Mild Cobalt‐Catalyzed Negishi Cross‐Couplings of (Hetero)arylzinc Reagents with (Hetero)aryl Halides

A catalytic system consisting of CoCl₂ ? 2 LiCl (5 mol %) and HCO₂Na (50 mol %) enables the cross‐coupling of various N‐heterocyclic chlorides and bromides as well as aromatic halogenated ketones with various electron‐rich and ‐poor arylzinc reagents. The reactions reached full conversion within a few hours at 25 °C.     

Alkene Carboboration Enabled by Synergistic Catalysis

A synergistic Pd/Cu system for the coupling of alkenes, (Bpin)₂ (pin=pinacolate), and aryl/vinyl bromides is disclosed. This method allows for the catalytic generation of secondary Csp³?Cu nucleophiles in situ and subsequent Pd‐catalyzed cross‐coupling.     

Visible‐Light‐Driven Palladium‐Catalyzed Radical Alkylation of C−H Bonds with Unactivated Alkyl Bromides

Reported herein is a novel visible‐light photoredox system with Pd(PPh₃)₄ as the sole catalyst for the realization of the first direct cross‐coupling of C(sp³)−H bonds in N‐aryl tetrahydroisoquinolines with unactivated alkyl bromides. Moreover, intra‐ and intermolecular alkylations of heteroarenes were also developed under mild reaction conditions. A variety of tertiary, secondary, and primary alkyl bromides undergo reaction to generate C(sp³)−C(sp³) and C(sp²)−C(sp³) bonds in moderate to excellent yields. These redox‐neutral reactions feature broad substrate scope (>60 examples), good functional‐group tolerance, and facile generation of quaternary centers. Mechanistic studies indicate that the simple palladium complex acts as the visible‐light photocatalyst and radicals are involved in the process.     

Synthesis of 4‐(trihalomethyl)dipyrimidin‐2‐ylamines from β‐alkoxy‐α,β‐unsaturated trihalomethyl ketones

The synthesis of a novel series of twelve 4‐(trihalomethyl)dipyrimidin‐2‐ylamines, from the cyclo‐condensation reaction of 4‐(trichloromethyl)‐2‐guanidinopyrimidine, with β‐alkoxyvinyl trihalomethyl ketones, of general formula: X₃C‐C(O)‐C(R²)=C(R¹)‐OR, where: X = F, Cl; R = Me, Et, ‐(CH₂)₂‐, ‐(CH₂)₃‐; R¹ = H, Me; R² = H, Me, ‐(CH₂)₂‐, ‐(CH₂)₃‐, is reported. The reactions were carried out in acetonitrile under reflux for 16 hours, leading to the dipyrimidin‐2‐ylamines in 65‐90% yield. Depending on the substituents of the vinyl ketone, tetrahydropyrimidines or aromatic pyrimidine rings were obtained from the cyclization reaction. When X = Cl, elimination of the trichloromethyl group was observed during the cyclization step. The structure of 4‐(trihalomethyl)dipyrimidin‐2‐ylamines was studied in detail by ¹H‐, ¹³C‐ and 2D‐nmr spectroscopy.     

Pd‐PEPPSI‐IPent‐SiO2: A Supported Catalyst for Challenging Negishi Coupling Reactions in Flow

A silica‐supported precatalyst, Pd‐PEPPSI‐IPent‐SiO₂, has been prepared and evaluated for its proficiency in the Negishi cross‐coupling of hindered and electronically deactivated coupling partners. The precatalyst Pd‐PEPPSI‐IPent loaded onto packed bed columns shows high catalytic activity for the room‐temperature coupling of deactivated/hindered biaryl partners. Also for the first time, the flowed Csp³–Csp² coupling of secondary alkylzinc reagents to (hetero)aromatics has been achieved with high selectivity with Pd‐PEPPSI‐IPent‐SiO₂. These couplings required residence times as short as 3 minutes to effect completion of these challenging transformations with excellent selectivity for the nonrearranged product.     

An Efficient Palladium and Bis(2‐pyridylmethyl)amine‐based System for Suzuki‐Miyaura Cross‐Coupling under Aqueous and Aerobic Condition

A novel PdCl₂/bis(2‐pyridylmethyl)amine‐based ligand ( 1 ) catalytic system, which is water‐soluble and air‐stable, has been successfully synthesized and applied for Suzuki‐Miyaura cross‐coupling reaction. In the presence of catalytic amount of PdCl₂/ 1 system, arylboronic acids can couple with a wide range of aryl halides, including aryl bromides and aryl chlorides. The reactions proceed under mild conditions to give excellent yields, and a wide range of functionalities is tolerated.     

Oxidative β‐Csp3−H Functionalization of tBuOH: A Selective Radical/Radical Cross‐Coupling Access to β‐Hydroxy Thioethers

An oxidative β‐Csp³?H functionalization of tert‐butanol (tBuOH) for the construction of C?S bonds through an iodine‐catalyzed Csp³?H/S?H coupling was successfully achieved. Different kinds of mercaptans were shown to be good coupling partners, affording the desired products in good yields. This protocol not only offers a novel method for the synthesis of β‐hydroxy thioethers, but also provides an effective strategy for selective radical/radical cross‐coupling.     

Preparations of Saturated N‐P‐N Type Secondary Phosphine Oxides and their Applications in Cross‐Coupling Reactions

A series of cyclohexane‐1,2‐diamine ( 3a – 3d ) and benzene‐1,2‐diamine derivatives ( 3e – 3h ) were pre‐ pared. Followed by hydrolysis, the reaction of 3a – 3c with PCl₃ successfully led to the formation of cor‐ responding metastable saturated heteroatom‐substituted secondary phosphine oxides (HASPO 4a – 4c ), a tautomer of the saturated heteroatom‐substituted phosphinous acid (HAPA). Whereas ambient‐stable diamine‐coordinated palladium complexes were obtained, HAPA‐coordinated palladium complexes were not successfully synthesized. The molecular structures of HASPO 4c , Pd(OAc)₂(3a) , PdBr₂(3b) and Pd(OAc)₂(3c) and [Cu(NO₃)(3d)⁺][NO₃ ^? ] were determined by single‐crystal X‐ray diffraction method. Catalysis of in‐situ Suzuki‐Miyaura cross‐coupling reactions for aryl bromides and phenylboronic acid using diamine 3a as ancillary ligand showed that the optimized reaction condition at 60 °C is the combination of 2 mmol % 3a /3.0 mmol KOH/1.0 mL 1,4‐dioxane/1 mmol % Pd(OAc)₂. Moreover, moderate reactivity was observed when using aryl chlorides as substrates (supporting infor‐ mation). When diamine 3d was employed in Heck reaction, good tolerance of functional groups of aryl bromides were observed while using 4‐bromoanisole and styrene as substrates. The optimized condi‐ tion for Heck reaction at 100 °C is 3 mmol % 3d /3.0 mmol CsF/1.0 mL toluene/3 mmol % Pd(OAc)₂. In general, cyclohexane‐1,2‐diamine derivatives exhibited better catalytic properties than those of benzene‐1,2‐diamines.     

Nickel‐Catalyzed Cross‐Electrophile Coupling of Aryl Bromides with Pyrimidin‐2‐yl Tosylates

A new protocol for the NiCl₂ ‐catalyzed cross‐electrophile coupling of aryl bromides with pyrimidin‐2‐yl tosylates to give the corresponding C2 ‐arylation pyrimidine derivatives has been developed. This study provides an improvement over previous methods by using pyrimidin‐2‐yl tosylates instead of halides as coupling partners that are stable and easily available.     

Bulk cyclopolymerization of 1,2:5,6‐diepithio‐3,4‐di‐O‐methyl‐1,2:5,6‐tetradeoxy‐D‐mannitol with quaternary ammonium salts leading to gel‐free thiosugar polymer

The bulk cyclopolymerization of diepisulfide, 1,2:5,6‐diepithio‐3,4‐di‐O‐methyl‐1,2:5,6‐tetradeoxy‐D ‐mannitol ( 1 ), was studied using R₄N⁺Br^? (R = ? CH₃, C₂H₅, C₃H₇, C₄H₉, and C₇H₁₅) and (C₄H₉)₄N⁺X^? (X = Cl, I, NO₃, and ClO₄) as the initiators. All the bulk polymerizations of 1 using quaternary tetraalkylammonium salts at 90 °C proceeded without gelation even at high conversion to produce gel‐free polymers consisting of 2,5‐anhydro‐1,5‐dithio‐D ‐glucitol (I) as the major cyclic repeating unit along with 1,5‐anhydro‐2,5‐dithio‐D ‐mannitol (II) and the desulfurized acyclic unit (III) as the minor units. The polymerization rate and molar fraction of the I unit increased with the increasing alkyl chain length of the tetraalkylammonium cation and the increasing nucleophilicity of the counteranion. Tetrabutylammonium chloride exhibited the highest catalytic activity and the highest stereoselectivity, that is, the thiosugar polymer with I:II:III = 81:15:4 and a number‐average molecular weight of 31.9 × 10³ was obtained in 85% yield for a polymerization time of 0.5 h. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 965–970, 2002     

应用腙作为配体的铜催化二芳醚合成反应

一种简单易得的腙,2-吡啶醛 1-苯基腙 （1）,能够作为有效配体,极大地促进碘化铜催化的芳基溴与酚的C–O偶联反应。该偶联反应条件温和（二氧六环为溶剂、磷酸钾为碱、90–100 0C 的反应温度）,适用于各种芳基溴（电中性、贫电子和富电子）和酚（电中性和富电子）的底物,能够相容一些碱敏感官能团如酯基、醛基和羰基等。     

A tridentate CNO‐donor palladium(II) complex as efficient catalyst for direct C―H arylation: Application in preparation of imidazole‐based push–pull chromophores

A series of imidazolium chlorides for the formation of tridentate CNO‐donor palladium(II) complexes featuring N‐heterocyclic carbene moieties have been developed from cheap and readily available starting materials with high yields. Their palladium complexes were prepared by reactions between the ligand precursors and PdCl₂ using K₂CO₃ as base in pyridine with reasonable yields. These air‐stable metal complexes were characterized using ¹H NMR and ¹³C{¹H} NMR spectroscopy and elemental analyses. Heteronuclear multiple bond correlation experiments were performed to identify key NMR signals of these compounds. The structures of two of the complexes were also established by single‐crystal X‐ray diffraction analysis. One of these complexes was successfully applied in the direct C―H functionalization reactions between heterocyclic compounds and aryl bromides, producing excellent yields of coupled products. The coupling reactions were scalable, allowing grams of coupled products to be obtained with a mere 2 mol% of Pd loading. The catalyst system developed allowed the large‐scale preparation of several push–pull chromophores straightforwardly. Photophysical properties based on UV–visible and fluorescence spectroscopy for these chromophores were investigated. Deep blue photoluminescence with moderate quantum efficiency and twisted intramolecular charge transfer excited state were observed for these chromophores. Density functional theory (DFT) and time‐dependent DFT calculations were performed to support the experimental results.     

One‐pot Chemoenzymatic Synthesis of Chiral 1,3‐Diols Using an Enantioselective Aldol Reaction with Chiral Zn2+ Complex Catalysts and Enzymatic Reduction Using Oxidoreductases with Cofactor Regeneration

We previously reported on enantioselective aldol reactions of acetone and some aldehydes catalyzed by chiral Zn²⁺ complexes of L ‐prolyl‐pendant [12]aneN₄ (L ‐ZnL¹) and L ‐valyl‐pendant [12]aneN₄ (L ‐ZnL²) in aqueous solution. Here, we report on the one‐pot chemoenzymatic synthesis of chiral 1,3‐diols in an aqueous solvent system at room temperature by a combination of enantioselective aldol reactions catalyzed by Zn²⁺ complexes of L ‐ and D ‐phenylalanyl‐pendant [12]aneN₄ (L ‐ZnL³ and D ‐ZnL³) and the successive enantioselective reduction of the aldol products using oxidoreductases with the regeneration of the NADH (reduced form of nicotinamine adenine dinucleotide) cofactor. The findings indicate that all four stereoisomers of 1,3‐diols can be produced by appropriate selection of a chiral Zn²⁺‐complex and an oxidoreductase commercially available from the “Chiralscreen OH” kit.     

Synthesis and characterizations of arsine– and stibine–ligated Schiff base palladacycles and their applications in Suzuki–Miyaura cross‐coupling reactions

A series of arsine‐ and stibine‐ligated Schiff base palladacycles were synthesized by the reaction of μ‐Cl‐bridged Schiff base palladacycles [Pd(C₆H₄CH]NC₆H₂R)(μ‐Cl)]₂ (R = 2,4,6‐trimethyl or 2,6‐diisopropyl) with AsPh₃ or SbPh_3. The new arsine‐ and stibine‐ligated palladacycles were fully characterized using ¹H NMR, ¹³C NMR and infrared spectroscopies, high‐resolution mass spectrometry, elemental analysis and single‐crystal X‐ray diffraction. Further exploration of the catalytic application of the palladacycles for Suzuki–Miyaura cross‐coupling reactions of aryl bromides with arylboronic acids was carried out. It was found that the new palladacycles are considerably active for these coupling reactions. Copyright © 2016 John Wiley & Sons, Ltd.     

Synthesis of star‐shaped poly(D,L‐lactic acid‐alt‐glycolic acid)‐b‐poly(L‐lactic acid) with the poly(D,L‐lactic acid‐alt‐glycolic acid) macroinitiator and stannous octoate catalyst

Two types of three‐arm and four‐arm, star‐shaped poly(D,L ‐lactic acid‐alt‐glycolic acid)‐b‐poly(L ‐lactic acid) (D,L ‐PLGA50‐b‐PLLA) were successfully synthesized via the sequential ring‐opening polymerization of D,L ‐3‐methylglycolide (MG) and L ‐lactide (L ‐LA) with a multifunctional initiator, such as trimethylolpropane and pentaerythritol, and stannous octoate (SnOct₂) as a catalyst. Star‐shaped, hydroxy‐terminated poly(D,L ‐lactic acid‐alt‐glycolic acid) (D,L ‐PLGA50) obtained from the polymerization of MG was used as a macroinitiator to initiate the block polymerization of L ‐LA with the SnOct₂ catalyst in bulk at 130 °C. For the polymerization of L ‐LA with the three‐arm, star‐shaped D,L ‐PLGA50 macroinitiator (number‐average molecular weight = 6800) and the SnOct₂ catalyst, the molecular weight of the resulting D,L ‐PLGA50‐b‐PLLA polymer linearly increased from 12,600 to 27,400 with the increasing molar ratio (1:1 to 3:1) of L ‐LA to MG, and the molecular weight distribution was rather narrow (weight‐average molecular weight/number‐average molecular weight = 1.09–1.15). The ¹H NMR spectrum of the D,L ‐PLGA50‐b‐PLLA block copolymer showed that the molecular weight and unit composition of the block copolymer were controlled by the molar ratio of L ‐LA to the macroinitiator. The ¹³C NMR spectrum of the block copolymer clearly showed its diblock structures, that is, D,L ‐PLGA50 as the first block and poly(L ‐lactic acid) as the second block. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 409–415, 2002     

Nickel‐Catalyzed Csp2Csp3 Bond Formation by CarbonFluorine Activation

We report herein a general catalytic method for Csp²?Csp³ bond formation through C?F activation. The process uses an inexpensive nickel complex with either diorganozinc or alkylzinc halide reagents, including those with β‐hydrogen atoms. A variety of fluorine substitution patterns and functional groups can be readily incorporated. Sequential reactions involving different precatalysts and coupling partners permit the synthesis of densely functionalized fluorinated building blocks.     

Synthesis of substituted biaryls via Suzuki,Stille and Hiyama cross‐coupling and homo‐coupling reactions by CN‐dimeric and monomeric ortho‐palladated catalysts

The catalytic activity of dimeric [Pd{C₆H₂(CH₂CH₂NH₂)–(OMe)₂,2,3}(μ‐Br)]₂ and monomeric [Pd{C₆H₂(CH₂CH₂NH₂)–(OMe)₂,2,3}Br(PPh₃)] complexes as efficient, stable and air‐ and moisture‐tolerant catalysts was investigated in the Suzuki, Stille and Hiyama cross‐coupling and homo‐coupling reactions of various aryl halides. Substituted biaryls were produced in excellent yields in short reaction times using catalytic amounts of these complexes. The monomeric complex was demonstrated to be more active than the corresponding dimeric catalyst for the cross‐coupling reaction of unreactive aryl bromides and chlorides. The combination of homogeneous metal catalysts and microwave irradiation gave higher yields of products in shorter reaction times. Copyright © 2013 John Wiley & Sons, Ltd.     

Chemo‐Enzymatic Synthesis of 3‐Deoxy‐β‐D‐ribofuranosyl Purines

9‐(3‐Deoxy‐β‐D ‐erythro‐pentofuranosyl)‐2,6‐diaminopurine ( 6 ) was synthesized by an enzymatic transglycosylation of 2,6‐diaminopurine ( 2 ) with 3′‐deoxycytidine ( 1 ) as a donor of 3‐deoxy‐D ‐erythro‐pentofuranose moiety. This transformation comprises i) deamination of 1 to 3′‐deoxyuridine ( 3 ) under the action of whole cell (E. coli BM‐11) cytidine deaminase (CDase), ii) the phosphorolytic cleavage of 3 by uridine phosphorylase (UPase) giving rise to the formation of uracil ( 4 ) and 3‐deoxy‐α‐D ‐erythro‐pentofuranose‐1‐O‐phosphate ( 5 ), and iii) coupling of the latter with 2 catalyzed by whole cell (E. coli BMT‐4D/1A) purine nucleoside phosphorylase (PNPase). Deamination of 6 by adenosine deaminase (ADase) gave 3′‐deoxyguanosine ( 7 ). Treatment of 6 with NaNO₂ afforded 9‐(3‐deoxy‐β‐D ‐erythro‐pentofuranosyl)‐2‐amino‐6‐oxopurine (3′‐deoxyisoguanosine; 8 ). Schiemann reaction of 6 (HF/HBF₄+NaNO₂) gave 9‐(3‐deoxy‐β‐D ‐erythro‐pentofuranosyl)‐2‐fluoroadenine ( 9 ).     

Synthesis and characterization of poly(L‐lactide)s and poly(D‐lactide)s of controlled molecular weight

High molecular weight poly(L ‐lactide)s (PLLAs) and poly(D ‐lactide)s (PDLAs) were synthesized in toluene at 70 °C by ring‐opening polymerization of optically pure L ‐lactide and D ‐lactide, using tin(II) 2‐ethylhexanoate (SnOct₂) and 2‐(2‐methoxyethoxy)ethanol as initiator and coinitiator, respectively. Under these conditions, polarimetry as well as ¹³C NMR spectroscopy indicated that the synthesized poly(lactide)s (PLAs) are more than 99% isotactic. The molecular weight was successfully controlled by adjusting the monomer‐to‐initiator molar ratio. Gel permeation chromatography and MALDI‐TOF mass spectrometry analyses showed that the polydispersity index of the PLAs is below 1.1. Moreover, MALDI‐TOF spectra showed two different chain distributions, one characterized by an even number of lactic acid repeat units and the other by an odd number of lactic acid repeat units. The second distribution, indicative of the presence of intermolecular transesterification reactions, appears at the very beginning of the polymerization and its intensity increases with the polymerization time. Finally, a reversible reaction kinetic model was used to determine the monomer equilibrium concentration ([M]_eq = 1.4 ± 0.5%) and the propagation rate constant (k_p = 14.4 ± 0.5 L mol^?1 h^?1) of the polymerization. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1944–1955, 2007     

Amidophosphine‐stabilized palladium complexes catalyse Suzuki–Miyaura cross‐couplings in aqueous media

We report a simple and efficient procedure for Suzuki–Miyaura reactions in aqueous media catalysed by amidophosphine‐stabilized palladium complexes trans‐{L³PPh₂}₂PdCl₂ ( 3 ), trans‐{L³PPhtBu}₂PdCl₂ ( 4 ), [Pd(η³‐C₃H₅)(L³PPh₂)Cl] ( 5 ) and {Pd[2‐(Me₂NCH₂)C₆H₄](L³PPh₂)Cl} ( 6 ). The acidity of the NH proton in complexes 3 , 4 , 5 , 6 plays an important role in their catalytic activity. In addition, the palladium complexes cis‐{L¹PPh₂}PdCl₂ ( 1 ) and trans‐{L²PPh₂}₂PdCl₂ ( 2 ) stabilized by phosphines containing Y,C,Y‐chelating ligands L^1,2 have also been found to be useful catalysts for Suzuki–Miyaura reactions in aqueous media. The method can be effectively applied to both activated and deactivated aryl bromides yielding high or moderate conversions. The catalytic activity of couplings performed in pure water increases when utilizing a Pd complex with more acidic NH protons. A decrease of palladium concentration from 1.0 to 0.5 mol% does not lead to a substantial loss of conversion. In addition, Pd complex 1 can be efficiently recovered using two‐phase system extraction. Copyright © 2016 John Wiley & Sons, Ltd.