Novel Route to Arylacetones (Chem Commun 1984)

[Aurelius]

A Novel Route to Arylacetones via a Masked alpha-Acylcarbonium Intermediate
Shimon Shatzmiller, Ramy Lidor, Eytan Shalom and Eliezer Bahar
J. Chem. Soc. Chem. Commun. 795 (1984)

The Ag⁺ induced aromatic substitution reaction of bromoacetone O-methyloxime is described.

Abstract:

Oxime ethers can be efficiently metallated at the alpha-carbon atoms and the derived enolate equivalents (1) can then participate in a variety of useful C-C bond forming reactions. ¹ The alpha-carbon might also support a positive charge [i.e. (2)] stabilized by n-type electron delocalization from the oxime group, and this cation could act as a synthetic equivalent of an l-acylcarbonium ion ².  In this communication we describe a method for the conversion of oxime ethers into functionalized ketones using reactive intermediates of type (1) or (2), employing acetone O-methyloxime as a model compound.

Example 1:

Litiation of acetone O-methyloxime (3) was achieved with 1.2M solution of ⁿBuLi in THF-hexane in 5 min at –65°C.  Addition of lithiated (3) to molecular bromine in THF at –65°C over 15 min resulted in the formation of the Z-bromo-oxime ether, (4).  Isomerization of (4) in CHCl₃-HBr gave the thermodynamically favored E-isomer.  (5) ⁺  The halogen atom could be exchanged for alkoxy by treatment of (5) with 1.1eq. of MeO[CH₂]₂Ona in THF for 12hr to (6) in 88% yield.

The bromo-oxime ethers (4) and (5) were also converted into a reactive intermediate of type (2) which reacted in aromatic substitution reactions.  Addition of 10mmol of either (4) or (5) in 20 ml of dry DCE to a solution of 10 mmol of AgBF₄ and 10mmol of the aromatic compound in 20ml of DCE at 25°C followed by efficient stirring in the dark for 18hr and then work-up with a 10% KCN-H₂ solution gave good  (82-91%) yields of the aromatic substitution products (7a-e)   ⁺   as the E-isomers.  Acid treatment of (7a-e) (HCl-H₂O-MeOH 1:5:5) for 10 hrs at 65°C and distillation gave the corresponding arylacetones (8a-e) in high (90%) yield.



References:

1.  V. Jaeger. H. Grund, and W. Schwab, Agnew. Chem. Int. Ed. Engl., 1979, 18, 78; S. Shatzmiller and R. Lidor, JACS 1981, 103, 5916.

2.  J.-P. Begue and M. Charpentier-Morize, Acc. Chem. Res.  1980, 13, 207.

3.  G. J. Karbatsos and N. His Tetrahedron 1967, 23, 1079.

4.   S. Shatzmiller, P. Gygax, D. Hall and A. Eschenmoser. Helv. Chim. Acta.  1973, 56, 2961



⁺  The geometry of the oxime ether moiety was elucidated on the basis of the chemical shift of the ketone Me group in the ²Hn.m.r. spectrum (CCl₄) e.g. the methyl hydrogens resonate at 2.01 in (4) but in (5) they are at 1.96.  In (6), it is at 1.79 (E-isomer having 1.91) for (7a-e) the resonances are at 1.71, 1.70, 1.70, 1.71 and 1.74 respectively.   Whereas the corresponding Z-isomers are at 1.75, 1.73, 1.74, 1.75 and 1.76 respectively.  (see also Ref. 3).