Palladium-Catalyzed Three-Component Synthesis of Oxazolines and Oxazines

Key words

oxazolines - oxazines - carbon monoxide - multicomponent reaction - palladium catalysis

Significance

Described is the synthesis of oxazolines via a three-component process, in which readily available aryl bromides, carbon monoxide and 2-chloroethylamine undergo a palladium-catalyzed carbonylation and a subsequent cyclization to afford 2-aryloxazolines in good yield. Replacing 2-chloroethylamine with 3-chloropropylamine also works well and in this case the corresponding 2-aryloxazine derivatives are formed. Notably, both electron-donating and electron-withdrawing groups are tolerated in this process. However, the scope of the three-component process was not well investigated, especially for ortho- and meta-substituted aryl bromides.

Comment

Oxazolines and oxazoles are important heterocycles for organic synthesis and materials chemistry (see Book below). A number of methodologies for the construction of the oxazoline ring from aryl aldehydes, nitriles, carboxylic acids and related derivatives have been developed (e.g., S. Takahashi, H. Togo Synthesis 2009, 2329). In comparison with those, the present carbonylation–cyclization strategy offers a straight-forward way for the synthesis of oxazolines and their analogues from easily available starting materials. A drawback of this method is the high pressure required (10 bar).

Book

Oxazoles: synthesis, reactions, and spectroscopy, Part 2; D. C. Palmer, Ed.; Wiley: Hoboken, 2004.