The Twofold Heck Reaction on 1,2-Dihalocycloalkenes and Subsequent 6π-Electrocyclization of the Resulting (E, Z, E)-1,3,5-Hexatrienes: A New Formal {2+2+2}-Assembly of Six-Membered Rings

Voigt, K.; Zezschwitz, Paultheo von; Rosauer, Keith G.; Lansky, Annegret; Adams, Amy; Reiser, Oliver; Meijere, Armin de

doi:10.1002/(sici)1099-0690(199808)1998:8<1521::aid-ejoc1521>3.0.co;2-e

Cited by 75 publications

(44 citation statements)

References 44 publications

(11 reference statements)

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“…The substrate was reacted with the alkyl acrylates 12a (R 1 = Me) and 12b (R 1 = t- Bu) under phosphine-free conditions [33–34] using 6 mol % of palladium(II) acetate, triethylamine as base and lithium chloride [35] leading to the expected coupling products syn - 13 and syn - 14 in 39% and 82% yield, respectively (Scheme 5). In both cases, only the E -configured 2-substituted alkyl acrylates were isolated.…”

Section: Resultsmentioning

confidence: 99%

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

Medvecký

Linder

Schefzig

et al. 2016

Beilstein J. Org. Chem.

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Iodination of carbohydrate-derived 3,6-dihydro-2H-1,2-oxazines of type 3 using iodine and pyridine in DMF furnished 5-iodo-substituted 1,2-oxazine derivatives 4 with high efficacy. The alkenyl iodide moiety of 1,2-oxazine derivatives syn-4 and anti-4 was subsequently exploited for the introduction of new functionalities at the C-5 position by applying palladium-catalyzed carbon–carbon bond-forming reactions such as Sonogashira, Heck, or Suzuki coupling reactions as well as a cyanation reaction. These cross-coupling reactions led to a series of 5-alkynyl-, 5-alkenyl-, 5-aryl- and 5-cyano-substituted 1,2-oxazine derivatives being of considerable interest for further synthetic elaborations. This was exemplarily demonstrated by the hydrogenation of syn-21 and anti-24 and by a click reaction of a 5-alkynyl-substituted precursor.

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Section: Resultsmentioning

confidence: 99%

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

Medvecký

Linder

Schefzig

et al. 2016

Beilstein J. Org. Chem.

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“…Starting with the 2-chlorocyclohexenylnonaflate 37 prepared in one step from chlorocyclohexanone [219], the first Heck coupling with methyl acrylate is achieved in 96 % yield at 60 hC and ambient pressure. The chlorine in the product 38 can be substituted by a styryl group at 60 hC and 10 kbar to give the hexatriene 39 (Scheme 5-9) [192].…”

Section: 25mentioning

confidence: 99%

“…accessible by treatment of the hexatrienes 214 with peracids or dimethyldioxirane, rearrange smoothly to the bridgehead-bridgehead dienes 218 [320]. Alternatively, palladium(0)-catalyzed reduction of the diethenylepoxides 217 leads to 1,5-hexadien-3-ols which readily undergo an anionic oxy-Cope rearrangement to give the ring-enlarged ketones 216 diastereoselectively (Scheme 5-53) [219,321]. The strategy of a vicinal two-fold Heck reaction was applied on tetrabromo[2.2] paracyclophanediene 219.…”

Section: The Heck Coupling In Combination With Other Reactionsmentioning

confidence: 99%

Cross‐Coupling of Organyl Halides with Alkenes: the Heck Reaction

Bräse

Meijere

2004

Metal‐Catalyzed Cross‐Coupling Reactions

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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 35 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 bond-forming process, however, started only around the mid-1980s, and by now an impressive number of publications has established the meanwhile socalled Heck reaction [2] as an indispensable method in organic synthesis [3]. The applications range from the preparation of hydrocarbons, novel polymers and dyes to new advanced enantioselective syntheses of natural products and biologically active non-natural compounds. The more or less simultaneous developments of mechanistically related variants, namely the Suzuki, Stille, Hiyama, Kumada and Negishi coupling reactions (see Chapters 2, 3, 4, 12 and 15 in this book, 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, also applies vice versa. 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 2400 relevant publications during the past 10 years, and a continuous annual growth in publications of 15 % per year. Therefore, it is appropriate to say that the Heck reaction is one of the true "power tools" in contemporary organic synthesis [4], competing favorably with the Diels-Alder reaction (25 000 references), olefin metathesis (1500 references), Wittig reaction (15 000 references), or Claisen rearrangement (15 000 references). Scheme 5-1 Mechanism of the Heck reaction [7]. Pd(OTfa) 2 , P(2-furyl) 3 , iPr 2 EtN; Pd(OTfa) 2 or Pd(F 6 -acac) 2 ] and fluorinated phosphanes [90] [91]

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“…Unsymmetrically 1,6‐disubstituted 1,3,5‐hexatrienes can be obtained by a sequence of chemoselective Stille cross‐coupling of a 2‐bromocycloalk‐1‐enyl triflate with an alkenylstannane at the site of the triflate leaving group and a subsequent Heck coupling on the resulting 2‐bromo‐1,3‐butadiene 2f,g. The symmetrical as well as the unsymmetrical 1,3,5‐( E , Z , E )‐hexatrienes do undergo thermal 6π‐electrocyclizations affording ring‐annelated cyclohexadienes 2a,f,g. These should be adequate dienes for Diels–Alder reactions3 with suitable dienophiles which would lead to functionalized tri‐ and tetracyclic compounds.…”

Section: Introductionmentioning

confidence: 99%

Domino 6π‐Electrocyclization/Diels–Alder Reactions on 1,6‐Disubstituted (E,Z,E)‐1,3,5‐Hexatrienes: Versatile Access to Highly Substituted Tri‐ and Tetracyclic Systems

Essen

Frank

Sünnemann

et al. 2005

Chemistry A European J

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The (E,Z,E)-1,3,5-hexatrienes 1a, 2a,b and 3b undergo 6pi-electrocyclization within 15-30 min upon heating to 200-215 degrees C. While the cyclohexene-annelated products 8a,b were stable, the analogous cyclopentene- and cycloheptene-annelated derivatives 7a and 9b easily underwent dehydrogenation to the corresponding aromatic compounds 10a and 12b during the work-up. The cyclohexadiene derivatives 8a,b were employed in thermal Diels-Alder reactions with 4-phenyl-3H-1,2,4-triazoline-3,5-dione (PTAD) and tetracyanoethylene (TCNE) to give the expected [4+2] cycloadducts 13a and 14a in good yields (60 and 78%). The initially formed cycloadduct of 8a and dimethyl acetylenedicarboxylate (DMAD) underwent a subsequent retro-Diels-Alder reaction to give the tetrahydronaphthalene 11b (47%). Under high pressure (10 kbar), the cycloadduct 15a was formed at room temperature and could be isolated in 44% yield. TCNE and N-phenylmaleimide with 8a under high pressure also led to the [4+2] cycloadducts 14a and 16a in good yields (60 and 77%). The 6pi-electrocyclization and subsequent Diels-Alder reaction, when performed as a one-pot domino process, provided direct access to Diels-Alder products of intermediately formed 6pi-electrocyclization products, for example from the 1,3,5-hexatrienes 1a,b, 2a,b, 3b and TCNE to the corresponding tricyclic products 17a,b, 14a,b, 18b in moderate to good yields (27-80%) depending on the nature of the alkoxycarbonyl group. Such sequential reactions with N-phenylmaleimide, maleic anhydride, dimethyl maleate and fumarodinitrile, the latter two under high pressure (10 kbar), worked as well to yield 16b (70%), 19a,b (19, 32%) and 20b (39%) and 21b (76%), respectively. With PTAD, however, the hexatrienes 2a,b reacted at ambient temperature without 6pi-electrocyclization to give the formal [4+2] cycloadducts 27a,b (48 and 46%), most probably via zwitterionic intermediates 23a,b and 25a,b.

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The Twofold Heck Reaction on 1,2-Dihalocycloalkenes and Subsequent 6π-Electrocyclization of the Resulting (E, Z, E)-1,3,5-Hexatrienes: A New Formal {2+2+2}-Assembly of Six-Membered Rings

Cited by 75 publications

References 44 publications

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

Cross‐Coupling of Organyl Halides with Alkenes: the Heck Reaction

Domino 6π‐Electrocyclization/Diels–Alder Reactions on 1,6‐Disubstituted (E,Z,E)‐1,3,5‐Hexatrienes: Versatile Access to Highly Substituted Tri‐ and Tetracyclic Systems

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