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1. Chiral π-Conjugated Double Helical Aminyl Diradical with the Triplet Ground State

   https://doi.org/10.1055/a-2379-9406  

   Guo, Haoxin; Rajca, Andrzej (February 2025, Synlett)

   Abstract We describe effective development of the highly diastereoselective synthesis of double helical tetraamine 2-H2-C2 and propose a mechanism for its formation. The resolution of 2-H2-C2 is facilitated by a high racemization barrier of 43 kcal mol–1 and it is implemented via either a chiral auxiliary or preparative supercritical fluid chromatography. This enables preparation of the first high-spin neutral diradical, with spin density delocalized within an enantiomeric double helical π-system. The presence of two effective 3-electron C–N bonds in the diradical leads to: (1) the triplet (S = 1) high-spin ground state with a singlet-triplet energy gap of 0.4 kcal mol–1 and (2) the long half-life of up to 6 days in 2-MeTHF at room temperature. The diradical possesses a racemization barrier of at least 26 kcal mol–1 in 2-MeTHF at 293 K and chiroptical properties, with an absorption anisotropy factor |g| ≈ 0.005 at 548 nm. These unique magnetic and optical properties of our diradical form the basis for the development of next-generation spintronic devices. 1 Introduction 2 Synthesis and Resolution of the C 2-Symmetric Double Helical Tetraamine 2-H2-C 2 3 Synthesis and Characterization of Neutral High-Spin Aminyl Diradical 22• -C 2 4 Conclusion 

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2. Remote C–H Functionalization via Selective Hydrogen Atom Transfer

   https://doi.org/10.1055/s-0036-1591930  

   Stateman, Leah; Nakafuku, Kohki; Nagib, David (April 2018, Synthesis)

   The selective functionalization of remote C–H bonds via intramolecular hydrogen atom transfer (HAT) is transformative for organic synthesis. This radical-mediated strategy provides access to novel reactivity that is complementary to closed-shell pathways. As modern methods for mild generation of radicals are continually developed, inherent selectivity paradigms of HAT mechanisms offer unparalleled opportunities for developing new strategies for C–H functionalization. This review outlines the history, recent advances, and mechanistic underpinnings of intramolecular HAT as a guide to addressing ongoing challenges in this arena. 1 Introduction 2 Nitrogen-Centered Radicals 2.1 sp3 N-Radical Initiation 2.2 sp2 N-Radical Initiation 3 Oxygen-Centered Radicals 3.1 Carbonyl Diradical Initiation 3.2 Alkoxy Radical Initiation 3.3 Non-alkoxy Radical Initiation 4 Carbon-Centered Radicals 4.1 sp2 C-Radical Initiation 4.2 sp3 C-Radical Initiation 5 Conclusion 

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3. Reduction‐Induced C─C Cleavage and Site‐Specific Hydrogenation of a Highly Strained Bilayer Spironanographene

   https://doi.org/10.1002/anie.202510209  

   Lión‐Villar, Juan; Torchon, Herdya S; Zhu, Yikun; Wei, Zheng; Fernández‐García, Jesús M; Fernández, Israel; Petrukhina, Marina A; Martín, Nazario (August 2025, Angewandte Chemie International Edition)

   Abstract The chemical reduction of a bilayer spironanographene,spiro‐NG(C₁₃₇H₁₂₀), with Na and K metals in the presence of [2.2.2]cryptand to yield [Na⁺(2.2.2‐cryptand)](C₁₃₇H₁₂₁⁻) (1) and [K⁺(2.2.2‐cryptand)](C₁₃₇H₁₂₁⁻) (2), respectively, is reported. X‐ray crystallography reveals the formation of a new “naked” anion (spiro‐NG_H⁻), in which spirocyclic ring cleavage and subsequent hydrogenation have occurred. Density Functional Theory (DFT) calculations suggest that the generation of the radical anion of the parent nanographene (spiro‐NG^•−), upon electron acceptance from Na and K metals, induces the cleavage of the strained spirobifluorene core. The resulting spin density localizes on a particular carbon atom, previously attached to the spiranic sp³carbon atom, facilitating a site‐specific hydrogenation to afford (spiro‐NG_H⁻). The electrostatic potential map of this anion reveals electron density concentrated at the five‐membered ring of the readily formed indenyl fragment, thus enhancing the aromaticity of the system. Furthermore, nuclear magnetic resonance (NMR) and UV–vis absorption spectroscopy experiments allowed to follow the in situ reduction and hydrogenation processes in detail. 

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4. Synthesis and Evaluation of C2-Symmetric SPIROL-Based bis-Oxazoline Ligands

   https://doi.org/10.3390/sym13091667  

   Sun, Siyuan; Diaz, Nicolas A.; Nagorny, Pavel (September 2021, Symmetry)

   This communication describes the synthesis of new bis-oxazoline chiral ligands (SPIROX) derived from the C2-symmetric spirocyclic scaffold (SPIROL). The readily available (R,R,R)-SPIROL (2) previously developed by our group was subjected to a three-step sequence that provided key diacid intermediate (R,R,R)-7 in 75% yield. This intermediate was subsequently coupled with (R)- and (S)-phenylglycinols to provide diastereomeric products, the cyclization of which led to two diastereomeric SPIROX ligands (R,R,R,R,R)-3a and (R,R,R,S,S)-3b in 85% and 79% yield, respectively. The complexation of (R,R,R,R,R)-3a and (R,R,R,S,S)-3b with CuCl and Cu(OTf)2 resulted in active catalysts that promoted the asymmetric reaction of α-diazopropionate and phenol. The resultant O–H insertion product was formed in 88% yield, and with excellent selectivity (97% ee) when ligand (R,R,R,R,R)-3a was used. 

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5. 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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