Page 6 - 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

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TABLE 9. [H 2 N Pr 2 ] Accelerated Arylation of Vinyl Ether in DMF
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Speeding up with Hydrogen Bond Donors
The ionic liquid approach enables successful regiocontrol,
FIGURE 1. Effect of salt additives on the arylation of butyl vinyl ether at
circumventing the need for silver/thallium salts. However,
different reaction times: ([)Bu 4 NBr, 12 h; (2) [HNEt 3 ][BF 4 ], 1 h.
the observed TOF (<2 h 1 ) and TON (<40) values were low.
in ionic liquids. In line with this view, Amatore and Jutand The dramatic decrease in the arylation rate with increasing
have recently shown that a high ionic strength favors bromide concentration suggests that the HBr generated
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R-arylation. And an earlier study by Milstein et al. revealed from each arylation cycle must be effectively scavenged
that olefin insertion into the PdAr bond in [L 2 Pd(Ar)X] is by the base NEt 3 (Figure 1 and Scheme 3). The trapping of the
greatly facilitated in a polar solvent. 25 bromide anions most likely arises from possible hydrogen
Evidence in support of the ionic pathway B comes from bonding between [HNEt 3 ] and Br , rendering the equilibri-
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reactions in the presence of added halide anions. 15 As um in favor of the Pd cation (eq 4). Thus, we reasoned that
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shown in Figure 1 (line [), the arylation of butyl vinyl ether introduction of a potential hydrogen bond donor (HBD)
with 4-bromoacetophenone was notably slowed even should enhance the reaction rates. The remarkable effect
when 1 equiv of Br (relative to palladium) was introduced of [HNEt 3 ] is clearly revealed in Figure 1 (line 2). 29

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into [bmim][BF 4 ], and the reaction rate was progressively Indeed, in the presence of [HNEt 3 ][BF 4 ] (1.5 equiv), the
reduced when more Bu 4 NBr was added. This is consistent arylation in [bmim][BF 4 ] becomes much faster, with no
with there being an equilibrium (eq 4), which is shifted compromise on regioselectivity. 29 For instance, the reac-
toward the left on addition of the halide ions. Similar tions of butyl vinyl ether with various bromides all com-
observations have been made in arylation reactions using pleted in less than 3 h. This is significant, as the reactions
aryl triflates 7a,28 and in the stoichiometric reaction of required up to 36 h to complete without [HNEt 3 ][BF 4 ]. Worth
[L 2 Pd(Ar)Cl] with olefins in molecular solvents. 25 noting is that the palladium loading could be lowered to 0.1
mol % in the presence of the HBD, increasing the TOF and
TON to ca. 80 h 1 and 1000, respectively.
Significantly, the HBD is also shown to accelerate aryla-

A further demonstration of the ionic pathway is seen in tion in common solvents. 29 Thus, under conditions used for
the competition reaction shown in eq 5. 15 Of the three [bmim][BF 4 ] but replacing the ionic liquid with DMF or DMSO,
olefins, only the electron-rich vinyl ether reacted. This is a various aryl bromides reacted with vinyl ethers or enamides,
result of preferential bonding of an electron-deficient Pd II affording R-arylated olefins exclusively (Tables 9 and 10). In
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cation with an electron-rich olefin. By way of contrast, in contrast, the reaction in the absence of [H 2 N Pr 2 ][BF 4 ] was
7a,13a,13b,15
DMF, the opposite chemoselectivity was observed when sluggish and much less selective.
1-naphthyl iodide was reacted with a mixture of butyl vinyl Ammonium salts, such as [NBu 4 ][Cl], are known to accel-
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ether and methyl acrylate, due to preferential coordination erate the Heck reaction. Under the Jeffery conditions, the
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of the electron-poor acrylate to a neutral Pd center. 13b Heck reaction presumably proceeds via the neutral path-
way, involving anion-ligated palladium species. 31 In con-
trast, the HBD [H n NR 4n ] (n = 1, 2) promoted arylation is
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typical of the Heck reaction proceeding by the cationic
pathway B, and we believe that the primary role of

Vol. 44, No. 8 ’ 2011 ’ 614–626 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 619