You might try using the O-methyl oxime of the ketone - it's a known ortho-directing group for Pd(II) reactions.

Dear James,

Thanks for your answer. This will add a couple of stages to my total synthesis. Further, have seen that preparing the oxime and running the oxygenation in Ac2O-AcOH, the oxime undergoes in situ acylation and after the reaction proceeds (cannot use persulfate or oxone, just BTI) the protecting group can be removed under mild conditions, as part of the workup, but I am reluctant to add unnecessary steps. There has to be something very simple we are doing wrong....

Thanks again anyway!!!

According to Moriarty et al. acetophenone may be oxidized in wet acetonitrile to the corresponding alpha-hydroxy ketone whilst refluxing the mixture (so roughly the same conditions as the work by Dong, without the palladium cat. and other aprotic solvent).

So my suspicion is that your dichloroethane wasn't sufficiently dry enough.

Article ChemInform Abstract: Direct α-Hydroxylation of Ketones Under...

Thanks Lukas!

You're welcome, please let me know whether drying the solvent helps with your synthesis.

o-Acylphenols can be prepared by The Fries rearrangement which the reaction is catalyzed by AlCl3.

To avoid using Lewis acids, the synthesis of o-acylphenols derivatives can be achieved by the reaction of aryl acetate with p-toluenesulphonic acid (100-110 °C, 30 min., then poured in ice cold water).

Dear Atef,

Thanks for the tip; we have run Fries rearrangements as part of other projects; however, this will not be useful for our real molecule.

From the reaction conditions given in Scheme 2 of the Dong paper, I think both your substitutions (4-MeO and 4-Br) need the Pd(TFA)2 catalyst. Their 4-Br-compound needed directly Pd(TFA)2 to react at 100°C (Footnote c) and their 4-MeO-compound was oxidized in the presence of 2 mL trifluoroacetic acid, which presumably generated Pd(TFA)2 in situ. All compounds containing ethers were reacted in the presence of TFA according to method B. Did you use these conditions or only Pd(OAc)?

Dear Richard,

Thanks for the answer. We used Pd(OAc)2 because we do not have the trifluoroacetate; however, we also runu experiments in the presence of TFA. In addition, following the conjecture by Lukas, we prepared fresh anhydrous 1,2-DCE (reflux over CaH2 and distill). It still gives the ArC(O)CH2OH product. Maybe there has something to do with "catalyst preparation" (BTI + Pd catalyst), as it looks like the cat. is not working properly. We keep trying and will change the acetophenone to see whether it is an electronic problema and we, in fact, need the Pd(TFA)2 catalyst.

Thanks again very much!!!

Just an addendum: Did you consider the paper of Rao, right before the Dang paper in the same issue of ACIE? It's basically the same method, just with additional 10% TFA anhydride. They also use a large variety of oxidants, maybe you can find something fitting your needs. From their yields I guess enolization of the ketone, leading to your observed alpha-hydroxylation, is the key problem for decreasing arylhydroxylation. Maybe you could also add some coordinating ions like sodium or potassium (as palladate salts), similar to the Kolbe-Schmitt reaction. Is your intended target structure really an aryl methyl ketone or more complex? Anyway, good luck with your synthesis!

Dear Richard,

Thanks for your message and tips. My target is a natural product and this is supposed to be the last reaction. My target has actually 2 carbonyls; one of them is a,b-unsaturated, so I think will have some selectivity. Will check the ACIE paper you have just pointed out to.

Very thanful again!!!

Palladium-Catalyzed ortho-CH-Bond Oxygenation of Aromatic Ketones

Pui Ying Choy and Fuk Yee Kwong. https://www.google.com.eg/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0ahUKEwjN6uXS8drOAhXHvhQKHfJ1AjYQFggfMAA&url=https%3A%2F%2Fwww.researchgate.net%2Fpost%2FOrtho-oxygenation_of_aromatic_ketones_Any_clue&usg=AFQjCNHNDInuaz-C_RsF2dKG9HqexT1TOw&sig2=s4BWdL4udEeCniWMtXbqeA

Dear Teodoro S Kaufman ,

Please, find in attach, a paper on: Catalytic Hydroxylation DOI: 10.1002/anie.201207458

Pd-Catalyzed CH Oxygenation with TFA/TFAA: Expedient Access

to Oxygen-Containing Heterocycles and Late-Stage Drug Modification**

Gang Shan, Xinglin Yang, Linlin Ma, and Yu Rao*

Best wishes

C–H functionalization directed by transformable nitrogen heterocycles: synthesis of

ortho-oxygenated arylnaphthalenes from arylphthalazines†

Shiva K. Rastogi, Derek C. Medellin and Alexander Kornienko*

Dear Talaat, Thanks for your assistance. Our problem is that we need to use methyl ketones as starting materials. Under the reaction conditions, we get oxygenation of the aliphatic side chain (alpha carbonyl) instead of the aromatic ring (ortho carbonyl).

Dear Teodoro S Kaufman,

I may suggest that some sort of rearrangement reaction with uncertain mechanism have taken place.