Lee D.-H, Kwon K.-H, Yi CS * Marquette University, Milwaukee, USA
Dehydrative C–H Alkylation and Alkenylation of Phenols with Alcohols: Expedient Synthesis for Substituted Phenols and Benzofurans.
J. Am. Chem. Soc. 2012;
134: 7325-7328
Key words
benzofurans - C–H activation - ruthenium catalysis
Significance
Reported is the ruthenium-catalyzed dehydrative ortho-functionalization of phenols 1 with diols 2 affording benzofurans 4. When simple alcohols were employed, only ortho-functionalized phenols were obtained (not shown). When diols 2 were employed, the cyclized benzofurans 4 were the preferred products. Inclusion of an excess of a simple alkene (cyclopentene) promoted the coupling reaction. An impressive array of substrates were shown to undergo the transformation (4a–x), including more complex diols (4u) and structurally elaborate phenols (4s,4v,4w). A cursory investigation of the reaction mechanism is also reported.
Comment
The present report represents a highly convenient and robust method for the synthesis of substituted benzofurans, which are medicinally relevant heterocycles with a diverse range of biological activities (see Review below). The sheer scope and high yields of the reported process appear to make this method highly attractive for the synthesis of 2-substituted benzofurans. It would be interesting to know if the process performed as well on scale (10 g and above) as it does on more standard quantities (1 mmol).
Review
L. De Luca, G. Nieddu, A. Porcheddu,
G. Giacomelli Curr. Med. Chem. 2009, 16, 1–20.
