有机催化不对称Michael/环化串联反应的研究进展北大核心CSCD

串联反应能够减少反应步骤、简化操作、降低成本、实现高效率转化,符合原子经济性和绿色化学理念.特别是有机催化的不对称串联环化反应以一锅法连续催化多个化学反应,为高效合成多手性中心环状结构提供了新方法.不对称Michael/环化串联反应是构建光学活性状化合物的常用方法之一,近些年,各种有机小分子催化剂应用于不对称Michael/环化串联反应的报道不断增加,并且取得了重大进展.我们根据不同的催化剂类型综述了近5年来关于不对称Michael/环化串联反应的研究进展,并对有机催化不对称Michael/环化串联反应的发展趋势进行了展望.     

A Nazarov-Ene Tandem Reaction for the Stereoselective Construction of Spiro Compounds

The different reactivity of trienones under Lewis and Brønsted acids catalysis was investigated, resulting in distinct cyclization products and carbon backbones that originated either from a conjugate Prins cyclization or an interrupted Nazarov cyclization. In particular, an unprecedented Nazarov cyclization tandem reaction is presented, terminating the oxyallyl cation by an ene-type reaction, and leading stereoselectively to bicyclic spiro compounds. The terminal olefin of this motif represents a useful handle for further functionalization, making it a strategic intermediate in total syntheses. The tandem Nazarov/ene cyclization was shown to be preferred over a Nazarov/[3+2] tandem reaction for all our substrates, independent of chain length. Deuteration studies further support the mechanistic hypothesis of the terminating ene reaction.     

Gold-catalyzed reactions of 2-alkynyl-phenylamines with alpha,beta-enones

[reaction: see text] The gold-catalyzed reaction of 2-alkynyl-phenylamines with alpha,beta-enones represents a new general one-pot entry into C-3-alkyl-indoles by sequential reactions. Gold-catalyzed sequential cyclization/alkylation, N-alkylation/cyclization, or N-alkylation/cyclization/alkylation reactions leading to different indoles can be directed by changing the 2-alkynyl-phenylamine 1/alpha,beta-enone 3 ratio and the reaction temperature. Unusual gold-catalyzed rearrangement reaction of indoles are observed at 140 degrees C. New gold-catalyzed formation of propargyl-alkyl ether under mild conditions and the hydration reaction of N-acetyl-2-ethynyl-phenylamine are reported.     

Studies on the oxidative cyclization of 3-hydroxyalkyl-1,2,4-trialkoxynaphthalenes and synthetic application for the biologically active natural compound rhinacanthone

The oxidative intramolecular cyclization of 3-hydroxyalkyl-1,2,4-trimethoxynaphthalenes was investigated. A series of 1,2-naphthoquinone fused cyclic ethers were synthesized directly from 3-hydroxyalkyl-1,2,4-trimethoxynaphthalenes by exposure to diammonium cerium (IV) nitrate. To understand the reaction mechanism, the intramolecular cyclization of 3-hydroxyalkyl-naphthoquinones that were formed as reaction intermediates was also examined. The results suggested that the reaction proceeds by a stepwise oxidation–cyclization mechanism. Using this methodology, five-step synthesis of rhinacanthone was achieved with high yield.     

A study of vinyl radical cyclization using N-alkenyl-7-bromo-substituted hexahydroindolinones

A new method for the synthesis of the octahydropyrrolo[3,2,1-ij]quinoline ring system that possesses the characteristic skeleton of the aspidosperma family of alkaloids has been developed. The method utilizes an intramolecular Diels-Alder reaction of an amido-substituted furan across a tethered indole pi-bond. To apply this strategy to the synthesis of the indole alkaloid spegazzinidine, it was necessary to address the problem of assembling the final D-ring of the pentacyclic skeleton. Radical cyclization of a model N-allyl-7-bromo-3a-methylhexahydroindolinone system was found to preferentially lead to the 6-endo-trig cyclization product, with the best yield being obtained under high dilution conditions. The six-membered cyclized product is generated through two reaction pathways: (a) 6-endo-trig ring closure and (b) rearrangement of an intermediate methylene-cyclopentyl radical obtained by 5-exo-trig cyclization. A number of related 7-bromo-substituted hexahydroindolinones containing tethered olefinic groups were prepared and found to undergo efficient cyclization under both radical and palladium-mediated reaction conditions. Vinyl radical cyclization with several N-butenyl-substituted systems afforded a mixture of 6-exo and 7-endo cyclization products. A protocol to introduce an ethyl substituent into the C20-position of the aspidospermidine skeleton was also developed.     

Recent Progress on Nazarov Cyclizations: The Use of Iron Salts as Catalysts in Ionic Liquid Solvent Systems

Nazarov cyclization is an important and versatile method for the synthesis of five‐membered carbocycles, and extensive studies have been conducted to optimize the reaction. Among recent studies, several trends are recognized. One is the combination of different reactions with Nazarov cyclization in a one‐pot reaction system which enables the preparation of unique cyclization products. The second is the use of a transition‐metal catalyst, though Lewis or Brønsted acids have generally been used for the reaction. The third is the realization of the asymmetric Nazarov cyclization. The fourth is the base‐catalyzed Nazarov cyclization. Furthermore, several useful protocols for realizing Nazarov cyclization have also been developed. The recent progress on Nazarov cyclizations is summarized in Section 2. Section 3 is our chronicle in this field. We focused on the use of iron as the catalyst in Nazarov cyclizations and ionic liquids as solvents: Nazarov cyclization of thiophene derivatives using FeCl₃ as the catalyst was accomplished and we succeeded in demonstrating the first example of an iron‐catalyzed asymmetric Nazarov reaction. We next established Nazarov cyclization of pyrrole or indole derivatives using Fe(ClO₄)₃·Al₂O₃ as the catalyst with high trans selectivities in excellent yields. Since the cyclized product was reacted with a vinyl ketone in the presence of the same iron salt, the system allowed realization of the sequential type of Nazarov/Michael reaction of pyrrole derivatives. Furthermore, we demonstrated the recyclable use of the iron catalyst and obtained the desired Nazarov/Michael reaction products in good yields for five repetitions of the reactions without any addition of the catalyst using an ionic liquid, [bmim][NTf₂], as the solvent. We expect that the iron‐catalyzed Nazarov cyclization, in particular, in an ionic liquid solvent might become a useful method to synthesize functional molecules that include cycloalkene moieties.     

Zirconocene-promoted synthesis of substituted tetrahydropyrans

Zirconocene reagents derived from zirconocene dichloride and two equivalents of butyllithium react with allylic, homoallylic diene ethers. Hydrolysis of the reaction products yields substituted tetrahydropyrans. The reaction is postulated to occur via cyclization of the diene to form a zirconacyclopentane. This cyclization occurs without allylic rearrangement.     

分子内Friedel-Crafts环化反应在苯并环状物合成中的应用

Friedel-Crafts反应是有机合成中最有用的反应之一,它的应用范围十分广泛.Friedel-Crafts反应也是合成环状化合物的重要途径,尤其分子内的环化反应一直以来受到广泛的关注.对近年来应用分子内Friedel-Crafts环化反应合成苯并环状化合物进行了详细的综述,并对分子内Friedel-Crafts环化反应在有机合成上发展前景作了展望.     

Base-mediated intramolecular cyclization of (2-propargyl ether) arylimines: an approach to 3-amino-benzofurans

We present here a practical synthesis of functional 3-amino-benzofurans through base-promoted intramolecular cyclization of (2-propargyl ether) arylimines. A systematic study of the cyclization system revealed that the presence and the amount of base played an essential role in this reaction. The results showed that the cyclization proceeded cleanly and smoothly under mild reaction conditions, employing potassium tert-butoxide as base, THF as solvent, at room temperature in a short reaction time (1 h). The generality of this reaction has been established with (2-propargyl ether) arylimines having both electron-withdrawing and electron-donating groups.     

Oxidative cyclization of some aldehyde semicarbazones induced by metallic salts

The oxidative cyclization of some aldehyde semicarbazones 10 with four different oxidizing agents has been effected. The structure of the semicarbazones and the nature of cyclizing agent affected the rate and yield of cyclization but they did not show any influence on the regiochemistry of reaction. In fact, 1,2,4-triazoline 20 was the only heterocyclic ring obtained by the cyclization reaction.     

Coupling of Fischer carbene complexes with conjugated enediynes featuring radical traps: Novel structure and reactivity features of chromium complexed arene diradical species

The reaction of Fischer carbene complexes with conjugated enediynes that feature a pendant alkene group has been examined. The reaction proceeds through carbene–alkyne coupling to generate an enyne–ketene intermediate. This intermediate then undergoes Moore cyclization to generate a chromium complexed arene diradical, which then undergoes cyclization with the pendant alkene group. The radical cyclization prefers the 6-endo mode unless radical-stabilizing groups are present to favor the 5-exo mode. The intermediate diradical species were evaluated computationally in both the singlet and triplet configurations. Arene triplet diradicals feature minimal spin density at oxygen and delocalization to chromium. The 6-endo cyclization product was kinetically and thermodynamically favored.     

A synthesis of 6-azabicyclo[3.2.1]octanes. The role of N-substitution

The intramolecular cyclization reactions of aziridines with pi-nucleophiles can be a useful route to a number of heterocyclic and carbocyclic ring systems. We were particularly interested in the use of this cyclization reaction for the synthesis of 6-azabicyclo[3.2.1]octanes. We report here the development of a new synthesis of the aziridine necessary for the aziridine--pi-nucleophile cyclization. We also report on the cyclization of aziridines with three different substitutions on the aziridine nitrogen. We have found that N-diphenylphospinyl and N-H aziridines, while participating in the initial ring-opening reaction, do not lead to the desired bicyclic ring systems. In contrast, a nosyl group on the aziridine nitrogen leads efficiently to the bicyclic ring system and can be readily deprotected.     

Electrophilic cyclization of (Z)-selenoenynes: synthesis and reactivity of 3-iodoselenophenes

We present here our results of the electrophilic cyclization reaction of (Z)-selenoenynes with different electrophiles such as I(2), ICl, PhSeBr, and PhSeCl. The cyclization reaction proceeded cleanly under mild reaction conditions, and 3-substituted selenophenes were formed in moderate to excellent yields. We observed that the nature of solvent and structure of (Z)-selenoenyne were important to the cyclization reaction. In addition, the obtained 3-iodoselenophenes were readily transformed to more complex products using a metal-halogen exchange reaction with n-BuLi and trapping the intermediate formed with aldehydes, furnishing the desired secondary alcohols in good yields. Conversely, using the palladium or copper catalyzed cross-coupling reactions with terminal alkynes or alkyl alcohols, we were able to convert 3-iodoselenophene to Sonogashira or Ullmann type products, respectively, in good yields.     

Synthesis of indolequinones via a Sonogashira coupling/cyclization cascade reaction

A mild strategy for constructing indolequinone motifs is described on the basis of the Sonogashira reaction and a copper-catalyzed intramolecular cyclization cascade reaction. The first step involves the palladium- and copper-catalyzed reaction between halogenated naphthoquinone and terminal acetylene to generate a coupling product, which then reacts in a copper-catalyzed intramolecular cyclization with the nitrogen functional group adjacent to the carbon-carbon triple bond.     

Synthesis of the bis-spiroacetal moiety of spirolides B and D

An enantioselective synthesis of the bis-spiroacetal fragment of spirolides B and D is reported. The carbon framework was constructed via Barbier reaction of dihydropyran 3 with aldehyde 4, followed by a double oxidative radical cyclization to construct the bis-spiroacetal. A silyl-modified Prins cyclization and enantioselective crotylation successfully installed the stereocenters in the cyclization precursor. The initial unsaturated bis-spiroacetals 2a-d underwent equilibration during epoxidation to trans-epoxide 14 that was converted to a tertiary alcohol. [reaction: see text]     

Synthesis of imidazo-1,4-oxazinone derivatives and investigation of reaction mechanism

In this study, nine different C-2 aroyl imidazole derivatives were synthesized in a one pot reaction with two steps, and the reduction reactions of these derivatives with NaBH₄ were carried out under mild conditions. Substitution reaction of obtained imidazo methanol derivatives with chloroacetylchloride reagent and ring reaction of substitution products were investigated. It was determined that 1,4-imidazoxazinone derivative was obtained as a result of the cyclization reaction. The intermediate products obtained during the cyclization reaction were isolated, and the path of the reaction under different conditions was discussed.     

Photoinduced intramolecular cyclization of o-ethenylaryl isocyanides with organic disulfides mediated by diphenyl ditelluride

Photoinduced reaction of o-ethenylaryl isocyanides with organic disulfides in the presence of diphenyl ditellurides affords the corresponding bisthiolated indole derivatives via a radical cyclization process. The cyclization can proceed at room temperature upon visible-light irradiation and exhibits good tolerance to functional groups. Several organic disulfides also can be employed for this cyclization, and the corresponding bisthiolated indole derivatives are obtained selectively. In addition, the photoinduced reaction of o-ethenylaryl isocyanides with bis(2-aminophenyl) disulfide affords tetracyclic compounds in one portion.     

6-Substituted 2-(2-benzothiazolyl) [1, 2, 3] benzotriazol-1-oxides and the kinetics of their formation

6-Substituted 2-(2-benzothiazolyl) [1, 2, 3] benzotriazol-1-oxides were prepared by a base catalyzed cyclization reaction of 2-(4-substituted 2-nitrophenylhydrazino) benzothiazoles. Influence of substitution in position 4 on the cyclization reaction rate was followed and correlated with Hammett constants.     

Photochemical studies on aromatic γ,δ-epoxy ketones: efficient synthesis of benzocyclobutanones and indanones

Irradiation of terminal aromatic γ,δ-epoxy ketones with a 450 W UV lamp led to Norrish type II cyclization/semi-pinacol rearrangement cascade reaction which formed the benzocyclobutanones containing a full-carbon quaternary center, whereas irradiation of substituted aromatic γ,δ-epoxy ketones led to the indanones through a photochemical epoxy rearrangement and 1,5-biradicals cyclization tandem reaction.     

One-pot cyclizations of dilithiated oximes and hydrazones with epibromohydrin. Efficient synthesis of 6-hydroxymethyl-5,6-dihydro-4H-1,2-oxazines and oxazolo[3,4-b]pyridazin-7-ones

The one-pot cyclization of dilithiated oximes with epibromohydrin provided a convenient and regioselective approach to 6-hydroxymethyl-5,6-dihydro-4H-1,2-oxazines. The reaction of the latter with phosphorus tribromide resulted in a Beckmann rearrangement and formation of 5-bromomethyl-2-iminotetrahydrofurans. The reaction of dilithiated hydrazones with epibromohydrin afforded oxazolo[3,4-b]pyridazin-7-ones, which were formed by a novel domino cyclization.