Iron-Catalyzed Photoinduced LMCT: a 1° C-H Abstraction Enables Skeletal Rearrangements and C(sp3)-H Alkylation.

Herein we disclose an iron-catalyzed method to access skeletal rearrangement reactions akin to the Dowd-Beckwith ring expansion from unactivated C(sp3)-H bonds. Photoinduced ligand-to-metal charge transfer at the iron center generates a chlorine radical, which abstracts electron-rich C(sp3)-H bonds. The resulting unstable alkyl radicals can undergo rearrangement in the presence of suitable functionality. Addition to an electron deficient olefin, recombination with a photoreduced iron complex, and subsequent protodemetallation allows for redox-neutral alkylation of the resulting radical. Simple adjustments to the reaction conditions enable the selective synthesis of the directly alkylated or the rearranged-alkylated products. As a radical clock, these rearrangements also enable the measurement of rate constants of addition into various electron deficient olefins in the Giese reaction

Cobalt-catalyzed Wagner–Meerwein rearrangements with concomitant nucleophilic hydrofluorination

The authors acknowledge funding from the Royal Society (University Research Fellowship URF\R1\180017 (CPJ) and associated Enhancement Award RGF\EA\181022 (CPJ and RHH)), and the EaSI-CAT Centre for Doctoral Training (RHH and NM).We report a cobalt-catalyzed Wagner-Meerwein rearrangement of gem-disubstituted allylarenes that generates fluoroalkane products with isolated yields up to 84%. Modification of the counteranion of the N-fluoropyridinium oxidant suggests the substrates undergo nucleophilic fluorination during the reaction. Subjecting the substrates to other known metal-mediated hydrofluorination procedures did not lead to observable 1,2-aryl migration. Thus, indicating the unique ability of these cobalt-catalyzed conditions to generate a sufficiently reactive electrophilic intermediate capable of promoting this Wagner-Meerwein rearrangement.Publisher PDFPeer reviewe

The discovery and application of metal-free cyclobutanol ring expansion reactions

Cyclobutanol ring expansions have emerged as a powerful tool to access functionalised five- and six-membered rings and have thus, in particular over the last decade, attracted considerable interest from the synthetic community. Despite the surge of novel methodologies for the expansion of four-membered rings reported, those enabling the expansion to benzofused cyclohexanones (tetralones) remain notably underdeveloped. Herein, the discovery and development of functional group-tolerant, mild synthetic methodologies for the cyclobutanol ring expansion to tetralones is described. Initially, a regioselective N-bromosuccinimide-mediated cyclobutanol ring expansion to heteroaryl-fused tetralones is reported, which is characterised by its notably short reaction durations. Investigations into optimal reaction conditions, the substrate scope, and the underlying mechanism are detailed here. Our understanding gained through these studies culminated in the application of this methodology to the total synthesis of the 5-lipoxygenase inhibitor carbazomycin B. Then, in collaboration with Alessia Petti and Dr Kevin Lam from the University of Greenwich, a mild electrochemical cyclobutanol ring expansion to 1-tetralones was developed. This enabled the extension of the ring expansion substrate scope, as a variety of electronically and sterically different aryl-substituted cyclobutanols were found to be suitable ring expansion precursors. In addition, studies towards the total synthesis of the perfumery agent myrrhone are described.Open Acces

Asymmetric Migratory Tsuji–Wacker Oxidation Enables the Enantioselective Synthesis of Hetero- and Isosteric Diarylmethanes

Diarylmethanes play, in part, a pivotal role in the design of highly potent, chiral, nonracemic drugs whose bioactivity is typically affected by the substitution pattern of their arene units. In this context, certain arenes such as para-substituted benzenes or unsubstituted heteroarenes cause particular synthetic challenges, since such isosteric residues at the central methane carbon atom are typically indistinguishable for a chiral catalyst. Hence, the stereoselective incorporation of isosteric (hetero)arenes into chiral methane scaffolds requires the use of stoichiometrically differentiated building blocks, which is typically realized through preceding redox-modifying operations such as metalation or halogenation and thus associated with disadvantageous step- and redox-economic traits. As a counter-design, we report herein a generalized enantioselective synthesis of chiral diarylmethanes by means of an asymmetric migratory Tsuji–Wacker oxidation of simple stilbenes. The title protocol relies on the well-adjusted interplay of aerobic photoredox and selenium-π-acid catalysis to allow for the installation of a broad variety of arenes, including isosteric ones, into the methane core. Facial differentiation and regioselectivity are solely controlled by the selenium catalyst, which (a) renders the E/Z-configuration of the stilbene substrates inconsequential and (b) permits the stereodivergent synthesis of both product enantiomers from a single catalyst enantiomer, simply by employing constitutionally isomeric starting materials. Altogether, this multicatalytic platform offers the target structures with high levels of enantioselectivity in up to 97% ee, which has also been successfully exploited in expedited syntheses of antihistaminic (R)- and (S)-neobenodine

Asymmetric Ion-Pairing Catalysis

Chemistry and Chemical Biolog