A Parham cyclization approach to diaryl-fused seven-membered ring heterocyclic ketones

作者：Farrokh John; Campos Catherine; Hunt David A^*

来源：Tetrahedron Letters, 2015, 56(37): 5245-5247.

DOI：10.1016/j.tetlet.2015.07.043

• Parham cyclization
• Functionalized aryllithium
• Intramolecular cyclization
• 6,7,6 fused ring system

Aryl-fused seven membered heterocyclic frameworks appear in a variety of pharmaceutically pertinent compounds. However, only a very few methods for their preparation have been described. This work describes a novel synthesis route to diaryl-fused seven membered heterocyclic ketones through the generation of functionalized aryllithiums by bromine-lithium exchange, followed by intramolecular cyclization onto an electrophilic nitrile functional group. The resulting N-lithioimine can then be hydrolyzed to the desired ketone, generally in good yields. The order of addition of n-butyllithium is crucial to the process with inverse addition proving to mitigate side product formation and increase yields.

• 出版日期2015-9-9