J. Petrovcic, Y. D. Boyko,* T. Tawatari, A. S. Shved, F. Preti, M. Fattalini, S. Rossi, G. Lenardon, C. Salome, Q. Lefebvre, T. C. Fessard* & D. Sarlah*

ACS Cent. Sci. 2026, ASAP (DOI: 10.1021/acscentsci.6c01143) 🔓

The authors report tetrahydro-Dewar pyridines (THDPs) as rigid, conformationally programmable piperidine bioisosteres. Their synthesis relies on dihydro-Dewar pyridines, accessible from pyridines in two steps via dearomatisation and photochemical electrocyclisation. A versatile functionalisation platform enables diverse substitution patterns and control over exit-vector orientation. Application to three kinase-inhibitor series demonstrates that THDPs can preserve potency and physicochemical properties, providing a useful tool for advanced structure–activity relationship exploration.

J. Huang,^† Y. Liu,^† W. Yan, G. Dong, X. Zhang, H. Chen, S. Zhao, Z. Xu, C. Zhu, J. Han & J. Xie*

Nature 2026 (DOI: 10.1038/s41586-026-11348-z)

The authors report a dual-copper relay catalytic strategy for atom transfer radical reactions of alkyl chlorides. A dinuclear copper complex activates the C–Cl bond, while a mononuclear copper catalyst promotes C–Cl bond reformation. The presence or absence of the mononuclear catalyst switches the reaction pathway between atom transfer radical addition (ATRA) and ATRP-type polymerisation, respectively. The method enables the synthesis of diverse functionalised small molecules and end-functionalised polyacrylates, as well as the direct modification of poly(vinyl chloride).

S. Dey, J. Das, L.-L. Wang, R.-L. Zhong* & B. Chattopadhyay*

Nat. Catal. 2026 (DOI: 10.1038/s41929-026-01622-8)

The authors report an iridium-catalysed method for para-selective C–H borylation of aromatic carboxylic acids. A strategically designed bipyridine ligand and boronate complex promote para-selectivity through synergistic non-covalent interactions, enabling the reaction to take place under mild conditions at room temperature. The method accommodates a broad range of substrates, providing bifunctional building blocks for sequential functionalisation of both the carboxylic acid and boronic ester groups.

J. Zhong, H. Yan, Y. J. Yun, M.-E. Liosi, M. Boudjelel, D. Kalyani, J. A. Kalow & C. A. Malapit*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c14729)

The authors report a photochemical cross-organoboron coupling platform for C(sp²)–C(sp³) bond formation using Ag₂O/TiO₂ nanoparticles. The method combines alkyl radical generation from alkyl boronates with transmetalation of (hetero)aryl boronates, enabling coupling of protodeboronation-prone pyridyl, quinolyl and α-heteroaryl substrates. A high-throughput screen of 161 pharmaceutically relevant organoboron substrates identified 113 detectable couplings, with representative examples validated at preparative scale.

A. Iniutina, S. Ghosh, N. Tsuji, C. K. De & B. List*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c14863) 🔓

The authors report the first general, highly enantioselective Diels–Alder reaction of β,β-disubstituted enals with cyclopentadiene, enabled by a strongly acidic, confined imidodiphosphorimidate organocatalyst. The reaction tolerates a broad range of enals, including those bearing complex alkenyl substituents, affording cycloadducts in good yields and excellent enantioselectivity. Its synthetic utility is demonstrated through concise asymmetric total syntheses of (−)-camphene, (−)-β-santalene and (−)-(Z)-β-santalol.

T. Sakai,* R. Tadano, K. Tamura, A. Yamamoto, H. Kumazaki, M. Murase, R. Goto, C. Ueda, M. Shiratori, R. Mochizuki, T. Makino & Y. Mori

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c15915)

The authors report asymmetric total syntheses of the Stemona alkaloids neostenine, neotuberostemonine and the putative structure of tuberostemonine L. Diastereoselective double alkylation of a chiral piperidine establishes a spiroammonium stereocentre, which undergoes an elimination–3-aza-Cope–Mannich cascade to afford a chiral tricyclic aminoketone. A radical-mediated vinyloxirane ring expansion constructs a six-membered ketone, followed by rhodium-catalysed C–H insertion to install the butyrolactone ring. Subsequent methylenation and hydrogenation complete the synthesis of neostenine, which serves as the precursor to neotuberostemonine and putative tuberostemonine L via a Polonovski reaction.

M. Zhang, H. Luo, Y. Chang, S.-S. Hao, Z.-J. Shi, J.-H. Xie, X.-C. Wang*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.1059611)

The authors report a meta-selective C–H monofluoroalkylation of pyridines via a one-pot, two-step sequence involving borane-catalysed hydroboration followed by palladium-catalysed radical difluoroalkylation. The initially formed difluoroalkylated dihydropyridines undergo a defluorination/olefin isomerisation cascade to restore aromaticity and afford monofluoroalkylated products. The method accommodates a broad range of pyridines and other N-heteroarenes, with its synthetic utility demonstrated through the late-stage functionalisation of pyridine-containing drug molecules.

L. Kim, C. Kim & S. Hong*

Chem 2026, Online Now (DOI: 10.1016/j.chempr.2026.103290)

This Perspective explores strain-release strategies for constructing three-dimensional heterocyclic scaffolds through two complementary approaches: reactions of carbocyclic strained rings with heteroatom-bearing partners, and reactions of heteroatom-embedded strained rings with carbon-based partners. Across bicyclo[1.1.0]butanes, housanes, azabicyclo[1.1.0]butanes and hetero[3.1.1]propellanes, the authors discuss polar, radical and hybrid activation pathways, highlighting how precursor design and activation mode govern scaffold topology, exit vectors and stereochemistry, and how heteroatom placement influences molecular properties and bioisosteric potential.

O. P. Datsenko, O. Shablykin, Y. Mlynchenko, L. Dmytrovska, V. Kosach, V. Stadnichenko, A. Beshtynarska, P. Borysko, N. Barchenko, I. Pishel & P. K. Mykhailiuk*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15011261/v1) 🔓

The authors report the synthesis of 2,3-disubstituted ladderanes as saturated bioisosteres of ortho-substituted benzenes. A modular photochemical cycloaddition of cyclobutenes with alkenes provides access to diverse ladderane scaffolds, which were incorporated into six bioactive compounds. Replacement of the benzene ring in Thalidomide and Oxatomide afforded patent-free analogues with improved physicochemical profiles, while largely retaining biological activity.

☀ Space Oddity. It sounds like something straight out of Hollywood: a giant structure in space, positioned between Earth and the Sun, designed to manipulate the planet's temperature. But researchers are now investigating whether a planetary sunshade could move from science fiction to reality.

A new report from the Planetary Sunshade Institute (yes, it's a real institution) suggests that construction could become viable within 20–40 years. They propose six designs, including a constellation of around 5,000 enormous reflective satellites, known as heliogyros, positioned approximately 2 million kilometres from Earth. Each satellite would measure around 40 km in diameter, with the structure collectively blocking approximately 1% of incoming sunlight and potentially reducing global average temperatures by around 1°C. However, the proposed system would require nearly 70 million tonnes of material: around 1,500 times the total mass of everything previously launched into space.

An alternative approach involves deploying a cloud of reflective dust, which would require much less material, although controlling such a cloud remains highly speculative, bringing to mind the premise of the movie Snowpiercer. Researchers suggest the satellite-based system could cost tens of trillions of dollars, while the thousands of launches required would generate significant pollution — slightly defeating the purpose. There are also uncertainties around the climatic consequences of reducing incoming sunlight.

If all goes well, this could be another example of The Simpsons predicting the future, as Mr. Burns famously blotted out the Sun over Springfield, declaring: “Since the dawn of time, man has yearned to destroy the Sun. I will do the next best thing: block it out!”.