Rearrangement of 3,3-disubstituted indolenines and synthesis of 2,3-substituted indoles

Synthesis of 2,3-substituted indoles from phenylhydrazine and alpha-branched aldehydes via rearrangement of 3,3-disubstituted indolenine intermediates is reported. [reaction: see text]     

PtCl2-catalyzed reactions of o-alkynylanilines with ethyl propiolate and dimethyl acetylenedicarboxylate

The PtCl₂-catalyzed reactions between indoles and ethyl propiolate gave rise to mono and double addition products. The composition of the products was largely influenced by the substituents on the indoles as well as the amount of ethyl propiolate used. o-Alkynylanilines reacted with ethyl propiolate and dimethyl acetylenedicarboxylate under the catalysis of PtCl₂ to generate the corresponding 2,3-disubstituted indoles. The reaction proceeded by following a sequential cyclization/intermolecular addition pathway.     

A new synthesis of 2,3-disubstituted indoles

A novel synthesis of 2,3-disubstituted indoles starting from N-alkyl-N-propvnyl anilines is described. The reactions employed are analogous to the thermal rearrangement of aryl propynyl sulfoxides.     

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.     

Iridium- and ruthenium-catalysed synthesis of 2,3-disubstituted indoles from anilines and vicinal diols

A straightforward and atom-economical method is described for the synthesis of 2,3-disubstituted indoles. Anilines and 1,2-diols are condensed under neat conditions with catalytic amounts of either [Cp*IrCl(2)](2)/MsOH or RuCl(3)·xH(2)O/phosphine (phosphine = PPh(3) or xantphos). The reaction does not require any stoichiometric additives and only produces water and dihydrogen as byproducts. Anilines containing methyl, methoxy, chloro and fluoro substituents can participate in the cyclocondensation. Meta-substituted anilines give good regioselectivity for 6-substituted indoles, while unsymmetrical diols afford excellent regioselectivity for the indole isomer with an aryl or large alkyl group in the 2-position. The mechanism for the cyclocondensation presumably involves initial formation of the α-hydroxyketone from the diol. The ketone subsequently reacts with aniline to generate the α-hydroxyimine which rearranges to the corresponding α-aminoketone. Acid- or metal-catalysed electrophilic ring-closure with the release of water then furnishes the indole product.     

Efficient and Straightforward Synthesis of Tetrahydrocarbazoles and 2,3-Dimethyl Indoles Catalyzed by CAN

A simple protocol was established to synthesize 2,3-dialkyl indoles and various tetrahydrocarbazoles via Fischer indole synthesis. This method uses ceric ammonium nitrate as a catalyst for the Fischer indole synthesis with substituted phenyl hydrazine hydrochlorides and 2-butanone, phenyl propanal, and cyclohexanone. This process is a practical synthetic method for the preparation of various 2,3-disubstituted alkyl indoles and tetrahydrocarbazoles.     

An efficient route to 2,3-disubstituted indoles via reductive alkylation using H2 as reductant

An efficient route to 2,3-disubstituted indoles was developed via reductive alkylation of 2-substituted indoles using hydrogen as a clean and atom economic reductant under ambient pressure.     

Indole synthesis by radical cyclization of o-alkenylphenyl isocyanides and its application to the total synthesis of natural products

Development of indole synthesis by tin-mediated radical cyclization of o-alkenylphenyl isocyanide is described. Upon heating o-alkenylphenyl isocyanide in the presence of tri-n-butyltin hydride and AIBN, 2-stannyl-3-substituted indole was formed via 5-exo-trig cyclization of the imidoyl radical intermediate. After acidic workup, 3-substituted indoles were isolated. For substrates bearing simple alkyl groups, a substantial amount of tetrahydroquinoline derivatives were generated through 6-endo-trig cyclization. This undesired cyclization was suppressed by using an excess amount (five equivalents based on o-alkenylphenyl isocyanide) of ethanethiol instead of tri-n-butyltin hydride. The 2-stannylindole intermediates proved to be a suitable substrate for Stille coupling, giving 2,3-disubstituted indoles in a one-pot procedure. In addition, the 2-stannylindole intermediates could be converted to 2-iodoindoles by treatment with iodine or N-iodosuccinimide. The 2-iodoindoles thus obtained served as good substrates for Heck reactions, Stille couplings, Suzuki couplings, and palladium-mediated carbonylations, to afford a variety of 2,3-disubstituted indoles. The utility of this protocol was demonstrated by application to synthetic studies on gelsemine and discorhabdin A, and the total synthesis of an aspidosperma alkaloid, (-)-vindoline.     

Palladium-catalyzed beta-allylation of 2,3-disubstituted indoles

Given the prevalence of the indole nucleus in biologically active compounds, the direct C3-functionalization of 2,3-disubstituted indoles represents an important problem. Described is a general, high-yielding method for the palladium-catalyzed beta-allylation of carba- and heterocycle fused indoles, including complex natural product substrates.     

The photochemistry of 1-alkenylbenzotriazoles : Methodology for the synthesis of indoles

The synthesis of 2-substituted, 3-substituted, and 2,3-disubstituted indoles based on the photolysis of 1-alkenylbenzotriazoles is described along with the application of this method to the synthesis of the 2,3-dihydropyrrolo[1,2-a]indole nucleus of the mitomycin antitumor antibiotics.     

3-(2-Alken-1-one-2-yl)indoles through the palladium-catalyzed reaction of 2-alkynyltrifluoroacetanilides with cyclic α-iodoenones

α-Iodoenones can be efficiently employed as organic electrophiles in the Pd-catalyzed synthesis of 2,3-disubstituted indoles from 2-alkynyltrifluoroacetanilides. Best results were obtained using the weak ligand As(Ph)₃. The methodology reported provides an efficient entry to indoles bearing a 2-alkenon-2-yl moiety linked in the 3-position, that possesses a scarcely reported substitution pattern.     

Synthesis of carbazoles related to carbazomycin,hyellazole and ellipticine.

Two synthetic routes to 1,2-disubstituted carbazoles are described. The first involves condensation of 2-alkyl-substituted indoles with 2,3-unsaturated ketones in the presence of Pd/C and molecular sieves, the second is based on the reaction of a 2-vinylic indole with the Vilsmeier reagent. The vinylic indoles were prepared by a Fischer indole synthesis, or via 1-benzenesulphonyl-2-lithioindole.     

Pd-Catalyzed asymmetric hydrogenation of 3-(toluenesulfonamidoalkyl)indoles

A series of 2-substituted 3-(toluenesulfonamidoalkyl)indoles was synthesized by application of (EtO)(2)POH or iodine as the catalyst, and was hydrogenated using chiral Pd catalyst, giving the 2,3-disubstituted indolines with up to 97% ee.     

Facile Installation of 2‐Reverse Prenyl Functionality into Indoles by a Tandem N‐Alkylation–Aza‐Cope Rearrangement Reaction and Its Application in Synthesis

An unprecedented tandem N‐alkylation–ionic aza‐Cope (or Claisen) rearrangement–hydrolysis reaction of readily available indolyl bromides with enamines is described. Due to the complicated nature of the two processes, an operationally simple N‐alkylation and subsequent microwave‐irradiated ionic aza‐Cope rearrangement–hydrolysis process has been uncovered. The tandem reaction serves as a powerful approach to the preparation of synthetically and biologically important, but challenging, 2‐reverse quaternary‐centered prenylated indoles with high efficiency. Notably, unusual nonaromatic 3‐methylene‐2,3‐dihydro‐1H‐indole architectures, instead of aromatic indoles, are produced. Furthermore, the aza‐Cope rearrangement reaction proceeds highly regioselectively to give the quaternary‐centered reverse prenyl functionality, which often produces a mixture of two regioisomers by reported methods. The synthetic value of the resulting nonaromatic 3‐methylene‐2,3‐dihydro‐1H‐indole architectures has been demonstrated as versatile building blocks in the efficient synthesis of structurally diverse 2‐reverse prenylated indoles, such as indolines, indole‐fused sultams and lactams, and the natural product bruceolline D.     

Facile access to polysubstituted indoles via a cascade Cu-catalyzed arylation-condensation process

Cu(I)/L-proline-catalyzed cross-coupling of 2-halotrifluoroacetanilides with beta-keto esters and amides followed by in situ acidic hydrolysis delivered 2,3-disubstituted indoles. The halides bearing a strong electron-withdrawing group in the 4-position can undergo in situ basic hydrolysis to provide the corresponding indoles. Polysubstituted indoles can be prepared from substituted 2-halotrifluoroacetanilides with high regioselectivity.     

Divergent outcomes of gold(I)-catalyzed indole additions to 3,3-disubstituted cyclopropenes

Depending on the conditions employed, gold(I)-catalyzed addition of indoles to 3,3-disubstituted cyclopropenes can be controlled to yield either 3-(E)-vinylindoles (3) or bis-indolylalkanes (4). If the cyclopropene substituents are sterically bulky, unprecedented gold-catalyzed oxidation under air occurs to yield bis-indolylalkene (5) and epoxide (6) at room temperature.     

Construction of heterocyclic compounds by use of alpha-diazophosphonates: new one-pot syntheses of indoles and isocoumarins

[reaction: see text] alpha-Diazophosphonates, which have extremely useful properties from a synthetic point of view, are disclosed as 1,1-ambiphilic one-carbon building blocks for one-pot construction of various heterocyclic compounds. They are easily prepared and have higher stability by the effect of the phosphoryl group than corresponding alpha-diazocarbonyl compounds. Using this synthon, we have developed a novel, mild, and efficient synthetic method of 2,3-disubstituted indoles and 3,4-disubstituted isocoumarins.     

新型吲哚抗癌试剂的设计与合成

以邻碘苯胺和苯乙炔为原料,经10步反应合成了2,3-二取代的新型吲哚抗癌试剂,总收率33%~37%,其结构经1H NMR和MS表征。     

Heterodiene syntheses—XXIV: Changes in the reactivity of 2-oxoindolin-3-ylidene derivatives with ethylvinylether induced by electron-withdrawing groups. The importance of the lumo coefficients

Ethylvinylether reacts in acetonitrile with 1 - acetyl - 2 - oxoindolin - 3 - ylidene derivatives β,β -disubstituted with electron-withdrawing substituents. When the β-substituents act by inductive effect alone, a regiospecific β-attack² occurred giving rise, through a 1,4 - cycloaddition, to 2,3 - dihydropyran[2,3-b]indoles. As a by product Michael adduct can be obtained. When the β-substituent act by conjugative effect also, a regiospecific α-attack² occurred giving rise to spiro - dihydropyrane or - cyclobutane - 2 - oxoindolines depending on the nature of the substituents.In a less polar solvent, the latter ones are formed together with the adduct arising from the regioisomeric β-attack.The overall reactivity can be rationalized in terms of LUMO coefficients of the hetcrodiene and of different stabilization offered by the solvent to the various reaction pathways.     

2,3-disubstituted benzofuran and indole by copper-mediated C-C bond extension reaction of 3-zinciobenzoheterole

[reaction: see text] A metalative 5-endo-dig cyclization reaction of 2-ynylphenoles or anilines effected by BuLi and ZnCl(2) produces 3-zinciobenzoheteroles in excellent yield. These intermediates have been transmetalated to the corresponding cuprates and allowed to react with electrophiles to produce a variety of 2,3-disubstituted benzofurans and indoles.