Phenols can be made with KOH

Although it might sound straightforward, making phenols directly using a hydroxide salt has been a long-sought-after, previously unachieved goal. Phenols are versatile synthetic building blocks for pharmaceuticals and materials, and inexpensive direct routes to making them are desirable. Stephen L. Buchwald and coworkers at MIT have succeeded in making phenols via the palladium-catalyzed reaction of aryl halides using KOH as a nucleophile (J. Am. Chem. Soc., DOI: 10.1021/ja0639719). A key factor was the use of either a commercially available biaryl ligand or a newer, more hindered analog (shown), recently synthesized by Buchwald's group, to prepare phenols from ortho-substituted aryl or heteroaryl bromides and chlorides. Taking another new approach, the researchers also coupled the phenol synthesis with alkylation using alkyl halides to make alkyl aryl ethers. This one-pot conversion avoids limitations, such as competitive β-hydride elimination, of existing palladium-catalyzed coupling methods and expands the range of available alkyl aryl ethers. Minor drawbacks for practical use include high catalyst loadings and high reaction temperature (100 °C).