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J. J. Großkopf,^† J. Z. Wang,^† J. W. Gu, C. Bi, S. N. Dishman, X. Ma & D. W. C. MacMillan*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003261/v1) 🔓

The authors report a radical-based paradigm for general dialkyl ether synthesis enabled by a heteroatom homolytic substitution (het-S_H2) mechanism. This approach overcomes the steric limitations of classical polar substitution chemistry by employing carbon-centered radicals generated under mild conditions that are insensitive to congestion in the bond-forming transition state. Using a titanium-based catalytic platform in combination with visible-light photoredox catalysis, efficient coupling of carboxylic acid-derived redox-active esters with alcohols is achieved across a broad range of substitution patterns, including 3°–2°, 3°–1°, 2°–2°, and 2°–1° ether architectures. The method enables access to otherwise inaccessible dialkyl ether space, including sterically demanding BCP ether bioisosteres, and allows late-stage diversification of complex pharmaceutical scaffolds.

M. J. Anketell, E. Fung, W. Liu, M. Shinde, C. Q. He, K. W. C. Ng, S. M. Silverman, L.-C. Campeau, R. Pantophlet & R. Britton*

Science 2026, 392, 6799 (DOI: 10.1126/science.aed6880)

The authors report a flexible, robust and efficient platform for the high-throughput synthesis of nucleoside analogs (NAs) using a photoredox coupling strategy. This approach enables the synthesis of both carbon- and nitrogen-linked NAs and unifies access to several NA classes, including 4′-thio, 4′-imino, and ProTides, from a simple, scalable intermediate. Application of the platform generated a diverse NA library and identified several compounds with anti–HIV-1 activity.

A. A. Bikovtseva, M. M. Nielsen & E. N. Jacobsen*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c04849) 🔓

The authors report the development of chemo- and stereoselective phenolic β-mannosylations catalyzed by finely tuned bis-thiourea H-bond donors. Selective β-mannosylation of phenols is achieved in the presence of alcohols, thiols and thiophenols. Kinetic and computational studies support a general base-catalyzed nucleophile activation mechanism reinforced by matched aromatic and H-bonding interactions between catalyst and substrate. Selectivity over aliphatic alcohols arises from stronger nucleophile binding and higher reaction rates of the bound complex, whereas selectivity over thiophenols is governed by preferential catalyst binding.

Q. Zhu,^† W.-C. Zhao,^† C.-Y. Wang,^† C.-H. Jiang, S.-Y. Zhou, C. Dai, C. S. Day,* S.-Z. Sun* & X.-S. Wang*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06907)

The authors describe a Ni-catalyzed enantioconvergent decarboxylative arylation using racemic serine- and isoserine-derived redox-active esters (RAEs) as coupling partners. These RAEs serve as inexpensive, bench-stable and readily accessible alkyl radical precursors. The protocol provides a robust and versatile platform for the synthesis of enantioenriched α- and β-arylated vicinal amino alcohols, exhibiting broad substrate scope, excellent functional group tolerance and high stereocontrol under mild conditions. The utility of the method is further demonstrated through the late-stage functionalization of complex bioactive molecules.

T. J. Schubert, A. Carpentier, Y. Li, K. C. Hubbell, J. Oh, S.-L. Zheng, R. S. Paton* & Y. Dong*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c02555) 🔓

The authors report the first enantioconvergent alkylborane oxidation via a Cu-catalyzed single-electron mechanism. By combining low-temperature conditions with photochemical activation, the protocol suppresses undesired radical–polar crossover pathways while enabling enantioselective C–O bond formation. The method exhibits broad functional-group tolerance, accommodating benzyl- and allylboronic esters alongside diverse carboxylic acids, including pharmaceutical substructures and heterocycle-containing substrates. The reaction is scalable to gram quantities and was applied to the asymmetric synthesis of an immunosuppressant drug candidate.

Z. Wang,^† Y. Ji,^† Z. Wang, X. Zhang, Y. Chen, J. Hu* & Y. Huang*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05805)

The authors present a linear paired electrolysis strategy for iron-catalyzed C(sp²)–C(sp³) coupling of nitro(hetero)arenes with alkyl bromides, enabling the one-pot synthesis of diverse para-alkylated nitro(hetero)arenes. The protocol exhibits broad functional group tolerance, scalability and mild reaction conditions, enabling late-stage functionalization of biorelevant molecules and synthesis of pharmaceutical intermediates, including clinically relevant IDO inhibitors.

P. Rai,^† S. Wagulde^† & V. Gevorgyan*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05461)

The authors report a nickel-catalyzed enantioselective cross-dehydrogenative coupling of alkenes with aldehydes, enabling direct access to skipped enones from two C–H feedstocks. An aryl radical acts as an intermolecular hydrogen atom transfer agent to activate allylic and aldehydic C–H bonds, facilitating selective radical heterocoupling under nickel catalysis, while enantiocontrol is achieved using a chiral pyridine imidazoline ligand. The reaction proceeds under mild conditions with broad substrate scope, high functional-group tolerance, and excellent site- and enantioselectivity.

M. C. Deem, D. Lehnherr, T. Wang, X. Wang, Y.-h. Lam, S. M. Silverman, J. A. Newman, Q. Lin, E. M. Phillips, M. Christensen, C. K. Chung, Z. Zhou* & H. Yang*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05870)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15000548/v1) 🔓

The authors report a homogeneous catalytic asymmetric cyclopropanation strategy combining chiral pyridine bis-oxazoline (PyBox)-cobalt catalysts with readily accessible zinc carbenoids. The method enables the synthesis of chiral cyclopropanes bearing pyridyl, pyrimidyl and other nitrogen-containing heterocyclic substituents with high enantioselectivity. The protocol is compatible with green solvents, amenable to scale-up and applicable across a broad range of heteroaryl substrates.

A. Paul, V. Chang, E. M. Simmons, M. D. Mandler, J. Ma, J. L. Sloane, R. D. Sommer, T. G. M. Dhar & T. C. Sherwood*

ACS Catal. 2026, ASAP (DOI: 10.1021/acscatal.6c01419)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv-2025-xptw1) 🔓

Metallaphotoredox conditions employing an iridium photocatalyst and a nickel(II) oxidative addition complex as a precatalyst have been developed for the direct decarboxylative C(sp²)–C(sp³) cross-coupling of bicyclo[1.1.1]pentane and cubane carboxylic acids with (hetero)aryl halides. The reaction exhibits broad substrate scope and is applicable to the late-stage functionalization of pharmaceutically relevant substrates.

S. Manna, H. F. Janning, N. V. Tzouras, J. A. S. Sagayaraj, F. F. Mannighayil, A. Doppiu & L. J. Gooßen*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.3359287) 🔓

Methylnaphthyl (MeNAP) palladium trifluoroacetate dimers are presented as stable and easy-to-handle precatalysts that rapidly activate under cross-coupling conditions, even in the presence of weakly coordinating, non-reducing nucleophiles. The precatalysts significantly enhance the efficiency and scope of challenging Pd-catalyzed cross-coupling reactions.

T.-H. Chao, E. B. Barrois, C. W. Johnston* & H. Renata*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.6162176)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.10001470/v1) 🔓

The authors describe the total synthesis of allocyclinone A, an angucyclinone antibiotic with an unprecedented aromatic trichloromethyl motif. While attempts to effect late-stage enzymatic halogenation with the native halogenases from allocyclinone biosynthesis were unsuccessful, a late-stage halogen swap to convert an aromatic trifluoromethyl to its trichloromethyl counterpart proved facile, affording the first synthesis of the natural product.

L. H. Ramu, D. Narasimman, J. Ghosh & V. Palani*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003306/v1) 🔓

The authors report a general and conceptually distinct platform for formal transannular 1,3-migration of aroyl groups across saturated carbocycles, enabling access to 1,3-disubstituted frameworks. The strategy proceeds via a neutral bicyclic intermediate generated through Norrish–Yang photocyclization, followed by oxidative cleavage with hydrogen-atom trapping. By decoupling cyclization from migration, the method overcomes kinetic constraints that have historically limited 1,3-translocation. Applicable to both radical and ionic pathways, the approach enables ring expansion, scaffold hopping, distal editing through iterative translocation, and stereospecific modification of chiral substrates.

P. Meiners, L. S. Rindt, W.-S. Zhang, H. Du, H. Sezen, J. P. Hofmann, J. Mayer & T. Morack*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003307/v1) 🔓

The authors report a simple strategy for generating a highly active heterogeneous catalyst in situ that enables efficient hydrogenation of benzene and pyridine derivatives under ambient conditions. The approach combines bench-stable Ru(NH₃)₅(OTf)₃ and Pd/C pre-catalysts, which form a recyclable nanocrystalline Ru–Pd solid solution under the reaction conditions. Mechanistic and materials studies reveal the distinctive role of Ru(NH₃)₅(OTf)₃ in catalyst formation, demonstrating stepwise reductive decomposition of pentaammineruthenium.

A. Vaezghaemi, S. I. Khan, M. D. Martínez, B. Altamimi & S. G. Newman*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003005/v1) 🔓

The authors report the direct use of ketones as coupling partners in the Suzuki–Miyaura reaction to access valuable alkenyl arenes using a Ni/bipyridine catalyst, Piv₂O, and KOt-Bu. Mechanistic studies suggest that ketones undergo rapid in situ activation to form alkenyl pivalate intermediates, which act as pseudohalides in the Ni-catalyzed coupling. The success of the transformation relies on the compatibility of base, activating agent and low-valent nickel catalyst, enabling concurrent ketone activation and cross-coupling in a streamlined alternative to multistep enolate-based protocols.

B. Funk, M. Yasuda & J. G. West*

Org. Lett. 2026, ASAP (DOI: 10.1021/acs.orglett.6c01341) 🔓

The authors report a redox-neutral, cobaloxime-photocatalyzed isomerization of terminal epoxides to methyl ketones under visible-light irradiation. Operating under mildly basic conditions, the protocol provides complementary regioselectivity to the classical Meinwald rearrangement while exhibiting broad functional-group tolerance. Preliminary mechanistic studies suggest the transformation proceeds through a radical pathway.

🪨 A Rocky Career Choice. In everyone’s favourite movie about a team of oil drillers attempting to blow up an asteroid with a nuclear bomb before it hits Earth (Armageddon) a geologist, played by Steve Buscemi, is one of the lucky few to make it back alive.

Now, a new study has confirmed that despite Steve’s success, being a movie geologist is surprisingly dangerous. Researchers publishing in Geology Today analysed 141 films released between 1919 and 2023, identifying 202 on-screen geologists — 69 of whom die, giving the profession an on-screen mortality rate of ~34%. The decade-long study, “Geologists on the Silver Screen — The Sequel”, found murder to be the leading cause of death, followed by geological disasters and alien encounters. Falling into craters, volcanic eruptions, quicksand and extraterrestrial attacks all featured prominently.

The paper also uncovered some unusual moments in cinema history. In the 1971 film Walkabout, a geologist in the Australian outback seemingly snaps after reading a geology textbook before setting his car on fire. The authors dryly note they “hope this does not provoke demands for warning texts on structural geology textbooks”.

The analysis also raises an interesting question: how would chemists fare under the same criteria? Unlike geologists, who are usually portrayed as heroic scientists trying to stop disasters, fictional chemists can range from brilliant scientists (e.g. Bryan Cranston at the start of Breaking Bad) to morally grey criminal masterminds (e.g. Bryan Cranston by the end of Breaking Bad).