Page 4 - 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

TABLE 2. Arylation with Heteroaryl Bromides in [bmim][BF 4 ] TABLE 3. Synthesis of Cyclic Ketals in [bmim][BF 4 ]

Inspired by the work of Hallberg and Larhed on the
arylation of hydroxyalkyl vinyl ethers to synthesize cyclic
ketals, using aryl triflates or aryl bromides combined with
TlOAc in DMF, 12c we performed the same reaction with aryl
bromides in an ionic liquid. As is shown in Table 3, cyclic
ketals are formed in good yields, via the intermediacy of R
arylated enol ethers. 17 We further demonstrated that both
the catalyst and ionic liquid are recyclable.
Other electron-rich olefins were also examined. Allyltri- TABLE 4. Arylation of Enamides in DMSO[bmim][BF 4 ]
methylsilane, the R carbon of which is more positively
charged, reacted with aryl bromides of diverse electronic
properties, furnishing exclusively the R-arylated allylsilanes
(eq 3). 15 Similar regioselective arylation could also be
achieved in CH 3 CN, but aryl triflates were necessary. 12b

Under the same reaction conditions, however, the aryla-
tion of enamides failed. This may partly stem from the
nitrogen lone pair being engaged in conjugation with the
carbonyl group. Somewhat surprisingly, when DMSO was
introduced as cosolvent, regioselective arylation took
place. 15 Table 4 summarizes the results obtained in a 1:1
(volume) mixture of [bmim][BF 4 ] and DMSO. All the reactions
were R-selective, affording synthetically important R-aryle- The ionic liquid protocol also finds use in the arylation of
namides. Further study showed that the amount of ionic unsaturated ketones. Table 6 shows examples from 5-hex-
liquid in the mixture could be substantially reduced. 18 en-2-one. Arylated unsaturated ketones were obtained in up
Using the DMSO[bmim][BF 4 ] cocktail, allyl alcohol was to 99/1 R/β ratios (Table 6). 22 In both this reaction and that
II
arylated with excellent R-regioselectivity (Table 5). 19 Homo- of the alcohols, the oxygen atom may coordinate to Pd ,
allyl alcohol and other unsaturated alcohols were less assisting bromide dissociation. It is interesting to note, how-
selective, however. The ability to arylate these alcohols in ever, that a similar regioselectivity was observed with 1-hex-
such a regioselective manner is pleasing, as their Heck ene when the ionic pathway B was made favorable. 5a
reaction usually leads to β-substitution. 19,20 Allyl alcohols Good regioselectivities necessitate careful choice of li-
with substituent next to the OH group were also arylated, gands, and dppp appears to be most effective thus far. This is
affording up to 70% R-products. It appears that increased seen in the effect of phosphines on the arylation of butyl
steric bulkiness diminishes the R/β ratios. 21 vinyl ether with 4-bromobenzaldehyde (Table 7). 15 There

Vol. 44, No. 8 ’ 2011 ’ 614–626 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 617