A Carbene Relay Strategy for Cascade Insertion Reactions

Insertion reactions that involve stabilized electrophilic metallocarbenes are of great importance for installing α-heteroatoms to carbonyl compounds. Nevertheless, the limited availability of carbene precursors restricts the introduction of only a single heteroatom. In this report, we describe a new approach based on an I^(III)/S^(VI) reagent that promotes the cascade insertion of heteroatoms. This is achieved by sequentially generating two α-heteroatom-substituted metal carbenes in one reaction. We found that this mixed I^(III)/S^(VI) ylide reacts efficiently with a transition metal catalyst and an X−H bond (where X=O, N). This transformation leads to the sequential formation of a sulfoxonium- and an X-substituted Rh-carbenes, enabling further reactions with another Y−H bond. Remarkably, a wide range of symmetrical and unsymmetrical α,α-O,O-, α,α-O,N-, and α,α-N,N-subsituted ketones can be prepared under mild ambient conditions. In addition, we successfully demonstrated other cascades, such as CN/CN double amidation, C−H/C−S double insertion, and C−S/Y−H double insertion (where Y=S, N, O, C). Notably, the latter two cascades enabled the simultaneous installation of three functional groups to the α-carbon of carbonyl compounds in a single step. These reactions demonstrate the versatility of our approach, allowing for the synthesis of ketones and esters with multiple α-heteroatoms using a common precursor.     

Correlation between Absorption and Substitution of Photochromic 1,2-Bis(thienyl)ethenes (BTEs) Using Modified Spectroscopic Hammett Equations

Series of photochromic 1,2-bis(thienyl)ethenes possessing perfluorocyclopentene backbones, either hydrogen or methyl groups at the β-positions of the thiophenes, and a variety of substituents in their α'-positions were prepared, which cover the range from electron-donating to electron-withdrawing (Me, −CH₂OH, −OTBS, −TMS, −Br, 1,3-dioxan-2-yl, pyridin-4-yl, −CH₂OH, −COOH). As a linear free energy relationship the spectroscopic Hammett equation gives fair to excellent fits to the excitation energy of the absorption maxima of the ring-opened as well as the ring-closed forms of the BTEs, when Hammett substituent constants σ_p were replaced by Brown's modified substituent constants σ_p⁺ and σ_p⁻. Vice versa, hitherto unknown Hammett-Brown substituent constants can be estimated from the UV spectra. Furthermore, we compared the experimentally measured absorption maxima with values which we calculated by three different methods (DFT STEOM-DLPNO-CCSD/def2-TZVPP, TD-DFT ωB97X-D3/6-31G*, TD-DFT ωB97X-D3/6-311++G**).     

A Fairly Stable Crystalline Silanone

Silanones 2 substituted by bulky amino‐ and phosphonium ylide substituents have been synthesized and isolated in crystalline form. Thanks to the steric protection and the strong electron‐donating ability of the substituents, silanones 2 are persistent and only slowly dimerizes at room temperature (t _1/2=0.5 or 5 h). Structural and theoretical analysis of 2 indicate a short Si=O bond (1.533 Å) and an enhanced polarization toward the O atom compared to Me₂Si=O owing to the strong π‐electron donation from the phosphonium ylide substituent.     

Cyclic (Amino)(Phosphonium Bora‐Ylide)Silanone: A Remarkable Room‐Temperature‐Persistent Silanone

A silanone substituted by bulky amino and phosphonium bora‐ylide substituents has been isolated in crystalline form. Thanks to the exceptionally strong electron‐donating phosphonium bora‐ylide substituent, the lifetime at room temperature of the silanone is dramatically extended (t _1/2=4 days) compared to the related (amino)(phosphonium ylide)silanone VI (t _1/2=5 h), allowing easier manipulation and its use as precursor of new valuable silicon compounds. The interaction of silanone with a weak Lewis acid such as MgBr₂ increases further its stability (no degradation after 3 weeks at room temperature).     

Polymer swelling. XXV. Structure‐affinity correlation studies that involve poly(styrene‐co‐divinylbenzene) exposed to acetylenic liquids

The adsorption parameters (α) established for the monosubstituted acetylenic liquids in this investigation are consistent with expectation based on analogies with the log α_f = log α_i ‐ D_s(N_f − N_i) relationships reported earlier for the many homologous series of liquids ZR, in which Z is a functional group having strong affinity for the pendent phenyl group of polystyrene and R is an alkyl substituent that is varied systematically. The order of relative Z‐affinities, based on α for the respective ZCH₂CH₃ molecules, confirm that the nature of Z is the major factor that affects α and that electronic and steric contributions from R are modifying effects, which are reflected in D_s. Comparisons of the results observed for HCC(CH₂)_nZ′ liquids with those for HCC(CH₂)_nH and with analogous pairs of Z(CH₂)_nZ′ series confirm that Z′ at the other end of the polymethylene chain can have a moderate positive effect or a marked negative effect on α, depending on whether the mode of adsorption to pendent phenyl groups is mono‐ or bidentate. This study also confirms that a sharp reversal in the roles played by the molecules participating in the adsorption process occurs when all of the hydrogen atoms covalently bonded to the center of unsaturation are replaced by alkyl substituents. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 2611–2633, 1999     

13C NMR spectra of p- and m-substituted phenyl N-methyl- and phenyl N,N-dimethyl-carbamates

¹³C NMR spectra of p- and m-substituted phenyl N-methylcarbamates, phenyl N,N-dimethylcarbamates and p- and m-substituted phenyl propionates were recorded, and their para ¹³C SCS (substituent chemical shifts) were analysed by DSP (dual substituent parameters) and DSP-NLR (non-linear resonance) equations. It was found that the fixed substituent Y, ? OCONHCH₃, ? OCON(CH₃)₂ and ? OCOC₂H₅, were all mild in the sense that DSP analysis gave a good correlation, leaving little room for improvement by the DSP-NLR treatment. Further, the three series of compounds gave similar ρ_I and ρ_R values (para derivatives, 3.2–3.3 and 17.7–18.0; meta derivatives, 5.1–5.2 and 21.8–22.0). Examination of the corresponding analyses of similar compounds indicated that the ρ_I and ρ_R values and, hence, their ratio ρ_R/ρ_R = λ, depended primarily on the nature of the atom through which the fixed substituent Y (e.g. α-C, α-N and α-O) was bonded to the aromatic ring when the Y substituents are mild. The extent of this tendency for compounds with active fixed substituents is also discussed.     

Diastereoselective cycloaddition of isatin azomethine ylides to 5-arylidene-2-thiohydantoins bearing 3-positioned chiral substituent

1,3-Dipolar cycloaddition of azomethine ylide, generated from isatin and sarcosine, with 5-arylidene-2-thiohydantoins equipped with various chiral substituents at the N³ atom occurs diastereoselectively. The highest selectivity with dr = 5 : 1 was observed for the 2-thiohydantoin bearing 1,2-diphenylethyl substituent.     

Stereoelectronic and steric effect in the Baeyer–Villiger rearrangement of steroidal α-chlorocyclobutanones

The regioselectivity of the Baeyer–Villiger oxidation of α-chlorocyclobutanone derivatives is markedly affected by substituents in position γ to the carbonyl group. The reaction of steroidal α-chlorocyclobutanones with m-chloroperoxybenzoic acid results in the formation of γ-chloro-γ-lactones and/or α-chloro-γ-lactones depending on the substitution pattern of the four-membered ring. In the reactions of γ-unsubstituted α-chlorocyclobutanones, the exclusive formation of γ-chloro-γ-lactone results from the migration of the chlorinated substituent (CHCl) versus the alkyl group (CH₂), contrary to the expected migratory aptitude. In explaining the unusual regioselectivity observed in these reactions, steric effects and dipole interactions in the formation of the reactive Criegee intermediates are considered and the stereoelectronic effect is postulated to be more important than the intrinsic migratory aptitude.     

Using Ylide Functionalization to Stabilize Boron Cations

The metalated ylide YNa [Y=(Ph₃PCSO₂Tol)⁻] was employed as X,L‐donor ligand for the preparation of a series of boron cations. Treatment of the bis‐ylide functionalized borane Y₂BH with different trityl salts or B(C₆F₅)₃ for hydride abstraction readily results in the formation of the bis‐ylide functionalized boron cation [Y−B−Y]⁺ ( 2 ). The high donor capacity of the ylide ligands allowed the isolation of the cationic species and its characterization in solution as well as in solid state. DFT calculations demonstrate that the cation is efficiently stabilized through electrostatic effects as well as π‐donation from the ylide ligands, which results in its high stability. Despite the high stability of 2 [Y−B−Y]⁺ serves as viable source for the preparation of further borenium cations of type Y₂B⁺←LB by addition of Lewis bases such as amines and amides. Primary and secondary amines react to tris(amino)boranes via N−H activation across the B−C bond.     

Synthesis,Crystal and Electronic Structures of a Thiophosphinoyl- and Amino-Substituted Metallated Ylide

α-Metallated ylides have revealed themselves to be versatile reagents for the introduction of ylide groups. Herein, we report the synthesis of the thiophosphinoyl and piperidyl (Pip) substituted α-metallated ylide [Ph₂(Pip)P=C−P(S)Ph₂]M (M=Li, Na, K) through a four-step synthetic procedure starting from diphenylmethylphosphine sulfide. Metallation of the ylide intermediate was successfully accomplished with different alkali metal bases delivering the lithium, sodium and potassium salts, the latter isolable in high yields. Structure analyses of the lithium and potassium compounds in the solid state with and without crown ether revealed different aggregates (monomer, dimer and hexamer) with the metals coordinated by the thiophosphoryl moiety and ylidic carbon atom. Although the piperidyl group does not coordinate to the metal, it significantly contributes to the stability of the yldiide by charge delocalization through negative hyperconjugation.     

Correlations of 95Mo NMR chemical shifts with ligand basicity in substituted pyridine pentacarbonylmolybdenum(O) complexes

Molybdenum-95 NMR chemical shifts are reported for a series of Mo(O) compounds of the type Mo(CO)₅L (L = pyridine derivatives). A good correlation is found between the δ(⁹⁵Mo) values and the Hammett sigma constant of the pyridine substituent or the pK_a of the substituted pyridine. The chemical shift values, which range from −1366 ppm (3-CN, σ = 0.62, pK_a = 1.35) to −1433 ppm (4-NMe₂, σ = −0.83, pK_a = 9.61), directly reflect the electronic properties of the pyridine derivatives even though the substituent is four or five bonds away from the molybdenum atom.     

Unexpected hydrobromic acid-catalyzed C-C bond-forming reactions and facile synthesis of coumarins and benzofurans based on ketene dithioacetals

Hydrobromic acid was found to be a unique catalyst in C? C bond‐forming reactions with ketene dithioacetals. Distinctly different from other acids (including Lewis and Brønsted acids), the remarkable catalytic performance of hydrobromic acid in catalytic amounts was observed in the “acid”‐catalyzed reactions of readily available functionalized ketene dithioacetals 1 with various electrophiles. Under the catalysis of 0.1 equivalents of hydrobromic acid, the reaction of 1 with carbonyl compounds 2 a – l gave polyfunctionalized penta‐1,4‐dienes 3 or conjugated dienes 4 in good to excellent yields. The reaction tolerated a broad range of substituents on both the ketene dithioacetals 1 and the carbonyl compounds 2 . Application of this efficient C? C bond‐forming method generated coumarins 5 and benzofurans 7 under mild, metal‐free conditions by hydrobromic acid‐catalyzed reactions of 1 with salicylaldehydes 2 m – o and p‐quinones 6 a – d , respectively. A new reactive species, a sulfur‐stabilized carbonium ylide, formed depending on the nature of the counterion, and this was proposed as the key intermediate in the unique catalysis of hydrobromic acid.     

Treatment of Silylene–Phosphinidene with Chalcogens Resulted Exclusively in the Formation of Silicon-Bonded Chalcogens

Chalcogen-bonded silicon phosphinidenes LSi(E)−P−^MecAAC (E=S ( 1 ); Se ( 2 ); Te ( 3 ); L=PhC(NtBu)₂; ^MecAAC=C(CH₂)(CMe₂)₂N-2,6-iPr₂C₆H₃)) were synthesized from the reactions of silylene–phosphinidene LSi−P−^MecAAC ( A ) with elemental chalcogens. All the compounds reported herein have been characterized by multinuclear NMR, elemental analyses, LIFDI-MS, and single-crystal X-ray diffraction techniques. Furthermore, the regeneration of silylene–phosphinidene ( A ) was achieved from the reactions of 2 – 3 with L′Al (L′=HC{(CMe)(2,6-iPr₂C₆H₃N)}₂). Theoretical studies on chalcogen-bonded silicon phosphinidenes indicate that the Si−E (E=S, Se, Te) bond can be best represented as charge-separated electron-sharing σ-bonding interaction between [LSi−P−^MecAAC]⁺ and E⁻. The partial double-bond character of Si−E is attributed to significant hyperconjugative donation from the lone pair on E⁻ to the Si−N and Si−P σ*-molecular orbitals.     

Synthesis of Low-Valent Dinuclear Group 14 Compounds with Element–Element Bonds by Transylidation

Dinuclear low-valent compounds of the heavy main group elements are rare species owing to their intrinsic reactivity. However, they represent desirable target molecules due to their unusual bonding situations as well as applications in bond activations and materials synthesis. The isolation of such compounds usually requires the use of substituents that provide sufficient stability and synthetic access. Herein, we report on the use of strongly donating ylide-substituents to access low-valent dinuclear group 14 compounds. The ylides not only impart steric and electronic stabilization, but also allow facile synthesis via transfer of an ylide from tetrylene precursors of type ^RY₂E to ECl₂ (E=Ge, Sn; ^RY=TolSO₂(PR₃)C with R=Ph, Cy). This method allowed the isolation of dinuclear complexes amongst a germanium analogue of a vinyl cation, [(^PhY)₂GeGe(^PhY)]⁺ with an electronic structure best described as a germylene-stabilized Ge^II cation and a ylide(chloro)digermene [^CyY(Cl)GeGe(Cl)^CyY] with an unusually unsymmetrical structure.     

Novel Ortho effects detected in the fast atom bombardment mass spectra of substituted bisaryl phosphate antagonists of platelet-activating factor

A series of substituted bisaryl phosphate compounds, (R¹CH₂)⁺ ArOP = O(O^?)(OArR²R₃), was analyzed and characterized by fast atom bombardment mass spectrometry. Abundant fragment ions were observed and correlated with the proposed structures. From fragmentation pattersn, ‘ortho effect’ reactions were demonstrated to have occurred when the phosphoryl oxygen reacted with the (CH₂R¹)⁺ and C?O(OCH₃) substituents in the ortho position, relative to the phosphate group, and displaced the R¹ and OCH₃ groups, respectively, to produce phosphorus containing six-membered rings fused to the aryl moiety. When the (CH₂R¹)⁺ substituents were in the meta position relative to the phosphate group, the ‘ortho effect’ reactions were not observed. However, when the C?O(OCH₃) substituent was in the meta position relative to the phosphate group, an abundant fragment ion containing a five-membered phosphate ring fused to the aryl ring was detected with the original phosphoryl oxygen ortho to both the phosphate oxygen and a formyl group, formed from the original C?O(OCH₃) substituent. All other fragmentations not involving the ‘ortho effect’ reactions were nearly identical for the different structural isomers of the substituted bisaryl phosphate compounds.     

Periphery-substituted [4+6] salicylbisimine cage compounds with exceptionally high surface areas: influence of the molecular structure on nitrogen sorption properties

The synthesis of various periphery‐substituted shape‐persistent cage compounds by twelve‐fold condensation reactions of four triptycene triamines and six salicyldialdehydes is described, where the substituents systematically vary in bulkiness. The resulting cage compounds were studied as permanent porous material by nitrogen sorption measurements. When the material is amorphous, the steric demand of the cages exterior does not strongly influence the gas uptake, resulting in BET surface areas of approximately 700 m² g^?1 for all cage compounds 3 c – e , independently of the substituents bulkiness. In the crystalline state, materials of the same compounds show a strong interconnection between steric demand of the peripheral substituent and the resulting BET surface area. With increasing bulkiness, the overall BET surface area decreases, for example 1291 m² g^?1 (for cage compound 3 c with methyl substituents), 309 m² g^?1 (for cage compound 3 d with 2‐(2‐ethyl‐pentyl) substituents) and 22 m² g^?1 (for cage compound 3 e with trityl substituents). Furthermore, we found that two different crystalline polymorphs of the cage compound 3 a (with tert‐butyl substituents) differ also in nitrogen sorption, resulting in a BET surface area of 1377 m²g^?1, when synthesized from THF and 2071 m²g^?1, when recrystallized from DMSO.     

A Convergent,Modular Approach to Trifluoromethyl-Bearing 5-Membered Rings via Catalytic C(sp3)−H Activation

Trifluoromethyl-bearing 5-membered rings are prevalent in bioactive molecules, but modular approaches to these compounds by functionalization of robust C(sp³)−H bonds in a direct and selective manner are extremely challenging. Herein we report the rhodium-catalyzed α-CF₃-α-alkyl carbene insertion into C(sp³)−H bonds of a broad range of substrates to access 7 types of CF₃-bearing saturated 5-membered carbo- and heterocycles. The reaction is particularly effective for benzylic C−H insertion exerting good site-, diastereo- and enantiocontrol, and applicable to the synthesis of chiral CF₃ analogues of bioactive molecules. Ruthenium α-CF₃-α-alkyl carbene complexes underwent stoichiometric reactions to give C−H insertion products, lending evidence for the involvement of metal α-CF₃-α-alkyl carbene species in the catalytic cycle. DFT calculations revealed that the π⋅⋅⋅π attraction and intra-carbene C−H⋅⋅⋅F hydrogen bond elucidate the origin of selectivity of the benzylic C−H insertion reactions.     

Well-Defined Ni(0) and Ni(II) Complexes of Bicyclic (Alkyl)(Amino)Carbene (MeBICAAC): Catalytic Activity and Mechanistic Insights in Negishi Cross-Coupling Reaction

Negishi cross-coupling reaction of organozinc compounds as nucleophiles with aryl halides has drawn immense focus for C−C bond formation reactions. In comparison to the well-established library of Pd complexes, the C−C cross-coupling of this particular approach is largely primitive with nickel-complexes. Herein, we describe the syntheses of Ni(II) complexes, [(^MeBICAAC)₂NiX₂] (X=Cl ( 1 ), Br ( 2 ), and I ( 3 )) by employing the bicyclic (alkyl)(amino)carbene (^MeBICAAC) ligand. The reduction of complexes 1 – 3 using KC₈ afforded the two coordinate low valent, Ni(0) complex, [(^MeBICAAC)₂Ni(0)] ( 4 ). Complexes 1 – 4 have been characterized by spectroscopic techniques and their solid-state structures were also confirmed by X-ray crystallography. Furthermore, complexes 1 – 4 have been applied in a direct and convenient method to catalyze the Negishi cross-coupling reaction of various aryl halides with 2,6-difluorophenylzinc bromide or phenylzinc bromide as the coupling partner in the presence of 3 mol % catalyst. Comparatively, among all-pristine complexes, 1 exhibit high catalytic potential to afford value-added C−C coupled products without the use of any additive. The UV-vis studies and HRMS measurements of controlled stochiometric reactions vindicate the involvement of Ni(I)−NI(III) cycle featured with a penta-coordinated Ni(III)-aryl species as the key intermediate for 1 whereas Ni(0)/Ni(II) species are potentially involved in the catalytic cycle of 4 .     

Linear free energy relationships for carbon-13 NMR chemical shifts of substituted benzoic acids1

In order to examine ¹³C-SCS of substituted benzoic acids, chemical shifts of the acid form (I) and the dissociated form (II) have been obtained separately. Single substituent parameters, σ⁰ or σ⁺ are correlated with the shifts for the carboxyl (δ_co) or ipso carbons (δ_ipso), respectively. Among the available five equations which are developed for the analysis with dual (or divided) substituent parameters (DSP), the Swain-Lupton equation (eqn 3) and the Taft-Swain-Lupton equation (eqn 4) give much better correlations, not only for δ_co and δ_ipso but also for the results for ring carbons (C(2), C(5), C(6)), except for those attached to or neighboured by substituents. It is concluded that the SCS of aromatic compounds are best analyzed with substituent parameters derived from reactions or equilibria on the basis of linear free energy relationships.