712-09-4Relevant academic research and scientific papers
Au(I)-Catalyzed Domino Cyclization of 1,6-Diynes Incorporated with Indole
Chen, Guzhou,Liu, Peng-Yu,Zou, Huanhuan,Hu, Jiadong,Fang, Xiaowu,Xu, Dongyang,He, Yu-Peng,Wei, Hongbo,Xie, Weiqing
supporting information, p. 2279 - 2284 (2021/04/05)
We disclose herein a Au(I)-catalyzed domino cyclization of 1,6-diynes incorporated with indole. This protocol enabled the diastereoselective buildup of indole-fused azabicyclo[3.3.1]nonanes from linear precursors. Density functional theory calculations showed that the reaction proceeded via an unprecedented cascade dearomatization/rearomatization/dearomatization process. Independent gradient model analysis revealed that a noncovalent attractive interaction between the distal alkyne and the Au/proximal complex was responsible for the chemoselectivity of the first spirocyclization step.
Enantioselective Construction of Spirooxindole-Fused Cyclopentanes
Do?ekal, Vojtěch,Vopálenská, Andrea,Měrka, Pavel,Kone?ná, Klára,Jand'Ourek, Ond?ej,Pour, Milan,Císa?ová, Ivana,Vesely, Jan
, p. 12623 - 12643 (2021/07/31)
The present study reports an asymmetric organocatalytic cascade reaction of oxindole derivates with α,β-unsaturated aldehydes efficiently catalyzed by simple chiral secondary amine. Spirooxindole-fused cyclopentanes were produced in excellent isolated yields (up to 98%) with excellent enantiopurities (up to 99% ee) and moderate to high diastereoselectivities. The synthetic utility of the protocol was exemplified on a set of additional transformations of the corresponding spiro compounds. In addition, a study showing the promising biological activity of selected enantioenriched products was accomplished.
AZEPINO-INDOLES AND OTHER HETEROCYCLES FOR TREATING BRAIN DISORDERS
-
Paragraph 0204, (2020/09/12)
The present invention provides azepino-indoles and other heterocycles and methods of using the compounds for treating brain disorders.
Improved and Flexible Synthetic Access to the Spiroindole Backbone of Cebranopadol
Christoffers, Jens,Schmidtmann, Marc,Wachtendorf, Daniel
supporting information, p. 6420 - 6423 (2020/09/02)
By changing the dimethylamino to a nitro group, a novel synthetic access to the spirocyclic opioid analgesic cebranopadol was developed that is much more efficient compared with the established route. On the basis of the α-acidity of α-nitrotoluene, the two-fold Michael addition to acrylate gave an acyclic precursor compound, which was easily transformed by Dieckmann condensation and decarboxylation to the cyclohexanone derivative needed for the annulation of the indole ring by an oxa-Pictet-Spengler reaction. As an additional benefit, the reduction of the nitro group furnished an amine, which could be late-stage-diversified to carboxamides, sulfonamides, ureas, and N-alkyl congeners. The transformation of the nitro group at the spirocyclic scaffold to the dimethylamino function of the actual title compound was achieved in one step with zinc/formic acid/formaldehyde in 83% yield.
Tandem Olefin Isomerization/Cyclization Catalyzed by Complex Nickel Hydride and Br?nsted Acid
Kathe, Prasad M.,Caciuleanu, Alexandru,Berkefeld, Andreas,Fleischer, Ivana
, p. 15183 - 15196 (2020/11/30)
We disclose a nickel/Br?nsted acid-catalyzed tandem process consisting of double bond isomerization of allyl ethers and amines and subsequent intramolecular reaction with nucleophiles. The process is accomplished by [(Me3P)4NiH]N(SO2CF3)2 in the presence of triflic acid. The methodology provides rapid access to tetrahydropyran-fused indoles and other oxacyclic scaffolds under very low catalyst loadings.
Development of the Vinylogous Pictet–Spengler Cyclization and Total Synthesis of (±)-Lundurine A
Nash, Aaron,Qi, Xiangbing,Maity, Pradip,Owens, Kyle,Tambar, Uttam K.
supporting information, p. 6888 - 6891 (2018/05/08)
A novel vinylogous Pictet–Spengler cyclization has been developed for the generation of indole-annulated medium-sized rings. The method enables the synthesis of tetrahydroazocinoindoles with a fully substituted carbon center, a prevalent structural motif in many biologically active alkaloids. The strategy has been applied to the total synthesis of (±)-lundurine A.
Palladium-Catalyzed Asymmetric Allylic Alkylation of 3-Substituted 1 H-Indoles and Tryptophan Derivatives with Vinylcyclopropanes
Trost, Barry M.,Bai, Wen-Ju,Hohn, Christoph,Bai, Yu,Cregg, James J.
supporting information, p. 6710 - 6717 (2018/05/24)
Vinylcyclopropanes (VCPs) are known to generate 1,3-dipoles with a palladium catalyst that initially serve as nucleophiles to undergo [3 + 2] cycloadditions with electron-deficient olefins. In this report, we reverse this reactivity and drive the 1,3-dipoles to serve as electrophiles by employing 3-alkylated indoles as nucleophiles. This represents the first use of VCPs for the completely atom-economic functionalization of 3-substituted 1H-indoles and tryptophan derivatives via a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA). Excellent yields and high chemo-, regio-, and enantioselectivities have been realized, providing various indolenine and indoline products. The method is amenable to gram scale and works efficiently with tryptophan derivatives that contain a diketopiperazine or diketomorpholine ring, allowing us to synthesize mollenine A in a rapid and ligand-controlled fashion. The obtained indolenine products bear an imine, an internal olefin, and a malonate motif, giving multiple sites with diverse reactivities for product diversification. Complicated polycyclic skeletons can be conveniently constructed by leveraging this unique juxtaposition of functional groups.
Rapid One-Pot Access to Unique 3,4-Dihydrothiopyrano[3,4-b]indol-1(9H)-imines via Bi(OTf)3-Catalysed Tandem Friedel–Crafts Alkylation/Thia-Michael Addition
Dethe, Dattatraya H.,Boda, Vijay Kumar,Mandal, Anupam
supporting information, p. 5417 - 5421 (2018/10/20)
A highly efficient and atom economical one-pot annulation strategy for novel tetrahydrothiopyrano[3,4-b]indoles is presented. This protocol involves a Bi(OTf)3 catalyzed tandem Friedel–Crafts alkylation and intramolecular thia-Michael addition reactions to furnish target molecules in an efficient manner. The method works effectively on substrates with unprotected indoles and also it is successfully employed to make tetrahydrothiepino[3,4-b]indoles. The scaffolds synthesized are diverse and first of the kind. The reaction is practically simple with broad substrate scope and vast functional group compatibility.
Scope of the Reactions of Indolyl- and Pyrrolyl-Tethered N-Sulfonyl-1,2,3-triazoles: Rhodium(II)-Catalyzed Synthesis of Indole- and Pyrrole-Fused Polycyclic Compounds
Fu, Liangbing,Davies, Huw M. L.
supporting information, p. 1504 - 1507 (2017/04/13)
An efficient synthesis of tetrahydrocarboline-type products and polycyclic spiroindolines has been achieved. The transformation proceeds via rhodium(II)-catalyzed intramolecular annulations of indolyl- and pyrrolyl-tethered N-sulfonyl-1,2,3-triazoles. The reaction could be tuned toward either the formal [3 + 2] cycloaddition or the C-H functionalization reaction depending on the electronic and structural features of the substrates, leading to the production of a variety of structurally related heterocyclic compounds.
A Photoredox-Induced Stereoselective Dearomative Radical (4+2)-Cyclization/1,4-Addition Cascade for the Synthesis of Highly Functionalized Hexahydro-1H-carbazoles
Alpers, Dirk,Gallhof, Malte,Witt, Julian,Hoffmann, Frank,Brasholz, Malte
supporting information, p. 1402 - 1406 (2017/01/24)
A stereoselective synthesis of functionalized hexahydrocarbazoles was developed based on an unprecedented photoredox-induced dearomative radical (4+2)-cyclization/1,4-addition cascade between 3-(2-iodoethyl)indoles and acceptor-substituted alkenes. The title reaction simultaneously generates three C?C bonds and one C?H bond, along with three contiguous stereogenic centers. The hexahydro-1H-carbazole products are highly valuable intermediates for the synthesis of novel antibiotics, as well as unnatural ring homologues of polycyclic indoline alkaloids.
