Pd(OAc)(2)-catalyzed Domino reactions of 1-chloro-2-haloarenes and 2-haloaryl tosylates with hindered Grignard reagents via palladium-associated arynes

The palladium-associated aryne generation strategy and Pd(OAc)(2)-catalyzed annulative Domino reactions of 1-chloro-2-halobenzenes and 2-haloaryl tosylates with hindered Grignard reagents via palladium-associated arynes are described. The palladium-associated aryne generation strategy described here not only allows the high yield, one-step access to potentially useful substituted fluorenes from readily available 1-chloro-2-halobenzenes and 2-haloaryl tosylates, but may also lead to the development of other tandem reactions based on these readily available ortho leaving group bearing haloarenes. [reaction: see text]     

Synthesis of hindered biphenyls by sequential non-transition metal-catalyzed reaction/palladium-catalyzed cross-couplings

The sequential reaction of 1,2-dihalobenzenes with aryllithiums followed by palladium-catalyzed cross-coupling reactions with Grignard reagents and arylboronic acids is described. This sequential reaction provides a convenient and expeditious access to tri-ortho substituted biaryl derivatives.     

Palladium‐Catalyzed CS Activation/Aryne Insertion/Coupling Sequence: Synthesis of Functionalized 2‐Quinolinones

The insertion of an aryne into a C? S bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)₂, a wide range of α‐carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2‐quinolinones in high yields under neutral reaction conditions by a C? S activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio‐substituted quinolinone products.     

A chemoselective Reformatsky–Negishi approach to α-haloaryl esters

A practical synthesis of α-haloaryl esters has been achieved via a chemoselective Negishi coupling of poly-halogenated aromatics and Reformatsky reagents in the presence of catalytic Pd(dba)₂ and Xantphos. This chemistry tolerates a variety of aryl halides and was successfully applied to the synthesis of Ibuprofen. The α-haloaryl ester products, exemplified by ethyl 2-(4-bromo-2-chlorophenyl)acetate (3a), can be further functionalized via palladium or copper catalysis to afford an array of α-aryl esters.     

Palladium‐Catalyzed C?S Activation/Aryne Insertion/Coupling Sequence: Synthesis of Functionalized 2‐Quinolinones

The insertion of an aryne into a C S bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)₂, a wide range of α‐carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2‐quinolinones in high yields under neutral reaction conditions by a C S activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio‐substituted quinolinone products.     

Spectrophotometric determination of palladium with 2-mercaptobenzoxazole

A new spectrophotometric method for the determination of palladium is described using 2-mercaptobenzoxazole as reagent. The color reaction has a sensitivity of 0.08 μg of Pd per cm² for log I₀/I = 0.001 and obeys Beer's law from 2 to 40 p.p.m. The effects of pH, time, order of addition of the reagents, temperature and diverse ions were investigated. The procedure was applied to synthetic solutions containing palladium plus a variety of foreign ions.     

Application of Pd-catalysed amines arylation for the synthesis of benzopolyazamacrocycles

Amination of 1,2- or 1,3-dihalobenzenes by linear polyamines in the presence of Pd(dba)₂/BINAP catalytic system can serve as a convenient one-pot procedure for the synthesis of benzopolyazamacrocycles.     

Stereoselective C(sp3)-C(sp2) Negishi coupling of (2-amido-1-phenylpropyl)zinc compounds through the steric control of β-amido group

A controllable diastereoselective C(sp2)-C(sp3) Negishi coupling reaction of secondary benzylic zinc reagents with aryl bromides has been demonstrated for the first time, forming medicinally important 1-arylphenylethylamines. In the presence of Pd(OAc) 2 and S-phos, open-chain (2-amido-1-phenylethyl)zinc reagents bearing a -NHAc or NHCHO group underwent cross-coupling reaction to give syn 1-arylphenylethylamine as the major products, whereas the zinc reagents bearing a sterically hindered-NHCOC(CH3)2 OTBS group specifically yielded anti 1-arylphenylethylamines.     

Stereospecific synthesis of alkenyl sulphides by cross-coupling reactions of secondary alkyl Grignard reagents with Z- or E-1-bromo-2-phenylthioethene in the presence of transition metal catalysts

Z- and E-1-bromo-2-phenylthioethenes were cross-coupled stereospecifically with s-alkyl Grignard reagents in the presence of a series of Ni^II, Pd^II or Fe^III catalysts with the aim of finding a catalyst which would not cause s-alkyl → n-alkyl isomerization. With PdCl₂(dppf) (dppf = 1,1′-bis(diphenylphosphino)ferrocene) and NiCl₂(dppe) (dppe = 1,2-bis(diphenylphosphino)ethane) there was still some isomerization contribution, but it was completely suppressed by using iron(III) catalysts.     

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.     

Cyclodehydration of cis-2-butene-1,4-diol with active methylene compounds catalyzed by a diphosphinidenecyclobutene-coordinated palladium complex

(π-Allyl)palladium triflate coordinated with 1,2-bis(4-methoxyphenyl)-3,4-bis(2,4,6-tri-t-butylphenylphosphinidene)cyclobutene (DPCB-OMe), [Pd(η³-C₃H₅)(DPCB-OMe)]OTf, efficiently catalyzes cyclodehydration of cis-2-butene-1,4-diol with active methylene compounds such as acetylacetone and ethyl acetoacetate in toluene in the presence of pyridine. The reactions can be performed in air, giving 2-vinyl-2,3-dihydrofurans in good to high yields.     

Grignard allylic substitution catalyzed by imidazol-2-ylidene- and imidazol-4-ylidene-magnesium complexes

In the presence of a catalytic amount of 1,2-disubstituted or 1,2,3-trisubstituted imidazolium salts, γ-substituted allyl chlorides reacted with alkyl Grignard reagents to undergo substitution reactions in an S_N2′-selective fashion, where the magnesium ate complexes [(N-heterocyclic carbene-MgR₃)⁻(MgX)⁺] of imidazol-2-ylidenes or imidazol-4-ylidenes, generated in situ, were postulated as the active species. It was observed that the reactions with imidazol-4-ylidene catalysts were faster than those with imidazol-2-ylidenes. Enantioselective catalysis using a chiral imidazolium salt was preliminarily investigated.     

Extraction-spectrophotometric determination of traces of palladium by reaction between zinc(II) dibenzyldithiocarbamate and palladium(II)/2-(5-bromo-2-pyridylazo)-5-diethylaminophenol

The simple and highly sensitive determination of palladium is based on the reaction between Pd(II)/5-Br-PADAP and Zn(II) DBDTC complexes in 1,2-dichloroethane or toluene at pH 9.7. At 530 nm, the molar absorptivity is about 0.8 × 10⁵ l mol ^?1 cm ^?1. Beer's law is obeyed in the concentration range 0.1–1.2 μg ml ^?1 Pd. Relative standard deviations are 2–5%. Metal ions reacting with either of the organic reagents interfere.     

N-methyl-2,2′-bipyridylium ion (bpyMe) complexes: Synthesis and cyclometallation of [Pd(bpyMe)2Cl2]2+

On prolonged heating in water Pd(bpyMe)Cl₃ (bpyMe = N-methyl-2,2′-bipyridylium cation) cyclometallates to give monomeric Pd(bpyMe-H)Cl₂, whereas the immediate products are a mixture of trans-[Pd(bpyMe)₂Cl₂]²⁺ and anionic palladium species. [Pd(bpyMe)₂Cl₂]²⁺ was synthesised directly from Na₂PdCl₄ and on heating gives Pd(bpyMe-H)Cl₂ with the elimination of bpyMe and H⁺.     

Synthesis and transformations of metallacycles 41. Cyclomagnesiation of O-containing 1,2-dienes with Grignard reagents in the presence of Cp2TiCl2

A Cp₂TiCl₂-catalyzed intermolecular homocyclomagnesiation of O-containing 1,2-dienes and cross-cyclomagnesiation of O-containing 1,2-dienes with aliphatic 1,2-dienes of cyclic and acyclic structure have been accomplished using Grignard reagents, which led to mono- and bicyclic organomagnesium compounds in 61–94% yields.     

Cis-homo addition-1,4 thiophile d'organomagnesiens avec des composes thiocarbonyles comportant un groupe carbonyle en β: Synthese stereoselective d'alcoylthio-2 et de bis (alcoylthio)-2,2 cyclopropanols

Aliphatic Grignard reagents react stereoselectively with β thioxo carbonyl compounds to give substituted cis 2-alkylthio or 2,2-bis (alkylthio) cyclopropanols with good yields. Two types of non-enethiolisable thiocarbonyl compounds of formulae MeCOC(Me)₂CSR undergo this reaction a thioketone (R = Me) and a number of dithioesters (R = SMe, SEt, S iso Pr). The cis configuration of cyclopropanols has been assigned by ¹H NMR-Eu(fod)₃. The cyclopropane ring closure is a concerted cis-1,4-homo addition.     

Synthesis, characterization and cytotoxicity of some palladium(II), platinum(II), rhodium(I) and iridium(I) complexes of ferrocenylpyridine and related ligands. Crystal and molecular structure of trans-dichlorobis(3-ferrocenylpyridine)palladium(II)

The preparation of a series of ferrocenyl nitrogen donor ligands including ferrocenylpyridines, ferrocenylphenylpyridines and 1,1^′-di(2-pyridyl)ferrocene is described. Coordination studies of the substituted pyridines (L) were carried out with platinum, palladium, rhodium and iridium. This resulted in the preparation of the following types of complexes: [MCl(CO)₂(L)] and [M(cod)(L)₂]ClO₄ where M=Rh or Ir, cod=1,5-cyclooctadiene; [M^′Cl₂(L)₂] where M^′=Pt or Pd. The X-ray crystal structure of trans-dichlorobis(3-ferrocenylpyridine)palladium was obtained. The complexes were screened for activity against two human cancer cell lines. At least two of the complexes displayed growth inhibition similar to that of the widely used chemotherapeutic agent, cisplatin.     

Highly stereoselective synthesis of 6-perfluoroalkyl-6-fluoroalka-2,3,5-(Z)-trienols through carbometallation-elimination of 5-perfluoroalkyl-substituted 4(E)-alken-2-ynols with Grignard reagents

A highly regio- and stereoselective sequential carbometallation and Z-selective β-elimination reaction of 5-perfluoroalkyl-4(E)-en-2-ynols with Grignard reagents in Et₂O has been developed to afford various 6-perfluoroalkyl-6-fluoroalka-2,3,5(Z)-trienols in good to excellent yields. Primary or secondary alkyl or aryl Grignard reagents may be used to introduce the R² group to the 2-position of the starting materials referring to the hydroxyl group. A mechanism for this transformation has been proposed.     

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.     

Palladium(II) complexes containing a bulky pyridinyl N-heterocyclic carbene ligand: Preparation and reactivity

Coordination chemistry of a pyridine imidazole-2-ylidene ligand (pyN ˆC) with sterically hindered substituents toward palladium(II) metal ions has been investigated. The palladium carbene complex [(C-pyN ˆC)Pd(η³-allyl)Cl] (3) is prepared via the transmetallation from the corresponding silver carbene complexes with [ClPd(η³-allyl)]₂. Upon the abstraction of chloride, coordination of pyridinyl-nitrogen becomes feasible to form [C,N-(pyN ˆC)Pd(η³-allyl)](BF₄) (4). Ligand substitution reaction of 4 with triphenylphosphine results in the formation of [(C-pyN ˆC)Pd(PPh₃)(η³-allyl)](BF₄)], which the pyridinyl-nitrogen donor is substituted by the phosphine. This palladium complex appears to be base sensitive. Treatment of 4 with t-butoxide causes the decomposition to yield the metal nano-particles. Furthermore, de-complexation of 4 takes place under hydrogen atmosphere to generate the carbene precursor, 1-(6-mesityl-2-picolyl)-3-mesitylimidazolium salt. Nevertheless, the palladium complex 4 shows good catalytic activity on the Suzuki-Miyaura and Mizoroki-Heck reactions.