Cationic rhodium(I)/bisphosphane complex-catalyzed isomerization of secondary propargylic alcohols to α,β-enones

Article abstract of DOI:10.1002/ejoc.200700071

We have determined that hydrogenated cationic Rh(I)/bisphosphane complexes are highly active catalysts for the isomerization of secondary propargylic alcohols to α,β-enones. A kinetic resolution of secondary propargylic alcohols proceeded with moderate selectivity with [Rh((R)-BINA-P)]OTf as a catalyst. Mechanistic studies revealed that the isomerization proceeds through intramolecular 1,3- and 1,2-hydrogen migration pathways. The isomerization of propargylic diol derivatives was also investigated, which revealed that 1,4-diketones, furans, and α,β-enones were obtained from 2-butyn-1,4-diol, 1-methoxy-2-butyn-4-ol, and 1-acetoxy-2-butyn-4-ol derivatives, respectively. Furthermore, chemoselectivity of the isomerization of an acetylenic diol was investigated, and preferential oxidation of a propargylic hydroxy group was observed. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200700071

FULL PAPER
DOI: 10.1002/ejoc.200700071
Cationic Rhodium(I)/Bisphosphane Complex-Catalyzed Isomerization of
Secondary Propargylic Alcohols to α,β-Enones
Ken Tanaka,*[a] Takeaki Shoji,[a] and Masao Hirano[a]
Keywords: Alcohols / Alkynes / Catalysis / Homogeneous / Isomerization / Rhodium
We have determined that hydrogenated cationic Rh(I)/
bisphosphane complexes are highly active catalysts for the
isomerization of secondary propargylic alcohols to α,β-en-
ones. A kinetic resolution of secondary propargylic alcohols
proceeded with moderate selectivity with [Rh((R)-BINA-
P)]OTf as a catalyst. Mechanistic studies revealed that the
isomerization proceeds through intramolecular 1,3- and 1,2-
hydrogen migration pathways. The isomerization of propar-
gylic diol derivatives was also investigated, which revealed
that 1,4-diketones, furans, and α,β-enones were obtained
from 2-butyn-1,4-diol, 1-methoxy-2-butyn-4-ol, and 1-ace-
toxy-2-butyn-4-ol derivatives, respectively. Furthermore,
chemoselectivity of the isomerization of an acetylenic diol
was investigated, and preferential oxidation of a propargylic
hydroxy group was observed.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
Transition-metal-catalyzed C–H bond cleavage and for-
mation through isomerization is a valuable transformation
in organic synthesis.[1] Notably, a number of efficient isom-
erizations of allylic alcohols to aldehydes or ketones, which
have significant synthetic utility, have been developed.[2] On
the other hand, a similar isomerization of propargylic
alcohols to α,β-enones and α,β-enals,[1d] which are typically
prepared from propargylic alcohols by sequential oxidation
and reduction (Scheme 1), has not been extensively studied
despite its high atom economy (Scheme 2).[3]
Scheme 2. Transition-metal-catalyzed isomerization of propargylic
alcohols.
RuCl2(PPh3)3/iPr3P as the catalyst at 110 °C for 30–48 h.[5]
A ruthenium(II)-indenyl complex, which is an efficient cata-
lyst for the isomerization of allylic alcohols, is also effective
for the rapid isomerization of primary propargylic alcohols
to α,β-enals in the presence of 20–40 mol-% InCl3 at 65 °C,
requiring only 1.5 h.[6] Although the isomerization of sec-
ondary propargylic alcohols also proceeds in high yield, a
prolonged reaction time (24 h) is required. Pd2(dba)3-
CHCl3/nBu3P catalyzes the isomerization of secondary pro-
pargylic diols to 1,4-diketones in high yield at 110 °C after
15–70 h.[7] In the presence of a catalytic amount of ethylene
glycol, Pd2(dba)3-CHCl3/iPr3P was able to isomerize sec-
ondary propargylic mono-ols to α,β-enones in high yield at
80 °C after 40–65 h, and active palladium hydride species
were supposed to be generated in situ.[8] An iridium com-
plex [IrH5(iPr3P)2] is also an effective catalyst for the isom-
erization of secondary propargylic mono-ols and diols to
the corresponding α,β-enones and 1,4-diketones at 110 °C
after 24–40 h.[9]
Scheme 1. Transformation of propargylic alcohols into α,β-enones
and α,β-enals by sequential oxidation and reduction.
In 1982, a catalytic isomerization of 2-butyne-1,4-diol to
butyrolactone was developed with RuH2(PPh3)4 as the cata-
lyst at 145 °C for 12 h, and this reaction was proposed to
proceed through an α,β-unsaturated aldehyde intermedi-
ate.[4] The first isolation of α,β-enals from the isomerization
of primary propargylic alcohols was realized with
[a] Department of Applied Chemistry, Graduate School of Engi-
neering, Tokyo University of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
Although there are many examples of cationic Rh(I)/
bisphosphane complex-catalyzed isomerizations of allylic
alcohols[10]
including
some
asymmetric
variants
Fax: +81-42-388-7037
E-mail: tanaka-k@cc.tuat.ac.jp
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
(Scheme 3),[11] the application of these complexes to the
isomerization of propargylic alcohols into α,β-enones and
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α,β-enals has not been reported. The only example of a Rh- tate phosphane ligands (dppe, dcpe, dppf, and rac-BINAP)
catalyzed isomerization of this kind was that of propargylic were highly effective catalysts at 80 °C (Table 1, Entries 5,
alcohols bearing an ethoxycarbonyl group at an alkyne ter- 7, 9, and 11), and the isomerization can proceed even at
minus, which isomerized in the presence of 3 mol-% ambient temperature (25 °C) with dcpe or rac-BINAP as
RhCl(PPh3)3 and 5 mol-% nBu3P at 110 °C after 12 h a ligand (Table 1, Entries 6 and 10). Among the ligands
(Scheme 4).[12]
examined, rac-BINAP was the most effective ligand
(Table 1, Entries 10 and 11), and the desired α,β-enone 2a
was obtained in Ͼ95% yield with complete E selectivity at
80 °C after only 1 h (Table 1, Entry 11). Importantly, pre-
treatment of the [Rh(cod)(rac-BINAP)]BF4 catalyst, pre-
pared in situ by mixing [Rh(cod)2]BF4 and rac-BINAP, with
hydrogen was essential for this isomerization (Table 1, En-
try 12).
Table 1. Screening of catalysts for Rh-catalyzed isomerization of
propargylic alcohol 1a.
Scheme 3. Cationic Rh(I)/bisphosphane complex-catalyzed asym-
metric isomerization of allylic alcohols.
Scheme 4. RhCl(PPh3)3/nBu3P-catalyzed isomerization of propar-
gylic alcohols.
[a] dppe: bis(diphenylphosphanyl)ethane, dcpe: bis(dicyclohexyl-
phosphanyl)ethane, dppf: 1,1Ј-bis(diphenylphosphanyl)ferrocene.
1
[b] Determined by H NMR spectroscopy.
In general, the existing methods for the isomerization of
secondary propargylic alcohols require long reaction times
and/or high reaction temperatures, so the development of
more active catalyst is highly desired. Herein, we describe a
cationic Rh(I)/bisphosphane complex-catalyzed isomeriza-
tion of secondary propargylic alcohols to α,β-enones.[13] We
also provide a mechanistic insight into the reaction path-
way, a kinetic resolution of secondary propargylic alcohols,
and isomerizations of various acetylenic alcohols (propar-
gylic diol derivatives and homopropargylic alcohols).
A series of secondary and primary propargylic alcohols
1a–t (R1 = aryl, heteroaryl, or alkenyl) were subjected to
the optimal reaction conditions described above (Table 2).
Primary (1a–d, Table 2, Entries 1–4), secondary (1e, Table 2,
Entry 5), and tertiary (1f, Table 2, Entry 6) alkyl-substituted
(R2) secondary propargylic alcohols cleanly afforded the
corresponding α,β-enones 2a–f in almost quantitative yield.
Unfortunately, the reaction of phenyl-substituted (R2) pro-
pargylic alcohol 1g afforded a complex mixture of products
(Table 2, Entry 7).[14] For the reaction of primary propar-
gylic alcohol 1h, [Rh(cod)(rac-BINAP)]BF4 was employed
to suppress the rapid Rh-catalyzed decarbonylation of alde-
hyde 2h, but 2h was obtained in low yield (Table 2, Entry 8).
The reaction of secondary propargylic alcohols 1i,j, bearing
Results and Discussion
Rh-Catalyzed Isomerization of Propargylic Alcohols
We first examined various Rh(I) catalysts (5 mol-% based coordinating substituents (R2), were sluggish, and the cor-
on the alcohol) for their ability to isomerize secondary pro- responding α,β-enones 2i,j were obtained in moderate yields
pargylic alcohol 1a (Table 1). The catalytic activities of (Table 2, Entries 9 and 10). The electronic and steric nature
RhCl(PPh3)3 and cationic Rh(I) complexes with mono- of substituents on the benzene ring did not affect the yields
dentate phosphane ligands (PPh3 and nBu3P) were very low of α,β-enones 2k–p (Table 2, Entries 11–16). The reactions
even at an elevated temperature (80 °C, Table 1, Entries 1– of heteroaryl-substituted (R1) secondary propargylic
3). On the other hand, cationic Rh(I) complexes with biden- alcohols were also investigated. The reaction of 2-furyl-sub-
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Isomerization of Propargylic Alcohols to α,β-Enones
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stituted secondary propargylic alcohol 1q proceeded to give
α,β-enone 2q in moderate yield (Table 2, Entry 17), but the
reaction of highly coordinating 2-pyridyl-substituted
alcohol 1r did not proceed, and 1r was recovered (Table 2,
Entry 18). In general, the [Rh(rac-BINAP)]BF4-catalyzed
isomerization of secondary propargylic alcohols 1 furnished
α,β-enones 2 with complete E selectivity, although a steri-
cally demanding substituent on the benzene ring sometimes
decreased the E/Z ratio of the α,β-enones 2 (Table 2, Entries
13 and 14). Alkenyl-substituted (R1) alcohols 1s,t cleanly
afforded the corresponding dienones 2s,t in high yield with
dppe as a ligand (Table 2, Entries 19 and 20).
Scheme 5. Cationic Rh(I)/dcpe complex-catalyzed isomerization of
propargylic alcohol 1u.
Table 2. Cationic Rh(I)/rac-BINAP complex-catalyzed isomeriza-
tion of propargylic alcohols.
Thus, the isomerizations of secondary propargylic
alcohols 1v,w were also conducted in the presence of 5 mol-
% of [Rh(dcpe)]BF4 at 25 °C. The reaction of 1-phenyl-sub-
stituted propargylic alcohol 1v furnished α,β-enone 2v in
good yield with complete E selectivity, and the reaction of
a sterically demanding propargylic alcohol 1w, bearing a
cyclohexyl group at the alkyne terminus, furnished α,β-en-
one 2w in good yield but with a decreased E/Z ratio
(Scheme 6). α,β-Enones 2u, 2v, and 2w could be separated
from enones 3u, 3v, and 3w, respectively, by silica gel
chromatography.
[a] Isolated yield. [b] Complex mixture of products. [c] Catalyst:
[Rh(rac-BINAP)(cod)]BF4. [d] Solvent: toluene, temperature:
110 °C. [e] Catalyst: [Rh(dppe)]BF4. [f] Catalyst: 10 mol-%.
Scheme 6. Cationic Rh(I)/dcpe complex-catalyzed isomerization of
propargylic alcohols 1v,w.
Unfortunately, the reaction of propargylic alcohol 1u
bearing a primary alkyl group at an alkyne terminus in the
presence of [Rh(rac-BINAP)]BF4 at 80 °C led to a complex
mixture of products including the corresponding α,β-enone
2u and the double-bond migration products 3u. To suppress
Rh-Catalyzed Kinetic Resolution of Secondary Propargylic
Alcohols
Next, a kinetic resolution of secondary propargylic
the formation of 3u, the isomerization of 1u was conducted alcohol 1a was investigated with chiral Rh(I) or iridium(I)
at 25 °C. Although no reaction was observed with [Rh(rac- complexes with various BINAP-type ligands (Table 3, Fig-
BINAP)]BF4 as the catalyst, the use of [Rh(dcpe)]BF4 sup- ure 1).[15–18] Among the ligands examined (Table 3, Entries
pressed the formation of 3u, and the desired α,β-enone 2u 1–4), BINAP was the most selective (Table 3, Entry 1). The
was obtained in 56% yield with complete E selectivity use of a neutral Rh(I) complex or a cationic iridium(I) com-
(Scheme 5).
plex led to a rather complex reaction mixture, the selectivity
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factors were very low (Table 3, Entries 5 and 6). The effect 7–9), and we found that the highest selectivity factor was
of counterions was also investigated (Table 3, Entries 1 and obtained with the OTf counterion (Table 3, Entry 9). A sim-
ilar counterion effect was observed in the enantioselective
isomerization of geraniol with RhI+/BINAP.[15c]
Table 3. Screening of catalysts for the Rh-catalyzed kinetic resolu-
A series of secondary propargylic alcohols 1 can be re-
solved with 5 mol-% [Rh{(R)-BINAP}]OTf as a catalyst
(Table 4). The length and steric demand of the alkyl groups
affected the enantioselectivity of the isomerization (Table 4,
Entries 1–6). Good selectivity factors were observed in Et-,
nBu-, and iPr-substituted (R) propargylic alcohols (Table 4,
Entries 2, 4, and 5). In general, both electronic and steric
nature of the substituents on the benzene ring appeared to
have a modest impact on the selectivity factor (Table 4, En-
tries 7–12), although the 2-methyl substituent on the ben-
zene ring significantly improved the selectivity factor
(Table 4, Entry 9).
tion of secondary propargylic alcohol 1a.
Mechanistic Consideration Regarding the Rh-Catalyzed
Isomerization of Propargylic Alcohols
[a] Determined by 1H NMR spectroscopy. [b] Solvent: (CH2Cl)2,
temperature: 80 °C.
The reaction of a deuterated propargylic alcohol in the
presence of a cationic Rh(I) complex with rac-BINAP or
dcpe was investigated to gain mechanistic insight into this
reaction (Scheme 7). The deuterium from propargylic
alcohol [D]-1b was incorporated into both the α-position
(25% D) and the β-position (75% D) of α,β-enone [D]-2b
with the electron-deficient phosphane ligand rac-BINAP.
On the contrary, exclusive deuterium incorporation into the
β-position of α,β-enone [D]-2b occurred with the electron-
rich phosphane ligand dcpe. Although the reaction of the
deuterated propargylic alcohol in the presence of 5 mol-%
[Rh(rac-BINAP)]BF4 proceeded smoothly, the reaction in
Figure 1. Structures of chiral BINAP-type ligands.
Table 4. Cationic Rh(I)/(R)-BINAP complex-catalyzed kinetic reso- the presence of 5 mol-% [Rh(dcpe)]BF4 was sluggish.
lution of secondary propargylic alcohols.
Scheme 7. Deuterium-labeling studies of propargylic alcohol [D]-
1b.
Furthermore, we have established that the isomerization
is an intramolecular process. Treatment of a 1:1 mixture
of deuterated propargylic alcohol [D]-1b and nondeuterated
propargylic alcohol 1d with [Rh(rac-BINAP)]BF4 or
[a] Determined by 1H NMR spectroscopy. [b] Calculated at the
[Rh(dcpe)]BF4 furnished deuterated [D]-2b and nondeuter-
observed conversion. [c] Catalyst: [Rh{(R)-BINAP}]BF4. [d] Sol-
ated 2d, and thus, no deuterium crossover was observed
vent: (CH2Cl)2, temperature: 40 °C. [e] Solvent: (CH2Cl)2, tempera-
ture: 50 °C.
(Scheme 8).[19]
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Isomerization of Propargylic Alcohols to α,β-Enones
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Scheme 10. Deuterium-labeling study of propargylic alcohol [D]-
1u.
enyl Rh intermediate C, which is protonated to give an α,β-
enone and regenerates the Rh(I) catalyst. In the case of a
cationic Rh(I)/dcpe complex, π-oxallyl Rh intermediate B
is generated exclusively, presumably due to the high nucleo-
philicity of an electron-rich Rh hydride. The isomerization
to the thermodynamically favored (E)-α,β-enone 2 may be
catalyzed by the cationic Rh(I) complex. α,β-Enone 2u may
be isomerized to 3u reversibly by the Rh catalyst.
Scheme 8. Crossover experiments.
Next, a mechanism for the isomerization of a propargylic
alcohol bearing an alkyl group at the alkyne terminus was
investigated. The time-course of the cationic Rh(I)/dcpe
complex-catalyzed isomerization of propargylic alcohol 1u
indicated that α,β-enone 2u and a mixture of enones 3u
formed initially, and that 2u may be generated through an
isomerization of 3u (Scheme 9).
Scheme 9. Time-course of cationic Rh(I)/dcpe complex-catalyzed
isomerization of propargylic alcohol 1u.
The reaction of deuterated propargylic alcohol [D]-1u in
the presence of the cationic Rh(I)/dcpe complex was investi-
gated to gain mechanistic insight into this reaction
(Scheme 10).[20] Deuterium from the propargylic alcohol
[D]-1u was incorporated into the β-position and the alkyl
chain of α,β-enone [D]-2u. Although the mechanism for
formation of 3u is not clear,[21] the isomerization of [D]-
Scheme 11. Plausible mechanism for the cationic Rh(I)/bisphos-
phane complex-catalyzed isomerization of propargylic alcohols.
Consistent with this proposed mechanism, an attempted
1u to [D]-2u catalyzed by the cationic Rh(I)/dcpe complex isomerization of propargylic ether 4 in the presence of
obviously proceeds through a 1,3-hydrogen migration and [Rh(rac-BINAP)]BF4 led to an unidentified complex mix-
not a 1,2-hydrogen migration.
ture of products (Scheme 12).
Scheme 11 depicts a plausible mechanism for the cationic
To determine if the unbound propargylic ketone is an
Rh(I)/bisphosphane complex-catalyzed isomerization of intermediate on the route to the desired α,β-enone, we
secondary propargylic alcohols to α,β-enones. The reaction carried out the isomerization of 1d in the presence of pro-
of a Rh(I) catalyst with a propargylic alcohol 1 furnishes pargylic ketone 5 (Scheme 13). If a portion of the desired
the Rh hydride complex A. The addition of Rh hydride to product is formed through dissociation/reassociation of the
the alkyne furnishes the π-oxallyl Rh intermediate B or alk- propargylic ketone, a fraction of 5 should be converted to
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Scheme 12. Reaction of propargylic ether 4 with the cationic Rh(I)/
rac-BINAP complex.
2b. However, no α,β-enone 2b was formed, which indicates
that the free propargylic ketone is not an intermediate in
the present isomerization reaction.
Figure 2. Electronic effect of substituents R1 on the E/Z values of
α,β-enones.
In the ruthenium(II)-catalyzed isomerization of allylic
alcohols, it was reported that β-hydride elimination from
the allylic alcohol and 1,2-addition of ruthenium hydride to
the carbonyl group is a reversible process.[23] To examine
the reversibility of the β-hydride elimination and the 1,2-
addition, we studied the time-course of a Rh-catalyzed ki-
netic resolution of secondary propargylic alcohol 1d
(Table 5). If part of the β-hydride elimination and the 1,2-
addition is reversible, calculated selectivity factors should
decrease with the progress of the reaction. The study re-
vealed that the calculated selectivity factor gradually de-
creased as the reaction proceeded, which indicates that race-
Scheme 13. Isomerization of propargylic alcohol 1d in the presence
of propargylic ketone 5.
To confirm the mechanism for the isomerization of (Z)-
α,β-enones to (E)-α,β-enones, an (E/Z) mixture of α,β-en-
one 2a was heated in the absence or presence of [Rh(rac-
BINAP)]BF4 (Scheme 14). No significant isomerization
proceeded in the absence of catalyst, but complete isomer-
ization to the E isomer proceeded in the presence of cata-
lyst. Therefore, we can conclude that the isomerization of
(Z)-α,β-enones to (E)-α,β-enones proceeds through coordi-
nation of the cationic Rh to the double bond, which is a
similar mechanism to that proposed in the palladium(II)-
catalyzed rapid isomerization of (Z)-α,β-enones to (E)-α,β-
enones.[22]
Table 5. Time-course of the Rh-catalyzed kinetic resolution of sec-
ondary propargylic alcohol 1d.
Scheme 14. Isomerization of α,β-enone 2a in the absence and pres-
ence of the cationic Rh(I)/rac-BINAP complex.
Consistent with this proposed mechanism, significant
electronic effects were observed in the E/Z values of α,β-
enones 2 obtained through the Rh-catalyzed isomerization
of propargylic alcohols 1 (Figure 2). The introduction of an
electron-deficient trifluoromethyl group (2n) onto the aro-
matic ring resulted in a decreased E/Z ratio. In contrast,
the incorporation of an electron-donating methyl (2m) or
methoxy (2o) group in the aromatic ring resulted in im-
proved E/Z values. These observations can be explained by
the electron deficiency of the benzylic carbon in the transi-
tion state of the Rh-catalyzed E/Z isomerization, which fa-
cilitates the isomerization.
[a] Determined by 1H NMR spectroscopy. [b] Calculated at the
observed conversion.
Scheme 15. β-Hydride elimination from propargylic alcohol and
1,2-addition of Rh hydride to the carbonyl group.
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Isomerization of Propargylic Alcohols to α,β-Enones
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mization through the reversible 1,2-addition proceeds be- phenyl group α to the acetoxy group, furnished α,β-enones
fore the irreversible hydride addition to the triple bond 13 with a skeletal rearrangement (Table 6, Entries 10 and
(Scheme 15).
11).
A time-course of the cationic Rh(I)/BINAP complex-cat-
alyzed isomerization of 8a was investigated at low tempera-
ture to gain mechanistic insight into this reaction
(Scheme 16). The study revealed that (Z)-α,β-enone (Z)-14a
was preferentially formed and might cyclize to give furan
9a. On the other hand, the yield of 1,4-diketone 7a, which
can be generated through the isomerization of α,β-enone
14a followed by hydrolysis, increased as the reaction pro-
gressed, so that 7a (or the corresponding enol ether 15a)
may not be the major intermediate in the formation of fu-
ran 9a.[24]
Rh-Catalyzed Isomerization of Propargylic Diol Derivatives
and Homopropargylic Alcohol
The procedure was applied to the isomerization of pro-
pargylic diol derivatives as shown in Table 6. 2-Butyne-1,4-
diol derivatives 6a–c were cleanly isomerized to the corre-
sponding diones 7a–c in high yield at 80 °C after a short
reaction time (1 h, Table 6, Entries 1–3) compared with
those previously reported for the Pd-catalyzed isomeriza-
tion (110 °C, 15–70 h).[7] The isomerization of protected 2-
butyne-1,4-diol derivatives 8, 10, and 11 was also investi-
gated. 4-Methoxy-2-butyn-1-ol derivatives 8a–d were iso-
merized to the corresponding furans 9a–d in moderate
yields (Table 6, Entries 4–7). On the other hand, 4-hy-
droxybut-2-ynyl acetate derivatives 10 and 11 were iso-
merized to two different α,β-enones 12 and 13 in moderate
yields (Table 6, Entries 8–11). Although alcohols 10, bear-
ing an alkyl group α to the acetoxy group, furnished α,β-
enones 12 (Table 6, Entries 8 and 9), alcohols 11, bearing a
Table 6. Cationic Rh(I)/BINAP complex-catalyzed isomerization of
2-butyn-1,4-diol derivatives [5 mol-% [Rh(rac-BINAP)]BF4 in
(CH2Cl)2 at 80 °C].
Scheme 16. Time-course of the cationic Rh(I)/BINAP complex-cat-
alyzed isomerization of 8a (yields were determined by 1H NMR
with 1,4-dimethoxybenzene as an internal standard).
A time-course of the cationic Rh(I)/BINAP complex-cat-
alyzed isomerization of 11a was also investigated
(Scheme 17). In this case, no α,β-enone 16a was detected in
the reaction mixture. Like the isomerization of propargylic
alcohols, an E/Z mixture of α,β-enone 13a was formed ini-
tially, and the E isomer was isolated after a prolonged reac-
tion.
Scheme 17. Time-course of the cationic Rh(I)/BINAP complex-cat-
1
alyzed isomerization of 11a (yields were determined by H NMR
with 1,4-dimethoxybenzene as an internal standard).
[a] Isolated yield. [b] Catalyst: 10 mol-%. [c] Ligand: dppf.
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Plausible mechanisms for the formation of furan 9 and
α,β-enone 13 are shown in Scheme 18. Furan 9 is generated
through the initial isomerization of alcohol 8 to (Z)-α,β-
enone (Z)-14, which cyclizes and aromatizes via cation in-
termediate F.[25] α,β-Enone 13 is generated through the ini-
tial isomerization of alcohol 11 to (Z)-α,β-enone (Z)-16,
which undergoes acetoxy-group migration and rearrange-
ment via epoxide G. The phenyl group α to the acetoxy
group in 11 may facilitate the acetoxy group migration be-
cause of the high stability of the conjugated product 13.
Scheme 20. Chemoselective isomerization of acetylenic diol 19 cat-
alyzed by the cationic Rh(I)/rac-BINAP complex.
Conclusions
In conclusion, we have determined that the isomerization
of secondary propargylic alcohols to α,β-enones proceeded
in the presence of hydrogenated, cationic, Rh(I) complexes
with the appropriate choice of bidentate phosphane ligands
(rac-BINAP, dppe, or dcpe). The asymmetric variant of this
reaction, a kinetic resolution of secondary propargylic
alcohols, was developed with moderate selectivity with
[Rh{(R)-BINAP}]OTf as a catalyst. Deuterium-labeling
studies revealed that the isomerization proceeds through in-
tramolecular 1,3- and 1,2-hydrogen migration pathways.
The isomerization of propargylic diol derivatives was also
investigated, which revealed that 1,4-diketones, furans, and
α,β-enones were obtained from 2-butyn-1,4-diol, 1-meth-
oxy-2-butyn-4-ol, and 1-acetoxy-2-butyn-4-ol derivatives,
respectively. Furthermore, the chemoselectivity of the isom-
erization of an acetylenic diol was investigated, and the
preferential oxidation of the propargylic hydroxy group was
observed.
Experimental Section
General Methods: 1H NMR spectra were recorded at 300 MHz
(JEOL AL 300 spectrometer). 13C NMR spectra were obtained
with complete proton decoupling at 75 MHz (JEOL AL 300 spec-
trometer). HRMS data were obtained with a JEOL JMS-700 spec-
trometer. Infrared spectra were obtained with a JASCO A-302
spectrometer. Anhydrous CH2Cl2 (No. 27,099-7) and anhydrous
(CH2Cl)2 (No. 28,450-5) were obtained from Aldrich and used as
received. H8-BINAP, tol-BINAP, and Segphos were obtained from
Takasago International Corporation. Solvents for the synthesis of
substrates were dried with molecular sieves (4 Å) prior to use. All
other reagents were obtained from commercial sources and used as
received. All reactions were carried out under an atmosphere of
argon in oven-dried glassware with magnetic stirring, unless other-
wise indicated.
Scheme 18. Plausible mechanism for the formation of 9 and 13.
The procedure was ultimately applied to the isomeriza-
tion of a homopropargylic alcohol. However, the reaction
of homopropargylic alcohol 18 in the presence of 5 mol-%
[Rh(rac-BINAP)]BF4 at 80 °C for 1 h did not furnish the
corresponding β,γ-enone product (Scheme 19).
Starting Materials: Propargylic alcohols 1a,[27] 1b,[28] 1c,[29] 1d,[27]
1f,[30] 1g,[31] 1k,[32] 1l, 1m, 1n, 1o,[33] 1p, 1q, 1r, 1s,[34] 1t, 1u,[35] 1v,[36]
and 1w[37] were synthesized through the reaction of the correspond-
ing lithium acetylides and aldehydes. Propargylic alcohols 1e, 1h,
and 6a were commercially available. Propargylic ether 4[38] was pre-
pared according to the literature. Deuterated propargylic alcohols
[D]-1b and [D]-1u were synthesized through a Jones oxidation of
1b and 1u followed by a reduction with LiAlD4.
Scheme 19. Reaction of homopropargylic alcohol 18 with the cat-
ionic Rh(I)/rac-BINAP complex.
This failure of isomerization of homopropargylic alcohol
18 prompted us to investigate the chemoselective isomeriza-
tion of an acetylenic alcohol. The isomerization of acetyle-
nic diol 19 bearing both propargylic and homopropargylic
hydroxy groups selectively furnished α,β-enone 20 in 55%
yield, but the homopropargylic hydroxy group remained
unchanged (Scheme 20).[26]
Alcohol 1j: nBuLi (1.56  in hexane, 6.4 mL, 10.0 mmol) was added
to a stirred solution of phenylacetylene (1.0 g, 10.0 mmol) in THF
(30 mL) at –78 °C, and the mixture was stirred at –78 °C for
30 min. Methoxyacetyl chloride (1.9 mL, 20 mmol) was added to
the resulting solution at 0 °C, and the mixture was gradually
warmed to room temp. The reaction was quenched with water and
extracted with Et2O. The organic layer was washed with brine,
2694
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2687–2699

Isomerization of Propargylic Alcohols to α,β-Enones
FULL PAPER
dried with Na2SO4, and concentrated. The residue was purified by
silica gel column chromatography (hexane/EtOAc, 9:1), which fur-
nished 1-methoxy-4-phenylbut-3-yn-2-one (1.1 g, 6.60 mmol, 66%
yield) as a pale yellow oil. A mixture of 1-methoxy-4-phenylbut-
3-yn-2-one (0.50 g, 2.87 mmol), NaBH4 (81 mg, 2.15 mmol), and
CeCl3·7H2O (1.0 g, 2.68 mmol) in MeOH (7 mL) was stirred at
room temp. for 10 min. The reaction was hydrolyzed with dilute
HCl, brine was added, and the mixture was extracted with CH2Cl2.
The organic layer was concentrated, and the residue was purified
by silica gel column chromatography (hexane/EtOAc, 7:1), which
furnished alcohol 1j (0.50 g, 2.61 mmol, 91% yield) as a pale yellow
oil. 1H NMR (CDCl3, 300 MHz): δ = 7.50–7.38 (m, 2 H), 7.36–
7.27 (m, 3 H), 4.82–4.70 (m, 1 H), 3.67 (dd, J = 9.9, 3.9 Hz, 1 H),
3.60 (dd, J = 9.9, 7.5 Hz, 1 H), 3.47 (s, 3 H), 2.53 (d, J = 4.8 Hz,
1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 131.7, 128.4, 128.1,
cm–1. HRMS (EI): calcd. for C10H11NO [M – OH] 144.0814; found
144.0773.
Alcohol 1t: Pale yellow oil. 1H NMR (CDCl3, 300 MHz): δ = 6.12–
6.00 (m, 1 H), 4.48 (t, J = 6.6 Hz, 1 H), 2.38–2.00 (m, 5 H), 1.85–
1.42 (m, 8 H), 0.95 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 134.9, 120.1, 87.5, 86.5, 62.6, 40.0, 29.1, 25.5, 22.2,
21.4, 18.4, 13.7 ppm. IR (neat): ν = 3300, 2900, 1010, 920 cm–1.
˜
HRMS (EI): calcd. for C12H18O [M] 178.1358; found 178.1344.
Alcohol [D]-1b: Colorless oil. 1H NMR (CDCl3, 300 MHz): δ =
7.46–7.40 (m, 2 H), 7.35–7.27 (m, 3 H), 2.05–1.96 (m, 1 H), 1.55
(s, 3 H) ppm.
Alcohol [D]-1u: Colorless oil. 1H NMR (CDCl3, 300 MHz): δ =
2.20 (t, J = 7.2 Hz, 2 H), 1.74 (s, 1 H), 1.70–1.58 (m, 2 H), 1.56–
1.20 (m, 10 H), 0.95 (t, J = 7.2 Hz, 3 H), 0.89 (t, J = 6.9 Hz, 3 H)
ppm.
Alcohol 6c:[7] To a stirred mixture of LiAlH4 (64.6 mg, 1.70 mmol)
in THF (10 mL) at 0 °C was added a solution of 8d (600 mg,
2.27 mmol) in Et2O (5 mL). The resulting mixture was stirred at
0 °C for 30 min. The reaction was quenched with water (2.0 mL),
and stirred at 0 °C for 10 min. The reaction mixture was extracted
with Et2O. The organic layer was washed with water and brine,
dried with Na2SO4, and concentrated. The residue was purified by
silica gel column chromatography (hexane/EtOAc, 5:1), which fur-
nished alcohol 6c (340.0 mg, 1.43 mmol, 63% yield) as a colorless
solid, m.p. 121–122 °C. 1H NMR (CDCl3, 300 MHz): δ = 7.60–
7.50 (m, 4 H), 7.44–7.30 (m, 6 H), 5.57 (d, J = 6.0 Hz, 2 H), 2.30–
2.21 (m, 2 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 140.2, 128.7,
128.5, 126.6, 86.4, 64.6 ppm.
122.2, 86.5, 85.5, 76.0, 61.9, 59.2 ppm. IR (neat): ν = 3350, 2900,
˜
1120, 758, 690 cm–1. HRMS (EI): calcd. for C11H12O2 [M]
176.0837; found 176.0813.
Alcohol 1l: Pale yellow oil. 1H NMR (CDCl3, 300 MHz): δ = 7.40–
7.34 (m, 2 H), 6.86–6.80 (m, 2 H), 4.54 (q, J = 6.3 Hz, 1 H), 3.80
(s, 3 H), 2.06–1.96 (m, 1 H), 1.90–1.74 (m, 2 H), 1.07 (t, J = 7.5 Hz,
3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 159.6, 133.1, 114.7,
113.8, 88.5, 84.8, 64.2, 55.2, 31.0, 9.5 ppm. IR (neat): ν = 3350,
˜
2950, 1600, 1508, 1245, 1180, 1030, 835 cm–1. HRMS (EI): calcd.
for C12H14O2 [M] 190.0994; found 190.0970.
Alcohol 1m: Pale yellow oil. 1H NMR (CDCl3, 300 MHz): δ = 7.42–
7.37 (m, 1 H), 7.25–7.09 (m, 3 H), 4.64 (q, J = 6.0 Hz, 1 H), 2.43
(s, 3 H), 2.00–1.93 (m, 1 H), 1.90–1.78 (m, 2 H), 1.09 (t, J = 7.5 Hz,
3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 140.0, 131.8, 129.3,
128.3, 125.4, 122.3, 93.8, 83.7, 64.3, 31.1, 20.8, 9.6 ppm. IR (neat):
Alcohol 6b: The title compound was prepared in 59% isolated yield
from 10b according to the procedure used for 6c. Colorless solid;
ν = 3300, 2950, 1015, 745 cm–1. HRMS (EI): calcd. for C H O
˜
12 14
1
[M] 174.1045; found 174.1011.
m.p. 57–58 °C. H NMR (CDCl3, 300 MHz): δ = 7.70–7.50 (m, 2
H), 7.50–7.26 (m, 3 H), 5.55–5.48 (m, 1 H), 4.54–4.40 (m, 1 H),
2.40–2.35 (m, 1 H), 1.95–1.85 (m, 1 H), 1.80–1.65 (m, 2 H), 1.55–
1.40 (m, 2 H), 1.40–1.20 (m, 4 H), 0.89 (t, J = 6.6 Hz, 3 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 140.4, 128.6, 128.4, 126.63,
126.61, 87.8, 84.5, 64.4, 62.5, 37.5, 31.4, 24.8, 22.5, 14.0 ppm. IR
Alcohol 1n: Pale yellow oil. 1H NMR (CDCl3, 300 MHz): δ = 7.65
(d, J = 7.5 Hz, 1 H), 7.58 (d, J = 7.5 Hz, 1 H), 7.49 (t, J = 7.5 Hz,
1 H), 7.41 (t, J = 7.5 Hz, 1 H), 4.58 (q, J = 6.3 Hz, 1 H), 1.92–1.78
(m, 3 H), 1.08 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 134.0, 131.8, 131.3, 128.1, 125.8 (q), 125.3, 121.7,
(neat): ν = 3200, 2850, 990, 680 cm–1. HRMS (EI): calcd. for
˜
95.7, 80.8, 64.2, 30.7, 9.1 ppm. IR (neat): ν = 3250, 2850, 1300,
˜
C15H20O2 [M] 232.1463, found 232.1413.
1100, 750 cm–1. HRMS (EI): calcd. for C12H11F3O [M] 228.0762;
found 228.0719.
Alcohol 8a: To a stirred suspension of NaH (55% in paraffin oil,
0.48 g, 20.0 mmol) in THF (30 mL) was added a THF (5 mL) solu-
tion of tetradec-7-yn-6,9-diol (2.26 g, 10.0 mmol) at room temp.,
and the resulting mixture was stirred at room temp. for 30 min. To
the resulting solution was added iodomethane (0.6 mL,
10.0 mmol), and the mixture was stirred at room temp. overnight.
The mixture was extracted with Et2O. The organic layer was
washed with brine, dried with Na2SO4, and concentrated. The resi-
due was purified by silica gel column chromatography (hexane/
EtOAc, 10:1), which furnished alcohol 8a (1.2 g, 5.15 mmol, 55%
yield) as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ = 4.48–
4.35 (m, 1 H), 3.97 (dt, J = 6.6, 1.5 Hz, 1 H), 3.39 (s, 3 H), 2.00–
1.87 (m, 1 H), 1.80–1.57 (m, 4 H), 1.55–1.36 (m, 4 H), 1.36–1.15
(m, 8 H), 0.97–0.80 (m, 6 H) ppm. 13C NMR (CDCl3, 75 MHz): δ
= 86.98, 86.94, 83.6, 71.3, 62.5, 56.35, 56.33, 37.84, 37.81, 35.5,
1
Alcohol 1p: Orange oil. H NMR (CDCl3, 300 MHz): δ = 8.30 (d,
J = 8.1 Hz, 1 H), 7.90–7.75 (m, 2 H), 7.67 (dd, J = 7.2, 1.5 Hz, 1
H), 7.62–7.45 (m, 2 H), 7.46–7.35 (m, 1 H), 4.71 (q, J = 6.3 Hz, 1
H), 2.04–1.84 (m, 3 H), 1.16 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 133.2, 133.1, 130.5, 128.8, 128.2, 126.8,
126.4, 126.0, 125.1, 120.3, 94.9, 82.9, 64.2, 31.1, 9.6 ppm. IR (neat):
ν = 3220, 2850, 1370, 1000, 760 cm–1. HRMS (EI): calcd. for
˜
C15H14O [M] 210.1045; found 210.1009.
Alcohol 1q: Orange oil. 1H NMR (CDCl3, 300 MHz): δ = 7.76 (dd,
J = 1.8, 0.9 Hz, 1 H), 6.57 (dd, J = 3.6, 0.9 Hz, 1 H), 6.38 (dd, J
= 3.6, 1.8 Hz, 1 H), 4.56 (q, J = 6.3 Hz, 1 H), 1.90–1.76 (m, 3 H),
1.07 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
143.4, 136.5, 115.2, 110.7, 94.2, 75.1, 64.0, 30.5, 9.3 ppm. IR (neat):
ν = 3250, 2850, 1620, 720 cm–1. HRMS (EI): calcd. for C H O
˜
31.49, 31.41, 24.9, 24.8, 22.5, 13.97, 13.94 ppm. IR (neat): ν = 3325,
˜
9
10
2
2850, 1440, 1320, 1090 cm–1. HRMS (EI): calcd. for C15H28O2 [M –
[M] 150.0681; found 150.0647.
H] 239.2011; found 239.2034.
Alcohol 1r: Orange oil. 1H NMR (CDCl3, 300 MHz): δ = 8.60–8.55
(m, 1 H), 7.66 (dt, J = 7.8, 1.8 Hz, 1 H), 7.43 (d, J = 7.8 Hz, 1 H),
7.28–7.20 (m, 1 H), 4.70–4.50 (m, 1 H), 3.10–2.80 (m, 1 H), 2.93
(q, J = 7.2 Hz, 2 H), 1.26 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 149.6, 142.8, 136.2, 127.1, 122.8, 91.1, 83.6,
Alcohol 8d:[39] To a stirred suspension of NaH (55% in paraffin oil,
1.1 g, 44.0 mmol) in THF (40 mL) was added a THF (5 mL) solu-
tion of 1-phenylprop-2-yn-1-ol (2.6 g, 20.0 mmol) at room temp.,
and the resulting mixture was stirred at room temp. for 30 min. To
the resulting solution was added iodomethane (5.0 mL,
63.6, 30.6, 9.5 ppm. IR (neat): ν = 3150, 2810, 1560, 1410, 760
˜
Eur. J. Org. Chem. 2007, 2687–2699
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2695

K. Tanaka, T. Shoji, M. Hirano
FULL PAPER
80.0 mmol), and the mixture was stirred at room temp. for 30 min.
The reaction was quenched with water and extracted with Et2O.
The organic layer was washed with brine, dried with Na2SO4, and
concentrated. The residue was purified by silica gel column
fied by silica gel column chromatography (hexane/EtOAc, 9:1),
which furnished alcohol 11b (0.46 g, 1.76 mmol, 61% yield) as a
1
pale yellow oil. H NMR (CDCl3, 300 MHz): δ = 7.58–7.46 (m, 4
H), 7.44–7.28 (m, 6 H), 6.58–6.52 (m, 1 H), 5.59–5.52 (m, 1 H),
chromatography (hexane/EtOAc, 20:1), which furnished (1-meth- 2.34–2.26 (m, 1 H), 2.10 (s, 3 H) ppm. 13C NMR (CDCl3, 75 MHz):
oxyprop-2-ynyl)benzene (1.6 g, 10.8 mmol, 54% yield) as a color-
δ = 169.9, 140.0, 136.5, 128.9, 128.5, 128.4, 128.2, 127.6, 126.6,
less oil. nBuLi (1.56  in hexane, 3.6 mL, 5.59 mmol) was added to
87.0, 82.7, 65.6, 64.2, 20.9 ppm. IR (neat): ν = 3350, 3000, 1700,
˜
a
stirred solution of (1-methoxyprop-2-ynyl)benzene (0.82 g,
1200, 1000 cm–1. HRMS (EI): calcd. for C18H16O3 [M] 280.1099;
found 280.1103.
5.59 mmol) in THF (15 mL) at 0 °C, and the mixture was stirred at
0 °C for 30 min. To the resulting solution was added benzaldehyde
(0.56 mL, 5.59 mmol) at 0 °C, and the mixture was gradually
warmed to room temp. The reaction was quenched with water and
extracted with Et2O. The organic layer was washed with brine,
dried with Na2SO4, and concentrated. The residue was purified by
silica gel column chromatography (hexane/EtOAc, 8:1), which fur-
nished alcohol 8d (1.32 g, 5.22 mmol, 93% yield) as a pale yellow
oil. 1H NMR (CDCl3, 300 MHz): δ = 7.58–7.42 (m, 4 H), 7.42–
7.26 (m, 6 H), 5.54 (s, 1 H), 5.17 (s, 1 H), 3.41 (s, 3 H), 2.60–2.34
(m, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 140.31, 140.30,
138.1, 128.6, 128.5, 128.4, 127.4, 126.6, 87.5, 84.2, 73.0, 64.61,
64.60, 55.9 ppm.
Alcohol 10a: The title compound was prepared as a pale yellow
oil in 47% isolated yield (2 steps) from oct-1-yn-3-ol and hexanal
1
according to the procedure used for 11b. Pale yellow oil. H NMR
(CDCl3, 300 MHz): δ = 5.43–5.34 (m, 1 H), 4.45–4.35 (m, 1 H),
2.08 (s, 3 H), 1.86–1.80 (m, 1 H), 1.80–1.60 (m, 4 H), 1.50–1.37 (m,
4 H), 1.37–1.22 (m, 8 H), 0.90 (t, J = 6.9 Hz, 6 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 170.1, 86.5, 82.3, 82.2, 64.11, 64.10, 62.3,
37.5, 34.6, 31.4, 31.2, 24.72, 24.71, 24.6, 22.5, 22.4, 21.0, 13.92,
13.91 ppm. IR (neat): ν = 3300, 2850, 1700, 1210, 1010 cm–1.
˜
HRMS (EI): calcd. for C16H28O3 [M – C5H11] 197.1177; found
197.1187.
Alcohol 10b: The title compound was prepared as a pale yellow oil
Alcohol 8b: The title compound was prepared as a pale yellow oil
in 77% isolated yield from (1-methoxyprop-2-ynyl)benzene and
hexanal according to the procedure used for 8d. Pale yellow oil. 1H
NMR (CDCl3, 300 MHz): δ = 7.53–7.43 (m, 2 H), 7.43–7.30 (m, 3
H), 5.12 (s, 1 H), 4.53–4.41 (m, 1 H), 3.42 (s, 3 H), 2.00–1.80 (m,
1 H), 1.80–1.53 (m, 2 H), 1.53–1.40 (m, 2 H), 1.40–1.25 (m, 4 H),
0.94–0.83 (m, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 138.3,
129.5, 128.44, 128.40, 127.3, 88.99, 88.98, 82.2, 72.9, 62.5, 55.77,
in 51% isolated yield (2 steps) from oct-1-yn-3-ol and benzaldehyde
according to the procedure used for 11b. Pale yellow oil. H NMR
1
(CDCl3, 300 MHz): δ = 7.60–7.49 (m, 2 H), 7.48–7.26 (m, 3 H),
5.50 (d, J = 6.3 Hz, 1 H), 5.44 (tt, J = 6.6, 2.1 Hz, 1 H), 2.35–2.25
(m, 1 H), 2.09 (s, 3 H), 1.85–1.70 (m, 2 H), 1.50–1.37 (m, 2 H),
1.37–1.24 (m, 4 H), 0.89 (t, J = 6.9 Hz, 3 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 170.1, 140.2, 128.5, 128.3, 126.6, 85.1, 85.0,
84.1, 64.36, 64.34, 64.12, 64.10, 34.5, 31.2, 24.61, 24.59, 22.4, 21.0,
14.0 ppm. IR (neat): ν = 3350, 2850, 1700, 1210, 1000 cm–1. HRMS
55.76, 37.7, 31.4, 24.8, 22.5, 13.9 ppm. IR (neat): ν = 3100, 2850,
˜
˜
1050, 690 cm–1. HRMS (EI): calcd. for C16H22O2 [M] 246.1620;
found 246.1637.
(EI): calcd. for C17H22O3 [M] 274.1569; found 274.1524.
Alcohol 11a: The title compound was prepared as a pale yellow oil
in 61% isolated yield (2 steps) from 1-phenylprop-2-yn-1-ol and
hexanal according to the procedure used for 11b. Pale yellow oil.
1H NMR (CDCl3, 300 MHz): δ = 7.54–7.49 (m, 2 H), 7.49–7.30
(m, 3 H), 6.49 (s, 1 H), 4.51–4.40 (m, 1 H), 2.10 (s, 3 H), 1.87–1.80
(m, 1 H), 1.80–1.65 (m, 2 H), 1.52–1.39 (m, 2 H), 1.39–1.20 (m, 4
H), 0.89 (t, J = 6.3 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ
= 169.8, 136.82, 136.81, 128.9, 128.6, 127.7, 88.4, 81.2, 65.57, 65.56,
Alcohol 8c: The title compound was prepared as a pale yellow oil
in 17% isolated yield (2 steps) from oct-1-yn-3-ol and benzaldehyde
1
according to the procedure used for 8d. Pale yellow oil. H NMR
(CDCl3, 300 MHz): δ = 7.60–7.50 (m, 2 H), 7.44–7.30 (m, 3 H),
5.53 (d, J = 6.6 Hz, 1 H), 4.03 (t, J = 6.6 Hz, 1 H), 3.42 (s, 3 H),
2.20 (d, J = 6.6 Hz, 1 H), 1.80–1.65 (m, 2 H), 1.55–1.38 (m, 2 H),
1.38–1.20 (m, 4 H), 0.94–0.83 (m, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 140.6, 128.6, 128.4, 126.64, 126.61, 85.8, 85.5, 71.3,
62.4, 37.45, 37.43, 31.3, 24.7, 22.5, 21.1, 13.9 ppm. IR (neat): ν =
˜
3300, 2850, 1700, 1210, 680 cm–1. HRMS (EI): calcd. for C17H22O3
[M] 274.1569; found 274.1534.
64.6, 56.5, 35.5, 31.5, 24.9, 22.5, 14.0 ppm. IR (neat): ν = 3300,
˜
2850, 1070, 690 cm–1. HRMS (EI): calcd. for C16H22O2 [M]
246.1620; found 246.1663.
Alcohol 19: The title compound was prepared as a colorless oil in
31% isolated yield (2 steps) from 1-methylbut-3-ynyl acetate[40] and
propionaldehyde according to the procedure used for 6c. Colorless
oil. 1H NMR (CDCl3, 300 MHz): δ = 4.40–4.25 (m, 1 H), 4.05–
3.88 (m, 1 H), 2.44 (ddd, J = 16.2, 6.9, 1.8 Hz, 1 H), 2.35 (ddd, J
= 16.2, 6.6, 1.8 Hz, 1 H), 2.12–1.80 (m, 2 H), 1.78–1.58 (m, 2 H),
1.26 (d, J = 6.3 Hz, 3 H), 1.00 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 83.7, 81.6, 66.4, 66.3, 63.8, 31.0, 29.2, 22.3,
Alcohol 11b: 1-Phenylprop-2-yn-1-ol (1.5 g, 11.4 mmol) was added
to a stirred solution of triethylamine (1.9 mL, 13.6 mmol), DMAP
(69.3 mg, 0.57 mmol) and acetic anhydride (1.2 mL, 12.5 mmol) in
CH2Cl2 (20 mL) at room temp., and the mixture was stirred at
room temp. for 1 h. The reaction was quenched with water and
extracted with Et2O. The organic layer was washed with brine,
dried with Na2SO4, and concentrated. The residue was purified by
silica gel column chromatography (hexane/EtOAc, 20:1), which fur-
nished 1-phenylprop-2-ynyl acetate (1.9 g, 10.6 mmol, 94% yield)
as a colorless oil. nBuLi (1.54  in hexane, 1.9 mL, 2.87 mmol) was
9.5 ppm. IR (neat): ν = 3200, 2900, 1050, 920 cm–1. HRMS (FAB):
˜
calcd. for C8H14O2 [M + H] 143.1072; found 143.1084.
Representative Procedure for the Isomerization of Propargylic
Alcohols: (Table 2, Entry 1): A CH2Cl2 (0.5 mL) solution of rac-
BINAP (15.6 mg, 0.025 mmol) was added to a CH2Cl2 (0.5 mL)
solution of [Rh(cod)2]BF4 (10.2 mg, 0.025 mmol) at room temp.,
and the mixture was stirred for 5 min at room temp. H2 was intro-
duced to the resulting solution in a Schlenk tube. After stirring
for 0.5 h at room temp., the resulting solution was concentrated to
dryness and dissolved in (CH2Cl)2 (1.0 mL). To this solution was
added a (CH2Cl)2 (0.5 mL) solution of 4-phenylbut-3-yn-2-ol (1b,
73.1 mg, 0.5 mmol), and additional (CH2Cl)2 (0.5 mL) was used to
added to
a stirred solution of diisopropylamine (0.5 mL,
3.16 mmol) in THF (20 mL) at 0 °C, and the mixture was stirred
at 0 °C for 30 min. 1-Phenylprop-2-ynyl ester (0.50 g, 2.78 mmol)
was added to the resulting solution at –78 °C, and the solution was
stirred at –78 °C for 15 min. To the resulting solution was added
benzaldehyde (0.26 mL, 2.58 mmol) at –78 °C, and the mixture was
gradually warmed to room temp. The reaction was quenched with
water and extracted with Et2O. The organic layer was washed with
brine, dried with Na2SO4, and concentrated. The residue was puri-
2696
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Eur. J. Org. Chem. 2007, 2687–2699

Isomerization of Propargylic Alcohols to α,β-Enones
FULL PAPER
transfer the material completely from its original flask. The solu-
tion was stirred at 80 °C for 1 h. The resulting solution was concen-
trated and purified by silica gel column chromatography (Et2O),
giving ketone 2b[41] (72.5 mg, 0.495 mmol, 99% yield). Orange so-
2.30–2.06 (m, 4 H), 1.77–1.55 (m, 6 H), 0.95 (t, J = 7.5 Hz, 3 H)
ppm. 13C NMR (CDCl3, 75 MHz): δ = 201.1, 145.9, 139.5, 135.1,
123.2, 42.3, 26.5, 24.1, 21.95, 21.91, 17.9, 13.7 ppm. IR (neat): ν =
˜
2900, 1590, 1190, 980 cm–1. HRMS (EI): calcd. for C12H18O [M]
lid; m.p. 35–37 °C. 1H NMR (CDCl3, 300 MHz): δ = 7.60–7.48 (m, 178.1358; found 178.1320.
3 H), 7.48–7.30 (m, 3 H), 6.72 (d, J = 15.9 Hz, 1 H), 2.37 (s, 3 H)
Ketone 12a: (Table 6, Entry 8) Yield 71% (19.0 mg). Colorless oil.
ppm. 13C NMR (CDCl3, 75 MHz): δ = 198.4, 143.4, 134.3, 130.5,
128.9, 128.2, 127.1, 27.5 ppm.
1H NMR (CDCl3, 300 MHz): δ = 6.68 (dd, J = 16.2, 5.4 Hz, 1 H),
6.19 (dd, J = 16.2, 1.2 Hz, 1 H), 5.45–5.33 (m, 1 H), 2.55 (t, J =
7.5 Hz, 2 H), 2.10 (s, 3 H), 1.72–1.50 (m, 4 H), 1.49–1.10 (m, 10
Ketone 2k: (Table 2, Entry 11) Yield 99% (112.5 mg). Pale brown
1
solid; m.p. 62–64 °C. H NMR (CDCl3, 300 MHz): δ = 7.65 (s, 4 H), 0.94–0.84 (m, 6 H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
H), 7.57 (d, J = 16.2 Hz, 1 H), 6.81 (d, J = 16.2 Hz, 1 H), 2.72 (q,
J = 7.5 Hz, 2 H), 1.18 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 200.2, 140.0, 137.9, 131.8, 128.2, 127.9, 125.7 (q),
200.3, 170.1, 142.9, 129.2, 72.7, 40.7, 33.8, 31.42, 31.37, 24.6, 23.6,
22.4, 21.0, 13.93, 13.89 ppm. IR (neat): ν = 2850, 1660, 1350, 1220
˜
cm–1. HRMS (EI): calcd. for C16H28O3 [M – Ac] 225.1854; found
122.3, 34.4, 8.1 ppm. IR (neat): ν = 2950, 1660, 1320, 1160, 1120,
225.1798.
˜
985, 840 cm–1. HRMS (EI): calcd. for C12H11F3O [M] 228.0762,
found 228.0736.
Ketone 12b: (Table 6, Entry 9) Yield 59% (76.8 mg). Pale yellow
oil. 1H NMR (CDCl3, 300 MHz): δ = 7.98–7.90 (m, 2 H), 7.62–
7.52 (m, 1 H), 7.52–7.36 (m, 2 H), 7.02 (d, J = 15.6 Hz, 1 H), 6.91
(dd, J = 15.6, 5.4 Hz, 1 H), 5.51 (q, J = 5.4 Hz, 1 H), 2.14 (s, 3 H),
Ketone 2m (E/Z = 67:33): (Table 2, Entry 13) Yield 94% (81.6 mg).
1
Orange oil. H NMR (CDCl3, 400 MHz) E isomer: δ = 7.86 (d, J
= 15.6 Hz, 1 H), 7.60–7.54 (m, 1 H), 7.37–7.10 (m, 3 H), 6.67 (d, 1.88–1.58 (m, 2 H), 1.47–1.35 (m, 6 H), 0.89 (t, J = 6.6 Hz, 3 H)
J = 15.6 Hz, 1 H), 2.70 (q, J = 7.2 Hz, 2 H), 2.25 (s, 3 H), 1.18 (t, ppm. 13C NMR (CDCl3, 75 MHz): δ = 190.1, 170.1, 145.3, 137.4,
J = 7.2 Hz, 3 H) ppm; Z isomer: δ = 7.37–7.10 (m, 4 H), 7.05 (d,
132.9, 128.51, 128.49, 125.3, 73.0, 33.8, 31.4, 24.6, 22.4, 21.0, 13.9
J = 12.4 Hz, 1 H), 6.22 (d, J = 12.4 Hz, 1 H), 2.30 (s, 3 H), 2.30 ppm. IR (neat): ν = 2900, 1620, 1220, 1010 cm–1. HRMS (EI):
˜
(q, J = 7.2 Hz, 2 H), 0.96 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 203.8, 200.7, 139.5, 139.1, 137.7, 135.6,
135.3, 133.4, 130.7, 129.9, 129.8, 129.7, 128.8, 128.5, 126.8, 126.2,
calcd. for C17H22O3 [M – Ac] 232.1463; found 232.1413.
Ketone 13a: (Table 6, Entry 10) Yield 45% (58.6 mg). Orange oil.
1H NMR (CDCl3, 300 MHz): δ = 7.72 (d, J = 15.9 Hz, 1 H), 7.63–
7.50 (m, 2 H), 7.50–7.30 (m, 3 H), 6.86 (d, J = 15.9 Hz, 1 H), 5.29
(dd, J = 7.8, 7.2 Hz, 1 H), 2.18 (s, 3 H), 1.90–1.70 (m, 2 H), 1.51–
1.36 (m, 2 H), 1.36–1.20 (m, 4 H), 0.89 (t, J = 6.9 Hz, 3 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 196.0, 170.6, 144.4, 134.3, 130.8,
128.9, 128.5, 121.0, 78.0, 31.4, 30.8, 24.9, 22.4, 20.8, 14.0 ppm. IR
126.1, 125.5, 36.1, 34.3, 19.9, 19.8, 8.3, 8.1 ppm. IR (neat): ν =
˜
2925, 1660, 1600, 1120, 1040, 980, 745 cm–1. HRMS (EI): calcd.
for C12H14O [M] 174.1045; found 174.1028.
Ketone 2n (E/Z = 57:43): (Table 2, Entry 14) Yield 97% (110.6 mg).
1
Orange oil. H NMR (CDCl3, 300 MHz) E isomer: δ = 7.85–7.80
(m, 1 H), 7.80–7.65 (m, 2 H), 7.58 (t, J = 7.5 Hz, 1 H), 7.49 (t, J
(neat): ν = 2900, 1700, 1230, 1030, 690 cm–1. HRMS (EI): calcd.
˜
= 7.5 Hz, 1 H), 6.66 (d, J = 16.2 Hz, 1 H), 2.74 (q, J = 7.2 Hz, 2 for C17H22O3 [M] 274.1569; found 274.1576.
H), 1.18 (t, J = 7.2 Hz, 3 H) ppm; Z isomer: δ = 7.68 (d, J =
Ketone 13b: (Table 6, Entry 11) Yield 50% (66.3 mg). Orange oil.
7.5 Hz, 1 H), 7.56–7.38 (m, 2 H), 7.36 (d, J = 7.5 Hz, 1 H), 7.20–
7.08 (m, 1 H), 6.33 (d, J = 12.3 Hz, 1 H), 2.33 (q, J = 7.2 Hz, 2
H), 0.97 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ
= 202.6, 200.6, 137.7, 136.4, 135.0, 133.6, 131.4, 132.1, 130.7, 130.6,
130.2, 129.6, 128.2, 127.8, 126.5 (q), 125.80, 125.77, 125.74 (q),
1H NMR (CDCl3, 300 MHz): δ = 7.70 (d, J = 15.9 Hz, 1 H), 7.65–
7.10 (m, 10 H), 6.78 (d, J = 15.9 Hz, 1 H), 6.26 (s, 1 H), 2.22 (s, 3
H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 192.5, 170.2, 144.6,
134.0, 133.3, 130.8, 129.3, 129.1, 128.8, 128.5, 128.4, 121.0, 80.2,
20.8 ppm. IR (neat): ν = 3050, 1680, 1200, 910, 700 cm–1. HRMS
˜
122.2, 122.1, 36.6, 33.5, 8.0, 7.7 ppm. IR (neat): ν = 3300, 1600,
˜
(EI): calcd. for C18H16O3 [M – C2H2O] 238.0993; found 238.0976.
1290, 1100, 750 cm–1. HRMS (EI): calcd. for C12H11F3O [M – Et]
Ketone 20: (Scheme 20) Yield 55% (31.1 mg). Orange oil. 1H NMR
(CDCl3, 300 MHz): δ = 6.86 (dd, J = 15.9, 7.5 Hz, 1 H), 6.18 (dd,
J = 15.9, 1.2 Hz, 1 H), 3.98 (sext, J = 6.3 Hz, 1 H), 2.59 (q, J =
7.5 Hz, 2 H), 2.42–2.32 (m, 2 H), 2.30–1.82 (m, 1 H), 2.25 (d, J =
6.3 Hz, 3 H), 1.10 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 201.1, 142.8, 132.2, 66.7, 42.0, 33.3, 23.3, 8.0 ppm.
199.0371; found 199.0338.
Ketone 2o: (Table 2, Entry 15) Yield 96% (97.9 mg). Orange oil. 1H
NMR (CDCl3, 300 MHz): δ = 7.91 (d, J = 16.2 Hz, 1 H), 7.54 (dd,
J = 7.8, 1.5 Hz, 1 H), 7.43–7.28 (m, 1 H), 7.00–6.85 (m, 2 H), 6.78
(d, J = 16.2 Hz, 1 H), 3.88 (s, 3 H), 2.66 (t, J = 7.2 Hz, 2 H), 1.71
(sext, J = 7.2 Hz, 2 H), 0.98 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 201.1, 158.3, 137.5, 131.5, 128.3, 126.9,
IR (neat): ν = 3300, 2900, 1620, 980 cm–1. HRMS (FAB): calcd.
˜
for C8H14O2 [M + H] 143.1072; found 143.1031.
123.4, 120.7, 111.1, 55.4, 42.2, 17.8, 13.8 ppm. IR (neat): ν = 2850,
˜
1580, 1440, 1230, 730 cm–1. HRMS (EI): calcd. for C13H16O2 [M]
204.1150; found 204.1125.
Representative Procedure for the Kinetic Resolution of Secondary
Propargylic Alcohols: (Table 4, Entry 4): AgOTf (6.4 mg,
0.025 mmol) and [Rh(cod)Cl]2 (6.2 mg, 0.0125 mmol) were dis-
solved in acetone (1.0 mL), and the mixture was stirred at room
temp. for 5 min. An acetone (0.5 mL) solution of (R)-BINAP
(15.6 mg, 0.025 mmol) was added, and the mixture was stirred at
room temp. for 5 min. The resulting solution was concentrated to
dryness and dissolved in CH2Cl2 (0.5 mL). H2 was introduced to
the resulting solution in a Schlenk tube. After stirring at room
temp. for 0.5 h, the resulting solution was concentrated to dryness
and dissolved in CH2Cl2 (1.0 mL). To this solution was added a
CH2Cl2 (0.5 mL) solution of 1d (94.1 mg, 0.500 mmol), and ad-
ditional CH2Cl2 (0.5 mL) was used to transfer the material com-
Ketone 2s: (Table 2, Entry 19) Yield 84% (58.1 mg). Pale yellow oil.
1H NMR (CDCl3, 300 MHz): δ = 7.23 (d, J = 15.9 Hz, 1 H), 6.15
(d, J = 15.9 Hz, 1 H), 5.43–5.34 (m, 2 H), 2.58 (t, J = 7.5 Hz, 2
H), 1.92–1.86 (m, 3 H), 1.67 (sext, J = 7.5 Hz, 2 H), 0.96 (t, J =
7.5 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 201.0, 144.7,
140.9, 127.0, 124.9, 42.5, 18.5, 17.7, 13.8 ppm. IR (neat): ν = 2900,
˜
1660, 1190, 980 cm–1. HRMS (EI): calcd. for C9H14O [M – Pr]
95.0497; found 95.0452.
Ketone 2t: (Table 2, Entry 20) Yield 79% (70.2 mg). Pale yellow oil.
1H NMR (CDCl3, 300 MHz): δ = 7.16 (d, J = 15.9 Hz, 1 H), 6.38–
6.15 (m, 1 H), 6.07 (d, J = 15.9 Hz, 1 H), 2.55 (t, J = 7.2 Hz, 2 H), pletely from its original flask. The solution was stirred at 25 °C for
Eur. J. Org. Chem. 2007, 2687–2699
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2697

K. Tanaka, T. Shoji, M. Hirano
FULL PAPER
W. A. Herrmann), Wiley, Weinheim, 2002, vol. 3, pp. 1119–
1130; d) K. Tanaka in Comprehensive Organometallic Chemis-
try, 3rd ed. (Eds.: R. H. Crabtree, D. M. P. Mingos), Elsevier,
Oxford, 2006, vol. 10, pp. 71–100.
For reviews, see: a) R. Uma, C. Crévisy, R. Grée, Chem. Rev.
2003, 103, 27–51; b) R. C. Van der Drift, E. Bouwman, E.
Drent, J. Organomet. Chem. 2002, 650, 1–24.
a) B. M. Trost, Science 1991, 254, 1471–1477; b) B. M. Trost,
Angew. Chem. 1995, 34, 259–281; Angew. Chem. Int. Ed. Engl.
1995, 34, 259–281.
Y. Shvo, Y. Blum, D. Reshef, J. Organomet. Chem. 1982, 238,
C79–C81.
D. Ma, X. Lu, J. Chem. Soc., Chem. Commun. 1989, 890–891.
a) B. M. Trost, R. C. Livingston, J. Am. Chem. Soc. 1995, 117,
9586–9587; for an example of a synthesis of an α,β-enal as a
key intermediate in the total synthesis of sphingofungin ana-
logues, see: b) B. M. Trost, C. Lee, J. Am. Chem. Soc. 2001,
123, 12191–12201.
14 h. The conversion of the reaction was determined to be 59.8%
by H NMR with 1,4-dimethoxybenzene as an internal standard.
The solution was concentrated and purified by preparative TLC
1
(hexane/EtOAc, 4:1), which furnished 2d (50.1 mg, 0.270 mmol,
[2]
[3]
[4]
53% yield) and (+)-1d [33.8 mg, 0.180 mmol, 36% yield, [α]2D5
=
+1.29 (c = 1.69 in CHCl3, 81.5% ee)]. Selectivity factor: 8.2. HPLC:
CHIRALCEL OD-H, hexane/2-PrOH, 95:5, 1.0 mL/min, retention
times: 8.3 min (minor isomer) and 27.7 min (major isomer).
Table 4, Entry 7: (–)-1k {[α]2D5 = –1.05 (c = 1.76 in CHCl3, 78.0%
ee)} was obtained for 64 h in 60.0% conversion. Selectivity factor:
7.2. HPLC: CHIRALCEL OD-H, hexane: 2-PrOH, 99:1, 1.0 mL/
min, retention times: 19.7 min (minor isomer) and 22.6 min (major
isomer).
[5]
[6]
Table 4, Entry 8: (–)-1l {[α]2D5 = –1.15 (c = 1.74 in CHCl3, 62.3%
ee)} was obtained for 45 h at 54.5% conversion. Selectivity factor:
5.8. HPLC: CHIRALCEL OD-H, hexane:2-PrOH, 95:5, 1.0 mL/
min, retention times: 11.5 min (minor isomer) and 40.8 min (major
isomer).
[7]
[8]
X. Lu, J. Ji, D. Ma, W. Shen, J. Org. Chem. 1991, 56, 5774–
5778.
X. Lu, J. Ji, C. Guo, W. Shen, J. Organomet. Chem. 1992, 428,
259–266.
D. Ma, X. Lu, Tetrahedron Lett. 1989, 30, 2109–2112.
Table 4, Entry 9: (–)-1m {[α]2D5 = –3.07 (c = 1.79 in CHCl3, 80.0%
ee)} was obtained for 42 h at 54.9% conversion. Selectivity factor:
11.5. HPLC: CHIRALCEL OD-H, hexane/2-PrOH, 95:5, 1.0 mL/
min, retention times: 8.9 min (minor isomer) and 15.8 min (major
isomer).
[9]
[10]
a) C. Bianchini, A. Meli, W. Oberhauser, New J. Chem. 2001,
25, 11–12; b) C. de Bellefon, N. Tanchoux, S. Caravieilhes, P.
Grenouillet, V. Hessel, Angew. Chem. 2000, 39, 3442–3445; An-
gew. Chem. Int. Ed. 2000, 39, 3442–3445; c) G.-J. Boons, A.
Burton, S. Isles, Chem. Commun. 1996, 141–142; d) R. Takeu-
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For Rh-catalyzed enantioselective isomerization of allylic
alcohols, see: a) K. Tanaka, G. C. Fu, J. Org. Chem. 2001, 66,
8177–8186; b) K. Tanaka, S. Qiao, M. Tobisu, M. M.-C. Lo,
G. C. Fu, J. Am. Chem. Soc. 2000, 122, 9870–9871. For Rh-
catalyzed kinetic resolution of an allylic alcohol, see: c) M.
Kitamura, K. Manabe, R. Noyori, H. Takaya, Tetrahedron
Lett. 1987, 28, 4719–4720.
Table 4, Entry 10: (–)-1n {[α]2D5 = –0.76 (c = 2.44 in CHCl3, 51.8%
ee)} was obtained for 12 h (50 °C) at 50.5% conversion. Selectivity
factor: 5.0. HPLC: CHIRALCEL OD-H, hexane/2-PrOH, 97:3,
0.8 mL/min, retention times: 9.2 min (minor isomer) and 11.6 min
(major isomer).
Table 4, Entry 11: (–)-1o {[α]2D5 = –0.56 (c = 2.26 in CHCl3, 68.0%
ee)} was obtained for 22 h at 53.4% conversion. Selectivity factor:
[11]
7.8. HPLC: CHIRALCEL OD-H, hexane/2-PrOH
= 90:10,
1.0 mL/min, retention times: 11.9 min (minor isomer) and 36.7 min
(major isomer).
Table 4, Entry 12: (–)-1p {[α]2D5 = –4.00 (c = 2.42 in CHCl3, 60.4%
ee)} was obtained for 94 h at 51.9% conversion. Selectivity factor:
[12]
[13]
[14]
M. K. E. Saiah, R. Pellicciari, Tetrahedron Lett. 1995, 36,
4497–4500.
For a preliminary communication, see: K. Tanaka, T. Shoji,
6.4. HPLCL CHIRALPAK AD-H, hexane/2-PrOH
= 97:3,
0.8 mL/min, retention times: 22.9 min (minor isomer) and 24.2 min
(major isomer).
Org. Lett. 2005, 7, 3561–3563.
A base-catalyzed isomerization of electron-deficient α-arylpro-
pargylic alcohols into chalcone derivatives and α,β-alkenyl es-
ters was reported; see: a) J. P. Sonyne, K. Koide, J. Org. Chem.
2006, 71, 6254–6257; b) R. Erenler, J.-F. Biellmann, Tetrahe-
dron Lett. 2005, 46, 5683–5685; c) R. C. Bernotas, Synlett 2004,
2165–2166; d) A. Coelho, E. Sotelo, E. Ravina, Tetrahedron
2003, 59, 2477–2484; e) T. Ishikawa, T. Mizuta, K. Hagiwara,
T. Aikawa, T. Kudo, S. Saito, J. Org. Chem. 2003, 68, 3702–
3705; f) T. J. Muller, M. Ansorge, D. Aktah, Angew. Chem.
2000, 39, 1253–1256; Angew. Chem. Int. Ed. 2000, 39, 1253–
1256; g) K. Minn, Synlett 1991, 115–116; h) A. W. Nineham,
R. A. Raphael, J. Chem. Soc., Chem. Commun. 1949, 118–121.
Supporting Information (see also the footnote on the first page of
this article): Experimental procedures and compound characteriza-
tion data for 1i, 18, 2a, 2c, 2d, 2e, 2f, 2h, 2i, 2j, 2l, 2p, 2q, 2u, 2v,
2w, [D]-2b, [D]-2u, 7a, 7b, 7c, 9a, 9b, 9d, and Entries 1, 2, 3, 5, and
1
6 of Table 4. H and 13C NMR spectra of all new compounds (1j,
1l, 1m, 1n, 1p, 1q, 1r, 1t, 6b, 8a, 8b, 8c, 10a, 10b, 11a, 11b, 19, 2k,
2m, 2n, 2o, 2s, 2t, 12a, 12b, 13a, 13b, and 20).
Acknowledgments
[15]
[16]
For examples of transition-metal-catalyzed enantioselective
isomerizations of allylic alcohols, see: a) F. Boeda, P. Mosset,
C. Crévisy, Tetrahedron Lett. 2006, 47, 5021–5024; b) M. Ito,
S. Kitahara, T. Ikariya, J. Am. Chem. Soc. 2005, 127, 6172–
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1991, 665–680; e) K. Tani, Pure Appl. Chem. 1985, 57, 1845–
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106, 1131–1134; see also ref.[11a,11b]
For examples of transition-metal-catalyzed kinetic resolutions
of allylic alcohols, see: J. A. Wiles, C. E. Lee, R. McDonald,
S. H. Bergens, Organometallics 1996, 15, 3782–3784; see also
ref.[11c]
We thank Takasago International Corporation for a gift of modi-
fied BINAP ligands (tol-BINAP, H8-BINAP, and Segphos).
[1] a) W. A. Herrmann in Applied Homogeneous Catalysis with Or-
ganometallic Compounds (Eds.: B. Cornils, W. A. Herrmann),
Wiley, Weinheim, 1996, vol. 2, pp. 980–991; b) S. Otsuka, K.
Tani in Transition Metals for Organic Synthesis (Eds.: M.
Beller, C. Bolm), Wiley, Weinheim, 1998, vol. 1, pp. 147–157;
c) W. A. Herrmann, M. Prinz in Applied Homogeneous Cataly-
sis with Organometallic Compounds, 2nd ed. (Eds.: B. Cornils,
2698
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2687–2699

Isomerization of Propargylic Alcohols to α,β-Enones
FULL PAPER
[17] For a kinetic resolution of propargylic alcohols with chiral nu-
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[18] For a recent example of an enzymatic kinetic resolution of pro-
pargylic alcohols, see: C. Raminelli, J. V. Comasseto, L. H. An-
drade, A. L. M. Porto, Tetrahedron: Asymmetry 2004, 15,
3117–3122, and references therein.
[19] The deuterium-labeling studies revealed that the isomerization
of allylic alcohols proceeds through an intramolecular 1,3-hy-
drogen migration pathway; see: a) D. V. McGrath, R. H.
Grubbs, Organometallics 1994, 13, 224–235; b) B. M. Trost,
R. J. Kuliawec, J. Am. Chem. Soc. 1993, 115, 2027–2036; c)
S. H. Bergens, B. Bosnich, J. Am. Chem. Soc. 1991, 113, 958–
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[20] J. Yu, M. J. Gaunt, J. B. Spencer, J. Org. Chem. 2002, 67, 4627–
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Received: January 27, 2007
Published Online: March 30, 2007
Eur. J. Org. Chem. 2007, 2687–2699
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2699