Wojciech Chaładaj

Activation of aryl halides across a broad reactivity spectrum remains a central challenge in photoredox catalysis, particularly due to the kinetic barriers associated with C–Cl bond reduction. Herein, we report on a photocatalytic platform that enables substrate-dependent access to distinct reductive regimes through the synergistic integration of formate-derived CO2·– and excitation pathways. Under the developed conditions, aryl bromides and chlorides, despite exhibiting demanding reduction potentials, display markedly different reactivity, governed by kinetic factors specific to the substrate and catalytic system. CO2·– mediates thermodynamically matched reduction of aryl bromides, whereas more recalcitrant aryl chlorides are activated via a two-photon reductive manifold, consistent with either a ConPET-type mechanism or solvated electron involvement. Notably, formate serves as both the precursor to CO2·– and the electron donor enabling a two-photon, strongly reductive manifold, obviating the need for sacrificial amines. This adaptive system facilitates a variety of transformations, including the efficient cyclization-carboxylation of (2-halophenoxy)allenes with CO2 under mild conditions. Mechanistic studies, including kinetic analysis, competition experiments, isotopic labelling, spectroscopic studies, and DFT calculations, support a dual-regime mechanism governed by substrate-dependent activation barriers. This work establishes a framework for kinetically gated control of reductive strength in photoredox catalysis by harnessing CO2·– as a reductant.

An efficient Cu-catalyzed protocol for the carbotrifluoromethylation of alkynes has been developed using Ruppert-Prakash reagent as the CF ₃ source. The reaction proceeds under mild conditions to deliver a broad range of β-trifluoromethylated alkenes with excellent regio- and stereoselectivities. The selectivity was achieved via a merge of Cu-catalyzed carboboration with subsequent trifluoromethylation of the resulting vinyl-borate.

Over the past few years, isodiazenes have reemerged as an important class of intermediates with substantial synthetic potential. The most direct route to these reactive species is via reactions of N ‐nucleophiles with nitrenium ion precursors (e.g., anomeric amides). While emerging methodologies are almost exclusively focused on amine‐derived isodiazenes, analogous transformations based on other nitrogen functionalities (e.g., oximes, heterocycles) are largely overlooked. Herein, we present evidence that the reactivity of nitrenium ion precursors can be expanded beyond its current scope, supported by the development of an unprecedented reaction between anomeric amides and isoxazol‐5‐ones. This unorthodox transformation provides an operationally simple, scalable, and highly chemoselective route to challenging sterically hindered alkynes. Moreover, we demonstrate that anomeric amides can behave as surrogates of nitrosonium cation.

Over the past few years, isodiazenes have reemerged as an important class of intermediates with substantial synthetic potential. The most direct route to these reactive species is via reactions of N ‐nucleophiles with nitrenium ion precursors (e.g., anomeric amides). While emerging methodologies are almost exclusively focused on amine‐derived isodiazenes, analogous transformations based on other nitrogen functionalities (e.g., oximes, heterocycles) are largely overlooked. Herein, we present evidence that the reactivity of nitrenium ion precursors can be expanded beyond its current scope, supported by the development of an unprecedented reaction between anomeric amides and isoxazol‐5‐ones. This unorthodox transformation provides an operationally simple, scalable, and highly chemoselective route to challenging sterically hindered alkynes. Moreover, we demonstrate that anomeric amides can behave as surrogates of nitrosonium cation.

Hydro- and heteroboration of alkynes typically delivers a boron substituent at the β-position. Herein, syn-selective α-borylation-arylation is accomplished through a one-pot Ni-catalyzed carbomagnesiation followed by borylation. The regio- and stereoselectivity is established in the carbometalation step, while utilization of B(pin)H is essential for high efficiency of borylation of the sterically hindered vinylmagnesium intermediate. The resulting trisubstituted vinyl boronates are versatile building blocks, in particular, for the synthesis of configurationally defined tetrasubstituted olefins through cross-coupling. A two-step synthesis of Tamoxifen is presented.

Trifluoromethylthiolative difunctionalization of alkynes typically proceeds in an anti-fashion delivering the SCF₃ group in the β-position (anti-Markovnikov). Herein, we disclose a vicinal syn-arylation-trifluoromethylthiolation of alkynes enabling α-selective introduction of the SCF₃ group (Markovnikov). The unique selectivity was achieved via a merge of Ni-catalyzed carbomagnesiation with a subsequent Cu-mediated trifluoromethylthiolation of the resulting vinyl-magnesium species. The former component of the sequential process determines both the regio- and stereoselectivity of the overall transformation.

A sustainable method for the synthesis of 2-deoxy lactones as direct precursors to 2-deoxy sugars via regioselective UV-light-driven dealkyloxylation of carbohydrate-derived lactones is detailed. This catalyst- and additive-free protocol utilizes light irradiation, providing high step economy and functional group compatibility. This environmentally friendly and straightforward approach enhances the synthetic toolbox for 2-deoxy sugars, which is vital in numerous biologically active molecules and drug candidates.

Drastic changes to the character of the acidic catalyst enable the reversal of the double alkyne benzannulation reaction output. In the presence of a strong Brønsted acid, 1,4-dihydropyrrolopyrroles undergo transformation which results in the formation of two 7-membered rings. Computational studies imply that the thermodynamically unfavored 7-membered ring is forged via the kinetically favored 6-endo-dig attack of a protonated alkyne at the position 3a of pyrrolopyrrole followed by a 1,2-vinyl shift.

Fixation of carbon dioxide from its waste streams into value added products, in organic synthesis processes, whilst challenging, would lead to great ecological benefits. To this end, a CO2 cycloaddition to epoxides seems most promising as it is a 100% atom economic reaction leading to valuable cyclic carbonates. However, many of the reaction systems utilized for their synthesis employ organic solvents, high temperatures, and high pressure. Thus, the micellar conditions reported here achieve a metal and organic solvent free approach, giving access to not only carbonates but also carbamates without the need for pressurization or heating. Extensive studies of interactions between micelles and carbon dioxide opens up pathways to use this gaseous reagent in aqueous media.

Tight chelation of enolate by lithium alters the selectivity of tandem palladium-catalyzed cyclization/coupling of terminal alpha-homopropargyl-beta-ketoesters with aryl halides. In the presence of LiOH, substituted cyclopentenes are preferentially formed via 5-endo-dig carbocyclization, in contrast to the 6-exo-dig oxocyclization exclusively observed in the absence of a hard, chelating metal center. The disclosed transformation, featuring mild conditions and broad functional group tolerance, can be applied for a variety of (hetero)aryl bromides as well as aryl and vinyl triflates.