Transition-metal-catalyzed rearrangement of 1,1-(Oligomethylene)-4-aryl-2- butene-1,4-diols: Ring expansion vs. aryl group migration

Article abstract of DOI:10.1055/s-0029-1218274

The transition-metal-catalyzed rearrangement of 1,1-(oligomethylene)-4- aryl-2-butene-1,4-diols was investigated. In the presence of PdCl ₂(MeCN)₂ and Cu(OTf)₂, a rapidly equilibrating 1,3-isomerization is followed by 1,2-

Full text of DOI:10.1055/s-0029-1218274

LETTER
2987
Transition-Metal-Catalyzed Rearrangement of 1,1-(Oligomethylene)-4-aryl-
2-butene-1,4-diols: Ring Expansion vs. Aryl Group Migration
Rearrangement of
l
1,1-(O
l
e
igomethyle
x
ne)-4-aryl-2-buten
L
Department Chemie and Catalysis Research Center, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany
Fax +49(89)13115; E-mail: stefan.kirsch@ch.tum.de
Received 13 July 2009
X
O
Abstract: The transition-metal-catalyzed rearrangement of 1,1-
(oligomethylene)-4-aryl-2-butene-1,4-diols was investigated. In the
presence of PdCl2(MeCN)2 and Cu(OTf)2, a rapidly equilibrating
1,3-isomerization is followed by 1,2-migration to produce cyclo-
pentanones or cyclohexanones through expansion of four- or five-
membered ring systems. When employing larger ring systems or
acyclic cores, aryl migration provides 2-aryl aldehydes.
O
R
– X+
R
R
(1)
(2)
R
R
R
R
R
A
B
X
R
O
O
– X+
R
R
Key words: rearrangements, alkenes, diols, transition metals, ca-
R
talysis
A'
B'
Scheme 1 Pinacol-type rearrangements of carbocations
The scope and synthetic value of pinacol-type rearrange-
ments have expanded greatly since the initial discovery of
the pinacol–pinacolone rearrangement1,2 about 150 years
ago. While the classical rearrangement is the acid-cata-
lyzed rearrangement of vicinal diols to aldehydes or ke-
tones,3 one might generally term all such 1,2-migrations
that proceed through a carbocationic species with an adja-
cent hydroxyl group pinacol-type rearrangements (A →
B; Scheme 1). Their utility has been demonstrated for a
wide variety of synthetic applications,4 in particular for
the termination of cationic cyclization reactions.5–8 Fur-
thermore, the generation of carbocations A through direct
alkene activation of vinyl carbinols also has been devel-
oped extensively,9 and shown to be effective at ring ex-
pansion of cyclopropane and cyclobutane derivatives.
col-type rearrangement under formation of b,g-unsaturat-
ed ketones and/or aldehydes was not evaluated.
As part of our program to explore pinacol-terminated cas-
cade reactions,8 we became interested in the synthetic po-
tential of rearrangements resulting from putative cations
of type A¢. We felt that 2-butene-1,4-diol moieties may
possess a greater value than shown before, and are prone
to undergo 1,2-shifts in the presence of fairly mild protic
acid and/or transition-metal catalysts. As will be demon-
strated subsequently, pinacol-type rearrangements that
yield carbonyl compounds can indeed be performed with
aryl-substituted 2-butene-1,4-diols. Our studies also clar-
ify the role of several reaction intermediates that occur in
the course of the conversion.
Although extensive studies have been conducted on the
utility of pinacol-type rearrangements (through A), the re-
lated ‘vinylogous’ rearrangement of allylic cations of type
A¢ has received much less attention (Scheme 1, eq. 2). In
part, this neglect is due to the fact that the release of ring
strain plays an important role to achieve clean rearrange-
ment of allylic cation A¢ produced from a 2-butene-1,4-
diol unit. Thus, this strategy was used almost exclusively
for the pinacol-type ring expansion of vinylcyclopro-
panols.10,11 Few protocols allow the pinacol-type rear-
rangement of other 2-butene-1,4-diol-containing
substrates, all of which requiring strong protic acids and
elevated temperatures.12 For example, the trans-vinylog
of benzpinacol was shown to undergo 1,2-phenyl group
migration to give the b,g-unsaturated ketone in boiling
acetic acid.12a To our surprise, the general capability of
substrates with 2-butene-1,4-diol units to trigger a pina-
As illustrated in Scheme 2, treatment of 2-butene-1,4-di-
ols of type 1 with protic acids or Lewis acids was expected
to give allylic cations (A1 or A2) and subsequent 1,2-mi-
gration. At the outset of our studies, the focus was clearly
on the ring expansion of cyclic systems other than cyclo-
propanols to produce cyclic ketones 2. The first strategy
identified for obtaining rearranged products involved sub-
strates that would form an extended conjugated system
upon cation formation in the presence of protic acids. We
proposed that the rearrangement of 1-aryl-2-alkenol sub-
strates would result in the direct formation of the ring-
expansion product 2 due to the greater thermodynamic
stability of cationic intermediate A1 when R = 4-
MeOC6H4. Indeed, rearrangement of the four-membered
ring system 1a to afford cyclopentanone 2a occurred
readily at 23 °C in CH2Cl2 in the presence of catalytic
amounts of various Brønsted acids. For example, pyridin-
ium 4-toluenesulfonate (PPTS) was employed as a mild
acid to provide 2a in 69% yield after 12 hours (Scheme 3,
eq. 1). Side products were not identified under the reac-
tion conditions. To our surprise, the corresponding five-
membered ring system 1b did not undergo ring expansion
SYNLETT 2009, No. 18, pp 2987–2991
x
x
.x
x
.2
0
0
9
Advanced online publication: 09.10.2009
DOI: 10.1055/s-0029-1218274; Art ID: G23209ST
© Georg Thieme Verlag Stuttgart · New York

2988
A. Lange et al.
LETTER
O
R
n
X
R
R
– X+
O
A1
vs.
O
n
2
3
H+ or LA
– XO–
4
n
X
1
X
R
O
O
1
O
X
– X+
n
n
A2
R
Scheme 2 Possible pathways
on treatment with a number of protic acids (Scheme 3, eq. regioselective substitution might be useful to construct
2). Experiments performed with 1b at 23 °C in CH2Cl2 various ethers as exemplified for the smooth formation of
showed rapid consumption of the starting material. In all 1d and 1e.
cases, conjugated system 4b was formed in good yields
upon isomerization. The use of other solvents led to no
improvement with regard to the desired pinacol shift. In-
Next, we examined the use of transition-metal catalysts to
trigger a pinacol-type rearrangement with substrates other
than 1a as this four-membered ring system is prone to ring
expansion. Initial survey experiments showed that the re-
creasing the reaction temperature to 50 °C in CDCl3 re-
sulted in complete decomposition.13
arrangement of five-membered ring systems 1b to the cor-
responding cyclohexanone 2b was promoted in CDCl3 at
OMe
PPTS (5 mol%)
23 °C, CH2Cl2
O
23 °C by addition of 1 mol% of various Lewis acids:
Zn(OTf)2 (13%, 12 h), KAuCl4 (92%, 1 h), Yb(OTf)3
(16%, 12 h), PtCl2 (96%, 12 h), AgSbF6 (98%, 10 min),
PdCl2(MeCN)2 (84%, 12 h), Cu(OTf)2 (94%, 30 min),
Bi(OTf)3 (79%, 12 h).17 In particular with PdCl2(MeCN)2
and Cu(OTf)2 (Table 1, entries 2 and 3), the reaction was
remarkably free of competing side reactions proceeding
more rapidly with the latter catalyst.18 Analogous sub-
strates such as allylic alcohol 1c and silyl ether 1f also un-
dergo the rearrangement indicating that the exact type of
leaving group (XO–) at C1 has only a minor influence on
the reaction outcome (Table 1).
Ar
Ar
Ar
Ar
(1)
(2)
69%
OH
1a
2a
OMe
acid (5 mol%)
23 °C, CH2Cl2
MeO
PPTS 95%
PTSA 96%
OTES
OTES
1b
4b
Ar = 4-MeOC6H4
Scheme 3 H+-catalyzed rearrangements of allylic ethers
As shown in Table 1, substrates containing a six-mem-
bered and a seven-membered ring system 1g–i do not un-
dergo ring expansion under the reaction conditions.19
Instead, exclusive aryl-group migration takes place to
yield cleanly aldehydes 3a and 3b.20 In the presence of
Cu(OTf)2, these reactions were considerably slower than
the corresponding reactions with smaller ring systems that
gave carbonyls of type 2. In the case of acyclic substrate
1j with R = Et, a mixture of aldehyde 3c (63% formed by
It merits note that the ease with which methyl ether 1b
converts into isomer 4b is somewhat uncommon although
proton catalysis and transition-metal catalysis were re-
ported to be highly effective for promoting the direct
isomerization of arylpropenyl carbinols.14,15 Accordingly,
allylic alcohol 1c also underwent clean 1,3-isomerization
in the presence of PPTS under open-flask conditions
(Scheme 4). This rearrangement proceeds through the
rapid formation of diallylic ether intermediate 5.16 The
PPTS (5 mol%)
48 h
OH
HO
23 °C, CH2Cl2
Ar
Ar
99%
1c
4c
OTES
OTES
Ar
Ar
PPTS (5 mol%)
1 h
23 °C, CH2Cl2
PPTS (5 mol%)
72 h
23 °C, CH2Cl2
O
OTES
OTES
5
97%
99%
PPTS (5 mol%)
1 h
23 °C, CH2Cl2–EtOH
OH
OEt
R
R
R
R
Ar
Ar
OTES
OTES
R = Et
R = -(CH2)5-
1d 88%
1e 80%
Ar = 4-MeOC6H4
Scheme 4 H+-catalyzed rearrangements of allylic alcohols
Synlett 2009, No. 18, 2987–2991 © Thieme Stuttgart · New York

LETTER
Rearrangement of 1,1-(Oligomethylene)-4-aryl-2-butene-1,4-diols
2989
Table 1 Transition-Metal-Catalyzed Rearrangementsa
cat. (1 mol%)
A: Cu(OTf)2
B: PdCl2(MeCN)2
OX
R
O
R
R
R
+
R
Ar
Ar
23 °C, CH2Cl2
1
2
3
OTES
O
Ar
R
Ar = 4-MeOC6H4
Entry
1d,f
2d
R
X
1
Cat.
A
A
B
Time (h)
0.5
0.5
12
Yield of 2 (%)b
Yield of 3 (%)b
-(CH2)3-
Me
1a
1b
1b
1c
1f
72 (2a)
0
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)5-
-(CH2)5-
-(CH2)5-
-(CH2)6-
-(CH2)6-
Et
Me
Me
H
94 (2b)
0
3d
84 (2b)
0
4d
A
B
0.5
12
96 (2b)
0
5
TES
H
78c (2b)
0
6
1g
1g
1g
1h
1i
A
A
B
0.5
12
0
9c (3a)
79 (3a)
81 (3a)
80 (3b)
82 (3b)
63 (3c)
7e
H
0
8e
H
12
0
9e
H
B
12
0
10e
11
Me
H
A
A
12
0
1j
12
12 (2c)
a Conditions: 1 mol% catalyst [A: Cu(OTf)2; B: PdCl2(CH3CN)2], [substrate] = 0.1 M, 23 °C, CH2Cl2.
b Yield after column chromatography unless otherwise indicated.
c Determined by 1H NMR.
d Formation of 3 was not observed in the 1H NMR of the crude reaction mixture.
e Formation of 2 was not observed in the 1H NMR of the crude reaction mixture.
f Compound 1a contains a free hydroxy instead of triethylsilyloxy.
aryl-group migration) and ketone 2c (12% formed by
ethyl-group migration) was obtained. The use of other sol-
vents and other transition-metal catalysts led to little
alteration in the product distribution.
OX
R
R
Ar
1
OTES
O
R
R
R
To confirm that the substituent R at C1 plays a significant
Ar
role in the catalyzed rearrangements reported here, sub-
strates with R ≠ 4-MeOC6H4 were examined under similar
conditions. When 1k (R = Ph) was treated with 10 mol%
of Cu(OTf)2, the reaction required 72 hours to obtain full
conversion, thus indicating a significant rate contribution
Ar
R
O
2
3
OX
R
R
Ar = 4-MeOC6H4
Ar
4
OTES
PdCl2(MeCN)2
(1 mol %)
Cu(OTf)2
(1 mol%)
through the methoxy substituent at the para position of
the phenyl (Scheme 5, eq. 1). As exemplified for the reac-
tion of 1l (R = Bn), if substrates with substituents other
4c
X = H
R = -(CH2)4-
2b
4d
X = H
R = -(CH2)5-
3a
23 °C, CDCl3
23 °C, CDCl3
quant.
quant.
than aryl are employed, no rearrangement occurs leading
instead to elimination products.21
Scheme 6 Evidence for rapid equilibrium of 1 and 4 in the presence
of Lewis acids
Cu(OTf)2 (10 mol%)
72 h, 23 °C, CH2Cl2
OH
Although we feel a detailed discussion of the mechanism
of the transition-metal-catalyzed rearrangement is prema-
ture at this point, 1H NMR monitoring of the reaction of
1c in the presence of PdCl2(MeCN)2 shows the expected
1,3-isomerization into intermediate 4c (via 5), which sub-
sequently undergoes ring expansion to 2b. When monitor-
ing the conversion of 1g in the presence of Cu(OTf)2, we
observed that 1,3-isomerization providing 4d occurs more
rapidly than transformation into aldehyde 3a. Since both
(1)
Ph
Ph
Ph
84%
2d
1k
O
OTES
OH
Cu(OTf)2 (5 mol%)
12 h, 23 °C, CH2Cl2
OH
Ph
(2)
56%
6
1l
OTES
Scheme 5 Influence of substituents at C1 on the reaction outcome
Synlett 2009, No. 18, 2987–2991 © Thieme Stuttgart · New York

2990
A. Lange et al.
LETTER
Overman, L. E. J. Am. Chem. Soc. 1993, 115, 2992.
(d) Mulzer, J.; Greifenberg, S.; Buschmann, J.; Luger, P.
Angew. Chem., Int. Ed. Engl. 1993, 32, 1173.
isolated 4c and isolated 4d undergo quantitative 1,2-mi-
gration to the corresponding rearrangement products (2b
and 3a) when transition-metal catalysts are present
(Scheme 6), these observations are most consistent with
the rapid equilibrium of 1 and 4.22 Nevertheless, that 1 and
4 are equilibrated more rapidly than they undergo a pina-
col-type shift does not explain why the selectivity (forma-
tion of 2 vs. 3) is completely reversed when going from
the five-membered to the six-membered ring system.
(e) MacMillan, D. W. C.; Overman, L. E.; Pennington, L. D.
J. Am. Chem. Soc. 2001, 123, 9033.
(7) For a review on the use of carbophilic Lewis acids in
combination with pinacol-type rearrangments, see: Crone,
B.; Kirsch, S. F. Chem. Eur. J. 2008, 14, 3514.
(8) For our works in the field, see: (a) Kirsch, S. F.; Binder,
J. T.; Crone, B.; Duschek, A.; Haug, T. T.; Liébert, C.;
Menz, H. Angew. Chem. Int. Ed. 2007, 46, 2310. (b) Menz,
H.; Binder, J. T.; Crone, B.; Duschek, A.; Haug, T. T.;
Kirsch, S. F.; Klahn, P.; Liébert, C. Tetrahedron 2009, 65,
1880. (c) Kirsch, S. F.; Binder, J. T.; Liébert, C.; Menz, H.
Angew. Chem. Int. Ed. 2006, 45, 5878. (d) Binder, J. T.;
Crone, B.; Kirsch, S. F.; Liébert, C.; Menz, H. Eur. J. Org.
Chem. 2007, 1636. (e) Crone, B.; Kirsch, S. F. J. Org.
Chem. 2007, 72, 5435. (f) Baskar, B.; Bae, H. J.; An, S. E.;
Cheong, J. Y.; Rhee, Y. H.; Duschek, A.; Kirsch, S. F. Org.
Lett. 2008, 10, 2605.
In conclusion, we have described the first studies on tran-
sition-metal-catalyzed rearrangements of aryl-substituted
2-butene-1,4-diol units. While cyclobutane 1a and cyclo-
pentanes 1b–f and 1k were shown to undergo clean ring
expansion to 2-styryl-substituted cyclopentanones and
cyclohexanones of type 2, aryl-group migration yielding
2-aryl aldehydes 3 was found to be the preferred pathway
when employing substrates that possess either other ring
sizes or an acyclic core.23 The reaction outcome is predict-
able, and the 1,2-migration follows a rapidly equilibrating
1,3-isomerization.
(9) (a) Wassermann, H. H.; Cochoy, R. E.; Baird, M. S. J. Am.
Chem. Soc. 1969, 91, 2375. (b) Wassermann, H. H.; Hearn,
M. J.; Cochoy, R. J. Org Chem. 1980, 45, 2874.
(c) Wienand, A.; Reissig, H.-U. Chem. Ber. 1991, 124, 957.
(d) Nishimura, T.; Ohe, K.; Uemura, S. J. Am. Chem. Soc.
1999, 121, 2645. (e) Hegedus, L. S.; Ranslow, P. B.
Synthesis 2000, 953. (f) Nishimura, T.; Ohe, K.; Uemura, S.
J. Org. Chem. 2001, 66, 1455. (g) Markham, J. P.; Staben,
S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 9708.
(10) For seminal works, see: (a) Ollivier, J.; Legros, J.-Y.; Fiaud,
J.-C.; de Meijere, A.; Salaün, J. Tetrahedron Lett. 1990, 31,
4135. (b) Ollivier, J.; Salaün, J. Tetrahedron Lett. 1984, 25,
1269. (c) Salaün, J.; Karkour, B. Tetrahedron Lett. 1988, 29,
1537. (d) Funayama, S.; Eda, S.; Komiyama, K.; Ohmura,
S.; Tokunaga, T. Tetrahedron Lett. 1989, 30, 3151.
(e) Salaün, J.; Karkour, B. Tetrahedron Lett. 1987, 28, 4669.
(11) For an asymmetric Wagner–Meerwein shift related to this
pinacol rearrangement, see: Trost, B. M.; Yasukata, T.
J. Am. Chem. Soc. 2001, 123, 7162.
(12) (a) Lutz, R. E.; Bass, R. G.; Boykin, D. W. J. Org. Chem.
1964, 29, 3660. (b) Saito, K.; Horie, Y.; Mukai, T.; Toda, T.
Bull. Chem. Soc. Jpn. 1985, 58, 3118. (c) Uyehara, T.;
Kawai, Y.; Yamada, J.-i.; Kato, T. Chem Lett. 1987, 16, 137.
(13) Exposure of six-membered ring substrate 1c to 5 mol% of
PPTS at 23 °C in CH2Cl2 provided an inseparable mixture of
3c and 4c in low yields (e.g., 29% after 14 h).
(14) Protic acid catalysis: (a) Braude, E. A.; Fawcett, J. S.;
Newman, D. D. E. J. Chem. Soc. 1950, 793. (b) Braude,
E. A.; Jones, E. R. H.; Stern, E. S. J. Chem. Soc. 1946, 396.
(c) Braude, E. A.; Jones, E. R. H. J. Chem. Soc. 1944, 436.
(d) Braude, E.; Stern, E. J. Chem. Soc. 1947, 1096.
(e) Sanz, R.; Martínez, A.; Miguel, D.; Álvarez-Gutiérres,
J. M.; Rodríguez, F. Adv. Synth. Catal. 2006, 348, 1841.
(15) Lewis acid catalysis: (a) Mukhopadhyay, M.; Reddy, M.
M.; Maikap, G. C.; Iqbal, J. J. Org. Chem. 1995, 60, 2670.
(b) Li, C.-J.; Wang, D.; Chen, D.-L. J. Am. Chem. Soc. 1995,
117, 12867. (c) Malkov, A. V.; Baxendale, I.; Mansfield,
D. J.; Kocovsky, P. Tetrahedron Lett. 1995, 38, 6351.
(d) Morrill, C.; Beutner, G. L.; Grubbs, R. H. J. Org. Chem.
2006, 71, 7813. (e) Kitamura, M.; Hayashi, H.; Yano, M.;
Tanaka, T.; Maezaki, M. Heterocycles 2007, 71, 2669.
(16) For a related case, see inter alia: Wang, J.; Huang, W.;
Zhang, Z.; Xiang, X.; Liu, R.; Zhou, X. J. Org. Chem. 2009,
74, 3299.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
This project was supported by the Deutsche Forschungsgemein-
schaft (DFG). We thank Prof. Dr. Th. Bach for fruitful discussions
and generous support.
References and Notes
(1) (a) Fittig, R. Justus Liebigs Ann. Chem. 1859, 110, 23.
(b) Butlerov, A. Justus Liebigs Ann. Chem. 1874, 174, 125.
(c) Mundy, B. P.; Otzenberger, R. D. J. Org. Chem. 1973,
38, 2109.
(2) For an Essay on the discovery, see: Berson, J. A. Angew.
Chem. Int. Ed. 2002, 114, 4849.
(3) Collins, C. J. Q. Rev. Chem. Soc. 1960, 14, 357.
(4) For recent examples, see inter alia: (a) Suzuki, K.;
Takikawa, H.; Hachisu, Y.; Bode, J. W. Angew. Chem. Int.
Ed. 2007, 46, 3252. (b) Reisman, S. E.; Ready, J. M.;
Hasuoka, A.; Smith, C. J.; Wood, J. L. J. Am. Chem. Soc.
2006, 128, 1448. (c) Alvarez-Manzaneda, E.; Chahboun, R.;
Barranco, I.; Cabrera, E.; Alvarez, E.; Lara, A.; Alvarez-
Manzaneda, R.; Hmamouchi, M.; Es-Samti, H. Tetrahedron
2007, 63, 11943. (d) Frongia, A.; Girard, C.; Ollivier, J.;
Piras, P. P.; Secci, F. Synlett 2008, 2823.
(5) (a) Trost, B. M.; Lee, D. C. J. Am. Chem. Soc. 1988, 110,
6556. (b) Trost, B. M.; Brandi, A. J. Am. Chem. Soc. 1984,
106, 5041. (c) Sworin, M.; Neumann, W. L. J. Org. Chem.
1988, 53, 4894. (d) Nakamura, T.; Matsui, T.; Tanino, K.;
Kuwajima, I. J. Org. Chem. 1997, 62, 3032. (e) Youn,
J.-H.; Lee, J.; Cha, J. K. Org. Lett. 2001, 3, 2935.
(6) For a review on Prins pinacol cascades, see: (a) Overman,
L. E.; Pennington, L. D. J. Org. Chem. 2003, 68, 7143.
For selected examples and synthetic applications, see:
(b) Grese, T. A.; Hutchinson, K. D.; Overman, L. E. J. Org.
Chem. 1993, 58, 2468. (c) Hirst, G. C.; Johnson, T. O.;
(17) Reaction of 1b in the presence of MgBr2 (5 mol%) led to
clean formation of 4b without traces of 2b (or 3b).
Synlett 2009, No. 18, 2987–2991 © Thieme Stuttgart · New York

LETTER
Rearrangement of 1,1-(Oligomethylene)-4-aryl-2-butene-1,4-diols
2991
(18) Synthesis of (E)-2-(4-Methoxystyryl)cyclohexanone (2b)
Cu(OTf)2 (1 mg, 0.003 mmol, 1 mol%) was added to a
solution of (E)-1-(4-methoxyphenyl)-3-(1-(triethylsilyl-
oxy)cyclopentyl)prop-2-en-1-ol (1c, 100 mg, 0.28 mmol) in
CH2Cl2 (2.8 mL) and stirred at r.t. for 30 min (until TLC
analysis indicated complete conversion). The reaction
mixture was concentrated under reduced pressure, and the
residue was purified by flash chromatography on silica
(pentanes–Et2O = 95:5). Compound 2b was obtained as a
colorless solid in 96% yield (62 mg, 0.27 mmol). 1H NMR
(360 MHz, CDCl3): d = 1.69–1.83 (m, 3 H), 1.89–1.96 (m, 1
H), 2.01–2.09 (m, 1 H), 2.14–2.20 (m, 1 H), 2.31–2.40 (m, 1
H), 2.45–2.51 (m, 1 H), 3.17 (ddd, J = 0.9, 6.4, 11.3 Hz, 1
H), 3.80 (s, 3 H), 6.27 (dd, J = 5.9, 16.1 Hz, 1 H), 6.33 (d,
J = 16.1 Hz, 1 H), 6.77–6.91 (m, 2 H), 7.29–7.33 (m, 2 H).
13C NMR (90.6 MHz, CDCl3): d = 24.4 (t), 27.6 (t), 34.5 (t),
41.7 (t), 54.0 (d), 55.3 (d), 113.9 (d), 125.3 (d), 127.4 (d),
130.0 (s), 130.8 (d), 159.0 (s), 211.3 (s). LRMS (EI): m/z =
230 (100)[M+], 202 (26), 173 (25), 159 (21), 134 (38), 121
(37). HRMS: m/z calcd for C15H18O2 [M+]: 230.1307; found:
230.1307.
pressure, and the residue was purified by flash
chromatography on silica (pentanes–Et2O = 95:5).
Compound 3a was obtained in 79% yield (50 mg, 0.20
mmol). 1H NMR (360 MHz, CDCl3): d = 1.45–1.59 (m, 6 H),
2.12–2.20 (m, 4 H), 3.80 (s, 3 H), 4.41 (dd, J = 2.6, 8.8 Hz,
1 H), 5.39–5.46 (m, 1 H), 6.88–6.94 (m, 2 H), 7.13–7.19 (m,
2 H), 9.55 (d, J = 2.6 Hz, 1 H). 13C NMR (90.6 MHz,
CDCl3): d = 26.6, 27.6, 28.5, 29.6, 37.3, 55.3, 56.3, 114.4,
115.1, 128.9, 129.4, 145.7, 158.8, 198.5. LRMS (EI): m/z =
244 (2) [M+], 215 (100), 147 (23), 121 (25). HRMS: m/z
calcd for C16H20O2 [M+]: 244.1463; found: 244.1468.
(21) We also observed a high-yielding elimination when using 2-
butene-1,4-diols that possess Bz-protected primary allylic
alcohols. According to preliminary studies, this elimination
appears to be quite general (Scheme 7).
Cu(OTf)2 (1 mol%)
1 h, 23 °C, CH2Cl2
BzO
BzO
OTES
99%
Scheme 7
(19) For the construction of seven-membered ring systems
through pinacol-type ring expansion, see the following
review: Kantorowski, E. J.; Kurth, M. J. Tetrahedron 2000,
56, 4317.
(22) In seminal studies on related 1,3-isomerizations of
phenylpropenyl carbinols, chirality transfer was reported:
(23) (a) Kenyon, J.; Partridge, S. M.; Phillips, H. J. Chem. Soc.
1937, 207. (b) See also: Vikhe, Y. S.; Hande, S. M.; Kawai,
N.; Uenishi, J. J. Org. Chem. 2009, 74, 5174.
(20) Synthesis of 3-Cyclohexylidene-2-(4-methoxyphenyl)-
propanal (3a)
Following the procedure to prepare 2b,18 allylic alcohol 1g
(100 mg, 0.26 mmol) was converted into the corresponding
aldehyde 3a in the presence of Cu(OTf)2 (1 mg, 1 mol%).
The reaction mixture was concentrated under reduced
(24) This correlates with the migratory aptitude observed in
Wagner–Meerwein shifts.
Synlett 2009, No. 18, 2987–2991 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.