I was looking at my dearly departed best bee Slappy's posts and found this gem.
P2P's by Pd-catalyzed arylation of acetoacetates
(Rated as: excellent)
The yields are no good. You need to use a beta-ketoester as the acetone source, then decarboxylate.
That is why I present...
Synthesis of substituted Phenylacetone derivatives via Pd-catalysed alpha-Arylation of Acetoacetate esters.
The efficent large scale synthesis of Phenylacetone and it's derivatives can be accomplished from economical precursors via a Pd-catalysed coupling reaction, and subsequent decarboxylation. First, Methyl (or Ethyl) Acetoacetate is alpha-Arylated with an Aryl Halide (Ph-Br, Ph-I, Ph-OTf), to form 1-Carbomethoxy-Phenylacetone. This ester is then decarboxylated by boiling in dilute HCl, yielding P2P. The attractivness of this route is that it starts from cheap, commodity chemicals (Bromobenzene, Ethyl Acetoacetate, and tribasic Potassium Phosphate are less than $30/kg), low catalyst loading (1-2 mol% Pd), and high efficiancy (yield 80-90%).
The mechanism involves oxidative addition of Ar-X to the Pd center to give Ln(Ar)Pd-X (where L=1 or 2),which then coordinates to the enolate (formed by the beta-Ketoester and base, like K3PO4), and eliminates a mole of KX, giving Ln(Ar)Pd-Enolate, which couples the coordinated Aryl moiety, and reductivly eliminates.
Aryl Halide (1 eq) = R-Ph-Br, R-Ph-I, R-Ph-OTf
Alkyl Acetoacetate (1.2 eq)
Base (2 eq) = K3PO4
Pd pre-catalyst (1 mol%) = Pd(OAc)2, Pd2(dba)3
Phosphine ligand (2.2 mol%) = PPh3, PtBu3, PCy3
Sutible solvents:
THF, Toluene, Dioxane
Reaction conditions:
10-48h at 70-100°C
Ref:
Buchwald et al., "Highly Active and Selective Catalysts for the Formation of a-Aryl Ketones", J. Am. Chem. Soc. 2000, 122, 1360-1370
Hartwig et al., "Transition metal-catalysed process for preparing alpha-arylated carbonyl containing compounds", Patent US6057456