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1. Experimental and computational studies of the mechanism of iron-catalysed C–H activation/functionalisation with allyl electrophiles

   https://doi.org/10.1039/d1sc01661j  

   DeMuth, Joshua C.; Song, Zhihui; Carpenter, Stephanie H.; Boddie, Theresa E.; Radović, Aleksa; Baker, Tessa M.; Gutierrez, Osvaldo; Neidig, Michael L. (July 2021, Chemical Science)

   Synthetic methods that utilise iron to facilitate C–H bond activation to yield new C–C and C–heteroatom bonds continue to attract significant interest. However, the development of these systems is still hampered by a limited molecular-level understanding of the key iron intermediates and reaction pathways that enable selective product formation. While recent studies have established the mechanism for iron-catalysed C–H arylation from aryl-nucleophiles, the underlying mechanistic pathway of iron-catalysed C–H activation/functionalisation systems which utilise electrophiles to establish C–C and C–heteroatom bonds has not been determined. The present study focuses on an iron-catalysed C–H allylation system, which utilises allyl chlorides as electrophiles to establish a C–allyl bond. Freeze-trapped inorganic spectroscopic methods ( 57 Fe Mössbauer, EPR, and MCD) are combined with correlated reaction studies and kinetic analyses to reveal a unique and rapid reaction pathway by which the allyl electrophile reacts with a C–H activated iron intermediate. Supporting computational analysis defines this novel reaction coordinate as an inner-sphere radical process which features a partial iron–bisphosphine dissociation. Highlighting the role of the bisphosphine in this reaction pathway, a complementary study performed on the reaction of allyl electrophile with an analogous C–H activated intermediate bearing a more rigid bisphosphine ligand exhibits stifled yield and selectivity towards allylated product. An additional spectroscopic analysis of an iron-catalysed C–H amination system, which incorporates N -chloromorpholine as the C–N bond-forming electrophile, reveals a rapid reaction of electrophile with an analogous C–H activated iron intermediate consistent with the inner-sphere radical process defined for the C–H allylation system, demonstrating the prevalence of this novel reaction coordinate in this sub-class of iron-catalysed C–H functionalisation systems. Overall, these results provide a critical mechanistic foundation for the rational design and development of improved systems that are efficient, selective, and useful across a broad range of C–H functionalisations. 

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2. Isomer-selected ion–molecule reactions of acetylene cations with propyne and allene

   https://doi.org/10.1039/D0CP03953E  

   Schmid, P. C.; Greenberg, J.; Nguyen, T. L.; Thorpe, J. H.; Catani, K. J.; Krohn, O. A.; Miller, M. I.; Stanton, J. F.; Lewandowski, H. J. (September 2020, Physical Chemistry Chemical Physics)

   null (Ed.)

   One of the fundamental goals of chemistry is to determine how molecular structure influences interactions and leads to different reaction products. Studies of isomer-selected and resolved chemical reactions can shed light directly on how form leads to function. In the following, we present the results of gas-phase reactions between acetylene cations (C 2 D 2 + ) with two different isomers of C 3 H 4 : propyne (DC 3 D 3 ) and allene (H 2 C 3 H 2 ). Our highly controlled, trapped-ion environment allows for precise determination of reaction products and kinetics. From these results, we can infer details of the underlying reaction dynamics of C 2 H 2 + + C 3 H 4 . Through the synergy of experimental results and high-level quantum chemical potential energy surface calculations, we are able to identify distinct reaction mechanisms for the two isomers. We find long-range charge exchange with no complex formation is favored for allene, whereas charge exchange leads to an intermediate reaction complex for propyne and thus, different products. Therefore, this reaction displays a pronounced isomer-selective bi-molecular reactive process. 

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3. Photoinduced C(sp ³ )–H sulfination empowers the direct and chemoselective introduction of the sulfonyl group

   https://doi.org/10.1039/D1SC04245A  

   Jin, Shengfei; Haug, Graham C.; Trevino, Ramon; Nguyen, Viet D.; Arman, Hadi D.; Larionov, Oleg V. (October 2021, Chemical Science)

   Direct installation of the sulfinate group by the functionalization of unreactive aliphatic C–H bonds can provide access to most classes of organosulfur compounds, because of the central position of sulfinates as sulfonyl group linchpins. Despite the importance of the sulfonyl group in synthesis, medicine, and materials science, a direct C(sp 3 )–H sulfination reaction that can convert abundant aliphatic C–H bonds to sulfinates has remained elusive, due to the reactivity of sulfinates that are incompatible with typical oxidation-driven C–H functionalization approaches. We report herein a photoinduced C(sp 3 )–H sulfination reaction that is mediated by sodium metabisulfite and enables access to a variety of sulfinates. The reaction proceeds with high chemoselectivity and moderate to good regioselectivity, affording only monosulfination products and can be used for a solvent-controlled regiodivergent distal C(sp 3 )–H functionalization. 

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4. Intermediates and mechanism in iron-catalyzed C–H methylation with trimethylaluminum

   https://doi.org/10.1039/D1CC05607G  

   Bhatia, Shilpa; DeMuth, Joshua C.; Neidig, Michael L. (November 2021, Chemical Communications)

   A mechanistic study is performed on the reaction method for iron-catalyzed C–H methylation with AlMe 3 reagent, previously proposed to involve cyclometalated iron( iii ) intermediates and an iron( iii )/( i ) reaction cycle. Detailed spectroscopic studies ( 57 Fe Mössbauer, EPR) during catalysis and in stoichiometric reactions identify iron( ii ) complexes, including cyclometalated iron( ii ) intermediates, as the major iron species formed in situ under catalytic reaction conditions. Reaction studies identify a cyclometalated iron( ii )-methyl species as the key intermediate leading to C–H methylated product upon reaction with oxidant, consistent with a previously proposed iron( ii )/iron( iii )/iron( i ) reaction manifold for C–H arylation. 

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5. Access to unsaturated bicyclic lactones by overriding conventional C(sp3)–H site selectivity

   https://doi.org/10.1038/s41557-023-01295-x  

   Das, Jayabrata; Ali, Wajid; Ghosh, Animesh; Pal, Tanay; Mandal, Astam; Teja, Chitrala; Dutta, Suparna; Pothikumar, Rajagopal; Ge, Haibo; Zhang, Xinglong; et al (November 2023, Nature Chemistry)

   Abstract Transition metal catalysis plays a pivotal role in transforming unreactive C–H bonds. However, regioselective activation of distal aliphatic C–H bonds poses a tremendous challenge, particularly in the absence of directing templates. Activation of a methylene C–H bond in the presence of methyl C–H is underexplored. Here we show activation of a methylene C–H bond in the presence of methyl C–H bonds to form unsaturated bicyclic lactones. The protocol allows the reversal of the general selectivity in aliphatic C–H bond activation. Computational studies suggest that reversible C–H activation is followed by β-hydride elimination to generate the Pd-coordinated cycloalkene that undergoes stereoselective C–O cyclization, and subsequent β-hydride elimination to provide bicyclic unsaturated lactones. The broad generality of this reaction has been highlighted via dehydrogenative lactonization of mid to macro ring containing acids along with the C–H olefination reaction with olefin and allyl alcohol. The method substantially simplifies the synthesis of important bicyclic lactones that are important features of natural products as well as pharmacoactive molecules. 

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