Ketones, 2-haloalkyl aryl

The rearrangement of acetals of 2-haloalkyl aryl ketones is a well-documented process yielding esters of 2-arylalkanoic acids by 1,2-aryl shift (equation 7). The mechanism of this rearrangement is reminiscent of other semipinacol rearrangements. Loss of the halogen (usually assisted by Lewis acid), yields a carbocation (4), which then undergoes a 1,2-aryl shift with carbonyl group formation. 

Reduction of a-halo ketones, This complex in combination with sodium iodide reduces a-halo ketones to the parent ketone in 80-90% yield. Sodium iodide and triethylamine-sulfur dioxide is more selective in that only aryl a-haloalkyl ketones are reduced. 

Several analgesic and anti-inflammatory drugs such as ibuprofen and naproxen belong to the general class of a-arylalkanoic acids. An often used synthetic route to these molecules is the C-C bond cleavage by Lewis acid catalyzed rearrangement of the ketals of aryl a-haloalkyl ketones (Rieu et al., 1986). Methods based on asymmetric catalysis have also been developed (see Chapter 9). It has recently been shown (Baldovi et al., 1992) that zinc-exchanged Y-zeolites can catalyze the transformation of the ethylene ketal (14) of 2-bromopropiophenone to the a-phenylpropanoic ester (15) (reaction 6.8). 

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