Gas-phase nazarov cyclization of protonated 2-methoxy and 2-hydroxychalcone: an example of intramolecular proton-transport catalysis.

Upon CA, ESI generated [M + H](+) ions of chalcone (benzalacetophenone) and 3-phenyl-indanone both undergo losses of H(2)O, CO, and the elements of benzene. CA of the [M + H](+) ions of 2-methoxy and 2-hydroxychalcone, however, prompts instead a dominant loss of ketene. In addition, CA of the [M + H](+) ions of 2-methoxy-beta-methylchalcone produces an analogous loss of methylketene instead. Furthermore, the [M + D](+) ion of 2-methoxychalcone upon CA eliminates only unlabeled ketene, and the resultant product, the [M + D - ketene](+) ion, yields only the benzyl-d(1) cation upon CA. We propose that the 2-methoxy and 2-hydroxy (ortho) substituents facilitate a Nazarov cyclization to the corresponding protonated 3-aryl-indanones by mediating a critical proton transfer. The resultant protonated indanones then undergo a second proton transport catalysis facilitated by the same ortho substituents producing intermediates that eliminate ketene to yield 2-methoxy- or 2-hydroxyphenyl-phenyl-methylcarbocations, respectively. The basicity of the ortho substituent is important; for example, replacement of the ortho function with a chloro substituent does not provide an efficient catalyst for the proton transports. The Nazarov cyclization must compete with an alternate cyclization, driven by the protonated carbonyl group of the chalcone that results in losses of H(2)O and CO. The assisted proton transfer mediated by the ortho substituent shifts the competition in favor of the Nazarov cyclization. The proposed mechanisms for cyclization and fragmentation are supported by high-mass resolving power data, tandem mass spectra, deuterium labeling, and molecular orbital calculations.