Preparation of 2,2-difluoro-1-trialkylsilylethenylstannanes and their cross-coupling reactions

Reaction of 2 with bis(tributyltin) in the presence of 3 mol % Pd₂(dba)₃, 6 mol % XPhos, and 30 equiv of LiBr in wet and air bubbled THF at reflux for 8 h afforded the desired products 3 in 73–74% yields. The cross-coupling reaction of 3a with aryl iodides in the presence of 10 mol % Pd(PPh₃)₄ and 10 mol % CuI afforded the coupled products 4a–p in 47–90% yields. The coupling reaction of 3b with various alkynyl bromides having aryl-, alkyl, or trialkylsilyl group also afforded the corresponding 1,3-enynes 5a–g in 61–77% yields.     

Preparation of perfluorocyclopentenylmetal species and their cross-coupling reaction with electrophiles—Remarkable accesses to versatile perfluorocyclopentene derivatives

On treating perfluorocyclopentene with bis(tributylstannyl)cyanocuprate in THF at −78 °C for 1 h, perfluorocyclopentenylstannane was obtained in good yield. The reaction of the fluorinated vinylstannane with n-BuLi in THF at −78 °C for 1 h, followed by addition of carbonyl compounds, gave the corresponding allyl alcohols in good yields. On the other hand, Pd(0)-catalyzed cross-coupling reaction of perfluorocyclopentenylstannane with benzyl chloroformate in THF at reflux temperature for 2 h proceeded smoothly to form the decarbonated coupling product in high yield.     

Cobalt-catalyzed cross-coupling reactions of alkyl halides with aryl Grignard reagents and their application to sequential radical cyclization/cross-coupling reactions

Reactions of alkyl halides with arylmagnesium bromides in the presence of cobalt(II)(diphosphine) complexes are discussed. Treatment of 1-bromooctane with phenylmagnesium bromide with the aid of a catalytic amount of CoCl₂(dppp) [DPPP=1,3-bis(diphenylphosphino)propane] yielded octylbenzene in good yield. The reaction mechanism would include single electron transfer from an electron-rich cobalt complex to alkyl halide to generate the corresponding alkyl radical. The mechanism was justified by CoCl₂(dppe)-catalyzed [DPPE=1,2-bis(diphenylphosphino)ethane] sequential radical cyclization/cross-coupling reactions of 6-halo-1-hexene derivatives that yielded benzyl-substituted cyclopentane skeletons.     

A novel method for (Z)-stereoselective preparation of CF3-substituted enediynes and their coupling reactions

Trifluoromethylated enynyl sulfones 3 were reacted with 2-4 equiv of phenyl, n-hexyl, trimethylsilyl, or triisopropylsilyl substituted ethynyllithium reagents in THF or ether at 0 °C to give trifluoromethylated enediynes 6 (Z)-stereoselectively in 41-96% yields. The reactions of β-fluoro-β-trifluoromethylvinyl sulfone 5 with same ethynyllithium reagents (4 equiv) afforded the corresponding enediynes 6 in 41-90% yields. The cross-coupling reactions of 6 bearing TMS group with aryl iodides in the presence of Pd(PPh₃)₂Cl₂, Ag₂CO₃, and n-Bu₄NBr provided the corresponding enediynes 6 in 20-71% yields. Dimerization of (Z)-6 bearing TMS group in the presence of CuBr₂ and K₂CO₃ yielded dimer (Z,Z)-7 in good yield.     

A guideline for the arylation of positions 4 and 5 of thiazole via Pd-catalyzed cross-coupling reactions

The arylation of thiazoles in 4- and 5-position was investigated in detail. Suzuki-Miyaura and Stille cross-coupling reactions were tested using thiazoles either as halide or organometal species. The obtained results were critically compared to develop helpful guidelines for selection of the cross-coupling methodology with the best potential for good and reliable results for a given synthetic problem without the need for tedious optimization of reaction parameters.     

Selective Approaches to α- and β-Arylated Vinyl Ethers

We developed simple and efficient protocols for palladium-catalyzed regioselective α- and β-arylations of structurally diverse vinyl ethers. Both catalytic methods proceed under relatively mild reactions conditions applying to a broad substrate range including more complex compounds providing arylated glucal or isochromene. Lacking the common requirement of a large reagent excess, the transformations are highly economic and limiting the waste production. Results from computational studies (DFT) provided insight into the key factors determining the pronounced regioselectivities of the investigated reactions.     

Asymmetric lithiation of 2-alkynyl aryl sulfides—Enantio- and diastereoselective formation of allenyl aryl sulfides and their application in nickel-catalyzed cross-coupling reactions

The enantio- and diastereoselective synthesis of allenyl aryl sulfides by asymmetric lithiation of 2-alkynyl (2-hetero)aryl sulfides is described. A dynamic thermodynamic resolution by selective crystallization of the intermediate lithium complexes derived from deprotonation, applying a bis(oxazoline) ligand, was achieved to give enantioselectivities up to 85% ee. Subsequent stereospecific nickel-catalyzed cross-coupling reactions with arylzinc reagents established a versatile access to threefold carbon-substituted allenes.     

Kinetics of the reactions of cyclopropane derivatives. V. The gas-phase unimolecular reactions of 1 α-chloro-2α,3α-dimethylcyclopropane and 1α-chloro-2α,3β-dimethylcyclopropane

Thermolysis of the “all-cis” compound 1α-chloro-2α,3α-dimethylcyclopropane (A) at 550–607 K and 6–115 torr is a first-order homogeneous non-radical-chain process giving penta-1,3-diene (PD) and HCl as products. The Arrhenius parameters are log₁₀A(sec^?1) = 13.92 ± 0.08 and E = 199.6 ± 0.9 kJ/mol. The isomer with trans-methyl groups, 1α-chloro-2α,3β-dimethylcyclopropane (B) reacts by two parallel first-order processes giving as observed products trans-4-chloropent-2-ene (4CP) and PD + HCl, with log₁₀A(sec^?1) = 14.6 and 13.8, respectively, and E = 199.5 and 190.2 kJ/mol, respectively. The 4CP undergoes secondary decomposition to PD + HCl (as investigated previously). Comparison of the results for compounds (A) and (B) with those for other gas-phase and solution reactions leads to the conclusion that the gas-phase thermolyses proceed by rate-determining ring opening to form olefins which may decompose further by thermal or chemically activated reactions, and that the ring opening is a semiionic electrocyclic reaction in which alkyl groups in the 2,3-positions trans to the migrating chlorine semianion move apart, with appropriate consequences for the rate of reaction and the stereochemistry of the products.     

Divergent synthesis of arylated pyridin-2(1H)-one derivatives via metal-catalysed cross-coupling processes

1,5-Di(hetero)arylated-pyridin-2(1H)-one derivatives have been readily obtained in good yields starting from 2-fluoro-5-pyridylboronic acid. The sequence comprises three steps: (i) palladium-catalysed Suzuki-Miyaura reaction; (ii) base-catalysed hydrolysis; (iii) copper-catalysed C-N coupling. X-ray crystal structures are reported for selected pyridin-2(1H)-one derivatives. These compounds are of interest as new scaffolds for drug discovery.     

Synthesis of non-symmetrical alkynylpyridines by chemoselective Sonogashira cross-coupling reactions

4-Bromo-2,3,5-trichloro-6-iodopyridine was studied as a new substrate in chemoselective Sonogashira reactions. This approach provides an efficient access to non-symmetrical mono-, di-, tri- and pentaalkynylated pyridines in good yields. Selected pentaalkynylated pyridines were studied with regard to their UV/Vis- and emission properties showing moderate to high fluorescence quantum yields.     

Asymmetric Diels–Alder Reaction of α‐Substituted and β,β‐Disubstituted α,β‐Enals via Diarylprolinol Silyl Ether for the Construction of All‐Carbon Quaternary Stereocenters

The asymmetric Diels–Alder reaction of α‐substituted acrolein proceeds in the presence of the trifluoroacetic acid salt of trifluoromethyl‐substituted diarylprolinol silyl ether to afford the exo‐isomer with both excellent diastereoselectivity and high enantioselectivity. In the Diels–Alder reaction of a β,β‐disubstituted α,β‐unsaturated aldehyde, good exo‐selectivity and excellent enantioselectivity was obtained when the perchloric acid salt of the bulky triisopropyl silyl ether of trifluoromethyl substituted diarylprolinol was employed as an organocatalyst in the presence of water. In both cases, all‐carbon quaternary stereocenters are constructed enantioselectively.     

Stereoselective synthesis of 1,3-dienylstannanes by palladium catalyzed cross-coupling reactions

(Z)-α-Bromovinylstannanes are new difunctional group reagents, which undergo palladium catalyzed cross-coupling reactions with (E)-alkenylzirconium complexes to give stereoselectively 1,3-dienylstannanes in good yields.     

Enantioselective Palladium‐Catalyzed Oxidative β,β‐Fluoroarylation of α,β‐Unsaturated Carbonyl Derivatives

The site‐selective palladium‐catalyzed three‐component coupling of deactivated alkenes, arylboronic acids, and N‐fluorobenzenesulfonimide is disclosed herein. The developed methodology establishes a general, modular, and step‐economical approach to the stereoselective β‐fluorination of α,β‐unsaturated systems.     

Condensation of α- and β-acetylnaphthalene with dimethy1 β,β-dimethyl glutarate

α- and β-Acetylnaphthalenes condensed with dimethyl β,β-dimethyl glutarate in the presence of sodium hydride to give the corresponding half-esters, the E-isomers 2a and 2b being predominant. The structure and configuration of the half-esters were characterized by chemical and spectroscopic means.     

Carbon Magnetic Resonance Spectra of α, β, γ, δ- and α, β, α′, β′- Unsaturated Ketones

Carbon-13 spectra of a series of 26 unsaturated ketones (ortho- and para-cyclo-hexadienones and corresponding open-chain analogues) have been measured by Fourier-transform. Pulse spectroscopy. A complete analysis has been achieved by means of double resonance experiments using noise-modulated and coherent off-resonance proton irradiation and with the aid of non-decoupled spectra. Chemical shifts are interpreted in terms of charge distribution in the dienone system and of methyl substituent effects. Carbon chemical shifts were also obtained for O-protonated ortho- and para-cyclohexadienones. One-bond and long-range carbon-proton and carbon-fluorine spin coupling constants are reported for several compounds.     

Direct preparation of arylethynylzinc bromides and their application to cross-coupling reactions

A novel synthetic protocol for the preparation of arylethynylzinc bromides has been developed. Thus-obtained organozinc reagents were successfully employed in the subsequent cross-coupling reactions with a broad range of aryl halides providing the corresponding alkynylated compounds in good to excellent yields.