Acid + Amine ≠ Amide

Deaminative C(sp³ )–C(sp³ ) Cross-Coupling of Benzylamines with Alcohols and Carboxylic Acids via Radical Sorting

W. Y. Zhao,^† N. Takanashi,^† A. Cabré, J. R. Martinelli & D. W. C. MacMillan*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c04676) 🔓

The authors report two metallaphotoredox C(sp³ )–C(sp³ ) cross-coupling reactions that expand the utility of benzylamines as building blocks through deaminative coupling with carboxylic acids and tertiary alcohols. In both transformations, C–C bond formation proceeds via an Fe-porphyrin-catalysed S_H2 radical sorting pathway. The methodology exhibits broad substrate scope, including heterocyclic benzylamines and complex bioactive molecules, and is further applied to couple-close sequences and asymmetric synthesis.

Quaternary Carbons from Amines and Acids

R. Zhao,^† S. Wang,^† P. Shi, S. K. Das, S. Meng, A. Lei & T. Cernak*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05065) 🔓

The authors report an Fe-catalysed C(sp³ )–C(sp³ ) cross-coupling reaction between amines and carboxylic acids that enables the construction of densely functionalised carbon frameworks containing quaternary carbon centres. Preactivation of the amine and acid coupling partners enables S_H2-mediated coupling under reducing conditions, providing access to sterically congested architectures from widely available feedstock building blocks. The methodology exhibits broad substrate scope, excellent functional group tolerance, and applicability to the late-stage diversification of pharmaceuticals and natural products.

Biocatalytic Cascades Enable Manufacture of the Macrocyclic Peptide Enlicitide

A. Klapars,* A. Fryszkowska, S. Galanie* et al.

Science 2026, 392, 643–647 (DOI: 10.1126/science.aed8713)

The authors report a convergent biocatalytic synthesis of the macrocyclic peptide therapeutic enlicitide enabled by a suite of engineered enzymes for selective peptide fragment formation, coupling, and macrocyclisation under protecting group-free conditions. Combined with crystallisation-based purifications that avoid chromatography, the approach more than halves the number of synthetic steps compared with previous routes and provides an efficient, scalable strategy for the synthesis of complex peptide therapeutics.

👉️ Science write-up, here / C&EN write-up, here.

Synthesis of Aryl-Fused Bicyclo[3.1.1]heptanes and Validation as Naphthyl Bioisosteres

A. Kerckhoffs, M. Tregear, P. Hernández-Lladó, M. Runfola, H. Shearsmith, N. Frank, M. Panosetti, S. E. Squire, L. Moir, K. E. Christensen, F. Duarte, K. E. Davies & A. J. Russell*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02129-2) 🔓

The authors report derivatizable aryl-fused bicyclo[3.1.1]heptanes (BCHeps) as sp³ -rich bioisosteric replacements for naphthalene and other fused bicyclic (hetero)aromatics, including underrepresented β-naphthyl units. The BCHeps were accessed via an intramolecular crossed [2+2] photocycloaddition enabled by visible-light energy transfer and subsequently diversified into a range of scaffolds. Incorporation of BCHep-based naphthyl isosteres into the AhR antagonist ezutromid preserved key geometric exit vectors while reducing sp² carbon content. The resulting analogues retained biological activity and displayed improved metabolic stability towards CYP1A-mediated metabolism. Structural, cellular and microsomal studies confirmed reduced reactive metabolite formation, validating aryl-fused BCHeps as bioisosteric replacements for meta-substituted arenes and 2-naphthalenes.

[2+2] Photocycloaddition Reactions of Sulfinylamines with Alkenes to Access β-Sultam Derivatives

Y. Yuan, X. Zhu, Z. Cheng, Z. Zhao, K. Hu, J. Zhang* & J. Yang*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02146-1)

The authors report a visible-light-mediated intermolecular [2+2] photocycloaddition between alkenes and sulfinylamines, enabling the synthesis of four-membered cyclic sulfinamides (β-sultam analogues). The reaction proceeds via triplet energy transfer activation of sulfinylamines and enables efficient access to diverse four-membered cyclic sulfinamides. Experimental and computational studies identified the origins of the observed regio- and diastereoselectivities.

Photoactive Iminobismuthanes for Catalytic C–H Amination

T. Tsuruta, H. W. Moon, M. Leutzsch, B. A. Williams, D. Spinnato, R. Maray-Antolín, A. Ullman & J. Cornella*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c04805) 🔓

The authors report a photoactive iminobismuthane catalyst for direct α-C–H amination and azidation reactions that parallels transition-metal nitrenoid reactivity. Upon blue-light irradiation, the iminobismuthane undergoes ligand-to-ligand charge transfer, enabling hydrogen-atom transfer and subsequent C–N bond formation. Depending on the azide coupling partner, the system enables either α-C–H amination or azidation of amines. The distinct electronic properties of bismuth suppress undesired N-amination and catalyst deactivation.

Iridium-Catalyzed Asymmetric Hydrogenation of Carbocation Precursors via Wagner–Meerwein Rearrangement

R. K. Mallick, L. Eriksson, F. Gong & P. G. Andersson*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c01858) 🔓

The authors report an iridium-catalysed Wagner–Meerwein rearrangement/asymmetric hydrogenation cascade that enables the synthesis of chiral gem-dimethyl cycloalkanes. The transformation proceeds through formal deoxygenation of tertiary alcohols to generate carbocation intermediates that undergo ring expansion and alkyl migration prior to olefination and asymmetric hydrogenation. The method provides access to a range of optically active cycloalkanes in excellent yields and enantioselectivities.

Ligand Control Overrides Intrinsic Site Selectivity in C–H Borylation of Phenol and Aniline Derivatives

S. Qin,^† J. Ma,^† Z. Deng,^† Y. Xie, H. Ang, S. Lu, Y. Wang, W. Chang, F. Liu,* K. N. Houk* & Y. Liang*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c01983)

By using a designed ligand for an iridium catalyst, the authors report a meta-selective C–H borylation of phenols, anilines, and related compounds that overrides the substrates’ intrinsic para-selectivity. The method provides access to a range of meta-borylated electron-rich arenes with excellent regioselectivity under mild conditions. Mechanistic experiments and DFT calculations suggest that hydrogen-bonding interactions between the ligand and sulfur oxyanions are responsible for the observed inversion from para- to meta-selectivity while also enhancing reactivity.

Direct α-C−H Heteroarylation of Unprotected Primary Amines

G. D. Johnson, S. A. Corio, J. D. Grayson, J. D. Tibbetts, G. Ballantyne, Q. Cao, H. E. Askey, J. J. Bell-Tyrer, O. P. Datsenko, M. A. Graham, P. K. Mykhailiuk, J. S. Hirschi* & A. J. Cresswell*

ACS Catal. 2026, ASAP (DOI: 10.1021/acscatal.6c01036) 🔓

The authors report the α-C–H heteroarylation of unprotected, non-benzylic primary alkylamines, enabling direct catalytic access to unprotected α-azolyl primary amines, including sterically congested α-tertiary motifs. The transformation proceeds via photoredox-catalysed hydrogen-atom transfer to achieve selective C–H activation and heteroaryl coupling. A key case study shows that low-temperature continuous-flow photochemistry suppresses rapid N-functionalisation by a highly electrophilic azolyl chloride, enabling C-centred reactivity that is inaccessible under batch conditions.

Enabling Access to sp³ -Enriched Targeted Protein Degraders via Redox-Neutral Radical Cross-Coupling

P. Neigenfind, C. Gathmann, E. C. Cherney,* C. G. Parker* & P. S. Baran*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.3989307)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.10001725/v1) 🔓

A modular redox-neutral cross-coupling/hydrogenation sequence enables access to C3(sp³ )–C(sp³ ) linked glutarimides, expanding the chemical space of cereblon (CRBN) ligands. The operationally simple method delivers sp³ -rich, three-dimensional scaffolds with broad functional-group tolerance. These building blocks enable rapid exploration of targeted protein degraders and demonstrate CRBN-dependent BRD4 degradation in cellular assays.

Iron-Photocatalyzed C(sp³ )–H Phosphonylation of Alkanes

Y. Dong,^† W. Han,^† H. Zhang,^† S. K. Pagire, H. Meats, A. Noble* & V. K. Aggarwal*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.6650940) 🔓

Alkyl phosphonates are valuable motifs that can be prepared by phosphonylations of various common functional groups. However, direct phosphonylations of C(sp³ )–H bonds are limited to activated positions. Here, the authors report an iron-photocatalyzed phosphonylation of unactivated C(sp³ )–H bonds using a novel phosphite radical trap, which is equipped with an oxidizing radical leaving group to enable effective photocatalyst turnover.

Aldehyde–Olefin Couplings by Photoinduced Reduction of Electron-Deficient Olefins with Hantzsch Ester Anions

Z. Li & A. Noble*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.9744019) 🔓

Single-electron transfer-mediated reductive carbonyl–olefin couplings are valuable carbon–carbon bond forming reactions. However, limitations persist for couplings of aliphatic aldehydes with electron-deficient olefins. Here, the authors report a simple, photocatalyst-free protocol that overcomes these limitations by using a Hantzsch ester anion as a photoreductant for olefin radical anion generation, and water as a crucial protic additive for aldehyde activation.

An Iridium Catalyst Switches the Regioselectivity of Michael Addition Reactions

F. Hong,^† W. Mao,^† R. S. Aggarwal,^† Y. Wang, C. M. Robertson & John F. Bower*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15002845/v1) 🔓

The authors describe an iridium-catalysed α-selective “anti-Michael” C(sp³ )–H addition to conjugate acceptors that reverses the conventional regioselectivity of the Michael reaction. Directing-group-enabled chelated Ir-(aza)-enolates undergo inner-sphere carbometallation to favour α-selective C–C bond formation under steric control. The methodology accommodates a broad range of pro-nucleophiles with high regio-, diastereo-, and enantiocontrol and is further applied to cascade lactamisation reactions and the synthesis of complex α-amino acids.

Safety Letter: Non-Pyrophoric tert-Butyllithium in Base Oils: Preparation by Mechanochemistry and Conventional Methods and Use in Activating Alkylboronic Esters

K. T. Palka, J. C. Pratt & J. P. Morken*

Org. Lett. 2026, ASAP (DOI: 10.1021/acs.orglett.6c00217)

Alkylboronic esters are shown to undergo stereospecific transformations upon activation with non-pyrophoric solutions of tert-butyllithium in base oil solvents. Methods for the preparation of alkyllithium reagent from the direct mechanochemical reaction of tert-butyl chloride and lithium metal, in addition to conventional solvent-swapping strategies, are equally effective and enable a broad range of safe, selective, and efficient alkylboronic ester transformations.

Attenborough at 100

🎂 Attenborough at 100. In an increasingly divisive world of politics, there’s one thing most British people can agree on: if asked to name a national treasure, Sir David Attenborough would likely top the list. In fact, he did exactly that, finishing first in a recent YouGov poll.

Attenborough’s career began at the BBC in the early 1950s, where few could have imagined that he would go on to become one of the most influential science communicators in history. He created landmark series including Planet Earth, Blue Planet, and Life of Birds. Across more than 100 film and television projects, he brought audiences face-to-face with the natural world, from tropical oceans to Antarctic penguin colonies.

On Friday 8^th May, Attenborough celebrated his 100th birthday and to mark the occasion, Nature has produced a striking visual retrospective, entitled “A Life in Pictures: Celebrating David Attenborough at 100”. One of his most memorable moments came from The Life of Birds, when an Australian superb lyrebird was filmed mimicking the sounds of its forest environment—including chainsaws and camera shutters.

In later years, his focus has turned towards conservation and climate change with programmes such as The Truth About Climate Change and Our Planet, highlighting habitat destruction, pollution and biodiversity loss. Following the release of Blue Planet II in 2017, awareness of plastic pollution surged in what became known as the “Blue Planet Effect”, influencing public behaviour and political discussion around environmental issues.

Today, scientists have honoured Attenborough by naming more than 50 species after him. Even at 100, he remains the defining voice of the natural world, inspiring generations and reminding us that Earth is not simply ours to use, but ours to protect.