21909-49-9Relevant academic research and scientific papers
Direct Synthesis of Indoles from Azoarenes and Ketones with Bis(neopentylglycolato)diboron Using 4,4′-Bipyridyl as an Organocatalyst
Misal Castro, Luis C.,Sultan, Ibrahim,Nishi, Kohei,Tsurugi, Hayato,Mashima, Kazushi
, p. 3287 - 3299 (2021/03/01)
Multifunctionalized indole derivatives were prepared by reducing azoarenes in the presence of ketones and bis(neopentylglycolato)diboron (B2nep2) with a catalytic amount of 4,4′-bipyridyl under neutral reaction conditions, where 4,4′-bipyridyl acted as an organocatalyst to activate the B-B bond of B2nep2 and form N,N′-diboryl-1,2-diarylhydrazines as key intermediates. Further reaction of N,N′-diboryl-1,2-diarylhydrazines with ketones afforded N-vinyl-1,2-diarylhydrazines, which rearranged to the corresponding indoles via the Fischer indole mechanism. This organocatalytic system was applied to diverse alkyl cyclic ketones, dialkyl, and alkyl/aryl ketones, including heteroatoms. Methyl alkyl ketones gave the corresponding 2-methyl-3-substituted indoles in a regioselective manner. This protocol allowed us to expand the preparation of indoles having high compatibility with not only electron-donating and electron-withdrawing groups but also N- and O-protecting functional groups.
Allylic and Allenylic Dearomatization of Indoles Promoted by Graphene Oxide by Covalent Grafting Activation Mode
Lombardi, Lorenzo,Bellini, Daniele,Bottoni, Andrea,Calvaresi, Matteo,Monari, Magda,Kovtun, Alessandro,Palermo, Vincenzo,Melucci, Manuela,Bandini, Marco
supporting information, p. 10427 - 10432 (2020/07/24)
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 percent 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 percent) 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.
Biocatalytic Strategy for Highly Diastereo- and Enantioselective Synthesis of 2,3-Dihydrobenzofuran-Based Tricyclic Scaffolds
Vargas, David A.,Khade, Rahul L.,Zhang, Yong,Fasan, Rudi
supporting information, p. 10148 - 10152 (2019/07/04)
2,3-Dihydrobenzofurans are key pharmacophores in many natural and synthetic bioactive molecules. A biocatalytic strategy is reported here for the highly diastereo- and enantioselective construction of stereochemically rich 2,3-dihydrobenzofurans in high enantiopurity (>99.9% de and ee), high yields, and on a preparative scale via benzofuran cyclopropanation with engineered myoglobins. Computational and structure-reactivity studies provide insights into the mechanism of this reaction, enabling the elaboration of a stereochemical model that can rationalize the high stereoselectivity of the biocatalyst. This information was leveraged to implement a highly stereoselective route to a drug molecule and a tricyclic scaffold featuring five stereogenic centers via a single-enzyme transformation. This work expands the biocatalytic toolbox for asymmetric C–C bond transformations and should prove useful for further development of metalloprotein catalysts for abiotic carbene transfer reactions.
Photocatalytic Alkylation of Pyrroles and Indoles with α-Diazo Esters
Ciszewski, Lukasz W.,Durka, Jakub,Gryko, Dorota
supporting information, p. 7028 - 7032 (2019/09/12)
This article describes the photoalkylation of electron-rich aromatic compounds with diazo esters. C-2-alkylated indoles and pyrroles are obtained with good yields even though the photocatalyst loading is as low as 0.075 mol %. For EWG-substituted substrates, the addition of a catalytic amount of N,N-dimethyl-4-methoxyaniline is required. Both EWG-EWG- and EWG-EDG-substituted diazo esters are suitable as alkylating agents. The reaction selectivity and mechanistic experiments suggest that carbenes/carbenoid intermediates are not involved in the reaction pathway.
Myoglobin-Catalyzed C?H Functionalization of Unprotected Indoles
Vargas, David A.,Tinoco, Antonio,Tyagi, Vikas,Fasan, Rudi
supporting information, p. 9911 - 9915 (2018/07/31)
Functionalized indoles are recurrent motifs in bioactive natural products and pharmaceuticals. While transition metal-catalyzed carbene transfer has provided an attractive route to afford C3-functionalized indoles, these protocols are viable only in the presence of N-protected indoles, owing to competition from the more facile N?H insertion reaction. Herein, a biocatalytic strategy for enabling the direct C?H functionalization of unprotected indoles is reported. Engineered variants of myoglobin provide efficient biocatalysts for this reaction, which has no precedents in the biological world, enabling the transformation of a broad range of indoles in the presence of ethyl α-diazoacetate to give the corresponding C3-functionalized derivatives in high conversion yields and excellent chemoselectivity. This strategy could be exploited to develop a concise chemoenzymatic route to afford the nonsteroidal anti-inflammatory drug indomethacin.
Rapid access to spirocyclized indolenines via palladium-catalyzed cascade reactions of tryptamine derivatives and propargyl carbonate
Montgomery, Thomas D.,Nibbs, Antoinette E.,Zhu, Ye,Rawal, Viresh H.
supporting information, p. 3480 - 3483 (2014/07/21)
We report the intermolecular palladium-catalyzed reaction of tert-butyl propargyl carbonate with tryptamine derivatives or other indole-containing bis-nucleophiles. The reaction proceeds under mild conditions and with low catalyst loadings to afford novel spiroindolenine products in good to high yields.
Multitarget Compounds Active at a PPAR and Cannabinoid Receptor
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Page/Page column 53, (2011/04/13)
There is a need for pharmaceutical compounds which have activity at, at least one of a PPAR and a cannabinoid receptor. Thus there are provided such compounds, wherein the compound comprises: a PPAR pharmacophore and a cannabinoid pharmacophore linked together by a moiety comprising a fused bicyclic ring comprising a five membered ring fused with a six membered ring or a six membered ring fused with a six membered ring; wherein the cannabinoid pharmacophore comprises the fused bicyclic ring; and the PPAR pharmacophore comprises a salicylic acid, alkoxybenzylacetic acid or a alkoxyphenylacetic acid functionality; and wherein the PPAR pharmacophore is linked to the bicyclic ring of the cannabinoid pharmacophore through a linker comprising an amine or an amide functional group.
Amides as precursors of imidoyl radicals in cyclisation reactions
Bowman, W. Russell,Fletcher, Anthony J.,Pedersen, Jan M.,Lovell, Peter J.,Elsegood, Mark R.J.,Hernández López, Elena,McKee, Vickie,Potts, Graeme B.S.
, p. 191 - 203 (2007/10/03)
Amides have been successfully used as precursors of imidoyl radicals for radical cyclisation. The amides have been converted to imidoyl selanides via reaction with phosgene to yield imidoyl chlorides followed by reaction with potassium phenylselanide. Imidoyl selanides were reacted with tributyltin hydride (Bu3SnH) as the radical mediator with triethylborane or AIBN as initiators to yield imidoyl radicals for cyclisation reactions. Imidoyl radicals have been cyclised onto alkenes to yield 2,3-substituted-indoles and -quinolines and also onto pyrroles and indoles to give bi- and tricyclic heteroarenes.
Hypoglycemic imidazoline compounds
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Page/Page column 18-19, (2010/02/05)
This invention relates to certain novel imidazoline compounds and analogues thereof, to their use for the treatment of diabetes, diabetic complications, metabolic disorders, or related diseases where impaired glucose disposal is present, to pharmaceutical compositions comprising them, and to processes for their preparation.
Synthesis of indoles using cyclization of imidoyl radicals
Bowman, W. Russell,Fletcher, Anthony J.,Lovell, Peter J.,Pedersen, Jan M.
, p. 1905 - 1908 (2007/10/03)
Imidoyl radicals, generated from imidoyl phenylselanide precursors, have been used for the synthesis of 2,3-disubstituted indoles. A facile high yielding synthesis of imidoyl phenylselanides has been developed. The potential for neophyl rearrangement of 5
