A NaOH‐mediated protocol was developed for the syntheses of a series of 2′‐arylspirocyclopent3ene‐1,3′‐indoles and 6‐alkyl‐5,6,7,10‐tetrahydrocycloheptabindoles in good yields by cyclization through ...a sigmatropic rearrangement of suitable 2,3‐disubstituted indoles. These precursors that contain a 4‐chloro‐2‐butenyl side chain at the 3‐position were obtained as a mixture of (E) and (Z) isomers through the reactions of o‐alkynylanilines and 3,4‐dichloro‐1‐butene. The cyclization strategy is general, and both medicinally important scaffolds were achieved by changing the substituent at the 2‐position of methyl 3‐(4‐chlorobut‐2‐enyl)‐1H‐indole‐1‐carboxylate. The reaction likely proceeds through 1,3‐ and 3,3‐sigmatropic rearrangements of the vinylcyclopropane substituent of the indole intermediate.
Enantiomerically enriched indole-containing heterocycles play a vital role in bioscience, medicine, and chemistry. As one of the most attractive subtypes of indole alkaloids, highly substituted ...tetrahydro-γ-carbolines are the basic structural unit in many natural products and pharmaceuticals. However, the syntheses of tetrahydro-γ-carbolines with high functionalities from readily available reagents are significant challenging. In particular, the stereodivergent syntheses of tetrahydro-γ-carbolines containing multi-stereogenic centers remain quite difficult. Herein, we report an expedient and stereodivergent assembly of tetrahydro-γ-carbolines with remarkably high levels of stereoselective control in an efficient cascade process from aldimine esters and indolyl allylic carbonates via a synergistic Cu/Ir catalyst system. Control experiments-guided optimization of synergistic catalysts and mechanistic investigations reveal that a stereodivergent allylation reaction and a subsequent highly stereoselective iso-Pictet-Spengler cyclization are the key elements to success.
Covering: January 2013 to September 2018Sulfur-containing natural products are a large class of significant functional molecules. Many of these compounds exhibit potent biological activities and ...pharmacological properties; in fact, some of them have been developed into important drugs. The total synthesis of sulfur-containing natural products is a subject that has long attracted significant attention from synthetic organic chemists; to achieve this goal, various methods have been developed over the past years. This review surveys total syntheses of sulfur-containing natural products that introduce sulfur atoms using different sulfurization agents to construct related sulfur-containing moieties.
A robust and green electrochemical dearomatization of indoles was developed by merging a fluorine-containing group to an indole nucleus under oxidant-free conditions, delivering a diverse array of ...tri- and difluoromethylated 3,3-spiroindolines with good functional group tolerance.
Total Synthesis of Rucaparib Park, Jinjae; Cheon, Cheol-Hong
Journal of organic chemistry,
04/2022, Volume:
87, Issue:
7
Journal Article
Peer reviewed
A concise total synthesis of rucaparib, an FDA-approved drug for ovarian and prostate cancers, is reported. The Heck reaction of the commercially available aryl iodide with acrylonitrile provided the ...desired (
)-2-aminocinnamonitrile derivative. A subsequent imino-Stetter reaction of the aldimine derived from 2-aminocinnamonitrile and aldehyde furnished indole-3-acetonitrile bearing the desired substituents at appropriate positions. The construction of the final azepinone scaffold via reduction of the nitrile group followed by seven-membered lactamization afforded rucaparib. Notably, the synthesis of rucaparib is achieved using commercially available starting materials in only three separation operations with 54% overall yield.
Synthesis of Spirocyclic Indolenines James, Michael J.; O'Brien, Peter; Taylor, Richard J. K. ...
Chemistry : a European journal,
February 24, 2016, Volume:
22, Issue:
9
Journal Article
Peer reviewed
This Review provides an in‐depth account of the synthesis of spirocyclic indolenines. Over the last 77 years, a wide array of diverse synthetic methods has been developed in order to generate these ...synthetically useful and biologically important spirocyclic scaffolds. The main synthetic strategies discussed are grouped into three main categories, namely interrupted Fischer indolisations, dearomatisation reactions of indoles and condensation reactions. The historical background, common synthetic challenges, current state‐of‐the‐art and future perspectives of this field are examined.
Another round: A detailed account of spirocyclic indolenine synthesis over the last 77 years is provided. The synthetic strategies described include interrupted Fischer indolisations, dearomatisation reactions of indoles and condensation reactions, as well miscellaneous processes. Common synthetic challenges associated with these strategies are also examined.
An efficient arylsulfonylation/cyclization of 2-aryl-
-methacryloyl indoles with potassium metabisulfite and aryldiazonium tetrafluoroborates was developed. A series of variously substituted ...arylsulfonyl indolo2,1-
isoquinolin-6(5
)-ones were formed in moderate to good yields
utilization of the nature abundant inorganic salt potassium metabisulfite as a SO
surrogate. Additionally, this three-component protocol can also be employed for the synthesis of arylsulfonyl-substituted benzimidazo-2,1-
isoquinolin-6(5
)-ones.
An approach to hydrocarbazoles bearing an all‐carbon quaternary center at C4a position was developed via a Brønsted acid‐initiated Diels‐Alder cycloaddition/retro‐aza‐Michael addition cascade process ...from azepino4,5‐bindoles and commercially available dienophiles. The method provided a range of hydrocarbazoles in 63–99% yields. The practicality of this transformation was demonstrated by a scale‐up experiment and various transformations to several hydrocarbazole derivatives and the tetracyclic indoline scaffold. Moreover, hetero‐Diels‐Alder cycloadditions of azepino4,5‐bindoles were explored with 4‐phenyl‐3H‐1,2,4‐triazole‐3,5(4H)‐dione (PTAD) and 82–99% yields were obtained.
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