Photocatalytic phosphine-mediated water activation for radical hydrogenation.

The chemical activation of water would allow this earth-abundant resource to be transferred into value-added compounds, and is a topic of keen interest in energy research1,2. Here, we demonstrate water activation with a photocatalytic phosphine-mediated radical process under mild conditions. This reaction generates a metal-free PR3-H2O radical cation intermediate, in which both hydrogen atoms are used in the subsequent chemical transformation through sequential heterolytic (H+) and homolytic (H•) cleavage of the two O-H bonds. The PR3-OH radical intermediate provides an ideal platform that mimics the reactivity of a 'free' hydrogen atom, and which can be directly transferred to closed-shell π systems, such as activated alkenes, unactivated alkenes, naphthalenes and quinoline derivatives. The resulting H adduct C radicals are eventually reduced by a thiol co-catalyst, leading to overall transfer hydrogenation of the π system, with the two H atoms of water ending up in the product. The thermodynamic driving force is the strong P=O bond formed in the phosphine oxide by-product. Experimental mechanistic studies and density functional theory calculations support the hydrogen atom transfer of the PR3-OH intermediate as a key step in the radical hydrogenation process.

Light-enabled deracemization of cyclopropanes by Al-salen photocatalysis.

Privileged chiral catalysts-those that share common structural features and are enantioselective across a range of reactions-continue to transform the chemical-research landscape1. In recent years, new reactivity modes have been achieved through excited-state catalysis, processes activated by light, but it is unclear if the selectivity of ground-state privileged catalysts can be matched. Although the interception of photogenerated intermediates by ground-state cycles has partially addressed this challenge2, single, chiral photocatalysts that simultaneously regulate reactivity and selectivity are conspicuously scarce3. So far, precision donor-acceptor recognition motifs remain crucial in enantioselective photocatalyst design4. Here we show that chiral Al-salen complexes, which have well-defined photophysical properties, can be used for the efficient photochemical deracemization5 of cyclopropyl ketones (up to 98:2 enantiomeric ratio (e.r.)). Irradiation at λ = 400 nm (violet light) augments the reactivity of the commercial catalyst to enable reactivity and enantioselectivity to be regulated simultaneously. This circumvents the need for tailored catalyst-substrate recognition motifs. It is predicted that this study will stimulate a re-evaluation of many venerable (ground-state) chiral catalysts in excited-state processes, ultimately leading to the identification of candidates that may be considered 'privileged' in both reactivity models.

Polar covalent apex-base bonding in borapyramidanes probed by solid-state NMR and DFT calculations.

Pyramidane molecules have attracted chemists for many decades due to their regular shape, high symmetry and their correspondence in the macroscopic world. Recently, experimental access to a number of examples has been reported, in particular the rarely reported square pyramidal bora[4]pyramidanes. To describe the bonding situation of the nonclassical structure of pyramidanes, we present solid-state Nuclear Magnetic Resonance (NMR) as a versatile tool for deciphering such bonding properties for three now accessible bora[4]pyramidane and dibora[5]pyramidane molecules. 11 B solid-state NMR spectra indicate that the apical boron nuclei in these compounds are strongly shielded (around -50 ppm vs. BF3 -Et2 O complex) and possess quadrupolar coupling constants of less than 0.9 MHz pointing to a rather high local symmetry. 13 C-11 B spin-spin coupling constants have been explored as a measure of the bond covalency in the borapyramidanes. While the carbon-boron bond to the -B(C6 F5 )2 substituents of the base serves as an example for a classical covalent 2-center-2-electron (2c-2e) sp2 -carbon-sp2 -boron σ-bond with 1 J(13 C-11 B) coupling constants in the order of 75 Hz, those of the boron(apical)-carbon(basal) bonds in the pyramid are too small to measure. These results suggest that these bonds have a strongly ionic character, which is also supported by quantum-chemical calculations.

Borole/Borapyramidane Relationship.

Boroles and borapyramidanes are classical and nonclassical constitutional isomers, respectively. It is here shown that they can indeed be interconverted. Treatment of the bis(alkynyl)B(C6F5) SMe2 adduct 3·SMe2 with HB(C6F5)2 gave borole 1·SMe2, featuring trimethylsilyl substituents in both α positions to boron, by means of a 1,1-hydroboration/alkenylboration sequence. Photolysis of the classical borole adduct 1·SMe2 resulted in rearrangement to its nonclassical structural isomer, borapyramidane 2, in high yield, which exhibits a vicinal pair of trimethylsilyl substituents at the square pyramidane base. Neutral borapyramidane 2 is a rare example of an isoster of the (CH)5+ pyramidane cation. Thermolysis of borapyramidane 2 in the presence of SMe2 at 60 °C re-formed borole 1·SMe2, which converted at 100 °C to 2,3-bis-silyl-substituted borole isomer 8·SMe2. Its photolysis also gave borapyramidane 2. Prolonged photolysis of 2 at elevated temperatures converted this to borapyramidane isomer 10 containing a pair of trimethylsilyl groups in 1,3-position at its square C4-pyramidal base. The borole and borapyramidane isomers were characterized by X-ray diffraction, and the system was analyzed by density functional theory (DFT) calculations.

Formation of a Hybrid 1-Bora-3-boratabenzene Heteroarene Anion Derivative.

The B(C6 F5 )2 -substituted borole 2⋅SMe2 was obtained from the phenyl bis(trimethylsilylethynyl) borane SMe2 adduct (1⋅SMe2 ) by a synthetic sequence containing a rare 1,1-hydroboration reaction. Subsequent thermolysis at 50 °C converted it to the bicyclic borenium/borate zwitterion 3⋅SMe2 . Photolysis of 3⋅SMe2 gave the diboracyclohexadiene derivative 4⋅SMe2 , which after ligand exchange with N,N-dimesitylimidazolylidene and deprotonation gave the 1-bora-3-boratabenzene anion derivative as its potassium salt 6. Some unique follow-up reactions of the unsaturated diboron containing six-membered heterocycles were investigated.

Synthesis and Reactivity of a Neutral Homocyclic Silylene.

Isolation of the neutral homocyclic silylene 2 is possible via amine ligand abstraction with potassium graphite (KC8 ) and subsequent reaction with SiMe3 Cl from a bicyclic silicon(I) amide J. This reaction proceeds via an anionic homoaromatic silicon ring compound 1 as an intermediate. The twofold-coordinated silicon atom in the homocyclic silylene 2 is stabilized by an allyl-type π-electron delocalization. 2 reacts in an oxidative addition with two equivalents of MeOH and in cycloadditions with ethene, phenylacetylene, diphenylacetylene and with 2,3-dimethyl-1,3-butadiene to afford novel functionalized ring compounds.

Photoswitchable Nitrogen Superbases: Using Light for Reversible Carbon Dioxide Capture.

Using light as an external stimulus to alter the reactivity of Lewis bases is an intriguing tool for controlling chemical reactions. Reversible photoreactions associated with pronounced reactivity changes are particularly valuable in this regard. We herein report the first photoswitchable nitrogen superbases based on guanidines equipped with a photochromic dithienylethene unit. The resulting N-heterocyclic imines (NHIs) undergo reversible, near quantitative electrocyclic isomerization upon successive exposure to UV and visible irradiation, as demonstrated over multiple cycles. Switching between the ring-opened and ring-closed states is accompanied by substantial pKa shifts of the NHIs by up to 8.7 units. Since only the ring-closed isomers are sufficiently basic to activate CO2 via the formation of zwitterionic Lewis base adducts, cycling between the two isomeric states enables the light-controlled capture and release of CO2 .

Oxy-Borylenes as Photoreductants: Synthesis and Application in Dehalogenation and Detosylation Reactions.

While the range of accessible borylenes has significantly broadened over the last decade, applications remain limited. Herein, we present tricoordinate oxy-borylenes as potent photoreductants that can be readily activated by visible light. Facile oxidation of CAAC stabilized oxy-borylenes (CAAC)(IPr2 Me2 )BOR (R=TMS, CH2 CH2 C6 H5 , CH2 CH2 (4-F)C6 H4 ) to their corresponding radical cations is achieved with mildly oxidizing ferrocenium ion. Cyclovoltammetric studies reveal ground-state redox potentials of up to -1.90 V vs. Fc+/0 for such oxy-borylenes placing them among the strongest organic super electron donors. Their ability as photoreductants is further supported by theoretical studies and showcased by the application as stoichiometric reagents for the photochemical hydrodehalogenation of aryl chlorides, aryl bromides and unactivated alkyl bromides as well as the detosylation of anilines.

Radical Aryl Migration from Boron to Carbon.

Radical aryl migration reactions represent a unique type of organic transformations that involve the intramolecular migration of an aryl group from a carbon or heteroatom to a C- or heteroatom-centered radical through a spirocyclic intermediate. Various elements, including N, O, Si, P, S, Sn, Ge, and Se, have been reported to participate in radical aryl migrations. However, radical aryl migration from a boron center has not been reported to date. In this communication, radical 1,5-aryl migration from boron to carbon in aryl boronate complexes is presented. C-radicals readily generated through radical addition onto alkenyl aryl boronate complexes are shown to engage in 1,5-aryl migration reactions to provide 4-aryl-alkylboronic esters. As boronate complexes can be generated in situ by the reaction of alkenylboronic acid esters with aryl lithium reagents, the aryl moiety is readily varied, providing access to a series of arylated products starting from the same alkenylboronic acid ester via divergent chemistry. Reactions proceed with high diastereoselectivity under mild conditions, and also the analogous 1,4-aryl shifts are feasible. The suggested mechanism is supported by DFT calculations.

Synthesis of Stannylated Aryl Imines and Amines via Aryne Insertion Reactions into Sn-N Bonds.

The reaction of in situ generated arynes with stannylated imines to provide ortho-stannyl-aniline derivatives is reported. The readily prepared trimethylstannyl benzophenone imine is introduced as an efficient reagent to realize the aryne σ-insertion reaction. The imine functionality is an established N-protecting group and insertions proceed with good yields and good to excellent regioselectivities. The product anilines are valuable starting materials for follow-up chemistry thanks to the rich chemistry offered by the trimethylstannyl moiety.

Insights into Ergochromes of the Plant Pathogen Claviceps purpurea.

Claviceps purpurea is an ergot fungus known for its neurotropic alkaloids, which have been identified as the main cause of ergotism, a livestock and human disease triggered by ergot consumption. Tetrahydroxanthone dimers, the so-called ergopigments, presumably also contribute to this toxic effect. Overexpression of the cluster-specific transcription factor responsible for the formation of these pigments in C. purpurea led to the isolation of three new metabolites (8-10). The new pigments were characterized utilizing HRMS, NMR techniques, and CD spectroscopy and shown to be xanthone dimers. Secalonic acid A and its 2,4'- and 4,4'-linked isomers were also isolated, and their absolute configuration was investigated. The contribution of secalonic acid A, its isomers, and new metabolites to the toxicity of C. purpurea was investigated in HepG2 and CCF-STTG1 cells. Along with cytotoxic properties, secalonic acid A was found to inhibit topoisomerase I and II activity.

Trifluorinated Tetralins via I(I)/I(III)-Catalysed Ring Expansion: Programming Conformation by [CH2 CH2 ] → [CF2 CHF] Isosterism.

Saturated, fluorinated carbocycles are emerging as important modules for contemporary drug discovery. To expand the current portfolio, the synthesis of novel trifluorinated tetralins has been achieved. Fluorinated methyleneindanes serve as convenient precursors and undergo efficient difluorinative ring expansion with in situ generated p-TolIF2 (>20 examples, up to >95 %). A range of diverse substituents are tolerated under standard catalysis conditions and this is interrogated by Hammett analysis. X-ray analysis indicates a preference for the CH-F bond to occupy a pseudo-axial orientation, consistent with stabilising σC-H →σC-F * interactions. The replacement of the symmetric [CH2 -CH2 ] motif by [CF2 -CHF] removes the conformational degeneracy intrinsic to the parent tetralin scaffold leading to a predictable half-chair. The conformational behavior of this novel structural balance has been investigated by computational analysis and is consistent with stereoelectronic theory.

Mechanism of the Arene-Limited Nondirected C-H Activation of Arenes with Palladium*.

Recently palladium catalysts have been discovered that enable the directing-group-free C-H activation of arenes without requiring an excess of the arene substrate, thereby enabling methods for the late-stage modification of complex organic molecules. The key to success has been the use of two complementary ligands, an N-acyl amino acid and an N-heterocycle. Detailed experimental and computational mechanistic studies on the dual-ligand-enabled C-H activation of arenes have led us to identify the catalytically active species and a transition state model that explains the exceptional activity and selectivity of these catalysts. These findings are expected to be highly useful for further method development using this powerful class of catalysts.

Desymmetrization of Prochiral Cyclobutanones via Nitrogen Insertion: A Concise Route to Chiral γ-Lactams.

Asymmetric access to γ-lactams is achieved via a cyclobutanone ring expansion using widely available (1S,2R)-1-amino-2-indanol for chiral induction. Mechanistic analysis of the key N,O-ketal rearrangement reveals a Curtin-Hammett scenario, which enables a downstream stereoinduction (up to 88:12 dr) and is corroborated by spectroscopic, crystallographic, and computational studies. In combination with an easy deprotection protocol, this operationally simple sequence allows the synthesis of a range of optically pure γ-lactams, including those bearing all-carbon quaternary stereocenters. In addition, the formal synthesis of drug molecules baclofen, brivaracetam, and pregabalin further demonstrates the synthetic utility and highlights the general applicability of the presented method.

The Bis(η6 -benzene)lithium Cation: A Fundamental Main-Group Organometallic Species.

The synthesis and characterization of the bis(η6 -benzene)lithium cation, the benzene metallocene of the lightest metal, is reported. The boron compound FmesBCl2 [Fmes: 2,4,6-tris(trifluoromethyl)phenyl] reacted with three molar equivalents of the lithio-acetylene reagent Li-C≡C-Fmxyl [Fmxyl: 3,5-bis(trifluoromethyl)phenyl]. Subsequent crystallization from benzene gave the [bis(η6 -benzene)Li]+ cation with the [{FmesB(-C≡C-Fmxyl)3 }2 Li]- anion. This parent [(arene)2 Li]+ cation shows an eclipsed arrangement of the pair of benzene ligands at the central lithium cation with uniform carbon-lithium bond lengths. The corresponding [(η6 -toluene)2 Li]+ and [(η6 -durene)2 Li]+ containing salts were similarly prepared. The bis(arene)lithium cations were characterized by X-ray diffraction, by solid-state 7 Li MAS NMR spectroscopy and their bonding features were analyzed by DFT calculations.

1,n-Bisborylalkanes via Radical Boron Migration.

A systematic study of radical boron migration in diboronate complexes to form synthetically valuable 1,n-bisborylalkanes is reported. The boronate complexes are readily generated by reaction of commercial bis(pinacolato)diboron with alkyl Grignard compounds. C-radical generation at a defined position with respect to the diboron moiety is achieved either via intermolecular H-abstraction with a CF3-radical or via alkene perfluoroalkyl radical addition. It is shown that radical 1,2- and 1,4-boron migrations to provide geminal and 1,3-bisborylalkanes are efficient transformations. The 1,5-boron migration in the homologous series leading to 1,4-bisborylalkanes is also occurring, albeit with lower efficiency. Experimental results are supported by DFT calculations which also reveal the corresponding 1,3-boron migration in such diboronate complexes to be feasible.

A BH Borenium-Derived Thioxoborane, Its Persulfide, and Their Li+-Induced Reactions with Alkynes and with Carbon Dioxide.

Insertion of sulfur into the B-H bond of the BH borenium salt [IMes(C6F5)BH]+ followed by deprotonation gave the thioxoborane IMes(C6F5)B═S. Subsequent treatment with additional sulfur gave the corresponding boron persulfide, a NHC-stabilized boradithiirane. The B═S compound reacted with carbon dioxide in the presence of the lithium salt Li[B(C6F5)4] by formal [2+2] cycloaddition to give a boron thiocarbonate-type product. The boron persulfide formally inserted phenyl acetylene into the B-S bond in the presence of Li[B(C6F5)4] to give the respective five-membered heterocycle.

Reductive Cleavage of the CO Molecule by a Reactive Vicinal Frustrated PH/BH Lewis Pair.

A dimeric ethylene-bridged PH/BH system reduced carbon monoxide to the -CH2-O- state. In the presence of B(C6F5)3, the frustrated PH/BH Lewis pair reacted with carbon monoxide by reductive coupling of two CO molecules at the template. Removal of the B(C6F5)3 borane with pyridine liberated one equiv of carbon monoxide to give a cyclic five-membered P(═O)-CH2-B compound, the product of reductive cleavage of carbon monoxide. It reacted as a borylated Horner P(═O)CH2B carbon nucleophile with carbon dioxide to give a bicyclic product by P-CH2 attack on CO2 combined with internal P═O to boron coordination.

Design of Ru(II)-NHC-Diamine Precatalysts Directed by Ligand Cooperation: Applications and Mechanistic Investigations for Asymmetric Hydrogenation.

A modular synthesis of Ru(II)-NHC-diamine complexes from readily available chiral N-heterocyclic carbenes (NHCs) and chiral diamines is disclosed for the first time. The well-defined Ru(II)-NHC-diamine complexes show unique structure and coordination chemistry including an unusual tridentate coordination effect of 1,2-diphenylethylenediamine. The isolated air- and moisture-stable Ru(II)-NHC-diamine complexes act as versatile precatalysts for the asymmetric hydrogenation of isocoumarines, benzothiophene 1,1-dioxides, and ketones. Moreover, on the basis of the identification of reaction intermediates by stoichiometric reactions and NMR experiments, together with the DFT calculations, a possible catalytic cycle was proposed.

Conformational Analysis of Acyclic α-Fluoro Sulfur Motifs.

Bioactive small molecules containing α-fluoro sulfur motifs [RS(O)n CH2 F] are appearing with increasing frequency in the pharmaceutical and agrochemical sectors. Prominent examples include the anti-asthma drug Flovent® and the phenylpyrazole insecticide pyrafluprole. Given the popularity of these structural units in bioactive small molecule design, together with the varying oxidation states of sulfur, a conformational analysis of α-fluoro sulfides, sulfoxides, and sulfones, would be instructive in order to delineate the non-covalent interactions that manifest themselves in structure. A combined crystallographic and computational analysis demonstrates the importance of hyperconjugative donor-acceptor interactions in achieving acyclic conformational control. The conformational disparity in the syn- and anti-diastereoisomers of α-fluorosulfoxides is particularly noteworthy.