metal-Catalyzed SET-Mediated Transformations3 Developments Based on SET-Mediated Transformations of Carboxylic Acids4 Developments Based on SET-Mediated Transformations of Carboxylic Acid Equivalents5 Conclusion and Outlook
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Nature Reviews Chemistry, Published online: 09 October 2024; doi:10.1038/s41570-024-00642-x

Chiral phase-transfer catalysts are practical and powerful organocatalysts for asymmetric synthesis. This Review illustrates notable recent advances of chiral phase-transfer catalysts, including challenges, limitations and potential solutions, as well as future opportunities to improve sustainability.

Nature, Published online: 08 October 2024; doi:10.1038/d41586-024-03267-8

The geography of science is changing. As a result, a big push is needed to broaden the pool of scientists eligible to nominate their peers for Nobel prizes.

Nature, Published online: 08 October 2024; doi:10.1038/s41586-024-08138-w

Emergence of a distinct mechanism of C–N bond formation in photoenzymes

Nature, Published online: 08 October 2024; doi:10.1038/d41586-024-03213-8

John Hopfield and Geoffrey Hinton pioneered computational methods that enabled the development of neural networks.

Nature, Published online: 07 October 2024; doi:10.1038/d41586-024-03212-9

Victor Ambros and Gary Ruvkun identified a class of tiny molecules that have a crucial role in controlling gene expression.

A designer enzyme consisting of an abiological molecule incorporated into a natural protein has been developed as an exceptionally chemoselective catalyst, highlighting that the internal space of proteins is highly beneficial for enhancing catalytic performance. However, other superior features of proteins have received less attention in designer enzymes: e.g., their use as ligands to construct abiological (multinuclear) metal centers and an intrinsic protein function that has often been traded off for a new function. Here, grafting a synthetic trinuclear zinc complex inside a human cytokine macrophage migration inhibitory factor (MIF) scaffold using solely amino-acid side chains led to a designer multi-metalloenzyme with extrinsic and intrinsic functions. The crystal structure of the designer tri-zinc enzyme verified the high accuracy of our design process based on geometry optimizations and quantum-chemical calculations. The extrinsic catalytic performance of this designer enzyme is of the highest class and comparable to that of previously reported designer zinc hydrolases. Importantly, an intrinsic function of MIF, i.e., its tautomerase activity, was maintained in this designer tri-zinc enzyme. Considering that cytokines are originally expressed in response to in vivo events, this cytokine-based designer metalloenzyme shows promising potential as a synthetic biological tool for the self-adaptive regulation of life phenomena.

Nature Chemistry, Published online: 03 October 2024; doi:10.1038/s41557-024-01636-4

Adam Noble discusses the diverse uses of eosin Y over its 150-year history, from its origin as a dye and pigment used by post-impressionist masters to its versatile reactivity as a catalyst in visible light photochemistry.

Nature Chemistry, Published online: 04 October 2024; doi:10.1038/s41557-024-01592-z

Malononitriles are widely used precursors for the synthesis of diverse enantioenriched nitrogen-containing molecules, but controlling the stereochemistry of their asymmetric transformations is challenging. Now, the desymmetric reduction of disubstituted malononitriles to chiral amines has been achieved, enabled by a bidentate ligand with extended flanks that can differentiate between the precursor’s nitrile groups through tailored steric pairings.

Nature Chemistry, Published online: 27 September 2024; doi:10.1038/s41557-024-01647-1

Aldolases have been a mainstay in synthesis, but their scope has been limited to activated electrophiles. Now carbon–carbon bond formation with ketone electrophiles is enabled by transaldolases, which form a strong nucleophile that is resistant to protonation. This chemistry enables convergent synthesis of non-canonical amino acids bearing tertiary alcohol side chains.