Angewandte
Chemie
addition product was observed at room temperature or at
708C in the absence of catalyst, and the reaction yields were
similar to the conversions.
Table 3 summarizes reactions of acyclic dienes with aryl
alcohols and carboxylic acids in the presence of [Pd(PPh3)4]
catalyst. These reactions demonstrate that acyclic allylic
product in 71% yield (Table 2, entry 1), whereas the reaction
at 608C consumed 51% of the phenol and formed the
addition product in 46% yield. Second, the addition of a
second portion of catalyst did not lead to further reaction.
To determine definitively if the reaction was reversible,
we subjected 4-tert-butylphenyl cyclohexenyl ether to cata-
lytic quantities of [Pd(PPh3)4]at room temperature, along
with 4-tert-butylphenol (0.1 equiv) to activate the catalyst.
Consistent with the proposed equilibrium, 55% of the ether
was consumed to give a 1.1:1.5:1 ratio of ether/4-tert-
butylphenol, and cyclohexadiene after 24 h [Eq. (2)]. The
final concentrations from both the forward and reverse
reactions at room temperature indicated that the Keq was
1.7 Æ 0.7; with estimated activity coefficients, the equilibrium
constant was 0.62 Æ 0.25. These values are smaller than those
for the addition of methanol to isobutylene.[19]
À
ethers can also be prepared by the O H addition process.
Table 3: Pd-catalyzed addition of acidic OH groups to acyclic dienes.[a]
Entry Diene
Product
Yield [%] Conversion [%][c]
(E/Z)[b]
63
(88:12)
1
2
68
59
(89:11)
62
3[d]
62
64
41
(85:15)
4[e]
42[f]
This thermodynamic analysis of the addition process
[a] Reaction conditions: 4-tert-butylphenol or benzoic acid (1.0 mmol),
dienes (4.0 mmol), [Pd(PPh3)4] (0.01 mmol), toluene (0.5 mL), room
temperature, 24 h, unless otherwise noted. [b] Yields of isolated products.
[c] Calculated by GC. [d] Diene (2.0 mmol), [Pd(PPh3)4] (0.05 mmol).
[e] Diene (8.0 mmol), [Pd(PPh3)4] (0.02 mmol), toluene (1.0 mL), 508C.
[f] Calculated by 1H NMR spectroscopy.
À
underscores that the value of DG for O H addition across
olefins is close enough to 0 that small changes in the structures
and concentrations of the reactants can influence the
conversion. Catalysts active enough to allow the reactions
to be conducted under low temperatures conditions with high
reactant concentrations are important to obtain high yields of
products. Under these conditions, we have shown that the
transition-metal-catalyzed addition of phenolic and carbox-
ylic acids across dienes occurs in good yields and with broad
scope.
The reactions of 4-tert-butylphenol and benzoic acid with
trans-1,3-pentadiene and (E)-3-methyl-1,3-pentadiene gave
products with the aryloxy group at the more hindered,
internal position by either 1,2- or 1,4-addition (Table 3,
entries 1–2, 4). The reaction of 2,3-dimethoxybutadiene with
4-tert-butylphenol also formed the product with the more
substituted carbon atom, this time by a clear 1,2-addition Experimental Section
General procedure (Table 2, entry 1): In a glovebox, 1,3-cyclohex-
(Table 3, entry 3).
adiene (381 mL, 4.00 mmol) and phenol (94 mg, 1.00 mmol) were
added to a suspension of [Pd(PPh3)4](12 mg, 0.01 mmol) in toluene
(0.5 mL) in a screw-capped vial. The vial was sealed with a teflon-
lined septum, capped, and removed from the glovebox. The reaction
mixture was then stirred at room temperature for 24 h. The mixture
was absorbed onto silica gel and purified by flash column chroma-
tography to give a colorless oil (124 mg, 71%).
The reaction of [D1]4-tert-butylphenol with 1,3-penta-
diene formed products with the deuterium label at the two
methyl groups in a 1:1 ratio, and the reaction of [D1]4-tert-
butylphenol with cyclohexadiene formed four products in
equal amounts from both syn and anti additions with 1,2- and
1,4-regiochemistry. These labeling experiments suggest the
À
intermediacy of a p-allyl intermediate and reversible C O
Received: August 11, 2003
Revised: September 23, 2003 [Z52621]
bond cleavage in the product. Indeed, catalytic exchange of
the phenoxy group of the ether with another aryl alcohol was
faster than the catalytic addition of phenol across cyclo-
hexadiene.[18]
Keywords: addition · alcohols · alkenes · carboxylic acids ·
.
dienes · palladium
The similarities between the yields and conversions of the
reactions between dienes and phenols or carboxylic acids
suggest that the addition processes are reversible and that
thermodynamic factors affect the conversion. This hypothesis
was supported by two sets of results: First, reactions at lower
temperatures provided higher yields than those conducted at
higher temperatures. For example, the reaction of phenol and
cyclohexadiene catalyzed by [Pd(PPh3)4]at room temper-
ature consumed 73% of the phenol and formed the addition
[1]S. A. Godleski, B. M. Trost, I. Fleming in Comprehensive
Organic Synthesis, Vol. 4 (Eds.: S. A. Godleski, B. M. Trost, I.
Fleming), Pergamon, New York, 1991, p. 585.
[2]L. J. Gooßen, Angew. Chem. 2002, 114, 3929; Angew. Chem. Int.
Ed. 2002, 41, 3775.
[3]T. Pei, R. A. Widenhoefer, J. Am. Chem. Soc. 2001, 123, 11290.
Angew. Chem. Int. Ed. 2003, 42, 5865 –5868
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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