Organocatalytic Dynamic Kinetic Resolution Enabled Asymmetric Synthesis of Phosphorus-Containing Chiral Helicenes

The catalytic asymmetric synthesis of phosphorus-containing helicenes remains a formidable challenge, presumably due to the lack of rational design of substrates, right choice of reactions together with highly effective catalysis systems. Herein, we disclosed an efficient and practical DKR-involving (dynamic kinetic resolution) cascade strategy toward synthesizing a novel family of phosphorus-installing helicenes by peptide-mimic phosphonium salt (PPS) catalysis. The sequential process of PPS-catalyzed phospha-Michael attack and copper salt-facilitated aromatization led to the formation of unprecedented phosphorus-containing oxa[5]helicene scaffolds. A wide variety of substrates bearing an assortment of functional groups were compatible with this protocol, furnishing the expected helical compounds in high yields and excellent stereoselectivities. Additionally, the helical products could be conveniently elaborated to promising phosphine ligands with perfectly retained helical chirality, which turned out to be highly efficient chiral ligands in transition metal-catalyzed reactions. These findings not only expand the current library of phosphorus-containing helicenes but also offer insights to explore other challenging scaffolds with molecular chirality.     

Silver-Catalyzed Dearomative [2π+2σ] Cycloadditions of Indoles with Bicyclobutanes: Access to Indoline Fused Bicyclo[2.1.1]hexanes**

Bicyclo[2.1.1]hexanes (BCHs) are becoming ever more important in drug design and development as bridged scaffolds that provide underexplored chemical space, but are difficult to access. Here a silver-catalyzed dearomative [2π+2σ] cycloaddition strategy for the synthesis of indoline fused BCHs from N-unprotected indoles and bicyclobutane precursors is described. The strain-release dearomative cycloaddition operates under mild conditions, tolerating a wide range of functional groups. It is capable of forming BCHs with up to four contiguous quaternary carbon centers, achieving yields of up to 99 %. In addition, a scale-up experiment and the synthetic transformations of the cycloadducts further highlighted the synthetic utility.     

Stereospecific Conversion of Boronic Esters into Enones using Methoxyallene: Application in the Total Synthesis of 10-Deoxymethynolide

Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three-carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated-methoxyallene, protonation triggers a stereospecific 1,2-migration before oxidation generates the enone. The protocol shows broad substrate scope and complete enantiospecificity is observed with chiral migrating groups. In addition, various electrophiles could be used to induce 1,2-migration and give a much broader range of α-functionalized enones. Finally, the methodology was applied to a 14-step synthesis of the enone-containing polyketide 10-deoxymethynolide.     

Synergistic Activation of Nitrite and Thiocarbonyl Compounds Affords NO and Sulfane Sulfur via (Per)thionitrite (SNO−/SSNO−)

(Per)thionitrite (SNO⁻/SSNO⁻) intermediates play vital roles in modulating nitric oxide (NO) and hydrogen sulfide (H₂S) dependent bio-signalling processes. Whilst the previous preparations of such intermediates involved reactive H₂S/HS⁻ or sulfane sulfur (S⁰) species, the present report reveals that relatively stable thiocarbonyl compounds (such as carbon disulfide (CS₂), thiocarbamate, thioacetic acid, and thioacetate) react with nitrite anion to yield SNO⁻/SSNO⁻. For instance, the reaction of CS₂ and nitrite anion (NO₂⁻) under ambient condition affords CO₂ and SNO⁻/SSNO⁻. A detailed investigation involving UV/Vis, FTIR, HRMS, and multinuclear NMR studies confirm the formation of SNO⁻/SSNO⁻, which are proposed to form through an initial nucleophilic attack by nitrite anion followed by a transnitrosation step. Notably, reactions of CS₂ and nitrite in the presence of thiol RSH show the formation of organic polysulfides R-S_n-R, thereby illustrating that the thiocarbonyls are capable of influencing the pool of bioavailable sulfane sulfurs. Furthermore, the availability of both NO₂⁻ and thiocarbonyl motifs in the biological context hints at their synergistic metal-free activations leading to the generation of NO gas and various reactive sulfur species via SNO⁻/SSNO⁻.     

Ni-Catalyzed Regio- and Enantioselective Homoallylic Coupling: Synthesis of Chiral Branched 1,5-Dienes Featuring a Quaternary Stereogenic Center and Mechanistic Analysis

Asymmetric synthesis of small molecules comprising quaternary stereogenic carbon centers represents a challenging objective. Here regio- and enantioselective synthesis of chiral 1,5-dienes featuring quaternary stereocenters is reported via nickel-promoted by reductive homoallylic coupling. The developed methodology features an atypical preference for the formation of unusual branched regioisomers (rr >20 : 1) in a sterically challenging allylic substitution event and furnishes the products with enantiomeric ratios of up to 98 : 2 and with high chemo- and E-selectivity. A range of experimental evidences suggest that zinc plays a dual role to generate electrophilic and nucleophilic Ni(II)-allyl intermediates empowering a unique formal bimetallic cross-electrophile manifold in two separate kinetic regimes.     

Controlling Electron Delocalization in Vanadium-Based Hybrid Bronzes through Molecular Templation

We show that the conductivity of hybrid vanadium bronzes—mixed-valence organic–inorganic vanadium oxides—can be tuned over six orders of magnitude through judicious choice of molecular component. By systematically varying the steric profile, charge density, and propensity to hydrogen bond across a series of eight diammonium-based molecules, we engender multiple distinct motifs of V−O connectivity within the two-dimensional vanadium oxide layers of a family of bulk crystalline hybrid materials. A combination of single-crystal and powder X-ray diffraction analysis, variable-temperature electrical transport measurements, and a range of spectroscopic methods, including UV/Visible diffuse reflectance, X-ray photoelectron, and electron paramagnetic resonance are employed to probe how vanadium oxide layer topology correlates with electron localization. Specifically, alkylammonium molecules yield hybrids featuring more corrugated layers that contain V−O tetrahedra as well as a higher ratio of corner-sharing to edge-sharing polyhedra and that exhibit highly localized electronic behavior, while alkyl bipyridinium molecules yield more regular layers with polyhedral edge-sharing that show substantially delocalized electronic behavior. This work allows for the development of design principles based on structure–property relationships and brings the charge transport capabilities of hybrid vanadium bronzes to more technologically relevant levels.     

A Photoenzymatic Strategy for Radical-Mediated Stereoselective Hydroalkylation with Diazo Compounds

Carbene insertion reactions initiated with diazo compounds have been widely used to develop unnatural enzymatic reactions. However, alternative functionalization of diazo compounds in enzymatic processes has been unexploited. Herein, we describe a photoenzymatic strategy for radical-mediated stereoselective hydroalkylation with diazo compounds. This method generates carbon-centered radicals through an ene reductase catalyzed photoinduced electron transfer process from diazo compounds, enabling the synthesis of γ-stereogenic carbonyl compounds in good yields and stereoselectivities. This study further expands the possible reaction patterns in photo-biocatalysis and offers a new approach to solving the selectivity challenges of radical-mediated reactions.     

Low-Valent MxAl3 Cluster Salts with Tetrahedral [SiAl3]+ and Trigonal-Bipyramidal [M2Al3]2+ Cores (M=Si/Ge)

Schnöckel's [(AlCp*)₄] and Jutzi's [SiCp*][B(C₆F₅)₄] (Cp*=C₅Me₅) are landmarks in modern main-group chemistry with diverse applications in synthesis and catalysis. Despite the isoelectronic relationship between the AlCp* and the [SiCp*]⁺ fragments, their mutual reactivity is hitherto unknown. Here, we report on their reaction giving the complex salts [Cp*Si(AlCp*)₃][WCA] ([WCA]⁻=[Al(OR^F)₄]⁻ and [F{Al(OR^F)₃}₂]⁻; R^F=C(CF₃)₃). The tetrahedral [SiAl₃]⁺ core not only represents a rare example of a low-valent silicon-doped aluminium-cluster, but also—due to its facile accessibility and high stability—provides a convenient preparative entry towards low-valent Si−Al clusters in general. For example, an elusive binuclear [Si₂(AlCp*)₅]²⁺ with extremely short Al−Si bonds and a high negative partial charge at the Si atoms was structurally characterised and its bonding situation analysed by DFT. Crystals of the isostructural [Ge₂(AlCp*)₅]²⁺ dication were also obtained and represent the first mixed Al−Ge cluster.     

Peptide Bond Formation in the Protonated Serine Dimer Following Vacuum UV Photon-Induced Excitation

Possible routes for intra-cluster bond formation (ICBF) in protonated serine dimers have been studied. We found no evidence of ICBF following low energy collision-induced dissociation (in correspondence with previous works), however, we do observe clear evidence for ICBF following photon absorption in the 4.6–14 eV range. Moreover, the comparison of photon-induced dissociation measurements of the protonated serine dimer to those of a protonated serine dipeptide provides evidence that ICBF, in this case, involves peptide bond formation (PBF). The experimental results are supported by ab initio molecular dynamics and exploration of several excited state potential energy surfaces, unraveling a pathway for PBF following photon absorption. The combination of experiments and theory provides insight into the PBF mechanisms in clusters of amino acids, and reveals the importance of electronic excited states reached upon UV/VUV light excitation.     

Carbene Formation or Reduction of the Diazo Functional Group? An Unexpected Solvent-Dependent Reactivity of Cyclic Diazo Imides

The control of the reactivity of diazo compounds is commonly achieved by the choice of a suitable catalyst, e.g. via stabilization of singlet carbenes or radical intermediates. Herein, we report on the light-promoted reactivity of cyclic diazo imides with thiols, where the choice of solvent results in two fundamentally different reaction pathways. In dichloromethane (DCM), a carbene is formed initially and engages in a cascade C−H functionalization/thiolation reaction to deliver indane-fused pyrrolidines in good to excellent yields. When switching to acetonitrile solvent, the carbene pathway is shut down and an unusual reduction of the diazo compound occurs under otherwise identical reaction conditions, where the aryl thiol acts as reductant. A combined set of experimental and computational studies was carried out to obtain mechanistic understanding and to support that indane formation proceeds via the insertion of a triplet carbene, while the reduction of diazo imides proceeds via an electron transfer process.