Recent research in the Donohoe has demonstrated that methanol can be used in hydrogen borrowing catalysis to form α-branched methylene ketones. This was shown to proceed via initial oxidation of methanol to formaldehyde, which subsequently underwent an aldol reaction with a methylene ketone. E1cB elimination, followed by reduction of the enone delivered the α-branched product. This protocol failed to work with alcohols larger than methanol and we speculated that the initially formed aldol adduct was too strained, resulting in a retro-aldol process. In order to prevent the retro-aldol reaction, we searched for methylene ketones substituted with motifs that would (i) be ‘small’ enough to relieve strain in the aldol adduct and (ii) have a motif that could be easily manipulated to expand the product’s synthetic utility. We found cyclopropyl ketones (1) to be suitable candidates. The products (4) then underwent homoconjugate addition with various nucleophiles to give several branched ketones (5). Further advances in Hydrogen Borrowing-related processes will also be discussed.

Expanding the scope of hydrogen borrowing catalysis using cyclopropyl ketones as key structural motifs

253rd National Meeting (2017)

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