1-Benzoxepines from 2-Acylmethoxyaryl Boronic Acids and Allenoates

Significance

As a continuation of previous work from these laboratories (G. Liu, X. Lu Adv. Synth. Catal. 2007, 349, 2247), reported is a convenient synthesis of 1-benzoxepine derivatives by a cationic Pd-catalyzed [5+2]-annulation reaction of 2-acylmethoxyaryl boronic acids with allenoates. The reaction was optimized in terms of solvent and cationic palladium complex, showing that the counteranion played a very important role. Additives had an unfavorable effect on the reaction. The yields range from mediocre to good, and the substrate scope could have benefited from study of substrates containing functional groups which would be useful for further transformations. The starting boronic acids were synthesized from the corresponding substituted ortho-iodophenols and 1-bromopropan-2-one via substitution, followed by acyl protection, metal-halogen exchange/boron quench, and deprotection in ˜30% overall yield. An asymmetric version of this reaction was briefly tested, but resulted in products with low enantioselectivities.