Synthetic methodologies for preparing N-alkyl pyridones
The Anderson group is focused on developing new synthetic methodologies for preparing N-alkyl pyridones, including amino acid homologues.
N-Alkyl pyridones are interesting motifs due to their prevalence in natural products as well as their potential to serve as amino acid mimics and engage in strong intermolecular hydrogen bonds. As such, the development of a simple means for achieving selective nitrogen alkylation within pyridone motifs continues to be a synthetic goal. To this end, our group has recently disclosed a novel lithium iodide mediated O- to N-benzyl migration, with current studies directed towards elucidating the transformation’s mechanism (Scheme 1, JOC 2008).
Scheme 1. Lithium Iodide-Promoted O- to N-Benzyl Migration.
Extension of the lithium iodide-promoted migration to propargylic systems, such as 7, has lead to not only the expected product 8, but also a wealth of addition new reactions (Scheme 2). Utilizing either a modified lithium iodide method or a gold catalyzed process, we can now access a wide range of synthetically useful, N-alkyl pyridone containing products 8-10 by simply modifying reaction conditions. Further studies to optimize these reactions and determine their scope and mechanism are ongoing in our laboratory.
Scheme 2. Reactivity of Propargyloxypyridines.
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