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Volumn 129, Issue 19, 2007, Pages 6328-6335

Two-faced reactivity of alkenes: cis- versus trans-aminopalladation in aerobic Pd-catalyzed intramolecular Aza-Wacker reactions

Author keywords

[No Author keywords available]

Indexed keywords

AMINATION; CYCLIZATION; NITROGEN COMPOUNDS; NUCLEOPHILES; PALLADIUM COMPOUNDS; STEREOCHEMISTRY;

EID: 34249028505     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja070424u     Document Type: Article
Times cited : (203)

References (102)
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    • In most cases, reactions of this type employ amine nucleophiles bearing electron-withdrawing groups (amides, sulfonamides, carbamates, etc.). In order to avoid modifying the nomenclature for each type of nucleophile, we use generic terms such as aminopalladation and oxidative amination to describe these reactions.
    • In most cases, reactions of this type employ amine nucleophiles bearing electron-withdrawing groups (amides, sulfonamides, carbamates, etc.). In order to avoid modifying the nomenclature for each type of nucleophile, we use generic terms such as "aminopalladation" and "oxidative amination" to describe these reactions.
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    • For leading references, see: a
    • For leading references, see: (a) Larock, R. C.; Hightower, T. R. J. Org. Chem. 1993, 58, 5298-5300.
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    • For asymmetric oxidative cyclization reactions that employ benzoquinone as the oxidant, see: a
    • For asymmetric oxidative cyclization reactions that employ benzoquinone as the oxidant, see: (a) Uozumi, Y.; Kato, K.; Hayashi, T. J. Am. Chem. Soc. 1997, 119, 5063-5064.
    • (1997) J. Am. Chem. Soc , vol.119 , pp. 5063-5064
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    • No well-defined examples of alkene insertion into a Pd-N bond are currently known, but examples of alkene insertion into other transition-metal amido complexes have been reported: (a) Cowan, R. L.; Trogler, W. C. Organometallics 1987, 6, 2451-2453.
    • No well-defined examples of alkene insertion into a Pd-N bond are currently known, but examples of alkene insertion into other transition-metal amido complexes have been reported: (a) Cowan, R. L.; Trogler, W. C. Organometallics 1987, 6, 2451-2453.
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    • For related Wacker-type cyclizations involving cis-oxypalladation, see ref. 13c and Hayashi, T.; Yamasaki, K.; Mimura, M.; Uozumi, Y. J. Am. Chem. Soc. 2004, 126, 3036-3037.
    • For related Wacker-type cyclizations involving cis-oxypalladation, see ref. 13c and Hayashi, T.; Yamasaki, K.; Mimura, M.; Uozumi, Y. J. Am. Chem. Soc. 2004, 126, 3036-3037.
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    • Anti-β-hydride elimination reactions have been implicated in a number of Heck-type reactions, but the substrates possess unique structural properties and the examples are extremely rare relative to the ubiquitous cases of syn-β-hydride elimination. For a leading reference describing reactions that proceed via (formal) anti-elimination, see: Ikeda, M.; El Bialy, S. A. A.; Yakura, T. Heterocycles 1999, 51, 1957-1970.
    • Anti-β-hydride elimination reactions have been implicated in a number of Heck-type reactions, but the substrates possess unique structural properties and the examples are extremely rare relative to the ubiquitous cases of syn-β-hydride elimination. For a leading reference describing reactions that proceed via (formal) anti-elimination, see: Ikeda, M.; El Bialy, S. A. A.; Yakura, T. Heterocycles 1999, 51, 1957-1970.
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    • For previous examples of the use of deuterium-labeled substrates to probe the stereochemistry of palladium-catalyzed reactions with alkenes, see refs 13c, 19, and (a) Grennberg, H, Simmon, V, Bäckvall, J.-E. J. Chem. Soc, Chem. Commun. 1994, 265-266
    • For previous examples of the use of deuterium-labeled substrates to probe the stereochemistry of palladium-catalyzed reactions with alkenes, see refs 13c, 19, and (a) Grennberg, H.; Simmon, V.; Bäckvall, J.-E. J. Chem. Soc., Chem. Commun. 1994, 265-266.
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    • For synthesis details of deuterium-labeling substrates, see the Supporting Information
    • For synthesis details of deuterium-labeling substrates, see the Supporting Information.
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    • For a detailed experimental description and compound-characterization data, see the Supporting Information
    • For a detailed experimental description and compound-characterization data, see the Supporting Information.
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    • The low yield obtained with the Pd/(-)-sparteine catalyst might reflect the fact that chelating ligands tend to inhibit Pd-catalyzed oxidative heterocyclization. In addition, this result could arise from selective oxidation of a single enantiomer of trans-3-d-13 (i.e., kinetic resolution of this substrate). Analysis of the product mixture by chiral SFC (Chiralcel OD-H), however, reveals that kinetic resolution of the substrate can only partly account for the low yield: the reaction of 13 catalyzed by the Pd/(-)-sparteine catalyst system produces 14 in 27% yield/44% ee and 15 in 17% yield/71% ee. We were unable to resolve the recovered starting material (56%) by chiral SFC.
    • The low yield obtained with the Pd/(-)-sparteine catalyst might reflect the fact that chelating ligands tend to inhibit Pd-catalyzed oxidative heterocyclization. In addition, this result could arise from selective oxidation of a single enantiomer of trans-3-d-13 (i.e., kinetic resolution of this substrate). Analysis of the product mixture by chiral SFC (Chiralcel OD-H), however, reveals that kinetic resolution of the substrate can only partly account for the low yield: the reaction of 13 catalyzed by the Pd/(-)-sparteine catalyst system produces 14 in 27% yield/44% ee and 15 in 17% yield/71% ee. We were unable to resolve the recovered starting material (56%) by chiral SFC.
  • 72
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    • A reviewer correctly noted that the stereochemical course of the reaction could be influenced by the presence of a deuterium kinetic isotope effect on the β-hydride elimination step. In order to address this possibility, we also prepared the diastereomeric substrate, cis-3-d-13. Oxidation cyclization of this substrate with the Pd(OAc)2/DMSO and Pd(OAc)2/py catalyst systems confirms that the reaction proceeds via cis-aminopalladation. For full details, see the Supporting Information
    • 2/py catalyst systems confirms that the reaction proceeds via cis-aminopalladation. For full details, see the Supporting Information.
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    • II species via C-H activation from the 3-position of trans-3-d-13 is expected to be unproductive because formation of the cis-fused bicyclic product would require cis-reductive elimination of the C-N bond. It has been shown that attack of soft nucleophiles such as sulfonamide on π-allyl-Pd species generally occurs via external (i.e., trans) attack on the π-allyl fragment: Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395-422.
    • II species via C-H activation from the 3-position of trans-3-d-13 is expected to be unproductive because formation of the cis-fused bicyclic product would require cis-reductive elimination of the C-N bond. It has been shown that attack of "soft" nucleophiles such as sulfonamide on π-allyl-Pd species generally occurs via external (i.e., trans) attack on the π-allyl fragment: Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395-422.
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    • In a recent study of PdII-catalyzed oxidative cyclization of o-allylphenols, Hayashi et al. observed primarily trans- oxypalladation of the alkene under the same conditions see ref 19 for details
    • II-catalyzed oxidative cyclization of o-allylphenols, Hayashi et al. observed primarily trans- oxypalladation of the alkene under the same conditions (see ref 19 for details).
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    • In our mechanistic studies of Pd(OAc)2/py-catalyzed aerobic alcohol oxidation, we obtained NMR spectroscopic evidence that an acetate ligand serves as an internal base to promote formation of a PdII-alkoxide species: Steinhoff, B. A, Guzei, I. A, Stahl, S. S. J. Am. Chem. Soc. 2004, 126, 11268-11278
    • II-alkoxide species: Steinhoff, B. A.; Guzei, I. A.; Stahl, S. S. J. Am. Chem. Soc. 2004, 126, 11268-11278.
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    • tBu is 8.5. See: Koppel, I.; Koppel, J.; Degerbeck, F.; Grehn, L.; Ragnarsson, U. J. Org. Chem. 1991, 56, 7172-7174.
    • tBu is 8.5. See: Koppel, I.; Koppel, J.; Degerbeck, F.; Grehn, L.; Ragnarsson, U. J. Org. Chem. 1991, 56, 7172-7174.
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    • For example, see ref 4b and (a) Lei, A.; Lu, X.; Liu, G. Tetrahedron Lett. 2004, 45, 1785-1788.
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    • For leading references, see ref 15 and (a) Stille, J. K, James, D. E. J. Organomet. Chem. 1976, 108, 401-408
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    • For extensive analysis of the mechanistic pathway of the parent Wacker process, see:, D. Reidel Publishing Co, Boston
    • For extensive analysis of the mechanistic pathway of the parent Wacker process, see: Henry, P. M. Palladium Catalyzed Oxidation of Hydrocarbons; D. Reidel Publishing Co.: Boston, 1980.
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    • The apparent discrepancy between our observations (which favor cis-aminopalladation reactions) and the early studies of Pd-mediated alkene animation (which favor trans-aminopalladation reactions; ref 15) undoubtedly reflects differences between the substrates (sulfonamides vs alkylamines) and/or reaction conditions (catalytic vs precomplexation of the alkene at low temperature followed by addition of stoichiometric amine nucleophile).
    • The apparent discrepancy between our observations (which favor cis-aminopalladation reactions) and the early studies of Pd-mediated alkene animation (which favor trans-aminopalladation reactions; ref 15) undoubtedly reflects differences between the substrates (sulfonamides vs alkylamines) and/or reaction conditions (catalytic vs precomplexation of the alkene at low temperature followed by addition of stoichiometric amine nucleophile).
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    • Another mechanism that could account for cis-aminopalladation of an alkene involves a six-membered electrocyclic transition state see below, See ref 16a, Chemical Equation Presented
    • Another mechanism that could account for cis-aminopalladation of an alkene involves a six-membered electrocyclic transition state (see below). See ref 16a. (Chemical Equation Presented)
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    • a of acetic acid in DMSO is 12.3: Maran, F.; Celadon, D.; Severin M. G.; Vianello, E. J. Am. Chem. Soc. 1991, 113, 9320-9329.
    • a of acetic acid in DMSO is 12.3: Maran, F.; Celadon, D.; Severin M. G.; Vianello, E. J. Am. Chem. Soc. 1991, 113, 9320-9329.


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