Selective Carbonyl−C(sp3) Bond Cleavage To Construct Ynamides,Ynoates, and Ynones by Photoredox Catalysis

Carbon–carbon bond cleavage/functionalization is synthetically valuable, and selective carbonyl−C(sp³) bond cleavage/alkynylation presents a new perspective in constructing ynamides, ynoates, and ynones. Reported here is the first alkoxyl‐radical‐enabled carbonyl−C(sp³) bond cleavage/alkynylation reaction by photoredox catalysis. The use of novel cyclic iodine(III) reagents are essential for β‐carbonyl alkoxyl radical generation from β‐carbonyl alcohols, including alcohols with high redox potential ( >2.2 V vs. SCE in MeCN). β‐Amide, β‐ester, and β‐ketone alcohols yield ynamides, ynoates, and ynones, respectively, for the first time, with excellent regio‐ and chemoselectivity under mild reaction conditions.     

Alkynylation of C (O)–H Bonds Enabled by Photoredox‐Mediated Hydrogen‐Atom Transfer

The development of new hydrogen‐atom transfer (HAT) strategies within the framework of photoredox catalysis is highly appealing for its power to activate a desired C−H bond in the substrate leading to its selective functionalization. Reported here is the first photoredox‐mediated hydrogen‐atom transfer method for the efficient synthesis of ynones, ynamides, and ynoates with high regio‐ and chemoselectivity by direct functionalization of C (O)−H bonds. The broad synthetic application of this method has been demonstrated by the selective functionalization of C(O)−H bonds within complex molecular scaffolds.     

Rapid Room‐Temperature,Chemoselective C −C Coupling of Poly(pseudo)halogenated Arenes Enabled by Palladium(I) Catalysis in Air

While chemoselectivities in Pd⁰‐catalyzed coupling reactions are frequently non‐intuitive and a result of a complex interplay of ligand/catalyst, substrate, and reaction conditions, we herein report a general method based on Pd^I that allows for an a priori predictable chemoselective C −C coupling at C−Br in preference to C−OTf and C−Cl bonds, regardless of the electronic or steric bias of the substrate. The C−C bond formations are extremely rapid (<5 min at RT) and are catalyzed by an air‐ and moisture‐stable Pd^I dimer under open‐flask conditions.     

The β‐Agostic Structure in (C5Me5)2Sc(CH2CH3): Solid‐State NMR Studies of (C5Me5)2Sc−R (R=Me,Ph, Et)

Multinuclear solid‐state NMR studies of Cp*₂Sc?R (Cp*=pentamethylcyclopentadienyl; R=Me, Ph, Et) and DFT calculations show that the Sc?Et complex contains a β‐CH agostic interaction. The static central transition ⁴⁵Sc NMR spectra show that the quadrupolar coupling constants (C_q) follow the trend of Ph≈Me>Et, indicating that the Sc?R bond is different in Cp*₂Sc?Et compared to the methyl and phenyl complexes. Analysis of the chemical shift tensor (CST) shows that the deshielding experienced by Cβ in Sc?CH₂CH₃ is related to coupling between the filled σ_C‐C orbital and the vacant orbital.     

Donor–Acceptor Complex Enables Alkoxyl Radical Generation for Metal‐Free C(sp3)–C(sp3) Cleavage and Allylation/Alkenylation

The alkoxyl radical is an essential and prevalent reactive intermediate for chemical and biological studies. Here we report the first donor–acceptor complex‐enabled alkoxyl radical generation under metal‐free reaction conditions induced by visible light. Hantzsch ester forms the key donor–acceptor complex with N ‐alkoxyl derivatives, which is elucidated by a series of spectrometry and mechanistic experiments. Selective C(sp³)‐C(sp³) bond cleavage and allylation/alkenylation is demonstrated for the first time using this photocatalyst‐free approach with linear primary, secondary, and tertiary alkoxyl radicals.     

Catalytic and Atom‐Economic C −C Bond Formation: Alkyl Tantalum Ureates for Hydroaminoalkylation

Atom‐economic and regioselective C ?C bond formation has been achieved by rapid C?H alkylation of unprotected secondary arylamines with unactivated alkenes. The combination of Ta(CH₂SiMe₃)₃Cl₂, and a ureate N,O‐chelating‐ligand salt gives catalytic systems prepared in situ that can realize high yields of β‐alkylated aniline derivatives from either terminal or internal alkene substrates. These new catalyst systems realize C?H alkylation in as little as one hour and for the first time a 1:1 stoichiometry of alkene and amine substrates results in high yielding syntheses of isolated amine products by simple filtration and concentration.     

Reentrant Structural and Optical Properties and Large Positive Thermal Expansion in Perovskite Formamidinium Lead Iodide

The structure of the hybrid perovskite HC(NH₂)₂PbI₃ (formamidinium lead iodide) reflects competing interactions associated with molecular motion, hydrogen bonding tendencies, thermally activated soft octahedral rotations, and the propensity for the Pb²⁺ lone pair to express its stereochemistry. High‐resolution synchrotron X‐ray powder diffraction reveals a continuous transition from the cubic α‐phase (Pm m, #221) to a tetragonal β‐phase (P4/mbm, #127) at around 285 K, followed by a first‐order transition to a tetragonal γ‐phase (retaining P4/mbm, #127) at 140 K. An unusual reentrant pseudosymmetry in the β‐to‐γ phase transition is seen that is also reflected in the photoluminescence. Around room temperature, the coefficient of volumetric thermal expansion is among the largest for any extended crystalline solid.     

Kinetics of the Antibody Recognition Site in the Third IgG‐Binding Domain of Protein G

Protein dynamics occurring on a wide range of timescales play a crucial role in governing protein function. Particularly, motions between the globular rotational correlation time ( ) and 40 μs (supra‐ window), strongly influence molecular recognition. This supra‐ window was previously hidden, owing to a lack of experimental methods. Recently, we have developed a high‐power relaxation dispersion (RD) experiment for measuring kinetics as fast as 4 μs. For the first time, this method, performed under super‐cooled conditions, enabled us to detect a global motion in the first β‐turn of the third IgG‐binding domain of protein G (GB3), which was extrapolated to 371±115 ns at 310 K. Furthermore, the same residues show the plasticity in the model‐free residual dipolar coupling (RDC) order parameters and in an ensemble encoding the supra‐ dynamics. This β‐turn is involved in antibody binding, exhibiting the potential link of the observed supra‐ motion with molecular recognition.     

Visible Light-Enabled sp3-C−H Functionalization with Chloro- and Bromoalkynes: Chemoselective Route to Vinylchlorides or Alkynes

An unprecedented direct atom-economic chemo- and regioselective hydroalkylation of chloroalkynes and an sp³-C−H alkynylation of bromoalkynes was achieved. The reaction partners are unfunctionalized ethers, alcohols, amides, and even non-activated hydrocarbons. We found that a household fluorescent bulb was able to excite a diaryl ketone, which then selectively abstracts a H-atom from an sp³-C−H bond. The product of a formal alkyne insertion into the sp³-C−H bond was obtained with chloroalkynes, providing valuable vinyl chlorides. The photo-organocatalytic hydrogen atom transfer strategy gives rise to a broad range of diversely functionalized olefins. When bromoalkynes are applied in the presence of a base, a chemoselectivity switch to an alkynylation is observed. This reaction can even be performed for the alkynylation of unactivated sp³-C−H bonds, in this case with a preference of the more substituted carbon. Accompanying quantum chemical calculations indicate a vinyl radical intermediate with pronounced linear coordination of the carbon radical center, thus enabling the formation of both diastereoisomers after H-atom abstraction, suggesting that the (Z)-diastereoisomer is preferred, which supports the experimentally observed (E/Z)-distribution.     

Cooperative Light-Activated Iodine and Photoredox Catalysis for the Amination of C −H Bonds

An unprecedented method that makes use of the cooperative interplay between molecular iodine and photoredox catalysis has been developed for dual light-activated intramolecular benzylic C−H amination. Iodine serves as the catalyst for the formation of a new C−N bond by activating a remote C −H bond (1,5-HAT process) under visible-light irradiation while the organic photoredox catalyst TPT effects the reoxidation of the molecular iodine catalyst. To explain the compatibility of the two involved photochemical steps, the key N−I bond activation was elucidated by computational methods. The new cooperative catalysis has important implications for the combination of non-metallic main-group catalysis with photocatalysis.     

Dual Hypervalent Iodine(III) Reagents and Photoredox Catalysis Enable Decarboxylative Ynonylation under Mild Conditions

A combination of hypervalent iodine(III) reagents (HIR) and photoredox catalysis with visible light has enabled chemoselective decarboxylative ynonylation to construct ynones, ynamides, and ynoates. This ynonylation occurs effectively under mild reaction conditions at room temperature and on substrates with various sensitive and reactive functional groups. The reaction represents the first HIR/photoredox dual catalysis to form acyl radicals from α‐ketoacids, followed by an unprecedented acyl radical addition to HIR‐bound alkynes. Its efficient construction of an mGlu5 receptor inhibitor under neutral aqueous conditions suggests future visible‐light‐induced biological applications.     

The β‐Agostic Structure in (C5Me5)2Sc(CH2CH3): Solid‐State NMR Studies of (C5Me5)2Sc−R (R=Me,Ph, Et)

Multinuclear solid‐state NMR studies of Cp*₂Sc−R (Cp*=pentamethylcyclopentadienyl; R=Me, Ph, Et) and DFT calculations show that the Sc−Et complex contains a β‐CH agostic interaction. The static central transition ⁴⁵Sc NMR spectra show that the quadrupolar coupling constants (C_q) follow the trend of Ph≈Me>Et, indicating that the Sc−R bond is different in Cp*₂Sc−Et compared to the methyl and phenyl complexes. Analysis of the chemical shift tensor (CST) shows that the deshielding experienced by Cβ in Sc−CH₂CH₃ is related to coupling between the filled σ_C‐C orbital and the vacant orbital.     

Radical‐Induced Metal‐Free Alkynylation of Aldehydes by Direct CH Activation

A direct C(sp²)?H alkynylation of aldehyde C(O)?H bonds with hypervalent iodine alkynylation reagents provides ynones under metal‐free conditions. In this method, 1‐[(triisopropylsilyl)ethynyl]‐1,2‐benziodoxol‐3(1H)‐one (TIPS‐EBX) constitutes an efficient alkynylation reagent for the introduction of the triple bond. The substrate scope is extended to a variety of (hetero)aromatic, aliphatic, and α,β‐unsaturated aldehydes.     

Deriving Structural Information from Experimentally Measured Data on Biomolecules

During the past half century, the number and accuracy of experimental techniques that can deliver values of observables for biomolecular systems have been steadily increasing. The conversion of a measured value Q^exp of an observable quantity Q into structural information is, however, a task beset with theoretical and practical problems: 1) insufficient or inaccurate values of Q^exp, 2) inaccuracies in the function used to relate the quantity Q to structure , 3) how to account for the averaging inherent in the measurement of Q^exp, 4) how to handle the possible multiple‐valuedness of the inverse of the function , to mention a few. These apply to a variety of observable quantities Q and measurement techniques such as X‐ray and neutron diffraction, small‐angle and wide‐angle X‐ray scattering, free‐electron laser imaging, cryo‐electron microscopy, nuclear magnetic resonance, electron paramagnetic resonance, infrared and Raman spectroscopy, circular dichroism, Förster resonance energy transfer, atomic force microscopy and ion‐mobility mass spectrometry. The process of deriving structural information from measured data is reviewed with an eye to non‐experts and newcomers in the field using examples from the literature of the effect of the various choices and approximations involved in the process. A list of choices to be avoided is provided.     

Ligand‐Enabled Enantioselective C –H Activation of Tetrahydroquinolines and Saturated Aza‐Heterocycles by RhI

The first rhodium(I)‐catalyzed enantioselective intermolecular C –H activation of various saturated aza‐heterocycles including tetrahydroquinolines, piperidines, piperazines, azetidines, pyrrolidines, and azepanes is presented. The combination of a rhodium(I) precatalyst and a chiral monodentate phosphonite ligand is shown to be a powerful catalytic system to access a variety of important enantio‐enriched heterocycles from simple starting materials. Notably, the C –H activation of tetrahydroquinolines is especially challenging due to the adjacent C −H bond. This redox‐neutral methodology provides a new synthetic route to α‐N‐arylated heterocycles with high chemoselectivity and enantioselectivity up to 97 % ee.     

Silver‐Catalyzed Oxidative C(sp3)−P Bond Formation through C−C and P−H Bond Cleavage

The silver‐catalyzed oxidative C(sp³)−H/P−H cross‐coupling of 1,3‐dicarbonyl compounds with H‐phosphonates, followed by a chemo‐ and regioselective C(sp³)−C(CO) bond‐cleavage step, provided heavily functionalized β‐ketophosphonates. This novel method based on a readily available reaction system exhibits wide scope, high functional‐group tolerance, and exclusive selectivity.     

Ni‐Catalyzed Stannylation of Aryl Esters via C−O Bond Cleavage

A Ni‐catalyzed stannylation of aryl esters with air‐ and moisture‐insensitive silylstannyl reagents via C −O cleavage is described. This protocol is characterized by its wide scope, including challenging combinations, thus enabling access to versatile building blocks and orthogonal C−heteroatom bond formations.     

A Unified Treatment of the Relationship Between Ligand Substituents and Spin State in a Family of Iron(II) Complexes

The influence of ligands on the spin state of a metal ion is of central importance for bioinorganic chemistry, and the production of base‐metal catalysts for synthesis applications. Complexes derived from [Fe(bpp)₂]²⁺ (bpp=2,6‐di{pyrazol‐1‐yl}pyridine) can be high‐spin, low‐spin, or spin‐crossover (SCO) active depending on the ligand substituents. Plots of the SCO midpoint temperature (T ) in solution vs. the relevant Hammett parameter show that the low‐spin state of the complex is stabilized by electron‐withdrawing pyridyl (“X”) substituents, but also by electron‐donating pyrazolyl (“Y”) substituents. Moreover, when a subset of complexes with halogeno X or Y substituents is considered, the two sets of compounds instead show identical trends of a small reduction in T for increasing substituent electronegativity. DFT calculations reproduce these disparate trends, which arise from competing influences of pyridyl and pyrazolyl ligand substituents on Fe‐L σ and π bonding.     

Formal Nickelate(−I) Complexes Supported by Group 13 Ions

Formal nickelate(?I) complexes bearing Group 13 metalloligands (M=Al and Ga) were isolated. These 17 e^? complexes were synthesized by one‐electron reduction of the corresponding Ni⁰→M^III precursors, and were investigated by single‐crystal X‐ray diffraction, EPR spectroscopy, and quantum chemical calculations. Collectively, the experimental and computational data support: 1) the strengthening of the Ni?M bond upon one‐electron reduction, and 2) the delocalization of the unpaired spin across the Ni and M atoms. An intriguing electronic configuration is revealed where three valence electrons occupy two σ‐type bonding interactions: Ni(3d )²→M and σ‐(Ni?M)¹. The latter is an unusual Ni?M σ‐bonding molecular orbital that comprises primarily the Ni 4p_z and M np_z/ns atomic orbitals.     

Theoretical investigation toward organophosphine‐catalyzed [3 + 3] annulation of Morita–Baylis–Hillman carbonates with azomethine imines: Mechanism,origin of stereoselectivity,and role of catalyst

A computational study on the detailed mechanism and stereoselectivity of the chiral phosphine‐catalyzed C(sp²)? H activation/[3 + 3] annulation between Morita–Baylis–Hillman (MBH) carbonates and C,N‐cyclic azomethine imines has been performed. Generally, the catalytic cycle consists of two stages, that is, C(sp²)? H activation companied by the dissociation of the t‐BuO group forming phosphonium enolate, and [3 + 3] cycloaddition process followed by regeneration of the catalyst. The calculated results indicate that C(sp²)? H activation is rate‐determining while [3 + 3] cycloaddition is stereoselectivity‐determining. Furthermore, the advantageous hydrogen bond interactions and less steric hindrance in the RR configurational C? C bond forming transition states should be responsible for the favorability of RR‐configured product among the four possible products. The special role of the organocatalyst was also identified by natural bond orbital (NBO) and global reactivity index (GRI) analyses. The mechanistic insights obtained in the present study should be useful for understanding the novel organocatalytic C(sp²)? H activation and cycloaddition cascade reaction of MBH carbonates, and thus provide valuable clues on rational design of efficient organocatalysts for the C(sp²)? H activation/functionalizations.