Cp*Co(III) catalyzed annulation of N-Cbz hydrazones for the redox-neutral synthesis of isoquinolines via C–H/N–N bond activation

Abstract

A new cascade oxidative cyclization reaction of N-Cbz hydrazones with internal alkynes has been explored for the preparation of isoquinoline derivatives using Cp*Co^III-catalyst through C–H and N–N bond functionalization. N-Cbz hydrazones are rarely explored as directing group for redox-neutral [4?+?2] cyclization reaction through the cyclometallation and this catalyst system does not require any external oxidizing agent, as well as, silver or antimony salt. The current efficient approach has been utilized for the synthesis of different isoquinoline derivatives with good regioselectivity and yields.     

Reaction of 2-acyl-3-aminobenzofurans with hydrazines

While 2-acetyl and 2-benzoyl-3-aminobenzofurans did not react with hydrazine, monomethyl- and N,N-dimethylhydrazine to give the related hydrazones, their 3-N-(p-toluenesulfonyl) derivatives afforded them smoothly in good yields. Depending upon reaction conditions, products arising from hydrazone cyclization to benzofuropyrazoles and/or from furan ring cleavage at the C2 O bond to give 5-(2-hydroxyphenyl)pyrazoles were also formed. The formation of these products depends upon hydrazones configuration and is discussed. Only (E)-isomers appear to undergo furan ring opening. In acidic media at room temprature either the hydrazones or the monomethylhydrazones gave the same related α-azines. Microanalyses, ir, uv, ¹H-nmr and ms spectra are in agreement with the proposed structures.     

N-(4-苯基-噻唑-2-基)芳醛腙类化合物的合成

以芳醛与氨基硫脲进行缩合得到缩氨基硫脲, 分别与ω-溴苯乙酮进行成环反应得到了一系列含噻唑环和芳基的腙类化合物, 并通过用¹H NMR、质谱、红外光谱等对化合物进行了结构表征.     

Synthesis,Dissociation Constants,and Some Pharmacological Properties of Schiff Base Hydrazones and their Cyclization to 1,3‐Thiazolidin‐4‐one Derivatives

This study presents the synthesis, dissociation constants, and pharmacological properties of Schiff base hydrazones. The derivatives were synthesized by the condensation reaction of carboxylic acid hydrazides containing 1,2,4‐triazole system with various aldehydes. The new derivatives of 1,3‐thiazolidin‐4‐one were prepared by the cyclization reaction of Schiff base hydrazones with the mercaptoacetic acid in the presence of 1,4‐dioxane. The structure of all obtained compounds was confirmed by means of ¹H NMR and ¹³C NMR spectra. The dissociation constants were determined using spectrophotometric method. The effects of four synthesized Schiff base hydrazones 6 , 7 , 11 and 12 on the central nervous system of mice in behavioral tests were examined.     

Catalytic Dibenzocyclooctene Synthesis via Cobalt(III)–Carbene Radical and ortho‐Quinodimethane Intermediates

The metalloradical activation of ortho‐benzallylaryl N‐tosyl hydrazones with [Co(TPP)] (TPP=tetraphenylporphyrin) as the catalyst enabled the controlled exploitation of the single‐electron reactivity of the redox non‐innocent carbene intermediate. This method offers a novel route to prepare eight‐membered rings, using base metal catalysis to construct a series of unique dibenzocyclooctenes through selective C_carbene?C_aryl cyclization. The desired eight‐membered‐ring products were obtained in good to excellent yields. A large variety of aromatic substituents are tolerated. The proposed reaction mechanism involves intramolecular hydrogen atom transfer (HAT) to Co^III–carbene radical intermediates followed by dissociation of an ortho‐quinodimethane that undergoes 8π cyclization. The mechanism is supported by DFT calculations, and the presence of radical‐type intermediates was confirmed by trapping experiments.     

Iodine-Mediated One-Pot Synthesis of 1,4,5-Substituted Pyrazoles from MBH Acetates via Allyl Hydrazone Intermediate

Herein, we report the regioselective one-pot synthesis of 1,4,5-trisubstituted pyrazoles by reacting Morita-Baylis-Hillman (MBH) acetates derived from aryl aldehydes with alkyl or aryl hydrazines in the presence of iodine under aerobic conditions. The reaction proceeds through sequential S_N2′ nucleophilic substitution of substituted hydrazine onto the MBH acetate, I₂-catalyzed oxidation of the allylic hydrazine to allylic hydrazone, heating-induced intramolecular aza-Michael reaction and cyclization, and oxidative aromatization. The key intermediate, the s-trans allyl hydrazones were isolated in good yields by performing the reactions at room temperature. However, the allyl hydrazones prepared from the MBH acetates of aliphatic aldehydes did not furnish the pyrazole owing to the absence of an activated methylene group in the substrate. The synthetic applications of the pyrazoles in Ugi reactions, decarboxylative halogenation, Pd-catalyzed benzoylation of the N-aryl ring, and metal-free tetrazole synthesis has been demonstrated.     

A Convenient One‐Pot Synthesis of Triazolopyridine and Related Heterocycle Fused‐Triazole Analogs Through Copper Catalyzed Oxidative Cyclization Strategy

One‐pot synthesis of heterocycle fused‐triazole analogs from the corresponding aldehydes and heteroarylhydrazines is demonstrated. Transformation of hydrazones to the desired systems was achieved by employing the oxidative cyclization with catalytic CuBr₂ and oxone. This reaction condition is mild and selective, and a wide range of functional groups were able to sustain. An array of biologically important triazolopyridines, triazolopyridazines, triazolopyrimidines, and triazoloquinolines were obtained in fairly good yield.     

Action des Hydrazines Fluoroalkylées Sur Les α-Cetophosphonates: Synthèse des Hydrazones α-Phosphonylées N-Fluoroalkylées

In the present work, we study the reaction of fluorinated hydrazines H ₂ N-NHR _F with α-ketophosphonates 1, which lead to N-fluoroalkylated α-phosphonylated hydrazones 2. The stereochemistry of the hydrazones 2 was determined by multinuclear NMR experiments ( ¹ H, ¹³ C, ¹⁹ F, and ³¹ P) and IR spectroscopy.     

Platinum-promoted cyclization reactions of amino-olefins : I. The cyclization of 4-aminopentene and related compounds

Olefinic amines of the ytpe CH₂CH(CH₂)_nNHR undergo cyclization in acidic aqueous solution at 60°C in the presence of PtCl₄^2?. The PtCl₄^2? is regenerated at the end of the cyclization so that the reaction may be considered as catalytic. Both pyrrolidines and piperidines may be formed although the former are favored.     

Palladium‐Catalyzed Aerobic Intermolecular Cyclization of Acrylic Acid with 1‐Octene to Afford α‐Methylene‐γ‐butyrolactones: The Remarkable Effect of Continuous Water Removal from the Reaction Mixture and Analysis of the Reaction by Kinetic,ESI‐MS,and XAFS Measurements

Further study of our aerobic intermolecular cyclization of acrylic acid with 1‐octene to afford α‐methylene‐γ‐butyrolactones, catalyzed by the Pd(OCOCF₃)₂/Cu(OAc)₂ ? H₂O system, has clarified that the accumulation of water generated from oxygen during the reaction causes deactivation of the Cu cocatalyst. This prevents regeneration of the active Pd catalyst and, thus, has a harmful influence on the progress of the cyclization. As a result, both the substrate conversion and product yield are efficiently improved by continuous removal of water from the reaction mixture. Detailed analysis of the kinetic and spectroscopic measurements performed under the condition of continuous water removal demonstrates that the cyclization proceeds in four steps: 1) equilibrium coordination of 1‐octene to the Pd acrylate species, 2) Markovnikov‐type acryloxy palladation of 1‐octene (1,2‐addition), 3) intramolecular carbopalladation, and 4) β‐hydride elimination. Byproduct 2‐acryloxy‐1‐octene is formed by β‐hydride elimination after step 2). These cyclization steps fit the Michaelis–Menten equation well and β‐hydride elimination is considered to be a rate‐limiting step in the formation of the products. Spectroscopic data agree sufficiently with the existence of the intermediates bearing acrylate (Pd? O bond), η³‐C₈H₁₅ (Pd? C bond), or C₁₁H₁₉O₂ (Pd? C bond) moieties on the Pd center as the resting‐state compounds. Furthermore, not only Cu^II, but also Cu^I, species are observed during the reaction time of 2–8 h when the reaction proceeds efficiently. This result suggests that the Cu^II species is partially reduced to the Cu^I species when the active Pd catalytic species are regenerated.     

About the synthesis of [1,2]diazepinoindole derivatives from ethyl 2-(1-methylindole)acetate, 2-indole and 3-indoleacetohydrazones

The Vilsmeier-Haack reaction with ethyl 2-(1-methylindole)acetate and N,N-Dimethylamides/phosphorus oxychloride gave (65–85%) of ethyl 2-(3-acyl-1-methylindole)acetates 2 , which when boiled with hydrazine yielded about 90% of 4,5-dihydro-6-methyl-4-oxo-3H[1,2]diazepino[5,6-b]indoles 3. The attempted cyclization of 2-(1-methylindole)acetohydrazones 6 with acyl (acetyl and benzoyl) chlorides/triethylamine, to [1,2]diazepino[5,6-b]indole derivatives was fruitless and the bis(acyl)hydrazones 9 were obtained. Several transformations of 9 are reported. Similarly, the attempted cyclization of 3-indoleacetohydrazones 14 with acetyl chloride/triethylamine to [1,2]diazepino[4,5-b]indole derivatives was also fruitless and the bis(acyl)hydrazones 16 were again obtained.     

Transformation of 1,2,3‐Thiadiazolyl Hydrazones as Method for Preparation of 1,2,3‐Triazolo[5,1‐b][1,3,4]thiadiazines

The transformation of 1,2,3‐thiadiazolyl hydrazones of aldehydes and ketones including Dimroth rearrangement giving 1‐alkylidenamino‐5‐mercapto‐1,2,3‐triazoles, alkylation of mercapto group of these heterocyclic compounds by α‐bromoacetophenones and cyclization giving 6,7‐dihydro‐5H‐[1,2,3]triazolo[5,1‐b ][1,3,4]thiadizines have been investigated. It was shown that the reaction for hydrazones of acetophenones and benzoaldehydes is diastereoselective. Triazolothiadiazine spiro derivatives were prepared with transformation of hydrazones of cyclic ketones.     

New acyclic aminocarbene palladium(ii) complexes as convenient catalysts for the Sonogashira and Suzuki cross-coupling

A reaction of isocyanide complex cis-[PdCl₂(CNAr)₂] with hydrazones H₂N-N=CR¹R² proceeded at the carbon atom of one of the isocyanide groups and gave the corresponding diaminocarbene isocyanide palladium(ii) complexes. These complexes showed high catalytic activity in the Sonogashira and Suzuki cross-coupling reactions.     

Cobalt‐Catalyzed Cyclization of N‐Methoxy Benzamides with Alkynes using an Internal Oxidant through C−H/N−O Bond Activation

The cyclization of substituted N‐methoxy benzamides with alkynes in the presence of an easily affordable cobalt complex and NaOAc provides isoquinolone derivatives in good to excellent yields. The cyclization reaction is compatible with a range of functional group‐substituted benzamides, as well as ester‐ and alcohol‐substituted alkynes. The cobalt complex [Co^IIICp*(OR)₂] (R=Me or Ac) serves as an efficient catalyst for the cyclization reaction. Later, isoquinolone derivatives were converted into 1‐chloro and 1‐bromo substituted isoquinoline derivatives in excellent yields in the presence of POCl₃ or PBr₃.     

Transition metal complexes of novel tridentate S,N,O donor ligands

Summary Complexes of chromium(III), iron(III), cobalt(III), nickel(II) and copper(II) with salicylaldehyde N(1-piperidyl) thiocarbonyl hydrazone (spthH₂), salicylaldehyde N-(1-morpholyl) thiocarbonyl hydrazone (smthH₂), 2-hydroxy 4-methyl acetophenone N-(1-piperidyl) thiocarbonyl hydrazone (apthH₂) and 2-hydroxy 4-methyl acetophenone N-(1-morpholyl) thiocarbonyl hydrazone (amthH₂) have been prepared and characterized by analytical, spectral and magnetic measurements. Mixed ligand complexes of Cu^II-thiocarbonyl hydrazones and heterocyclic bases have been isolated. Depending on the nature of the metal salts used and the reaction conditions the thiocarbonyl hydrazones act as neutral or dibasic tridentate ligands.     

Nucleophilic Addition to CC Bonds,Part X

A mechanistic model is presented for the base‐catalyzed intramolecular cyclization of polycyclic unsaturated alcohols of type A to ethers D (Scheme 1). The alkoxide anion B is formed first in a fast acid‐base equilibrium. For the subsequent reaction to D , a carbanion‐like transition state C is proposed. This mechanism is in full agreement with our results regarding the influence of substituents on the regioselectivity and the rate of cyclization. We studied the effect of alkyl substituents in allylic position (alkylated endocylic olefinic alcohols 1 – 3 ) and, especially, at the exocyclic double bond ( 12 – 15 ). The fastest cyclization (k_rel=1) is 12 → 16 , which proceeds via a primary carbanion‐like transition state ( E : R¹=R²=H). The corresponding processes 13 → 17 and 14 → 17 are characterized by a less‐stable secondary carbanion‐like transtition state ( E : R¹=Me, R²=H, or vice versa) and are slower by a factor of 10⁴. The slowest reaction (k_rel ca. 10⁻⁶) is the cyclization 15 → 18 via a tertiary carbanion‐like transition state ( E : R¹=R²=Me).     

Functionalization of Intramolecular Frustrated Lewis Pairs by 1,1‐Carboboration with Conjugated Enynes

The vicinal P/B frustrated Lewis pair (FLP) Mes₂PCH₂CH₂B(C₆F₅)₂ undergoes 1,1‐carboboration reactions with the Me₃Si‐substituted enynes to give ring‐enlarged functionalized C₃‐bridged P/B FLPs. These serve as active FLPs in the activation of dihydrogen to give the respective zwitterionic [P]H⁺/[B]H^? products. One such product shows activity as a metal‐free catalyst for the hydrogenation of enamines or a bulky imine. The ring‐enlarged FLPs contain dienylborane functionalities that undergo “bora‐Nazarov”‐type ring‐closing rearrangements upon photolysis. A DFT study had shown that the dienylborane cyclization of such systems itself is endothermic, but a subsequent C₆F₅ migration is very favorable. Furthermore, substituted 2,5‐dihydroborole products are derived from cyclization and C₆F₅ migration from the photolysis reaction. In the case of the six‐membered annulation product, a subsequent stereoisomerization reaction takes place and the resultant compound undergoes a P/B FLP 1,2‐addition reaction with a terminal alkyne with rearrangement.     

Synthesis and ring-chain tautomerism of salts of alkylidene(arylidene) derivatives of amidrazones

A number of salts of alkylidene (arylidene) derivatives of amidrazones was obtained by the reaction of S-methylthioamidium iodides with hydrazones of monocarbonyl compounds. According to the ¹H and ¹³C NMR data, these compounds in solutions are capable of ring-chain tautomerism of the 1-alkylideneamidrazone-1,2,4-triazoline type. The position of the equilibrium is determined chiefly by steric interactions of the substituents attached to the C-N₂ bond.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1264–1267, September, 1982.     

Protolytic properties of 8-quinolylhydrazones of substituted salicylaldehydes and physicochemical properties of their copper(II) complexes

Acid-base properties of hydrazones derived from 8-hydrazinoquinoline and substituted salicylaldehydes were studied. Under the experimental conditions, only the first step of ionization of the hydrazones is realized. The ionization constants were calculated quantum-chemically. Copper(II) complexes of these hydrazones, (HL)Cu(X)(CH₃OH)_n, were isolated (HL^? is the monodeprotonated form of hydrazones, and X^? is the acid residue). According to the data of elemental analysis, IR spectroscopy, conductometry, and magnetochemistry, the majority of the complexes have a binuclear structure. The copper(II) ions in the dimeric complex show antiferromagnetic exchange coupling. The ionization constants of the hydrazones and the exchange parameters strongly depend on the substituent in the salicylaldehyde moiety.     

Unprecedented cyclization of α-diazo hydrazones upon N-H functionalization: A Et3N base promoted one-step synthetic approach for the synthesis of N-amino-1,2,3-triazole derivatives from α-diazo hydrazone

In this communication, for the first time, we are reporting α-diazo hydrazone synthesis from hydrazones derived from β-keto esters and 2,4-dinitro phenyl hydrazine via diazo transfer reaction. We also report an unexpected cyclization of the α-diazo hydrazones upon N-H functionalization to give highly functionalized N-amino-1,2,3-triazole derivatives under metal-free condition. This one-step synthetic protocol can serve as a general tool to access nitrogen rich 5- and 6-membered heterocycles in excellent yields.