DoubleN-Arylation of Primary Amines: Carbazole Synthesis from 2,2‘-Biphenyldiols (original) (raw)
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Recent trends in the synthesis of carbazoles: an update
Tetrahedron, 2012
The carbazole nucleus is a predominant feature of a vast array of heterocyclic compounds. It occurs in naturally occurring alkaloids, optoelectronic materials, and anion-binding ligands. Due to their various applications, there have appeared a plethora of synthetic methods for the construction of carbazoles. In this update, we focus on the recent developments and studies related to the synthesis of carbazoles spanning the period 2008e2011. Particular emphasis is placed on the methods involving cycloadditions and transition metal-assisted intramolecular aminations.
Synthesis of Carbazoles by Intramolecular Arylation of Diarylamide Anions
Journal of Organic Chemistry, 2009
The synthesis of a series of substituted 9H-carbazoles by the photostimulated S RN 1 substitution reaction with diarylamines as starting substrate was performed. The diarylamines were obtained by two approaches, the Pd-catalyzed reactions (Buchwald-Hartwig) or Cu-catalyzed reactions of 2-haloanilines with aryl halides, or 2-bromoiodobenzene with anilines, with moderate to very good isolated yields (45-89%).
The Journal of organic chemistry, 2014
An efficient and simple protocol for the preparation of a series of 9H-carbazoles by photostimulated SRN1 substitution reactions is presented. Substituted 9H-carbazoles were synthesized in low to excellent yields (up to 96%) through an intramolecular C-N bond formation of 2'-halo[1,1'-biphenyl]-2-amines by the photoinitiated SRN1 mechanism under mild and "transition-metal-free" conditions. The biphenylamines used as substrates were obtained with isolated yields ranging from 21% to 84% by two approaches: (A) the cross-coupling Suzuki-Miyaura reaction and (B) the radical arylation of anilines. Some key aspects of the proposed mechanism were evaluated at the B3LYP/6-311+G* level.
Synthesis of Carbazoles by a Diverted Bischler–Napieralski Cascade Reaction
Organic Letters
An unforeseen twist in a seemingly trivial Bischler− Napieralski reaction led to the selective formation of an unexpected carbazole product. The reaction proved to be general, providing access to a range of diversely substituted carbazoles from readily available substrates. Judicious variation of substituents revealed a complex cascade mechanism comprising no less than 10 elementary steps, that could be diverted in multiple ways toward various other carbazole derivatives. S ince its first report in 1893, the Bischler−Napieralski reaction has been widely employed for the synthesis of dihydro-β-carbolines and-isoquinolines owing to its robustness and broad functional group tolerance. 1 Even currently, the Bischler−Napieralski reaction and its contemporary variations are still the object of intensive study in many areas, including natural product synthesis. 2 In light of our interest in bioactive indole alkaloids and related compounds, 3 we employed the Bischler−Napieralski reaction to access a series of dihydro-βcarbolines. However, when we subjected styrylacetamide 1a to typical Bischler−Napieralski conditions (POCl 3 , MeCN, reflux, 1 h) we serendipitously found near-quantitative formation of 3phenylcarbazole (3a) instead of the expected dihydro-βcarboline 2a (Scheme 1A). The structure of 3a was confirmed by 1 H and 13 C NMR, HRMS, and X-ray crystallography. Although carbazoles are less common than the related indoles among natural products and medicinal compounds, various carbazoles displaying interesting properties have been reported (Scheme 1B). 4 Notable examples include the anticancer natural products staurosporine 5 (and its clinically used semisynthetic derivative, midostaurin 6) and ellipticine. 7 Recently, carbazole derivative 4 was identified as a lead for new antitrypanosomiasis drugs, 8 while glycozoline is known for its antibacterial, antifungal, antifeedant, and anti-inflammatory properties. 9 Typical methods for the synthesis of carbazoles involve high temperature, long reaction times, and often metal catalysis (sometimes replaced by iodine or Lewis acids). 10,11 Intrigued by our preliminary result, we decided to further explore the synthetic potential of this novel, mild, and metalfree route to carbazoles in more detail. Puzzled by the surprising, but highly efficient formation of 3a, we set out to investigate the generality of the process. A series of diversely substituted tryptamides 1a−t was subjected to the reaction conditions (POCl 3 , MeCN, reflux, 1 h). Pleasingly, we observed that all substrates underwent full conversion within 1 h (Scheme 2). Both electron-withdrawing and electron-donating substituents on the indole (R 2) are tolerated without significant influence on the yield, affording the corresponding products 3b−k in mostly good yield, with 5
Molecules, 2013
A palladium-catalyzed synthesis of the carbazole framework is described, including the preparation of 2-, 5-, and 7-oxygenated natural and unnatural carbazole alkaloids. A series of N-arylcyclohexane enaminones, generated by condensation of cyclohexane-1,3-dione with diverse anilines, were aromatized by a Pd(0)-catalyzed thermal treatment to afford the corresponding diarylamines. The latter were submitted to a Pd(II)-catalyzed cyclization and methylation processes to provide the desired carbazoles, including clausine V. Following an inverse strategy, a new and short total synthesis of glycoborine is also reported.
ChemInform Abstract: A One-Pot Synthesis of Annulated Carbazole Analogues
ChemInform, 2009
www.cheminform.wiley-vch.de Carbazole derivatives R 0150 A One-Pot Synthesis of Annulated Carbazole Analogues.-Optimized conditions A) allow the preparation of a broad spectrum of target compounds including higher systems which are of interest for technological application. Whereas toluene leads to formation of a 1:1 mixture of regioisomers, anisole reacts selectively [cf.(XIII)]. In the case of benzothiophene (VIII), the annulation is unsuccessful. Finally, a two-step process leads to formation of the isomeric carbazoles (IX) and (X).-(MOHANAKRISHNAN*, A.
ChemistrySelect, 2016
A general and mild strategy has been developed for the selective N-arylation of tautomerizable heterocycles with a series of arylboronic acids, using CuOTf as the catalyst and 1,10-Phen as the ligand, under base free conditions at ambient atmosphere. The reaction mechanism explored by using density functional methods revealed that both kinetic and thermodynamic controls favour N-arylation. This "open-flask" chemistry successfully applied for N-arylation of benzo[d] oxazol-2(3H)-one and the designed N-arylated product was subsequently manipulated in synthesizing various naturally occurring oxygenated carbazole alkaloids (e. g. clausenine, clauraila A, clausenal).
ChemistrySelect, 2019
Practical access to diversely functionalized carbazoles has been developed by consecutive Cu‐catalyzed Chan‐Lam N−arylation of various o‐iodoanilines and boronic acids, and Pd‐catalyzed intramolecular aryl C−H activation of 2‐iodo‐N‐arylanilines. Use of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) as base was found beneficial for both steps. In the Pd‐catalyzed C−H activation step, DBU acts as ligand as well as base, resulting in improved functional tolerance and higher yields than those observed with inorganic or other nitrogen bases. This DBU‐assisted sequence offers access to a variety of carbazoles with various electron‐donating and electron‐withdrawing substituents, including halogens or other reactive functional groups. Twenty‐seven cabazoles with various substitution paterns, including two naturally‐occurring carbazoles ‐ clausine L and clausine H ‐ have been successfully synthesized using these DBU‐promoted metal‐catalyzed coupling reactions.