Thursday, September 19, 2019

organic chemistry - Does a Grignard reagent react with enones to give the 1,2- or 1,4- product?


Reaction of phenylmagnesium bromide with cyclohex-2-en-1-one


Cyclohexenone, an α,β-unsaturated ketone, is electrophilic at both the carbonyl carbon, as well as the β-carbon. So, it can either undergo 1,2-addition to give the allylic alcohol 1, or 1,4-addition to give the ketone 2.


Where does the Grignard reagent add to?



Answer



The correct answer is the 1,2-addition product (i.e. the allylic alcohol 1). In general, Grignard reagents and organolithium reagents add directly to the carbonyl carbon, while organocuprates (organocopper reagents) add to the beta-position of an unsaturated ketone.



This exact transformation was reported by Akai and coworkers recently (Org. Lett. 2010, 12, 4900) and they obtained compound 1 in 95% yield (the supplementary information (PDF) is free).


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