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Catalysis of Heterocyclic Azadiene Cycloaddition Reactions by Solvent Hydrogen Bonding: Concise Total Synthesis of Methoxatin.

ABSTRACT: Although it has been examined for decades, no general approach to catalysis of the inverse electron demand Diels-Alder reactions of heterocyclic azadienes has been introduced. Typically, additives such as Lewis acids lead to nonproductive consumption of the electron-rich dienophiles without productive activation of the electron-deficient heterocyclic azadienes. Herein, we report the first general method for catalysis of such cycloaddition reactions by using solvent hydrogen bonding of non-nucleophilic perfluoroalcohols, including hexafluoroisopropanol (HFIP) and trifluoroethanol (TFE), to activate the electron-deficient heterocyclic azadienes. Its use in promoting the cycloaddition of 1,2,3-triazine 4 with enamine 3 as the key step of a concise total synthesis of methoxatin is described.

SUBMITTER: Glinkerman CM

PROVIDER: S-EPMC5042865 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Catalysis of Heterocyclic Azadiene Cycloaddition Reactions by Solvent Hydrogen Bonding: Concise Total Synthesis of Methoxatin.

Glinkerman Christopher M CM Boger Dale L DL

Journal of the American Chemical Society 20160914 38

Although it has been examined for decades, no general approach to catalysis of the inverse electron demand Diels-Alder reactions of heterocyclic azadienes has been introduced. Typically, additives such as Lewis acids lead to nonproductive consumption of the electron-rich dienophiles without productive activation of the electron-deficient heterocyclic azadienes. Herein, we report the first general method for catalysis of such cycloaddition reactions by using solvent hydrogen bonding of non-nucleo ...[more]

PMID: 27571404

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