M. Pitchai,* S. Ulaganathan, K. C. Nanjundaswamy, M. Javeed, P. Srinivas, S. Roy, S. Ansar, L. B. Jarugu, I. Teleuca, R. Guo, M. S. Oderinde, T. C. Sherwood, E. C. Cherney, H. Pham, L. Collier, G. Everlof, J. Mignone, E. A. Jurica, S. Pieniazek, S. H. Spergel, E. K. Kick, S. C. Traeger, C. Jorge, K. B. Pabbisetty, M. Vetrichelvan, A. Gupta, R. Y. Liu* & M. D. Mandler*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15009866/v1) 🔓

The authors report a convergent synthesis of “mousanes”, dispirodecane scaffolds comprising three cyclobutanes, via regioselective triplet-sensitized [2+2] homodimerization of a functionalized methylenecyclobutene. The cycloaddition constructs the central cyclobutane and both spiro junctions in a single step, while hydrolysis and stereoconvergent hydrogenation provide a bifunctional mousane on multigram scale. Diversification gives amino acid, diamine and diol building blocks, while mousane-containing drug analogues and a BRD4-targeting degrader demonstrate its utility as a rigid, sp³-rich linker.

J. Zhong,^† M. Boudjelel,^† J. M. Evans, I. Vanswearingen & C. A. Malapit*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02237-z)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv-2025-bw2xl) 🔓

The authors report a redox-matched alternating-polarity electrolysis for direct C(sp³)–C(sp³) cross-coupling of alkyl carboxylic acids and alkyl boronic acids via transient radicals. Fluoride activation converts both precursors into redox-active species with matching redox potentials, enabling efficient cross-coupling. The method also enables formal carboxylic acid–alkene coupling via in situ hydroboration and is compatible with tandem Suzuki–Miyaura and Buchwald–Hartwig reactions.

Q. Sun, J. Liu & T. Ritter*

Nat. Synth. 2026 (DOI: 10.1038/s44160-026-01183-5) 🔓

The authors report a modular synthesis of 3,3-diaryloxetanes via nickel-catalysed cross-coupling of readily available 3-oxetanone derivatives. Sequential installation of two aryl groups, from an aryl halide and an arylboronic ester, enables difunctionalisation at the fully substituted oxetane C3 centre to access a variety of benzophenone bioisosteres. The use of a tetrafluoropyridone leaving group enables programmable arylation, providing access to diverse oxetane analogues of bioactive compounds.

M. J. Zeiler, M. F. Maciejewski, C. A. MacAllister & T. P. Yoon*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c15884) 🔓

The authors report a one-step skeletal editing strategy for inserting nitrogen atoms into saturated carbocycles via deconstructive β-scission of nitrogen-centred radicals. A Cu(II)/2,6-di-tert-butylpyridine system generates sulfonamidyl radicals directly from sulfonamides and mediates oxidative cyclisation of the resulting ring-opened radical intermediates. The method tolerates diverse functional groups and enables late-stage scaffold hopping under mild conditions without light or strong oxidants. Cyclobutyl sulfonamides can also be intercepted with external nucleophiles to access substituted pyrrolidines.

Y. Xu,^† P.-P. Xie,^† K. Chen, P. Liu* & G. Dong*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c14241)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15005200/v1) 🔓

The authors report an Ir-catalysed, redox-neutral decarboxylative aromatization that converts carboxylated cyclohexanes into arenes via transfer dehydrogenation. The carboxylic acid acts as a traceless anchor, enabling selective aromatization even in the presence of cyclohexenes, cyclohexanones, and other cyclohexanes. The method tolerates diverse functional groups and enables modular synthesis of multisubstituted benzenes and naphthalenes through late-stage aromatization.

R. Kim,^† J. N. Gruhin,^† X. Wu,^† R. S. Semenick, A. Vasilopoulos, E. A. Voight, H. Renata* & E. J. Alexanian*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c14950)

The authors report a modular chemoenzymatic strategy for the asymmetric synthesis of noncanonical amino acids (ncAAs) from readily available carboxylic acids. The acids are converted into α-ketoesters, followed by a biocatalytic lipase hydrolysis–transamination cascade. L- and D-selective transaminases enable access to either enantiomer with control over side-chain length, including ncAAs bearing complex polycycles, bioisosteres and peptide-derived substituents. The process can be telescoped into a one-pot reaction and scaled to gram quantities.

O. M. Schneider,^† J. J. Blackner,^† J. Sugiarto, R. M. P. Ylagan, M. Paladino, M. Boghi, K. Robinson, D. J. Konowalchuk, M. Sutherland, K. Mah & D. G. Hall*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c17387)

The authors report a systematic pK_a-guided evaluation of >15 hemiboronic benzoborine scaffolds to identify alternatives to benzoxaboroles for medicinal chemistry. The study identifies borylureas as a particularly promising chemotype, combining a near-neutral pK_a with favourable lipophilicity, aqueous stability and metabolic stability. The scaffold is readily diversified and exhibits high permeability, while NMR studies reveal efficient complexation with monosaccharides and ribonucleosides, matching or exceeding benzoxaborole depending on the medium.

G. Kim, D. Kim, S. Han, S. Park & S. H. Cho*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c14748)

The authors report a highly diastereoselective and stereospecific 1,2-metalate rearrangement of enantioenriched α-chloroalkylboronic esters using gem-diborylalkanes as pronucleophiles, simultaneously constructing two contiguous stereogenic centres. Controlled in situ generation of α-borylcarbanions enables boron-ate complex formation and subsequent Lewis acid-promoted rearrangement to furnish vicinal diboronic esters in high yields and with excellent stereoselectivity. The products undergo site-selective and sequential functionalisation, providing diverse enantioenriched building blocks.

V. Levterov, O. Shablykin, O. Stashkevych, V. Kokhalskyi, V. Konashuk, I. Sadkova, O. Shevchuk, P. Borysko, H. S. Rzepa & P. K. Mykhailiuk*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.5080799)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.10002101/v1) 🔓

The authors report a stable aliphatic N-unprotected α-fluoroamine by incorporating a CH₂ group into the α-fluoropiperidine framework to generate a 2-azabicyclo[2.2.1]heptane core. The minimal structural modification prevents dehydrofluorination because of Bredt’s rule, enabling the previously inaccessible α-fluoroamine to be stored in air, comprehensively functionalised, and applied in medicinal chemistry.

Y. Tan, H. Toh, C.-Y. Chang & P. S. Grant*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15009852/v1) 🔓

The authors report a one-pot consecutive hydrodefluorination of perfluoroarenes that provides regioselective access to partially fluorinated arenes with precise control over the degree of defluorination. The method uses in situ generated hydridosilicates from phenylsilane and Cs₂CO₃ in DMSO as the reducing species. Complementary thermal and photochemical pathways broaden the substrate scope, enabling rapid preparation of difluoro- and trifluoroarenes from readily available perfluoroarenes.

🏆 Champions of Catalysis. The 2026 Nobel Prize in Chemistry has been awarded to Henri B. Kagan and Kenso Soai “for the discovery of non-linear effects and autocatalysis in asymmetric organic synthesis”.

In the 19th century, Louis Pasteur discovered that crystals of tartaric acid could exist in two mirror-image forms which, when separated and dissolved independently, rotated plane-polarised light in opposite directions; combined, their effects cancelled. With remarkable foresight, Pasteur then tested the two forms with bacteria, finding that they consumed the one naturally found in grapes while leaving its mirror image untouched—raising the possibility that life itself might be chiral.

Chiral molecules, as we know, are not superimposable on their mirror images, the classic example being our left and right hands. Life is homochiral: proteins use almost exclusively L-amino acids, while DNA and RNA contain D-sugars. This asymmetry is particularly important in drug discovery, because enantiomers can interact very differently with biological targets. Darvon (dextropropoxyphene) was developed as an opioid painkiller, while its mirror image, Novrad (levopropoxyphene), was used as a cough suppressant—even their names are mirror images.

In 1986, Kagan showed that the relationship between the enantiomeric excess (ee) of a chiral ligand and the ee of its reaction product need not be linear. A chiral ligand containing only a small excess of one enantiomer can produce either amplification or reduction in product ee. These non-linear effects revealed how chirality could potentially be enhanced during asymmetric catalysis and became an important tool for understanding and designing new catalytic reactions.

Soai took this further with asymmetric autocatalysis. In his eponymous reaction, diisopropylzinc adds to pyrimidine-5-carbaldehyde to form a chiral alcohol that catalyses its own formation. The reaction is even capable of generating enantioenriched products from achiral starting materials: when diisopropylzinc reacts with the aldehyde, the initial zinc alkoxide is formed as a racemate; however, tiny statistical fluctuations can nevertheless give one enantiomer a microscopic advantage. The reaction’s positive nonlinear effect can detect and amplify this imbalance, ultimately producing a strongly enantioenriched product. Across 37 experiments, 18 favoured one enantiomer and 19 the other, with final ee values ranging from 15% to 91%. This enantioamplification can be extraordinary: when starting with a ligand containing just 0.00005% ee, three consecutive runs ultimately gave the alcohol with more than 99.5% ee—a 630,000-fold amplification.

For further reading, see the Nobel Committee’s Scientific Background to the Nobel Prize in Chemistry 2026.