Page 7 - 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 11. Arylation of Butyl Vinyl Ether in EG

N
FIGURE 2. Effect of the solvent parameter E T on ln(TOF) in the
R-arylation of butyl vinyl ether with 4-bromoacetophenone.
TABLE 12. Arylation of Enamides in EG

i
TABLE 10. [H 2 N Pr 2 ] Accelerated Arylation of Enamides in DMSO
þ

Gratifyingly, the arylation in alcohols such as EG indeed
þ
[H n NR 4n ] is to hydrogen-bond with the bromide anion, 33a
proceeds fast and R-regioselectively. Examples obtained
shifting the equilibrium shown in eq 6 toward the Pd(II)
with butyl vinyl ether and enamides are summarized in
olefin cation.
Tables 11 and 12. A further study has revealed remarkably
high activity (TOF up to 15 625 h 1 ) and productivity (TON
5
up to 3.75 10 ) in the arylation of vinyl ethers, with the
5 34
substrate-to-catalyst (S/C) ratio reaching 5 10 . These
Salty No Longer: r-Arylation in Alcohols numbers far surpass those observed in ionic liquids or when
The observations made with the ammonium HBD raise an using ammonium HBDs, representing actually the highest
interesting question. Could much cheaper and environmen- values ever reported for the Heck reaction of electron rich
tally friendlier alcohols be used as solvent to replace the olefins. In particular, sterically demanding vinyl ethers also
imidazolium or HBD salts? Alcohols are known to act as reacted under these conditions, leading to interesting aryl
receptors for halide anions, and in particular ethylene glycol alkyl ketones (eq 7).
N
(EG) is a good HBD as judged by its high E T value of 0.790. 32
This belief was strengthened by the study of an arylation
in more than 20 solvents, which revealed that hydrogen-
bond donating, protic solvents indeed accelerate R-regiose-
lective arylation. 33 As shown in Figure 2, the higher the E T N Heteroaryl bromides could also be brought to arylate the
values, the faster this reaction becomes, with EG affording electron-rich olefins. However, better yields were obtained
the fastest arylation. with Pddppf than Pddppp. 35 As shown in Table 13, high

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