Page 3 - From -Arylation of Olefins to Acylation with Aldehydes: A Journey in Regiocontrol of the Heck Reaction

R-Arylation of Olefins to Acylation with Aldehydes Ruan and Xiao

SCHEME 3. Two Competing Pathways in the Heck Reaction

species. It is also apparent that a monodentate ligand would TABLE 1. Arylation of Vinyl Ethers with Aryl Bromides in [bmim][BF 4 ]
make pathway A more likely, whereas a bidentate ligand
would encourage pathway B. These tactics have also been
widely exploited in enantioselective Heck reactions, where
the ionic pathway is generally believed to give high
enantioselectivities. 3c,d
There are, however, shortcomings associated with these
methods. Silver introduces added cost, thallium salts are toxic,
and triflates are generally commercially unavailable in addition
to being base sensitive and thermally labile. Hence, there clearly
exists an incentive to develop cleaner, faster, and more econom-
ical R-regioselective catalytic systems that tolerate aryl halides
while obviating the need for expensive or toxic inorganic
additives. Summarized below isajourneywehave undertaken
since the early 2000s, aiming to address these issues.

Promoting the Ionic Pathway with Ionic
Liquids
Ionic liquids such as imidazolium salts are entirely composed of the reaction was subsequently explored. 15 Selected ex-
of ions. Thus, electrostatic interactions would be expected to amples of arylation of vinyl ethers with aryl bromides are
favor the generation of a Pdolefin cation and a halide shown in Table 1. The arylation proceeded with >99/1 R/β-
anion from two neutral precursors over that of a neutral regioselectivities, furnishing aryl methyl ketones in high
Pdolefin intermediate from the same (pathway B vs A, yields after acidic hydrolysis of the arylated enol ethers.
Scheme 3). This seemingly naive, likelikeslike approach The regioselectivity was not affected by the electronic
proves to be highly effective. In 2001 in a project aimed to property of substituents on the aryl rings, and aryl iodides
develop catalysis in ionic liquids, we quickly found that by worked equally well.
simply switching solvent from the traditional CH 3 CN, DMF, Heteroaryl bromides could also be brought to couple with
or DMSO to the ionic liquid 1-butyl-3-methylimidazolium vinyl ethers. 16 Table 2 shows examples obtained with
tetrafluoroborate ([bmim][BF 4 ]), the benchmark electron-rich n-butyl vinyl ether. Excellent R-selectivities were obtained,
olefin butyl vinyl ether is arylated exclusively R-regioselec- providing an alternative way to acetyl heteroaromatics
tively with aryl bromides under the catalysis of Pddppp which would be difficult to access via the traditional Friedel
(dppp =1,3-bis(diphenylphosphino)propane). 14 The scope Crafts acylation.

616 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 614–626 ’ 2011 ’ Vol. 44, No. 8