A new entry to polycyclic indole skeletons via palladium-catalyzed intramolecular heteroannulation

[reaction: see text] A one-step method was developed for elaboration of a variety of polycyclic indole skeletons via a novel palladium-catalyzed intramolecular indolization of 2-chloroanilines bearing tethered acetylenes. This novel intramolecular indolization method unveils an unusual syn amidopalladation pathway of a tethered alkyne.     

Synthesis of 1,2-five-ring-annellated barrelenes via the intramolecular Diels-Alder reaction of acetylenic derivatives

The intramolecular Diels-Alder reaction conducted with acetylenic acylureas, obtained from carbodiimides, and the acetylenic acid 5 and its derivatives 13 gave the 1,2-annellated barrelene 14 (from 13a ) and the benzobarrelenes 8 (from 5 ) and 15 (from 13b ); in the case of 3-butynoic acid ( 1 ),[1,3]-H shift were observed. The formation of the azabarrelenes 16 (from 13c ) as an intermediate is postulated which looses HCN to afford the indolinone 17 . The acylureas 6 and 9 underwent isocyanate cleavage instead of [4+2] cyclization.     

Highly diastereoselective synthesis of new indolopyrroloquinolines through intramolecular imino Diels-Alder reactions

A new, efficient and highly diastereoselective one-pot synthesis of cis-fused indolopyrroloquinoline derivatives is described through imino Diels-Alder reaction of substituted anilines or naphthylamines with N-prenylated-2-formyl-3-chloroindoles catalyzed by La(OTf)₃.     

Copper-catalyzed domino intramolecular cyclization: a facile and efficient approach to polycyclic indole derivatives

A mild and efficient Cu(2)O-catalyzed domino intramolecular C-N coupling/C-Y (Y = O, S, N) bond formation was successfully achieved. Thus oxazino[3,2-a]indole, thiazino[3,2-a]indole and indolo[2,1-b]quinazoline derivatives were facilely assembled from readily accessible gem-dibromovinyl systems. The protocol is general and practical, affording a variety of the indole-incorporated products in good to excellent yields even under air atmosphere.     

A one-pot synthetic approach to the functionalized isomeric ellipticine derivatives through an imino Diels-Alder reaction

An efficient, three component, one-pot synthesis of new isomeric ellipticine derivatives prepared through an imino Diels-Alder reaction of 3-aminocarbazoles and substituted benzaldehydes with electron-rich alkenes such as 3,4-dihydro-2H-pyran, 2,3- dihydrofuran and ethyl vinyl ether catalyzed by InCl₃ (10 mol %) in ionic liquid is reported. In the case of substituted benzaldehydes, reductive amination is observed.     

Versatile and mild HCl-catalyzed cationic imino Diels-Alder reaction for the synthesis of new tetrahydroquinoline derivatives

A simple, inexpensive, and mild one-pot methodology for the synthesis of novel 4-aryl-3-methyl-1,2,3,4-tetrahydroquinolines derivatives using aqueous HCl as catalyst has been developed. The key step involves the formal inverse-electron-demand [4π⁺ + 2π] cycloaddition reaction of in situ–generated cationic 2-azadienes with arylpropenes (isoeugenol and trans-anethole). Iminium ion intermediates are generated through the condensation between N-benzylanilines and formalin. The products are obtained with good to excellent yields and high trans-diastereoselectivity. Further catalytic hydrogenation (Pd/C) allowed debenzylation to successfully obtain the respective 4-aryl-3-methyl-N-H-tetrahydroquinolines of interest. Recent reports suggest that these compounds could serve as interesting models in pharmacological studies against parasites that cause the most common tropical diseases.     

Novel ring transfer reaction of furans via intramolecular Diels-Alder reaction of allene intermediate: a new double annulation reaction

A novel ring tansfer reaction of furans to fused furans by tandem intramolecular Diels-Alder reaction and base-catalyzed ring-opening of the adducts has been developed.     

Facile entry to polycyclic indolylhydroquinoline skeletons via tandem C-alkylation and intramolecular S-alkylation

An efficient, single step synthesis of hitherto unknown indole-annulated pentacyclic indolylhydroquinolines via tandem C-alkylation and intramolecular S-alkylation of indolin-2-thiones with N-alkylquinolinium salts in excellent yields (83-95%) is reported. This facile approach provides a powerful entry into polycyclic structures containing nitrogen and sulfur related to alkaloids. The structure of the product was determined by Röntgen crystal structure analysis.     

Synthesis of N-substituted indole derivatives via PIFA-mediated intramolecular cyclization

[Structure: see text] A variety of N-arylated and N-alkylated indole derivatives were synthesized by way of a phenyliodine bis(trifluoroacetate) (PIFA)-mediated intramolecular cyclization. This novel method allows for the construction of an indole skeleton by joining the N-atom on the side chain to the benzene ring at the last synthetic step. Other novel pyrrole-fused aromatic compounds can also be achieved by this method.     

Synthesis of aza polycyclic compounds derived from pyrrolidine, indolizidine, and indole via intramolecular Diels-Alder cycloadditions of neutral 2-azadienes

A method for the preparation of novel oxaza and diaza polycyclic 9-oxa-4-azaphenanthrene, 5H-pyrido[2,3-a]pyrrolizine, 5H,6H-pyrido[3,2-g]indolizine, and 5H,6H-indeno[2,1-a]indole is described, based on tandem reactions: aza-Wittig reaction of N-vinylic phosphazenes with functionalized aldehydes and an intramolecular aza-Diels-Alder reaction.     

A novel heterotricyclic assembly through intramolecular imino Diels-Alder reaction: synthesis of pyrrolo[3,4-b]quinolines

The synthesis of a series of hexahydropyrrolo[3,4-b]quinolines has been achieved in excellent yields by the reaction of aldimines derived from aromatic amines and N-prenylated aliphatic aldehydes in acetonitrile with InCl₃ as a catalyst in a short duration of time.     

Consecutive Rh(I)-catalyzed Alder-ene/Diels-Alder/Diels-Alder reaction sequence affording rapid entry to polycyclic compounds

Conversion of acyclic allenynes to polycyclic compounds using consecutive transition metal catalyzed carbon-carbon bond forming reactions in a single chemical operation is described. Reaction of an allenyne with a Rh(I) catalyst affords a cross-conjugated triene via a formal Alder-ene reaction. The triene then participates in a Rh(I)-catalyzed intramolecular [4+2] cycloaddition reaction to generate a new conjugated diene. An external dienophile is added to this diene which then undergoes a second [4+2] cycloaddition reaction to afford a complex polycyclic ring system. This reaction sequence demonstrates the synthetic potential of allenynes and cross conjugated trienes and highlights the rapid increases in molecular complexity that are possible by one-pot sequential transition metal catalyzed carbon-carbon bond forming reactions.     

Total synthesis of suaveoline and norsuaveoline via intramolecular oxazole-olefin Diels-Alder reaction

Total synthesis of two Rauwolfia alkaloids, suaveoline (1) and norsuaveoline (2), has been achieved through a highly stereoselective route starting from l-tryptophan methyl ester (9) and exploiting the intramolecular Diels-Alder reaction of the oxazole-olefin 16.     

Synthesis of the tricyclic core of vinigrol via an intramolecular Diels-Alder reaction

[reaction: see text] Herein, we present a successful synthesis of the tricyclic core of vinigrol (1). Our approach takes advantage of a highly regioselective intramolecular Diels-Alder reaction of the diene 11 to construct two rings of the tricyclic vinigrol skeleton 12.     

A novel entry to xanthones by an intramolecular Diels-Alder reaction involving 2-(1,2-dichlorovinyloxy) aryl dienones

A wide array of synthetic methods are described in the literature for the preparation of xanthones—a prominent class of tricyclic molecules that occur widely in nature. Majority of these reported methods involve linking the two aromatic rings and forming the central pyrone ring using a variety of classical and non-classical cyclization strategies. In a conceptually different approach, we describe here a new xanthone synthesis wherein both the pyrone and the second aromatic rings were forged in a single step by an intramolecular cycloaddition reaction involving 2-(1,2-dichlorovinyloxy) aryldienones.     

First asymmetric hetero Diels-Alder reaction of 1-sulfinyl dienes with nitroso derivatives. A new entry to the synthesis of optically pure 1,4-imino-L-ribitol derivatives

Hetero Diels-Alder (HDA) cycloaddition of chiral 1-p-tolylsulfinyl-1,3-pentadiene with benzyl nitrosoformate, under mild conditions, yields 2H-1,2-oxazine 3 with complete regioselectivity and pi-facial diastereoselectivity. Sequential osmylation and protection of the resulting glycol gives the oxazine 5 which is directly transformed into enantiomerically pure 1,4,5-trideoxy-1,4-imino-L-ribitol 8 by reduction under Pd/C.     

Allylic stereocontrol of the intramolecular Diels-Alder reaction

The stereochemical outcome of the intramolecular Diels-Alder reaction of ester-linked 1,3,8-nonatrienes can be controlled by substituents about a stereogenic center attached to C1. The scope and limitations of this approach have been investigated, with variation in substrate structure about the allylic stereocenter and the dienophile. The stereochemical outcomes of these reactions are explained by reference to B3 LYP/6-31G(d) transition structures. New insights into the conformational preferences of allylic alcohol derivatives are reported, results which allow an explanation of the differing levels of pi-diastereofacial selectivity and cis/trans (i.e. endo/exo) selectivity from the reaction.     

Three-component imino Diels-Alder reaction with essential oil and seeds of anise: generation of new tetrahydroquinolines

A simple and efficient one-pot method for the synthesis of 4-anisyl-2-phenyl-1,2,3,4-tetrahydroquinoline derivatives using a three-component imino Diels-Alder cycloaddition (Povarov reaction) between anilines, benzaldehyde, and trans-anethole in the presence of acidic catalysts is shown. New substituted tetrahydroquinolines are reported and their direct preparation from the anise essential oil is described. Also, a simple procedure of the same tetrahydroquinolines from the anise seeds under supercritical fluid (CO₂) conditions has been reported.     

Synthesis of latonduine derivatives via intramolecular Heck reaction

The synthesis of indole ring-fused benzazepinone series as latonduine derivatives has been developed via an intramolecular Heck reaction. The scope has been enlarged not only to indole moiety but also to pyrrolo and benzo[b]thiophene nuclei. Several derivatives prepared have been evaluated in vitro for their antiproliferative activities on breast cancer cell lines. Some of them showed promising cytotoxic activities.