Enantioselective Dearomative Difunctionalization of Indoles by Palladium-Catalyzed Heck/Sonogashira Sequence

Palladium-catalyzed enantioselective dearomative arylalkynylation of N-substituted indoles, through a Heck/Sonogashira sequence, was established using a new BINOL-based phosphoramidite as the chiral ligand. A wide range of 2,3-disubstituted indolines, bearing vicinal quaternary and tertiary stereocenters, were efficiently constructed in one step with excellent enantioselectivities (up to 97 % ee) and diastereoselectivities (>20:1).     

Direct Synthesis of Highly Substituted Pyrroles and Dihydropyrroles Using Linear Selective Hydroacylation Reactions

Rhodium(I) catalysts incorporating small bite‐angle diphosphine ligands, such as (Cy₂P)₂NMe or bis(diphenylphosphino)methane (dppm), are effective at catalysing the union of aldehydes and propargylic amines to deliver the linear hydroacylation adducts in good yields and with high selectivities. In situ treatment of the hydroacylation adducts with p‐TSA triggers a dehydrative cyclisation to provide the corresponding pyrroles. The use of allylic amines, in place of the propargylic substrates, delivers functionalised dihydropyrroles. The hydroacylation reactions can also be combined in a cascade process with a Rh^I‐catalysed Suzuki‐type coupling employing aryl boronic acids, providing a three‐component assembly of highly substituted pyrroles.     

Gadolinium Photocatalysis: Dearomative [2+2] Cycloaddition/Ring‐Expansion Sequence with Indoles

Lanthanide photocatalysts are much less investigated in synthetic chemistry than rare and expensive late transition metals. We herein introduce Gd^III photocatalysis of a highly regioselective, intermolecular [2+2] photocycloaddition/ring‐expansion sequence with indoles, which could provide divergent access to cyclopenta[b]indoles and indolines. A simple and commercially available Gd(OTf)₃ salt is sufficient for this visible‐violet‐light‐induced transformation. The reaction proceeds either through a transient or start‐to‐end dearomatization cascade and shows excellent regioselectivity (usually >95:5 r.r.), broad scope (59 examples), good functional group tolerance and facile scale‐up under mild, direct visible‐light‐excitation conditions. Mechanistic investigations reveal that direct excitation of the Gd(OTf)₃/indole mixture gives an excited state intermediate, which undergoes the subsequent [2+2] cycloaddition and cyclobutane‐expansion cascade.     

微波辅助一步合成2-取代吲哚

微波辐射下以取代苯胺1, 2-溴芳基乙酮2为原料, 在无催化剂条件下一步合成了一系列2-取代吲哚3. 该方法具操作简单、反应时间短、产率高等特点.     

Visible‐Light‐Induced Direct Photocatalytic Carboxylation of Indoles with CBr4/MeOH

Photocatalysis enables the cascade reactions of indoles and CBr₄ in MeOH through a C(sp²)?H functionalization/methanolysis sequence. The title reaction provides an efficient access to indole 2‐ and 3‐carboxylates in a single operation (no preinstallation of protecting as well as directing groups was required) with good yields under mild reaction conditions.     

Efficient Synthesis of 2-Ethoxycarbonyl Indoles

An efficient one-pot procedure for the synthesis of 2-ethoxycarbonyl indoles from commercially available materials has been developed. The one-step procedure involves in situ formation of the hydrazones from phenylhydrazine hydrochloride and ethyl pyruvate in the presence of bismuth nitrate followed by Fischer cyclization in polyphosphoric acid and ethanol. This method is efficient and simple.     

Palladium(0)‐Catalyzed Intermolecular Allylic Dearomatization of Indoles by a Formal [4+2] Cycloaddition Reaction

Bridged indoline derivatives were synthesized by an intermolecular Pd‐catalyzed allylic dearomatization reaction of substituted indoles. The reaction between indoles and allyl carbonates bearing a nucleophilic alcohol side‐chain proceeds in a cascade fashion, providing bridged indolines in excellent enantioselectivity.     

Allylic and Allenylic Dearomatization of Indoles Promoted by Graphene Oxide by Covalent Grafting Activation Mode

The site-selective allylative and allenylative dearomatization of indoles with alcohols was performed under carbocatalytic regime in the presence of graphene oxide (GO, 10 wt % loading) as the promoter. Metal-free conditions, absence of stoichiometric additive, environmentally friendly conditions (H₂O/CH₃CN, 55 °C, 6 h), broad substrate scope (33 examples, yield up to 92 %) and excellent site- and stereoselectivity characterize the present methodology. Moreover, a covalent activation model exerted by GO functionalities was corroborated by spectroscopic, experimental and computational evidences. Recovering and regeneration of the GO catalyst through simple acidic treatment was also documented.     

Palladium-Catalyzed Direct C2-and Further C7-Acylation of Indoles with Aldehydes

The palladium‐catalyzed direct C2‐ and further C7‐acylation of indoles with aldehydes have been developed. This method provides a convenient pathway toward a variety of mono‐ and diacylated indoles.     

Enantioselective Synthesis of 3a‐Amino‐Pyrroloindolines by Copper‐Catalyzed Direct Asymmetric Dearomative Amination of Tryptamines

A direct asymmetric dearomative amination of tryptamines with O‐(2,4‐dinitrophenyl)hydroxylamine (DPH) was achieved using CuBr‐bisoxazoline complex as a catalyst, affording 3a‐amino‐pyrroloindolines in good to excellent enantioselectivity under mild reaction conditions. Furthermore, the synthetic value of this method was demonstrated in the total synthesis of (?)‐psychotriasine in a highly concise manner.     

Stereodivergent Synthesis of Tetrahydrofuroindoles through Pd‐Catalyzed Asymmetric Dearomative Formal [3+2] Cycloaddition

A stereodivergent synthesis of tetrahydrofuroindoles through palladium‐catalyzed asymmetric dearomative formal [3+2] cycloaddition of nitroindoles with epoxybutenes was developed. The polarity of the solvent was found to play a key role in the diastereoselectivity. In toluene, good to excellent yields (70–99 %), diastereoselectivity (87/13‐>95/5 d.r.), and enantioselectivity (85/15–94/6 e.r.) were obtained, regardless of the properties of the substituents on nitroindoles. In acetonitrile, tetrahydrofuroindoles of a different diastereoisomer were produced with good to excellent yields (75–98 %) and stereoselectivity (78/22–93/7 d.r., 93/7–99/1 e.r.). Mechanistic studies were conducted to illustrate the origin of the diastereodivergency. The kinetic experiments indicate that the rate‐determining step of this reaction is different in different solvents. ESI‐MS experiments also support the existence of key palladium complex intermediates and the catalytic cycle of the reaction.     

手性磷酸催化的C（3）-取代吲哚和甲基乙烯基酮不对称串联反应

3位含有季碳手性中心的吲哚啉并环化合物是一类非常重要的化合物, 广泛存在于各种天然产物和具有生物活性的分子中. 化学家们发展了多种有效的途径来合成这类化合物. 其中以方便易得的吲哚衍生物为起始原料, 利用不对称去芳构化\环化串联的方法最为简单高效, 但多数工作都是从色胺或色醇衍生物出发, 合成二氢吡咯并吲哚啉或二氢呋喃并吲哚啉化合物. 因此, 发展其他类型的吲哚衍生物的不对称去芳构化\环化反应显得非常有必要. 作者课题组发展了手性磷酸催化的吲哚衍生物与甲基乙烯基酮的不对称Michael加成\环化串联反应. 以5 mol% (R)-SPINOL为骨架的手性磷酸(R)-4c为催化剂, 以中等到良好的收率和优秀的对映选择性构建了一系列手性吲哚[2,3-b]并氢化喹啉化合物, 而且该催化体系对于克级规模反应同样能够获得很好的结果.     

Asymmetric Dearomative Fluorination of 2-Naphthols with a Dicarboxylate Phase-Transfer Catalyst

A linked dicarboxylate phase-transfer catalyst enables smooth asymmetric dearomative fluorination of 2-naphthols with Selectfluor under mild conditions to give the corresponding 1-fluoronaphthalenone derivatives in a highly enantioselective manner. This reaction, which is compatible with a range of functional groups, is the first example of catalytic asymmetric fluorination of 2-naphthols, and is expected to be useful in the synthesis of bioactive molecules.     

One‐Pot Asymmetric Synthesis of Quaternary Pyrroloindolones through a Multicatalytic N‐Allylation/Hydroacylation Sequence

An intramolecular, quaternary carbon center forming hydroacylation of α‐substituted acrylates has been discovered. This interesting transformation can be readily incorporated into a multicatalytic tandem process enabled by a combination of nucleophilic tertiary amine and N‐heterocyclic carbene catalysis. With no additional stoichiometric base required, this transformation affords the quaternary pyrroloindolones with high levels of enantioselectivity.     

5-取代吲哚类化合物的合成

5－取代吲哚类化合物是一种重要的医药中间体。从古典的Fischer方法开始，有关合成5－取代吲哚类化合物的方法不断出现。本文对各种合成方法进行了介绍和评价。参考文献30篇。     

Enantioselective Cobalt-Catalyzed Intermolecular Hydroacylation of 1,6-Enynes

We report a cobalt-catalyzed hydroacylation of 1,6-enynes with exogenous aldehydes in a domino sequence to construct enantioenriched ketones. The products were obtained in good yields with excellent regio-, diastereo-, and enantioselectivity. Furthermore, the chiral products served as valuable precursors to access complex spirocyclic scaffolds with three contiguous stereocenters. The asymmetric hydroacylation process exhibited no C−H crossover and no KIE, thus indicating that the C−H bond cleavage was not involved in the turnover-limiting step.     

Iridium‐Catalyzed Coupling Reaction of Primary Alcohols with 2‐Alkynes Leading to Hydroacylation Products

A novel iridium‐catalyzed intermolecular coupling reaction of primary alcohols or aldehydes with 2‐alkynes was successfully achieved with high regioselectivity to give hydroacylation products such as α,β‐unsaturated ketones in good yields. The mechanistic investigation of the reaction strongly indicated that the coupling proceeds through the initial formation of homoallylic alcohols followed by dehydrogenation to β,γ‐unsatutated ketones and then isomerisation, which leads to the hydroacylation products.     

Gold(I)‐Catalyzed Dearomative [2+2]‐Cycloaddition of Indoles with Activated Allenes: A Combined Experimental–Computational Study

The gold‐catalyzed synthesis of methylidene 2,3‐cyclobutane‐indoles is documented through a combined experimental/computational investigation. Besides optimizing the racemic synthesis of the tricyclic indole compounds, the enantioselective variant is presented to its full extent. In particular, the scope of the reaction encompasses both aryloxyallenes and allenamides as electrophilic partners providing high yields and excellent stereochemical controls in the desired cycloadducts. The computational (DFT) investigation has fully elucidated the reaction mechanism providing clear evidence for a two‐step reaction. Two parallel reaction pathways explain the regioisomeric products obtained under kinetic and thermodynamic conditions. In both cases, the dearomative C?C bond‐forming event turned out to be the rate‐determining step.