Synthesis of 3,4-Disubstituted Isoquinolines via Palladium-Catalyzed Cross-Coupling of 2-(1-Alkynyl)benzaldimines and Organic Halides

Dai, Guangxiu; Larock, Richard C.

doi:10.1021/jo026294j

Cited by 132 publications

(22 citation statements)

References 35 publications

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“…However, we were not able to isolate it from the crude reaction mixture by column chromatography. Iodine may also be used as electrophile [8,13] in these cyclization reactions to afford the I-substituted product 8 in 35 % yield (heating at 60°C in chloroform for 8 h) (Scheme 11). We propose the following mechanism for the observed silver(I)-induced reaction (Scheme 12).…”

Section: Resultsmentioning

confidence: 99%

Indole as Neutral Leaving Group in Silver Nitrate Induced Cyclization Reactions of N‐{2‐[Alkynyl(hetero)aryl]methylene}indolin‐1‐amines for the Synthesis of Annulated Pyridine Derivatives

2010

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N‐{2‐[Alkynyl(hetero)aryl]methylene}indolin‐1‐amines 3 undergo, upon treatment with silver nitrate in chloroform at 60 °C, electrophilic cyclization reactions to afford annulated pyridine derivatives 4. Mechanistically, the silver(I)‐assisted 6‐endo‐dig ring‐closure process of compounds 3 leads to the formation of an intermediate pyridinium cation, which releases – besides the products 4 – indole as unusual but efficient neutral leaving group after N–N bond cleavage. It is shown that among the hydrazones studied, only the 1‐aminoindoline‐derived substrates N‐{2‐[alkynyl(hetero)aryl]methylene}indolin‐1‐amines 3 are suitable to produce annulated pyridine derivatives 4 in high yield. The reaction can be performed in air and even in the presence of water in the reaction medium. Since during the course of the reaction indole is oxidized by the silver(I) ions, stoichiometric amounts of silver salt are required. Quantum chemical calculations have been applied in order to gain additional information on the reaction mechanism and the key reactive intermediates.

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Section: Resultsmentioning

confidence: 99%

Indole as Neutral Leaving Group in Silver Nitrate Induced Cyclization Reactions of N‐{2‐[Alkynyl(hetero)aryl]methylene}indolin‐1‐amines for the Synthesis of Annulated Pyridine Derivatives

2010

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“…Nitrogen heterocycles such as β-and γ-carbolines [567,568], isoquinolines [569,570], indoles [288], oxindoles [97], pyrrolidines [317], and indolo[2,1-b]isoquinolin-7(5H)-ones [571], indolizidinones [572], quinolizidinones [572], and benzoazepinones/benzazepines [179,572] have been prepared using Heck reactions as the heterocycle-forming step (Figure 8.6, see also Scheme 8.41).…”

Section: Syntheses Of Heterocycles Natural Products and Other Biolomentioning

confidence: 99%

“…This transformation involves a carbopalladation of the triple bond in 398 with concomitant attack by the imine moiety and subsequent loss of the tert-butyl group as isobutene [570]. Despite the great potential of the Heck reaction for the arylation and alkenylation of alkenes on a wide scope, its applications in natural product syntheses were rather limited in the first 20 years.…”

Section: Syntheses Of Heterocycles Natural Products and Other Biolomentioning

confidence: 99%

Cross‐Coupling of Organyl Halides with Alkenes – The Heck Reaction

Bräse¹,

Meijere²

2013

Metal‐Catalyzed Cross‐Coupling Reactions and More

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The carbopalladation of an alkene by an organylpalladium halide is the essential step in one of the major contemporary metal-catalyzed C-C coupling reactions. About 45 years ago, a Japanese and an American group almost simultaneously designed and executed palladium-mediated coupling reactions of aryl and alkenyl halides with alkenes [1]. In subsequent investigations, Richard Heck and his group developed this reaction into a catalytic transformation and started to demonstrate its usefulness as well as its rather broad scope. The real push to utilize this powerful C-C-bondforming process, however, started only around the mid-1980s, and by now, an impressive number of publications have established the meanwhile so-called Heck reaction [2] 1) as an indispensable method in Organic Synthesis [3][4][5][6][7]. The universal recognition of the importance of the Heck reaction and the Negishi as well as the Suzuki coupling eventually won the Nobel Prize for Richard Heck along with Ei-ichi Negishi and Akira Suzuki in 2010. The applications of the Heck reaction range from the preparation of -functionalized and unfunctionalized -hydrocarbons, novel polymers, and dyes to new advanced enantioselective syntheses of natural products and biologically active nonnatural compounds. The more or less simultaneous developments of mechanistically related variants, namely, the Kumada, Suzuki, Stille, Hiyama, and Negishi coupling reactions (Chapters 12, 2, 3, 4, and 15, respectively) of metallated alkenes and arenes with aryl and alkenyl halides or the metal-catalyzed formation and cycloisomerization of enynes have drawn profit from the improvement of and mechanistic insights into the Heck reaction. This, of course, applies vice versa as well. Using only a catalytic amount of a palladium(0) complex or a precursor to a palladium species, the Heck reaction can bring about unprecedented structural changes, particularly when conducted intramolecularly. The full potential of this palladium-catalyzed process is still being further explored as demonstrated by a total of over 7000 publications in the past 40 years by 1) The alkynylation of aryl and alkenyl halides, frequently also considered as Heck reactions, is described in Chapter 6.

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“…For example, Larock has developed a new method for the synthesis of 3,4-disubstituted isoquinolines via Pd-catalyzed reactions of 2-(1-alkynyl)benzaldimines with aryl, vinyl, allyl, alkynyl, and benzyl halides (eq 73) [106]. This transformation is mechanistically related to the Wacker-type reactions described above insofar as the alkyne is activated by the electrophilic Pd(Ar)(X) complex towards intramolecular nucleophilic attack by the imine, which generates 50.…”

Section: Heterocycle Synthesis Via Intramolecular Wackertype Reactionmentioning

confidence: 99%

Recent Developments in Palladium-Catalyzed Heterocycle Synthesis and Functionalization

Wolfe¹,

Thomas²

2005

COC

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Synthesis of 3,4-Disubstituted Isoquinolines via Palladium-Catalyzed Cross-Coupling of 2-(1-Alkynyl)benzaldimines and Organic Halides

Cited by 132 publications

References 35 publications

Indole as Neutral Leaving Group in Silver Nitrate Induced Cyclization Reactions of N‐{2‐[Alkynyl(hetero)aryl]methylene}indolin‐1‐amines for the Synthesis of Annulated Pyridine Derivatives

Indole as Neutral Leaving Group in Silver Nitrate Induced Cyclization Reactions of N‐{2‐[Alkynyl(hetero)aryl]methylene}indolin‐1‐amines for the Synthesis of Annulated Pyridine Derivatives

Cross‐Coupling of Organyl Halides with Alkenes – The Heck Reaction

Recent Developments in Palladium-Catalyzed Heterocycle Synthesis and Functionalization

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