Mechanistic insights into the palladiumII-catalyzed hydroxyalkoxylation of 2-allylphenols

Article abstract of DOI:10.1021/jo062491x

The Pd(OCOCF₃)₂/[(HOCH₂CH ₂NHCOCH₂)₂NCH₂]₂- catalyzed oxidation of o-allylphenol with H₂O₂ in water/methanol affords a syn and anti mixture of 2-(1,2-dihydroxypropyl)phenol and 2-(2-hydroxy-1-methoxypropyl)phenol. Mechanistic experiments and ESI-MS studies support a pathway wherein isomerization of the C=C bond followed by its epoxidation and oxirane opening led to the products. Recycling of the catalytic system led to gradual lost of activity.

Full text of DOI:10.1021/jo062491x

SCHEME 1. Proposed Steps and Intermediates for
Formation of 2-(1,2-Dihydroxypropyl)phenol and
2-(2-Hydroxy-1-methoxypropyl)phenol from o-Allylphenol
Mechanistic Insights into the
PalladiumII-Catalyzed Hydroxyalkoxylation of
2-Allylphenols
Emilie Thiery, Carole Chevrin, Jean Le Bras,
Dominique Harakat, and Jacques Muzart*
Unite´ Mixte de Recherche “Re´actions Se´lectiVes et
Applications”, Boˆıte n° 44, CNRS-UniVersite´ de Reims
Champagne-Ardenne, BP 1039, 51687 Reims cedex 2, France
Shortly after our report, Schultz and Sigman disclosed the
Pd-catalyzed aerobic dialkoxylation of 1 and 4 in methanol
(eq 3).2 Although both the reaction conditions and the proposed
jacques.muzart@uniV-reims.fr
ReceiVed December 5, 2006
mechanisms are strongly different, the results are rather similar.
Sigman’s paper2,3 urges us to report our studies devoted to the
mechanism of the Pd(OCOCF3)2/LH-catalyzed formation of 2
and 3 from 1.
Heating a 1:1 H2O/MeOH solution of 1 at 50 °C for 24 h in
the presence of catalytic amounts of Pd(OCOCF3)2 and LH (0.05
equiv each) led to 2-((E)-prop-1-enyl)phenol (4).4 Furthermore,
carrying out the oxidation of 1 for 4.5 h instead of 24 h led to
a mixture of 1, 2, 3, and 4 (1 + 4, 22%; 2, 14%; 3, 17%).5
Since 4 has been oxidized into 2 and 3 (eq 2), step a of Scheme
1 can be considered as demonstrated. Such a step was also
involved in the reaction mechanism proposed by Sigman et al.
for their dialkoxylation of 1.2 The second step of the Sigman
mechanism is a Wacker-type addition of MeOH to the â-carbon
of the propenyl moiety.2 Such a possibility was discarded under
our conditions because the Pd(OCOCF3)2/LH-catalyzed oxida-
tion of 1 with 35% aqueous H2O2 in MeOH (eq 4) instead of
1:1 H2O/MeOH (eq 1) solution did not produced the dimethox-
ylation adduct.
The Pd(OCOCF3)2/[(HOCH2CH2NHCOCH2)2NCH2]2-cata-
lyzed oxidation of o-allylphenol with H2O2 in water/methanol
affords a syn and anti mixture of 2-(1,2-dihydroxypropyl)-
phenol and 2-(2-hydroxy-1-methoxypropyl)phenol. Mecha-
nistic experiments and ESI-MS studies support a pathway
wherein isomerization of the CdC bond followed by its
epoxidation and oxirane opening led to the products.
Recycling of the catalytic system led to gradual lost of
activity.
Recently, we disclosed the one-pot transformation of 2-al-
lylphenols into 2-(1,2-dihydroxypropyl)phenol derivatives under
the conditions depicted in eq 1 (LH ) [(HOCH2CH2NHCOCH2)2-
NCH2]2) for the reaction of o-allylphenol (1) in aqueous
methanol.1 This transformation has been explained by the
cascade reaction shown in Scheme 1, and we have demonstrated
the large palladium increase of the oxidation efficiency of 2-((E)-
prop-1-enyl)phenol (4) into 2 and 3 by an aqueous methanolic
solution of H2O2 (eq 2).1 Nevertheless, the different steps of
Scheme 1 were only suggested.
At this level, we have to point out that the careful analysis
of H NMR spectra of 2 and 3 (obtained from 1 and 4 as
1
(2) Schultz, M. J.; Sigman, M. S. J. Am. Chem. Soc. 2006, 128, 1460-
1461.
(3) Sigman et al. have subsequently reported the Pd-catalyzed aerobic
hydroalkoxylation of 4 using PdCl2[(-)-sparteine] as the catalyst: (a)
Gligorich, K. M.; Schultz, M. J.; Sigman, M. S. J. Am. Chem. Soc. 2006,
128, 2794-2795. (b) Zhang, Y.; Sigman, M. S. Org. Lett. 2006, 8, 5557-
5560.
(4) For PdII-catalyzed isomerization of allylphenol, see: (a) Golborn,
P.; Scheimann, F. J. Chem. Soc., Perkin Trans. 1 1973, 2870-2875. (b)
Davies, N. R.; DiMichiel, A. D. Aust. J. Chem. 1973, 26, 1529-1543. (c)
Gross, J. L. Tetrahedron Lett. 2003, 44, 8563-8565. (d) ref. 2.
(5) The oxidation of 2-allyl-6-methylphenol with the same catalytic
system, at room temperature for 72 h in a 1:2 H2O/MeOH solution, led to
2-((E)-prop-1-enyl)-6-methylphenol (17%), 2-(1,2-dihydroxypropyl)-6-me-
thylphenol (15%), and 2-(2-hydroxy-1-methoxypropyl)-6-methylphenol
(30%).
(1) Chevrin, C.; Le Bras, J.; He´nin, F.; Muzart, J. Synthesis 2005, 2615-
2618.
10.1021/jo062491x CCC: $37.00 © 2007 American Chemical Society
Published on Web 02/03/2007
J. Org. Chem. 2007, 72, 1859-1862
1859

depicted in eqs 1 and 2) has shown that these two products
were in fact a 75:25 mixture of syn and anti diastereoisomers.6
Under the experimental conditions of eq 1, 1-allyl-2-meth-
oxybenzene (1Me) afforded 1-methoxy-2-((E)-prop-1-enyl)-
benzene (4Me) and 1-(2-methoxyphenyl)propan-2-one (6Me) (eq
5). The formation of methyl ketone 6Me could occur via a
affording 2Bn and 3Bn (eq 8); their Pd-catalyzed hydrogenolysis
produced 2 and 3 quantitatively. The formation of both a diol
and an hydroxyether from 5Bn is in agreement with step c of
Scheme 1, and the absence of 1-(2-benzyloxyphenyl)propan-
2-one (6Bn) demonstrates that in eq 5, the appearance of 6Me
occurs via a Wacker-type reaction of 1Me rather than from the
rearrangement of 5Me. The diastereoselectivity of the oxirane
opening was also examined using CF3CO2H, i.e., a Bro¨nstedt
acid, instead of Pd(OCOCF3)2. In water at 50 °C for 3 h, the
conversion of 5Bn induced by 0.05 equiv of CF3CO2H was low
and a 80:20 mixture of 2Bn-syn and 2Bn-anti was isolated (10%
yield). The reaction was much more efficient in MeOH, a 60:
40 mixture of 3Bn-syn and 3Bn-anti being obtained in 95% yield
for a reaction time of 1.5 h. Therefore, it appears that the
diastereoselectivity of the epoxide opening of 5Bn is not greatly
dependent on the nature of the reagent and catalyst. Furthermore,
it seems interesting to note the similarity of the diol/hydroxy-
ether ratios obtained from the Pd-catalyzed reactions of 1, 4,
and 5Bn carried out in 1:1 H2O/MeOH solutions (eqs 1, 2, and
8).
Wacker-type reaction2,7 or from the rearrangement of 2-(2-
methoxyphenyl)-3-methyloxirane (5Me),8,9 this latter compound
being produced by epoxidation of 4Me. The exchange of 1Me
for allylbenzene as the substrate led to a 54:46 mixture of
propenylbenzene and 1-phenylpropan-2-one (conversion 100%).
These results demonstrate the requirement of the o-hydroxy
substitutent to obtain the 1,2-dihydroxypropyl derivatives.
Before examining the hypothesis of epoxide 5 as intermediate,
we verified that 3 was not obtained from 2 under our Pd-
catalyzed oxidation conditions. This implies that 2 is not an
intermediate leading to 3 in the oxidations depicted in eqs 1
and 2.
We tested the epoxidation of 4 using the VO(acac)2/t-BuOOH
catalytic system, but only 1-(2-hydroxyphenyl)propan-2-one (6)
instead of 5 was isolated. Such a reaction pathway was already
reported from 4 using either peracetic acid8 or metal-catalyzed
oxidation with t-BuOOH,9 and it was proposed that 6 was
produced from the rearrangement of the intermediate epoxide
5 via benzylic C-O bond cleavage followed by 1,2 hydride
migration.9 This led us to investigate the preparation of 5 via
2-(2-(benzyloxy)phenyl)-3-methyloxirane (5Bn), which was ob-
tained from 1 as depicted in eq 6.10 However, the Pd-catalyzed
hydrogenolysis of 5Bn (eq 7) induced also the cleavage of the
epoxide ring to afford a mixture of 3-syn and 3-anti.11
According to the literature,8,9,12 epoxide 5 cannot be isolated
under our conditions that use a catalyst having Lewis acid
properties. Nevertheless, epoxidation of alkenes using Pd
catalysts and peroxides13 or palladium superoxo complexes
obtained from reaction of PdII with H2O2 has been reported.
14
Furthermore, the phenol-mediated epoxidation of alkenes by
H2O2 disclosed by Jacobs et al.15 can rationalize the results of
eq 2 obtained in the absence of palladium and the absence of
the formation of 2Me and 3Me from 1Me under conditions depicted
in eq 5. In eq 2, 2 and 3 would be obtained via epoxidation of
4 by H2O2 promoted intramolecularly by the phenolic moiety,
whereas in eq 5, the protection of the hydroxy group precludes
such an assistance and, consequently, the appearance of 2Me
and 3Me
.
We have recently disclosed the interest of ESI-MS analysis
to determine the mechanism of Pd/LH-catalyzed allylic substitu-
(11) The Pd-catalyzed hydrogenolysis of epoxides leads usually to the
corresponding alcohols even in alcoholic solvents (Schultze, L. M.;
Chapman, H. H.; Dubree, N. J. P.; Jones, R. J.; Kent, K. M.; Lee, T. T.;
Louie, M. S.; Postich, M. J.; Prisbe, E. J.; Rohloff, J. C.; Yu, R. H.
Tetrahedron Lett. 1998, 39, 1853-1856), but the formation of 2-methoxy-
2-phenylethanol from styrene oxide under such conditions is documented
(Sajiki, H.; Hattori, K.; Hirota, H. Chem. Commun. 1999, 1041-1042).
(12) For Lewis acid catalyzed alcoholysis of epoxides, see: (a) Chini,
M.; Crotti, P.; Gardelli, C.; Macchia, F. Synlett 1992, 673-676. (b) Chini,
M.; Crotti, P.; Gardelli, C.; Macchia, F. Synlett 1992, 673-676. (c) Iranpoor,
N.; Salehi, P. Synthesis 1994, 1152-1154. (d) Likhar, P. R.; Kumar,
M. P.; Bandyopadhyay, A. K. Synlett 2001, 836-838.
Subjecting a 1:1 H2O/MeOH solution of 5Bn to catalytic
amounts of Pd(OCOCF3)2 and LH at 50 °C led to a fast reaction
(6) See Supporting Information for the determination of the syn and anti
structures via the synthesis of 2-(2,2,5-trimethyl-1,3-dioxolan-4-yl)phenol
1
and H NMR analysis.
(13) (a) Nagata, R.; Matsumura, T.; Saito, I. Tetrahedron Lett. 1984,
25, 2691-2694. (b) Zhou, X.-G.; Huang, J.-S.; Yu, X.-Q.; Zhou, Z.-Y.;
Che, C.-M. J. Chem. Soc., Dalton Trans. 2000, 1075-1080. (c) Nishida,
M.; Torii, A. Jpn. Kokai, Tokkyo, Koho, JP 187,792; Chem. Abstr. 2001,
135, 92546. (d) Corey, E. J.; Yu, J.-Q. Org. Lett. 2002, 4, 2727-2730.
(14) (a) Talsi, E. P.; Babenko, V. P.; Likholobov, V. A.; Nekipelov,
V. M.; Chinakov, V. D. J. Chem. Soc., Chem. Commun. 1985, 1768-1769.
(b) Talsi, E. P.; Babenko, V. P.; Shubin, A. A.; Chinakov, V. D.; Nekipelov,
V. M.; Zamarev, K. I. Inorg. Chem. 1987, 26, 3871-3878.
(7) (a) Roussel, M.; Mimoun, H. J. Org. Chem. 1980, 45, 5387-5390.
(b) Barak, G.; Sasson, Y. J. Chem. Soc., Chem. Commun. 1987, 1266-
1267. (c) Alandis, N.; Rico-Lattes, I.; Lattes, A. New J. Chem. 1984, 18,
1147-1149. (d) Namboodiri, V. V.; Varma, R. S.; Sahle-Demessie, E.;
Pillai, U. R. Green Chem. 2002, 4, 170-173.
(8) Tinsley, S. W. J. Org. Chem. 1959, 24, 1197-1199.
(9) Lattanzi, A.; Senatore, A.; Massa, A.; Scettri, A. J. Org. Chem. 2003,
68, 3691-3694.
(10) 5Bn has also been prepared from 4 in two steps (benzylation followed
by epoxidation), but this procedure was less convenient.
(15) Wahlen, J.; De Vos, D. E.; Jacobs, P. A. Org. Lett. 2003, 5, 1777-
1780.
1860 J. Org. Chem., Vol. 72, No. 5, 2007

FIGURE 1. ESI(+)-MS spectrum of the reaction medium after 4 h and expanded ESI(+)-MS spectrum of the species detected at m/z ) 719 with
its corresponding theoretical spectrum.
tions in water.16 The tandem version, ESI-MS/MS, is also a
valuable tool for identification and structural assignments of
charged palladium complexes.17 We have used these analytical
techniques to study the reaction depicted in eq 1, the identifica-
tion of the detected species being aided by comparison between
the observed and calculated isotope distribution patterns.
Because palladium displays six isotopes, the ions containing
this atom should be mass-detected as clusters of isotopomeric
ions centered on the most abundant isotope, i.e., 106.
The ESI(+)-MS spectrum of an equimolecular amount of Pd-
(OCOCF3)2 and LH dissolved in a 1:1 H2O/MeOH mixture
showed three clusters at m/z ) 569, 683, and 705 (Figure S1,
Supporting Information) attributable to the cationic species [LH-
Pd - H]+, [LHPdOCOCF3]+, and [LHPdOCOCF3 - H + Na]+,
respectively. The analysis of the ESI(-)-MS spectrum of the
same mixture revealed three clusters at m/z ) 567, 681, and
795 (Figure S2, Supporting Information) corresponding to [LH-
Pd - 3H]-, [LHPdOCOCF3 - 2H]-, and [LHPd(OCOCF3)2 -
H]-, respectively. All of these clusters are consistent with the
formation of the LHPd(OCOCF3)2 complex. After addition of
1 (5 equiv/Pd) and H2O2 (20 equiv/Pd) to the solution and
heating at 50 °C for 4 h, the ESI(+)-MS spectrum contained a
cluster at m/z ) 719 (Figure 1), confirmed by high resolution
(C27H45N6O10104Pd calcd 717.2237, obsd 717.2231), attributable
to [LHPd(5) - H)]+. The ESI(+)-MS/MS spectrum of this
cluster with the proposed fragmentations is shown in Figure 2.
According to these analysis, the solution contains [LHPdX(5)
- H] species, X being probably OCOCF3 (eq 9).
From the above experiments and analytical studies, we can
now conclude that the formation of 2-(1,2-dihydroxypropyl)-
phenols and 2-(1-alkoxy-2-hydroxypropyl)phenols from 2-al-
lylphenols occurs via the cascade reaction depicted in Scheme
1, i.e., isomerization of the CdC bond, followed by its
epoxidation and the opening of the resulting oxirane.
In the framework of this study, we have also examined the
recycling of the catalytic system. After extraction of the products
with diethyl ether, a new batch of substrate and H2O2 was added
to the aqueous phase, and the reaction proceeded as previously,
leading to 2 (24%) and 3 (49%). The recycling was repeated
(16) (a) Chevrin, C.; Le Bras, J.; He´nin, F.; Muzart, J.; Pla-Quintana,
A.; Roglans, A.; Pleixats, R. Organometallics 2004, 23, 4796-4799. (b)
Chevrin, C.; Le Bras, J.; Roglans, A.; Harakat, D.; Muzart, J. New J. Chem.
2007, 31, 121-126.
(17) (a) Sabino, A. A.; Machado, A. H. L.; Correia, C. R. D.; Eberlin,
M. N. Angew. Chem., Int. Ed. 2004, 43, 2514-2518. (b) Guo, H.; Qian,
R.; Liao, Y.; Ma, S.; Guo, Y. J. Am. Chem. Soc. 2005, 127, 13060-13064.
(c) Enquist, P.-A.; Nilsson, P.; Sjo¨berg, P.; Larhed, M. J. Org. Chem. 2006,
71, 8779-8786.
J. Org. Chem, Vol. 72, No. 5, 2007 1861

FIGURE 2. ESI(+)-MS/MS spectrum for the cluster at m/z ) 719.
2-anti) 13C NMR (CDCl3): δ 19.2 (CH3), 70.6 (CH), 80.1 (CH),
117.3 (CH), 120.1 (CH), 124.5 (C), 129.1 (CH), 129.6 (CH), 155.5
(C).
four times (Graph S1, Supporting Information) affording in the
last run 2 and 3 in 35% and 24% yields, respectively.
2-(2-Hydroxy-1-methoxypropyl)phenol 3-syn and 3-anti. Yel-
low gum. IR (film): ν 3336, 1606, 1458, 1240, 1100. H NMR-
Experimental Section
1
Oxidation of o-Allylphenol and Recycling Experiments. To
a stirred solution of Pd(OCOCF3)2 (25 mg, 0.075 mmol) and LH
(35 mg, 0.075 mmol) in water (1 mL) were added o-allylphenol
(206 mg, 1.5 mmol), 35% aqueous H2O2 (0.51 mL, 6 mmol) and
methanol (1 mL). After stirring at 50 °C for 24 h, extraction with
Et2O, following by drying of the organic phases over MgSO4,
evaporation of the solvent, and column chromatography (silica gel,
petroleum ether/EtOAc, 70:30) led to 2 (88 mg, 0.52 mmol, 35%)
and 3 (128 mg, 0.70 mmol, 47%). To the recovered aqueous phase
was added a new batch of o-allylphenol and 35% aqueous H2O2,
and the reaction proceeded as above.
(CDCl3): δ 1.05 (d, J ) 6.3, 2.25H, syn), 1.20 (d, J ) 6.2 Hz,
0.75H, anti), 3.40 (s, 0.75H, anti), 3.45 (s, 2.25H, syn), 4.03-4.15
(m, 2H), 6.84-6.90 (m, 2H), 6.99-7.03 (m, 1H), 7.20-7.27 (m,
1H). 3-syn (measured in a mixture with 3-anti) 13C NMR
(CDCl3): δ 18.7 (CH3), 57.9 (CH3), 69.5 (CH), 90.6 (CH), 117.2
(CH), 120.1 (CH), 121.5 (C), 129.9(CH), 130.0 (CH), 155.6 (C).
Acknowledgment. We are indebted to “Re´gion Champagne-
Ardenne” and “Ville de Reims” for Ph.D. studentships to C.C.
and E.T., respectively.
2-(1,2-Dihydroxypropyl)phenol 2-syn and 2-anti. Yellow oil.
IR (film): ν 3326, 1590, 1490, 1456, 1242, 1021. 1H NMR-
(CDCl3): δ 1.09 (d, J ) 6.3 Hz, 2.25H, syn), 1.14 (d, J ) 6.7 Hz,
0.75H, anti), 3.92-4.20 (m, 1H), 4.48 (d, J ) 8.0 Hz, 0.75H, syn),
4.75 (d, J ) 4.1, 0.25H, anti), 6.74-6.89 (m, 2H), 7.02 (d, J )
7.5, 1H), 7.20 (t, J ) 8.0, 1H). 2-syn (measured in a mixture with
Supporting Information Available: Experimental procedures;
determination of the syn and anti structures; characterization data
and 1H and 13C NMR spectra of products; ESI(+)-MS spectra This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
JO062491X
1862 J. Org. Chem., Vol. 72, No. 5, 2007