Total synthesis of the COPD biomarker desmosine via Sonogashira and Negishi cross-coupling reactions

Desmosine, a crosslinking pyridinium amino acid of elastin, is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the total synthesis of (+)-desmosine is reported utilizing chemo- and regioselective Sonogashira and Negishi cross-coupling reactions in 15% yield over six steps.     

Nickel-catalyzed carbonylative Negishi cross-coupling reactions

Catalytic carbonylative Negishi cross-coupling reactions are described. This method readily provides various enones from enol triflates and diorganozinc reagents with catalytic amounts of nickel(II) chloride-4,4′-dimethoxyl-2,2′-bipyridyl under carbon monoxide atmosphere. The rate of carbon monoxide insertion is increased by the addition of lithium or magnesium halides and the use of polar solvents. Alkenyl iodides can also be used in place of enol triflates.     

A Negishi cross-coupling reaction enables the total synthesis of (+)-stachyflin

We present a full account on the development of the total synthesis of the antiviral meroterpenoid (+)-stachyflin. The decalin subunit is rapidly accessed by an exo-selective Diels–Alder reaction, whereas the isonindolinone was synthesized via a highly efficient and practical de novo route starting from dimedone. A challenging sp²–sp³ Negishi cross-coupling reaction enabled construction of the crucial C15–C16 bond that connects the arene with the decalin subunit. For the final installation of the cis-decalin framework, a Lewis acid-catalyzed cyclization was applied.     

Stereoselective sp-sp bond formation via Negishi cross-coupling of vinylic tellurides and 2-heteroarylzinc chlorides

The Negishi cross-coupling reaction of vinylic- and aryltellurides with heteroarylzinc chlorides catalyzed by PdCl₂/CuI is described. This cross-coupling reaction is general and permits the formation of a new sp²-sp² carbon bond in good yields and high stereoselectivity.     

An efficient palladium-catalyzed Negishi cross-coupling reaction with arylvinyl iodides: facile regioselective synthesis of E-stilbenes and their analogues

A general synthetic route for the Pd-catalyzed cross-coupling of an arylzinc reagent with arylvinyl iodides (Negishi cross-coupling) has been developed. The system permits efficient and selective preparation of E-stilbenes and their analogues. It also functions effectively at low levels of catalyst loading without the need for an additional ligand and tolerates a wide range of functional groups including heteroaromatic substrates. A systematic study of various parameters was performed and correlated with catalyst-substrate activity.     

3-Iodoselenophene derivatives: a versatile substrate for Negishi cross-coupling reaction

3-Iodoselenophene derivatives undergo a direct Negishi cross-coupling reaction with several organozinc compounds in the presence of a catalytic amount of Pd(PPh₃)₄ in THF at room temperature. This cross-coupling reaction proceeded cleanly under mild conditions and permitted the formation of polyaromatic compounds in good yields.     

Synthesis of analogs of the phenylamino-pyrimidine type protein kinase C inhibitor CGP 60474 utilizing a Negishi cross-coupling strategy

Analogs of 3-{4-[2-(3-chlorophenylamino)-pyrimidin-4-yl]-pyridin-2-yl-amino}-propanol (CGP 60474) were synthesized as useful models for the evaluation of structure-activity relationships of phenylamino-pyrimidine-type protein kinase C inhibitors. The approach involved Pd-assisted cross-coupling as the key step. Negishi-type coupling was performed both with free amino functionalities and Boc-protected amines present and showed that the protection-cross-coupling-deprotection sequence leads to significantly higher yields.     

Synthesis of chiral amino acids with metal ion chelating side chains from l-serine using Negishi cross-coupling reaction

The scope of the Negishi cross-coupling reaction of organozinc compounds derived from chiral amino acids was extended to electron rich iodoanilines and iodobenzylamines as coupling reagents. The protocol allows the direct modification of serine into phenylalanine derivatives bearing metal ion chelating ligands in their side chain, such as amino esters 6 and 7. The preparation of metal complex labeled peptides, the construction of synthetic receptors and hybrid materials are potential applications of the modified chiral amino acids.     

The facile synthesis of a series of tryptophan derivatives

This study reports a facile method for the synthesis of a variety of 5- and 6-substituted tryptophan derivatives that are difficult to prepare using alternative enzymatic approaches. Acylation of an activated amino acid, derived from serine in situ, is coupled with an enzymatic resolution step to furnish enantiopure analogues bearing a range of electron withdrawing and releasing substituents. Isolation of a dehydroalanine derivative as a by-product from some reactions provides some insights into the likely mechanism of the reaction.     

Negishi cross-coupling of arenediazonium o-benzenedisulfonimides

Diazonium salts, precisely arenediazonium o-benzenedisulfonimides, have been used for the first time as efficient electrophilic partners in Negishi coupling reactions. The synthetic protocol was general, easy and gave biaryls in satisfactory yields (34 examples, average yield 69%). o-Benzenedisulfonimide was recovered at the end of the reactions and reused to prepare the starting salts once again.     

仲烷基卤化锌与6-氯嘌呤类化合物的Negishi偶联反应

在室温条件下,以邻菲罗啉作为配体,无水氯化镍催化的Negishi偶联反应合成了一系列6位链状仲烷基取代的嘌呤化合物.该方法反应条件温和、原料易得、产物收率高.     

Improved synthesis of phenylethylamine derivatives by Negishi cross-coupling reactions

Trifluoroacetamido-protected β-aminoalkylzinc iodides undergo Negishi cross-coupling reaction with aryl iodides in moderate to excellent yields (42-84%) based on the corresponding trifluoroacetamido-protected β-aminoalkyl iodides, employing a catalyst prepared in situ from Pd₂(dba)₃ and SPhos (1:2 M ratio). In general, meta- and para-substituted aryl iodides give good results using relatively low levels of catalyst [0.25 mol % Pd₂(dba)₃], but more hindered ortho-substituted examples require higher catalyst loadings. The preparation of trifluoroacetamido-protected β-aminoalkyl iodides is straightforward, and the intermediates are significantly more stable than the corresponding Boc-protected derivatives.     

Negishi cross-coupling of organotellurium compounds: synthesis of biaryls, aryl-, and diaryl acetylenes

A functional group tolerant palladium-catalyzed Negishi coupling of diaryl tellurides with organozinc has been developed. This methodology permits efficient preparation of biaryls, aryl acetylenes and diaryl acetylenes in moderate to good yields. A preliminary study to gain further insight into the reaction was performed using in situ ReactIR technology.     

A new protecting group for tryptophan in solid-phase peptide synthesis which protects against acid-catalyzed side reactions and facilitates purification by HPLC

The indole nucleus of Z-Trp-OBzl is modified by acylation of the indole nitrogen using Boc-N-methyl butyric acid followed by catalytic hydrogenation and introduction of the Fmoc group. The resulting derivative, Fmoc-Trp(Boc-Nmbu)-OH, is incorporated into peptide chains via solid-phase peptide synthesis (SPPS). After assembly of the peptide chain, the Boc group is cleaved by treatment with TFA. The peptide is isolated with the tryptophan residue modified with a cationic 4-(N-methylamino) butanoyl group, which improves the solubility of the peptide during HPLC purification. On treatment of the purified peptide at pH 9.5, the Nmbu group undergoes an intramolecular cyclization reaction; this results in the fully deprotected peptide and N-methylpyrrolidone.     

Protection of the indole nucleus of tryptophan in solid-phase peptide synthesis with a dipeptide that can be cleaved rapidly at physiological pH

The synthesis of a new derivative of tryptophan Fmoc-Trp(Boc-Sar-Sar)-OH is described. Fmoc-Trp(Boc-Sar-Sar)-OH is introduced into peptides by solid-phase peptide synthesis and during treatment with TFA at the end of the synthesis, the Boc group is cleaved and the peptide is obtained with the indole nucleus modified with the sarcosinyl-sarcosinyl (Sar-Sar) moiety. This modification will introduce a cationic charge that improves the solubility of the peptide during HPLC purification. The Sar-Sar moiety is cleaved upon exposure to physiological pH. The Boc-Sar-Sar group might, therefore, also find use in the design of pro-drugs of indole-containing compounds.     

Oxidative addition of heteroaromatic halides to Negishi reagent and subsequent cross-coupling reactions

Heteroarylzirconocene halides were prepared via the oxidative addition of heteroaryl halides to the Negishi reagent ‘Cp₂ZrBu₂’. The palladium-catalyzed cross-coupling of the in situ generated organozirconium reagents with functionalized aryl and heteroaryl halides proceeded smoothly in the presence of CuCl to produce the cross-coupling products in high yields.     

The efficient synthesis of 2-arylpyrimidine acyclic nucleoside phosphonates using Liebeskind-Srogl cross-coupling reaction

A series of novel acyclic nucleoside phosphonates with various aryls attached to the C-2 position of the pyrimidine moiety has been prepared using the Liebeskind-Srogl cross-coupling protocol. The reactions of highly functionalised 2-(methylsulfanyl)pyrimidines with various arylboronic acids were studied and optimised.     

Microwave assisted asymmetric Suzuki-Miyaura and Negishi cross-coupling reactions: synthesis of chiral binaphthalenes

Microwave assisted asymmetric Suzuki-Miyaura and Negishi enantioselective cross-coupling reactions are reported for the first time, and have been applied to the rapid synthesis of chiral sterically hindered binaphthalene derivatives in reasonable to excellent yields (65–96%) and fair to good enantioselectivities (43–70% ee).     

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.     

手性膦过渡金属配合物催化不对称交叉偶联反应的研究

自1973年Consiglio和Botteghi首次报道用(一)-DIOP的NiCl_2配合物催化芳基或乙烯基卤代物与仲烷基卤化镁交叉偶联生成光学活性的偶联产物以来,化学家们对不对称交叉偶联反应进行了深入研究。Hayashi等用手性二茂铁膦和手性β-氨基烷基膦的NiCl_2和PdCl_2配合物催化1-苯基乙基氯化