Palladium-Catalyzed Isomerization of Aryl-Substituted Epoxides: A Selective Synthesis of Substituted Benzylic Aldehydes and Ketones

Article abstract of DOI:10.1021/jo970743b

Aryl-substituted epoxides bearing multiple methyl substituants on the epoxide ring isomerize in the presence of 5 mol % Pd(OAc)₂/PR₃ (R = n-Bu, Ph) to form the corresponding benzylic aldehyde or ketone, with complete regioselectivity for the carbonyl compound formed via cleavage of the benzylic C-O bond. No allylic alcohols or products arising from alkyl migration are observed. Rapid reaction rates and nearly quantitative yields are obtained, even with highly sterically hindered epoxides, using tri-n-butylphosphine as ligand and tert-butyl alcohol as solvent. 2-Aryl-substituted epoxides with two methyl substituents on C3 are completely unreactive, consistent with an oxidative addition/β-hydride elimination mechanism. Catalyst variation studies show that both Pd(OAc)₂ and PR₃ are essential for optimal activity and that palladium catalysts formed in this manner are superior to other Pd(0) catalysts (e.g., Pd(PPh₃)₄). The reactivity of catalytic Pd(OAc)₂/PR₃ toward multiply-substituted epoxides is compared to traditional Lewis acid catalysts; the former is found to be much more selective for isomerization without skeletal rearrangement. A mechanistic rationale involving turnover-limiting S_N2-like attack of Pd(0) at the benzylic carbon is proposed.

Full text of DOI:10.1021/jo970743b

J . Org. Chem. 1997, 62, 6547-6561
6547
P a lla d iu m -Ca ta lyzed Isom er iza tion of Ar yl-Su bstitu ted Ep oxid es:
A Selective Syn th esis of Su bstitu ted Ben zylic Ald eh yd es a n d
Keton es
Sanjitha Kulasegaram and Robert J . Kulawiec*,1
Department of Chemistry, Georgetown University, Washington, D.C. 20057-1227
Received April 25, 1997X
Aryl-substituted epoxides bearing multiple methyl substituents on the epoxide ring isomerize in
the presence of 5 mol % Pd(OAc)2/PR3 (R ) n-Bu, Ph) to form the corresponding benzylic aldehyde
or ketone, with complete regioselectivity for the carbonyl compound formed via cleavage of the
benzylic C-O bond. No allylic alcohols or products arising from alkyl migration are observed.
Rapid reaction rates and nearly quantitative yields are obtained, even with highly sterically hindered
epoxides, using tri-n-butylphosphine as ligand and tert-butyl alcohol as solvent. 2-Aryl-substituted
epoxides with two methyl substituents on C3 are completely unreactive, consistent with an oxidative
addition/â-hydride elimination mechanism. Catalyst variation studies show that both Pd(OAc)2
and PR3 are essential for optimal activity and that palladium catalysts formed in this manner are
superior to other Pd(0) catalysts (e.g., Pd(PPh3)4). The reactivity of catalytic Pd(OAc)2/PR3 toward
multiply-substituted epoxides is compared to traditional Lewis acid catalysts; the former is found
to be much more selective for isomerization without skeletal rearrangement. A mechanistic
rationale involving turnover-limiting SN2-like attack of Pd(0) at the benzylic carbon is proposed.
In tr od u ction
of interesting and useful isomerization reactions have
been reported. Notably, epoxides activated by adjacent
aryl, vinyl, silyl, or carbonyl substituents are isomerized
to carbonyl compounds or allylic alcohols by complexes
of Rh,9 Pd,10 Mo,11 Sm,12 and Fe.13 For example, Milstein
studied the rearrangement of trans-stilbene oxides to 1,2-
diarylethanones by RhCl(PPh3)3,9b and Vankar described
the isomerization of aryl-substituted epoxides to carbonyl
compounds with Pd(PPh3)4;10d both observed electronic
influences on the regioselectivity of attack. Vinyl ep-
oxides are commonly employed as precursors to alkoxy-
substituted π-allylpalladium intermediates, which are
useful in Pd-catalyzed allylic alkylations.14 Suzuki et al.
demonstrated that the chemoselectivity in isomerization
of vinyl epoxides depends on the substrate structure:
highly-substituted vinyl epoxides tend to form allylic
alcohols (presumably via â-hydride elimination in a (π-
allyl)palladium intermediate), while cyclic epoxides (such
as cyclopentadiene monoepoxide) afford â,γ-unsaturated
ketones.10a The same workers also reported the Pd-
catalyzed rearrangement of R,â-epoxy ketones to the
corresponding â-diketones.10b
Epoxides are one of the more versatile classes of
organic compounds available to the synthetic chemist.2
They can be prepared by a wide variety of methods,3 often
with high levels of relative and absolute stereocontrol,4
and also undergo numerous modes of subsequent trans-
formation. While epoxides are frequently employed as
electrophiles in ring-opening nucleophilic addition
reactions,2a,3 another common, useful, and atom-economi-
cal reaction is isomerization to form other functional
groups. In the presence of a strong, bulky base, an
epoxide may undergo a deprotonation-elimination se-
quence to form an allylic alcohol,5 frequently with high
stereoselectivity. More commonly, epoxides react with
Lewis acids to form carbonyl compounds, generally via
hydride, alkyl, or aryl 1,2-migration pathways.6 The
synthetic applications of epoxides have been the subject
of a number of recent and thorough reviews.2a,3,7
In recent years, the promise of increased chemo-, regio-,
and stereoselectivity available via transition metal ca-
talysis8 has led investigators to study the interactions of
epoxides with transition metal complexes, and a number
X Abstract published in Advance ACS Abstracts, August 15, 1997.
(1) Camille and Henry Dreyfus Foundation New Faculty Awardee,
1992. E-mail: kulawiecr@guvax.georgetown.edu.
(8) Hegedus, L. S. Transition Metals in the Synthesis of Complex
Organic Molecules; University Science Books: Menlo Park, CA, 1994.
(9) (a) Adames, G.; Bibby, C.; Grigg, R. J . Chem. Soc., Chem.
Commun. 1972, 491-492. (b) Milstein, D.; Buchman, O.; Blum, J . J .
Org. Chem. 1977, 42, 2299-2308. (c) Milstein, D. J . Am. Chem. Soc.
1982, 104, 5227-5228.
(2) (a) Gorzynski Smith, J . Synthesis 1984, 8, 629-656. (b) Lewars,
E. G. Oxiranes and Oxirenes. In Comprehensive Heterocyclic Chemistry,
Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984; Vol. 7,
Chapter 5.05, pp 95-129. (c) Barto´k, M.; La´ng, K. L. Oxiranes. In
Small Ring Heterocycles, Part 3; Vol. 42 of The Chemistry of Hetero-
cyclic Compounds; Hassner, A., Ed.; Wiley Interscience: New York,
1983; Chapter 1, pp 1-196.
(10) (a) Suzuki, M.; Oda, Y.; Noyori, R. J . Am. Chem. Soc. 1979,
101, 1623-1625. (b) Suzuki, M.; Watanabe, A.; Noyori, R. J . Am. Chem.
Soc. 1980, 102, 2095-2096. (c) Hirao, T.; Yamada, N.; Ohshiro, Y.;
Agawa, T. Chem. Lett. 1982, 1997-2000. (d) Vankar, Y. D.; Chaudhuri,
N. C.; Singh, S. P. Synth. Commun. 1986, 16, 1621-1626. (e) Visentin,
G.; Piccolo, O.; Consiglio, G. J . Mol. Catal. 1990, 61, L1-L5.
(11) Alper, H.; Des Roches, D.; Durst, T.; Legault, R. J . Org. Chem.
1976, 41, 3611-3613.
(3) Rao, A. S.; Paknikar, S. K.; Kirtane, J . G. Tetrahedron 1983,
39, 2323-2367.
(4) (a) Pedragossa-Moreau, S.; Archelas, A.; Furstoss, R. Bull. Soc.
Chim. Fr. 1995, 132, 769-800. (b) Besse, P.; Veschambre, H. Tetra-
hedron 1994, 50, 8885-8927.
(12) Prandi, J .; Namy, J . L.; Menoret, G.; Kagan, H. B. J . Organo-
met. Chem. 1985, 285, 449-460.
(5) Crandall, J . K.; Apparu, M. Org. React. (N.Y.) 1983, 29, 345-
443.
(13) (a) Aumann, R.; Fro¨hlich, K.; Ring, H. Angew. Chem., Int. Ed.
Engl. 1974, 13, 275-276. (b) Hayakawa, K.; Schmid, H. Helv. Chim.
Acta 1977, 60, 1942-1960. (c) Kauffmann, T.; Neiteler, C.; Neiteler,
G. Chem. Ber. 1994, 127, 659-665.
(6) (a) Rickborn, B. In Comprehensive Organic Synthesis; Trost, B.
M., Ed.; Pergamon: Oxford, 1991; Vol. 3; Chapter 3.3, pp 733-775
and references therein. (b) Parker, R. E.; Isaacs, N. S. Chem. Rev. 1959,
59, 737-799.
(7) Rossiter, B. E. In Asymmetric Synthesis; Morrison, J . D., Ed.;
Academic Press: Orlando, FL, 1983; Vol. 5, pp 194-246.
(14) (a) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1989, 28, 1173-
1192. (b) Trost, B. M.; Molander, G. A. J . Am. Chem. Soc. 1981, 103,
5969-5972.
S0022-3263(97)00743-3 CCC: $14.00 © 1997 American Chemical Society

6548 J . Org. Chem., Vol. 62, No. 19, 1997
Kulasegaram and Kulawiec
Sch em e 1. Syn th esis of Ar yl-Su bstitu ted Ep oxid es
Less commonly observed are transition metal-catalyzed
isomerizations of unactivated epoxides (i.e., those bearing
only alkyl substituents). One of the earliest reports of
such a reaction described the simple rearrangement of
propylene oxide to acetone, catalyzed by dicobalt octa-
carbonyl.15 Kagan showed that Mn-, Co-, Ce-, and Sm-
based catalysts are effective for the isomerization of
simple alkyl-substituted epoxides to carbonyl com-
pounds.12 Miyashita and co-workers have reported the
rearrangement of alkyl- and aryl-substituted epoxides
with a variety of Ni-based catalysts and observed variable
chemoselectivity in product formation.16 More recently,
Cabrera et al. demonstrated that the chemoselectivity for
catalytic rearrangement of propylene oxide to acetone vs
propanal by Sn[Co(CO)4]4 can be controlled by external
CO pressure.17 In some cases, tandem isomerization/
carbonylation sequences are possible.18
Our general interest in the metal-mediated transfor-
mations of small-ring heterocycles led us to investigate
the reactivity of low-valent, electron-rich transition metal
complexes toward several different classes of epoxides.
Recently, we reported the selective, palladium-catalyzed
conversion of monoalkyl-substituted epoxides to methyl
ketones and aryl-substituted epoxides to carbonyl com-
pounds via benzylic C-O cleavage.19 While epoxide
isomerization processes employing both main-group Lewis
acids (as described in a recent excellent review by
Rickborn)6a and d-block metal catalysts are well-prece-
dented, many of them suffer from a lack of regioselec-
tivity, giving more than one isomeric carbonyl compound.
Many such isomerization reactions also exhibit low
chemoselectivity, resulting in skeletal rearrangements
concomitant with simple functional group transforma-
tion. In the present study, we have investigated the
rearrangement of epoxides with multiple aryl and alkyl
substituents, because these substrates are particularly
prone to unselective reactions with traditional Lewis acid
catalysts. We now report that Pd(OAc)2/PR3 smoothly
catalyzes the isomerization of many multiply-substituted
epoxides to afford carbonyl compounds, via exclusive
benzylic C-O cleavage, under mild conditions, in good
to excellent yields, representing an efficient route to
substituted benzylic aldehydes and ketones.
carbonyl compound, acid-catalyzed dehydration to pro-
vide the vinylarene, and then epoxidation with MCPBA.
Thus, addition of ethyl- and isopropylmagnesium bromide
to 2-naphthaldehyde gave secondary alcohols 4 and 5,
respectively, while addition to 2-acetonaphthenone gave
tertiary alcohols 6 and 7. Dehydration of these benzylic
alcohols with substoichiometric p-toluenesulfonic acid in
refluxing benzene afforded the vinylarenes 8-11; alkenes
8 and 10 were formed as the (E) isomers exclusively.
Finally, epoxidation with MCPBA in CH2Cl2 provided the
epoxides 12-15 in good yields. 1-Phenyl-1,2-epoxycyclo-
hexane (16) was synthesized by a similar three-step
route, from cyclohexanone and phenylmagnesium bro-
mide.
Resu lts a n d Discu ssion
Su bstr a te Syn th esis. The aryl-substituted epoxides
employed in this study were synthesized either by
methylenation of aryl ketones or aldehydes or via epoxi-
dation of the appropriate vinylarene, as depicted in
Schemes 1 and 2. Reaction of 2-naphthaldehyde, 2-
acetonaphthenone, and benzophenone with dimethyl-
sulfonium methylide20 gave the 2-substituted epoxides
1-3 in excellent yield. Aryl-substituted epoxides with
multiple methyl groups were prepared by a three-step
protocol involving Grignard addition to the appropriate
Aryl-substituted epoxides bearing a variety of func-
tionalized side chains were prepared as shown in Scheme
2. A common precursor to each of the functionalized
epoxides, 1-phenyl-10-undecen-1-ol (17), was prepared via
addition of phenylmagnesium bromide to 10-undecenal.
Acid-catalyzed dehydration of 17 and subsequent epoxi-
dation with MCPBA gave a separable mixture of epoxide
18 and the previously reported diepoxide.19 Hydrobora-
tion of 17, followed by acid-catalyzed dehydration, gave
(E)-11-phenyl-10-undecen-1-ol, the primary hydroxyl group
of which was elaborated into a variety of functional
groups (cyano, ethoxycarbonyl, acetyl, alkynyl, and bro-
mo) as depicted. Epoxidation of the resulting vinylarenes
gave the functionalized epoxides 19-24.
(15) Eisenmann, J . L. J . Org. Chem. 1962, 27, 2706.
(16) Miyashita, A.; Shimada, T.; Sugawara, A.; Nohira, H. Chem.
Lett. 1986, 1323-1326.
(17) Cabrera, A.; Mathe´, F.; Castanet, Y.; Mortreux, A.; Petit, F. J .
Mol. Catal. 1991, 64, L11-L13.
(18) (a) Eisenmann, J . L.; Yamartino, R. L.; Howard, J . F. J . Org.
Chem. 1961, 26, 2102-2104. (b) Heck, R. F. J . Am. Chem. Soc. 1963,
85, 1460-1463. (c) Fukumoto, Y.; Chatani, N.; Murai, S. J . Org. Chem.
1993, 58, 4187-4188.
(19) Kulasegaram, S.; Kulawiec, R. J . J . Org. Chem. 1994, 59, 7195-
7196.
Isom er iza tion of Mu ltip ly-Su bstitu ted Ep oxid es.
Our preliminary investigations19 showed that the Pd(0)
complexes generated in situ from Pd(OAc)2 and PR3 (R
) n-Bu, Ph)21 are active catalysts for the isomerization
of naphthyl epoxides 1 and 12 to 2-naphthylacetaldehyde
(20) Trost, B. M.; Melvin, L. R. Sulfur Ylides: Emerging Synthetic
Intermediates; Academic Press: New York, 1975; pp 51-76.

Pd-Catalyzed Isomerization of Aryl-Substituted Epoxides
J . Org. Chem., Vol. 62, No. 19, 1997 6549
Sch em e 2. Syn th esis of F u n ction a lized Ep oxid esa
Ta ble 1. Isom er iza tion of Mu ltip ly-Su bstitu ted Ep oxid es
a
w ith P d (OAc)2-P R3
a
Reagents and conditions: (a) p-TsOH, C6H6, ∆; (b) MCPBA,
CH2Cl2; (c) BH3-THF, then NaOH-H2O2; (d) H3PO4, THF, ∆; (e)
p-TsCl, py; (f) NaCN, DMF, ∆; (g) CrO3, H2SO4; (h) EtOH, p-TsOH,
∆; (i) PCC/Celite, CH2Cl2; (j) CH3MgI, Et2O, then H3O+; (k) CBr4,
PPh3, CH2Cl2; (l) n-BuLi, THF, -78 °C, then H3O+; (m) NBS, PPh3,
DMF.
and 1-(2-naphthyl)propanone, respectively, in refluxing
benzene. We also saw that sterically hindered epoxides
(e.g., trans-stilbene oxide) require the more electron-rich
tributylphosphine for efficient isomerization. We quickly
learned that generation of the Pd(0) catalyst and subse-
quent catalytic epoxide isomerization may be carried out
in many common organic solvents (vide infra).
In order to determine precisely how the solvent,
phosphine ligand, and epoxide substitution pattern influ-
ence the efficiency of the Pd-catalyzed isomerization
reaction, we treated epoxides 1, 2, and 12-15 with
Pd(OAc)2/PR3 in refluxing benzene and tert-butyl alcohol.
These two test solvents were chosen because they differ
widely in polarity22 but have similar boiling points. We
also studied the effect of the phosphine ligand by employ-
ing PBu3 and PPh3, which differ significantly in steric
and electronic properties.23 In all cases, the isomerization
reactions were carried out by generating the Pd(0)
catalyst from Pd(OAc)2 (5%) and PR3 (15 mol %), adding
the epoxide substrate, and refluxing under N2 until the
epoxide was consumed, or until no further catalytic
turnovers were observed. The results are presented in
Table 1.
a
All isomerization reactions were carried out using 5 mol %
Pd(OAc)2, 15 mol % PR3, in refluxing solvent. Times required for
complete consumption of starting material (or time after which
reaction stopped) are indicated. Yields refer to isolated, pure
product; number in parentheses refers to percentage of unreacted
starting material recovered after the indicated time period. In all
cases, Ar ) 2-naphthyl.
Entries 1-4 (Table 1) show the isomerization of a
simple aryl-substituted epoxide to the corresponding
arylacetaldehyde (25). In all cases, reaction times were
short and yields of the aldehyde were moderate to
excellent. A clear preference for tert-butyl alcohol solvent
is seen; when combined with PBu3 as ligand, a near
quantitative yield of 2-naphthylacetaldehyde is obtained.
With this substrate, however, it is essential that the
reaction be stopped as soon as the epoxide is completely
consumed, or subsequent aldol condensation of the
product aldehyde to form the 2,4-diaryl-2-butenal ensues,
as we have recently described.24 In all cases, no other
isomeric carbonyl compounds were observed (i.e., 2-
1
(21) Mandai, T.; Matsumoto, T.; Tsuji, J .; Saito, S. Tetrahedron Lett.
1993, 34, 2513-2516.
acetonaphthenone) by capillary GC or H NMR. Using
the 2-aryl-3-methyl-substituted epoxide 12 (entries 5-8),
excellent yields of benzylic ketone 26 were obtained under
all conditions investigated. However, the advantage of
(22) (a) Dielectric constants:22b benzene ) 2.27; t-BuOH ) 12.47.
(b) Reichardt, C. Solvents and Solvent Effects in Organic Chemistry,
2nd ed.; VCH: Weinheim, 1988; pp 408-411.
(23) (a) Cone angles:23b PBu3 ) 132°, PPh3 ) 145°. Tolman electronic
parameters:23b PBu3 ) 2060.3 cm-1; PPh3 ) 2068.9 cm-1. (b) Tolman,
C. A. Chem. Rev. 1977, 77, 313-348.
(24) Kim, J .-H.; Kulawiec, R. J . J . Org. Chem. 1996, 61, 7656-7657.

6550 J . Org. Chem., Vol. 62, No. 19, 1997
Kulasegaram and Kulawiec
Ta ble 2. Isom er iza tion of Dip h en yloxir a n es w ith
tert-butyl alcohol is evident in comparing the times
required in entries 5 and 6: the isomerization is distinctly
faster in the alcohol solvent compared to benzene. This
effect is not noticeable, however, when the more electron-
rich trialkylphosphine is used as ligand (entries 7 and
8). Again, only one regioisomeric carbonyl compound was
formed in all cases.
a
P d (OAc)2-P R3
Disubstitution at the benzylic position is tolerated, as
shown in entries 9-12, in which the 2-arylpropanal 27
is cleanly formed. A nearly quantitative yield is obtained
in t-BuOH with PBu3. The greater reactivity of Pd(0)
catalysts bearing electron-rich trialkylphosphines is most
clearly exemplified in entries 13-16, in which the highly-
substituted epoxide 14 rearranges to the 3-aryl-2-bu-
tanone 28 only using Pd(OAc)2/PBu3 as catalyst. With
PPh3 as ligand, no isomerization occurs, and only starting
material is recovered. Again, improved yields are ob-
tained with the tertiary alcohol solvent, and no isomeric
carbonyl compounds (for example, as might be formed
via alkyl migration) were observed.
The limitations of this isomerization methodology are
apparent in entries 17 and 18. Here we applied the most
forcing isomerization conditions (Pd(OAc)2/PBu3 in re-
fluxing t-BuOH) but observed no traces of isomerization
product after 24 h, recovering only starting epoxide.
While the unreactivity of tetrasubstituted epoxide 15 is
perhaps to be expected, the trisubstituted epoxide 13 does
not appear to be significantly more sterically encumbered
than 14, which undergoes isomerization cleanly and
efficiently. The key appears to be the position of the two
methyl substituents: with two alkyl groups located â to
the aryl ring, epoxides 13 and 15 lack hydrogen atoms
capable of migrating in order to form benzylic carbonyl
compounds. The implications for this unreactivity on the
mechanism of the isomerization reaction are discussed
below.
a
All isomerization reactions were carried out using 5 mol %
Pd(OAc)2, 15 mol % PR3, in refluxing solvent. Times required for
complete consumption of starting material (or time after which
reaction stopped) are indicated. Yields refer to isolated, pure
product; number in parentheses refers to percentage of unreacted
starting material present after the indicated time period (either
isolated or quantified spectroscopically).
We also investigated the reactivity of epoxides bearing
two aryl substituents, under the catalytic conditions
described above; the results of these experiments are
depicted in Table 2. Both trans-stilbene oxide (29, entries
1-4) and cis-stilbene oxide (30, entries 5-8) isomerize
to form deoxybenzoin (31) in the presence of Pd(OAc)2/
PR3; only a trace (<3%) of cis to trans isomerization is
observed by GC during the isomerization of 30. The trans
isomer gives good yields using PBu3 in either solvent, or
PPh3 in t-BuOH; with PPh3 in benzene, however, only a
small amount of ketone is formed, with recovery of a
significant amount of unreacted epoxide. A similar
situation holds with the cis isomer: Pd(OAc)2/PPh3
affords only partial conversion of the epoxide after 1-2
days reflux, with significantly better reactivity in t-
BuOH. With PBu3 as ligand, nearly quantitative yields
of isomerization product are obtained, but again, the
reaction is noticeably faster in alcoholic solvent. The
mechanistic implications of this particular observation
are discussed below. The isomeric epoxide with both
phenyl rings at the same position (3) is largely unreactive
under our most forcing conditions (entries 9 and 10),
affording only a trace of diphenylacetaldehyde (32) after
prolonged reflux. In this case, the increased steric
hindrance of two aryl groups at the reactive site appears
to be too great to permit reaction, even with the more
reactive trialkylphosphine ligand.
refluxing benzene and hexadecane as an internal stand-
ard. The relative isomerization rates were estimated by
calculating the initial rate constants (measured over 2
half-lives of the reaction). Using standard pseudo-first-
order treatment of the kinetic data, plots of ln([epoxide]0/
[epoxide]t) vs time are linear (r2 g 0.97) and give rate
constants of 5.34((0.33) × 10-2 h-1 for 29 and 8.07((0.58)
× 10-2 h-1 for 30. The greater reactivity of cis-stilbene
oxide (by a factor of 50%) is not surprising, considering
that this isomer should experience a greater degree of
intrinsic steric strain, which is relieved upon isomeriza-
tion to the ketone. Additionally, an external reagent
(such as a metal catalyst) attacking the oxirane moiety
should encounter less steric hindrance in approaching the
cis isomer than the trans. This observation, plus the fact
that both substrates show clean first-order kinetics in
epoxide concentration, are consistent with a mechanism
involving turnover-limiting attack of a metal catalyst on
the epoxide, as discussed in detail below.
F u n ction a l Gr ou p Toler a n ce. In order to investi-
gate the chemoselectivity of the palladium(0) catalyst
toward epoxide isomerization, we have studied the reac-
tion of a number of aryl-substituted epoxides bearing
reactive functional groups. Epoxides 18-24, prepared
as outlined in Scheme 2, were subjected to the optimal
conditions identified above (5 mol % Pd(OAc)2, 3 equiv
of PBu3 per Pd, refluxing t-BuOH); the results of these
experiments are depicted in Table 3. The Pd(0) catalyst
clearly tolerates the terminal alkenyl (entry 1), primary
alcohol (entry 2), nitrile (entry 3), ester (entry 4), and
The relative reactivities of cis- and trans-stilbene oxide
were compared directly by monitoring the isomerization
of an equimolar mixture of 29 and 30 by capillary gas
chromatography, using Pd(OAc)2/PBu3 as catalyst in

Pd-Catalyzed Isomerization of Aryl-Substituted Epoxides
J . Org. Chem., Vol. 62, No. 19, 1997 6551
Ta ble 3. F u n ction a l Gr ou p Toler a n ce in Ep oxid e
Isom er iza tion
3), and ethereal (entries 4 and 5) solvents. Reaction in
refluxing acetonitrile requires a somewhat longer reac-
tion time for complete conversion; both acetonitrile and
N,N-dimethylformamide (entries 6 and 7) give noticeably
lower yields of ketone, possibly due to catalyst decom-
position.
To obtain a more quantitative picture of the influence
of solvent on the rate of isomerization, we monitored the
initial rates of conversion of 12 to 26 at ambient tem-
perature, in t-BuOH, benzene and acetonitrile. The
catalyst loading and substrate concentrations were iden-
tical in all cases, and the extent of reaction was deter-
mined by capillary gas chromatography, determining the
amount of remaining substrate at time intervals by
integration vs internal hexadecane. In the cases of
benzene and acetonitrile, plots of ln([epoxide]0/[epoxide]t)
vs time are linear (r2 g 0.97) for over 3 half-lives of the
reaction and pseudo-first order rate constants of
entry
X (substrate)
CHdCH2 (18)
CH2CH2OH (19)
CH2CH2CtN (20)
CH2CO2CH2CH3 (21)
CH2COCH3 (22)
CH2CtCH (23)
timeb
1 h
30 min
40 min
45 min
25 min
24 h
yield (%)c
1
2
3
4
5
6
7
80 (33)
90 (34)
80 (35)
96 (36)
98 (37)
0 (90)d
0 (98)d
CH2CH2Br (24)
24 h
a
b
Pd(OAc)2 (5 mol %), PBu3 (15 mol %), t-BuOH, reflux. Time
required for complete consumption of epoxide. c Yields refer to
d
isolated, pure product; compound number follows. Amount in
parentheses refers to unreacted starting material recovered after
24 h.
1.44((0.11) × 10-2 min-1 and 1.53((0.08) × 10-2 min-1
,
Ta ble 4. In flu en ce of Solven t on Isom er iza tion Yield
respectively, are obtained from the slopes. With t-BuOH,
it was not possible to obtain an accurate rate constant,
because the isomerization reaction was essentially com-
plete by the time the first measurement was taken (ca.
10 min), indicating a rate constant of at least 7 × 10-2
min-1, several times greater than those measured for
benzene and acetonitrile.
entry
solvent
time (min)a
yield (%)b
These experiments demonstrate a distinct solvent
effect on the rate of the isomerization reaction. Although
the observed reaction rates vary with solvent polarity,
they do not correlate directly with the dielectric constants
of the media. The isomerization reaction proceeds at
identical rates (within experimental error) in benzene
and acetonitrile, two solvents with widely differing
dielectric constants (2.27 and 35.94, respectively).22b
However, the reaction is much faster in tert-butyl alcohol,
a solvent of intermediate dielectric constant (12.47). We
suggest that the increased rate of the isomerization
reaction in t-BuOH is not a function of the polarity of
the solvent per se but rather a result of its ability to serve
as a hydrogen bond donor. The implications of this
suggestion for the mechanism of the isomerization reac-
tion are discussed below. From a synthetic standpoint,
the observation of fast isomerization in t-BuOH at room
temperature indicates that, at least with substrates such
as 12, the reflux temperature used in Table 1 is not
necessary and that ambient temperature suffices for
rapid reaction.
1
2
3
4
5
6
7
2-butanone
t-BuOH
C6H6
dioxane
THF
5
10
30
5
10
60
5
99
96
93
93
92
80
71
CH3CN
DMFc
a
Time required for complete consumption of starting material.
Yields refer to isolated, pure product. c Reaction carried out at
120 °C.
b
ketone (entry 5) functionalities, providing the function-
alized benzylic ketones 33-37 in excellent yields, within
reasonable time periods. Limitations on the range of
reactive functionality are clearly seen in entries 6 and
7, in which epoxides 23 and 24, bearing terminal alkynyl
and primary bromoalkyl groups, respectively, are com-
pletely unreactive. Although we have not determined the
fate of the Pd catalyst in the presence of these substrates,
catalyst poisoning via oxidative addition of C-H or C-Br
is a reasonable hypothesis, since these bonds are known
to react with Pd(0).25
Ca ta lyst Effects. Our method for the in situ genera-
tion of a zero-valent Pd complex as catalyst is based
directly on literature precedent. The reduction of Pd(OAc)2
by PPh3 has been known for some time,26 but our use of
PBu3 to generate a catalyst presumed to be Pd(PBu3)n
(where n ) 1-3) is inspired by the recent work of Mandai
et al.,21 who showed by 31P NMR and comparative
reactivity studies that formation of a Pd(0) complex is
highly likely under these conditions. Our first question,
then, was whether both components of the catalyst
“recipe” are indeed necessary for maximum efficiency or
whether the active catalyst might instead be traces of
Pd(II) or tertiary phosphine present in the reaction
mixture. To address this issue, we carried out a series
of control experiments using Pd(OAc)2 and PBu3 alone,
in both benzene and tert-butyl alcohol. The results of
these experiments are depicted in Table 5.
Solven t Effects. Although the substrate studies
described above were performed only in benzene and tert-
butyl alcohol, we have also investigated a number of
other reaction media for the isomerization reaction. We
find that the Pd(0) catalyst may be generated, and the
subsequent isomerization efficiently carried out, in sev-
eral common organic solvents. Table 4 shows the yields
of 1-(2-naphthyl)propanone (26) obtained by refluxing
epoxide 12 with Pd(OAc)2 (5 mol %) and PBu3 (15 mol
%) in the indicated solvent, for the specified time period.
As shown, nearly quantitative yields of 26 are obtained
using ketone (entry 1), alcohol (entry 2), aromatic (entry
(25) (a) For a report on the direct oxidative addition of the C-H
bond of a terminal alkyne to Pd(0), see: Chukhadzhyan, G. A.; Evoyan,
Z. K.; Melkonyan, L. N. Zh. Obshch. Khim. 1975, 45, 1114-1117;
Chem. Abstr. 83, 97535c. (b) For a recent report on Pd-catalyzed
reactions of terminal alkynes that proceed via C-H activation, see:
Trost, B. M.; Matsubara, S.; Caringi, J . J . Am. Chem. Soc. 1989, 111,
8745-8746. (c) For oxidative addition reactions of Pd(0) with organic
bromides, see: Stille, J . K.; Lau, K. S. Y. Acc. Chem. Res. 1977, 10,
434-442.
(26) (a) Heck, R. F. Palladium Reagents in Organic Synthesis;
Academic Press: London, 1985. (b) Heck, R. F. Org. React. (N.Y.) 1982,
27, 345-390.

6552 J . Org. Chem., Vol. 62, No. 19, 1997
Kulasegaram and Kulawiec
Ta ble 5. Ca ta lyst Con tr ol Exp er im en ts
t-BuOH; after 45 h, 88% of the unreacted epoxide was
recovered, with no trace of 2-phenylcyclohexanone, the
expected isomerization product. We propose that this
unreactivity is due to the inability of the â-hydrogen and
PBu3 substituents to attain a mutually antiperiplanar
arrangement, thus preventing the concerted 1,2-hydride
migration suggested in eq 1. We believe that traces of
free PBu3 are not responsible for the catalytic epoxide
isomerization observed in the experiments described in
Tables 1-4 above primarily because the rate of isomer-
ization of epoxide 12 using Pd(OAc)2/PBu3 (Table 1, entry
8) is significantly greater than that observed using only
PBu3. Furthermore, while PBu3 does not isomerize cyclic
epoxide 16, Pd(OAc)2/PBu3 does so quite efficiently (vide
infra), arguing in favor of a direct role for the Pd(0)
complex. The nucleophilic properties of tertiary phos-
phines have been exploited in a number of other useful
catalytic (but metal-free) processes,28 and we are continu-
ing to explore this potentially useful transformation.
The remaining control experiment depicted in Table 5
(entry 5) demonstrates that the polar solvent alone is not
responsible for the isomerization of 12. In contrast,
however, extremely electron-rich epoxides, such as p-
methoxystyrene oxide, are known to rearrange spontane-
ously in aqueous medium.29 Finally, the catalytic effi-
ciency of Pd(OAc)2/PBu3 is depicted in entry 6 for
comparison to the control experiments and is clearly
much higher than any of the other conditions tested.
The next question to be addressed concerns the nature
of the catalyst formed from Pd(OAc)2 and PPh3. While
the reduction of Pd(OAc)2 to zero-valent palladium by
tertiary phosphines is fairly well-accepted,26 the precise
nature of the reduction product (and, in fact, the active
catalyst in the Heck reaction) has only recently been
identified by Amatore et al. as Pd(PPh3)3(OAc)-, in
equilibrium with the bis-phosphine complex via PPh3
dissociation.30 Since our methodology involves genera-
tion of Pd(0) under the same conditions studied by
Amatore, it is reasonable to suspect that the catalytically
active species in the epoxide isomerization reaction is also
the anionic acetoxypalladium(0) complex. In order to
determine precisely how the mode of preparation of a
Pd(0)-PPh3 catalyst influences its reactivity toward
catalytic epoxide isomerization, we studied the re-
arrangement of epoxide 12 to ketone 26 using a variety
of palladium(0) catalysts, all with triphenylphosphine as
the supporting ligand. Isomerization reactions were
carried out in DMF (in order to closely approximate the
conditions employed by Amatore et al.) at ambient
temperature. After 24 h, the product ketone 26 and any
unreacted epoxide 12 present were isolated and quanti-
fied. The results of these experiments are depicted in
Table 6.
entry
catalyst
solvent
time
45 h
95 h
12 (%)a 26 (%)a
1
2
3
4
5
6
Pd(OAc)2 (5%)
PBu3 (15%)
Pd(OAc)2 (5%)
PBu3 (15%)
none
C6H6
C6H6
t-BuOH 45 h
t-BuOH 45 h
t-BuOH 72 h
100
85
76
0
96
0
0
0
23
85
0
Pd(OAc)2 (5%) + t-BuOH 10 min
PBu3 (15%)
96
a
Yields refer to isolated, pure products.
Reaction of disubstituted epoxide 12 with substoichio-
metric amounts of either Pd(OAc)2 (entry 1) or tributyl-
phosphine (entry 2) in refluxing benzene led to no
observable isomerization to form ketone 26; in both cases,
only starting material was recovered, in high yield. In
contrast, when the same catalysts were employed in tert-
butyl alcohol, we observed slow but significant formation
of ketone 26 with Pd(OAc)2 (entry 3) and complete
conversion of the epoxide with PBu3, leading to a quite
nice yield of the benzylic ketone (entry 4). In the former
case, we suspect that palladium(II) acetate, which is quite
soluble in alcoholic solvents, behaves as a simple Lewis
acid catalyst and that the ketone is formed by the
traditional acid-catalyzed isomerization mechanism.6 In
the latter case, we suggest that the phosphine-catalyzed
isomerization may proceed as described in eq 1. Nucleo-
philic attack of the phosphine at the benzylic carbon can
lead to the betaine intermediate; rapid 1,2-hydride
migration, with concomitant CdO bond formation and
phosphine expulsion, may afford ketone 26. Interest-
ingly, the intermediate betaine is the same as would be
expected from addition of a phosphorus ylide to an
aldehyde; however, we see no evidence of alkene forma-
tion via phosphine oxide elimination. In contrast, the
deoxygenation of stilbene oxide and other aryl-substitut-
ed epoxides by PR3 (R ) Ph, n-Bu) is well-known,27
although the conditions employed differ considerably
from ours. Support for the mechanistic proposal in eq 1
arises from the attempted PBu3-catalyzed isomerization
of bicyclic epoxide 16 (eq 2). In contrast to the monocyclic
Entries 1-3 demonstrate that the catalysts obtained
via reduction of Pd(OAc)2 with 3, 4, or 5 equiv of PPh3,
respectively, are all about equally effective for the
isomerization of 12 to 26; in each case, 80-90% of the
product ketone is formed, with <10% of unreacted
epoxide recovered. Significantly, the preformed catalyst
case, 16 is completely inert toward PBu3 in refluxing
(28) (a) Ono, N.; Miyake, H.; Kaji, A. J . Chem. Soc., Chem. Commun.
1983, 875-876. (b) Trost, B. M.; Kazmaier, U. J . Am. Chem. Soc. 1992,
114, 7933-7935. (c) Vedejs, E.; Diver, S. T. J . Am. Chem. Soc. 1993,
115, 3358-3359. (d) Trost, B. M.; Li, C.-J . J . Am. Chem. Soc. 1994,
116, 10819-10820.
(29) For a recent example, see: Blumenstein, J . J .; Ukachukwu, V.
C.; Mohan, R. S.; Whalen, D. L. J . Org. Chem. 1993, 58, 924-932.
(30) Amatore, C.; Carre´, E.; J utand, A.; M’Barki, M. A.; Meyer, G.
Organometallics 1995, 14, 5605-5614.
(27) Bissing, D. E.; Speziale, A. J . J . Am. Chem. Soc. 1965, 87, 2683-
2690. In these studies, the intermediacy of a betaine and its reversible
fragmentation to phosphorane and benzaldehyde were proven by the
isolation of m-chlorostilbene from the deoxygenation reaction of stilbene
oxide with PBu3 in the presence of m-ClC6H4CHO, thus implicating
exchange with added aldehyde. However, all of the deoxygenation
reactions were carried out neat, and at temperatures exceeding 100
°C.

Pd-Catalyzed Isomerization of Aryl-Substituted Epoxides
J . Org. Chem., Vol. 62, No. 19, 1997 6553
Ta ble 6. Ep oxid e Isom er iza tion u sin g P d (0)-P P h 3
Ca ta lysts
Sch em e 3. Tw o-Step Syn th esis of Ben zylic
Ca r bon yl Com p ou n d s
entry
catalyst
12 (%)a
26 (%)a
1
2
3
4
5
6
7
5% Pd(OAc)2, 15% PPh3
5% Pd(OAc)2, 20% PPh3
5% Pd(OAc)2, 25% PPh3
5% Pd(PPh3)4
5% Pd(PPh3)4 + 5% KOAc
5% Pd(PPh3)4 + 5% HOAc
2.5% Pd2(dba)3 + 20% PPh3
0
6
3
28
18
14
89
82
86
91
61
76
59
0
formed per mole of catalyst) prior to catalyst deactivation,
we treated a solution of Pd(OAc)2/PBu3 with a large
excess (1000 equiv per Pd) of disubstituted epoxide 12
and carried out the isomerization reaction as described
previously. After 48 h of reflux under N2, the isolated
yield of isomerization product 26 was 93%, with no
unreacted epoxide observed, indicating that at least 930
catalytic turnovers are achievable. Clearly, although 5
mol % Pd(0) works conveniently for a number of substi-
tution patterns, some substrates can be isomerized quite
efficiently with a much lower catalyst loading.
Syn th etic Utility of P d-Catalyzed Epoxide Isom er -
iza tion . The primary goal of this research is to develop
a selective and efficient synthesis of carbonyl compounds
from epoxides. In general, our reaction can be viewed
as the key process in a two-step protocol for the homolo-
gation of an aryl aldehyde or ketone to a higher carbonyl
compound. This protocol involves (1) conversion of the
aryl aldehyde or ketone to an epoxide followed by (2)
selective isomerization of the epoxide to a benzylic
aldehyde or ketone, as depicted in Scheme 3. The first
step may be carried out in a number of ways. The
shortest route (method a) involves addition of an alkyl-
idene fragment to the starting carbonyl compound, via
sulfur ylide technology,20 providing the epoxide in one
step. Alternatively (path b), a Wittig or other olefina-
tion,32 followed by epoxidation with any of a variety of
oxygen-atom transfer reagents,2-4 affords the epoxide in
two steps. In this case, the stereochemistry of olefination
is not important, since the â-carbon eventually attains
sp2-hybridization. Finally (path c), the three-step se-
quence demonstrated in Scheme 1 (Grignard addition,
dehydration, epoxidation) is also a viable route.
The crucial step, however, is the Pd-catalyzed epoxide
isomerization. As mentioned previously, Lewis acids
have long been known to catalyze the rearrangement of
epoxides to carbonyl compounds.6 Although certain
epoxide substrates reliably give a single isomeric carbonyl
compound upon rearrangement with Lewis acids, some
classes of epoxides are notoriously prone to unselective
reactions. For example, House showed that trans-stil-
bene oxide undergoes isomerization with catalytic MgBr2
to afford a mixture of deoxybenzoin and diphenyl-
acetaldehyde33a and that 2,3-epoxybutane also gives
mixtures of products arising from competitive hydride
and alkyl migration.33b Likewise, Rickborn and co-
workers found that lithium salts rearrange simple
monoalkyl-substituted epoxides to give both the methyl
ketone and the corresponding aldehyde.34 More recently,
Yamamoto investigated the use of bulky aluminum-based
a
Yields refer to isolated, purified product.
Pd(PPh3)4 is much less reactive (entry 4) even than the
catalyst mixture formed from 5 equiv of PPh3 per Pd,
which, presumably, still has 4 equiv of unoxidized PPh3
present (based on the hypothesis that reduction of
Pd(OAc)2 with PPh3 affords Pd(0), OdPPh3, and HOAc,
in the presence of trace water).30 Clearly, the mode of
preparation of the Pd(0) catalyst has a major effect on
its reactivity. In order to probe whether the presence of
acetate leads to higher catalytic activity, we repeated the
experiment in entry 4, except with 1 equiv of anhydrous
potassium acetate per Pd. Interestingly, the reactivity
increased (entry 5) compared to Pd(PPh3)4, but not quite
to the level observed in entry 3. This observation
contrasts with Amatore’s work,30 in which Pd(OAc)2/PPh3
and Pd(PPh3)4 + OAc- displayed identical physicochem-
ical properties. Thus, although acetate increases the
reactivity of Pd(PPh3)4 in catalytic epoxide isomerization,
possibly by formation of the anionic acetoxypalladate
anion identified by Amatore, the catalyst mixture is not
identical to that obtained by reduction of Pd(OAc)2 with
PPh3. Acetic acid (5 mol %), in contrast, has little effect
on the catalytic efficiency of Pd(PPh3)4 (entry 6); although
less unreacted epoxide was recovered, the yield of ketone
25 was about the same as with Pd(PPh3)4 alone. As we
have no direct evidence concerning the nature of the
catalyst formed in our experiments, we can only surmise
that some other component present in the mixtures
formed in entries 1-3 but absent from the Pd(PPh3)4
reaction facilitates the epoxide isomerization but has no
influence on the rate of the Heck reaction. Finally, in
entry 7, we show that the catalyst obtained by treatment
of the palladium(0)-dibenzylideneacetone complex with
PPh3 (4 equiv/Pd) is completely unreactive in epoxide
isomerization. Clearly, displacement of dba by PPh3 is
incomplete,31 and the resulting enone- or phosphine-
enone complexes that may be present are simply insuf-
ficiently nucleophilic to activate epoxides. This obser-
vation, as well as those in entries 3-5, should serve as a
warning to those who might mistakenly assume that all
Pd(0)/PPh3 catalysts are equivalent in reactivity.
The high efficiency of isomerization observed using
Pd(OAc)2/PBu3 in t-BuOH prompted us to question
whether 5 mol % Pd per epoxide, as was employed
throughout this study, was really necessary for maximum
yield. In order to determine the maximum possible
turnover number (i.e., moles of isomerization product
(32) (a) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863-
927. (b) For an excellent overview of carbonyl olefination reactions,
see: Kelly, S. E. In Comprehensive Organic Synthesis; Trost, B. M.,
Ed.; Pergamon: Oxford, 1991; Vol. 1, Chapter 3.1.
(31) Amatore et al. have also shown that excess PPh3 is necessary
for complete displacement of dibenzylideneacetone from Pd(dba)2.
Amatore, C.; J utand, A.; Khalil, F.; M’Barki, M. A.; Mottier, L.
Organometallics 1993, 12, 3168-3178.
(33) (a) House, H. O. J . Am. Chem. Soc. 1955, 77, 3070-3075. (b)
House, H. O. J . Am. Chem. Soc. 1955, 77, 5083-5089.
(34) Rickborn, B.; Gerkin, R. M. J . Am. Chem. Soc. 1971, 93, 1693-
1700.

6554 J . Org. Chem., Vol. 62, No. 19, 1997
Kulasegaram and Kulawiec
Lewis acids for rearrangement of both aryl- and alkyl-
substituted epoxides and found that trisubstituted ep-
oxides consistently form aldehydes by selective alkyl
group (rather than hydride) migration.35
bromo-2,6-di-tert-butylphenoxide) (MABR), led to isola-
tion of the ring-contracted aldehyde 40 with complete
selectivity, and in high yield.35 In fact, all trisubstituted
epoxides tested with MABR showed complete selectivity
for the high-yield formation of aldehyde via alkyl-group
migration. Thus, the present study demonstrates the
complementary nature of our Pd(0) system to Lewis acid
catalysts: the latter give variable amounts of alkyl
migration (in some cases, such as with MABR, with
complete selectivity), while the former operates only via
hydride migration, even with multiply-substituted sub-
strates. It should be noted that Sankararaman and
colleagues have recently reported the use of 5 M LiClO4-
Et2O as a catalyst for the isomerization of epoxides to
carbonyl compounds.36 These workers observe high
selectivity for rearrangement via C-O cleavage at the
more substituted oxirane carbon, followed by hydride
(rather than alkyl or aryl) migration, regardless of
whether that position is aryl- or alkyl-substituted. The
high selectivity of LiClO4-Et2O system for substituted
oxiranes (monoalkyl-substituted epoxides are inert) also
makes it highly complementary to the two isomerization
catalysts discussed above.
The extremely high regioselectivity we observe in the
isomerization of aryl-substituted epoxides to benzylic
carbonyl compounds offers a synthetic advantage over
another possible pathway to aldehydes and ketones,
namely, Wacker oxidation of vinylarenes. Although such
compounds do undergo direct aerobic oxidation with
PdCl2/CuCl to form carbonyl compounds, the selectivity
is generally poor. For example, Keinan observed that
Wacker oxidation of â-methylstyrene gave a 3:1 mixture
of 1-phenyl-2-propanone and 1-phenyl-1-propanone (eq
6).37 In contrast, we find that the two-step protocol of
In contrast to these results, we find that all of our aryl-
substituted epoxide substrates that react with Pd(OAc)2/
PBu3 (i.e., those bearing at least one hydrogen â to the
aryl ring) do so with complete regioselectivity for forma-
tion of a single carbonyl compound, via cleavage of the
benzylic C-O bond. In order to make a direct comparison
between our catalyst system and a traditional Lewis acid
catalyst, boron trifluoride etherate, we reacted epoxides
12 and 14 with the latter reagent. With the disubstituted
epoxide 12 (eq 3), we obtained ketone 26 in 70% yield.
Although the chemoselectivity with respect to product
formation is very high, the yield is considerably lower
than we observe using Pd(OAc)2/PR3 (compare to Table
1, entries 5-8), which gives a near quantitative yield of
ketone within minutes. Furthermore, the Pd catalyst
operates under nearly neutral (or, in fact, Lewis basic)
conditions and thus may be preferable with substrates
that are sensitive to strong Lewis acids. With trisubsti-
tuted epoxide 14, however, a very different picture
emerges. Isomerization with BF3‚OEt2 (eq 4) gave ketone
28, formed via hydride migration, as well as aldehyde
38, via methyl migration. The overall isolated yield was
only 66%, and the chemoselectivity was a mere 2.8:1,
slightly favoring the hydride migration pathway. This
result stands in stark contrast to that obtained with
Pd(OAc)2/PBu3 in t-BuOH, wherein we saw formation of
ketone 28 as the only isomerization product, in a satisfy-
ing 96% yield (Table 1, entry 16). Clearly, the pal-
ladium(0) route is the method of choice for rearrangement
of highly substituted epoxides which are otherwise prone
to isomerization via alkyl migration. Finally, isomeriza-
tion of the cyclic, trisubstituted epoxide 16 using Pd(OAc)2/
PBu3 in t-BuOH provided 2-phenylcyclohexanone (39) in
89% yield (eq 5), again as the only isomerization product
epoxidation of (E)-1-(2-naphthyl)-1-propene (8), followed
by Pd-catalyzed isomerization, affords the 1-aryl-2-pro-
panone 26 as the sole product (Table 1, entry 8), albeit
in lower overall yield. This observation suggests that
epoxidation/isomerization may be preferable to direct
oxidation for the conversion of some alkenes to carbonyl
compounds in a highly regioselective manner.
Mech a n istic Ra tion a le. The mechanism of epoxide
isomerization by late-transition metal complexes is gen-
erally thought to involve cleavage of a C-O bond by an
oxidative addition process, followed by â-hydride elimina-
tion to a metal hydrido-enolate complex, which reduc-
tively eliminates the carbonyl compound. In support of
this general scenario, Milstein has shown that low-valent,
electron-rich Ir and Rh complexes react with monosub-
stituted epoxides to form stable, isolable hydrido-enolate
complexes mer-(PMe3)3M(H)(Cl)(CH2COR), one of which
(M
) Ir, R ) H) was characterized by X-ray
crystallography.9c The rhodium complex was shown to
undergo a dissociative reductive elimination to form
methyl ketones (RCOCH3, where R ) Me, Ph); in fact,
the precursor to the Rh enolate complex, RhCl(PMe3)3,
observed. In contrast, Yamamoto’s work showed that
treatment of epoxide 16 with a variety of Lewis acids,
such as BF3‚OEt2, SbF5, and methylaluminum bis(4-
(36) Sudha, R.; Malola Narasimhan, K.; Geetha Saraswathy, V.;
Sankararaman, S. J . Org. Chem. 1996, 61, 1877-1879.
(37) Keinan, E.; Seth, K. K.; Lamed, R. J . Am. Chem. Soc. 1986,
108, 3474-3480.
(35) Maruoka, K.; Murase, N.; Bureau, R.; Ooi, T.; Yamamoto, H.
Tetrahedron 1994, 50, 3663-3672.

Pd-Catalyzed Isomerization of Aryl-Substituted Epoxides
J . Org. Chem., Vol. 62, No. 19, 1997 6555
Sch em e 4. Mech a n istic Ra tion a le
nature of the Pd(0) complex formed by reduction with
PBu3; we must rely on the observations of Mandai et al.,21
who found the spectroscopy and reactivity of the catalysts
formed in situ to be consistent with highly nucleophilic
Pd(0)-tertiary phosphine complexes. (2) The turnover-
limiting nature of the initial attack of Pd(0) on the
epoxide is supported by the observation that more
sterically hindered substrates react more slowly (com-
pare, for example: entries 10 and 14 in Table 1; the
greater reactivity of cis-stilbene oxide compared to trans-
stilbene oxide; and the greater reactivity of either stilbene
oxide vs 2,2-diphenyloxirane in Table 2). Our assertion
that the structure of the initial oxidative addition product
is a zwitterionic species rather than a palladaoxetane is
based on the observation of increased reaction rates in
polar, protic solvents (see discussion above). Indeed, the
fastest isomerization reactions are observed in t-BuOH,
in which Pd(OAc)2/PBu3-catalyzed isomerization of 12 to
26 occurs within minutes at ambient temperature,
whereas the same reaction in benzene has a half-life of
48 min. It is easy to rationalize this phenomenon as a
lowering of the activation barrier in the turnover-limiting
step by stabilization of the transition state via hydrogen
bonding of the incipient alkoxide anion with the protic
solvent. The formation of a metallaoxetane on the
isomerization pathway is unlikely on stereoelectronic
grounds: such a coordination mode would preclude the
Pd complex from attaining the syn-coplanar geometry of
the Pd-C-C-H moiety necessary for â-H elimination.
(3) Monitoring the catalytic isomerization of 12 to 26 by
Pd(OAc)2/PBu3 using 1H NMR (270 MHz, C6D6) revealed
only signals attributable to 12, 26, and PBu3. Specifi-
cally, we saw no aliphatic resonances that might arise
from any of the other postulated intermediates in the
reaction (for example, the alkoxyalkyl or hydrido-enolate
complexes). In particular, we saw no evidence for metal
hydrides (to -50 ppm). This suggests that the resting
state of the catalyst is the simple Pd(0)-PR3 complex and
that none of the other intermediates are sufficiently long-
lived to be observable by NMR. (4) The observed unre-
activity of epoxides 13 and 15, which have no hydrogens
â to the aromatic ring capable of undergoing migration,
is consistent with the mechanism depicted. While â-
elimination of alkyl groups is not unknown in late
transition metal chemistry, it is nevertheless uncommon,
especially in the absence of any overwhelming driving
force (such as aromatization or relief of ring strain).40
Apparently the formation of a carbonyl group does not
provide sufficient exothermicity to force the migration of
a methyl group. This analysis assumes, of course, that
initial attack and C-O cleavage actually occurs with 13
and 15, which we have not yet rigorously proven, but
infer from the reactivity of epoxides with similar steric
profiles, such as 2 and 14. It is also noteworthy that
these latter substrates, which bear both a methyl group
and an aryl substituent at C2, do not undergo competitive
â-hydride elimination from the methyl group to form
allylic alcohols, as is seen with certain types of epoxides
and catalysts.10a,e,13a,b The full negative charge on the
oxygen apparently induces preferential hydrogen migra-
tion from the alkoxyalkyl group rather than from the
methyl group.
is a moderately active catalyst for the isomerization of
mono-substituted epoxides to methyl ketones. Another
possible intermediate in this process, a structurally
characterized oxametallacyclobutane complex of Rh(III),
was prepared via direct oxidative addition of a non-
isomerizable epoxide (isobutylene oxide) to a Rh(I) pre-
cursor.38 An exception to this general scenario of isomer-
ization via C-O oxidative addition-â-hydride elimina-
tion arises in the earlier work of Milstein, Buchman, and
Blum, who described the rearrangement of stilbene
oxides to 1,2-diarylethanones via RhCl(PPh3)3.9b In
contrast to the C-O cleavage route described above, this
reaction was shown to proceed via initial insertion of
Rh(I) into a C-H bond of the oxirane, followed by rate-
determining 1,3-hydride migration from Rh to C2 of the
oxiranyl ligand with concomitant ring-opening. In a
similar vein, Wu and Bergman demonstrated that the
reaction of a coordinatively unsaturated Rh(I) complex
with ethylene oxide to generate a formylmethyl hydride
complex also occurs via initial C-H insertion, followed
in this case by ring opening and subsequent hydride
migration from C2 of the oxiranyl ligand to C1, with
concomitant enolate ligand formation.39
In order to rationalize the chemistry we observe
between Pd(OAc)2/PR3 and aryl-substituted epoxides, we
tentatively propose the mechanistic scenario depicted in
Scheme 4. This rationale involves formation of a Pd(0)
species as the active catalyst by reduction of Pd(OAc)2
by tertiary phosphine; turnover-limiting attack of Pd(0)
at the benzylic carbon in an SN2-like process, generating
a zwitterionic â-alkoxyalkylpalladium(II) intermediate;
rapid â-hydride elimination to form a hydrido-enolate
intermediate (which is depicted as carbon-bound for
simplicity, but could instead be oxygen-bound); and rapid
reductive elimination affording the carbonyl compound,
with regeneration of Pd(0).
Although we have not yet completed a full mechanistic
study of this reaction, the following preliminary observa-
tions support the above proposal. (1) The literature
precedent for formation of Pd(0) from Pd(OAc)2 and PR3
(where R ) n-Bu or Ph) has been discussed above;26,30
the results of our catalysts studies (see Table 6) are
consistent with the formation of a Pd(0) catalyst system
that is distinctly more reactive than simple Pd(PR3)4.
However, we have no direct evidence concerning the
(38) (a) Zlota, A. A.; Frolow, F.; Milstein, D. J . Am. Chem. Soc. 1990,
112, 6411-6413. (b) Calhorda, M. J .; Galva˜o, A. M.; U¨ naleroglu, C.;
Zlota, A. A.; Frolow, F.; Milstein, D. Organometallics 1993, 12, 3316-
3325.
(39) Wu, J .; Bergman, R. G. J . Am. Chem. Soc. 1989, 111, 7628-
7630.
(40) (a) Crabtree, R. H. Chem. Rev. 1985, 85, 245-269. For specific
examples, see: (a) Benfield, F. W. S.; Green, M. L. H. J . Chem. Soc.,
Dalton Trans. 1974, 1324-1331. (b) Eilbracht, P.; Mayser, U. Chem.
Ber. 1980, 113, 2211-2220. (c) Crabtree, R. H.; Dion, R. P. J . Chem.
Soc., Chem. Commun. 1984, 1260-1261.

6556 J . Org. Chem., Vol. 62, No. 19, 1997
Kulasegaram and Kulawiec
0.32 mm, film thickness 0.52 mm). Mass spectra were
measured on a Fisons Instrument MD 800 quadrupole mass
spectrometer, with 70 or 30 eV electron ionization, and a GC
8000 Series gas chromatograph inlet, using a J & W Scientific
DB-5MS column of 15 m length, 0.25 mm i.d., and 0.25 mm
film thickness. Mass spectral data are given as m/e, with the
relative peak height following in parentheses.
The observed first-order dependence of the rate on
epoxide concentration (at least during the initial period
of the reaction), as demonstrated in the kinetic studies
of the isomerization of epoxide 12, does not necessitate
that attack by Pd(0) be the turnover-limiting step, but
is certainly consistent with such a hypothesis. We have
not yet determined the order of the reaction with respect
to Pd, but these and other experiments (including deter-
mination of activation parameters, isotopic labeling stud-
ies, and kinetic isotope effects) are in progress and will
be reported in a forthcoming manuscript.
Tri-n-butylphosphine, MCPBA (73.4%), p-toluenesulfonic
acid hydrate, p-toluenesulfonyl chloride, trimethylsulfonium
iodide, 2-naphthaldehyde, 2-acetonaphthenone, benzophenone,
benzaldehyde, cyclohexanone, magnesium turnings, bromo-
ethane, iodomethane, bromobenzene, 2-bromopropane, 10-
undecenal (which was distilled prior to use), carbon tetra-
bromide, n-BuLi, N-bromosuccinimide, trans-stilbene, cis-
stilbene, sodium hydride, BH3‚THF, and hexadecane were
purchased from Aldrich Chemical Company. Chromium tri-
oxide was purchased from Fisher Scientific, and pyridinium
chlorochromate was from Lancaster Synthesis. Triphenylphos-
phine was purchased from Fluka and purified by recrystalli-
zation from 95% ethanol. Sodium cyanide was purchased from
J . T Baker. Palladium acetate was from Strem Chemicals and
was recrystallized from benzene prior to use. Palladium(II)
chloride was purchased from J ohnson Matthey and used
Con clu sion s
In summary, this work demonstrates a useful protocol
for the high-yield, efficient, and selective synthesis of
benzylic aldehydes and ketones by palladium(0)-catalyzed
isomerization of the corresponding aryl-substituted ep-
oxides. The reaction is applicable to epoxides with a
variety of substitution patterns and functional groups
and, when coupled with the preparation of the precursor
epoxide (as depicted in Scheme 3), provides a convenient
homologation of aryl aldehydes and ketones to benzylic
aldehydes and ketones. The isomerization reaction is
most efficient using Pd(OAc)2/PBu3 in refluxing t-BuOH
or other polar solvents and provides the isomerization
product with complete chemoselectivity for hydride mi-
gration rather than alkyl migration, in a manner that is
complementary to commonly employed Lewis acidic
isomerization catalysts.
43
directly in the synthesis of Pd(PPh3)4 and Pd2(dba)3.44 All
new compounds are fully characterized by standard spectro-
scopic and analytical or mass spectrometric techniques. Known
compounds are identified by 1H NMR and have literature
references provided.
trans-Stilbene oxide (29),45 cis-stilbene oxide (30),45 and
1-phenyl-1,2-epoxycyclohexane (16)35 were prepared according
to the literature, and their identities and purities were verified
1
by H NMR.
P r ep a r a tion of Ep oxid es 1-3. Gen er a l Meth od .20
A
solution of dimethylsulfonium methylide was prepared from
trimethylsulfonium iodide and sodium hydride in DMSO-
THF, and a solution of the appropriate carbonyl compound in
THF was added at 0 °C. After completion of reaction, as
determined by TLC, the mixture was worked up by diluting
with water and extracting with diethyl ether; the epoxide was
purified by flash chromatography.
Exp er im en ta l Section
Gen er a l Con sid er a tion s. All reactions were carried out
under an atmosphere of nitrogen using standard Schlenk
techniques.41 The isomerization reactions were carried out in
Schlenk tubes with 19/22 outer joints and standard ground
glass gas inlets; the main body of the tube was 1.5 (o.d.) × 14
cm, that is, of sufficient length that refluxing solvent was
cooled by the ambient air (no condenser was required). Ether
and tetrahydrofuran were distilled from blue or purple solu-
tions of sodium benzophenone ketyl, and dichloromethane was
distilled from CaH2, immediately prior to use. Benzene, DMF,
DMSO, acetonitrile, t-BuOH, and dioxane were distilled from
CaH2, stored over 3 Å molecular sieves, and deaerated by
purging with nitrogen immediately before use. 2-Butanone
was distilled and purged with nitrogen before use. All other
solvents were used as received. Thin-layer chromatography
was performed using Merck glass plates precoated with F254
silica gel 60; compounds were visualized by UV and/or with
p-anisaldehyde stain solution. Flash chromatography was
performed using EM Science silica gel 60, following the
procedure of Still,42 with the solvent mixtures indicated.
Melting points were measured on a Thomas-Hoover capillary
melting point apparatus and are uncorrected. Combustion
analyses were performed by Desert Analytics of Tucson, AZ.
NMR spectra were measured on a Nicolet NT 270 spec-
trometer, modified with a Libra real-time NMR station, using
MacNMR software, provided by Tecmag Inc. of Houston, TX;
1H spectra were measured at 270 MHz and 13C{1H} NMR
spectra were measured at 67.9 MHz; and chemical shifts are
listed in δ (ppm) relative to Me4Si. All spectra are recorded
in CDCl3. IR spectra were measured on a Mattson Galaxy
2020 Series FTIR, as neat films or Nujol mulls; absorption
bands are reported in cm-1. Gas chromatograms were meas-
ured on a Hewlett-Packard 5890 Series II instrument, using
an Ultra 2 (cross-linked 5% Ph Me silicone) 50 m column (i.d
2-(2-Na p h th yl)oxir a n e (1):46 prepared from trimethyl-
sulfonium iodide (2.61 g, 13 mmol), NaH (0.31 g, 13 mmol),
DMSO (19.0 mL), THF (11.7 mL), and 2-naphthaldehyde (1.0
g, 6.4 mmol); yield ) 0.873 g (80%), Rf ) 0.45 (6:1 hexane-
ethyl acetate), mp 57-58 °C. 1H NMR: δ 7.88-7.72 (m, 4H),
7.63-7.50 (m, 2H), 7.37-7.29 (m, 1H), 4.03 (dd, J ) 4.0, 2.4
Hz, 1H), 3.23 (dd, J ) 4.2, 5.6 Hz, 1H), 2.91 (dd, J ) 2.4, 5.5
Hz, 1H).
2-Meth yl-2-(2-n a p h th yl)oxir a n e (2):47 prepared from tri-
methylsulfonium iodide (2.41 g, 12 mmol), NaH (0.29 g, 12
mmol), DMSO (15 mL), THF (11 mL), and 2-acetonaphthenone
(1.0 g, 5.9 mmol); yield ) 0.976 g (90%), Rf ) 0.50 (6:1 hexane-
ethyl acetate), mp 79-81 °C. 1H NMR: δ 7.91-7.81 (m, 3H),
7.49-7.46 (m, 4H), 3.07 (d, J ) 5.1 Hz, 1H), 2.90 (d, J ) 5.4
Hz, 1H), 1.57 (s, 3H).
2,2-Dip h en yloxir a n e (3):48 prepared from trimethyl-
sulfonium iodide (2.24 g, 11 mmol), NaH (0.26 g, 11 mmol),
DMSO (15 mL), THF (10.5 mL), and benzophenone (1.0 g, 5.5
mmol); yield ) 0.973 g (90%), Rf ) 0.56 (6:1 hexane-ethyl
acetate). 1H NMR: δ 7.51-7.26 (m, 10H), 3.28 (s, 2H).
P r ep a r a t ion of Ben zylic Alcoh ols 4-7. Gen er a l
Meth od . A solution of Grignard reagent was prepared from
the bromoalkane and magnesium in ether, cooled to 0 °C, and
treated with a solution of the appropriate carbonyl compound.
The mixture was warmed to room temperature and quenched
with water, and the phases were separated. The ethereal layer
(43) Coulson, D. R. Inorg. Synth. 1990, 28, 107-110.
(44) Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J . J .; Ibers, J . A. J .
Organomet. Chem. 1974, 65, 253-266.
(45) Curtin, D. Y.; Kellom, D. B. J . Am. Chem. Soc. 1953, 75, 6011-
6018.
(46) Shi, L.; Zhou, Z.; Huang, Y. Tetrahedron Lett. 1990, 31, 4173-
4174.
(47) Matsumoto, T.; Takeda, Y.; Iwata, E.; Sakamoto, M.; Ishida,
T. Chem. Pharm. Bull. 1994, 42, 1191-1197.
(48) Lopez, L.; Troisi, L. Tetrahedron Lett. 1989, 30, 3097-3100.
(41) Shriver, D. F.; Drezdzon, M. A. The Manipulation of Air-
Sensitive Compounds, 2nd ed.; Wiley Interscience: New York, 1986.
(42) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923-
2925.

Pd-Catalyzed Isomerization of Aryl-Substituted Epoxides
J . Org. Chem., Vol. 62, No. 19, 1997 6557
was washed with saturated solutions of NaHSO4, NaHCO3,
and brine, dried (MgSO4), and evaporated to afford the crude
alcohol, which was purified by flash chromatography.
NMR: δ 7.83-7.79 (m, 3H), 7.68 (m, 1H), 7.51-7.43 (m, 2H),
7.31 (dd, J ) 8.4, 1.9 Hz, 1H), 2.02 (s, 3H), 1.88 (s, 3H), 1.65
(s, 3H).
1-(2-Na p h th yl)-1-p r op a n ol (4):49 prepared from magne-
sium (1.49 g, 61.4 mmol), bromoethane (3.8 mL, 51.2 mmol),
2-naphthaldehyde (4.0 g, 25.6 mmol), and ether (40 mL); yield
) 4.07 g (85%), Rf ) 0.38 (6:1 hexane-ethyl acetate). 1H
NMR: δ 7.85-7.78 (m, 4H), 7.51-7.45 (m, 3H), 4.78 (dt, J )
3.1, 6.6 Hz, 1H), 1.94-1.82 (m, 2H), 0.95 (t, J ) 7.5 Hz, 3H).
2-Meth yl-1-(2-n a p h th yl)-1-p r op a n ol (5):50 prepared from
magnesium (0.88 g, 36 mmol), 2-bromopropane (2.8 mL, 30
mmol), 2-naphthaldehyde (2.34 g, 15 mmol), and ether (15 mL);
P r ep a r a tion of Ep oxid es 12-15. Gen er a l Meth od . A
solution of the vinylarene in CH2Cl2 (0.2-0.4 M) was cooled
to 0 °C, treated with MCPBA, and allowed to stir while
warming to room temperature for approximately an hour.
When TLC indicated completion of reaction, the mixture was
worked up by diluting with diethyl ether, separating phases,
and washing the organic phase with saturated aqueous
Na2S2O3 (2 × 10 mL), NaHCO3 (3 × 10 mL), 5% NaOH (10
mL), and brine (10 mL), followed by drying over MgSO4. After
evaporation, the epoxide was purified by flash chromatogra-
phy.
tr a n s-3-Meth yl-2-(2-n a p h th yl)oxir a n e (12):19 prepared
from (E)-1-(2-naphthyl)propene (8, 0.50 g, 2.9 mmol) and
MCPBA (0.84 g, 3.6 mmol, 73.4% pure) in CH2Cl2 (10 mL);
yield ) 0.45 g (81%), Rf ) 0.53 (9:1 hexane-ethyl acetate),
mp 56-57 °C. 1H NMR: δ 7.83-7.76 (m, 4H), 7.50-7.45 (m,
2H), 7.32 (dd, J ) 1.5, 8.6 Hz, 1H), 3.74 (d, J ) 2.2 Hz, 1H),
3.14 (dq, J ) 2.2, 5.3 Hz, 1H), 1.50 (d, J ) 5.3 Hz, 3H).
3,3-Dim eth yl-2-(2-n a p h th yl)oxir a n e (13): prepared from
2-methyl-1-(2-naphthyl)propene (9, 0.67 g, 3.7 mmol) and
MCPBA (1.0 g, 4.4 mmol, 73.4% pure) in CH2Cl2 (10 mL); yield
) 0.63 g (86%), Rf ) 0.61 (6:1 hexane-ethyl acetate), mp 52-
55 °C. 1H NMR: δ 7.84-7.75 (m, 4H), 7.49-7.43 (m, 3H), 4.03
(s, 1H), 1.54 (s, 3H), 1.11 (s, 3H). 13C NMR: δ 138.7, 133.2,
132.8, 128.1, 127.9, 127.6, 126.2, 125.9, 124.4, 123.2, 64.8, 61.4,
24.8, 18.1. IR: 2934, 2856, 1928, 1801, 1597, 1460, 1377, 1304,
1243, 1125, 954, 887, 756. MS: 198 (M+, 98.0), 183 (74.5),
169 (84.7), 155 (94.9), 140 (100.0), 127 (89.4), 115 (46.3), 101
(23.9), 89 (49.8), 77 (50.6), 63 (47.8), 51 (26.7). Anal. Calcd
for C14H14O: C, 84.81; H, 7.12. Found: C, 84.79; H, 7.22.
tr a n s-2,3-Dim et h yl-2-(2-n a p h t h yl)oxir a n e (14): pre-
pared from (E)-2-(2-naphthyl)-2-butene (10, 0.43 g, 2.4 mmol)
and MCPBA (0.67 g, 2.9 mmol, 73.4% pure) in CH2Cl2 (10 mL);
yield ) 0.33 g (75%), Rf ) 0.53 (8:1 hexane-ethyl acetate),
mp 51-53 °C. 1H NMR: δ 8.09 (m, 1H), 7.89 (m, 3H), 7.50
(m, 3H), 4.28 (q, J ) 6.8 Hz, 1H), 2.19 (s, 3H), 1.08 (d, J ) 6.8
Hz, 3H). 13C NMR: δ 140.6, 132.6, 128.2, 127.9, 127.6, 126.1,
125.8, 123.9, 123.2, 76.6, 62.5, 60.6, 21.5, 17.6, 14.5. IR: 2924,
2853, 1943, 1647, 1599, 1507, 1459, 1377, 1274, 1195, 1129,
1071, 858, 808, 744. MS: 198 (M+, 67.6), 169 (77.6), 155
(100.0), 141 (48.9), 128 (51.0), 115 (29.5), 102 (4.8), 89 (4.1),
77 (12.7), 63 (6.9), 43 (12.1). Anal. Calcd for C14H14O: C,
84.81; H, 7.12. Found: C, 84.91; H, 6.96.
2,3,3-Tr im eth yl-2-(2-n a p h th yl)oxir a n e (15): prepared
from 3-methyl-2-(2-naphthyl)-2-butene (11, 0.75 g, 3.8 mmol)
and MCPBA (1.07 g, 4.6 mmol, 73.4% pure) in CH2Cl2 (10 mL);
yield ) 0.60 g (74%), Rf ) 0.70 (6:1 hexane-ethyl acetate),
mp 37-38 °C. 1H NMR: δ 7.82-7.73 (m, 3H), 7.46-7.38 (m,
4H), 1.68 (s, 3H), 1.49 (s, 3H), 0.97 (s, 3H). 13C NMR: δ 133.1,
132.5, 128.0, 127.8, 127.7, 127.6, 126.1, 125.6, 124.7, 124.4,
69.1, 63.9, 21.7, 21.4, 20.8. IR: 2978, 2863, 1989, 1636, 1603,
1460, 1377, 1190, 1069, 911. MS: 212 (M+, 93.3), 197 (76.9),
169 (87.1), 152 (100.0), 141 (73.7), 127 (86.7), 115 (62.8), 101
(35.7), 89 (24.6), 77 (63.1), 63 (46.3), 51 (36.1). Anal. Calcd
for C15H16O: C, 84.87; H, 7.60. Found: C, 84.83; H, 7.45.
1-P h en yl-10-u n d ecen -1-ol (17).19 A solution of phenyl-
magnesium bromide was prepared from magnesium (0.56 g,
23.0 mmol), bromobenzene (2.0 mL, 19.0 mmol), and diethyl
ether (20 mL). The solution was cooled to 0 °C and treated
dropwise with freshly distilled 10-undecenal (1.98 mL, 9.5
mmol) via syringe. The mixture was allowed to warm to room
temperature with stirring, over 30 min, at which point no
aldehyde was observed by TLC (the product alcohol showed
Rf ) 0.36 in 6:1 hexane-ethyl acetate). The mixture was
poured onto ice, and the phases were separated; the organic
layer was washed with saturated NaHSO4 (20 mL), NaHCO3
(3 × 20 mL), and brine (20 mL). After drying (MgSO4) and
evaporation, the crude product was distilled (155 °C at 5 mm)
to afford 1.8 g (79%) of the alcohol. 1H NMR: δ 7.33 (m, 5H),
5.81 (ddt, J ) 17.1, 6.6, 7.0 Hz, 1H), 4.98 (d of m, J ) 17.1 Hz,
1H), 4.92 (d of m, J ) 12.3, 1H), 4.66 (t, J ) 7.0 Hz, 1H), 2.03
(m, 2H), 1.74 (m, 2H), 1.26 (m, 12H).
1
yield ) 2.1 g (70%), Rf ) 0.42 (6:1 hexane-ethyl acetate). H
NMR: δ 7.84-7.75 (m, 4H), 7.49-7.44 (m, 3H), 4.54 (dd, J )
7.1, 2.9 Hz, 1H), 2.14 (m, 1H), 1.94 (d, J ) 3.2 Hz, 1H), 1.05
(d, J ) 6.6 Hz, 3H), 0.83 (d, J ) 6.8 Hz, 3H).
2-(2-Na p h th yl)-2-bu ta n ol (6):51 prepared from ethylmag-
nesium bromide (11.0 mL of a 1.28 M ethereal solution, 14
mmol), 2-acetonaphthenone (2.0 g, 12 mmol), and ether (15
mL); yield ) 2.30 g (96%), Rf ) 0.38 (6:1 hexane-ethyl acetate).
1H NMR: δ 7.97 (m, 1H), 7.90-7.82 (m, 3H), 7.58 (dd, J )
1.7, 8.7 Hz, 1H), 7.52-7.49 (m, 2H), 1.96 (dq, J ) 2.7, 7.3 Hz,
2H), 1.67 (s, 3H), 0.88 (t, J ) 7.3 Hz, 3H).
3-Meth yl-2-(2-n a p h th yl)-2-bu ta n ol (7): prepared from
magnesium (1.03 g, 42.2 mmol), 2-bromopropane (3.3 mL, 35.2
mmol), 2-acetonaphthenone (3.0 g, 17.6 mmol), and ether (15
mL); yield ) 1.89 g (50%), Rf ) 0.39 (8:1 hexane-ethyl acetate).
1H NMR: δ 7.88-7.36 (m, 7H), 2.08 (m, 1H), 2.02 (s, 3H), 0.89
(d, J ) 6.8 Hz, 3H), 0.79 (d, J ) 6.8 Hz, 3H). 13C NMR: δ
145.5, 133.2, 132.3, 128.2, 127.5, 127.4, 125.9, 125.6, 124.1,
123.7, 76.9, 38.5, 26.9, 17.6, 17.3. IR: 3478, 3060, 2978, 2876,
1923, 1678, 1630, 1599, 1504, 1459, 1385, 1273, 1132, 1080,
1037, 903, 819, 746. MS: 214 (M+, 78.0), 196 (78.0), 181 (81.6),
171 (100.0), 165 (74.9), 155 (80.0), 141 (70.2), 128 (94.9), 115
(63.5), 101 (31.4), 89 (43.5), 77 (6.8), 63 (38.0), 51 (29.8). Anal.
Calcd for C15H18O: C, 84.07; H, 8.47. Found: C, 84.13; H, 8.31.
P r ep a r a tion of Vin yla r en es 8-11. Gen er a l Meth od .
A solution of benzylic alcohol (ca. 0.5-0.7 M) and p-toluene-
sulfonic acid hydrate (10 mol %) in benzene was refluxed under
N2 until the starting material was no longer visible by TLC
(ca. 0.5 h). The solution was cooled, diluted with ether, washed
with saturated aqueous NaHCO3 and water, dried over MgSO4,
and purified by flash chromatography.
(E)-1-(2-Na p h th yl)p r op en e (8):49 prepared from a solu-
tion of crude 1-(2-naphthyl)-1-propanol (4, 4.0 g, 21.0 mmol)
and p-toluenesulfonic acid hydrate (0.39 g, 2.1 mmol) in
benzene (30 mL); yield ) 3.18 g (90%), Rf ) 0.76 (9:1 hexane-
ethyl acetate), mp 40-42 °C. 1H NMR: δ 7.83-7.35 (m, 7H),
6.56 (dq, J ) 15.8, 1.8 Hz, 1H), 6.37 (dq, J ) 15.8, 6.6 Hz,
1H), 1.94 (dd, J ) 6.6, 1.8 Hz, 3H).
2-Meth yl-1-(2-n a p h th yl)p r op en e (9):52 prepared from a
solution of 2-methyl-1-(2-naphthyl)-1-propanol (5, 5.48 g, 27.4
mmol) and p-toluenesulfonic acid hydrate (0.52 g, 2.7 mmol)
in benzene (30 mL); yield ) 4.9 g (91%), Rf ) 0.49 (hexane).
1H NMR: δ 7.81-7.66 (m, 4H), 7.45-7.35 (m, 3H), 6.42 (s,
1H), 1.96 (d, J ) 1.5 Hz, 3H), 1.94 (d, J ) 1.2 Hz, 3H).
(E)-2-(2-Na p h th yl)-2-bu ten e (10):53 prepared from a solu-
tion of 2-(2-naphthyl)-2-butanol (6, 1.0 g, 5.0 mmol) and
p-toluenesulfonic acid hydrate (0.095 g, 0.5 mmol) in benzene
(10 mL); yield ) 0.69 g (76%), Rf ) 0.87 (8:1 hexane-ethyl
acetate). 1H NMR: δ 7.95-7.41 (m, 7H), 6.02 (qq, J ) 6.8,
1.4 Hz, 1H), 2.12 (pseudo dq, J ) 0.97 Hz, 3H), 1.85 (dq, J )
6.8, 0.98 Hz, 3H).
3-Meth yl-2-(2-n a p h th yl)-2-bu ten e (11):50 prepared from
3-methyl-2-(2-naphthyl)-2-butanol (7, 1.0 g, 4.7 mmol) and
p-toluenesulfonic acid hydrate (0.09 g, 0.47 mmol) in benzene
(10 mL); yield ) 0.75 g (82%), Rf ) 0.51 (petroleum ether). 1H
(49) Kon, G. A. R.; Spickett, R. G. W. J . Chem. Soc. 1949, 2725.
(50) Newsoroff, G. P.; Sternhell, S. Aust. J . Chem. 1996, 19, 1667-
1675.
(51) Weber, B.; Seebach, D. Tetrahedron 1994, 50, 6117-6128.
(52) Farkas, J .; Novak, J . J . K. Collect. Czech. Chem. Commun. 1960,
25, 1815-1823.
(53) Bergmann, F.; Weizmann, A. J . Org. Chem. 1946, 11, 592-
596.

6558 J . Org. Chem., Vol. 62, No. 19, 1997
Kulasegaram and Kulawiec
1,2-Ep oxy-1-p h en yl-10-u n d ecen e (18). A solution of 17
(1.0 g, 4.1 mmol) and p-TsOH (77.3 mg, 0.41 mmol) in benzene
(10 mL) was refluxed for 2.5 h. The solution was cooled and
diluted with diethyl ether and water (10 mL each), and the
phases were separated. The organic layer was washed with
NaHCO3 (3 × 15 mL) and brine (20 mL), dried (MgSO4), and
evaporated. Chromatography gave 805 mg (86%) of 1-phenyl-
1,10-undecadiene,19 Rf ) 0.64 (hexane). 1H NMR: δ 7.32 (m,
5H), 6.37 (d, J ) 15.8 Hz, 1H), 6.22 (dt, J ) 15.8, 6.6 Hz, 1H),
5.81 (ddt, J ) 17.1, 6.6, 7.0 Hz, 1H), 4.98 (d of m, J ) 17.1 Hz,
1H), 4.92 (d of m, J ) 12.3 Hz, 1H), 2.20 (dt, J ) 7.9, 14.5 Hz,
2H), 2.04 (dt, J ) 7.0, 14.1 Hz, 2H), 1.36 (m, 10H). 1,2-Epoxy-
1-phenyl-10-undecene was prepared from the above diene (554
mg, 2.3 mmol) and MCPBA (0.81 g, 4.7 mmol, 73% pure) in
CH2Cl2 (7 mL) using the general procedure described above;
yield ) 272 mg (46%) of the diepoxide, Rf ) 0.38 (6:1 hexane-
ethyl acetate), and 251 mg (43%) of the monoepoxide (18), Rf
) 0.69 (6:1 hexane-ethyl acetate). 1H NMR: δ 7.38-7.24 (m,
5H), 5.81 (ddt, J ) 17.1, 6.6, 7.0 Hz, 1H), 4.98 (d of m, J )
17.1 Hz, 1H), 4.92 (d of m, J ) 12.3 Hz, 1H), 3.60 (d, J ) 2.2
Hz, 1H), 2.95 (dt, J ) 2.2, 5.4 Hz, 1H), 2.05 (m, 2H), 1.67 (m,
2H), 1.51-1.34 (m, 10H). 13C NMR: δ 139.2, 138.1, 128.5,
127.9, 125.6, 114.2, 63.1, 58.7, 33.8, 32.4, 29.4, 29.3, 29.1, 28.9,
25.9. IR: 3074, 3036, 2977, 2927, 2856, 1947 (w), 1891 (w),
1819 (w), 1640, 1605, 1497, 1461, 1437, 1351, 1308, 1247, 1202,
1072, 1020, 994, 909, 880, 750, 697. MS: 244 (M+, 1.1), 228
(6.6), 153 (7.5), 135 (18.2), 117 (65.8), 104 (68.4), 91 (100), 83
(12.3), 69 (17.8), 55 (29.4). Anal. Calcd for C17H24O: C, 83.55;
H, 9.90. Found: C, 83.59; H, 9.58.
(E)-11-P h en yl-10-u n d ecen -1-ol. A solution of alcohol 17
(1.7 g, 6.9 mmol) in THF (8 mL) was cooled to 0 °C in a Schlenk
flask under nitrogen. BH3‚THF (17.0 mL, 1 M, 17 mmol) was
added to the solution dropwise, and the mixture was warmed
to room temperature. After 30 min at room temperature, the
mixture was cooled to 0 °C, aqueous sodium hydroxide (3 M,
2.4 mL) was added, and the mixture was stirred at 0 °C for a
further 30 min. Then 30% H2O2 (2.8 mL) was added to the
mixture, which was then heated to 60 °C for 1 h, at which
point TLC showed only the product. The reaction mixture was
diluted with diethyl ether (20 mL) and washed with 1 M HCl
(2 × 20 mL), water (3 × 10 mL), and brine (10 mL). The
organic phase was dried (MgSO4) to afford 1.8 g (99%) of crude
product, which was recrystallized from 20 mL of 3:1 hexane-
diethyl ether to provide 1.4 g (74%, mp 55 °C) of 1-phenyl-
1,11-undecanediol.54 1H NMR: δ 7.33 (m, 5H), 4.65 (t, J )
7.3 Hz, 1H), 3.63 (t, J ) 6.6 Hz, 2H), 1.86-1.25 (m, 18H). A
solution of the above diol (525 mg, 1.9 mmol) in 5 mL of THF
and 5 mL of H3PO4 (85%) was refluxed for 45 min. After
cooling, the mixture was diluted with diethyl ether (15 mL)
and water (15 mL) and washed with NaHCO3 (15 mL) and
brine (15 mL). After drying (MgSO4) and evaporation, the
crude product was chromatographed (Rf ) 0.48, 1:1 hexane-
diethyl ether) to give 272 mg (56%) of (E)-11-phenyl-10-
undecen-1-ol; mp 35-37 °C. 1H NMR: δ 7.36-7.15 (m, 5H),
6.37 (d, J ) 15.6 Hz, 1H), 6.21 (dt, J ) 15.8, 6.6 Hz, 1H), 3.61
(t, J ) 6.6 Hz, 2H), 2.19 (q, J ) 6.6 Hz, 2H), 1.30 (m, 14H).
13C NMR: δ 137.9, 131.1, 129.7, 128.4, 126.7, 125.9, 62.8, 32.9,
32.6, 29.7, 29.4, 29.3, 29.2, 29.0, 25.6. IR: 3251, 3025, 2923,
2853, 1947-1811 (w), 1664, 1599, 1577, 1466, 1377, 1073, 964,
898, 735, 691. MS: 246 (M+, 100), 228 (7.7), 171 (2.9), 157
(4.2), 144 (6.4), 137 (2.9), 129 (13.7), 117 (12.6), 104 (48.9), 96
(4.6), 82 (7.4). Anal. Calcd for C17H26O: C, 82.87; H, 10.64.
Found: C, 83.09; H, 10.82.
244 (M+ - H2O, 3.9), 216 (25.7), 171 (45.8), 153 (92.9), 135
(65.1), 107 (100), 95 (21.1), 81 (26.8). Anal. Calcd for
C17H26O2: C, 77.82; H, 9.99. Found: C, 78.21; H, 10.15.
11,12-Ep oxy-12-p h en yld od eca n en itr ile (20). A solution
of (E)-11-phenyl-10-undecen-1-ol (1.3 g, 5.3 mmol) in pyridine
(15 mL) was cooled to 0 °C and treated with p-toluenesulfonyl
chloride (2.02 g, 11 mmol). The mixture was maintained at 0
°C for 1 h at which point TLC showed only the product (Rf )
0.44, 6:1 hexane-ethyl acetate). The mixture was poured onto
50 g of ice, which was extracted with diethyl ether (2 × 25
mL). The organic layer was washed with saturated NaHSO4
(2 × 25 mL) and water (25 mL), dried (MgSO4), and evaporated
to give 1.87 g (89%) of crude (E)-11-phenyl-10-undecen-1-yl
p-toluenesulfonate, which was sufficiently pure for the next
step. 1H NMR: δ 7.81-7.18 (m, 9H), 6.38 (d, J ) 15.6 Hz,
1H), 6.22 (dt, J ) 15.6, 6.6 Hz, 1H), 4.02 (t, J ) 6.6 Hz, 2H),
2.44 (s, 3H), 2.19 (q, J ) 6.8 Hz, 2H), 1.63-1.17 (m, 14H). 13C
NMR: δ 144.6, 137.9, 133.4, 131.1, 129.8, 129.7, 128.5, 127.9,
126.7, 125.9, 70.6, 32.9, 29.4, 29.2, 29.1, 28.9, 28.7, 28.6, 25.2,
21.4. IR: 3025, 2922, 2849, 1933, 1886, 1654, 1597, 1494,
1467, 1352, 1312, 1189, 1098, 1069, 959, 915, 864, 822, 746,
691, 662, 581, 552. MS: 246 (M+ - SO2C6H4CH3, 6.0), 157
(22.0), 144 (4.3), 129 (11.8), 117 (24.9), 104 (100), 96 (5.9), 82
(11.2). A solution of the crude tosylate (1.72 g, 4.3 mmol) and
NaCN (0.32 g, 6.5 mmol) in DMF (13 mL) was refluxed for 1
h, whereupon TLC showed only the nitrile (Rf ) 0.38, 6:1
hexane-ethyl acetate). The mixture was partitioned between
water and hexane (50 mL each) and separated; the organic
layer was washed with water (25 mL), dried (MgSO4) and
evaporated to yield 970 mg (88%) of crude (E)-12-phenyl-11-
1
dodecenenitrile, which was used directly in the next step. H
HMR: δ 7.37-7.19 (m, 5H), 6.38 (d, J ) 15.4 Hz, 1H), 6.22
(dt, J ) 15.9, 6.6 Hz, 1H), 2.32 (t, J ) 7.1 Hz, 2H), 2.21 (q, J
) 6.8 Hz, 2H), 1.70-1.17 (m, 14H). 13C NMR: δ 137.9, 131.1,
129.7, 128.4, 126.6, 125.8, 119.7, 32.8, 29.1, 29.0, 28.9, 28.6,
28.5, 28.4, 25.1, 16.9. IR: 3025, 2926, 2854, 2245, 1945, 1875,
1802, 1650, 1598, 1494, 1465, 1351, 1086, 965, 744, 693. MS:
227 (M+ - HCN - H, 1.7), 212 (3.4), 164 (12.4), 151 (27.5),
145 (7.2), 131 (22.5), 117 (44.9), 104 (100.0), 97 (2.6).
A
solution of the olefinic nitrile (943 mg, 3.7 mmol) in CH2Cl2
(10 mL) was cooled to 0 °C and treated with MCPBA (1.05 g,
73%, 4.44 mmol). After warming to room temperature over 2
h, the mixture was worked up as described above, and the
product was purified by flash chromatography (Rf ) 0.29, 6:1
hexane-ethyl acetate), affording 520 mg (88%) of 11,12-epoxy-
12-phenyldodecanenitrile (20). 1H NMR: δ 7.38-7.25 (m, 5H),
3.61 (d, J ) 1.9 Hz, 1H), 2.94 (dt, J ) 2.2, 5.4 Hz, 1H), 2.33 (t,
J ) 6.8 Hz, 2H), 1.69-1.68 (m, 16H). 13C NMR: δ 137.9, 128.3,
127.8, 125.4, 119.7, 63.0, 62.9, 58.4, 32.1, 29.2, 28.9, 28.4, 25.7,
25.5, 25.1, 16.8. IR: 3029, 2930, 2855, 2245, 1954, 1890, 1811,
1719, 1604, 1497, 1462, 1426, 1370, 1309, 1201, 1072, 1027,
882, 752, 699. MS: 271 (M+, 4.1), 180 (100.0), 152 (39.2), 135
(7.4), 119 (14.1), 107 (38.8), 97 (13.6), 83 (5.1). Anal. Calcd
for C18H25NO: C, 79.66; H, 9.28. Found: C, 79.95; H, 8.81.
Eth yl 10,11-Ep oxy-11-p h en ylu n d eca n oa te (21). Using
the general procedure reported in the literature,55 a solution
of chromium trioxide (0.77 g, 7.7 mmol) in 1 M H2SO4 (20 mL)
was maintained between 5 and 10 °C while a solution of (E)-
11-phenyl-10-undecen-1-ol (0.5 g, 2.03 mmol) in acetone (20
mL) was slowly added. The reaction mixture was stirred at
rt for 4 h. Ether (50 mL) was added, and the mixture was
washed with brine (3 × 50 mL). The organic phase was
concentrated under reduced pressure and then taken up in
ether (50 mL), which was extracted with 1 M NaOH (2 × 30
mL). The combined basic extracts were acidified with 6 M
H2SO4 and back-extracted with ether (3 × 50 mL). The
combined ethereal extracts were washed with water and brine,
dried over MgSO4, and concentrated to give 362 mg (69%) of
crude (E)-11-phenyl-10-undecenoic acid. 1H NMR: δ 7.34-
7.13 (m, 5H), 6.36 (d, J ) 15.6 Hz, 1H), 6.20 (dt, J ) 15.9, 6.6
Hz, 1H), 4.04 (t, J ) 6.6 Hz, 1H), 2.28 (t, J ) 7.3 Hz, 2H), 2.18
(m, 2H), 1.69-1.17 (m, 12H). 13C NMR: δ 173.7, 137.8, 130.9,
129.7, 128.3, 126.6, 125.8, 64.3, 34.3, 32.9, 29.3, 29.1, 28.6, 25.9,
10,11-Ep oxy-11-p h en yl-1-u n d eca n ol (19): prepared from
(E)-11-phenyl-10-undecen-1-ol (197 mg, 0.801 mmol), MCPBA
(226 mg, 73.4%, 0.96 mmol), and CH2Cl2 (5 mL), using the
general procedure described above; yield ) 162 mg (77%); Rf
) 0.29 (1:1 hexane-diethyl ether), mp 50-53 °C. 1H NMR:
δ 7.28 (m, 5H), 3.63 (t, J ) 6.3 Hz, 2H), 3.61 (d, J ) 2.2 Hz,
1H), 2.95 (dt, J ) 2.2, 5.9 Hz, 1H), 1.69-1.17 (m, 16H). 13C
NMR: δ 137.8, 128.3, 127.8, 125.4, 63.1, 62.9, 58.6, 32.7, 32.3,
29.4, 29.3, 29.2, 29.1, 25.8, 25.7. IR: 3247, 3020, 2925, 2853,
1945-1811, 1599, 1466, 1377, 1073, 964, 898, 735, 691. MS:
(54) Kim, S.; Chung, K.; Yang, S. J . Org. Chem. 1987, 52, 3917-
3919.
(55) Loeschorn, C. A.; Nakajima, M.; McCloskey, P. J .; Anselme, J .-
P. J . Org. Chem. 1983, 48, 4407-4410.

Pd-Catalyzed Isomerization of Aryl-Substituted Epoxides
J . Org. Chem., Vol. 62, No. 19, 1997 6559
24.9. IR: 3500-2600 (broad), 3028, 2927, 2854, 1962-1885
(w), 1704, 1603, 1494, 1451, 1411, 1288, 1241, 1187, 1094,
1048, 964, 744, 693. MS: 242 (M+ - H2O, 5.0), 159 (2.5), 145
(6.8), 131 (20.3), 117 (25.0), 104 (100.0), 91 (7.3), 78 (3.7). A
solution of this carboxylic acid (1.97 g, 7.58 mmol) in anhy-
drous ethanol (0.79 g, 1.0 mL, 0.017 mol) was treated with
p-toluenesulfonic acid hydrate (0.29 g, 1.52 mmol) and refluxed
for 1 h. After cooling, the mixture was diluted with ether and
water (10 mL each) and washed with NaHCO3 (10 mL) and
brine (10 mL). After drying and evaporation, the crude
product was chromatographed (Rf ) 0.77, 6:1 hexane-ethyl
acetate) to give 1.13 g (52%) of ethyl (E)-11-phenyl-10-
undecenoate. 1H NMR: δ 7.35-7.26 (m, 5H), 6.37 (d, J ) 15.9
Hz, 1H), 6.22 (dt, J ) 15.9, 6.6 Hz, 1H), 4.12 (q, J ) 7.1 Hz,
2H), 2.29 (t, J ) 7.1 Hz, 2H), 2.19 (m, 2H), 1.31-1.22 (m, 12
H), 1.25 (t, J ) 7.1 Hz, 3H). IR: 3061, 3028, 2928, 2854, 1946,
1874, 1738, 1689, 1598, 1494, 1453, 1371, 1249, 1180, 1099.
1029, 964, 910, 735, 701. MS: 242 (M+ - C2H5OH, 58.9), 224
(6.6), 214 (3.3), 200 (3.9), 173 (2.4), 155 (11.4), 145 (9.8), 131
(21.5), 117 (41.0), 104 (100.0), 91 (6.3). The ester (1.13 g, 3.92
mmol) was epoxidized with MCPBA (1.11 g, 4.71 mmol, 73%
pure) in CH2Cl2 (10 mL) according to the above procedure; the
usual workup and chromatography gave 950 mg (80%) of ethyl
10,11-epoxy-11-phenylundecanoate (21); Rf ) 0.81 (6:1, hex-
ane-ethyl acetate). 1H NMR: δ 7.37-7.23 (m, 5H), 4.11 (q,
J ) 7.1 Hz, 2H), 3.59 (d, J ) 1.9 Hz, 1H), 2.94 (td, J ) 5.5, 2.2
Hz, 1H), 2.28 (t, J ) 7.3 Hz, 2H), 1.71-1.19 (m, 16H), 1.24 (t,
J ) 7.3 Hz, 3H). 13C NMR: δ 173.8, 137.9, 128.2, 127.8, 125.3,
63.0, 62.9, 59.9, 58.4, 34.1, 32.1, 29.1, 28.9, 25.7, 24.7, 23.6,
14.0. IR: 3062, 3029, 2931, 2855, 1950, 1881, 1730, 1689,
1604, 1497, 1452, 1371, 1303, 1246, 1180, 1099, 1029, 880, 752,
700. MS: 241 (M+ - C2H5O - H2O, 2.5), 213 (100.0), 199
(10.8), 183 (5.8), 167 (22.6), 155 (17.2), 134 (17.5), 121 (22.9),
108 (20.2), 91 (46.5).
11,12-Ep oxy-12-p h en yl-2-d od eca n on e (22). To a sus-
pension of pyridinium chlorochromate (3.13 g, 0.145 mol) and
Celite (6.3 g) in CH2Cl2 (20 mL) was added (E)-11-phenyl-10-
undecen-1-ol (2.38 g, 9.67 mmol); the oxidation was complete
after 2 h at rt, by TLC. The reaction mixture was diluted with
100 mL of pentane-ether (1:1) and filtered. After evaporation,
chromatography gave 1.86 g (79%) of (E)-11-phenyl-10-un-
decenal;56 Rf ) 0.58 (6:1 hexane-ethyl acetate), mp 48-49 °C.
1H NMR: δ 9.74 (t, J ) 1.9 Hz, 1H), 7.36-7.17 (m, 5H), 6.37
(d, J ) 15.9, 1H), 6.22 (dt, J ) 15.9, 6.6 Hz, 1H), 2.19 (m, 2H),
1.42-1.30 (m, 14H), 1.17 (d, J ) 6.1 Hz, 3H). To a cooled
solution of methylmagnesium iodide (10 mL, 1.9 M in ether,
0.019 mol) was slowly added a solution of the above aldehyde
(1.86 g, 7.59 mmol) in ether (5 mL). The reaction mixture was
stirred at rt for 30 min at which point TLC indicated only the
product alcohol (Rf ) 0.28, 6:1 hexane-ethyl acetate). The
reaction mixture was quenched with 15 mL of ice water,
washed with saturated aqueous NaHSO4 (3 × 15 mL), NaH-
CO3 (3 × 15 mL), and brine (15 mL), and dried (MgSO4).
Evaporation of solvent gave 1.42 g (72%) of crude (E)-12-
phenyl-11-dodecen-2-ol, which was sufficiently pure to continue
with the next step. 1H NMR: δ 7.35-7.15 (m, 5H), 6.37 (d, J
) 15.9 Hz, 1H), 6.22 (dt, J ) 15.9, 6.6 Hz, 1H), 2.19 (m, 2H),
1.42-1.30 (m, 14H), 1.17 (d, J ) 6.1 Hz, 3H). 13C NMR: δ
137.9, 131.1, 129.7, 128.4, 126.7, 125.9, 68.1, 68.0, 39.3, 33.0,
29.5, 29.4, 29.3, 29.2, 25.7, 23.4. IR: 3378, 3025, 2927, 2854,
1941-1798 (w), 1651, 1598, 1494, 1449, 1373, 1308, 1119,
1071, 963, 743, 692. MS: 243 (M+ - H2O, 18.2), 199 (3.1),
185 (8.4), 171 (9.1), 158 (8.1), 143 (15.6), 138 (86.1), 129 (69.1),
117 (23.5), 104 (67.9), 96 (44.2), 82 (26.7). The above alcohol
(1.42 g, 5.44 mmol) was added to a mixture of PCC (1.76 g,
8.16 mmol) and Celite (3.52 g) in CH2Cl2 (10 mL). After 20 h
at rt, the reaction mixture was worked up as described above;
chromatography gave 867 mg (62%) of (E)-12-phenyl-11-
dodecen-2-one; Rf ) 0.59 (6:1 hexane-ethyl acetate). 1H
NMR: δ 7.36-7.15 (m, 5H), 6.37 (d, J ) 15.9 Hz, 1H), 6.22
(dt, J ) 15.9, 6.6 Hz, 1H), 2.41 (t, J ) 7.3 Hz, 2H), 2.19 (m,
2H), 2.12 (s, 3H), 1.59-1.24 (m, 12H). 13C NMR: δ 209.1,
137.8, 131.0, 129.6, 128.3, 126.5, 125.7, 43.7, 32.9, 29.7, 29.3,
29.2, 29.1, 29.0, 23.8, 23.7. IR: 3034, 2927, 2850, 1954, 1885,
1715, 1598, 1494, 1461, 1375, 1161, 1082, 965, 742, 694. MS:
242 (M+ - OH, 100.0), 227 (4.6), 202 (4.0), 186 (8.9), 171 (7.8),
157 (9.4), 143 (20.2), 138 (31.4), 129 (68.6), 117 (37.3), 104
(86.8), 95 (36.3), 82 (60.3). The ketone (867 mg, 3.35 mmol)
was dissolved in CH2Cl2 (10 mL), cooled to 0 °C, and epoxidized
with MCPBA (950 mg, 73% pure, 4.02 mmol). After stirring
at rt for 3 h, the mixture was worked up as described above;
chromatography gave 718 mg (78%) of pure 11,12-epoxy-12-
phenyl-2-dodecanone (22); Rf ) 0.39 (6:1 hexane-ethyl ace-
tate). 1H NMR: δ 7.34-7.23 (m, 5H), 3.59 (d, J ) 1.9 Hz, 1H),
2.93 (td, J ) 5.5, 1.9 Hz, 1H), 2.41 (t, J ) 7.6 Hz, 2H), 2.12 (s,
3H), 1.71-1.29 (m, 14H). 13C NMR: δ 209.0, 137.8, 128.3,
127.8, 125.5, 63.1, 62.9, 58.5, 43.6, 32.2, 29.7, 29.2, 29.1, 29.0,
25.8, 23.7. IR: 2922, 2849, 1940-1790 (w), 1715, 1653, 1499,
1461, 1373, 1207, 1161, 1128, 870, 782, 757, 741, 700. MS:
241 (M+ - C2H4 - H2O, 1.7), 228 (19.7), 217 (6.5), 183 (100.0),
165 (6.4), 147 (12.8), 133 (3.3), 121 (6.0), 107 (10.1), 95 (6.2),
81 (5.4). Anal. Calcd for C18H26O2: C, 78.79; H, 9.55.
Found: C, 79.20; H, 9.58.
11,12-Ep oxy-12-p h en yl-1-d od ecyn e (23). The general
procedure is taken from the literature.57 To a clear solution
of carbon tetrabromide (985 mg, 2.97 mmol) in CH2Cl2 (7 mL)
in a Schlenk flask under a positive flow of N2 was added
triphenylphosphine (1.56 g, 5.94 mmol) to give an orangish
red mixture. (E)-11-Phenyl-10-undecenal (364 mg, 1.49 mmol;
see first step in the preparation of 22) dissolved in CH2Cl2 (1
mL) was added, causing the color to change from orange to
yellow. After stirring at rt for 30 min, TLC showed no starting
material. The reaction mixture was diluted with pentane (30
mL) followed by filtration to remove triphenylphosphine oxide
and evaporation of solvent. This step was repeated twice. The
crude product was purified by chromatography to give (E)-1,1-
dibromo-12-phenyl-1,11-dodecadiene (327 mg, 55%); Rf ) 0.66
(6:1 hexane-ethyl acetate). 1H NMR: δ 7.36-7.17 (m, 5H),
6.38 (t, J ) 16.6 Hz, 1H), 6.22 (dt, J ) 15.9, 6.6 Hz, 1H), 2.21
(m, 2H), 2.08 (m, 2H), 1.53-1.25 (m, 12H). 13C NMR: δ 180.0,
138.7, 137.9, 130.9, 129.7, 128.3, 126.6, 125.8, 32.9, 32.8, 29.3,
29.2, 29.1, 29.0, 28.9, 27.7. IR: 3025, 2925, 2854, 1941-1796
(w), 1728, 1598, 1494, 1454, 1071, 1028, 963, 799, 743, 692.
MS: 239 (M+ - Br2, 4.5), 185 (3.1), 171 (12.2), 157 (16.5), 143
(10.7), 131 (24.7), 117 (60.4), 104 (100.0), 91 (13.1). A solution
of the dibromoalkene (296 mg, 0.74 mmol) in THF (4 mL) at
-78 °C under nitrogen was treated with n-butyllithium (1.2
mL, 1.3 M in hexane, 1.6 mmol). After being stirred for 1 h
at -78 °C, the reaction mixture was warmed to rt and
maintained at rt for a further hour, at which point TLC showed
only the product; Rf ) 0.90 (6:1 hexane-ethyl acetate). The
reaction mixture was diluted with hexane and water (10 mL
each). The organic layer was separated, washed with brine
(10 mL), and dried (MgSO4). After evaporation of solvent, 177
mg (99%) of crude (E)-12-phenyl-11-dodecen-1-yne was ob-
tained. 1H NMR: δ 7.36-7.15 (m, 5H), 6.38 (d, J ) 15.9 Hz,
1H), 6.22 (dt, J ) 15.9, 6.6 Hz, 1H), 2.24-2.15 (m, 4H), 1.93
(t, J ) 2.7 Hz, 1H), 1.52-1.26 (m, 12H). 13C NMR: δ 137.9,
131.0, 129.7, 128.3, 126.6, 125.8, 97.4, 84.6, 67.9, 32.8, 29.2,
28.9, 28.6, 28.5, 28.4, 18.2. IR: 3312, 3095, 3061, 3028, 2932,
2855, 2118, 1944-1801 (w), 1649, 1598, 1494, 1449, 1071,
1029, 964, 743, 692, 631. MS: 240 (M+, 35.2), 225 (2.0), 197
(7.7), 183 (23.9), 169 (33.2), 155 (33.7), 149 (68.3), 130 (86.1),
117 (89.6), 104 (100.0), 94 (41.6), 81 (35.2). The above enyne
(149 mg, 0.62 mmol) was epoxidized with MCPBA (176 mg,
73% pure, 0.75 mmol) in CH2Cl2 (5 mL) according to the above
procedure; chromatography gave 107 mg (67%) of pure 11,12-
epoxy-12-phenyl-1-dodecyne (23); Rf ) 0.76 (6:1 hexane-ethyl
acetate). 1H NMR: δ 7.38-7.24 (m, 5H), 3.60 (d, J ) 1.9 Hz,
1H), 2.95 (td, J ) 5.5, 2.2 Hz, 1H), 2.19 (td, J ) 6.8, 2.9 Hz,
2H), 1.94 (t, J ) 2.9 Hz, 1H), 1.69-1.25 (m, 14H). 13C NMR:
δ 137.9, 128.3, 127.8, 125.4, 97.4, 84.5, 67.9, 62.9, 58.4, 32.1,
29.2, 28.8, 28.5, 28.3, 25.7, 18.2. IR: 3310, 2931, 2856, 2117,
1962-1729 (w), 1605, 1497, 1462, 1071, 1027, 880, 750, 698,
627. MS: 199 (M+ - CH2CCH - H2O, 1.7), 173 (9.9), 157
(57) (a) Corey, E. J .; Fuchs, P. L. Tetrahedron Lett. 1972, 36, 3769-
3772. (b) Ramirez, F.; Desai, N. B.; McKelvie, N. J . Am. Chem. Soc.
1962, 84, 1745-1747.
(56) Han, N.; Lei, X.; Turro, N. J . J . Org. Chem. 1991, 56, 2927-
2930.

6560 J . Org. Chem., Vol. 62, No. 19, 1997
Kulasegaram and Kulawiec
(21.1), 143 (16.4), 131 (26.8), 107 (100.0), 93 (47.5), 81 (81.9).
Anal. Calcd for C18H24O: C, 84.32; H, 9.43. Found: C, 84.11;
H, 9.12.
2-(2-Na p h th yl)p r op a n a l (27):61 prepared as in Table 1,
entry 10, from 2-methyl-2-(2-naphthyl)oxirane (2, 50 mg, 0.27
mmol), Pd(OAc)2 (3.1 mg, 13.6 µmol), PPh3 (10.7 mg, 40.8
µmol), and t-BuOH (0.5 mL); yield ) 46.3 mg (93%), Rf ) 0.54
(6:1 hexane-ethyl acetate). 1H NMR: δ 9.77 (d, J ) 1.5 Hz,
1H), 7.88-7.81 (m, 3H), 7.68 (m, 1H), 7.51-7.48 (m, 2H), 7.32
(dd, J ) 8.4, 1.9 Hz, 1H), 3.81 (dq, J ) 1.5, 7.8 Hz, 1H), 1.54
(d, J ) 7.1 Hz, 3H).
1-Br om o-10,11-epoxy-11-ph en ylu n decan e (24). The gen-
eral procedure is taken from the literature.58 N-Bromo-
succinimide (566 mg, 3.18 mmol) was slowly added to a
solution of (E)-11-phenyl-10-undecen-1-ol (391 mg, 1.59 mmol)
and triphenylphosphine (834 mg, 3.18 mmol) in DMF (3 mL).
After 5 min at rt, TLC showed completion of reaction (the new
product was observed at Rf ) 0.86 in 6:1 hexane-ethyl
acetate). Methanol (2 mL) was added to destroy the excess
reagent. After a further 5 min, ether was added and the
organic layer was washed with water, saturated NaHCO3 (10
mL), and brine (10 mL) and dried (MgSO4). After evaporation
of solvent, the product was extracted twice into hexane, leaving
a residue of triphenylphosphine oxide. After evaporation of
solvent, 383 mg (78%) of crude (E)-1-bromo-11-phenyl-10-
undecene was obtained, which was sufficiently pure for the
next step. 1H NMR: δ 7.36-7.15 (m, 5H), 6.38 (d, J ) 15.9,
1H), 6.22 (dt, J ) 15.9, 6.6 Hz, 1H), 3.41 (t, J ) 6.8 Hz, 2H),
2.21 (m, 2H), 1.85 (m, 2H), 1.31-1.28 (m, 12H). 13C NMR: δ
137.9, 131.1, 129.6, 128.3, 126.5, 125.8, 33.9, 32.8, 32.7, 29.3,
29.2, 29.0, 28.6, 28.0, 25.7. IR: 3070, 3025, 2927, 2854, 1948-
1811 (w), 1727, 1654, 1598, 1494, 1448, 1369, 1308, 1259, 1199,
1070, 1027, 964, 743, 694. MS: 173 (M+ - C4H9Br, 1.4), 159
(3.6), 145 (5.6), 131 (14.9), 117 (74.9), 104 (100.0), 91 (11.9),
81 (3.0). The above alkene (383 mg, 1.24 mmol) was epoxidized
with MCPBA (350 mg, 73% pure, 1.48 mmol) in CH2Cl2 (5 mL)
according to the general procedure described above; chroma-
tography gave 356 mg (88%) of pure 1-bromo-10,11-epoxy-11-
phenylundecane (24); Rf ) 0.75 (9:1 hexane-ethyl acetate).
1H NMR: δ 7.38-7.24 (m, 5H), 3.60 (d, J ) 2.2 Hz, 1H), 3.40
(t, J ) 6.8 Hz, 2H), 2.95 (td, J ) 5.4, 2.2 Hz, 1H), 1.85 (m,
2H), 1.67 (m, 2H), 1.51-1.31 (m, 12H). 13C NMR: δ 137.9,
128.3, 127.8, 125.4, 62.9, 58.5, 33.7, 32.8, 32.3, 29.3, 29.2, 29.1,
28.7, 28.1, 25.8. IR: 3031, 2929, 2855, 1962-1819 (w), 1728,
1617, 1497, 1461, 1378, 1307, 1260, 1175, 1072, 1027, 881, 751,
698. MS: 233 (M+ - CH3Br, 29.4), 217 (13.2), 175 (3.9), 161
(14.7), 133 (29.3), 107 (100.0), 91 (54.3), 83 (30.7). Anal. Calcd
for C17H25BrO: C, 62.77; H, 7.75. Found: C, 62.74; H, 7.74.
Isom er iza t ion of E p oxid es in Ta b les 1-3 Gen er a l
Meth od . To a small Schlenk flask was added Pd(OAc)2 (0.05
equiv per substrate) and distilled, deoxygenated solvent
(enough to make the final solution 0.1-0.3 M in substrate),
followed by tri-n-butylphosphine (3 equiv per Pd) via microliter
syringe. In the case of PPh3, solid ligand was added to the
flask prior to dissolution. The substrate was then added to
the solution of the Pd(0) catalyst, and the mixture was refluxed
under N2, until TLC or GC indicated complete consumption
of the substrate, or no further conversion. The product was
isolated and purified by flash chromatography on silica gel,
using the indicated solvent mixture. In some cases, mixtures
of unreacted starting material and product were isolated by
3-(2-Na p h th yl)-2-bu ta n on e (28):62 prepared as in Table
1, entry 15, from trans-2,3-dimethyl-2-(2-naphthyl)oxirane (14,
50 mg, 0.25 mmol), Pd(OAc)2 (2.9 mg, 12.7 µmol), PBu3 (9.5
µL, 38.1 µmol), and benzene (0.5 mL); yield ) 34.5 mg (69%),
Rf ) 0.46 (6:1 hexane-ethyl acetate). 1H NMR: δ 7.83-7.79
(m, 1H), 7.51-7.43 (m, 2H), 7.31 (dd, J ) 8.4, 1.9 Hz, 1H),
3.89 (q, J ) 6.8 Hz, 1H), 2.06 (s, 3H), 1.47 (d, J ) 6.8 Hz, 3H).
1,2-Dip h en yleth a n on e (31):9b prepared as in Table 2,
entry 7, from cis-stilbene oxide (29, 50 mg, 0.26 mmol),
Pd(OAc)2 (2.9 mg, 12.7 µmol), PBu3 (9.5 µL, 38.2 µmol), and
benzene (0.5 mL); yield ) 49.7 mg (99%), Rf ) 0.48 (6:1
hexane-ethyl acetate). 1H NMR: δ 8.03-8.00 (m, 5H), 7.59-
7.22 (m, 5H), 4.29 (s, 2H).
Dip h en yla ceta ld eh yd e (32):63 prepared as in Table 2,
entry 9, from 2,2-diphenyloxirane (3, 50 mg, 0.26 mmol),
Pd(OAc)2 (2.9 mg, 12.8 µmol), PPh3 (10.1 mg, 38.4 µmol), and
t-BuOH (0.5 mL); yield ) 1.3 mg (3%) of aldehyde (identified
1
and quantified by H NMR) and 41.8 mg (84%) of epoxide; Rf
) 0.65 (6:1 hexane-ethyl acetate). 1H NMR: δ 9.91 (d, J )
1.7 Hz, 1H), 4.89 (d, J ) 1.7 Hz, 1H), 7.50-7.15 (m, 10H).
1-P h en yl-10-u n d ecen -2-on e (33). Isomerization of 1,2-
epoxy-1-phenyl-10-undecene (18, 50 mg, 0.19 mmol) using
Pd(OAc)2 (2.1 mg, 9.5 mmol) and PBu3 (7.1 mL, 28.6 mmol) in
t-BuOH (0.5 mL) for 1 h gave the ketone (44 mg, 80%), Rf )
0.60 (6:1 hexane-ethyl acetate). 1H NMR: δ 7.36-7.19 (m,
5H), 5.81 (ddt, J ) 17.1, 6.6, 7.0 Hz, 1H), 4.98 (d of m, J )
17.1 Hz, 1H), 4.92 (d of m, J ) 12.3 Hz, 1H), 3.67 (s, 2H), 2.44
(t, J ) 7.1 Hz, 2H), 2.02 (m, 2H), 1.54 (m, 2H), 1.27-1.23 (m,
10H). 13C NMR: δ 208.3, 138.9, 134.3, 129.3, 128.6, 126.8,
114.0, 50.0, 49.9, 41.8, 33.6, 28.8, 28.7, 23.6, 23.4. IR: 3065,
3030, 2958, 2857, 1946 (w), 1878 (w), 1825 (w), 1714, 1640,
1603, 1496, 1454, 1412, 1359, 1187, 1087, 1031, 995, 909, 699.
MS: 244 (M+, 1.7), 153 (84.5), 135 (100), 107 (36.7), 91 (87.4),
83 (69.6), 69 (80.7), 55 (77.8). Anal. Calcd for C17H24O: C,
83.55; H, 9.90. Found: C, 83.48; H, 9.99.
11-Hyd r oxy-1-p h en yl-2-u n d eca n on e (34). Isomerization
of 10,11-epoxy-11-phenyl-1-undecanol (19, 30 mg, 0.114 mmol)
using Pd(OAc)2 (1.3 mg, 5.7 µmol) and PBu3 (4.3 µL, 17.2 µmol)
in t-BuOH (0.5 mL) for 1 h gave the ketone (29 mg, 97%), Rf
) 0.21 (1:1 hexane-diethyl ether). 1H NMR: δ 7.35-7.18 (m,
5H), 3.68 (s, 2H), 3.63 (t, J ) 6.4 Hz, 2H), 2.44 (t, J ) 7.3 Hz,
2H), 1.54-1.16 (m, 14H). 13C NMR: δ 208.4, 134.3, 129.3,
128.5, 126.8, 62.9, 60.1, 50.1, 41.9, 32.7, 29.2, 29.1, 28.9, 25.6,
23.7. IR: 3280, 2925, 2850, 1950, 1889, 1708, 1463, 1418,
1377, 1118, 1073, 1036, 1007, 952, 910, 750, 701. MS: 171
(M+ - C6H5CH2, 52.5), 153 (100.0), 135 (64.7), 111 (18.4), 97
(16.2), 83 (9.9).
11-Oxo-12-p h en yld od eca n en itr ile (35). Isomerization of
11,12-epoxy-12-phenyldodecanenitrile (20, 50 mg, 0.185 mmol)
using Pd(OAc)2 (2.1 mg, 9.2 µmol) and PBu3 (6.9 µL, 27.7 µmol)
in t-BuOH (0.5 mL) for 40 min gave the ketone (40 mg, 80%),
Rf ) 0.19 (6:1 hexane-ethyl acetate). 1H NMR: δ 7.36-7.19
(m, 5H), 3.68 (s, 2H), 2.44 (t, J ) 7.3 Hz, 2H), 2.32 (t, J ) 6.8
Hz, 2H), 1.71-1.24 (m, 14H). 13C NMR: δ 208.3, 134.3, 129.3,
128.6, 126.8, 119.7, 50.1, 50.0, 41.9, 29.1, 28.9, 28.6, 25.3, 25.2,
23.6, 17.1. IR: 3064, 3030, 2931, 2858, 2245, 1970-1829 (w),
1731, 1603, 1498, 1463, 1425, 1364, 1187, 1113, 1066, 1031,
916, 730, 700. MS: 181 (M+ - C6H5CH2 + H, 37.3), 152 (78.9),
135 (8.5), 110 (4.6), 96 (6.2), 82 (2.8).
1
chromatography and analyzed by GC or H NMR to determine
extent of conversion. Specific amounts of reagents used for a
representative synthesis of each carbonyl compound shown in
Tables 1-3 are given below; spectroscopic characterization
data follow.
2-Na p h th yla ceta ld eh yd e (25):59 prepared as in Table 1,
entry 4, from 2-(2-naphthyl)oxirane (1, 50 mg, 0.29 mmol),
Pd(OAc)2 (3.3 mg, 14.7 µmol), PBu3 (11.0 µL, 44.1 µmol), and
t-BuOH (0.5 mL); yield ) 49 mg (98%), Rf ) 0.36 (6:1 hexane-
ethyl acetate). 1H NMR: δ 9.82 (t, J ) 2.2 Hz, 1H), 7.86-
7.79 (m, 3H), 7.68 (m, 1H), 7.52-7.45 (m, 2H), 7.32 (dd, J )
8.4, 1.8 Hz, 1H), 3.84 (d, J ) 2.2 Hz, 2H).
1-(2-Na p h th yl)p r op a n on e (26):60 prepared as in Table 1,
entry 5, from trans-3-methyl-2-(2-naphthyl)oxirane (12, 50 mg,
0.27 mmol), Pd(OAc)2 (3.1 mg, 13.6 µmol), PPh3 (10.7 mg, 40.8
µmol), and benzene (0.5 mL); yield ) 46.0 mg (92%), Rf ) 0.34
(6:1 hexane-ethyl acetate). 1H NMR: δ 7.81-7.28 (m, 7H),
3.83 (s, 2H), 2.16 (s, 3H).
Eth yl 10-Oxo-11-p h en ylu n d eca n oa te (36). Isomeriza-
tion of ethyl 10,11-epoxy-11-phenylundecanoate (21, 47 mg,
0.155 mmol) using Pd(OAc)2 (1.7 mg, 7.8 µmol) and PBu3 (5.8
(58) Bates, H. A.; Farina, J .; Tong, M. J . Org. Chem. 1986, 51, 2637-
(61) Tinnemans, A. H. A.; Laarhoven, W. H. J . Chem. Soc., Perkins
Trans. 2 1976, 1104-1111.
(62) Tuinman, A. Helv. Chim. Acta 1968, 51, 1778-1781.
(63) Gensler, W. J .; Koehler, W. R. J . Org. Chem. 1962, 27, 2754-
2762.
2641.
(59) Kluge, A. F. Tetrahedron Lett. 1978, 3629-3632.
(60) Newman, M. S.; Mangham, J . R. J . Am. Chem. Soc. 1949, 71,
3342-3347.

Pd-Catalyzed Isomerization of Aryl-Substituted Epoxides
J . Org. Chem., Vol. 62, No. 19, 1997 6561
µL, 23.3 µmol) in t-BuOH (0.5 mL) for 45 min gave the ketone
(45 mg, 96%), Rf ) 0.80 (9:1 hexane-ethyl acetate). 1H
NMR: δ 7.36-7.19 (m, 5H), 4.12 (q, J ) 7.3 Hz, 2H), 4.08 (s,
2H), 2.43 (t, J ) 7.3 Hz, 2H), 2.27 (t, J ) 7.3 Hz, 2H), 1.69-
1.22 (m, 12H), 1.25 (t, J ) 7.1 Hz, 3H). 13C NMR: δ 208.3,
173.7, 134.4, 129.3, 128.6, 126.8, 59.9, 49.9, 41.7, 34.1, 29.1,
29.0, 28.8, 25.6, 24.7, 23.4, 13.9. IR: 2932, 2856, 1968-1890
(w), 1732, 1603, 1498, 1371, 1181, 1098, 1032, 916, 733, 700.
MS: 214 (M+ - C6H5CH2 + H, 12.4), 213 (100.0), 185 (3.1),
167 (6.3), 149 (7.5), 139 (16.3), 121 (8.0).
1-P h en yl-2,11-dodecan edion e (37). Isomerization of 11,12-
epoxy-12-phenyl-2-dodecanone (22, 50 mg, 0.182 mmol) using
Pd(OAc)2 (2.0 mg, 9.1 µmol) and PBu3 (6.8 µL, 27.3 µmol) in
t-BuOH (0.5 mL) for 25 min gave the ketone (49 mg, 98%), Rf
) 0.27 (6:1 hexane-ethyl acetate); mp 50-52 °C. 1H NMR: δ
7.36-7.18 (m, 5H), 3.67 (s, 2H), 2.43 (t, J ) 7.3 Hz, 2H), 2.39
(t, J ) 7.6 Hz, 2H), 2.13 (s, 3H), 1.53-1.24 (m, 12H). 13C
NMR: δ 209.1, 208.4, 134.3, 129.3, 128.5, 126.7, 50.1, 43.6,
41.8, 29.7, 29.2, 29.1, 29.0, 28.9, 23.7, 23.6. IR: 3031, 2930,
2856, 1956, 1895, 1713, 1603, 1481, 1454, 1409, 1365, 1259.
MS: 274 (M+, 3.6), 183 (100.0), 165 (3.9), 14.7 (15.1), 121 (4.1),
107 (10.2), 91 (64.9), 71 (19.1), 55 (48.0), 43 (81.4).
Kin etic Stu d ies of th e Isom er iza tion of 29 a n d 30 to
31. A mixture of trans-stilbene oxide (29, 25 mg, 0.13 mmol),
cis-stilbene oxide (30, 25 mg, 0.13 mmol), and hexadecane (3.7
µL) was isomerized as described above using the Pd(0) catalyst
formed from Pd(OAc)2 (2.9 mg, 12.7 µmol) and PBu3 (9.5 µL,
38.1 µmol) in benzene (0.5 mL). Aliquots were removed
periodically using a TLC pipet, filtered through silica gel, and
analyzed by capillary GC. Amounts of 29, 30, and 31 were
normalized by dividing the integrated area for each compound
by the area of the internal standard. The data were subjected
temperature (ambient or reflux) for the indicated time period.
The product and any unreacted starting material were isolated
by flash chromatography on silica gel, quantified, and identi-
fied by the 1H NMR data provided above.
Isom er iza tion of 12 w ith BF 3‚OEt2. trans-3-Methyl-2-
(2-naphthyl)oxirane (12, 50 mg, 0.27 mmol) was dissolved in
benzene (2 mL) and stirred at room temperature under a
positive flow of nitrogen. Freshly distilled boron trifluoride
etherate (50 µL, 0.41 mmol) was added to the flask, and the
reaction was left for 24 h. The reaction mixture was quenched
with 1 M NaOH and extracted with ether; the extracts were
dried (MgSO4) and evaporated and the product purified by
flash chromatography (6:1 hexane-ethyl acetate); yield ) 35
1
mg (70%) of ketone 26, identified by H NMR.
Isom er iza tion of 14 w ith BF 3‚OEt2. trans-2,3-Dimethyl-
2-(2-naphthyl)oxirane (14, 50 mg, 0.25 mmol) was dissolved
in benzene (2 mL) and treated with BF3‚OEt2 (50 µL, 0.41
mmol) under the same conditions as described above. Puri-
fication by flash chromatography (6:1 hexane-ethyl acetate)
gave 33.0 mg (66%) of a mixture of ketone 28 (Rf ) 0.46) and
aldehyde 38 (Rf ) 0.41). The product ratio was estimated as
74% ketone 28 (49% yield) and 26% aldehyde 38 (17% yield)
by capillary GC, and the products were identified by 1H NMR.
Characterization of 38. 1H NMR: δ 9.61 (s, 1H), 7.89-7.26
(m, 7H), 1.57 (s, 6H). MS: 198 (M+, 83.1), 169 (100), 155 (100),
141 (81.9), 128 (79.6), 115 (69), 101 (13.2), 89 (11.5), 77 (45.5),
63 (24.3), 51 (16.4), 43 (51.8).
2-P h en ylcycloh exa n on e (39).64 1-Phenyl-1,2-epoxycyclo-
hexane (16, 50 mg, 0.29 mmol) was isomerized as described
above, using Pd(OAc)2 (8.9 mg, 14.3 µmol) and PBu3 (10.7 µL,
42.9 µL) in refluxing t-BuOH (0.5 mL) for 3.5 h, giving 44.6
mg (89%) of 2-phenylcyclohexanone, Rf ) 0.41 (6:1 hexane-
ethyl acetate), as identified by 1H NMR: δ 7.42-7.11 (m, 5H),
3.61 (dd, J ) 5.1, 5.6 Hz, 1H), 2.51 (m, 2H), 2.35-1.81 (m,
6H).
to
a standard first-order kinetic treatment by plotting
ln([epoxide]0/[epoxide]t) vs time; using the plotting program
MacCurveFit (version 1.1), a slope was calculated, from which
the pseudo-first-order rate constants were determined. The
uncertainties on the rate constants were estimated by least-
squares curve fitting available on the same program.
Kin etic Stu d ies of th e Isom er iza tion of 12 to 26. Rate
constants for the isomerization of trans-3-methyl-2-(2-naph-
thyl)oxirane (12) to 1-(2-naphthyl)propanone (26) were ob-
tained as described above, in benzene and acetonitrile. In both
cases, 29.5 mg (0.16 mmol) of substrate, 1.8 mg (8.1 µmol) of
Pd(OAc)2, 6.1 µL (24.4 µmol) of PBu3, and 0.5 mL of solvent
were employed.
Ep oxid e Isom er iza tion Stu d ies in Ta bles 4-6. Gen -
er a l Meth od . For each entry in Tables 4-6, the appropriate
catalyst or catalyst precursors were placed in a Schlenk tube
and dissolved in the indicated solvent, the substrate was
added, and the mixture was allowed to react at the specified
Ack n ow led gm en t. The authors thank Georgetown
University for financial support of this research. RJ K
thanks the Camille and Henry Dreyfus Foundation for
a New Faculty Award.
Su p p or tin g In for m a tion Ava ila ble: Additional spectro-
scopic data for known compounds described in this work (2
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O970743B
(64) Sacks, C. E.; Fuchs, P. L. Synthesis 1976, 456-457.