Sciencemadness Discussion Board
Not logged in [Login ]
Go To Bottom

Printable Version  
Author: Subject: Enolate arylation without palladium?
arclightshroom
Harmless
*




Posts: 7
Registered: 17-4-2023
Member Is Offline


[*] posted on 5-8-2023 at 00:33
Enolate arylation without palladium?


I was researching alkylation of enolates, and I was interested in trying one with the alkylating agent being bromobenzene. Unfortunately from what I've read online aryl groups do not react with enolates on their own, and palladium catalysts as well as ligands are used in this reaction. Are there any other (cheaper) catalyst one could use? I unfortunaly didn't manage to find any papers.

The plan was to create the enolate of cyclohexanone with NaH and react it with bromobenzene.
View user's profile View All Posts By User
clearly_not_atara
International Hazard
*****




Posts: 2722
Registered: 3-11-2013
Member Is Offline

Mood: Big

[*] posted on 5-8-2023 at 07:17


There are also copper-catalyzed versions. Sometimes the ligands are not so complex (e.g. prolinol, N-monomethyl ethylenediamine).



Quote: Originally posted by bnull  
you can always buy new equipment but can't buy new fingers.
View user's profile View All Posts By User
SyntheticFunk
Harmless
*




Posts: 21
Registered: 30-12-2022
Member Is Offline


[*] posted on 6-8-2023 at 10:43


As was pointed out above, copper can be used for alpha arylation of enolates without the need of exotic ligands/reagents. However, the reaction may not give you the desired product depending on the exact enolate you're using. In the linked paper, the authors used acetylacetone as their enolate. There are three very notable features of this. 1. Following bond formation between the alpha carbon and aromatic ring, deacetylation occurs. 2. This deacetylation seems to occur if a nucleophilic oxygen is present in the reaction (i.e. water, alcohols, etc). Anhydrous conditions appear to avoid the deacetylation. 3. IIRC from another, similar paper, bidentate coordination of the 2 carbonyl oxygens in acetylacetone to copper is involved in the mechanism, which means you're somewhat limited in the enolates that can be used. So acetoacetic esters can be used (yielding phenylacetic acids), as can acetylacetone (yielding aryl-2-propanones), but I am unsure if enolates outside of beta dicarbonyl compounds can be used. EDIT: The scope is not limited beta dicarbonyl species. though a bidentate ligand seems to be necessary, it does not have to be the enolate species. There are also many examples of a variety of enolates being used. However, the more acidic the alpha proton, and thus the easier the enolate is formed, the more facile conditions required. This implies that enamines could be excellent candidates for alpha arylations as enamine formation is much more facile than enolate formation. However, I don’t have any sources to support this idea.

Alternatively, isopropenyl acetate can be used with aryl diazonium salts to achieve alpha arylations. Im sure other enol esters can be used as well. Fortunately this reaction also does not require expensive or exotic catalysts, with 10mol% of salicylic acid performing the catalysis in this reaction. t-butyl nitrite is used here as it is more soluble in organic solvents than NaNO2 and is therefore more efficient at forming the diazonium species from the aromatic amine. However, I don't believe it serves any special purpose beyond that and with some effort, NaNO2 could be used in place of tBuONO. However, this reaction suffers from requiring 10mol excess of enol ester : amine, which is quite a waste.

Attachment: AlphaArylationCopper.pdf (299kB)
This file has been downloaded 164 times

Attachment: ArylationIsopropenylAcetate.pdf (2.2MB)
This file has been downloaded 159 times

[Edited on 7-8-2023 by SyntheticFunk]
View user's profile View All Posts By User
SyntheticFunk
Harmless
*




Posts: 21
Registered: 30-12-2022
Member Is Offline


[*] posted on 11-8-2023 at 23:50


Just wanted to add I've had success with the diazonium based method using n-butyl nitrite instead of t-butyl. It makes me wonder the scope of organic nitrites than can be used successfully. The yield was decent (50-70%, I forget exactly) and GC-MS suggests byproduct formation was minimal.

[Edited on 12-8-2023 by SyntheticFunk]
View user's profile View All Posts By User

  Go To Top