Krohnke annulation

KrOhnke annulation involves the condensation reaction of an a-pyridinium methyl ketone salt such as phenacylpyridinium bromide 191 to an enones such as benzalacetophenone 193 to afford 2,4,6-triphenylpyridine 194 in 90% yield. Krdhnke found that glacial acetic acid and ammonium acetate were the ideal conditions to promote the desired Michael addition. 

METHOX (22) was synthesized in three steps from the commercially available pinocarvone (47) using the Krohnke annulation (47 + 48 —> 50). Pinocarvone itself, commercially available only in one enantiomeric form, can be readily obtained from the much cheaper oi-pinene (46) via an ene-reaction with singlet oxygen. Since both enantiomers of oi-pinene are commercially available, this procedure can be utilized for the preparation of both enantiomers of METHOX (22) [28b], The Krohnke reagent 48 [52] is readily obtained in one pot via iodination of the corresponding acetophenone (49) in pyridine [28bj. 

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