Indole synthesis by controlled carbolithiation of o-aminostyrenes

An effective synthesis of the functionalized indole ring system has been developed from substituted o-aminostyrene starting material. Our methodology involves a novel cascade reaction sequence of alkyllithium addition to the styrene double bond and subsequent trapping of the intermediate organolithium with a suitable electrophile, followed by an in situ ring closure and dehydration to generate the indole ring. This new reaction sequence allows for the introduction of molecular diversity at all positions on the indole scaffold. The procedure was shown to be successful with a range of both C and N substituents on the o-aminostyrenes. The reaction sequence was tolerant to the reactivity range of alkyllithiums such as tert-, sec-, and n-butyllithium. The electrophiles used were DMF, which generated indole products with C-2 unsubstituted, and nitriles, which incorporated the nitrile substituent at C-2. The o-aminostyrene starting materials were generated by a Pd-catalyzed cross-coupling reaction of a vinyl boronic acid equivalent with the readily available substituted o-bromoanilines.     

Ytterbium triflate catalyzed synthesis of β-functionalized indole derivatives

Ytterbium triflate was shown to be effective in promoting the synthesis of substituted indole derivatives starting from indole, aldehydes, and dimethyl malonate by a Yonemitsu-type three component reaction. The whole process was carried out in solvent-free conditions and furnished the desired adducts in 42-67% yield.     

Tandem hydroformylation/Fischer indole synthesis: a novel and convenient approach to indoles from olefins

[reaction: see text] A novel one-pot synthesis of indole systems via tandem hydroformylation/Fischer indole synthesis starting from olefins and arylhydrazines is described. This tandem procedure leads directly to 3-substituted indoles if unsubstituted phenylhydrazine is used and to 3,5- respectively 3,7-disubstituted indoles if para- or ortho-substituted arylhydrazines are used.     

The first method for protection-deprotection of the indole 2,3-pi bond

[reaction: see text] The scope and generality of a new reaction of indoles with MTAD is discussed. In most cases the ene-type reaction proceeds within seconds or minutes at 0 degrees C to provide the urazole adducts in high yield. This reaction provides the first method for protecting the indole 2,3-double bond since the urazole adducts can be reconverted to the starting indole (retro-ene) simply by heating.     

Tetramic acids and indole derivatives from amino acid β-keto esters. Fine-tuning the conditions of the key Cu-catalyzed reaction

1,3,5-Trisubstituted tetramic acids and 2,3-disubstituted indole derivatives were prepared from β-keto esters derived from amino acids by their reaction with iodophenyl-2-trifluoroacetylamine under Cu-catalysis. Both heterocyclic systems were generated from the same starting materials by choice of the appropriate reaction conditions.     

Bismuth nitrate-catalyzed novel synthesis of pyrrole-substituted indolinones

Synthesis of indole derivatives bound to pyrroles is a challenge. In this letter, an expeditious synthesis of these types of molecules starting from isatins and 4-hydroxy proline via a bismuth nitrate-catalyzed reaction is described.     

Efficient, one-pot transformation of indoles into functionalized oxindole and spirooxindole systems under Swern conditions

The reaction of indole derivatives bearing a 3- or 4-hydroxyalkyl chain with dimethylsulfoxide and oxalyl chloride under Swern conditions led to a one-pot, three-component process involving three different synthetic transformations, namely oxidation of indole to oxindole, introduction of a chlorine substituent at the oxindole C-3 position and substitution of the hydroxyl group in the side chain by chlorine, in good to excellent overall yields. The same conditions, applied to a 2-methylindole, afforded a 2-formylindole derivative oxidized at its side chain. The reaction starting from one indole with a 2-hydroxyalkyl chain furnished 3-(2-hydroxyalkyl)oxindoles. Finally, application of the Swern conditions to derivatives of indole-3-propionic or -butyric acid afforded 3-spirooxindole lactones.     

NaBF4催化合成二吲哚甲烷类化合物

在乙醇水溶液中,以Na BF4为催化剂,通过吲哚与芳香醛间的串联反应合成了二吲哚甲烷衍生物。考察了催化剂种类、反应介质、温度、反应时间等因素对反应的影响,在优化条件下以较高产率得到了一系列目标产物。     

A straightforward one-pot multicomponent synthesis of polysubstituted pyrroles

Polysubstituted pyrroles were efficiently synthesized in moderate yields by a one-pot multicomponent reaction starting from primary amines, ethyl glyoxalate and 2-bromoacetophenones in the presence of pyridine in refluxing acetonitrile. This methodology was utilized to synthesize a highly substituted benz[g]indole.     

Stereoselective transformation of indole diazabicyclo[3.2.2]nonedione to azepinoindole

[reaction: see text] The synthesis of an indole diazabicyclo[3.2.2]nonedione derivative was achieved in a few steps starting from L-tryptophan. Reduction with borane-THF complex leads to fragmentation of the bicycle and the stereoselective formation of an azepinoindole derivative was observed.     

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.     

Intramolecular cyclization of delta-iminoacetylenes: a new entry to pyrazino[1,2-a]indoles

[reaction: see text] The synthesis of the pyrazino[1,2-a]indole nucleus was achieved by intramolecular cyclization of several 2-carbonyl-1-propargylindoles in the presence of ammonia. The reaction conditions were optimized using microwave heating and a pool of catalysts. Cyclization of 1-alkynylindole-2-carbaldehydes was easily accomplished under standard heating conditions, whereas microwave heating contributed to reduced reaction times and improved overall yields. Moreover, a fine-tuning of the microwave irradiation time made possible the selective synthesis of both pyrazino[1,2-a]indole isomers. TiCl4 proved the catalytic system of choice to achieve pyrazinoindoles in satisfactory yields starting from 1-alkynyl-2-acetylindoles and 1-alkynyl-2-benzoylindole derivatives. Also in these cases, microwave heating contributed to faster reactions and improved yields. The uncatalyzed versus catalyzed reaction mechanism is discussed.     

Alcaloides indoliques—CV: Préparation de dérives du yohimbane à partir de la corynanthéine. Réaction de prins intramoléculaire

Three yohimbane derivatives, 17,19β-dihydroxy yohimbane 2a and 2b and 19β-chloro-β-yohimbine 3, have been prepared starting from corynantheine. The reaction involved is a Prins cyclisation reaction, the mechanism of which is compared to the biosynthetic route proposed for yohimbane-type indole alkaloids.     

Efficient solvent-free synthesis of bis(indolyl)methanes on SiO<Subscript>2</Subscript> solid support under microwave irradiation

An efficient synthesis of bis(indolyl)methanes was developed. Bis(indolyl)methanes were synthesized starting from various aromatic aldehydes with indole under microwave irradiation and solvent-free conditions (85–98 %). Solid support SiO₂ was found to possess favorable catalytic and dispersancy parameters for the condensation reaction. Moreover, novel bis(indolyl)methanes containing an isoxazole ring were synthesized via this method in excellent yields (> 94 %) using 3-substituted isoxazole-5-carbaldehydes and indole.     

Unprecedented Multicomponent Reaction of Indoles,CS2 and Nitroarenes: Stereoselective Synthesis of (Z)-3-((Arylamino)methylene)indoline-2-thiones

An efficient method for the stereoselective synthesis of (Z)-3-((arylamino)methylene)indoline-2-thiones have been developed via a novel multicomponent reaction of indoles, CS₂ and nitroarenes. A range of functionalized indoline-2-thiones were prepared in moderate to good yields from easily available starting materials. The indoline-2-thione products can be easily derivatized to give biologically active thieno[2,3-b]indole and thiopyrano[2,3-b]indole skeletons in high yields.     

Total synthesis of (+/-)-goniomitine via a formal nitrile/donor-acceptor cyclopropane [3 + 2] cyclization

The total synthesis of (+/-)-goniomitine has been accomplished in 17 linear steps with 5.2% overall yield starting from commercially available delta-valerolactam. A synthetic highlight includes the first application of a formal [3 + 2] cycloaddition between a highly functionalized nitrile and a donor-acceptor cyclopropane to prepare an indole nucleus. The use of a microwave reactor is shown to greatly improve the reaction times for two steps.     

Synthesis the Analog of Strictosidine and Vincoside from Geniposide

Strictosidine (1), a well-known monoterpene indole alkaloid glycoside^[1,2], is the precursor and building stone of nearly 2200 indole and related alkaloids and was first isolated by G. N. Smith from Rhazya^[3]. It is constructed in vivo from secologanin (2) and tryptamine (3) by plant species^[1], as well as in vitro in the presence of the enzyme strictosidine synthase, or under biomimetic conditions in aqueous solution at pH 4.5 (Scheme 1). In the coupling reaction, a new chiral center is formed with complete stereoselectivity in the presence of the enzyme, or together with vincoside (4) in a 1:1 ratio in the absence of the enzyme. Here we describe the preparation of the analog of strictosidine and vincoside from geniposide via the biomimetic conditions. 7 and 8 can be used as the starting material to synthesize other analogs of indole and related alkaloids.     

Synthesis of Arcyriarubin A and Arcyriaflavin A via Cross-Coupling of Indolylboronic Acid with Dibromomaleimides

Arcyriarubin A was first isolated by Steglich in 1980; it is also the key intermediate in the synthesis of indolocarbazole compounds. A new synthetic approach to the natural products arcyriaflavin A and arcyriarubin A is described. The key step is a Suzuki cross-coupling reaction using indolylboronic acid as the starting material. The preparation of arcyriaflavin A was accomplished in eight steps from indole for a total yield of 21%.     

Dienamine and Friedel–Crafts One‐Pot Synthesis,and Antitumor Evaluation of Diheteroarylalkanals

An asymmetric synthesis of diheteroarylalkanals through one‐pot dienamine and Friedel–Crafts reaction is presented. The reaction tolerates a large variety of substituents at different positions of the starting aldehyde and also in the indole nucleophile, and a range of diheterocyclic alkanals can be achieved. Furthermore, we have studied the antiproliferative activity of these new compounds in representative cancer tumor cell lines.     

Photoreaction between 2-benzoylthiophene and phenol or indole

Laser flash photolysis, density functional theory (DFT) calculations, and product studies have been performed to understand the mechanism of photoreduction of 2-benzoylthiophene (BT) in the presence of phenol or indole. Time-resolved experiments showed that BT ketyl (BTH) and phenoxy (PhO) or indolyl (In) radicals are generated with high rate constants and quantum yields close to 1. However, low conversions (specially in the case of indole) of the starting reagents are obtained upon prolonged lamp irradiation, indicating that recombination within the radical pairs must occur to a large extent, regenerating the starting materials. The solvent-dependence of the quenching rate constants, together with DFT theoretical studies, indicate fundamental differences between the mechanisms of the reaction of BT triplet with phenol and indole. Thus, data for phenol agree with the involvement of a hydrogen-bonded exciplex BT(.)HOPh, where concerted electron and proton transfer leads to the BTH(.)OPh radical pair. However, in the case of indole, electron transfer at the BT(.)HIn stage precedes proton transfer. Finally, C-C cross-coupling products have been isolated and characterized in the preparative irradiation of BT in the presence of phenol and indole. The structures of the products have been confirmed by alternative synthesis.