Divergent synthetic routes for ring expansion or cyclization from 1,4-allylic diol derivatives via gold(I) catalysis or zinc(II) mediation

Article abstract of DOI:10.1021/jo2015517

A new efficient method was developed to transform cyclic alkanols into one-carbon higher homologated ketones using various esters as the leaving groups through gold-catalyzed allylic cation-promoted pinacol-type rearrangement. This reaction, coupled with

Full text of DOI:10.1021/jo2015517

ARTICLE
pubs.acs.org/joc
Divergent Synthetic Routes for Ring Expansion or Cyclization from
1,4-Allylic Diol Derivatives via Gold(I) Catalysis or Zinc(II) Mediation
LiꢀLi Zhu,† Xiao-Xiao Li,† Wen Zhou,† Xin Li,† and Zili Chen*,†,‡
†Department of Chemistry, Renmin University of China, Beijing 100872, China
‡Beijing National Laboratory of Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of
Chemistry, Chinese Academy of Sciences, Beijing 100190, China
S Supporting Information
b
ABSTRACT: A new efficient method was developed to transform
cyclic alkanols into one-carbon higher homologated ketones using
various esters as the leaving groups through gold-catalyzed allylic
cation-promoted pinacol-type rearrangement. This reaction, coupled
with oxy-Cope rearrangement, provided a new strategy to synthesize
five-carbon homologated ring ketones. In addition, using ZnBr2, 2,5-
dihydrofuran products were obtained in moderate to good yields via
an intramolecular cyclization process.
Scheme 1. Divergent Reaction Routes
’ INTRODUCTION
Ring expansion or carbon chain extension by means of carbon-
insertion procedures have been employed frequently in organic
synthesis.1 In this field, the carbon cation-induced pinacol-type
rearrangement is of particular importance, with its utility being
demonstrated in a variety of synthetic applications.2 However, a
similar transformation, the allylic cation-promoted pinacol-type
rearrangement, as exemplified by the reaction (route a) shown in
Scheme 1, has received much less attention. This may be because
of the improved stability and low isomerization activity of this
vinyl conjugated carbon cation system and the possible compe-
titive formation of the 2,5-dihydrofurans (route b) and the
elimination products.3,4
Methods for ring expansion of the small ring molecules using
transition metal catalysts have been well developed. For example,
Toste’s group reported the intramolecular ring expansion of
alkynyl cyclopropanols/cyclobutanols via gold catalysis5 and
then extended this to an asymmetric version by using allenyl
cyclopropanols as substrates.6,7 Yu developed a cation-triggered
ring expansion process, in which alkynyl cyclopropanes were
transformed into alkylidene cyclobutylamines using gold catalysts.8
Nevertheless, from the same substrates, Liu’s group found that
cyclobutenyl ketones can be obtained through an oxidative ring-
expansion pathway, which was triggered by gold-catalyzed nu-
cleophilic addition of oxygen-delivering oxidants, such as diphe-
nylsulfoxide, onto alkynes.9 Besides these gold-catalyzed reac-
tions,10 other transition metal catalysts, such as Fe,11 Ru,12
Rh,13 Co,14 Pd,15 and Pt16 complexes, have also been utilized success-
fully in numerous ring-expansion reactions. However, all of these
studies focused on the small ring structures, primarily on
cyclopropane derivatives.
intermediate, generated from allylic esters via gold catalysis,
might promote the cyclic alkanol’s ring expansion. As a con-
tinuation of our previous research, we herein report a new ring-
expansion pathway to synthesize one-carbon higher homolo-
gated ring ketones from cycloalkanols through gold-catalyzed
allylic cation-promoted pinacol-type rearrangement, in which the
medium- and large-sized ring substrates worked very well.
Additionally, we also prepared a series of 2,5-dihydrofurans
from the same substrates using ZnBr2 as the reaction mediator.
2,5-Dihydrofurans and their derivatives are structural motifs that
are found frequently in a wide variety of natural products18,19 and
therefore have aroused great interest for the development of new
synthetic methods.
’ RESULTS AND DISCUSSION
Considering that six-membered rings are the most stable cyclic
structure, we chose the cyclohexanol derivative A (entry 1, Table 1)
as the model system for our initial investigation. When com-
pound A was treated with AuCl3 in DCE at rt, cycloheptanone 2a
was obtained in 11% yield, along with a mixture of β-elimination
products,20 without formation of dihydrofuran 3a. UsingAuPPh3Cl/
AgSbF6 as catalyst, 2a was obtained in 21% yield (entry 2,
On the basis of our previous studies of the gold-catalyzed
Received: July 26, 2011
Published: September 15, 2011
reaction of allylic esters,17 we presumed that the allylic cation
r
2011 American Chemical Society
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Table 1. Optimization of the Reaction of 1a To Give Ring-Expansion Product 2a or Cyclization Product 3aa
(R1/R2)
catalyst (%)
AuCl3 (10)
solvent/temp (°C)
yield (%) (2a/3a)
1
H/H (A)
DCE/rt
11/0
21/0
18/0
28/0
13/0
0/0
2
H/H (A)
AuPPh3Cl/AgSbF6 (10)
AuCl3 (10)
DCM/30
DCE/rt
3
H/THP (B)
Ac/H (C)
4
AuCl3 (10)
DCE/rt
5
Ac/THP (D)
Bz/H (E)
AuCl3 (10)
DCE/rt
6
AuCl3 (10)
DCE/rt
7
Bz/H (E)
AuPPh3Cl/AgSbF6 (10)
AuPPh3Cl/AgSbF6 (10)
AuPPh3Cl/AgSbF6 (10)
AuPPh3Cl/AgSbF6 (10)
AuPPh3Cl (10)
DCE/rt
47/0
71/0
63/0
84/0
0/0
8
Bz/H (E)
DCM/30
DCM/30
DCM/30
DCM/30
DCM/30
DCM/30
DCM/30
DCM/rt
DCM/30
DCM/30
DCM/30
DCM/30
9
Piv/H (F)
10
11
12
13
14
15
16
17
18
19
TCBz/H (1a)
TCBz/H (1a)
TCBz/H (1a)
TCBz/H (1a)
TCBz/H (1a)
TCBz/H (1a)
TCBz/H (1a)
TCBz/H (1a)
TCBz/H (1a)
TCBz/H (1a)
AgSbF6 (10)
43/0
81/0
59/0
Trace/80
0/0
AuPPh3Cl/AgSbF6 (5)
AuPPh3Cl/AgSbF6 (2)
b
ZnBr2
HCl (10)
CF3SO3H (10)
22/18
26/0
48/14
BF3 Et2O (10)
3
Cu(OTf)2 (5)
a Unless noted, all reactions were carried out at 0.1 mmol scale in 4 mL of solvent for 4 h. b 1 mol % of ZnBr2 was used at rt. Ac = acetate, Bz = benzoate,
Piv = pivalate, TCBz = 2,4,6-trichlorobenzoate.
Table 1). Replacement of the hydroxyl group by THP ether (R2
position, compound B, entry 3, Table 1) and acetate
(R1 position, compound C, entry 4, Table 1) either separately or
simultaneously (compound D, entry 5, Table 1) did not improve
the yield of 2a. Investigation of benzoate substrate E afforded
no desired product using AuCl3, but when AuPPh3Cl/AgSbF6
(10 mol %) was used as catalyst, 2a was obtained in 47% yield
(entries 6 and 7, Table 1). Solvent and reaction temperature were
optimized, which led to a considerable improvement in 2a’s yield
(entry 8, Table 1). Using pivalate as the protecting group to
increase the steric bulk (F, entry 9, Table 1) was ineffective, so we
turned to exploring the electronic effect on the reaction yield.
When electron-deficient 2,4,6-trichloro benzoate (TCBz) was
used as the protecting group (1a, entry 10, Table 1), 2a was
obtained in 84% yield. Employing AgSbF6 alone led to a lower
yield, and Ph3PAuCl alone was totally inactive (Table 1, entries
11 and 12). When 5 mol % catalyst was used, 2a’s yield was
slightly reduced (Table 1, entry 13). A variety of other Lewis and
Brønsted acids were also tested.21 When 1 mol % of ZnBr2 was
used as catalyst, 2,5-dihydrofuran 3a was obtained in 80% yield
(Table 1, entry 15). In control experiments, Brønsted acids HCl
group played a pivotal role in this transformation. However, the
use of different metal complexes (such as Cu or Au) also affected
the reaction outcomes.
Using the conditions from entry 13 in Table 1, the scope and
limitations of the ring expansion reaction were explored. A
number of cyclic and linear substrates with different protection
patterns were tested, which provided the corresponding higher
homologated cyclic and linear ketones. As shown in Table 2, in
the reaction of three- and four-membered rings, unprotected
2-butene-1,4-diols 1b and 1c were used, which provided cyclic
butanone 2b and pentanone 2c in 81% and 72% yield, respec-
tively. For the five-membered substrates, allylic acetate contain-
ing cyclopentanols were employed. Both electron-rich and
electron-poor reactants worked very well, giving the correspond-
ing cyclohexanones in moderate to good yields (Table 2, entries
3ꢀ6). It was notable that the catalyst loading in all of the small
rings' reactions was less than 5%.
We then investigated the transformation of cyclohexanol. For
electron-deficient arene substrates, TCBz was used as protecting
group, which gave the desired products in good yields (Table 2,
entries 7ꢀ9), but for their electron-rich analogues, the acetyl
group was employed instead.22 This provided the desired
products in moderate yields (Table 2, entries 10 and 11).
Large-sized ring compounds, such as cycloheptanol, cycloocta-
nol, and cyclododecanol, were also tested. They exhibited higher
reactivities, giving the homologated cyclic ketones in good yields
(Table 2, entries 12ꢀ14). However, although 10 mol % of
catalyst was used, the reaction of styryl substrate 1p gave 2p in
a low yield (Table 2, entry 15). Furthermore, the alkyl substrate
and CF3SO3H afforded no product, whereas BF3 Et2O gave 2a
3
in 26% yield (Table 1, entries 16ꢀ18).
Kirsch’s group has developed a similar ring-expansion pathway
using Cu(OTf)2 as catalyst,4 but this method did not work for
six-membered rings. As a comparison, we investigated cyclohexane
substrate 1a’s reaction using 5 mol % Cu(OTf)2 catalyst, which
interestingly provided 2a in 48% yield and 3a in 14% yield
(Table 1, entry 19). This meant that the presence of the OTCBz
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Table 2. Preparation of One-Carbon Higher Homologated Cyclic Ketones through Gold-Catalyzed Ring Expansiona
a Unless noted, all reactions were carried out at 0.1 mmol scale in 4 mL of CH2Cl2 at 30 °C.
only afforded a mixture of elimination products, which meant
that the presence of a phenyl or vinyl group to stabilize
the allylic cation intermediate was vital to this reaction.
Transformation of adamantanol 1q to the homologated cyclic
ketone 2q proceeds smoothly, though with a lower reac-
tion yield (Table 2, entry 16). Two linear substrates were
then examined. The reaction of 1r and 1s provided ketone 2r
and 2s in high yields in which the hydrogen atom and
the benzene group migrated to the neighboring position
(Table 2, entries 17 and 18).
Using the conditions from entry 15 in Table 1, a series of 2,5-
dihydrofuran derivatives 3 can be prepared through ZnBr2-induced
intramolecular cyclization. Under these conditions, substrate 1h
and 1i (Table 3, entries 2 and 3), which had an electron-
withdrawing phenyl group, worked better than the electron-rich
analogues 1j and 1k) (Table 3, entries 4 and 5). The bulky
adamantanol 1q can also be transformed into the derivative 3q in
moderate yield. The large-sized rings, such as cycloheptanol 1m,
cyclooctanol 1n and cyclododecanol 1o, underwent a similar
transformation to give the desired dihydrofurans, together with
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Table 3. Preparation of a Series of 2,5-Dihydrofuran Derivatives through ZnBr2-Mediated Cyclization Reactiona
a Unless noted, all reactions were carried out at 0.1 mmol scale in 4 mL of CH2Cl2 at rt. b The data in parentheses are the yields of 2m, 2n, and 2o.
the formation of the ring-expansion products. However, small
ring substrates (1bꢀ1g) and linear substrates (1sꢀ1t) did not
work very well using ZnBr2, which primarily provided the ring-
enlargement products. Their yields were lower than those of the
gold-catalyzed reactions.
To examine the effect of alkene’s Z/E configuration on the
reaction yield, compound Z-1a was prepared and treated with
5 mol % of Ph3PAuCl/AgSbF6 in DCM. 2a was obtained in 71%
yield, together with 15% yield of 3a, which is lower than that of 1a
(Scheme 2, eq 1). It seemed that the Z-configuration substrate is
prone to take cyclization route b (Scheme 1). When 1 mol % of
ZnBr2 was used as catalyst, only 3a was obtained in 81% yield
(Scheme 2, eq 1).
In the course of 1a’s reaction, 1a’s regioisomer 4 can be
detected and separated.23 Treating 4 with 5 mol % of Ph3PAuCl/
AgSbF6 gave 2a in 90% yield. Furthermore, when ZnBr2 was
added, 3a was obtained in 88% yield (Scheme 2, eq 2). These
results indicated that compound 4 is a possible reaction inter-
mediate. Further investigation into compound 4 was performed
to elucidate the reaction mechanism.
The different reactivity exhibited by the Au(I) cation and
ZnBr2 are intriguing. On the basis of our previous results, the
allylic cation intermediates were presumably generated from
allylic esters via gold catalysis,17 to which the neighboring cyclic
CꢀC bonds might serve as intramolecular nucleophiles that
react with allylic cations, thereby triggering the pinacol-type
rearrangement in a gold-catalyzed transformation. Using ZnBr2,
however, the exposed hydroxyl group attacked the allylic cation.
Inspired by the previous studies of the tricoordinated gold(I)
species,24 we thought that complexation of the auric cation with
the hydroxyl group might prohibit route b (Scheme 1). To
elucidate the effect of the complexation mode on the reaction
outcomes, Lewis acid BF3 Et2O, which had only one vacant
3
coordination site available, was then examined. According to the
assumption, monocoordinated BF3 Et2O would leave the hy-
3
droxyl group exposed, thereby leading to the cyclization products.
However, the reaction result did not support this theory; BF3 Et2O
3
gave 2a as a sole product in 45% yield (Scheme 2, eq 2).
We then explored the possible chirality transfer in these
reactions.25 Chiral substrate (R)-E was prepared and investi-
gated, which gave 2a in 0% ee using gold catalysis and provided
3a in 3% ee in the ZnBr2-mediated reaction (Scheme 3, eq 3).
Treating 3a with the gold catalyst gave no reaction, which
indicated that furan 3a was not the reaction intermediate to
afford 4a (Scheme 3, eq 4).26 4-Methyl cyclohexanol substrates
with either syn (syn-1t) or anti (anti-1t) configuration were then
treated with 5 mol % of Ph3PAuCl/AgSbF6 in DCM. It was
found that anti-1t mainly provided the anti-2t (anti/syn = 12/1),
whereas syn-1t gave a mixture of anti-2t and syn-2t (anti/syn = 1/1.2)
(Scheme 3, eq 5).21
Although the detailed explanation for the divergent reactivity
of the gold and zinc salts was still unclear, a plausible mechanism
was proposed. This reaction might have started from the forma-
tion of 1a’s regioisomer 4,21 which underwent subsequent ring
expansion via gold catalysis or underwent cyclization using
ZnBr2. There are two possible transition states in the pinacol
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Scheme 2. Examination of the Gold-Catalyzed Reaction of Compound Z-1a and 4
Scheme 3. Examination of the Gold-Catalyzed Reaction of Compound (R)-E, 3a, and 1t
rearrangement process (Scheme 4), in which an allylic cation
intermediate was presumably generated. As compared with
transition state I, transition state II was energetically unfavored,
because of the higher 1,3-axial steric hindrance between the
hydrogen atom and the bulky allylic ester group. This assumption
was further approved by the reactions in eq 5.21 In the reaction of
anti-1t, the anti-methyl group occupied an equatorial position in
transition I and an axial position in transition II, thus making
transition I more favorable. However, in the reaction of syn-1t,
the syn-methyl group occupied an axial position in transition I
and an equatorial position in transition II, which counteracted
the allylic cation group and led to a mixture of anti-2t/syn-2t with
a low ratio. Using ZnBr2, we presumed that an SN20-type intramo-
lecular cyclization (transition III) might occur to give the 2,5-
dihydrogen furan 3a (Scheme 4). Although no chirality transfer was
observed in the reaction of eq 3, which would be implied in a
concerted SN20 transfer, the racemization, however, might occur at
the isomerization step. Although compound 4is thermodynamically
more stable than 1a, the competitive processes, such as pinacol type
rearrangement from 4 (route e) to give 2a and direct SN2 (or SN1)
addition to give 3a (route f), cannot be excluded.
Further derivations for the obtained cyclic ketones were then
performed. Ketone 2 can be extended into the higher homo-
logated cyclic ketones. As shown in Scheme 5, addition of ethynyl
Grignard to 2a, followed by hydrogenation and oxy-Cope
rearrangement, gave cycloundecanone 7 in high yield.27 There-
fore, a formal five-carbon expansion product was obtained from
cyclohexanol 1a through a pinacol-type rearrangement and then
an oxy-Cope rearrangement. Similarly, compound 2p can be
transformed into cycloheptadecanone 8. Meanwhile, treating 2a
with NaBH4 in MeOH/THF at ꢀ20 °C, followed by iodine-
induced cyclization, gave bicyclic 10 in 89% yield (syn/anti = 2.6/1).
Compound 2b can be transformed into butyrolactone 11 using
m-CPBA as the oxidant.
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Scheme 4. A Plausible Mechanism
Scheme 5. Further Transformation of Compound 2a, 2p, and 2b
’ CONCLUSION
monitoring). The solvent was removed by rotary evaporation, and the
residue was purified by column chromatography on silica gel to afford 2a
(81%).
In summary, we have developed an efficient gold-catalyzed
method to transform cyclic alkanols into one-carbon higher
homologated cyclic ketones through an allylic cation-promoted
pinacol-type rearrangement, in which various esters, including
acetate, benzoate, and electron-deficient 2,4,6-trichlorobenzoate
(TCBz), were used as leaving groups. This reaction, coupled with
oxy-Cope rearrangement, also provided a new strategy to yield
five-carbon homologated ring ketones. In contrast, when 1 mol %
of ZnBr2 was utilized, a series of 2,5-dihydrofuran products were
obtained in moderate to good yields via a cyclization process.
Typical Procedure for the Zinc(II)-Catalyzed Ring Cycliza-
tion from Allylic Ester Substituted Cycloalkanols 1a. To a
solution of ZnBr2 (1.0 equiv) in 2 mL DCM, was added 1a (0.1 mmol)
in 2 mL DCM under N2. The resulting mixture was stirred at room
temperature. Complete consumption of the starting material was
monitored by TLC analysis. The solvent was then removed by rotary
evaporation, and the residue was purified by column chromatography on
silica gel to afford 3a (80%).
(E)-2-Styrylcycloheptanone 2a.28 1H NMR (400 MHz, CDCl3)
δ 7.36 (d, J = 7.3 Hz, 2H), 7.30 (t, J = 7.3 Hz, 2H), 7.21 (t, J = 7.2 Hz,
1H), 6.42 (d, J = 16.1 Hz, 1H), 6.31 (dd, J = 16.0, 7.4 Hz, 1H),
3.37ꢀ3.32 (m, 1H), 2.62ꢀ2.48 (m, 2H), 2.04ꢀ1.88 (m, 4H),
1.70ꢀ1.62 (m, 2H), 1.48ꢀ1.41 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 213.6, 137.1, 130.9, 128.6, 128.5, 127.4, 126.3, 56.3, 42.5, 31.6, 29.7,
’ EXPERIMENTAL SECTION
Typical Procedure for the Gold(I)-Catalyzed Ring Expan-
sion from Allylic Ester Substituted Cycloalkanols 1a. The gold
catalyst was generated in an oven-dried Schlenk tube containing a
magnetic stirrer bar under N2 by addition of 0.05 mmol AuPPh3Cl,
0.05 mol AgSbF6, and 2 mL DCM. After the catalyst mixture stirred at
room temperature for 2 min, a solution of 1a (0.1 mmol) in 2 mL DCM
was added. The resulting mixture was allowed to stand at 30 °C, until
complete consumption of the starting material (as determined by TLC
28.0, 24.8; IR (neat) 2926, 2854, 1701, 1452, 964, 748, 696 cmꢀ1
.
(E)-2-Styrylcyclobutanone (2b). 1H NMR (400 MHz, CDCl3)
δ 7.35 (d, J = 8.0 Hz, 2H), 7.31 (t, J = 7.8 Hz, 2H), 7.25ꢀ7.21 (m, 1H),
6.50 (dd, J = 16.0, 1.2 Hz, 1H), 6.22 (dd, J = 16.0, 6.7 Hz, 1H),
4.18ꢀ4.10 (m, 1H), 3.21ꢀ3.11 (m, 1H), 3.07ꢀ2.98 (m, 1H),
2.44ꢀ2.34 (m, 1H), 2.09ꢀ1.99 (m, 1H); 13C NMR (100 MHz, CDCl3)
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δ 208.2, 136.7, 131.7, 128.5, 127.6, 126.2, 124.1, 63.1, 45.0, 17.1; IR
(neat) 2956, 2922, 1783, 1072, 966, 750, 964 cmꢀ1; HRMS (EI) calcd
for C12H12O [M] + 172.0895, found 172.0882.
intensity) 292 (M+, 62), 183(89), 181 (100), 128 (45), 95 (10), 77 (4),
67 (3); HRMS (EI) calcd for C15H17BrO [M] 292.0463, found
292.0469.
+
(E)-2-Styrylcyclopentanone 2c.29 1H NMR (400 MHz, CDCl3)
δ 7.34 (d, J = 7.3 Hz, 2H), 7.29 (t, J = 7.3 Hz, 2H), 7.21 (t, J = 7.2 Hz,
1H), 6.47 (d, J = 16.0 Hz, 1H), 6.24 (dd, J = 16.1, 6.3 Hz, 1H), 2.96 (dd,
J = 15.9, 8.0 Hz, 1H), 2.42ꢀ2.35 (m, 2H), 2.26ꢀ2.18 (m, 1H),
2.13ꢀ2.07 (m, 1H), 1.96ꢀ1.86 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 218.0, 137.0, 132.0, 128.5, 127.4, 126.2, 126.1, 52.4, 37.8, 29.8, 20.8: IR
(E)-2-(4-Methylstyryl)cycloheptanone 2j. 1H NMR (400 MHz,
CDCl3) δ 7.18 (d, J = 7.8 Hz, 2H), 7.03 (d, J = 7.9 Hz, 2H), 6.32 (d, J =
16.0 Hz, 1H), 6.17 (dd, J = 16.0, 7.5 Hz, 1H), 3.28ꢀ3.22 (m, 1H),
2.54ꢀ2.40 (m, 2H), 2.25 (s, 3H), 1.96ꢀ1.80 (m, 4H), 1.65ꢀ1.52
(m, 2H), 1.42ꢀ1.34 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 213.7,
137.1, 134.3, 130.7, 129.2, 127.5, 126.1, 56.3, 42.4, 31.5, 29.7, 27.9, 24.9,
21.1; IR (neat) 3022, 2923, 2854, 1703, 1452, 966, 808 cmꢀ1; MS (m/z,
rel intensity) 228 (M+, 14), 119 (100), 91 (26), 65 (6), 41 (4); HRMS
(EI) calcd for C16H20O [M] + 228.1514, found 228.1518.
(neat) 2960, 1732, 1647, 1182, 1028, 750, 698 cmꢀ1
.
(E)-2-styrylcyclohexanone 2d.4 1H NMR (400 MHz, CDCl3) δ
7.31 (d, J = 8.0 Hz, 2H), 7.22 (t, J = 7.3 Hz, 2H), 7.14 (t, J = 7.3 Hz, 1H),
6.37 (dd, J = 16.1, 6.5 Hz, 1H), 6.30 (d, J = 16.2 Hz, 1H), 3.15ꢀ3.09 (m,
1H), 2.41 (td, J = 13.6, 4.4 Hz, 1H), 2.33ꢀ2.25 (m, 1H), 2.14ꢀ2.09 (m,
1H), 2.02ꢀ1.95 (m, 1H), 1.89ꢀ1.83 (m, 1H), 1.74ꢀ1.65 (m, 3H); 13C
NMR (100 MHz, CDCl3) δ 211.0, 137.1, 131.4, 128.4, 127.6, 127.3,
126.3, 54.0, 41.7, 34.4, 27.6, 24.4.
(E)-2-(2-Methylstyryl)cycloheptanone 2k. 1H NMR (400 MHz,
CDCl3) δ 7.44ꢀ7.42 (m, 1H), 7.16ꢀ7.11 (m, 3H), 6.33 (d, J = 15.8 Hz,
1H), 6.18 (dd, J = 15.8, 7.7 Hz, 1H), 3.40ꢀ3.34 (m, 1H), 2.63ꢀ2.49
(m, 2H), 2.33 (s, 3H), 2.05ꢀ1.88 (m, 4H), 1.75ꢀ1.60 (m, 2H),
1.52ꢀ1.38 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 213.6, 136.2,
135.2, 130.1, 130.0, 128.8, 127.3, 126.0, 125.7, 56.6, 42.4, 31.7, 29.7, 27.9,
24.8, 19.7; IR (neat) 2927, 2854, 1708, 1454, 964, 752 cmꢀ1; MS (m/z,
rel intensity) 228 (M+, 100), 157 (21), 143 (45), 129 (33), 118 (41), 104
(E)-2-(4-Methylstyryl)cyclohexanone 2e. 1H NMR (400 MHz,
CDCl3) δ 7.27 (d, J = 8.1 Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 6.41ꢀ6.32
(m, 2H), 3.21ꢀ3.16 (m, 1H), 2.48 (td, J = 13.7, 3.6 Hz, 1H), 2.40ꢀ2.35
(m, 1H), 2.32 (s, 3H), 2.21ꢀ2.15 (m, 1H), 2.09ꢀ2.02 (m, 1H),
1.94ꢀ1.90 (m, 1H), 1.81ꢀ1.73 (m, 3H); 13C NMR (100 MHz, CDCl3)
δ 211.4, 137.1, 134.3, 131.2, 129.2, 126.4, 126.2, 54.1, 41.7, 34.5, 27.6,
24.4, 21.2; IR (neat) 2929, 2858, 1712, 1446, 1124, 966, 792 cmꢀ1; MS
(m/z, rel intensity) 214 (M+, 100), 143 (23), 129 (28), 115 (14), 105
(37), 91 (11), 77 (5): HRMS (EI) calcd for C15H18O [M] + 214.1358,
found 214.1357.
+
(6), 91 (9), 77 (3); HRMS (EI) calcd for C16H20O [M] 228.1514,
found 228.1516.
1
(E)-2-Styrylcyclooctanone 2m. H NMR (400 MHz, CDCl3)
δ 7.35 (d, J = 8.0 Hz, 2H), 7.29 (t, J = 7.2 Hz, 2H), 7.21 (t, J = 7.2 Hz,
1H), 6.44 (d, J = 16.0 Hz, 1H), 6.28 (dd, J = 16.0, 7.8 Hz, 1H),
3.42ꢀ3.36 (m, 1H), 2.54ꢀ2.47 (m, 1H), 2.43ꢀ2.37 (m, 1H),
2.04ꢀ1.82 (m, 4H), 1.76ꢀ1.65 (m, 2H), 1.58ꢀ1.41 (m, 4H); 13C
NMR (100 MHz, CDCl3) δ 217.0, 137.0, 131.1, 128.5, 127.4, 126.2,
55.2, 40.8, 32.6, 27.0, 26.2, 25.9, 24.6; IR (neat) 2921, 2854, 1699, 1446,
966, 748, 696 cmꢀ1; MS (m/z, rel intensity) 228 (M+, 80), 143 (40), 129
(100), 117 (22), 115 (32), 104 (67), 91 (29), 65 (3), 41 (5); HRMS
(EI) calcd for C16H20O [M] + 228.1514, found 228.1516.
(E)-2-(4-Methoxystyryl)cyclohexanone 2f.4 1H NMR (400 MHz,
CDCl3) δ 7.31 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 6.33 (d, J =
16.1 Hz, 1H), 6.27 (dd, J = 16.1, 6.1 Hz, 1H), 3.80 (s, 3H), 3.20ꢀ3.14
(m, 1H), 2.48 (td, J = 13.8, 3.8 Hz, 1H), 2.39ꢀ2.31 (m, 1H), 2.20ꢀ2.14
(m, 1H), 2.08ꢀ2.02 (m, 1H), 1.95ꢀ1.90 (m, 1H), 1.79ꢀ1.72 (m, 3H);
13C NMR (100 MHz, CDCl3) δ 211.4, 159.0, 130.8, 130.0, 127.4, 125.3,
113.9, 55.3, 54.0, 41.7, 34.5, 27.6, 24.4; IR (neat) 2933, 2860, 1708, 1606,
1
(E)-2-Styrylcyclononanone 2n. H NMR (400 MHz, CDCl3)
δ 7.34 (d, J = 7.7 Hz, 2H), 7.29 (t, J = 7.2 Hz, 2H), 7.21 (t, J = 7.1 Hz,
1H), 6.44 (d, J = 15.9 Hz, 1H), 6.22 (dd, J = 15.9, 8.3 Hz, 1H),
3.49ꢀ3.43 (m, 1H), 2.54ꢀ2.45 (m, 2H), 2.08ꢀ1.99 (m, 1H),
1.95ꢀ1.81 (m, 3H), 1.72ꢀ1.64 (m, 1H), 1.60ꢀ1.54 (m, 3H),
1.48ꢀ1.38 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 216.5, 137.0,
131.2, 128.8, 128.5, 127.4, 126.2, 57.3, 41.7, 31.6, 25.7, 25.3, 24.8, 24.5,
24.0; IR (neat) 2930, 2852, 1701, 1450, 946, 748, 695 cmꢀ1; MS (m/z,
rel intensity) 242 (M+, 51), 340 (5), 143 (32), 129 (100), 115 (26), 104
1508, 1249, 1174, 1031, 966, 839 cmꢀ1
.
(E)-2-(4-Fluorostyryl)cyclohexanone 2g. 1H NMR (400 MHz,
CDCl3) δ 7.35 (d, J = 8.4 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 6.98 (t, J =
8.7 Hz, 2H), 6.34ꢀ6.33 (m, 2H), 3.20ꢀ3.17 (m, 1H), 2.48 (td, J = 13.7,
3.6 Hz, 1H), 2.40ꢀ2.32 (m, 1H), 2.21ꢀ2.16 (m, 1H), 2.11ꢀ2.04 (m,
1H), 1.95ꢀ1.91 (m, 1H), 1.79ꢀ1.72 (m, 3H); 13C NMR (100 MHz,
CDCl3) δ 211.1, 162.2 (d, J = 245.0 Hz), 133.3, 130.2, 127.7 (d, J = 7.9
Hz), 127.3, 115.3 (d, J = 21.5 Hz), 53.9, 41.8, 34.4, 27.6, 24.5; IR (neat)
2935, 2864, 1714, 1508, 1226, 966, 850, 804 cmꢀ1; MS (m/z, rel
intensity) 218 (M+, 100), 174 (36), 146 (34), 122 (77), 109 (31), 95
(3), 81 (13); HRMS (EI) calcd for C14H15FO [M] + 218.1107, found
218.1110.
+
(38), 91 (23), 77 (7), 41 (5); HRMS (EI) calcd for C17H22O [M]
242.1671, found 242.1674.
(E)-2-Styrylcyclotridecanone 2o. 1H NMR (400 MHz, CDCl3)
δ 7.35 (d, J = 8.1 Hz, 2H), 7.30 (t, J = 7.3 Hz, 2H), 7.22 (t, J = 7.1 Hz,
1H), 6.46 (d, J = 15.8 Hz, 1H), 6.18 (dd, J = 15.8, 9.0 Hz, 1H), 3.41 (td,
J = 9.3, 3.8 Hz, 1H), 2.66 (ddd, J = 16.1, 9.2, 3.5 Hz, 1H), 2.42 (ddd, J =
16.1, 8.0, 3.7 Hz, 1H), 2.02ꢀ1.93 (m, 1H), 1.81ꢀ1.72 (m, 1H),
1.60ꢀ1.50 (m, 2H), 1.40ꢀ1.27 (m, 16H); 13C NMR (100 MHz,
CDCl3) δ 212.3, 136.9, 131.6, 128.6, 127.5, 126.2, 56.4, 40.9, 31.8,
26.5, 26.1, 26.0, 25.7, 25.4, 25.1, 24.4, 24.2, 22.8; IR (neat) 2926, 2858,
1708, 1460, 966, 748, 692 cmꢀ1; MS (m/z, rel intensity) 298 (M+, 100),
143 (23), 129 (54), 118 (55), 91 (20), 41 (5); HRMS (EI) calcd for
C21H30O [M]+ 298.2297, found 298.2299.
(E)-2-(4-Fluorostyryl)cycloheptanone 2h. 1H NMR (400 MHz,
CDCl3) δ 7.33 (d, J = 8.6 Hz, 1H), 7.31 (d, J = 8.6 Hz, 1H), 7.00 (t, J =
8.7 Hz, 2H), 6.38 (d, J = 16.0 Hz, 1H), 6.22 (dd, J = 16.0, 7.6 Hz, 1H),
3.35ꢀ3.30 (m, 1H), 2.61ꢀ2.48 (m, 2H), 2.03ꢀ1.86 (m, 4H),
1.72ꢀ1.58 (m, 2H), 1.50ꢀ1.40 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 213.7, 162.6 (d, J = 245.3 Hz), 133.2, 129.6, 128.3, 127.7 (d, J = 7.6
Hz), 115.4 (d, J = 21.5 Hz), 56.1, 42.5, 31.6, 30.0, 28.0, 24.8; IR (neat)
2927, 2854, 1701, 1508, 1226, 1157, 1095, 823 cmꢀ1; MS (m/z, rel
intensity) 232 (M+, 39), 161 (23), 147 (27), 123 (100), 109 (27), 95
2-((1E,3E)-4-Phenylbuta-1,3-dien-1-yl)cycloheptanone
2p. 1H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 7.6 Hz, 2H), 7.30 (t, J =
7.4 Hz, 2H), 7.21 (t, J = 7.3 Hz, 1H), 6.75 (dd, J = 15.6, 10.4 Hz, 1H),
6.49 (d, J = 15.7 Hz, 1H), 6.24 (dd, J = 15.3, 10.4 Hz, 1H), 5.90 (dd, J =
15.2, 7.6 Hz, 1H), 3.30ꢀ3.25 (m, 1H), 2.59ꢀ2.46 (m, 2H), 2.01ꢀ1.86
(m, 5H), 1.68ꢀ1.60 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 213.4,
137.3, 132.6, 131.8, 131.5, 128.7, 128.5, 127.4, 126.2, 56.1, 42.4, 31.4,
29.7, 27.9, 24.8; IR (neat) 2912, 2850, 1703, 1452, 1163, 987, 941, 748,
+
(28), 83 (9), 67 (5), 41 (8); HRMS (EI) calcd for C15H17FO [M]
232.1263, found 232.1265.
(E)-2-(4-Bromostyryl)cycloheptanone 2i. 1H NMR (400 MHz,
CDCl3) δ 7.41 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 6.36 (d, J =
16.0 Hz, 1H), 6.30 (dd, J = 16.0, 6.2 Hz, 1H), 3.36ꢀ3.31 (m, 1H),
2.61ꢀ2.50 (m, 2H), 2.03ꢀ1.86 (m, 4H), 1.72ꢀ1.59 (m, 2H),
1.51ꢀ1.41 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 213.4, 136.1,
131.6, 129.7, 129.6, 127.8, 121.1, 56.1, 42.6, 31.6, 29.6, 28.1, 24.7; IR
(neat) 2926, 2848, 1697, 1487, 1070, 812, 501 cmꢀ1; MS (m/z, rel
+
962 cmꢀ1; HRMS (EI) calcd for C17H20NaO [M + Na] 263.1406,
found 263.1402.
8820
dx.doi.org/10.1021/jo2015517 |J. Org. Chem. 2011, 76, 8814–8823

The Journal of Organic Chemistry
ARTICLE
(1S,3R, 6S,8S)-1-((E)-Styryl)tricyclo[4.3.1]undecan-2-one
2q. 1H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 7.3 Hz, 2H), 7.29 (t,
J = 7.3 Hz, 2H), 7.20 (t, J = 7.3 Hz, 1H), 6.41 (d, J = 16.1 Hz, 1H), 6.33
(dd, J = 16.0, 6.7 Hz, 1H), 3.29 (d, J = 6.5 Hz, 1H), 2.84 (t, J = 6.2 Hz,
1H), 2.21ꢀ2.18 (m, 2H), 2.05ꢀ2.00 (m, 3H), 1.94ꢀ1.88 (m, 3H),
1.82ꢀ1.76 (m, 3H), 1.72ꢀ1.69 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 217.1, 137.3, 131.7, 129.4, 128.4, 127.2, 126.2, 60.8, 49.0, 39.0, 35.4,
33.0, 32.6, 32.0, 31.9, 29.6, 26.9, 26.8; IR (neat) 2912, 2848, 1691, 1446,
1074, 939, 738, 694 cmꢀ1; HRMS (EI) calcd for C19H23O [M + H] +
267.1743, found 267.1738.
(2S*,3R*,3aS*,8aR*)-3-Iodo-2-phenyloctahydro-2H-cyclo-
hepta[b]furan 10. 1H NMR (400 MHz, CDCl3) δ 7.45 (dd, J = 8.0,
1.6 Hz, 2H), 7.38ꢀ7.30 (m, 3H), 4.89 (d, J = 9.7 Hz, 1H), 4.28 (td, J =
10.0, 3.6 Hz, 1H), 3.56 (t, J = 9.6 Hz, 1H), 2.78ꢀ2.70 (m, 1H),
2.10ꢀ2.00 (m, 2H), 1.90ꢀ1.73 (m, 4H), 1.52ꢀ1.43 (m, 1H),
1.41ꢀ1.26 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 137.9, 128.4,
128.3, 126.9, 88.0, 82.2, 54.9, 36.4, 32.1, 31.2, 28.4, 27.4, 25.0; IR (neat)
2922, 2850, 1452, 1039, 1024, 758, 696 cmꢀ1; MS (m/z, rel intensity)
342 (M+, 2), 215 (100), 129 (22), 105 (48), 91 (22), 77 (8), 41 (4);
HRMS (EI) calcd for C15H19IO [M]+ 342.0481, found 342.0482.
(E)-5-Styryldihydrofuran-2(3H)-one 11.17a 1H NMR (400 MHz,
CDCl3) δ 7.40 (d, J = 7.8 Hz, 2H), 7.34 (t, J = 8.0 Hz, 2H), 7.28 (t, J =
7.1 Hz, 1H), 6.69 (d, J = 15.9 Hz, 1H), 6.20 (dd, J = 15.9, 6.6 Hz, 1H),
5.12 (td, J = 14.6, 7.9 Hz, 1H), 2.66ꢀ2.56 (m, 2H), 2.54ꢀ2.45 (m, 1H),
2.15ꢀ2.06 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 176.8, 135.6,
132.8, 128.7, 128.4, 126.7, 126.4, 80.6, 28.9, 28.5.
(E)-1-Phenylhept-1-en-4-one 2r.30 1H NMR (400 MHz,
CDCl3) δ 7.37 (d, J = 7.3 Hz, 2H), 7.31 (t, J = 7.3 Hz, 2H), 7.22 (t,
J = 7.2 Hz, 1H), 6.47 (d, J = 15.9 Hz, 1H), 6.31 (td, J = 15.7, 7.0 Hz, 1H),
3.31 (d, J = 6.9 Hz, 2H), 2.47 (t, J = 7.3 Hz, 2H), 1.63 (sext, J = 7.4 Hz,
2H), 0.93 (t, J = 7.4 Hz, 3H).
(E)-3,5-Diphenylpent-4-en-2-one 2s.31 1H NMR (400 MHz,
MeOD) δ 7.39ꢀ7.36 (m, 4H), 7.32ꢀ7.26 (m, 5H), 7.20 (t, J = 7.2 Hz,
1H), 6.65 (dd, J = 15.9, 8.2 Hz, 1H), 6.25 (d, J = 15.9 Hz, 1H), 4.66 (d,
J = 8.2 Hz, 1H), 2.14 (s, 3H); 13C NMR (100 MHz, MeOD) δ 207.9,
138.5, 137.0, 132.3, 128.6, 128.1, 128.0, 127.3, 127.2, 127.0, 125.9,
62.4, 27.
(2R*,5S*)-5-Methyl-2-((E)-styryl)cycloheptanone anti-2t.
1H NMR (400 MHz, CDCl3) δ 7.35 (d, J = 7.3 Hz, 2H), 7.29 (d, J = 7.3
Hz, 2H), 7.21 (t, J = 7.2 Hz, 1H), 6.43 (d, J = 16.0 Hz, 1H), 6.25 (dd,
J = 16.0, 7.5 Hz, 1H), 3.33ꢀ3.27 (m, 1H), 2.66 (td, J = 13.4, 3.3 Hz, 1H),
2.44 (ddd, J = 13.6, 6.0, 2.8 Hz, 1H), 2.05ꢀ1.98 (m, 1H), 1.94ꢀ1.84 (m,
2H), 1.78ꢀ1.67 (m, 1H), 1.63ꢀ1.56 (m, 1H), 1.42ꢀ1.31 (m, 1H),
1.26ꢀ1.13 (m, 1H), 0.98 (d, J = 6.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 213., 137.0, 130.9, 128.5, 128.4, 127.4, 126.2, 56.7, 41.2, 36.7,
36.5, 33.2, 30.9, 23.5; IR (neat) 2924, 2868, 1711, 1450, 966, 752,
692 cmꢀ1; MS (m/z, rel intensity) 228 (M+, 84), 143 (100), 130 (48),
128 (48), 115 (30), 104 (50), 91 (19),77 (5), 41 (4); HRMS (EI) calcd
for C16H20O [M] + 228.1514, found 228.1516.
(2S*,5S*)-5-Methyl-2-((E)-styryl)cycloheptanone syn-2t.
1H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 8.0 Hz, 2H), 7.30 (d, J =
7.8 Hz, 2H), 7.21 (t, J = 7.2 Hz, 1H), 6.41ꢀ6.39 (m, 2H), 3.39ꢀ3.35 (m,
1H), 2.60ꢀ2.57 (m, 2H), 1.99-.94 (m, 2H), 1.90ꢀ1.83 (m, 2H),
1.76ꢀ1.70 (m, 1H), 1.49ꢀ1.40 (m, 2H), 0.97 (d, J = 6.7 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 213.7, 127.2, 131.2, 128.5, 128.2, 127.4,
126.3, 55.3, 40.6, 34.1, 33.8, 31.9, 28.3, 21.4; MS (m/z, rel intensity) 228
(M+, 100), 143 (71), 130 (42), 128 (41), 115 (23), 104 (21), 91 (5),77
(6); HRMS (EI) calcd for C16H20O [M] + 228.1514, found 228.1517.
(E)-4-Phenylcycloundec-5-enone 7. 1H NMR (400 MHz,
CDCl3) δ 7.31ꢀ7.27 (m, 2H), 7.25ꢀ7.23 (m, 2H), 7.18 (tt, J = 7.1,
1.4 Hz, 1H), 5.46 (ddd, J = 15.0, 10.5, 4.6 Hz, 1H), 5.29 (ddd, J = 14.6,
10.1, 1.3 Hz, 1H), 3.11 (ddd, J = 12.5, 10.1, 3.4 Hz, 1H), 2.71ꢀ2.61 (m,
2H), 2.50 (q, J = 12.8 Hz, 1H), 2.28 (dd, J = 15.7, 7.7 Hz, 1H),
2.22ꢀ2.14 (m, 2H), 1.92ꢀ1.83 (m, 1H), 1.81ꢀ1.73 (m, 1H),
1.71ꢀ1.63 (m, 3H), 1.45ꢀ1.35 (m, 1H), 1.14ꢀ1.02 (m, 2H) ; 13C
NMR (100 MHz, CDCl3) δ 211.1, 145.0, 134.7, 130.8, 128.5, 126.9,
126.1, 52.5, 42.6, 40.6, 34.0, 30.4, 25.7, 24.4, 24.3; IR (neat)3026, 2926,
2852, 1708, 1438, 974, 752, 698 cmꢀ1; MS (m/z, rel intensity) 242 (M+,
20), 224 (100), 143 (42), 129 (61), 91 (26), 77 (5), 41(3); HRMS (EI)
calcd for C17H22O [M]+ 242.1671, found 242.1673.
2-Phenyl-1-oxaspiro[4.5]dec-3-ene 3a. 1H NMR (400 MHz,
CDCl3) δ 7.27ꢀ7.17 (m, 5H), 5.94ꢀ5.92 (m, 1H), 5.72ꢀ5.70 (m, 2H),
1.67ꢀ1.60 (m, 5H), 1.49ꢀ1.35 (m, 5H); 13C NMR (100 MHz, CDCl3)
δ 142.4, 133.9, 129.0, 128.4, 127.5, 126.5, 90.2, 86.4, 38.3, 37.4, 25.5,
23.6, 23.3; IR (neat) 2958, 2946, 2854, 1448, 1259, 1085, 1062, 1041,
+
1022, 800, 696 cmꢀ1; HRMS (EI) calcd for C15H19O [M + H]
215.1430, found 215.1426.
2-(4-Fluorophenyl)-1-oxaspiro[4.5]dec-3-ene 3h. 1H NMR
(400 MHz, CDCl3) δ 7.29 (t, J = 7.6 Hz, 2H), 7.01 (t, J = 8.6 Hz, 2H),
6.02 (d, J = 4.0 Hz, 1H), 5.76ꢀ5.74 (m, 2H), 1.73ꢀ1.64 (m, 5H),
1.56ꢀ1.47 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 162.6 (d, J = 234.9
Hz), 138.2, 134.2, 128.8, 128.2 (d, J = 8.0 Hz), 115.2 (d, J = 21.3 Hz),
90.2, 85.7, 38.4, 37.3, 25.4, 23.5, 23.3; IR (neat) 2946, 2852, 1508, 1220,
1068, 1041, 835, 825, 792 cmꢀ1; HRMS (EI) calcd for C15H18FO [M +
H] + 233.1336, found 233.1335.
1
2-(4-Bromophenyl)-1-oxaspiro[4.5]dec-3-ene 3i. H NMR
(400 MHz, CDCl3) δ 7.45 (d, J = 7.7 Hz, 2H), 7.21 (d, J = 7.7 Hz, 2H),
6.02ꢀ6.01 (m, 1H), 5.80ꢀ5.75 (m, 2H), 1.76ꢀ1.64 (m, 6H),
1.55ꢀ1.44 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 141.6, 134.4,
131.4, 128.5, 128.1, 121.3, 90.4, 85.7, 38.3, 37.3, 25.4, 23.5, 23.3; IR
(neat) 3076, 2946, 2854, 1487, 1446, 1068, 1047, 1010, 846, 817, 777,
725 cmꢀ1; HRMS (EI) calcd for C15H18BrO [M + H] + 293.0536, found
293.0545.
2-(p-Tolyl)-1-oxaspiro[4.5]dec-3-ene 3j. 1H NMR (400 MHz,
CDCl3) δ 7.23 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 7.9 Hz, 2H), 6.01 (dd, J =
6.2, 2.7 Hz, 1H), 5.78ꢀ5.77 (m, 2H), 2.34 (s, 3H), 1.78ꢀ1.74 (m, 4H),
1.71ꢀ1.65 (m, 2H), 1.54ꢀ1.44 (m, 4H); 13C NMR (100 MHz, CDCl3)
δ 139.5, 137.1, 133.8, 129.1, 129.0, 126.5, 90.0, 86.2, 38.4, 37.4, 25.5,
23.6, 23.3, 21.1; IR (neat) 2946, 2854, 1512, 1445, 1083, 1070, 1049,
1041, 1020, 815, 779 cmꢀ1; HRMS (EI) calcd for C16H21O [M + H] +
229.1587, found 229.1582.
2-(o-Tolyl)-1-oxaspiro[4.5]dec-3-ene 3k. 1H NMR (400 MHz,
CDCl3) δ 7.43 (d, J = 7.3 Hz, 1H), 7.22ꢀ7.12 (m, 3H), 6.04ꢀ6.03 (m,
1H), 6.00 (dd, J = 6.0, 2.4 Hz, 1H), 5.83 (dd, J = 5.9, 1.3 Hz, 1H), 2.38 (s,
3H), 1.83ꢀ1.62 (m, 6H), 1.53ꢀ1.42 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 140.3, 134.6, 134.0, 130.1, 128.1, 127.1, 126.2, 126.0, 89.8,
83.1, 38.1, 37.3, 25.5, 23.6, 23.3, 19.1; IR (neat) 3020, 2946, 2854, 1448,
1267, 1068, 1043, 748, 713 cmꢀ1; HRMS (EI) calcd for C16H21O
[M + H] + 229.1587, found 229.1582.
(E)-4-Phenylcycloheptadec-5-enone 8. 1H NMR (400 MHz,
CDCl3) δ 7.29 (t, J = 7.4 Hz, 2H), 7.23ꢀ7.16 (m, 3H), 5.52ꢀ5.43 (m,
2H), 3.22ꢀ3.17 (m, 1H), 2.55ꢀ2.45 (m, 2H), 2.43ꢀ2.32 (m, 2H),
2.14ꢀ1.91 (m, 5H), 1.67ꢀ1.62 (m, 2H), 1.39ꢀ1.29 (m, 15H); 13C
NMR (100 MHz, CDCl3) δ 211.8, 145.1, 133.3, 131.5, 128.4, 127.1,
126.1, 48.4, 42.6, 41.0, 31.8, 30.1, 29.6, 28.7, 27.9, 27.7, 27.6, 27.2, 26.9,
23.9; IR (neat) 3026, 2926, 2854, 1710, 1452, 968, 756, 698 cmꢀ1; MS
(m/z, rel intensity) 326 (M+, 47), 157 (22), 143 (100), 129 (68), 91
(34), 77 (3), 41 (13); HRMS (EI) calcd for C23H34O [M]+ 326.2610,
found 326.2607.
2-Phenyl-1-oxaspiro[4.6]undec-3-ene 3m. 1HNMR(400MHz,
CDCl3) δ 7.33ꢀ7.31 (m, 4H), 7.28ꢀ7.35 (m, 1H), 5.99ꢀ5.97 (m, 1H),
5.74ꢀ5.71 (m, 2H), 1.98ꢀ1.93 (m, 2H), 1.78ꢀ1.68 (m, 5H),
1.66ꢀ1.59 (m, 2H), 1.53ꢀ1.46 (m, 3H); 13C NMR (100 MHz, CDCl3)
δ 142.2, 135.6, 128.3, 128.0, 127.5, 126.6, 93.6, 86.2, 41.3, 40.0, 29.6,
23.0, 22.9; IR (neat) 2946, 2852, 1454, 1085, 1045, 1028, 752,
+
696 cmꢀ1; HRMS (EI) calcd for C16H21O [M] 229.1587, found
229.1583.
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The Journal of Organic Chemistry
ARTICLE
2-Phenyl-1-oxaspiro[4.7]dodec-3-ene 3n. 1H NMR (400 MHz,
CDCl3) δ 7.33ꢀ7.32 (m, 4H), 7.29ꢀ7.24 (m, 1H), 6.02 (dd, J = 6.2,
2.8 Hz, 1H), 5.75ꢀ5.73 (m, 2H), 2.10ꢀ2.03 (m, 1H), 1.99ꢀ1.93
(m, 1H), 1.88ꢀ1.82 (m, 1H), 1.78ꢀ1.58 (m, 8H), 1.52ꢀ1.47 (m, 3H);
13C NMR (100 MHz, CDCl3) δ 142.6, 135.0, 128.5, 128.3, 127.5, 126.6,
93.4, 86.2, 36.6, 35.6, 28.4, 28.2, 24.9, 22.7, 22.6; IR (neat) 2946, 2850, 1456,
1082, 1066, 1028, 696 cmꢀ1; HRMS (EI) calcd for C17H23O [M + H] +
243.1743, found 243.1741.
(4) A recent example for Pd/Cu catalyzed ring expansion of 1,4-
allylic diol derivative, which worked only in four- or five-membered
substrates:Lange, A.; Heydenreuter, W.; Menz, H.; Kirsch, S. F. Synlett
2009, 2987.
(5) Recent reviews on gold catalysis: (a) Hashmi, A. S. K. Chem. Rev.
2007, 107, 3180. (b) F€urstner, A.; Davies, P. W. Angew. Chem., Int. Ed.
2007, 46, 3410. (c) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008,
108, 3239. (d) Arcadi, A. Chem. Rev. 2008, 108, 3266. (e) Jimenez-
Nunez, E.; Echavarren, A. M. Chem. Rev. 2008, 108, 3326. (f) Gorin,
D. J.; Sherry, B. D.; Toste, F. D. Chem. Rev. 2008, 108, 3351.
(g) F€urstner, A. Chem. Soc. Rev. 2009, 38, 3208. (h) Nevado, C. Chimia
2010, 64, 247. (i) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2010, 49, 5232.
A recent review on gold-catalyzed ring expansions: (j) Garayalde, D.;
Nevado, C. Beilstein J. Org. Chem. 2011, 7, 767.
(6) The first gold-catalyzed ring expansion example was described by
Hashmi group, which focused on the ring expansion of the heterocyclic
epoxide: Hashmi, A. S. K.; Sinha, P. Adv. Synth. Catal. 2004, 346, 432.
(7) (a) Markham, J. P.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc.
2005, 127, 9708. (b) Kleinbeck, F.; Toste, F. D. J. Am. Chem. Soc. 2009,
131, 9178.
2-Phenyl-1-oxaspiro[4.11]hexadec-3-ene 3o. 1H NMR (400
MHz, CDCl3) δ 7.36ꢀ7.31 (m, 4H), 7.28ꢀ7.24 (m, 1H), 5.97 (dd, J =
6.0, 2.4 Hz, 1H), 5.75ꢀ5.73 (m, 2H), 1.85ꢀ1.76 (m, 2H), 1.74ꢀ1.66
(m, 1H), 1.63ꢀ1.59 (m, 1H), 1.51ꢀ1.47 (m, 4H), 1.40ꢀ1.35 (m, 14H);
13C NMR (100 MHz, CDCl3) δ 142.3, 134.5, 128.5, 128.3, 127.5, 126.5,
93.3, 86.6, 34.8, 33.9, 26.5, 26.0, 22.6, 22.2, 20.3, 19.7; IR (neat) 2946,
2848, 1469, 1446, 1058, 1041, 1016, 746, 696 cmꢀ1; HRMS (EI) calcd
for C21H31O [M + H] + 299.2369, found 299.2371.
(1R*,2R*,5S*)-50-Phenyl-5H-spiro[adamantane-2,20-furan]
1
3q. H NMR (400 MHz, CDCl3) δ 7.35ꢀ7.30 (m, 4H), 7.28ꢀ7.23
(m, 1H), 6.34 (dd, J = 5.8, 2.2 Hz, 1H), 5.84ꢀ5.81 (m, 2H), 2.30 (d, J =
12.2 Hz, 2H), 1.92ꢀ1.74 (m, 10H), 1.61 (d, J = 12.4 Hz, 2H) ; 13C NMR
(100 MHz, CDCl3) 142.9, 132.5, 129.9, 128.2, 127.3, 126.2, 94.1, 86.2,
39.2, 38.6, 37.9, 35.9, 35.7, 33.9, 33.2, 27.6, 26.8;δ IR (neat) 2945, 2849,
1452, 1043, 1040, 1021, 749, 696 cmꢀ1; HRMS (EI) calcd for C19H23O
[M + H] + 267.1743, found 267.1739.
(8) Ye, S. Y.; Yu, Z.-X. Org. Lett. 2010, 12, 804.
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(10) Other examples of gold-catalyzed ring-opening or ring-
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Synthesis 2007, 2107. (b) Garayalde, D.; Gꢀomez-Bengoa, E.; Huang, X.;
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Krinsky, J. L.; Toste, F. D. J. Am. Chem. Soc. 2009, 131, 4513.
(11) Chen, A.; Lin, R.; Liu, Q.; Jiao, N. Chem. Commun. 2009, 6842.
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(b) Trost, B. M.; Xie, J.; Maulide, N. J. Am. Chem. Soc. 2008, 130, 17258.
(13) Xu, H.-D.; Zhang, W.; Shu, D. X.; Werness, J. B.; Tang, W. P.
Angew. Chem., Int. Ed. 2008, 47, 8933.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures and
b
data for all new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
(14) (a) Iwasawa, N.; Matsuo, T.; Iwamoto, M.; Ikeno, T. J. Am.
Chem. Soc. 1998, 120, 3903. (b) Iwasawa, N.; Narasaka, K. Top. Curr.
Chem. 2000, 207, 69.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: zilichen@ruc.edu.cn.
(15) Shi, M.; Liu, L.-P.; Tang, J. J. Am. Chem. Soc. 2006, 128, 7430.
€
(16) Furstner., A.; Aissa, C. J. Am. Chem. Soc. 2006, 128, 6306.
(17) (a) Wang, Y. H.; Zhu, L. L.; Zhang, Y. X.; Chen, Z. Chem.
Commun. 2010, 46, 577. (b) Chen, Z.; Zhang, Y.-X.; Wang, Y.-H.; Zhu,
L.-L.; Liu, H.; Li, X.-X.; Guo, L. Org. Lett. 2010, 12, 3468. (c) Zhu, L.-L.;
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(19) Gold-catalyzed Prins cyclizations: Jimenez-Nunez, E.; Claverie,
C. K.; Nieto-Oberhuber, C.; Echavarren, A. M. Angew. Chem., Int. Ed.
2006, 45, 5452.
’ ACKNOWLEDGMENT
Support of this work by a grant from National Sciences
Foundation of China (nos. 20872176 and 21072224) and by the
Fundamental Research Funds for the Central Universities and the
Research Funds of Renmin University of China (11XNI003) is
gratefully acknowledged.
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