Decoding Key Transient Inter-Catalyst Interactions in a Reductive Metallaphotoredox-Catalyzed Allylation Reaction.

Metallaphotoredox chemistry has recently witnessed a surge in interest within the field of synthetic organic chemistry through the use of abundant first-row transition metals combined with suitable photocatalysts. The intricate details arising from the combination of two (or more) catalytic components during the reaction and especially the inter-catalyst interactions remain poorly understood. As a representative example of a catalytic process featuring such intricacies, we here present a meticulous study of the mechanism of a cobalt-organophotoredox catalyzed allylation of aldehydes. Importantly, the commonly proposed elementary steps in reductive metallaphotoredox chemistry are more complex than previously assumed. After initial reductive quenching, a transient charge-transfer complex forms that interacts with both the transition-metal catalyst and the catalytic base. Surprisingly, the former interaction leads to deactivation due to induced charge recombination, while the latter promotes deprotonation of the electron donor, which is the crucial step to initiate productive catalysis but is often neglected. Due to the low efficiency of this latter process, the overall catalytic reaction is photon-limited and the cobalt catalyst remains in a dual resting state, awaiting photoinduced reduction. These new insights are of general importance to the synthetic community, as metallaphotoredox chemistry has become a powerful tool used in the formation of elusive compounds through carbon-carbon bond formations. Understanding the underlying aspects that determine the efficiency of such reactions provides a conceptually stronger reactivity paradigm to empower future approaches to synthetic challenges that rely on dual metallaphotoredox catalysis.

Expedient Dual Co/Organophotoredox Catalyzed Stereoselective Synthesis of All-Carbon Quaternary Centers.

An efficient and attractive Co/organophotoredox dual catalysis protocol has been developed allowing the stereoselective access to a wide variety of syn-configured 1,3-diols featuring quaternary carbon centers. The synthesis of the target molecules is achieved under ambient reaction conditions using modular and accessible reagents, substituted vinyl cyclic carbonates and aldehydes, and in short reaction times. Mechanistic control experiments suggest that the stereoselectivity can be rationalized via a preferred Zimmerman-Traxler transition state comprising a Co(allyl) species and an activated aldehyde. This newly developed process thus expands the use of base metal catalysis in the construction of challenging quaternary carbon stereocenters.

Formal Synthesis of Indolizidine and Quinolizidine Alkaloids from Vinyl Cyclic Carbonates.

Cyclic carbonates have long been considered relatively inert molecules acting as protecting groups in complex multistep synthetic routes. This study shows that a concise, yet modular synthesis of indolizidine and quinolizidine alkaloids can be developed from vinyl-substituted cyclic carbonate (VCC) intermediates. Through a highly stereoselective palladium-catalyzed allylic alkylation reaction, these alkaloid motifs can be assembled in four synthetic and only two column purification steps. The combined results help to further advance functionalized cyclic carbonates as useful and reactive intermediates in natural product synthesis.

Copper-Catalyzed Enantioselective Construction of Tertiary Propargylic Sulfones.

Tertiary propargylic sulfones are of significant importance in organic synthesis and medicinal chemistry, but to date no general asymmetric synthesis approach has been developed. We disclose a versatile copper-catalyzed sulfonylation of propargylic cyclic carbonates using sodium sulfinates that allows the construction of propargylic sulfones featuring elusive quaternary stereocenters. This method provides the first successful example of such an enantioselective propargylic sulfonylation, features high asymmetric induction, wide functional group tolerance, and scalability, and enables attractive product diversification.

Palladium-Catalyzed ( Z)-Selective Allylation of Nitroalkanes: Access to Highly Functionalized Homoallylic Scaffolds.

Nitroalkanes undergo decarboxylative allylation in the presence of vinyl-substituted cyclic carbonates, providing a wide variety of functionalized homoallylated compounds with exquisite stereocontrol. This Pd-mediated procedure features operational simplicity, versatile substrate combinations, and also allows for the sequential introduction of different allyl groups in the nitroalkane scaffolds with high levels of stereocontrol through the intermediacy of a ( Z)-configured palladacyclic intermediate. As far as we know, the developed protocol is the first general Pd-mediated methodology toward ( Z)-configured homoallylic nitroalkanes with attractive functional group diversity.

Catalytic Transformations of Functionalized Cyclic Organic Carbonates.

Functionalized cyclic organic carbonates and related heterocycles have emerged as highly versatile heterocyclic substrates for ring-opening and decarboxylative catalytic transformations allowing for the development of new stereo- and enantioselective C-N, C-O, C-C, C-S and C-B bond formation reactions. Transition-metal-mediated conversions have only recently been rejuvenated as powerful approaches towards the preparation of more complex molecules. This minireview will highlight the potential of cyclic carbonates and structurally related heterocycles with a focus on their synthetic value and the mechanistic manifolds that are involved upon their conversion.

Unlocking the Potential of Substrate-Directed CO2 Activation and Conversion: Pushing the Boundaries of Catalytic Cyclic Carbonate and Carbamate Formation.

The unparalleled potential of substrate-induced reactivity modes in the catalytic conversion of carbon dioxide and alcohol or amine functionalized epoxides is discussed in relation to more conventional epoxide/CO2 coupling strategies. This conceptually new approach allows for a substantial extension of the substitution degree and functionality of cyclic carbonate/carbamate products, which are predominant products in the area of nonreductive CO2 transformations. Apart from the creation of an advanced library of CO2 -based heterocyclic products and intermediates, also the underlying mechanistic reasons for this novel reactivity profile are debated with a prominent role for the design and structure of the involved catalysts.