Petri M. Pihko

Organic electrolytes for aqueous redox flow batteries must be able to complete full redox cycles. Simple changes in the molecular design, such as adding a ring fusion, can result in irreversible steps in the redox cycle.

In this work, a series of chromium mixtures with N,O‐containing ligands were evaluated as candidate negolytes for iron–chromium flow batteries. Six systems were investigated, including three prepared with a single ligand and three prepared with pairs of chemically distinct ligands. The structurally characterized mixture‐1 was used as the reference, whereas the exact chromium coordination structures of mixtures 2–6 were not established. UV–vis spectroscopy was used to estimate the dissolved chromium concentrations of the studied mixtures in 1 M KCl. The results show that combining chemically distinct ligands increases dissolved chromium concentration, reaching up to approximately 150 mM compared with 13.5 mM for mixture 1. Cyclic voltammetry revealed that five electrochemically evaluated mixtures displayed quasireversible redox behavior, whereas one mixture did not show any clear redox activity. However, flow‐cell cycling of these electroactive mixtures at a nominal concentration of 10 mM revealed limited capacity utilization and substantial capacity fading. These results show that increasing the dissolved chromium concentration alone does not ensure improved electrochemical accessibility or stable flow‐cell cycling. Further optimization and solution‐speciation studies are required to improve cycling stability and identify the chromium species responsible for the observed electrochemical behavior.

An O– silylative carboxylate–catalyzed Favorskii reaction for terminal alkynes with aldehydes, ketones or α–ketoesters is described, using a quaternary ammonium carboxylate catalyst and silylating agent, bis(trimethylsilyl)acetamide as the probase system. A wide range of alkynes and carbonyl electrophiles are tolerated as substrates, providing the propargylic alcohol products in up to 96% yield under metal‐free, catalytic conditions. Chiral cinchona alkaloid‐derived quaternary ammonium catalysts afforded moderate enantioselectivity (up to 73:27 er). Mechanistic studies with p ‐substituted aryl alkynes and α‐keto ester electrophiles provided additional evidence for a mechanism that involves the turnover‐determining deprotonation to give quaternary ammonium ion – acetylide ion pairs, which then react with the electrophiles in the chemo‐ and enantioselectivity‐determining step.

Claisen rearrangement sequences with propargyl alcohols, where the propargyl enol ether intermediate formation is catalyzed by acids, suffer from concomitant isomerization of the desired allenyl ketone products to the corresponding conjugated dienones. We report that diarylthiourea catalysts effectively promote the reaction sequence, but suppress the isomerization, providing the allenyl ketones in generally good yields and chemoselectivities. Density functional theory calculations of the reaction pathway and control experiments support the role of the thiourea as a Brønsted acid catalyst.

The selective activation of aliphatic C–H bonds remains a fundamental challenge in synthetic chemistry. Here we disclose a palladium‐catalyzed cross‐dehydrogenative coupling (CDC) that joins the α‐carbon of β‐ketoesters with the C3‐benzylic position of indoles, forging C(sp ³ )‐C(sp ³ ) bonds under mild oxidative conditions. This transformation uncovers an unprecedented directing effect of indolic π‐system, which engages in coordination with palladium to guide site‐selective C(sp ³ )‐H activation via an agostic interaction. The developed protocol exhibits high tunability, a broad substrate scope, and high yields under mild conditions, underscoring its potential for late‐stage functionalization in pharmaceutical and materials science applications. The transformation integrates well into one‐pot and multicomponent processes as well as enables stereoselective functionalization of the steroid core. Mechanistic investigations, supported by kinetic analysis and DFT calculations, indicate that the transformation proceeds with the involvement of Pd(IV) intermediates, with product decomplexation identified as the rate‐determining step.

Thioester chemistry is exploited in Nature by many CoA-dependent enzymes. However, the covalent nature of CoA attachment largely prevents the use of these enzymes in many applications. Replacing the CoA moiety with simpler, truncated fragments, such as its pantetheine (PAN) moiety, is also hampered by the lack of understanding of the function of the CoA moiety in enzymatic conversions. Herein, we describe the utilization of the enzyme (2E)-enoyl-CoA hydratase (ECH) using PAN thioesters and an activator, 3′,5′-ADP (PAP). ECH catalyzes the hydration of the carbon–carbon double bond of (2E)-enoyl-CoA substrates in the β-oxidation lipid-degrading pathway. The hydration reaction is very challenging to carry out by traditional chemical synthesis, as no selective catalysts are available. Structural enzymology of ECH and its complexes with (3S)-hydroxyacyl-CoA products show that hydrogen bonds between the adenine 6-amino group of the ADP moiety of CoA and loop-2 induce a small structural change in this active site loop, tightening the NN distance between the hydrogen bond donors of the oxyanion hole from 5.2 Å (unliganded) to 4.0 Å and forming a competent oxyanion hole at the catalytic site. A structurally similar and catalytically competent oxyanion hole is observed in the complex with (3S)-hydroxyhexanoyl PAN and the activator 3′,5′-ADP, both bound at the active site. The use of 3′,5′-ADP as the activator enables the synthetic use of ECH for the hydration of a wide range of (2E)-enoyl-PAN substrates with different steric demands and functionalities. The products, 3-hydroxyacyl-PAN thioesters, were obtained in good isolated yields and excellent stereoselectivities (typically >99:<1 3S:3R). Even for acyl chains that contain reactive groups such as bromide or methyl ester functionalities at C7, no side products resulting from potentially competing cyclization could be detected in the enzymatic hydration protocol.

The selective activation of aliphatic C-H bonds remains a fundamental challenge in synthetic chemistry. Here we disclose a palladium-catalyzed cross-dehydrogenative coupling (CDC) that joins the α-carbon of β-ketoesters with the C3-benzylic position of indoles, forging C(sp ³ )-C(sp ³ ) bonds under mild oxidative conditions. This transformation uncovers an unprecedented directing effect of indolic π-system, which engages in coordination with palladium to guide site-selective C(sp ³ )-H activation via an agostic interaction. The developed protocol exhibits high tunability, a broad substrate scope, and high yields under mild conditions, underscoring its potential for late-stage functionalization in pharmaceutical and materials science applications. The transformation integrates well into one-pot and multicomponent processes as well as enables stereoselective functionalization of the steroid core. Mechanistic investigations, supported by kinetic analysis and DFT calculations, indicate that the transformation proceeds with the involvement of Pd(IV) intermediates, with product decomplexation identified as the rate-determining step.

Connecting two carbon atoms is both a routine and fascinating challenge in modern synthetic chemistry. In this work, we establish a palladium-catalyzed cross-dehydrogenative coupling (CDC) of the α-carbon of β-ketoesters with the C3-benzylic position of indoles as a direct and efficient approach to C(sp3)-C(sp3) bond formation. This study uncovers the unexpected directing effect of indole in the selective activation of aliphatic C-H bonds, significantly broadening the scope of CDC reactions. The developed protocol exhibits high tunability, a broad substrate scope, and excellent yields under mild conditions, highlighting its potential for late-stage functionalization in pharmaceutical and material science applications. Additionally, the transformation integrates well into one-pot and multicomponent processes as well as enables stereoselective functionalization of the steroid core. Kinetic studies and density functional theory (DFT) calculations provide key mechanistic insights into the reaction pathway. Initial π-coordination of indole to palladium directs selective C(sp)–H activation via agostic interaction. The C–C coupling is proposed to proceed with the involvement of Pd(IV) intermediates, highlighting the critical role of the oxidant in the process. Product decomplexation emerges as the likely rate-determining step, consistent with the observed first-order dependence of the reaction rate on catalyst concentration.

We report a facile method for the functionalization of the 1,3‐diazaazulene core at the C4, C6, and C8 positions via regioselective bromination and subsequent substitution with amine nucleophiles. Both steps can be controlled to enable selective mono‐, di‐, or trisubstitution at C4, C6, or C8. Crystallographic studies revealed significant distortion from planarity in the aromatic core of the highly substituted 2,4,6,8‐tetra‐amino‐1,3‐diazaazulenes, further confirmed by density functional theory (DFT). The tetra‐aminosubstituted diazaazulenes displayed unusual hydrolytic reactivity in acidic media, a reaction that is rare with aminobenzenes and appears to be promoted in this case by structural distortion. The combinatorial functionalization of 1,3‐diazaazulene resulted in soft‐tunable optical properties observed in both solution and poly(methyl methacrylate) (PMMA) films. Strong low‐energy absorptions (ε = 11,800–38,500 M⁻¹·cm⁻¹), arise from π–π* transitions, as supported by our 2^nd order approximate coupled‐cluster (CC2) calculations. Consequently, the fluorescence relaxation mechanism involves a π*–π transition mixed with charge transfer, producing emission spanning from deep blue to yellow (λ_{em_max} = 428–535). We anticipate that the modular synthesis, tunable substitution patterns, and consequent modulation of both reactivity and photophysical properties renders the 1,3‐diazaazulene core an intriguing molecular platform for a variety of applications.