Dynamic stereomutation of vinylcyclopropanes with metalloradicals.

The ever increasing demands for greater sustainability and lower energy usage in chemical processes call for fundamentally new approaches and reactivity principles. In this context, the pronounced prevalence of odd-oxidation states in less precious metals bears untapped potential for fundamentally distinct reactivity modes via metalloradical catalysis1-3. Contrary to the well-established reactivity paradigm that organic free radicals, upon addition to a vinylcyclopropane, lead to rapid ring opening under strain release-a transformation that serves widely as a mechanistic probe (radical clock)4 for the intermediacy of radicals5-we herein show that a metal-based radical, that is, a Ni(I) metalloradical, triggers reversible cis/trans isomerization instead of opening. The isomerization proceeds under chiral inversion and, depending on the substitution pattern, occurs at room temperature in less than 5 min, requiring solely the addition of the non-precious catalyst. Our combined computational and experimental mechanistic studies support metalloradical catalysis as origin of this profound reactivity, rationalize the observed stereoinversion and reveal key reactivity features of the process, including its reversibility. These insights enabled the iterative thermodynamic enrichment of enantiopure cis/trans mixtures towards a single diastereomer through multiple Ni(I) catalysis rounds and also extensions to divinylcyclopropanes, which constitute strategic motifs in natural product- and total syntheses6. While the trans-isomer usually requires heating at approximately 200 °C to trigger thermal isomerization under racemization to cis-divinylcyclopropane, which then undergoes facile Cope-type rearrangement, the analogous contra-thermodynamic process is herein shown to proceed under Ni(I) metalloradical catalysis under mild conditions without any loss of stereochemical integrity, enabling a mild and stereochemically pure access to seven-membered rings, fused ring systems and spirocycles.

Rapid and Modular Access to Vinyl Cyclopropanes Enabled by Air-stable Palladium(I) Dimer Catalysis.

While vinyl cyclopropanes are valuable functional groups in drugs or natural products as well as established precursors to trigger a rich variety of synthetic transformations, their reactive nature can make their installation via direct catalytic approaches challenging. We herein present a modular access to (di)vinyl cyclopropanes under very mild conditions and full conservation of stereochemistry, allowing access to the cis or trans cyclopropane- as well as E or Z vinyl-stereochemical relationships. Our protocol relies on air-stable dinuclear PdI catalysis, which enables rapid (<30 min) and selective access to a diverse range of vinyl cyclopropane motifs at room temperature, even on gram scale.

Modular Generation of (Iodinated) Polyarenes Using Triethylgermane as Orthogonal Masking Group.

While the modular construction of molecules from suitable building blocks is a powerful means to more rapidly generate a diversity of molecules than through customized syntheses, the further evolution of the underlying coupling methodology is key to realize widespread applications. We herein disclose a complementary modular coupling approach to the widely employed Suzuki coupling strategy of boron containing precursors, which relies on organogermane containing building blocks as key orthogonal functionality and an electrophilic (rather than nucleophilic) unmasking event paired with air-stable PdI dimer based bond construction. This allows to significantly shorten the reaction times for the iterative coupling steps and/or to close gaps in the accessible compound space, enabling straightforward access also to iodinated compounds.

Catalysis with Palladium(I) Dimers.

Dinuclear PdI complexes have found widespread applications as diverse catalysts for a multitude of transformations. Initially their ability to function as pre-catalysts for low-coordinated Pd0 species was harnessed in cross-coupling. Such PdI dimers are inherently labile and relatively sensitive to oxygen. In recent years, more stable dinuclear PdI -PdI frameworks, which feature bench-stability and robustness towards nucleophiles as well as recoverability in reactions, were explored and shown to trigger privileged reactivities via dinuclear catalysis. This includes the predictable and substrate-independent, selective C-C and C-heteroatom bond formations of poly(pseudo)halogenated arenes as well as couplings of arenes with relatively weak nucleophiles, which would not engage in Pd0 /PdII catalysis. This Minireview highlights the use of dinuclear PdI  complexes as both pre-catalysts for the formation of highly active Pd0 and PdII -H species as well as direct dinuclear catalysts. Focus is set on the mechanistic intricacies, the speciation and the impacts on reactivity.

Site-Selective, Modular Diversification of Polyhalogenated Aryl Fluorosulfates (ArOSO2 F) Enabled by an Air-Stable PdI Dimer.

Since 2014, the interest in aryl fluorosulfates (ArOSO2 F) as well as their implementation in powerful applications has continuously grown. In this context, the enabling capability of ArOSO2 F will strongly depend on the substitution pattern of the arene, which ultimately dictates its overall function as drug candidate, material, or bio-linker. This report showcases the modular, substrate-independent, and fully predictable, selective functionalization of polysubstituted arenes bearing C-OSO2 F, C-Br, and C-Cl sites, which makes it possible to diversify the arene in the presence of OSO2 F or utilize OSO2 F as a triflate surrogate. Sequential and triply selective arylations and alkylations were realized within minutes at room temperature, using a single and air-stable PdI dimer.