Development and Scope of the Phenolic Aldol Reaction of 2-Formylpyridines

Abstract

2-Formylpyridines have been shown to be suitable electrophiles for the magnesium-promoted phenolic aldol reaction. Exceptionally mild reaction conditions have been developed and a brief survey of the reaction scope has been conducted. This process gives straightforward access to a range of functionalised 2-hydroxy­phenyl-2-pyridylmethanols and 2-hydroxyphenyl-2-pyridylmethanes via their subsequent reduction.

Key words

phenolic aldol reaction - arylation - magnesium phenoxides - 2-formylpyridines - 2-hydroxyphenyl-2-pyridylmethanols

References and Notes

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1

Current address: Peakdale Molecular Ltd, Peakdale Science Park, Sheffield Road, Chapel-en-le-Frith SK23 0PG, UK.

8

Use of Et₂O on scale is complicated by its high volatility and flammability, MTBE is a much preferred alternative.

11

Solvents investigated; acetone, MeCN, MTBE, chloro-benzene, cyclopentyl methyl ether, CH₂Cl₂, EtOH, EtOAc, i-PrOAc, 2-methyltetrahydrofuran, THF, α,α,α-trifluoro-toluene, and sulfolane.