Synthesis of Cyclopropenes and Fluorinated Cyclopropanes via Michael Initiated Ring Closure of Alkyl Triflones

A facile synthesis of cyclopropenes and fluorinated cyclopropanes from readily available alkyl triflones was developed. The reaction, regardless of electronic effect, gave products in good to excellent yields and moderate diastereoselectivity. The mechanism may involve tandem Michael addition of triflones/intramolecular nucleophilic cyclization (elimination of -SO₂CF₃)/elimination of fluoride.     

Organocatalytic Synthesis of Triflones Bearing Two Non-Adjacent Stereogenic Centers

Trifluoromethylsulfones (triflones) are useful compounds for synthesis and beyond. Yet, methods to access chiral triflones are scarce. Here, we present a mild and efficient organocatalytic method for the stereoselective synthesis of chiral triflones using α-aryl vinyl triflones, building blocks previously unexplored in asymmetric synthesis. The peptide-catalyzed reaction gives rise to a broad range of γ-triflylaldehydes with two non-adjacent stereogenic centers in high yields and stereoselectivities. A catalyst-controlled stereoselective protonation following a C−C bond formation is key to control over the absolute and relative configuration. Straightforward derivatization of the products into, e.g., disubstituted δ-sultones, γ-lactones, and pyrrolidine heterocycles highlights the synthetic versatility of the products.     

Diastereoselective Additive Trifluoromethylation/Halogenation of Isoxazole Triflones: Synthesis of All-Carbon-Functionalized Trifluoromethyl Isoxazoline Triflones

Highly functionalized 5-trifluoromethyl-2-isoxazoline derivatives featuring a triflyl (SO₂CF₃) group at the 4-position were successfully synthesized via diastereoselective trifluoromethylation and halogenation of isoxazole triflones using the Ruppert– Prakash reagent. The trifluoromethylation is quite general in terms of the substrates including 3,5-diaryl isoxazole triflones and 3-aryl-5-styrylisoxazole triflones to provide products in high yields with excellent diastereoselectivities. The highly functionalized 5-trifluoromethyl-2-isoxazoline derivatives are expected to be a new class of antiparasiticides. Thus the triflyl group both activates isoxazoles and the 4-postion of CF₃ adducts, and has a potential biological function.     

Ortho-lithiation reaction of aryl triflones

The ortho-lithiation of substituted arenes is a powerful methodology to synthesize ortho-substituted arenes. While a wide variety of directed metalation groups (DMGs) have been reported, trifluoromethyl sulfone has never been used. We disclose the first example of ortho-lithiation of aryl triflones. We found that the trifluoromethyl sulfonyl group is not only an important structural motif in biologically active molecules and specialty materials, but also an excellent DMG moiety for ortho-metalation reactions. The use of a base that causes steric hindrance, LTMP, is the key for successful transformation to furnish a variety of ortho-substituted aryl triflones in good yields. Further functionalization of resulting ortho-substituted aryl triflones was demonstrated by metal-catalyzed coupling reactions.     

Synthesis of Fischer indole derivatives using carboxyl-functionalized ionic liquid as an efficient and recyclable catalyst

Fischer indole cyclization of phenylhydrazine and various ketones using carboxyl-functionalized ionic liquid, 1-carboxymethyl-3-methylimidazolium tetrafluoroborate (abbreviated as [cmmim][BF4]) as catalyst was successfully performed. The yields of thetarget compounds were 80-92%, the purities were 96-98%. The catalyst could be rocovered and reused for at least six times without significant loss in activity.     

Comparative study of the Kumada, Negishi, Stille, and Suzuki-Miyaura reactions in the synthesis of the indole alkaloids hippadine and pratosine

The total synthesis of hippadine by a tandem metalation/cross-coupling/lactamization strategy was investigated starting from either 7-bromoindole or a 6-halogenated methyl piperonate. The Kumada and Negishi cross-coupling reactions failed to provide any of the desired product. However, the Stille and Suzuki reactions furnished hippadine in low yields starting from the electron-deficient methyl 6-iodo- and 6-bromopiperonate, respectively. Starting from the metalated indole, only the Suzuki reaction occurred, affording hippadine in 67-74% and pratosine in 62% isolated yield.     

Microwave Promoted and Improved Thermal Synthesis of Spiro[Indole‐Pyranobenzopyrans] and Spiro[Indole‐Pyranoimidazoles]

Spiro[indole‐pyranoimidazoles] ( 5 ) and spiro[indole‐pyranobenzopyrans] ( 6 ) are readily synthesized in one step in 86–92 and 91–97% yields by the Michael condensation of 3‐dicyanomethylene‐2H‐indol‐2‐ones ( 2 ) with 1‐phenyl‐2‐thiohydantoin ( 3 ) and 4‐hydroxy‐2H‐1‐benzopyran‐2‐one ( 4 ), respectively, without using any catalyst under different reaction conditions (conventional heating and microwave irradiation using (a) polar solvents (b) neutral alumina/silica gel as inorganic solid support in solvent free conditions). 2 was synthesized in situ by the Knoevenagel condensation of indole‐2,3‐dione ( 1 ) and malononitrile in the absence of any catalyst. 100% conversion was observed in most cases on TLC which also showed the formation of a single product. The comparison between the various methods is established.     

Synthesis of 3-alkenylated indole and bis(indol-3-yl) derivatives catalyzed by sulfonic acid-functionalized ionic liquid under ultrasound irradiation

A simple and efficient protocol has been developed for the synthesis of 3-alkenylated indoles and bis(indol-3-yl) derivatives by sulfonic acid-functionalized ionic liquid-catalyzed reaction of indole with 1,3-diketones/3-ketoesters under solvent-free ultrasound irradiation. Good to excellent yields (68–94%) are obtained in ultrasonication. The product of reaction is dependent on the substituent at C-2 position of indole. The catalyst is reusable and recyclable up to four cycles without significant loss of its catalytic activity. Compared with conventional heating, sound wave activation has the considerable advantages such as shorter reaction time, easy work-up, higher yields, and mild conditions.     

碘催化的2,2,2-三氟-1-(1H-吲哚-3-基)-乙醇与取代苯胺的傅-克苄基化反应

首次报道了分子碘I₂催化的吲哚衍生物与取代苯胺的傅-克苄基化反应, 合成了8个新型的3-取代吲哚的苯胺类衍生物,收率６５%～９８%,其结构经¹H NMR, ¹³C NMR和HR-ESI-MS表征。     

无溶剂、无催化剂条件下5-[(3-吲哚基)-芳甲基]-2,2-二甲基-l,3-二氧六环-4,6-二酮的合成

在无溶剂和催化剂条件下，由芳香醛、吲哚、丙二酸亚异丙酯的三组分缩合反 应，制备了5．[(3-吲哚基)-芳甲基]-2，2-二甲基-1，3-二氧六环-4，6-二酮，产 率为70％～85％，产物结构经～1H NMR，IR确证．     

Platinum-catalyzed multistep reactions of indoles with alkynyl alcohols

PtCl2 effectively catalyzes the multistep reaction of N-methyl indole (1 a) with pent-3-yn-1-ol (2 a) in THF at room temperature for 2 h to give indole derivative 3 a, which contains a five-membered cyclic ether group at C3 in 93% yield. Under similar reaction conditions, various substituted N-methyl indoles 1 b-h and indole (1 i) reacted efficiently with 2 a to afford the corresponding indole derivatives 3 b-h and 3 i in 48-91 and 72% yields. The results showed that N-methyl indoles with electron-donating substituents were more reactive affording higher product yields than those with electron-withdrawing groups. Likewise, various substituted but-3-yn-1-ols 2 b-e and other longer chain alkynyl alcohols 2 f-i also underwent a cyclization-addition reaction with N-methyl indole (1 a) to provide the corresponding cyclization-addition products 3 j-m and 3 a, 3 j, and 3 n-o in good to excellent yields. The present platinum-catalyzed cyclization-addition reaction can be further extended into N-methyl pyrrole. Mechanistically, the catalytic reaction proceeds by an intramolecular hydroalkoxylation of alkynyl alcohol to afford cyclic enol ether followed by the addition of the C--H bond of indole to the unsaturated moiety of cyclic enol ether providing the final product. Experimental evidence to support this proposed mechanism is provided.     

Synthesis of pyrrole and indole quinoxalinone and oxazinone derivatives by intramolecular copper-catalyzed reactions

Intramolecular N-arylation of pyrrole and indole carboxamides and carboxylates linked with a pendant haloarene by Cu-catalyzed reactions to synthesize pyrrole and indole quinoxalinone and oxazinone derivatives is reported. The ring closure reactions were carried out by conventional heating and MW irradiation. The use of conventional heating affords moderate to good yields of the quinoxalinone and oxazinone derivatives (34-72%), while by using MW heating the best results are obtained (41-99%).     

Regioselective 1,3-Dipolar Cycloaddition Reactions of Unsymmetrical Münchnones (1,3-Oxazolium-5-olates) with 2- and 3-Nitroindoles. A New Synthesis of Pyrrolo[3,4-b]indoles

The unsymmetrical mesoionic münchnones 13 (3-benzyl-2-methyl-4-phenyl-1,3-oxazolium-5-olate) and 14 (3-benzyl-4-methyl-2-phenyl-1,3-oxazolium-5-olate) react with the N-protected 2- and 3-nitroindoles 1 (ethyl 2-nitroindole-1-carboxylate), 6 (3-nitro-1-(phenylsulfonyl)indole), and 17 (ethyl 3-nitroindole-1-carboxylate) in refluxing THF to afford in good to excellent yields the pyrrolo[3,4-b]indoles 15 (2-benzyl-1-methyl-3-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 16 (2-benzyl-3-methyl-1-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 18 (2-benzyl-1-methyl-3-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole), and 19 (2-benzyl-3-methyl-1-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole). In several cases the regiochemistry, which is opposite to that predicted by FMO theory, is very high and leads essentially to a single pyrrolo[3,4-b]indole; e.g., 6+13→19 in 74% yield.     

TRANSIENT INTERMEDIATES IN INTRAMOLECULARLY PHOTOSENSITIZED PYRIMIDINE DIMER SPLITTING BY INDOLE DERIVATIVES

Abstract— Intramolecularly photosensitized pyrimidine dimer splitting can serve as a model for some aspects of the monomerization of dimers in the enzyme-substrate complex composed of a photolyase and UV-damaged DNA. We studied compounds in which a pyrimidine dimer was covalently linked either to indole or to 5-methoxyindole. Laser flash photolysis studies revealed that the normally observed photoejection of electrons from the indole or the 5-methoxyindole to solvent was diminished by an order of magnitude for indoles with dimer attached (dimer-indole and dimer-methoxyindole). The fluorescence lifetime of dimer-indole in aqueous methanol was 0.85 ns, whereas that of the corresponding indole without attached dimer (tryptophol) was 9.7 ns. Similar results were obtained for the dimer-methoxyindole (0.53 ns) and 5-methoxytryptophol (4.6 ns). The quantum yield of dimer splitting for the dimer-methoxyindole (φ₂₈₇K7 = 0.08) was only slightly greater than the value found earlier for the dimer bearing the unsubstituted indole (4>_2K7= 0.04). Transient absorption spectroscopy also revealed lower yields of indole radical cations following laser flash photolysis of dimer-indole compared to the indole without attached dimer. Dimer-methoxyindole behaved similarly. These results are interpreted in terms of an enhanced rate of radiationless relaxation of the indole and methoxyindole excited singlet states in dimer-indoles. The possible quenching of the indole and methoxyindole excited states via electron abstraction by the covalently linked dimer is discussed.     

Assembly of conjugated enynes and substituted indoles via CuI/amino acid-catalyzed coupling of 1-alkynes with vinyl iodides and 2-bromotrifluoroacetanilides

Cross-coupling of 1-alkynes with vinyl iodides occurs at 80 degrees C in dioxane catalyzed by CuI/N,N-dimethylglycine to afford conjugated enynes in good to excellent yields. Heating a mixture of 2-bromotrifluoroacetanilide, 1-alkyne, 2 mol % of CuI, 6 mol % of L-proline, and K(2)CO(3) in DMF at 80 degrees C leads to the formation of the corresponding indole. This conversion involves a CuI/L-proline-catalyzed coupling between aryl bromide and the 1-alkyne followed by a CuI-mediated cyclization process. An ortho-substituent effect directed by NHCOCF3 enables the reaction to proceed under these mild conditions. Both aryl acetylenes and O-protected propargyl alcohol can be applied, leading to 5-, 6-, or 7-substituted 2-aryl and protected 2-hydroxymethyl indoles in good yields. With simple aliphatic alkynes, however, lower yields were observed.     

A synthetic method for palladium-catalyzed stannylation at the 5- and 6-benzo positions of indoles

The stannylation of indole derivatives proceeds in good yields under palladium catalysis (5 mol %) without protection of the indolic nitrogen. The general utility of both PdCl(2)(PhCN)(2)/PCy(3) and Pd(2)dba(3)/PCy(3) as catalytic systems for the stannylation of three indole derivatives, with varying degrees of electron density, is presented.     

Novel biodegradable protonic ionic liquid for the Fischer indole synthesis reaction

Novel eco-friendly tetramethylguanidinium propanesulfonic acid trifluoromethylacetate ([TMGHPS][TFA]) ionic liquid was developed as catalyst and medium for the Fischer indole synthesis of a wide variety of hydrazines and ketones. The indole products were isolated in high yields and with minimal amounts of organic solvent. This reaction showed that [TMGHPS][TFA] can be regenerated and reused with reproducible yields without eroding the integrity of the ionic liquid.     

INFLUENCE OF THE ENVIRONMENT ON THE EXCITATION WAVELENGTH DEPENDENCE OF THE FLUORESCENCE QUANTUM YIELD OF INDOLE

Abstract— The influence of excitation wavelength, pH, oxygen and solvents, upon fluorescence quantum yields, were measured for insole Indole in neutral aqueous solution exhibits the same wavelength dependence as tryptophan, which indicates that COO- absorption is not responsible for the effect. Parameters such as pH and oxygen influence only the absolute fluorescence quantum yields but not their relative variation with wavelength, indicating competition with fluorescence emission for S1 deactivation. without any influence upon deactivation of higher excited states. In contrast, solvents exhibit a specific influence upon the wavelength dependence; for indole, the decrease of fluorescence yield excited around 215 nm, compared with the yield in the first absorption band is about 40% in water, 10% in acetonitrile, 70% in n-hexane and cyclohexane, whereas no appreciable decrease occurs in methanol, ethanol or n-butanol. These observations, together with the Stokes shifts of the emission spectra, may be well correlated with Kosower's Z-values, expressing microscopic solvent-solute interactions.     

无溶剂氧化亚锡催化合成2-[(3-吲哚基)-甲基]丙二酸二甲酯衍生物

在氧化亚锡催化下,吲哚、醛和丙二酸二甲酯在无溶剂条件下三组分反应合成了10种2-[(3-吲哚基)-甲基]丙二酸二甲酯衍生物。 反应无溶剂污染,反应条件温和,收率为58%~74%。 讨论了反应速度与取代基的关系,探讨了可能的缩合反应机理,并应用¹H NMR、¹³C NMR、IR等技术手段确定了产品的结构。     

Scope and mechanism of the Pd(II)-catalyzed arylation/carboalkoxylation of unactivated olefins with indoles

Treatment of 1-methyl-2-(4-pentenyl)indole (5) with a catalytic amount of [PdCl2(MeCN)2] (2; 5 mol %) and a stoichiometric amount of CuCl2 (3 equiv) in methanol under CO (1 atm) at room temperature for 30 min gives methyl (9-methyl-2,3,4,9-tetrahydro-4-carbazolyl)acetate (6), which was isolated in 83% yield. A number of 2- and 3-alkenyl indoles undergo a similar palladium-catalyzed cyclization/carboalkoxylation to give the corresponding polycyclic indole derivatives in moderate to excellent yields with excellent regio- and diastereoselectivity. Under similar conditions, vinyl arenes undergo intermolecular arylation/carboalkoxylation with indoles to give 3-(1-aryl-2-carbomethoxyethyl) indoles in moderate yield with high regioselectivity. Stereochemical analyses of the palladium-catalyzed cyclization/carboalkoxylation of both 2- and 3-alkenyl indoles are in agreement with mechanisms involving outer-sphere attack of the indole on a palladium-olefin complex followed by alpha-migratory insertion of CO and methanolysis of the resulting acyl palladium intermediate. CuCl2 functions as the terminal oxidant in this palladium-catalyzed cyclization/carboalkoxylation of alkenyl indoles and also significantly increases the rate of reaction of 2 with the alkenyl indole to form the corresponding acyl palladium complex. Spectroscopic studies are in agreement with the intermediacy of a heterobimetallic Pd/Cu complex as the active catalyst in this reaction.