Orthogonal Nanoparticle Catalysis with Organogermanes

Although nanoparticles are widely used as catalysts, little is known about their potential ability to trigger privileged transformations as compared to homogeneous molecular or bulk heterogeneous catalysts. We herein demonstrate (and rationalize) that nanoparticles display orthogonal reactivity to molecular catalysts in the cross‐coupling of aryl halides with aryl germanes. While the aryl germanes are unreactive in L_nPd⁰/L_nPd^II catalysis and allow selective functionalization of established coupling partners in their presence, they display superior reactivity under Pd nanoparticle conditions, outcompeting established coupling partners (such as ArBPin and ArBMIDA) and allowing air‐tolerant, base‐free, and orthogonal access to valuable and challenging biaryl motifs. As opposed to the notoriously unstable polyfluoroaryl‐ and 2‐pyridylboronic acids, the corresponding germanes are highly stable and readily coupled. Our mechanistic and computational studies provide unambiguous support of nanoparticle catalysis and suggest that owing to the electron richness of aryl germanes, they preferentially react by electrophilic aromatic substitution, and in turn are preferentially activated by the more electrophilic nanoparticles.     

Novel route to 5-position vinyl derivatives of thiolactomycin: Olefination vs. deformylation

Vinyl and diene derivatives of thiolactomycin have been prepared via Horner-Wadsworth-Emmons olefination from protected 5-formyl-3,5-dimethylthiotetronic acid. Several 4-position protecting groups and a variety of phosphonates were evaluated, with MOM protection and β-ketophosphonates yielding the highest ratio of the desired product to deformylated product.     

Allenes through Horner-Wadsworth-Emmons Olefination of Alkenylphosphonates

Mono- and di-substituted allenes 5 were synthesized by successive Horner-Wadsworth-Emmons olefination starting from methylene-bisphosphonate 1 and two carbonyl compounds. The key to success is KH or KH-18-crown-6 as a base for the second HWE olefination of hydroxyalkenylphosphonates 4 .     

Remote C−H Olefination of Heterocyclic Biaryls Enabled by Reversibly Bound Templates

Remote C−H functionalization of heterocyclic biaryls will be of great importance in synthesis and medicinal chemistry. Through adjusting the geometric relationship of the directing atom and target C−H bonds, two new catalytic templates have been developed to enable the functionalization of the more hindered ortho-C−H bonds of heterobiaryls bearing directing heteroatom at the meta- or para-positions, affording unprecedented site-selectivity. The use of template chaperone also overcomes product inhibition and renders the directing templates catalytic. The utility of this protocol was demonstrated by olefination of heterocyclic biaryls with various substituents, overriding conventional steric and electronic effects. These ortho-C−H olefinated heterobiaryls are sterically hindered and can often be challenging to prepare through aryl-aryl coupling reactions.     

Stereodivergent Zweifel Olefination and its Mechanistic Dichotomy

Stereoselective Zweifel olefination using boronate complexes carrying two different reactive π-systems was achieved to synthesize vinyl heteroarenes and conjugated 1,3-dienes in good yield and up to 100 % stereoselectivity, which remains unexplored until now. Most importantly, we report the unprecedented formation of E vs. Z-vinyl heteroarenes for different heteroarenes under identical conditions. Density functional theory (DFT) investigations unveil the mechanistic dichotomy between olefin and heteroarene activation followed by 1,2-migration, leading to E or Z-vinyl heteroarenes respectively. We also report a previously unknown reversal of stereoselectivity by using 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as an electrophile. The Zweifel olefination using a boronate complex that carries two different olefins was previously unexplored due to significant challenges associated with the site-selective activation of olefins. We have solved this problem and reported the site-selective activation of olefins for the stereoselective synthesis of 1,3-dienes.     

Scalable Electrochemical Decarboxylative Olefination Driven by Alternating Polarity**

A mild, scalable (kg) metal-free electrochemical decarboxylation of alkyl carboxylic acids to olefins is disclosed. Numerous applications are presented wherein this transformation can simplify alkene synthesis and provide alternative synthetic access to valuable olefins from simple carboxylic acid feedstocks. This robust method relies on alternating polarity to maintain the quality of the electrode surface and local pH, providing a deeper understanding of the Hofer-Moest process with unprecedented chemoselectivity.     

The catalytic olefination reaction of aldehydes and ketones with CBr3CF3

The new approach of catalytic olefination reaction (COR) has been used to convert aromatic and aliphatic aldehydes and ketones to 2-bromo-3,3,3-trifluoroprop-1-enes by the treatment of corresponding hydrazones with CBr₃CF₃ under copper(I) catalysis conditions. The reaction proceeds stereoselectively, the target alkenes were obtained in good yields.     

Immobilization of ruthenium(II) salen complexes on poly(4-vinylpyridine) and their application in catalytic aldehyde olefination

Two Ru(II)(salen)(PPh₃)₂ complexes grafted on poly(4-vinylpyridine) have been synthesized and characterized. An elemental analysis shows that both grafted samples contain ca. 0.6 wt % Ru. FTIR spectra confirm the formation of metal-salen complexes attached to the carrier polymer by an interaction between the ruthenium(II) compounds with the pyridine nitrogen atoms of the poly(4-vinylpyridine). Immobilization of both Ru(II) salen complexes on the polymer increases their thermal stability as demonstrated by TG-MS analysis. The grafted materials were applied as catalysts for the olefination of various aldehydes at 60 °C under an inert gas atmosphere, showing comparable yields as their homogeneous congeners and high trans-selectivities. The ruthenium(II) compound with a larger salen ligand shows a better recyclability and selectivity than the derivative with the smaller ligand.     

Reaction of CBrF2-CBrF2 with hydrazones of aromatic aldehydes: Novel efficient synthesis of fluorocontaining alkanes, alkenes and alkynes

An olefination of hydrazones of aromatic aldehydes by CBrF₂-CBrF₂ under copper catalysis was investigated. In situ prepared aldehydes hydrazones were converted to (3-bromo-2,2,3,3-tetrafluoropropyl)arenes by reaction with CBrF₂-CBrF₂ in the presence of CuCl. Subsequent elimination of HF by sodium hydroxide resulted in stereospecific formation of fluorocontaining alkenes. Elimination proceeds stereoselectively, only Z-isomers of alkenes are formed. Elimination of two molecules of HF from (3-bromo-2,2,3,3-tetrafluoropropyl)arenes by treatment with potassium tert-butoxide leads to formation of (bromodifluoromethyl)alkynes. As a result a simple and efficient transformation of aromatic aldehydes to range of various fluorinated alkanes, alkenes and alkynes was elaborated.     

Ti(Oi‐Pr)4 Mediated Olefination between Julia Reagent and Aldehydes under Mild Conditions: Facile Synthesis of Vinyl Sulfones

A novel Ti(Oi‐Pr)₄ mediated olifination between Julia reagent and aldehydes has been developed. By this method, a series of substituted vinyl sulfones are prepared under mild conditions, all products are exclusively E isomers. All the structures of these compounds were confirmed by ¹H NMR, ¹³C NMR HRMS and IR.     

A novel direct synthesis of (2,2-difluorovinyl)benzenes from aromatic aldehydes

A novel catalytic approach to (2,2-difluorovinyl)benzenes has been developed. It was found that hydrazones of aromatic aldehydes generated in situ could be converted to the corresponding (2,2-difluorovinyl)benzenes by catalytic olefination reaction (COR) with dibromodifluoromethane in the presence of CuCl.     

Synthesis of Ferrocene 1,3-Derivatives by Distal C−H Activation**

The third position of cyclopentadienyl ring of a monosubstituted ferrocene has remained as an inaccessible chemical space for direct functionalization. Until recently, functionalizing the C(3)-position while bypassing the predominantly active C(2)-position is the most challenging task. Herein, we report a distal C−H functionalization of monosubstituted ferrocenes using an easily removable directing group with precise site-selectivity, under a Pd^II/ mono-N-protected amino-acid ligand catalytic system. The robust synthetic protocol leads to the synthesis of ferrocene 1,3-derivatives with broad scope in olefins while functionalizing ferrocenyl methylamine in moderate to good yields via a highly strained ferrocene appended 12-membered palladacycle intermediate.     

Perspectives of Microwaves‐Enhanced Heterogeneous Catalytic Gas‐Phase Processes in Flow Systems

The paper discusses the currents status and future perspectives of the utilization of microwaves, as a selective and locally controlled heating method, in heterogeneous catalytic flow reactors. Various factors related to the microwave‐catalyst interaction and the design of microwave‐assisted catalytic reactor systems are analyzed. The analysis clearly shows the superiority of the traveling‐wave systems over the mono‐mode and multi‐mode cavity‐based systems when it comes to the design and application of microwave flow reactors at relevant production scales.     

Direct Catalytic Olefination of Alcohols with Sulfones

The synthesis of terminal, as well as internal, olefins was achieved by the one‐step olefination of alcohols with sulfones catalyzed by a ruthenium pincer complex. Furthermore, performing the reaction with dimethyl sulfone under mild hydrogen pressure provides a direct route for the replacement of alcohol hydroxy groups by methyl groups in one step.     

Hyperconjugative effect of C-Ge bonds: synthesis of multisubstituted alkenylgermanes via torquoselective olefination of acylgermanes with ynolates

The first highly Z-selective olefination of acylgermanes with ynolates affording multisubstituted alkenylgermanes was achieved. The torquoselectivity was ascribed to the hyperconjugative effect of C-Ge bonds in the transition state. The resulting (Z)-β-trialkylgermylacrylic acid has a hypervalent structure, which was converted into novel germalactones. A stereochemical complementary olefination via protonation of the β-lactone enolate, followed by decarboxylation, was also achieved.     

Stereoselective CrCl2-mediated condensation of aldehydes with functionalized 1,1,1-trichlorides: synthesis of trisubstituted (Z)-chloroolefins

The CrCl₂-mediated condensation of aldehydes 1 with a variety of functionalized 1,1,1-trichlorides 2 affords trisubstituted chloroolefins 4 in excellent yields and generally high Z-stereoselectivity. The intermediate dichlorohydrin adducts 3 can be isolated in good yields under conditions of limited reagent and reduced temperature.     

1-Methyl-1H-tetrazol-5-yl (MT) sulfones in the Julia-Kocienski olefination: Comparison with the PT and the TBT sulfones

The stability and the stereoselectivity of newly prepared n-pentyl 1-methyl-1H-tetrazol-5-yl (MT) sulfone 1a in the Julia-Kocienski reactions were compared with those of the PT sulfone 1b and the TBT sulfone 1c. The improved stability of the anion derived from the n-pentyl MT sulfone 1a enhanced the efficiency of the olefination reactions and gave higher yields of the product alkenes 3 compared with the PT sulfone 1b. Especially high E-selectivity and high yields were obtained from the reaction with aromatic aldehydes and α,β-unsaturated aldehydes. The selectivity of 1a was not so sensitive to the change of base counter ion compared with the PT sulfone 1b. The reaction of the MT sulfones having either ethyl or a longer alkyl chain also gave E-alkenes selectively in high yields.     

Iridium-Catalyzed Remote Site-Switchable Hydroarylation of Alkenes Controlled by Ligands

An iridium-catalyzed remote site-switchable hydroarylation of alkenes was reported, delivering the products functionalized at the subterminal methylene and terminal methyl positions on an alkyl chain controlled by two different ligands, respectively, in good yields and with good to excellent site-selectivities. The catalytic system showed good functional group tolerance and a broad substrate scope, including unactivated and activated alkenes. More importantly, the regioconvergent transformations of mixtures of isomeric alkenes were also successfully realized. The results of the mechanistic studies demonstrate that the reaction undergoes a chain-walking process to give an [Ar−Ir−H] complex of terminal alkene. The subsequent processes proceed through the modified Chalk–Harrod-type mechanism via the migratory insertion of terminal alkene into the Ir−C bond followed by C−H reductive elimination to afford the hydrofunctionalization products site-selectively.