Highly activated vinyl hydrogen in a significantly twisted styrene

Article abstract of DOI:10.1021/jo061092z

(Chemical Equation Presented) The novel example of a vinylic hydrogen more reactive than a benzylic hydrogen was found by treatment of a twisted styrene derivative with a strong base followed by D₂O quenching. In this paper, the full details of

Full text of DOI:10.1021/jo061092z

Highly Activated Vinyl Hydrogen in a Significantly Twisted Styrene
Hajime Mori,*,†,§ Takafumi Matsuo,† Yasunori Yoshioka,‡ and Shigeo Katsumura*,†
School of Science and Technology, Kwansei Gakuin UniVersity, 2-1 Gakuen, Sanda, Hyogo 669-1337,
Japan, and Department of Chemistry, Mie UniVersity, 1577 Kurimamachiya-cho, Tsu-shi, Mie 514-8507,
Japan
hmori@wakayama-kg.go.jp; katsumura@ksc.kwansei.ac.jp
ReceiVed May 26, 2006
The novel example of a vinylic hydrogen more reactive than a benzylic hydrogen was found by treatment
of a twisted styrene derivative with a strong base followed by D2O quenching. In this paper, the full
details of the examples of the highly activated vinyl hydrogens in twisted styrene derivatives are described,
with a discussion on the correlation between the reactivity of the vinyl hydrogens and the magnitude of
the twist. The highly reactive vinyl hydrogens could be rationalized by considering the novel orbital
interaction between the π* orbital of the benzene ring and the σ orbital of the vinylic C-H bond in the
twisted styrene derivatives.
Introduction
be regarded as the pioneering work to study the characteristic
nature of these twisted 1,3-dienes or styrenes, for 30 years their
unique character had not been paid any attention in other types
of reactions such as an anionic reaction.
Recently, during the course of our synthetic study of the allene
carotenoid peridinin, we have found the novel character of
significantly twisted 1,3-dienes in the ene reaction of singlet
oxygen.2 Thus, the vinyl hydrogen in the significantly twisted
cis-â-ionol derivatives was selectively abstracted by singlet
oxygen over the allyl hydrogen to give the corresponding allene
compound in good yield.2,3 The detailed consideration concern-
Vinylic σ bond activation based on σ-π orbital interaction,
which leads to a remarkable acceleration of the reactions, can
be found in the chemistry of stabilized vinyl cations reported
nearly 30 years ago.1 Thus, it was reported that the solvolysis
of vinyl halides, triflates, or tosylates in significantly twisted
1,3-dienes or styrenes around the central single bond was
strongly accelerated based on the pronounced stabilization on
the intermediary vinyl cations. Although this example can also
* To whom correspondence should be addressed. (H.M.) Tel: +81-73-477-
1271. Fax: +81-73-477-2880. (S.K.) Tel: +81-795-65-8314.
† Kwansei Gakuin University.
(2) (a) Mori, H.; Ikoma, K.; Isoe, S.; Kitaura, K.; Katsumura, S.
Tetrahedron Lett. 1996, 37, 7771. (b) Mori, H.; Ikoma, K.; Katsumura, S.
Chem. Commun. 1997, 2243. (c) Mori, H.; Ikoma, K.; Isoe, S.; Kitaura,
K.; Katsumura, S. J. Org. Chem. 1998, 63, 8704. (d) Mori, H.; Matsuo, T.;
Yamashita, K.; Katsumura, S. Tetrahedron Lett. 1999, 40, 6461.
(3) Although the first example of allene formation by the ene reaction
of vinyl hydrogen in trans-â-ionol derivatives has been already reported,
the yields of the allene were less than 10%. (a) Isoe, S.; Hyeon, B. S.;
Ichikawa, H.; Katsumura, S.; Sakan, T. Tetrahedron Lett. 1968, 5561. (b)
Isoe, S.; Katsumura, S.; Hyeon, S. B.; Sakan, T. Tetrahedron Lett. 1971,
1089. (c) Mousseron-Canet, M.; Dalle, J-P.; Mani, J-C. Tetrahedron Lett.
1968, 6037. (d) Foote, C. S.; Brenner, M. Tetrahedron Lett. 1968, 6041.
‡ Mie University.
§ Present address: Industrial Technology Center of Wakayama Prefecture,
Ogura 60, Wakayama, 649-6261, Japan.
(1) (a) Grob, C. A.; Spaar, R. Tetrahedron Lett. 1969, 1439. (b) Grob,
C. A.; Spaar, R. HelV. Chim. Acta 1970, 53, 2119. (c) Grob, C. A.; Pfaendlar,
H. R. HelV. Chim. Acta 1970, 53, 2130. (d) Lamparter, E.; Hanack, M.
Chem. Ber. 1973, 106, 3216. (e) Yates, K.; Rerie, J. J. J. Org. Chem. 1974,
39, 1902. (f) Hanack, M. Acc. Chem. Res. 1976, 9, 364. (g) Rappoport, Z.
Acc. Chem. Res. 1976, 9, 265. (h) Apeloig, Y.; Schleyer, P.; Pople, J. A. J.
Org. Chem. 1977, 42, 3004. (i) Hanack, M.; Sposser, L. J. Am. Chem. Soc.
1978, 100, 7066.
10.1021/jo061092z CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/27/2006
9004
J. Org. Chem. 2006, 71, 9004-9012

Highly ActiVated Vinyl Hydrogen
ing the results of both cis-â-ionol derivatives and acyclic twisted
1,3-dienes made it clear that their inherent reactivity toward
singlet oxygen is nearly equal to or higher than that of the allyl
hydrogen. The molecular mechanics and orbital calculations of
the twisted substrates revealed that the activation of the vinyl
hydrogen is due to the large orbital interaction between the σ*
orbital of the vinyl C-H bond and the π orbital of the double
bond. This unique character during the cationic and concerted
reactions has thus been demonstrated, and these results intro-
duced us to the investigation of the anionic reaction media.
It is well-known that allyl and benzyl hydrogens are more
reactive than vinyl hydrogens, and these sp3 hydrogens can be
gradually abstracted with a strong base.4 Their relatively higher
reactivity is attributable to activation due to orbital interaction
between the σ orbital of the allylic or benzylic C-H bond and
the π orbital of the neighboring double bond and to delocal-
ization of the generated anion into the neighboring double bond.
If we could design a vinylic C-H bond, the σ orbital of which
significantly interacts with the π orbital of the neighboring
double bond, it might be activated equal to the allylic or benzylic
C-H bond, and we might realize a chemoselective vinyl anion
formation rather than the allyl or benzyl one as a result of their
difference in pKa values. Therefore, these hydrogens would be
regarded as more reactive vinyl hydrogens than the allyl or
benzyl hydrogens. Some noticeable examples about the above
reactive vinyl hydrogen have been presented previously.5-8
Thus, the acidity of 1,3-butadiene was investigated by Fourier-
transform ion-cyclotron-resonance mass spectrometer and theo-
retical calculation.5 It was revealed that 2-butadienyl anions are
more stable than 1-butadienyl anions, and the former, which
have two orthogonal π-systems, show additional stabilization
due to charge delocalization. Furthermore, it was reported by
Bierbaum et al. that the vinyl hydrogens of cyclooctatetraene,
in which the double bonds are twisted in relation to each other,
are also activated and the bond strength was much weaker than
that of typical sp2 C-H bond.6
FIGURE 1. Designed styrene derivatives.
activated vinyl hydrogens rather than ally or benzyl hydrogens
in a 1,3-diene system have not been fully investigated, especially
with the discussion of the tendency of the twist.
In a preliminary communication, as a new entry for the unique
character of the twisted 1,3-dienes or styrene derivatives, we
have reported that the novel example of the vinyl hydrogens in
the significantly twisted styrenes are more reactive than the
benzyl hydrogens toward a base.11
In this paper, we describe the full details of the base treatment
of various kinds of twisted styrenes, along with a discussion
on the correlation between the magnitude of the twist and the
reactivity of the vinyl hydrogens. The mechanistic consideration
of the proton abstraction and the formation of the products,
whose vinylic positions were substituted by deuterium or the
triethylsilyl group, is also described.
Results and Discussion
Synthesis and Conformational Analysis of Twisted Styrene
Derivatives. We designed new twisted styrene derivatives 1-6,
based on our previous studies concerning the investigation of
the ene reaction of singlet oxygen (Figure 1).3
The pioneering results concerning the facile vinyl proton
abstraction by a strong base have been reported under specific
circumstances, such as the hydrogen contained in a small ring
system.9 It was concluded that the increase of s character of a
C-H bond in a strained ring system contributes to the ease of
vinyl proton abstraction. Another example, in which the vinyl
hydrogen is located at a seven-membersed ring, was also
reported,10 and the participation of the extra double bond for
the kinetic acidity of the vinyl hydrogen was proposed. Although
a few elegant examples have been demonstrated before,
To efficiently synthesize the wide variety of styrene deriva-
tives, our own Pd-catalyzed coupling method was adopted.9
Although during the synthesis of the acyclic twisted 1,3-dienes
the Pd catalyst worked well to give the corresponding coupling
compounds, the catalyst did not work well for the cross-coupling
between the aryl triflate 8, which was prepared from com-
mercially available 2,6-dimethylphenol 7, and acetylene deriva-
tives. The steric hindrance might be severe around the triflate
moiety. The reaction was investigated under various conditions,
and we finally found that the presence of tetrabutylammonium
iodide was extremely effective for this reaction.12 Thus, the
reaction of the aryltriflate 8 with 2-methyl-3-butyn-2-ol in the
presence of 3 equiv of tetrabutylammonium iodide, a catalytic
amount of PdCl2(PPh3)2, and CuI gave the coupling compound
9 in good yield (Scheme 1). Partial reduction of the acetylene
moiety with Pd-C under a hydrogen atmosphere gave the Z
isomer 1a, and LAH reduction in THF13 gave the E isomer 4a.
The methylation or silylation of the tertiary hydroxy group was
conducted under the usual conditions to afford the corresponding
(4) For example: Cram, D. J. Fundamentals of Carbanion Chemistry;
Academic Press: New York, London, 1965; p 19.
(5) (a) Visser, S. P.; Koning, L. J.; Hart, W. J.; Nibbering, N. M. M.
Recl. TraV. Chim. Pays-Bas 1995, 114, 267.
(6) (a) Kato, S.; Lee, H. S.; Gareyev, R.; Wenthold, P. G.; Lineberger,
W. C.; Depuy, C. H.; Bierbaum, V. M. J. Am. Chem. Soc. 1997, 119, 7863.
(b) Kato, S.; Gareyev, R.; Depuy, C. H.; Bierbaum, V. M. J. Am. Chem.
Soc. 1998, 120, 5033.
(7) The typical reactive vinyl hydrogens at allylic positions can be found
at an allene compound, and a strong base easily abstracted the vinyl protons.
(a) Dongen, J. P. C. M.; Dijkman, H. W. D.; Bie, M. J. A. Recl. TraV.
Chim. Pays-Bas, 1974, 93, 29. (b) Reich, H. J.; Holladay, J. E.; Walker T.
G.; Thompson, J. L. J. Am. Chem. Soc. 1999, 121, 9769.
(8) (a) Levin, G.; Jagur-Grodizinski, J.; Szwarc, M. J. Org. Chem. 1969,
34, 1702. (b) Levin, G.; Ward, T. A.; Szwarc, M. J. Am Chem. Soc. 1974,
96, 3590.
(11) Mori, H.; Matsuo, T.; Yoshioka, Y.; Katsumura, S. Tetrahedron
Lett. 2001, 42, 3093.
(9) (a) Morton, A. A.; Finnegan, R. A. J. Polym. Sci. 1959, 38, 19. (b)
Broaddus, C. D.; Muck, D. L. J. Am. Chem. Soc. 1967, 89, 6533.
(10) Sta¨hle, M.; Lehmann, R.; Kramar, J. Schlosser, M. Chimia 1985,
39, 229.
(12) Powell, N. A.; Rychnovsky, S. D. Tetrahedron Lett. 1996, 37, 7901.
(13) Grant, B.; Djerassi, C. J. Org. Chem. 1974, 39, 968. Doering. W.
E.; Benkhoff, J.; Carleton, P. S.; Pagnotta, M. J. Am. Chem. Soc. 1997,
119, 10947.
J. Org. Chem, Vol. 71, No. 24, 2006 9005

Mori et al.
SCHEME 1 a
a Reagents and conditions: (a) Tf2O, Et3N (99%); (b) 2-methyl-3-butyn-
2-ol, PdCl2(PPh3)2, CuI, Bu4NI, Et2NH (47%); (c) Pd/C, H2 (86%); (d) LAH/
THF (72%); (e) TESCl, DMAP, Et3N (90%); (f) NaH, Bu4NI, MeI (98%);
(g) TESCl, DMAP, Et3N (42%); (h) NaH, Bu4NI, MeI (75%).
FIGURE 2. Electronic spectra of various styrene derivatives.
methyl ether 1b and 4b and silyl ether 1c and 4c, respectively.
The other derivatives 2, 3, 5, and 6 (Figure 1) were also
synthesized in good yields by the Pd-catalyzed cross-coupling
strategy described above from the corresponding iodides,
respectively.
plex15 as a suitable base because of its simplicity of preparation
and sufficient stability. Thus, the reaction was carried out for 1
h at room temperature using 5 equiv of n-BuLi and 2.5 equiv
of TMEDA, and the resulting anion was quenched with D2O.
Since we obtained the twisted styrene derivatives 1-6, next
was the investigation of the magnitude of the twist between
the benzene ring and the double bond of these derivatives based
on both the electronic spectra and molecular orbital calculations.
The electronic spectra were taken in heptane. The maximum
absorption values of all Z isomers 1a-1c were less than 210
nm, and those of the E isomers 4a-c, 5, and 6 clearly appeared
between 230 and 260 nm. The spectrum of 2 showed a broad
absorption from 220-250 nm, and for compound 3 the
maximum absorption of the K-band clearly appeared at 251 nm
(ꢀ ) 13000), as shown in Figure 2. Compared with the spectrum
of styrene, the K-band of which clearly appears at 245 nm, we
easily noted that the Z isomers 1a-1c were definitely twisted
around the C4-C5 single bond. The geometries of the methyl
ethers 1b, 2, 3, 4b, 5, and 6 were optimized at the Hartree-
Fock/6-31G level using the Gaussian 94 program package, and
the dihedral angles between the benzene ring and the double
bond of the Z isomers 1b, 2, and 3 were 85°, 84°, and 53°,
respectively, whereas those of the E isomers 4b, 5, and 6 were
65°, 39°, and 21°, respectively.14
1
The obtained mixture was analyzed by H NMR without any
purification, and the yields were calculated on the basis of a
1
comparison of the integral value of the H NMR spectrum
between the signal of the starting material and that of the
deuterized compound. Treatment of the entirely twisted styrene
1b with the base in hexane produced the E isomer 10, whose
vinylic hydrogen was deuterized in approximately 60% yield,
along with the starting material (Scheme 2). The structure of
the obtained product 10 was confirmed by a comparison with
the independently synthesized compound, which was derived
from 9 by LAH reduction followed by D2O treatment and
methyl ether formation.
The base treatment of the Z silyl ether 1c produced the
unexpected product 11, despite D2O treatment of the reaction
mixture. No deuterium compound was detected by the 1H NMR
spectra (Scheme 2). The detailed analysis of the spectral data
(NMR, MS, IR) strongly suggested that the triethylsilyl group
migrated to the vinylic position to produce 11. Although the
precise structure, in particular, the geometry of the double bond,
could not be elucidated by the spectral data, the crystal structure
of the corresponding chromium tricarbonyl complex 12 was
fortunately determined by X-ray analysis to be the Z form, as
shown in Figure 3. The geometry of the C7-C8 double bond
of 11 was strongly suggested to be the Z form. The reaction
pathway for the formation of the compounds 10 and 11 will be
discussed in detail in the following paragraph.
Vinyl Proton Abstraction of E and Z Isomers of Twisted
Styrene. Among the various kinds of strong bases that can
abstract the proton of low acidic hydrocarbons, we chose the
BuLi/N,N,N′,N′,-tetramethylethylenediamine (TMEDA) com-
(14) Doering. W. E.; Benkhoff, J.; Carleton, P. S.; Pagnotta, M. J. Am.
Chem. Soc. 1997, 119, 10947. A detailed investigation of the conjugation
in substituted styrene was reported by Doering’s group. The dihedral angles
between the benzene ring and a double bond toward various types of styrene
derivatives were shown in his report. In the o-dimethylphenyl styrene
derivatives, they were nearly perpendicular to each other. A study on the
solvolysis of a twisted styrene was reported by Yate and coworkers, and
the o-dimethylphenyl styrene derivatives were adopted as a significantly
twisted substrate.2e
Under the same treatment, the moderately twisted E isomer
4b also gave compound 10 in 60% yield. The vinyl anion
formation of the E isomer would be partly assisted by the
(15) Klein, J.; Medlik-Balan, A. J. Am. Chem. Soc. 1977, 99, 1473.
9006 J. Org. Chem., Vol. 71, No. 24, 2006

Highly ActiVated Vinyl Hydrogen
SCHEME 2 a
same reaction proceeded even at -95 °C to give 10 and 4b in
a relatively lower yield (40% yield in a ratio of one to one),
and the Z isomer deuterized at the C4 vinylic position could
not be detected at all. None of the compounds deuterized at the
benzylic position were again detected by NMR (Scheme 2).
Plausible Reaction Pathway for the Formation of 10 and
11. The mechanistic pathway to the formation of 10 and 11
from the Z isomers 1b and 1c under the strong base treatment
is proposed as shown in Scheme 3. Compounds 1b and 1c
produced the corresponding Z vinyl anion 13, which entirely
isomerized to the E vinyl anion 15 as a result of stabilization
based on the coordination between the generated vinyl lithium
and the allylic oxygen function, then followed by quenching
by D2O (R ) Me) or retro-[1,4]-Brook rearrangement (R )
SiEt3) (Path A). This hypothetical pathway is strongly supported
by the study of Knorr and Panek,17,18 in which the vinyl anion
generated at the R-position of styrene derivatives easily isomer-
izes to give an equilibrium mixture of the corresponding E and
Z isomers. The intramolecular rearrangement of the anion from
the vinylic position to the thermodynamically more stable
benzylic position of the tolylstilbene derivatives was also
extensively investigated by Knorr and co-workers.18 In our
twisted styrene, the rearrangement pathway that arises from the
kinetically generated benzyl anion 14 to the E vinyl anion 15
stablilized by the chelation effect through the Z vinyl anion 13
(Path B) was completely excluded, because no observation of
the deuterized compound at the benzylic position of the twisted
styrene 1b was made even at -95 °C, although 1b produced a
mixture of 10 and 4b (1:1) in 40% yield at -95 °C. In addition,
the benzylic anion, if generated, is not situated close enough to
rearrange to the vinyl position in the significantly twisted styrene
derivatives. These described results clearly demonstrated that
the vinyl proton Ha in 1b or 1c is selectively abstracted by the
base in preference to the benzyl proton Hb.
a Reagents and conditions: (a) n-BuLi (5 equiv), TMEDA (2.5 equiv)/
hexane, rt, 1 h; (b) D2O; (c) LiAlH4 then D2O; (d) NaH, Bu4NI, MeI; (e)
Cr(CO)6/(Bu)2O-THF ) 10:1; (f) t-BuOK (1.0 equiv), n-BuLi (1.0 equiv),
TMEDA (1.0 equiv), hexane-THF ) 3:1, -43 °C, 1 h.
Correlation between the Twist Magnitude and the Reac-
tivity of the Vinyl Hydrogens. We then attempted to treat other
kinds of twisted styrene derivatives 2, 3, 5, and 6 (Figure 1)
with the base at -43 °C. The results of 1b, 2, and 3 are
summarized in Scheme 4. As previously described, the base
treatment of the entirely twisted Z isomer 1b gave compounds
10 (41%) and 4b (14%) along with the starting compound
(42%). In the case of the moderately twisted Z isomers 2 and
3, although vinyl proton abstraction was clearly observed,
benzylic proton abstraction was also observed. Thus, in the
o-methylphenyl styrene derivative 2, compound 16 deuterized
at the vinylic position was obtained as the major product (44%)
along with compound 17 deuterized at the benzylic position
(6%), compound 5 (14%), and the starting material (36%). With
the p-methylphenyl styrene derivative 3, the major reaction was
benzyl proton abstraction, 19 (40%); the vinyl proton abstraction
was also observed, 18 (30%). Thus the tendency of the proton
abstraction varied from the vinyl proton to the benzyl proton
in the three types of twisted styrene derivatives 1b, 2, and 3.
As previously described, the electronic spectra (Figure 2) and
the molecular orbital calculations of the Z isomers of styrene
FIGURE 3. ORTEP drawing of compound 12.
coordination between the base complex and the methoxy group.
Unfortunately, no proton abstraction or silyl ether migration of
the E silyl ether 4c was observed, probably due to the severe
steric hindrance around the vinyl hydogen Ha of 4c. For all of
the E and Z isomers, none of the compounds deuterated at the
benzylic methyl position were observed after this base treatment
(Scheme 2).
We then tried to treat the Z isomer 1b with a stronger base,
t-BuOK/BuLi/TMEDA,16 which can abstract a vinyl proton at
low temperature and can be easily prepared from the corre-
sponding commercially available reagents. Treatment of the Z
isomer 1b with the base in hexane and THF (3:1) at -43 °C
for 1 h followed by D2O quenching gave the deuterized com-
pound 10 (41%) and the protonated E isomer 4b (14%). The
(17) (a) Panek, E. J.; Neff, B. L.; Chu, H.; Panek, M. G. J. Am. Chem.
Soc. 1975, 97, 3996. (b) Zwaifel, G.; Rajagopalan, S. J. Am. Chem. Soc.
1985, 107, 700.
(18) (a) Knorr, R.; Lattke, E. Tetrahedron Lett. 1977, 45, 3969. (b) Knorr,
R.; Lattka, E.; Rapple, E. Chem. Ber. 1981, 114, 1581. (c) Knorr, R.; Lattke,
E.; Ruf, F.; Reissig, H.-U. Chem. Ber. 1981, 114, 1592. (d) Lattke, E.;
Knorr, R. Chem. Ber. 1981, 114, 1600. (e) Knorr, R.; Lattke, E. Chem.
Ber. 1981, 114, 2116. (f) Knorr, R.; Roman, T. Angew. Chem. 1984, 96,
349.
(16) (a) Schlosser, M.; Strunk, S. Tetrahedron Lett. 1984, 25, 741. (b)
Schlosser M. Pure Appl. Chem. 1988, 60, 1627. (c) Brandsma, L.;
Verkruijsse, H. D.; Schade, D.; Schleyer, P. R. J. Chem. Soc., Chem.
Commun. 1986, 260.
J. Org. Chem, Vol. 71, No. 24, 2006 9007

Mori et al.
SCHEME 3
SCHEME 4 a
a Reagents and conditions: (a) t-BuOK (1.0 equiv), n-BuLi (1.0 equiv), TMEDA (1.0 equiv), hexane-THF ) 3:1, -43 °C, 1 h, then D2O.
SCHEME 5 a
derivatives 1b, 2, and 3 indicated that the tendency of the twist
of these derivatives 1b, 2, and 3 arranges in this order. It is
easily noticed that the proportion between vinyl proton abstrac-
tion and benzyl proton abstraction shifted to the latter with
diminution of the twist. The results obtained here clearly showed
a correlation between the reactivity of the vinyl hydrogen at
the C4 position and the magnitude of the twist at the central
single bond. From the view point of the steric effect, the
surroundings of the vinyl hydrogen are croweded by an o-methyl
group at the benzene ring. Although the steric hindrance toward
the attack of the strong base would be severest in the o-
dimethylstyrene derivatives 1b, the vinyl proton of 1b was
mainly abstracted. This result is understandable by considering
the sufficient activation due to the novel orbital interaction
between the σ* orbital of the vinyl hydrogen and the π orbital
of the benzene ring resulting from the twist. The moderate vinyl
proton abstraction was observed in the other styrene derivatives
2 and 3, despite the low magnitude of the twist. The loose steric
hindrance around the vinyl hydrogen would contribute to the
facile access of the strong base to the vinyl hydrogen. On the
contrary, the treatment of the E isomers 4b, 5, and 6 with 2.5
equiv of the same base at -43 °C chemoselectively produced
the compound deuterized at the benzylic position to give 20-
22 in excellent yield (Scheme 5). In these cases, the surroundings
of the vinyl hydrogen are more crowded than those of Z isomers
and it would be difficult for the bulky base complex to access
a Reagents and conditions: (a) t-BuOK (2.5 equiv), n-BuLi (2.5 equiv),
TMEDA (2.5 equiv), hexane-THF ) 3:1, -43 °C, 1 h, then D2O.
the vinyl hydrogen. Furthermore, the coordination of the base
complex with the methoxy group would not be effective to
abstract the vinyl hydrogen, in addition to the low activation of
the vinyl hydrogen due to the small orbital interaction. None
of the possibilities concerning the intramolecular rearrangement
of the anion from the benzylic position to the vinylic position
are again proposed. The obtained results strongly suggested that
the abstraction of the vinyl proton was kinetically more favorable
than that of the benzylic proton, and the produced vinyl anion
was easily isomerized into the thermodynamically favorable E
isomer. Thus, we found a novel example of a vinyl hydrogen
more reactive than a benzyl hydrogen.
Trapping the Vinyl Anion with Aldehydes. Next, to
examine the potential of the generated vinyl anions, we tried to
9008 J. Org. Chem., Vol. 71, No. 24, 2006

Highly ActiVated Vinyl Hydrogen
SCHEME 6 a
mL) were added triethylamine (10.5 mL, 75 mmol) and trifluo-
romethanesulfonic anhydride (10 mL, 58 mmol) at -78 °C, and
the reaction mixture was gradually warmed to room temperature.
After being stirred at the same temperature for 25.5 h, the reaction
mixture was poured into saturated aqueous NaHCO3 solution, and
the resulting mixture was extracted with dichloromethane. The
organic layers were combined, washed with brine, dried over
MgSO4, filtered, and concentrated in vacuo to give crude products.
Column chromatography on silca gel (3% triethylamine in hexane)
gave 8 (12.4 g, 99%): IR (neat, cm-1) 2928, 1462, 1408, 1380,
a Reagents and conditions: (a) t-BuOK, n-BuLi, TMEDA, hexane-THF
) 3:1, -43 °C, 1 h, then LiBr (9 equiv), RCHO.
1
1210, 1144; H NMR (400 MHz, CDCl3) δ 7.16-7.11 (3H, m),
2.39 (6H, s); 13C NMR (100 MHz, CDCl3) δ 146.9, 131.5, 129.9,
128.0, 120.2, 117.0, 17.1.; ΕI HRMS m/e calcd for C9H9F3O3S
(M+) 254.0225, found 254.0223.
2-Methyl-4-(2,6-dimethylphenyl)-3-butyn-2-ol (9). To a solu-
tion of 8 (3.0 g, 11.8 mmol), diethylamine (25 mL, 242 mmol),
and tetra-n-butylammonium iodide (13.0 g, 35.4 mmol) in DMF
(22 mL) were added dichlorobis(triphenylphosphine) palladium (331
mg, 0.472 mmol) and copper iodide (270 mg, 1.42 mmol). The
reaction mixture was stirred for 5 min at room temperature, and
2-methyl-3-butyn-2-ol (2.3 mL, 24 mmol) was added at the same
temperature. After being stirred at 70 °C for 3 h, the mixture was
diluted with saturated NH4Cl solution and extracted with ether. The
organic layers were combined, washed with brine, dried over
MgSO4, filtered, and concentrated in vacuo to give crude products.
Column chromatography on silica gel (3% ethyl acetate in hexane)
gave 9 (1.05 g, 47%): mp 64-69 °C; IR (KBr disk, cm-1) 3328,
2980, 1576, 1468, 1376, 1246, 1160; 1H NMR (400 MHz, CDCl3)
δ 7.10-7.01 (3H, m), 2.41 (6H, s), 1.66 (6H, s); 13C NMR (100
MHz, CDCl3) δ 140.2, 127.7, 126.6, 122.3, 102.5, 79.7, 65.9, 31.7,
21.0; ΕI HRMS m/e calcd for C13H16O (M+) 188.1201, found
188.1202.
FIGURE 4. Orbital interaction of a twisted styrene derivative.
trap the vinyl anion using some aldehydes as an electrophile
(Scheme 6). The vinyl anion, which was produced from 1b
under the same conditions, was treated with 2 equiv of
benzaldehyde and n-propyl aldehyde in the presence of LiBr
(9 equiv) to yield the secondary alcohols 23 and 24 in 53%
and 45% yields, respectively, along with the corresponding E
isomer 4b in 7% and 16% yields in addition to 17-18% of the
starting material, respectively. In these cases, the absence of
LiBr did not produce the addition products. Thus, no adducts
at the benzylic position were again admitted. Attempts to trap
with other electrophiles, such as MeI and TMSCl, did not show
any clear results.
Orbital Interaction in a Twisted Styrene. The obtained
results described above clearly showed the remarkable activation
of the vinyl proton in twisted styrenes, and these phenomena
could be rationalized by considering orbital interaction due to
the twist around the single bond of the styrene derivatives. Thus,
in a significantly twisted styrene, the σ orbital of the vinyl C-H
bond effectively interacts with the π* orbital of another double
bond as shown in Figure 4 (A). In addition, the stabilizing effect
by the development of the vinyl anion to the neighboring π*
orbital (B) should be also considered. Since it is well-known
that the acidity of the hydrogen attaching at an sp2 carbon is
higher than that attaching at a sp3 carbon,19 the combination of
this well-known phenomenon with the present novel σ-π orbital
interaction made it possible to realize the presence of a more
acidic vinyl hydrogen rather than an allyl hydrogen. In other
words, the vinyl hydrogen of the significantly twisted 1,3-diene
derivatives is the allyl hydrogen attaching at the sp2 carbon.
The present results of the significantly twisted styrenes are a
new entry for the unique character of the twisted 1,3-unsaturated
compounds and novel examples of the highly activated vinyl
hydrogen.
(3Z)-2-Methyl-4-(2,6-dimethylphenyl)-3-buten-2-ol (1a). To a
solution of 9 (1.05 g, 5.58 mmol) in hexane (40 mL) was added
Pd-C (260 mg), and the mixture was stirred at room temperature
for 1 h under hydrogen atmosphere. The reaction mixture was
filtered, and the filtrate was concentrated in vacuo to give crude
products. Column chromatography on silica gel (10% ethyl acetate
in hexane) gave 1a (913 mg, 86%): mp 40-41.5 °C; IR (KBr disk,
1
cm-1) 3292, 2972, 1464; H NMR (400 MHz, CDCl3) δ 7.07-
7.00 (3H, m),), 6.22 (1H, d, J ) 12.4 Hz), 5.77 (1H, d, J ) 12.4
Hz), 2.23 (6H, s), 1.23 (6H, s); 13C NMR (100 MHz, CDCl3) δ
138.7, 136.5, 135.6, 127.1, 126.9, 124.4, 72.6, 29.8, 20.9.
(3Z)-2-Methoxy-2-methyl-4-(2,6-dimethylphenyl)-3-butene (1b).
To a solution of 1a (500 mg, 2.6 mmol) in THF (15 mL) were
added sodium hydride (150 mg, 3.7 mmol) and tetra-n-butylam-
monium iodide (1.45 g, 3.9 mmol). The reaction mixture was stirred
at room temperature for 3 h, and methyl iodide (0.3 mL, 4.8 mmol)
was added. After being stirred at room temperature for 14 h, the
mixture was diluted with saturated aqueous NH4Cl solution and
extracted with ethyl acetate. The organic layers were combined,
washed with brine, dried over MgSO4, filtered, and concentrated
in vacuo to give crude products. Column chromatography on silica
gel (5% ethyl acetate in hexane) gave 1b (524 mg, 98%): IR (neat,
cm-1) 2980, 1468, 1376, 1166, 1078; 1H NMR (400 MHz, CDCl3)
δ 7.06-6.98 (3H, m), 6.41 (1H, d, J ) 12.8 Hz), 5.72 (1H, d, J )
12.8 Hz), 3.22 (3H, s), 2.26 (6H, s), 1.03 (6H, s); 13C NMR (100
MHz, CDCl3) δ 137.8, 137.3, 135.2, 128.5, 126.9, 126.5, 76.2, 50.6,
25.4, 20.7; EI HRMS m/e calcd for C14H20O (M+) 204.1514, found
204.1513.
(3Z)-2-Methyl-4-(2,6-dimethylphenyl)-2-triethylsiloxy-3-
butene (1c). To a solution of 1a (2.23 g, 12 mmol), 4-(dimethy-
lamino)pyridine (400 mg, 3.3 mmol), and triethylamine (5.6 mL,
40 mmol) in DMF (80 mL) was added triethylsilyl chloride (5.8
mL, 35 mmol) at 0 °C, and the reaction mixture was gradually
warmed to room temperature. After being stirred at the same
temperature for 5 h, the reaction mixture was diluted with cold
water and then extracted with ethyl acetate. The organic layers were
combined, neutralized by saturated aqueous NaHCO3 solution,
Experimental Section
2,6-Dimethylphenyltrifluoromethanesulfonate (8). To a solu-
tion of 2,6-dimethylphenol (6.0 g, 49 mmol) in chloroform (100
(19) We also checked the coupling constant of C4-H4 in order to
examine the s character of the most “twisted” 1,3-diene 1a and found that
it was the normal value of an sp2 carbon (JC-H ) 157.5 Hz).
J. Org. Chem, Vol. 71, No. 24, 2006 9009

Mori et al.
washed with brine, dried over MgSO4, filtered, and concentrated
in vacuo to give crude products. Column chromatography on silica
gel (3% triethylamine in hexane) gave a colorless oil. In order to
remove hexaethyldisiloxane, the oil was heated in vacuo (1-2
mmHg) at 80 °C for 3 days to give pure silyl ether 1c (3.24 g,
and column chromatography (9% ethyl acetate in hexane), the
corresponding Z olefin (582 mg, 72%).
(3Z)-2-methyl-4-(4-methylphenyl)-3-buten-2-ol: IR (neat, cm-1
)
1
3410, 2975, 2928, 1613, 1510, 1462, 1632, 1144, 820; H NMR
(400 MHz, CDCl3) δ 7.25 (2H, d, J ) 7.8 Hz), 7.12 (2H, d, J )
7.8 Hz), 6.42 (1H, d, J ) 12.7 Hz), 5.71 (1H, d, J ) 12.7 Hz),
2.33 (3H, s), 1.68 (1H, s), 1.36 (6H, s); 13C NMR (100 MHz,
CDCl3) δ 138.9, 136.7, 134.4, 128.9, 128.7, 127.8, 72.0, 31.1, 21.1.
The Z olefin (582 mg, 3.3 mmol), sodium hydride (ca.60% in
oil, 190 mg, 4.95 mmol), tetra-n-butylammonium iodide (1.83 g,
4.95 mmol), and methyl iodide (0.41 mL, 6.6 mmol) in THF (20
mL) gave, after the usual workup and column chromatography
(from 1% to 4% ethyl acetate in hexane), the titled compound 3
(571 mg, 91%): IR (neat, cm-1) 2976, 2934, 2824, 1628, 1613,
1510, 1464, 1375, 1360, 1171, 1076, 833; UV (heptane) λmax 251.0
nm (ꢀ ) 12989); 1H NMR (400 MHz, CDCl3) δ 7.37 (2H, d, J )
8.05 Hz), 7.11 (2H, d, J ) 7.81 Hz), 6.48 (1H, d, J ) 12.9 Hz),
5.49 (1H, d, J ) 12.9 Hz), 3.11 (3H, s), 2.34 (3H, s), 1.31 (6H, s);
13C NMR (100 MHz, CDCl3) δ 136.6, 135.3, 134.2, 131.0, 129.5,
128.5, 75.5, 50.2, 27.3, 21.2.; EI HRMS m/e calcd for C13H18O
(M+) 190.1358, found 190.1353.
1
90%). : IR (neat, cm-1) 2956, 1464, 1144, 1040; H NMR (400
MHz, CDCl3) δ 7.03-6.96 (3H, m), 6.10 (1H, d, J ) 12.8 Hz),
5.73 (1H, d, J ) 12.8 Hz), 2.24 (6H, s), 1.15 (6H, s), 0.88 (9H, t,
J ) 8.0 Hz), 0.45 (6H, q, J ) 8.0 Hz); 13C NMR (100 MHz, CDCl3)
δ 140.2, 138.1, 135.2, 126.7, 126.0, 124.0, 74.2, 30.0, 20.9, 7.0,
6.4; EI HRMS m/e calcd for C19H32O1Si1 (M+) 304.2222, found
304.2224.
(3Z)-2-Methoxy-2-µethyl-4-(2-methylphenyl)-3-butene (2). Fol-
lowing the procedure of preparation of 1a, 2-iodotoluene (2.00 g,
9.17 mmol), 2-mehtyl-3-butyn-2-ol (1.8 mL, 18.4 mmol), diethy-
lamine (28.0 mL, 271 mmol), tetra-n-butylammonium iodide (10.2
g, 27.5 mmol), dichlorobis(triphenylphosphine)palladium (258 mg,
0.367 mmol), and copper iodide (210 mg, 1.10 mol) in DMF (25
mL) for 2.5 h gave, after the usual workup and column chroma-
tography (11% ethyl acetate in hexane), the corresponding coupling
compound (1.59 g, 99%).
(3E)-2-Methyl-4-(2,6-dimethylphenyl)-3-buten-2-ol (4a). To a
suspension of lithium aluminum hydride (420 mg, 11 mmol) in
THF (30 mL) was added a THF (10 mL) solution of 9 (2.0 g, 10.6
mmol) at 0 °C. After the reaction mixture was stirred under reflux
for 3.75 h, excess lithium aluminum hydride was carefully
decomposed by addition of water under ice-cooling. The mixture
was filtered, and the filtrate was extracted with ethyl acetate. The
organic layers were combined, washed with brine, dried over
MgSO4, filtered, and concentrated in vacuo to give crude products.
Column chromatography on silica gel (from 9 to 17% ethyl acetate
in hexane) gave the title compound (1.45 g, 72%): mp 57-58 °C;
IR (KBr disk, cm-1) 3352, 2972, 1468, 1362, 1146; UV (heptane)
2-Methyl-4-(2-methylphenyl)-3-butyn-2-ol: mp 32-33 °C; IR
(KBr disk, cm-1) 3227, 2984, 2930, 2866, 2224, 1952, 1919, 1883,
1
1838, 1804, 1599, 1485, 1454, 1377, 1362, 1200, 1157, 754; H
NMR (400 MHz, CDCl3) δ 7.39-7.37 (1H, m), 7.23-7.10 (3H,
m), 2.41 (3H, s), 2.10 (1H, s), 1.64 (6H, s); 13C NMR (100 MHz,
CDCl3) δ 140.1, 131.8, 129.4, 128.3, 125.5, 122.4, 97.9, 81.0, 65.7,
31.6, 20.6.
The coupling compound (925 mg, 5.31 mmol) and Pd-C (231
mg) under hydrogen atmosphere in hexane (50 mL) for 30 min
gave, after the usual workup and column chromatography (9% ethyl
acetate in hexane), the corresponding Z olefin (422 mg, 45%).
(3Z)-2-Methyl-4-(2-methylphenyl)-3-buten-2-ol: IR (neat, cm-1
)
1
λmax 237.4 nm (ꢀ ) 7910); H NMR (400 MHz, CDCl3) δ 7.03
3385, 2973, 2930, 2874, 1917, 1811, 1642, 1601, 1485, 1460, 1375,
1362, 1221, 1144, 754; 1H NMR (400 MHz, CDCl3) δ 7.20-7.12
(4H, m), 6.38 (1H, d, J ) 12.4 Hz), 5.80 (1H, d, J ) 12.4 Hz),
2.27 (3H, s), 1.56 (1H, s), 1.29 (6H, s); 13C NMR (100 MHz,
CDCl3) δ 139.2, 137.1, 136.03, 129.8, 128.7, 127.3, 126.5, 125.4,
72.3, 30.9, 20.2.
(3H, brs), 6.52 (1H, d, J ) 16.4 Hz), 5.83 (1H, d, J ) 16.4 Hz),
2.28 (6H, s), 1.44 (6H, s); 13C NMR (100 MHz, CDCl3) δ 142.7,
136.7, 135.8, 127.6, 126.4, 123.7, 71.2, 29.90, 20.8.
(3E)-1-Methoxy-2-methyl-4-(2,6-dimethylphenyl)-3-butene (4b).
To a solution of (3E)-2-mehtyl-4-(2,6-dimethylphenyl)-3-buten-2-
ol 4a (700 mg, 3.7 mmol) in THF (21 mL) was added sodium
hydride (210 mg, 5.3 mmol) and tetra-n-butylammonium iodide
(2.03 g, 5.5 mmol). The reaction mixture was stirred at room
temperature for 3 h, and methyl iodide (0.42 mmol, 6.7 mmol) was
added. After being stirred at room temperature for 1 h, the mixture
was diluted with saturated aqueous NH4Cl solution and extracted
with ethyl acetate. The organic layers were combined, washed with
brine, dried over MgSO4, filtered, and concentrated in vacuo to
give crude products. Column chromatography on silica gel (5%
The Z olefin (422 mg, 2.39 mmol), sodium hydride (ca. 60% in
oil, 144 mg, 3.59 mmol), tetra-n-butylammonium iodide (1.33 g,
3.59 mmol), and methyl iodide (0.3 mL, 4.79 mmol) gave, after
the usual workup and column chromatography (from 1% to 4%
ethyl acetate in hexane), the titled compound 2 (417 mg, 91%):
IR (neat, cm-1) 2976, 2934, 2822, 1601, 1485, 1460, 1373, 1362,
1
1171, 1076, 741; H NMR (400 MHz, CDCl3) δ 7.19-7.10 (4H,
m), 6.52 (1H, d, J ) 12.7 Hz), 5.68 (1H, d, J ) 12.7 Hz), 3.15
(3H, s), 2.26 (3H, s), 1.15 (6H, s); 13C NMR (100 MHz, CDCl3) δ
137.4, 137.2, 135.5, 129.7, 129.3, 129.1, 127.0, 125.1, 76.0, 50.4,
26.9, 20.1.
ethyl acetate in hexane) gave 4b (569 mg, 75%): IR (neat, cm-1
)
2976, 1470, 1170, 1076; UV (heptane) λmax 237.6 nm (ꢀ ) 8380);
1H NMR (400 MHz, CDCl3) δ 7.05 (3H, m), 6.45 (1H, d, J )
16.8 Hz), 5.67 (1H, d, J ) 16.8 Hz), 3.27 (3H, s), 2.30 (6H, s),
1.40 (6H, s); 13C NMR (100 MHz, CDCl3) δ 140.2, 136.9, 135.8,
127.7, 126.9, 126.5, 75.4, 50.7, 26.0, 20.9; EI HRMS m/e calcd
for C14H20O (M+) 204.1514, found 204.1513.
(3Z)-2-Μethoxy-2-methyl-4-(4-methylphenyl)-3-butene (3).
Following the procedure for the preparation of 1a, 4-iodotoluene
(1.00 g, 4.59 mmol), 2-methyl-3-butyn-2-ol (0.89 mL, 9.17 mmol),
diethylamine (14.0 mL, 135 mmol), tetra-n-butylammonium iodide
(5.08 g, 13.8 mmol), dichlorobis(triphenylphosphine)palladium (129
mg, 0.184 mmol), and copper iodide (105 mg, 0.55 mol) in DMF
(25 mL) for 2.5 h gave, after the usual workup and column
chromatography (17% ethyl acetate in hexane), the corresponding
coupling compound (1.59 g, 99%).
(3E)-2-Methyl-4-(2,6-dimethylphenyl)-2-triethylsiloxy-3-
butene (4c). To a solution of 4a (405 mg, 1.9 mmol), 4-(dimethy-
lamino)pyridine (70 mg, 0.57 mmol), and triethylamine (0.96 mL,
6.9 mmol) in DMF (10 mL) was added triethylsilyl chloride (0.96
mL, 5.7 mmol) at 0 °C, and the reaction mixture was gradually
warmed to room temperature. After being stirred at the same
temperature for 6 h, the reaction mixture was diluted with cold
water and extracted with ether. The organic layers were combined,
neutralized by saturated aqueous NaHCO3 solution, washed with
brine, dried over MgSO4, filtered, and concentrated in vacuo to
give crude products. Column chromatography on silica gel (3%
2-Methyl-4-(4-methylphenyl)-3-butyn-2-ol: mp 47 °C; IR (KBr
disk, cm-1) 3316, 2986, 2926, 2866, 2232, 1912, 1657, 1510, 1439,
1
1375, 1362, 1215, 1165, 1140, 818; H NMR (400 MHz, CDCl3)
δ 7.30 (2H, m), 7.10 (2H, m), 2.33 (3H, s), 2.15 (1H, s), 1.61 (6H,
s); 13C NMR (100 MHz, CDCl3) δ 138.3, 131.5, 129.0, 119.6, 93.0,
82.2, 65.6, 31.5, 21.4.
The coupling compound (800 mg, 4.59 mmol), quinoline (125
µL, 0.00106 mmol), and Pd-C (200 mg) under hydrogen atmo-
sphere in hexane (50 mL) for 30 min gave, after the usual workup
triethylamine in hexane) gave 4c (250 mg, 42%): IR (neat, cm-1
)
2960, 1466, 1236, 1044; UV λmax. (heptane); 237.4 nm (ꢀ ) 8950);
1H NMR (400 MHz, CDCl3) δ 7.03 (3H, brs), 6.50 (1H, d, J )
9010 J. Org. Chem., Vol. 71, No. 24, 2006

Highly ActiVated Vinyl Hydrogen
16.3 Hz), 5.77 (1H, d, J ) 16.3 Hz), 2.29 (6H, s), 1.42 (6H, s),
0.97 (9H, t, J ) 8.3 Hz), 0.62 (6H, q, J ) 8.1 Hz); 13C NMR (100
MHz, CDCl3) δ 143.6, 137.2, 136.0, 127.6, 128.2, 123.1, 73.4, 30.7,
20.9, 7.1, 6.8; EI HRMS m/e calcd for C19H32O1Si1 (M+) 304.2222,
found 304.2207.
(3E)-2-Methoxy-2-methyl-4-(2-methylphenyl)-3-butene (5).
Following the procedure of preparation of 4a, 2-methyl-4-(2-
methylphenyl)-3-butyn-2-ol (200 mg, 1.15 mmol) and lithium
aluminum hydride (44 mg, 1.15 mol) in THF (4.4 mL) gave, after
the usual workup and column chromatography (17% ethyl acetate
in hexane), the corresponding E olefin(188 mg, 93%).
2-Methyl-4-(2,6-dimethylphenyl)-4-triethylsilyl-3-buten-2-ol
(11). To a solution of n-butyllithium (1.6 M solution in hexane,
1.0 mL, 1.6 mmol) was added tetramethylethylenediamine (TME-
DA) (0.12 mL, 0.80 mmol) at 0 °C. A hexane (1 mL) solution of
1c (100 mg, 0.33 mmol) was added drop by drop at 0 °C, and the
reaction mixture was stirred at room temperature overnight. The
reaction was quenched by H2O (0.5 mL), and the mixture was stirred
at room temperature for 15 min, poured into saturated aqueous NH4-
Cl solution, and then extracted with ethyl acetate. The organic layers
were combined, washed with brine, dried over MgSO4, filtered,
and concentrated in vacuo to give crude products. Column
chromatography on silica gel gave 11 (76 mg, 76%): IR (neat,
(3E)-2-Methyl-4-(2-methylphenyl)-3-buten-2-ol: IR (neat, cm-1)
3366, 2973, 2928, 1806, 1603, 1487, 1460, 1375, 1148, 968, 750;
1H NMR (400 MHz, CDCl3) δ 7.44-7.40 (1H, m), 7.18-7.13 (3H,
m), 6.80 (1H, d, J ) 16.1 Hz), 6.23 (1H, d, J ) 15.9 Hz), 2.35
(3H, s), 1.61 (1H, s), 1.43 (6H, s); 13C NMR (100 MHz, CDCl3) δ
139.0, 136.0, 135.5, 130.2, 127.3, 126.1, 125.6, 124.1, 71.2, 30.0,
19.8.
1
cm-1) 3596, 3460, 2960, 1464, 1368, 1238, 1210; H NMR (400
MHz, CDCl3) δ 6.97 (3H, brs), 5.85 (1H, s), 2.15 (6H, s), 1.37
(6H, s), 0.88 (9H, t, J ) 7.2 Hz), 0.68 (6H, q, J ) 8.0 Hz); 13C
NMR (100 MHz, CDCl3) δ 151.7, 146.6, 137.4, 134.6, 127.1, 125.0,
72.6, 30.7, 21.3, 8.4, 7.1; EI HRMS m/e calcd for C19H32O1Si1 (M
- H)- 303.2136, found 303.2139.
Tricarbonyl-{2,6-dimethyl-1-(2-hydroxy-2-methyl-4-triethyl-
silyl-3-but-4-enyl)}benzene Chromium (12). To a solution of 11
(300 mg, 0.98 mmol) in dibutyl ether (12 mL) and THF (1.2 mL)
was added chromium hexacarbonyl (306 mg, 1.39 mmol). After
being stirred at 140 °C for 16 h, the reaction mixture was filtered
and concentrated in vacuo to give crude products. Recrystalization
of crude solid (471 mg) from hexane gave yellow crystal 12 (288
mg, 67%). The product contained very small amounts of impurities
derived from the substrate 11: mp 149.5-151.5 °C; IR (KBr disk,
The E olefin (1.35 g, 7.68 mmol), sodium hydride (ca.60% in
oil, 441 mg, 11.5 mmol), tetra-n-butylammonium iodide (4.25 g,
11.5 mmol), and methyl iodide (0.96 mL, 15.4 mmol) in THF (46
mL) gave, after the usual workup and column chromatography
(from 1% to 4% ethyl acetate in hexane), the title compound 5
(1.41 g, 96%): IR (neat, cm-1) 2976, 2934, 2824, 1912, 1806, 1603,
1487, 1460, 1377, 1362, 1169, 1076, 974, 748; UV λmax (heptane)
247.8 nm (ꢀ ) 13776), 207.0 nm (ꢀ ) 23472); 1H NMR (400 MHz,
CDCl3) δ 7.46-7.42 (1H, m), 7.19-7.11 (3H, m), 6.71 (1H, d, J
) 16.1 Hz), 6.06 (1H, d, J ) 16.1 Hz), 3.23 (3H, s), 2.36 (3H, s),
1.39 (6H, s); 13C NMR (100 MHz, CDCl3) δ 136.6, 136.1, 135.4,
130.2, 127.4, 127.0, 126.0, 125.6, 75.2, 50.5, 26.0, 19.8; EI HRMS
m/e calcd for C13Η18O (M+) 190.1358, found 190.1366.
(3Z)-2-Μethoxy-2-methyl-4-(4-methylphenyl)-3-butene (6).
Following the procedure of preparation of 4a, 2-Methyl-4-(4-
methylphenyl)-3-butyn-2-ol (100 mg, 0.57mmol) and lithium
aluminum hydride (22 mg, 0.57 mol) in THF(2.2 mL) gave, after
the usual workup and column chromatography (9% ethyl acetate
in hexane), the corresponding E olefin(86 mg, 85%).
1
cm-1) 3500, 2960, 1960, 1872, 1464, 1382; H NMR (400 MHz,
CDCl3) δ 6.39 (1H, s), 5.52 (1H, t, J ) 6.3 Hz), 4.90 (2H, d, J )
6.3 Hz), 2.15 (small impurity), 2.07 (6H, s), 1.44 (6H, s), 1.26 (small
impurity), 1.38 (small impurity), 0.91 (9H, t, J ) 7.8 Hz), 0.67
(6H, q, J ) 7.8 Hz) 0.51-0.54 (small impurity); 13C NMR (100
MHz, CDCl3) δ 234.4, 159.8, 130.8, 127.1, 126.4, 110.9, 96.6, 88.2,
72.4, 30.7 (small impurity) 30.6, 29.7 (small impurity), 20.5, 8.4,
8.3 (small impurity) 7.5, 7.2-6.4 (small impurity). The chemical
structure of 12 was also identified by X-ray crystallographic analysis
of a small amount of the purified crystal.
(3E)-2-Methyl-4-(4-methylphenyl)-3-buten-2-ol: mp 69 °C; IR
General Procedure for the Treatment with t-BuOK/n-BuLi/
TMEDA. To a suspension of 1 equiv of t-BuOK in hexane (1 mL)
was added 1 equiv of n-butyllithium (1.6 M solution in hexane) at
0 °C. After the reaction mixture was stirred at 0 °C for 5 min, 1
equiv of TMEDA was added at -43 °C. The mixture was stirred
at -43 °C for 5 min, and a solution of the substrate (1a-c, 0.2-
0.5 mmol) in hexane (0.5 mL) and THF (0.5 mL) was added at
-43 or -95 °C. After the reaction mixture was stirred at the same
temperature for 1 h, the reaction was quenched with D2O (0.5 mL).
The mixture was stirred for 10 min at the same temperature and
for 5 min at 0 °C, poured into saturated aqueous NH4Cl solution,
and then extracted with ethyl acetate. The organic layers were
combined, washed with brine, dried over MgSO4, filtered, and
concentrated in vacuo to give crude products. The NMR measure-
ment of the crude products was carried out without any purification.
Reaction with an Aldehyde. (2Z)-4-Methoxy-4-methyl-2-(2,6-
dimethylphenyl)-1-phenyl-2-penten-1-ol (23). To a suspension of
t-BuOK (82 mg, 0.73 mmol) in hexane (1 mL) was added
n-butyllithium (1.6 M solution in hexane, 0.46 mL, 0.73 mmol) at
0 °C. After the reaction mixture was stirred at 0 °C for 5 min,
TMEDA (0.11 mL, 0.73 mmol) was added at -43 °C. The mixture
was stirred at -43 °C for 5 min, and a solution of 1b (100 mg,
0.49 mmol) in hexane (0.5 mL) and THF (0.5 mL) was added at
-43 °C. After the reaction mixture was stirred at the same
temperature for 1 h, lithium bromide (383 mg, 4.41 mmol) and
then benzaldehyde (0.1 mL, 0.98 mmol) were added. The reaction
mixture was stirred for 40 min at -43 °C and for 35 min at room
temperature, poured into saturated aqueous NH4Cl solution, and
then extracted with ethyl acetate. The organic layers were combined,
washed with brine, dried over MgSO4, filtered, and concentrated
in vacuo to give crude products. Column chromatography (6% ethyl
acetate in hexane) on silica gel gave the title compound 23 (80
(KBr disk, cm-1) 3287, 2980, 2928, 1906, 1611, 1514, 1445, 1377,
1
1362, 1206, 1148, 978, 804; H NMR (400 MHz, CDCl3) δ 7.27
(2H, dt, J ) 8.1, 2.0 Hz), 7.12 (2H, d, J ) 8.1 Hz), 6.55 (1H, d,
J ) 16.1 Hz), 6.30 (1H, d, J ) 16.1 Hz), 2.33 (3H, s), 1.59 (1H,
s), 1.41 (6H, s); 13C NMR (100 MHz, CDCl3) δ 137.2, 136.5, 134.1,
129.2, 126.3, 126.2, 71.0, 29.9, 21.1.
The E olefin (553 mg, 3.14 mmol), sodium hydride (ca.60% in
oil, 180 mg, 4.71 mmol), tetra-n-butylammonium iodide (1.74 g,
4.71 mmol), and methyl iodide (0.39 mL, 6.27 mmol) in THF (19
mL) gave, after the usual workup and column chromatography
(from 1% to 4% ethyl acetate in hexane), the title compound 6
(537 mg, 96%): IR (neat, cm-1) 2976, 2934, 2824, 1628, 1613,
1510, 1464, 1375, 1360, 1171, 1076, 833; UV (heptane) λmax 251.0
nm (ꢀ ) 12989); 1H NMR (400 MHz, CDCl3) δ 7.30 (2H, d, J )
8.1 Hz), 7.13 (2H, d, J ) 7.8 Hz), 6.46 (1H, d, J ) 16.4 Hz), 6.14
(1H, d, J ) 16.4 Hz), 3.20 (3H, s), 2.34 (3H, s), 1.37 (6H, s); 13C
NMR (100 MHz, CDCl3) δ 137.3, 134.1, 129.2 129.0, 126.2, 75.1,
50.5, 25.9, 21.1; EI HRMS m/e calcd for C13Η18O (M+) 190.1358,
found 190.1380.
General Procedure for the Treatment with n-BuLi/TMEDA.
To a solution of 5 equiv of n-butyllithium (1.6 M solution in hexane)
was added 2.5 equiv of TMEDA at 0 °C, and then a hexane solution
(1.0 mL) of 1a-c, 4a-c (0.2-0.5 mmol) was added drop by drop.
After the reaction mixture was stirred for 1 h at room temperature,
the reaction was quenched with D2O (0.5 mL). The mixture was
stirred at room temperature for 15 min, poured into saturated
aqueous NH4Cl solution, and then extracted with ethyl acetate. The
organic layers were combined, washed with brine, dried over
MgSO4, filtered, and concentrated in vacuo to give crude products.
The NMR measurement of the crude products was carried out
without any purification.
J. Org. Chem, Vol. 71, No. 24, 2006 9011

Mori et al.
mg, 53%). The product contained small amounts of impurities
derived from the reagents and substrates: mp 61-63 °C; IR (KBr
disk, cm-1) 3422, 2975, 2936, 2834, 1742, 1578, 1454, 1383, 1366,
1.24 (signals contain small impurity; 2H, m), 0.9-1.0 (small
impurity), 0.84 (3H, t, J ) 7.08 Hz); 13C NMR (100 MHz, CDCl3)
δ 144.4, 142.6, 135.9, 135.7, 134.9, 127.5, 127.3, 126.4, 76.4, 72.4,
50.5, 38.0, 29.7 (small impurity), 27.1, 26.5, 21.0, 20.3, 19.8, 14.0;
EI HRMS m/e calcd for C17H24O (M - CH4O+) 244.1827, found
244.1832. The structure of compound 24 was also identified by
2D-NMR (COSY and C-H COSY) spectrum.
1
1196, 1065, 760, 727, 706; H NMR (400 MHz, CDCl3) δ 7.38
(small impurity), 7.15-6.85 (8H, m), 5.84 (1H, d, J ) 6.3 Hz),
5.58 (1H, brd, J ) 5.9 Hz), 5.23 (1H, d, J ) 1.2 Hz), 3.51 (3H, s),
3.20-3.40 (small impurity), (2.14 (3H, s), 1.79 (3H, s)), 1.54 (3H,
s)), 1.50 (3H, s)), 0.80-1.40 (small impurity); 13C NMR (100 MHz,
CDCl3) δ 142.6, 142.5, 141.5, 136.7, 136.0, 135.4, 127.6, 127.3,
127.3, 127.1, 127.0, 126.6, 76.4, 75.8, 50.5, 27.1, 26.6, 20.0, 19.9;
EI HRMS m/e calcd for C20H22O (M - CH4O+) 278.1671, found
278.1685.
Acknowledgment. We thank Mr. Tamotsu Yamamoto and
Ms. Kanako Yamashita of the Institute for Life Science Research
at Asahi Chemical Industry Co., Ltd. for their X-ray crystal-
lographic analysis and high-resolution mass spectra measure-
ments. This work was supported by a Grant-in-Aid for Scientific
Research on Priority Areas (no. 283, “Innovative Synthetic
Reactions”) from the Ministry of Education, Science, Sports,
and Culture of Japan.
(5Z)-7-Methoxy-7-methyl-5-(2,6-dimethylphenyl)-5-octen-4-
ol (24). According to the procedure described above, butyraldehyde
(0.09 mL, 0.98 mmol) gave the title compound 24 (61 mg, 45%)
after the usual workup and column chromatography. The product
contained small amounts of impurities derived from the reagents:
IR (neat, cm-1) 3380, 2961, 2936, 2872, 1927, 1740, 1578, 1464,
1379, 1362, 1100, 770; 1H NMR (400 MHz, CDCl3) δ 7.08-7.00
(3H, m), 5.15 (1H, d, J ) 1.2 Hz), 5.00 (1H, brd, J ) 7.1 Hz),
4.39 (1H, brdd, J ) 7.6, 7.3 Hz), 4.00-4.10 (small impurity), 3.41
(3H, s), 3.10-3.30 (small impurity), 2.31 (3H, s), 2.26 (3H, s),
1.68-1.54 (signals contain small impurity; 1H, m), 1.46 (3H, s),
1.43 (3H, s), 1.39 (signals contain small impurity; 1H, m), 1.35-
Supporting Information Available: 1H and 13C spectra for
compounds 1-6, 8-12, 23 and 24, X-ray crystallographic data for
compound 12 in CIF format, and Cartesian coordinates of optimized
structures for compounds 1b, 2, 3, 4b, 5, and 6. This material is
available free of charge via the Internet at http://pubs.acs.org.
JO061092Z
9012 J. Org. Chem., Vol. 71, No. 24, 2006