Hot water-promoted cyclopropylcarbinyl rearrangement facilitates construction of homoallylic alcohols

Article abstract of DOI:10.1039/c5ob00305a

In refluxing 9 : 1 (v/v) H₂O-1,4-dioxane and without an additional catalyst, the rearrangements of various types of cyclopropyl carbinols were attempted. It was found that the reactions generally gave homoallylic alcohols in good to very high chemical yields. Rearrangements of bicyclic or tricyclic cyclopropyl carbinols readily gave the desired ring-expanded cyclic homoallylic alcohols which are difficult to synthesize by other means.

Full text of DOI:10.1039/c5ob00305a

Organic &
Biomolecular Chemistry
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Hot water-promoted cyclopropylcarbinyl
rearrangement facilitates construction of
homoallylic alcohols†
Cite this: Org. Biomol. Chem., 2015,
13, 5012
Pei-Fang Li, Cheng-Bo Yi and Jin Qu*
In refluxing 9 : 1 (v/v) H2O–1,4-dioxane and without an additional catalyst, the rearrangements of various
types of cyclopropyl carbinols were attempted. It was found that the reactions generally gave homoallylic
alcohols in good to very high chemical yields. Rearrangements of bicyclic or tricyclic cyclopropyl carbi-
nols readily gave the desired ring-expanded cyclic homoallylic alcohols which are difficult to synthesize
by other means.
Received 12th February 2015,
Accepted 18th March 2015
DOI: 10.1039/c5ob00305a
www.rsc.org/obc
conjugated polyene or enyne structural motifs occur in hot
water in the absence of any additional catalyst,5f and we
Introduction
The homoallylic alcohol is a common structural motif in expected that cyclopropylcarbinyl rearrangements could be
natural products and pharmaceuticals. The most widely used conducted under similar reaction conditions.
strategy for the synthesis of homoallylic alcohols is allylation
of carbonyl compounds with allylmetal reagents, and very high
enantioselectivities can be achieved with the assistance of
Results and discussion
chiral ligands.1 Rearrangements of cyclopropyl carbinols can
also lead to homoallylic alcohols,2 including cyclic homoallylic
In this study, we found that in refluxing water, rearrangement
of phenyl-substituted cyclopropyl carbinol 1a gave the corres-
ponding homoallylic alcohol 2a, but in only 5% yield after
48 h (Table 1, entry 1). However, the addition of a small
amount of an organic co-solvent to improve substrate dis-
persion speeded up the reaction, and etheric solvents were
superior to other polar organic solvents (entries 2–7, note that
alcohols with the double bond and the hydroxy group in the
same ring, which are difficult to synthesize by other means.
However, most of the recent reports have focused on tetrasub-
stituted cyclopropyl carbinol substrates.2i–m Furthermore,
cyclopropylcarbinyl rearrangements in bicyclic and tricyclic
ring systems have not been systematically studied.3 Herein,
we report that hot water promotes rearrangements of various
types of cyclopropyl carbinols to afford acyclic or cyclic homo-
allylic alcohols in high yields.
In addition to being an extremely polar reaction medium,
water has unique chemical and physical properties that
allow it to catalyze organic reactions.4 As the temperature is
increased, the self-ionization of water increases substantially;
the pKw of water is 12.3 at 100 °C, at which both the strong
acid H3O+ and the strong base OH− are more abundant than
that at 25 °C. We previously found that hot water acts as a
mildly acidic catalyst to promote organic reactions traditionally
catalyzed by Brønsted or Lewis acids.5 Recently, we reported
that 1,n-rearrangements (n = 3, 5, 7, 9) of allylic alcohols to
Table 1 Rearrangement of 1a in aqueous solutions under reflux
conditionsa
Entry
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
H2O
48
27
48
30
33
48
48
48
48
5
91
50
87
86
11
40
82
22
H2O–dioxane, 9 : 1
H2O–THF, 9 : 1
H2O–DME, 9 : 1
H2O–diglyme, 9 : 1
H2O–CH3CN, 9 : 1
H2O–i-PrOH, 9 : 1
H2O–dioxane, 4 : 1
H2O–dioxane, 1 : 1
State Key Laboratory and Institute of Elemento-Organic Chemistry, Collaborative
Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University,
Tianjin, 300071, China. E-mail: qujin@nankai.edu.cn
†Electronic supplementary information (ESI) available: All 1H and 13C NMR
spectra. CCDC 1008768. For ESI and crystallographic data in CIF or other elec-
tronic format see DOI: 10.1039/c5ob00305a
a Reaction conditions: 1 mmol of 1a in solvent (25 mL), with vigorous
stirring. b Isolated yield.
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Table 2 Rearrangements of acyclic cyclopropyl carbinolsa
Entry
Substrate
Time (h)
Product
Yieldb (%)
1
2
3
4
1a
1b
1c
1d
R1 = C6H5
27
2
18
48
2a
2b
2c
2d
R1 = C6H5
91
82
81
66
R1 = 4-MeOC6H4
R1 = 2-HOC6H4
R1 = 4-ClC6H4
R1 = 4-MeOC6H4
R1 = 2-HOC6H4
R1 = 4-ClC6H4
5
6
1e
1f
R1 = C6H5, R2 = Me
R1, R2 = C6H5
24
24
2e
2f
R1 = C6H5, R2 = Me
R1, R2 = C6H5
75 E : Z = 13 : 1c
96
7d
1g
9
2g
85 E : Z = 8 : 1c
8d
1h
8
2h
88 E : Z = 7 : 1c
9
10
11
1i
1j
1k
R = H
R = C6H5
R = C3H5
16
24
26
2i
2j
2k
R = H
R = C6H5
R = C3H5
80
89
80
12d
1l
72
2l
83 E : Z = 1 : 1c
13
1m
15
2m
2n
95
14
1n
1o
36
24
97 E : Z = 4 : 1c
15d
N.R.
a Reaction conditions: 1 mmol substrate in mixed solvent (H2O–1,4-dioxane = 9 : 1, 25 mL), with vigorous stirring. b Isolated yield. c Determined
by 1H NMR spectroscopy. d H2O–1,4-dioxane = 4 : 1.
no reaction occurred in any of the organic co-solvents alone).
Various types of substituted cyclopropyl carbinol substrates
In 9 : 1 (v/v) H2O–1,4-dioxane,6 a 91% yield of 2a was obtained were subsequently investigated (Table 2).8 Secondary cyclo-
along with a small amount of an intermolecular etherification propyl carbinols with an electron-donating substituent reacted
product. When the volume fraction of 1,4-dioxane was more readily than a substrate with a weakly electron-withdraw-
increased, the reaction rate decreased substantially (entries 8 ing chloride substituent (compare entries 2 and 3 with entry
and 9), perhaps owing to a reduction in the extent of 4). Tertiary alcohol substrates provided the desired homoallylic
ionization of water,7 a decrease in the dielectric constant, or alcohols with a trisubstituted alkene (entries 5 and 6). Both
both.
the reaction of 1g, which has a double bond between the
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hydroxy group and the phenyl group, and the reaction of 1h,
which has a double bond between the hydroxy group and the
Conclusions
cyclopropyl ring, readily afforded the same diene with similar In summary, we report for the first time that without an
E/Z ratios (entries 7 and 8). Ring-opening reactions of alkyne- additional catalyst, cyclopropylcarbinyl rearrangements pro-
substituted cyclopropyl carbinols were also investigated for duced homoallylic alcohols in good to excellent yields in a
construction of conjugated enynes.2i–m Propargylic alcohol 1i, refluxing mixture of water and an organic solvent. Rearrange-
which is substituted with a terminal alkyne moiety, rearranged ments of bicyclic or tricyclic cyclopropyl carbinols readily gave
to afford conjugated enyne 2i in 80% yield (entry 9). Com- the desired ring-expanded cyclic homoallylic alcohols. More
pounds 1j and 1k, each bearing an internal alkyne moiety, importantly, the unique catalytic power of water observed in
reacted smoothly to afford the corresponding conjugated the current study adds to our understanding of water as both a
enynes, 2j and 2k (entries 10 and 11), respectively. Although reaction medium and a catalyst of organic reactions.
1-cyclopropyl-2-propyn-1-ol 1l does not undergo ring opening
upon treatment with trifluoromethanesulfonic acid,2l reaction
of this substrate under our optimized conditions gave a
1 : 1 mixture of ring-opened products E- and Z-2l in 83% yield
(entry 12). Cyclopropyl carbinol 1m, which bears a phenyl-sub-
Experimental section
General
stituted cyclopropane ring, provided the desired product 2m in
excellent yield (entry 13). Note that the reaction of cyclopropyl
carbinol 1n, which has an aliphatic substituent, proceeded
smoothly, and the homoallylic alcohol product did not
undergo elimination reaction (entry 14). However, 1o, which
has a geminally disubstituted cyclopropane ring, was unreac-
tive under our reaction conditions (entry 15).
With the aim of synthesizing seven- or eight-membered-
ring homoallylic alcohols via rearrangements of bicyclic cyclo-
propyl carbinols accompanied by ring enlargement, we investi-
gated the reactions of several bicyclo[4.1.0] or bicyclo[5.1.0]
substrates (Table 3). Phenyl-substituted secondary cyclopropyl
carbinol 3a afforded the ring-enlarged tertiary alcohol 4a in
80% yield along with 14% of cyclic dienes resulting from the
elimination of the hydroxy group (Table 3, entry 1). The same
substrate gave less desired product but more elimination pro-
ducts even under slightly acidic reaction conditions.2m,9 When
the rearrangement of 3a was carried out on a 1 gram scale, a
parallel chemical yield was obtained without elongation of the
reaction time (82% yield in 12 h). Other R1 substituents,
including electron-rich and electron-poor aryl groups, alkyl
All reactions were carried out under an air atmosphere. 1,4-
Dioxane (HPLC grade) was used as received from Alfa Aesar.
We used either water purified with a Milli-Q Ultrapure Water
Purification System or Watson’s distilled water (pH = 5.5–6.5).
Substrates were synthesized according to the known pro-
cedures. Flash column chromatography was performed using
the indicated solvent system on Qingdao Haiyang silica gel
(200–300 mesh). All of the compounds were characterized by
1H NMR and 13C NMR. Peaks recorded are relative to the
1
internal standards: TMS (δ = 0.00) for H NMR and CDCl3 (δ =
77.00) for 13C NMR spectra. High resolution mass spectral
analyses were performed on
spectrometer.
a Finnigan MAT95 mass
Preparation of cyclopropyl carbinols 1a–1o
Cyclopropyl carbinols 1a,2m 1b,12 1d,13 1e,14 1f,15 1g,16 1h,17
1i–1k,2k 1l,2l 1m,18 1n19 and 1o20 were prepared according to
previously reported procedures.
2-(Cyclopropyl(hydroxy)methyl)phenol (1c)
groups, hydrogen, and an alkynyl group, generally gave the To a solution of 2-bromophenol (865 mg, 5.0 mmol) in Et2O
corresponding seven-membered ring homoallylic alcohols in (20 mL) at 0 °C was added n-BuLi solution (2.4 M in hexane,
good to high yields (entries 2–8). Analogous reactions of alco- 4.2 mL, 10.0 mmol). The solution was stirred at 0 °C for
hols bearing alkyl or aryl R2 substituents also afforded the 30 min. The solution was cooled to −78 °C and cyclopropane-
ring-expanded products in yields of 54–85% (entries 9–12). carbaldehyde (350 mg, 5 mmol) in Et2O (5 mL) was added.
However, small amounts of bicyclo[3.2.0]heptan-2-ol products The reaction mixture was allowed to warm to 0 °C and stirred
such as 4k-2 and 4l-2 were also produced by the reaction.3h at 0 °C for 2 h. Diluted aqueous NH4Cl solution (20 mL) was
Substrates 3m and 3n reacted smoothly to give the corres- added to quench the reaction and the reaction mixture was
ponding eight-membered-ring products (entries 13 and 14). extracted with EtOAc (2 × 50 mL). The combined organic layers
Sequential rearrangements of 3o, which contains two cyclo- were washed with brine, dried over MgSO4, filtered and evapo-
propane rings, gave nine-membered-ring product 4o in an accept- rated under reduced pressure. The residue was purified by
able yield (entry 15). The rearrangement of androstanediol silica gel column chromatography (EtOAc–hexane = 1 : 5) to
1
derivative 3p gave the desired ring-expanded homoallylic afford the desired product 1c (460 mg, 56%). Colorless oil: H
alcohol, but the product underwent further dehydration under NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.24–7.15 (m, 1H), 7.07
the reaction conditions to give a diene product (entry 16), as (m, 1H), 6.93–6.81 (m, 2H), 4.13 (dd, J = 8.9, 2.6 Hz, 1H), 2.73
has been reported previously under the acidic reaction con- (d, J = 2.8 Hz, 1H), 1.46–1.35 (m, 1H), 0.70–0.62 (m, 2H),
ditions.10 The reaction of tricyclo[4.3.1.0]decanol 3q gave two 0.45–0.38 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 155.6, 129.1,
bicyclic homoallylic alcohols, 4q-1 and 4q-2, in 62% and 12% 127.3, 126.1, 119.7, 117.1, 80.5, 17.9, 3.63, 3.60; HRMS (EI) for
yields, respectively (entry 17).3g,i,11
C10H12O2 calcd for [M]+ m/z 164.0837, found 164.0841.
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Table 3 Rearrangements of cyclic cyclopropyl carbinolsa
Entry
Substrate
Time (h)
Product
Yieldb (%)
1
2
3
4
3a
3b
3c
3d
3e
3f
R1 = Ph
10
6
12
4
6
12
36
4a
4b
4c
4d
4e
4f
R1 = Ph
80
75
81
88
90
91
74
R1 = 4-MeC6H4
R1 = 4-ClC6H4
R1 = Me
R1 = 4-MeC6H4
R1 = 4-ClC6H4
R1 = Me
5
R1 = n-Bu
R1 = n-Bu
6c
7d
R1 = H
R1 = H
3g
R1 = PhCuC
4g
R1 = PhCuC
8
3h
5
4h
89
9
10
3i
3j
R2 = Me
24
8
4i
4j
R2 = Me
85
81
R2 = n-Bu
R2 = n-Bu
11
3k
R2 = Ph
12
4k-1 (77%)
4k-2 (11%)
4l-2 (15%)
12
3l
26
4l-1 (54%)
4m
13
14
3m
3n
12
22
85
80
4n
15d
16d
17
3o
3p
3q
24
8
4o
4p
66
73
22
4q-1 (62%)
4q-2 (12%)
a Reaction conditions: 1 mmol substrate in mixed solvent (H2O–1,4-dioxane = 9 : 1, 25 mL), with vigorous stirring. b Isolated yield. c 90 °C. d H2O–
1,4-dioxane = 4 : 1.
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General procedure for preparation of cyclopropyl carbinols
3a–3q
1.90–1.80 (m, 1H), 1.68–1.58 (m, 1H), 1.46–1.35 (m, 3H),
1.31–1.10 (m, 3H), 1.03–0.92 (m, 1H), 0.57 (td, J = 8.7, 4.7 Hz,
1H), 0.30 (q, J = 5.2 Hz, 1H); 13C NMR (100 MHz, CDCl3)
6-Phenylbicyclo[4.1.0]heptan-2-ol (3a). To a solution of di- δ 67.3, 29.9, 22.7, 20.7, 17.7, 12.8, 7.2.
iodomethane (5.36 g, 20.0 mmol) in dried CH2Cl2 (50 mL) was
6-(Phenylethynyl)bicyclo[4.1.0]heptan-2-ol (3g). Slight yellow
added diethylzinc (1.0 M in hexane, 10.0 mL, 10.0 mmol) solid (95%): mp = 57.5–59 °C; 1H NMR (400 MHz, CDCl3)
slowly at −20 °C. The reaction mixture was allowed to stir at δ 7.42–7.32 (m, 2H), 7.32–7.22 (m, 3H), 4.38–4.28 (m, 1H), 2.08
−20 °C for 0.5 h. Then 3-phenylcyclohex-2-enol (870 mg, (dt, J = 14.3, 6.1 Hz, 1H), 1.86 (ddd, J = 14.1, 9.0, 5.3 Hz, 1H),
5.0 mmol) in CH2Cl2 (5 mL) was added to the reaction mixture 1.76 (dt, J = 9.3, 6.4 Hz, 1H), 1.70–1.60 (m, 1H), 1.49 (d, J = 4.7
at −20 °C. After stirring at −20 °C for 0.5 h, the reaction Hz, 1H), 1.46–1.29 (m, 2H), 1.16–1.04 (m, 2H), 0.93 (dd, J = 6.4,
mixture was allowed to warm to room temperature and further 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 131.5, 128.1, 127.5,
stirred at room temperature for 3 h. Diluted aqueous NH4Cl 123.7, 96.4, 76.0, 65.5, 29.25, 29.19, 28.2, 19.3, 16.9, 14.1;
solution (5 mL) was added to quench the reaction, the reaction HRMS (EI) for C15H16O calcd for [M]+ m/z 212.1201, found
mixture was filtered through Celite and the filtrate was washed 212.1193.
with water (50 mL), and extracted with CH2Cl2 (2 × 100 mL).
4,4,6-Trimethylbicyclo[4.1.0]heptan-2-ol (3h). White solid
1
The combined organic layers were dried with MgSO4, filtered (54%): mp = 46–48 °C; H NMR (400 MHz, CDCl3) δ 4.36–4.24
and evaporated under reduced pressure. The residue was puri- (m, 1H), 1.48 (dd, J = 12.8, 6.3 Hz, 1H), 1.38–1.23 (m, 3H),
fied by silica gel column chromatography (MTBE–hexane = 1.13–1.05 (m, 1H), 1.10 (s, 3H), 0.87 (s, 3H), 0.83 (s, 3H), 0.69
1 : 4) to afford the title alcohol. Slight yellow oil (58%, 545 mg): (t, J = 12.0 Hz, 1H), 0.41 (dd, J = 8.9, 4.4 Hz, 1H), 0.26 (t, J =
1H NMR (400 MHz, CDCl3) δ 7.33–7.23 (m, 4H), 7.22–7.12 (m, 5.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 66.0, 44.6, 41.5,
1H), 4.41 (m, 1H), 2.01–1.86 (m, 2H), 1.71–1.58 (m, 2H), 32.2, 31.4, 28.3, 25.8, 25.4, 18.8, 16.0; HRMS (EI) for C10H18O
1.55–1.33 (m, 3H), 1.32–1.23 (m, 1H), 0.97–0.92 (m, 2H); 13C calcd for [M]+ m/z 154.1358, found 154.1353.
NMR (100 MHz, CDCl3) δ 148.0, 128.3, 127.4, 125.9, 65.9, 31.2,
30.2, 28.0, 26.2, 19.3, 13.6; HRMS (EI) for C13H16O calcd for 1H NMR (400 MHz, CDCl3) δ 3.86 (dd, J = 9.1, 5.8 Hz, 1H),
[M]+ m/z 188.1201, found 188.1203.
1.95–1.83 (m, 1H), 1.75–1.65 (m, 1H), 1.46–1.29 (m, 3H),
1-Methylbicyclo[4.1.0]heptan-2-ol (3i).23 Colorless oil (49%):
6-(p-Tolyl)bicyclo[4.1.0]heptan-2-ol (3b). White solid (59%): 1.22–1.10 (m, 1H), 1.18 (s, 3H), 0.98–0.86 (m, 2H), 0.45–0.31
1
mp = 38–39.5 °C; H NMR (400 MHz, CDCl3) δ 7.16 (d, J = 8.0 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 72.9, 30.5, 24.7, 23.6,
Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 4.46–4.35 (m, 1H), 2.32 (s, 22.6, 21.9, 21.2, 15.5.
1
3H), 1.97–1.83 (m, 2H), 1.67–1.55 (m, 2H), 1.52–1.42 (m, 2H),
1-Butylbicyclo[4.1.0]heptan-2-ol (3j). Colorless oil (76%): H
1.41–1.32 (m, 1H), 1.32–1.22 (m, 1H), 0.96–0.87 (m, 2H); 13C NMR (400 MHz, CDCl3) δ 4.09–3.96 (m, 1H), 1.89–1.77 (m, 1H),
NMR (100 MHz, CDCl3) δ 145.2, 135.4, 129.0, 127.4, 65.9, 31.4, 1.74–1.54 (m, 2H), 1.49–1.21 (m, 7H), 1.18–0.99 (m, 2H),
30.2, 27.6, 26.2, 21.0, 19.3, 13.5; HRMS (EI) for C14H18O calcd 0.98–0.83 (m, 5H), 0.44–0.37 (m, 1H), 0.37–0.29 (m, 1H); 13C
for [M]+ m/z 202.1358, found 202.1364.
NMR (100 MHz, CDCl3) δ 69.4, 38.1, 30.8, 29.0, 27.0, 23.6, 23.0,
6-(4-Chlorophenyl)bicyclo[4.1.0]heptan-2-ol
(3c). White 20.5, 19.8, 14.2; HRMS (EI) for C11H20O calcd for [M]+ m/z
solid (77%): mp = 55–56.5 °C; 1H NMR (400 MHz, CDCl3) 168.1514, found 168.1521.
δ 7.24 (d, J = 8.5 Hz, 2H), 7.18 (d, J = 8.5 Hz, 2H), 4.46–4.36 (m,
1-Phenylbicyclo[4.1.0]heptan-2-ol (3k).24 White solid (68%):
1H), 1.98–1.81 (m, 2H), 1.69–1.55 (m, 3H), 1.54–1.33 (m, 3H), mp = 58.5–60 °C (lit.24 mp = 57° C); 1H NMR (400 MHz, CDCl3)
1.33–1.23 (m, 1H), 0.96 (t, J = 5.3 Hz, 1H), 0.90 (dd, J = 9.4, 4.9 δ 7.38–7.27 (m, 4H), 7.21 (t, J = 7.0 Hz, 1H), 4.26–4.17 (m, 1H),
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 146.5, 131.5, 128.9, 2.10–2.00 (m, 1H), 1.87–1.77 (m, 1H), 1.65–1.46 (m, 3H),
128.4, 65.7, 31.1, 30.1, 27.5, 26.2, 19.2, 13.7; HRMS (EI) for 1.40–1.28 (m, 2H), 1.16–1.02 (m, 2H), 0.85 (t, J = 5.4 Hz, 1H);
C13H15ClO calcd for [M]+ m/z 222.0811, found 222.0812.
6-Methylbicyclo[4.1.0]heptan-2-ol
(3d).21 Colorless
13C NMR (100 MHz, CDCl3) δ 146.1, 128.8, 128.4, 126.3, 72.7,
oil 32.7, 29.8, 23.4, 22.6, 21.3, 15.1.
(67%): 1H NMR (400 MHz, CDCl3) δ 4.22 (m, 1H), 1.62 (ddd,
1-Methyl-4-(prop-1-en-2-yl)bicyclo[4.1.0]heptan-2-ol
(3l).3h
1
J = 13.6, 8.4, 5.2 Hz, 1H), 1.57–1.47 (m, 2H), 1.40–1.29 (m, 1H), Colorless oil: H NMR (400 MHz, CDCl3) δ 4.76 (s, 1H), 4.73 (s,
1.39 (s, 1H), 1.27–1.16 (m, 1H), 1.14–1.03 (m, 2H), 1.08 (s, 3H), 1H), 3.94–3.83 (m, 1H), 1.87–1.75 (m, 5H), 1.73 (s, 3H), 1.37–1.25
0.51 (t, J = 4.9 Hz, 1H), 0.31 (dd, J = 9.0, 4.4 Hz, 1H); 13C NMR (m, 1H), 1.12 (s, 3H), 1.00–0.90 (m, 1H), 0.41 (dd, J = 8.8, 4.8 Hz,
(100 MHz, CDCl3) δ 66.4, 30.03, 29.96, 27.2, 26.4, 19.3, 18.7, 1H), 0.23 (t, J = 5.1 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 150.3,
13.5.
6-Butylbicyclo[4.1.0]heptan-2-ol (3e).21 Colorless oil (66%):
109.1, 71.8, 36.5, 36.4, 28.7, 21.8, 20.8, 19.6, 17.0.
Bicyclo[5.1.0]octan-2-ol (3m).25 White solid (50%, 315 mg):
1H NMR (400 MHz, CDCl3) δ 4.25–4.12 (m, 1H), 1.66–1.54 (m, mp = 41.5–42.5 °C; H NMR (400 MHz, CDCl3) δ 4.29–4.12 (m,
2H), 1.53–1.44 (m, 1H), 1.44–1.24 (m, 6H), 1.23–1.09 (m, 3H), 1H), 1.91–1.79 (m, 1H), 1.79–1.68 (m, 2H), 1.67–1.35 (m, 4H),
1.09–0.95 (m, 2H), 0.88 (t, J = 6.8 Hz, 3H), 0.45 (t, J = 5.0 Hz, 1.34–1.21 (m, 1H), 1.19–0.94 (m, 3H), 0.60–0.51 (m, 1H),
1H), 0.35 (dd, J = 8.9, 4.5 Hz, 1H); 13C NMR (100 MHz, CDCl3) 0.48–0.36 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 71.2, 35.7,
1
δ 67.0, 41.0, 30.0, 28.8, 27.8, 25.6, 23.4, 22.9, 20.3, 14.2, 13.6.
Bicyclo[4.1.0]heptan-2-ol (3f).22 Colorless oil (74%): 1H
28.6, 26.9, 25.0, 22.7, 14.9, 3.1.
Compound 3n. White solid (90%): mp = 61–62 °C; H NMR
1
NMR (400 MHz, CDCl3) δ 4.19 (dt, J = 8.7, 5.8 Hz, 1H), (400 MHz, CDCl3) δ 7.37 (d, J = 7.4 Hz, 1H), 7.23–7.01 (m, 3H),
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4.29 (m, 1H), 3.18 (ddd, J = 13.9, 12.0, 5.4 Hz, 1H), 2.54 (dt, J = 3.77–3.71 (m, 2H), 2.51–2.43 (m, 2H), 1.51 (t, J = 5.6 Hz, 1H);
13.6, 4.0 Hz, 1H), 2.28–2.11 (m, 2H), 1.86–1.72 (m, 1H), 13C NMR (100 MHz, CDCl3) δ 158.9, 132.3, 130.0, 127.2, 124.0,
1.52–1.38 (m, 1H), 1.01 (td, J = 8.9, 4.5 Hz, 1H), 0.77 (dd, J = 113.9, 62.1, 55.3, 36.4.
10.3, 5.7 Hz, 1H), 0.47 (d, J = 9.2 Hz, 1H); 13C NMR (100 MHz,
(E)-2-(4-Hydroxybut-1-en-1-yl)phenol
(2c). White
solid
CDCl3) δ 140.9, 139.7, 130.9, 128.6, 126.7, 126.5, 68.3, 34.6, (133 mg, 81%): mp = 74–76 °C; 1H NMR (400 MHz, CDCl3)
29.9, 19.8, 17.3, 7.8; HRMS (EI) for C12H14O calcd for [M]+ m/z δ 7.31 (d, J = 7.7, 1H), 7.09 (t, J = 7.9, 1H), 6.87 (t, J = 7.5, 1H),
174.1045, found 174.1045.
6.79 (d, J = 8.1, 1H), 6.70 (d, J = 16.0 Hz, 1H), 6.29 (s, 1H), 6.15
Compound 3o. Yellow solid (11%): mp = 97–100 °C; 1H (dt, J = 15.9, 7.1 Hz, 1H), 3.77 (t, J = 5.8 Hz, 2H), 2.54–2.44 (m,
NMR (400 MHz, CDCl3) δ 7.53 (d, J = 7.2 Hz, 1H), 7.40 (d, J = 2H), 2.25 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 152.8, 128.3,
6.8 Hz, 1H), 7.30–7.19 (m, 2H), 4.73 (d, J = 9.2 Hz, 1H), 2.01 (br 128.1, 127.5, 127.3, 124.7, 120.7, 116.0, 61.8, 36.5; HRMS (ESI)
s, 1H), 1.94–1.86 (m, 1H), 1.29 (td, J = 9.1, 4.2 Hz, 1H), for C10H12O2 calcd for [M − H]− m/z 163.0759, found 163.0763.
1.15–1.06 (m, 2H), 1.04–0.94 (m, 1H), 0.84–0.77 (m, 1H), 0.73
(E)-4-(4-Chlorophenyl)but-3-en-1-ol (2d).26 Colorless oil
(dd, J = 9.8, 5.0 Hz, 1H), 0.44 (dd, J = 10.0, 5.7 Hz, 1H); 13C (120 mg, 66%): 1H NMR (400 MHz, CDCl3) δ 7.33–7.24 (m,
NMR (100 MHz, CDCl3) δ 143.6, 135.8, 131.9, 126.9, 126.3, 4H), 6.45 (d, J = 15.9 Hz, 1H), 6.19 (dt, J = 15.8, 7.1 Hz, 1H),
121.3, 74.1, 26.6, 18.7, 16.9, 15.3, 14.7, 11.3; HRMS (EI) for 3.81–3.71 (m, 2H), 2.48 (m, 2H), 1.54 (s, 1H); 13C NMR
C13H14O calcd for [M]+ m/z 186.1045, found 186.1040.
Compound 3p. White solid (52%): mp = 120–122 °C; 1H 61.9, 36.3.
NMR (400 MHz, CDCl3) δ 4.60 (t, J = 8.4 Hz, 1H), 4.38 (t, J =
(E or Z)-4-Phenylpent-3-en-1-ol (2e).2d,14 (E : Z = 13 : 1) Color-
6.9 Hz, 1H), 2.25–2.12 (m, 1H), 2.11–1.98 (m, 1H), 2.06 (s, 3H), less oil (121 mg, 75%): H NMR (400 MHz, CDCl3) δ 7.44–7.17
1.75 (dt, J = 12.4, 3.2 Hz, 1H), 1.71–1.56 (m, 3H), 1.56–1.43 (m, (m, 5H), 5.79 (td, J = 7.3, 1.3 Hz, 0.93H, E isomer), 5.48 (td, J =
3H), 1.38–1.02 (m, 10H), 1.00 (s, 3H), 0.97–0.88 (m, 1H), 0.81 7.5, 1.4 Hz, 0.07H, Z isomer), 3.75 (s, 1.86H, E isomer), 3.62 (s,
(s, 3H), 0.72 (t, J = 4.8 Hz, 1H), 0.60 (dt, J = 13.7, 3.2 Hz, 1H), 0.14H, Z isomer), 2.50 (m, 1.86H, E isomer), 2.26 (m, 0.14H),
0.10 (dd, J = 9.2, 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) 2.08 (s, 3H), 1.49 (s, 1H).
(100 MHz, CDCl3) δ 135.7, 132.8, 131.5, 128.6, 127.2, 127.1,
1
δ 171.2, 82.8, 63.7, 50.8, 46.1, 42.4, 37.0, 35.4, 34.1, 33.1, 30.4,
4,4-Diphenylbut-3-en-1-ol (2f).27 Colorless oil (215 mg,
30.2, 27.6, 27.5, 26.4, 26.3, 23.6, 21.3, 21.2, 21.0, 12.0, 10.6. 96%): 1H NMR (400 MHz, CDCl3) δ 7.41–7.15 (m, 10H), 6.11 (t,
HRMS (EI) for C22H34O3 calcd for [M]+ m/z 346.2508, found J = 7.5 Hz, 1H), 3.72 (s, 2H), 2.40 (m, 2H), 1.42 (s, 1H); 13C
346.2500.
NMR (100 MHz, CDCl3) δ 144.2, 142.3, 139.8, 129.8, 128.2,
1
Compound 3q. Slight yellow oil: H NMR (400 MHz, CDCl3) 128.1, 127.2, 127.1, 127.1, 125.2, 62.6, 33.3.
δ 4.23 (t, J = 8.1 Hz, 1H), 1.96–1.72 (m, 5H), 1.60–1.46 (m, 2H),
6-Phenylhexa-3(E or Z), 5(E)-dien-1-ol (2g).28 (3E : 3Z = 8 : 1)
1.38 (bs, 1H), 1.31–1.12 (m, 4H), 1.11–0.98 (m, 1H), 0.74 (d, J = Colorless oil (148 mg, 85%): 1H NMR (400 MHz, CDCl3)
4.5 Hz, 1H), 0.22 (d, J = 4.4 Hz, 1H); 13C NMR (100 MHz, δ 7.46–7.18 (m, 5H), 7.08 (ddd, J = 15.5, 11.1, 1.1 Hz, 0.11H,
CDCl3) δ 81.0, 32.7, 31.1, 30.2, 29.4, 27.3, 26.5, 21.4, 21.1, 14.3; Z isomer), 6.77 (dd, J = 15.7, 10.4 Hz, 0.89H, E isomer), 6.58 (d,
HRMS (EI) for C10H16O calcd for [M]+ m/z 152.1201, found J = 15.5 Hz, 0.11H, Z isomer), 6.49 (d, J = 15.7 Hz, 0.89H,
152.1197.
E isomer), 6.40–6.25 (m, 1H), 5.80 (dt, J = 14.9, 7.3 Hz, 0.89H,
E isomer), 5.53 (dt, J = 10.9, 7.9 Hz, 0.11H, Z isomer), 3.72 (m,
2H), 2.58 (qd, J = 6.5, 1.4 Hz, 0.22H, Z isomer), 2.43 (qd, J =
6.4, 1.0 Hz, 1.88H, E isomer), 1.50 (br s, 1H).
General procedure for rearrangements of cyclopropyl carbinols
in Table 2
Cinnamyl alcohol (2a).26 To a 50 mL round-bottom flask
6-Phenylhexa-3(E or Z), 5(E)-dien-1-ol (2h).28 (3E : 3Z = 7 : 1)
containing the substrate 1a (148 mg, 1 mmol) was added 1,4- Colorless oil (153 mg, 88%): 1H NMR (400 MHz, CDCl3)
dioxane (2.5 mL), and then to the solution was added H2O δ 7.45–7.17 (m, 5H), 7.07 (ddd, J = 15.5, 11.1, 0.9 Hz, 0.12H, Z
(22.5 mL). The flask was fitted with a condenser, stirred vigo- isomer), 6.76 (dd, J = 15.7, 10.4 Hz, 0.88H, E isomer), 6.57 (d, J
rously under reflux conditions. After completion confirmed by = 15.6 Hz, 0.12H, Z isomer), 6.49 (d, J = 15.7 Hz, 0.88H, E
TLC, the resulting solution was cooled to room temperature. isomer), 6.32 (ddd, J = 15.2, 10.4, 0.6 Hz, 1H), 5.80 (dt, J = 14.9,
The mixture was extracted with EtOAc (3 × 50 mL), washed 7.3 Hz, 0.88H, E isomer), 5.53 (dt, J = 10.7, 7.8 Hz, 0.12H, Z
with brine, dried over MgSO4 and evaporated under reduced isomer), 3.72 (m, 2H), 2.62–2.54 (m, 0.24H, Z isomer),
pressure. The residue was purified by silica gel column 2.47–2.37 (m, 1.76H, E isomer), 1.52 (br s, 1H).
chromatography (EtOAc–hexane = 1 : 5) to afford the desired
(E)-4-Phenylhex-3-en-5-yn-1-ol (2i).2i Brown oil (137 mg,
product 2a (134 mg, 91%). Colorless oil: 1H NMR (400 MHz, 80%): 1H NMR (400 MHz, CDCl3) δ 7.64–7.57 (m, 2H),
CDCl3) δ 7.39–7.34 (m, 2H), 7.33–7.27 (m, 2H), 7.25–7.18 (m, 7.37–7.24 (m, 3H), 6.54 (t, J = 7.5 Hz, 1H), 3.81 (t, J = 6.3 Hz,
1H), 6.50 (d, J = 15.9 Hz, 1H), 6.21 (dt, J = 15.8, 7.2 Hz, 1H), 2H), 3.35 (s, 1H), 2.83–2.74 (m, 2H), 1.61 (s, 1H); 13C NMR
3.76 (m, 2H), 2.49 (m, 2H), 1.55 (s, 1H); 13C NMR (100 MHz, (100 MHz, CDCl3) δ 137.3, 135.6, 128.4, 127.8, 125.9, 124.9,
CDCl3) δ 137.2, 132.8, 128.5, 127.3, 126.3, 126.0, 62.0, 36.4.
(E)-4-(4-Methoxyphenyl)but-3-en-1-ol (2b).26 White solid
83.5, 80.7, 61.9, 34.7.
(Z)-4,6-Diphenylhex-3-en-5-yn-1-ol
(2j).2m Colorless
oil
(146 mg, 82%): mp = 80–81 °C; 1H NMR (400 MHz, CDCl3) (220 mg, 89%): 1H NMR (400 MHz, CDCl3) δ 7.71–7.63 (m,
δ 7.30 (d, J = 8.7 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 6.45 (d, J = 2H), 7.57–7.50 (m, 2H), 7.40–7.26 (m, 6H), 6.51 (t, J = 7.5 Hz,
15.9 Hz, 1H), 6.06 (dt, J = 15.8, 7.2 Hz, 1H), 3.81 (s, 3H), 1H), 3.86 (t, J = 6.4 Hz, 2H), 2.87 (m, 2H), 1.55 (s, 1H); 13C
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NMR (100 MHz, CDCl3) δ 137.8, 133.8, 131.5, 128.39, 128.36, 1.8 Hz, 1H), 2.34 (s, 3H), 2.33–2.27 (m, 1H), 2.27 (s, 1H),
127.8, 126.0, 125.8, 123.2, 95.6, 86.4, 62.1, 34.9.
2.23–2.07 (m, 2H), 2.07–1.98 (m, 1H), 1.67–1.60 (m, 2H); 13C
(Z)-6-Cyclopropyl-4-phenylhex-3-en-5-yn-1-ol (2k). Colorless NMR (100 MHz, CDCl3) δ 146.6, 136.0, 128.80, 128.79, 126.2,
oil (170 mg, 80%): 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 124.1, 72.4, 45.7, 41.5, 28.7, 21.8, 20.9; HRMS (EI) for C14H18O
7.8 Hz, 2H), 7.32 (t, J = 7.5 Hz, 2H), 7.28–7.21 (m, 1H), 6.35 (t, J calcd for [M]+ m/z 202.1358, found 202.1356.
= 7.4 Hz, 1H), 3.79 (t, J = 6.3 Hz, 2H), 2.78–2.67 (m, 2H),
1-(4-Chlorophenyl)cyclohept-3-enol
(4c). Colorless
oil
1.53–1.44 (m, 1H), 0.94–0.84 (m, 2H), 0.84–0.76 (m, 2H); 13C (180 mg, 81%): 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.5 Hz,
NMR (100 MHz, CDCl3) δ 138.3, 132.4, 128.2, 127.5, 126.1, 2H), 7.30 (d, J = 8.6 Hz, 2H), 6.20–6.10 (m, 1H), 5.70–5.60 (m,
125.9, 100.0, 72.7, 62.1, 34.6, 8.9, 0.3; HRMS (EI) for C15H16O 1H), 2.87–2.78 (m, 1H), 2.42 (ddd, J = 14.8, 8.2, 1.4 Hz, 1H),
calcd for [M]+ m/z 212.1201, found 212.1200.
2.36 (s, 1H), 2.35–2.27 (m, 1H), 2.24–2.12 (m, 1H), 2.11–1.96
(E or Z)-6-Phenylhex-3-en-5-yn-1-ol (2l).29 (E : Z = 1 : 1) Slight (m, 2H), 1.71–1.55 (m, 2H); 13C NMR (100 MHz, CDCl3)
yellow oil (143 mg, 83%): 1H NMR (400 MHz, CDCl3) δ 148.1, 136.5, 132.1, 128.2, 125.8, 125.7, 72.1, 45.6, 41.4, 28.6,
δ 7.48–7.40 (m, 2H), 7.35–7.27 (m, 3H), 6.23 (dt, J = 15.8, 7.3 21.7; HRMS (EI) for C13H15ClO calcd for [M]+ m/z 222.0811,
Hz, 0.5H, E isomer), 6.03 (dt, J = 10.8, 7.4 Hz, 0.5H, Z isomer), found 222.0820.
5.88–5.76 (m, 1H), 3.77 (t, J = 6.3 Hz, 1H), 3.72 (t, J = 6.1 Hz,
1-Methylcyclohept-3-enol (4d). Colorless oil (111 mg, 88%):
1H), 2.68 (qd, J = 6.5, 1.3 Hz, 1H), 2.48–2.39 (m, 1H), 1.71 (br s, 1H NMR (400 MHz, CDCl3) δ 6.00 (dt, J = 12.0, 6.2 Hz, 1H),
1H); 13C NMR (100 MHz, CDCl3) δ 140.5, 139.5, 131.4, 128.28, 5.66–5.55 (m, 1H), 2.32 (d, J = 6.6 Hz, 2H), 2.23–2.04 (m, 2H),
128.26, 128.2, 128.0, 123.3, 112.4, 111.6, 94.0, 88.6, 87.7, 85.9, 1.91–1.82 (m, 2H), 1.80–1.70 (m, 1H), 1.58–1.49 (m, 2H), 1.24
61.8, 61.5, 36.5, 33.8.
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 135.0, 126.6, 69.8, 45.6,
(E)-1,4-Diphenylbut-3-en-1-ol (2m).30 White solid (212 mg, 41.5, 29.6, 28.4, 22.3; HRMS (EI) for C8H14O calcd for [M]+ m/z
95%): mp = 94–94.5 °C; 1H NMR (400 MHz, CDCl3) δ 7.43–7.18 126.1045, found 126.1041.
(m, 10H), 6.50 (d, J = 15.9 Hz, 1H), 6.20 (dt, J = 15.8, 7.3 Hz,
1-Butylcyclohept-3-enol (4e). Colorless oil (151 mg, 90%): 1H
1H), 4.85–4.75 (m, 1H), 2.71–2.61 (m, 2H), 2.11 (d, J = 3.3 Hz, NMR (400 MHz, CDCl3) δ 6.04–5.92 (m, 1H), 5.66–5.55 (m, 1H),
1H); 13C NMR (100 MHz, CDCl3) δ 143.9, 137.2, 133.4, 128.50, 2.36–2.23 (m, 2H), 2.23–2.04 (m, 2H), 1.84–1.75 (m, 2H), 1.67
128.45, 127.6, 127.3, 126.1, 125.9, 125.8, 73.7, 43.1.
(d, J = 1.6 Hz, 1H), 1.61–1.43 (m, 4H), 1.41–1.25 (m, 4H), 0.91
1-Phenylpent-3(E or Z)-en-1-ol (2n).30 (E : Z = 4 : 1) Colorless (t, J = 6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 134.8, 126.5,
1
oil (157 mg, 97%): H NMR (400 MHz, CDCl3) δ 7.40–7.23 (m, 71.6, 43.7, 41.3, 39.7, 28.5, 25.5, 23.3, 22.2, 14.1; HRMS (EI) for
5H), 5.69–5.54 (m, 1H), 5.49–5.36 (m, 1H), 4.75–4.62 (m, 1H), C11H20O calcd for [M]+ m/z 168.1514, found 168.1515.
2.63–2.33 (m, 2H), 2.09 (d, J = 2.1 Hz, 0.81H, E isomer), 2.04
(d, J = 4.2 Hz, 0.19H, Z isomer), 1.69 (d, J = 6.3 Hz, 2.43H, NMR (400 MHz, CDCl3) δ 5.99–5.89 (m, 1H), 5.69–5.57 (m, 1H),
Cyclohept-3-enol (4f).31 Colorless oil (102 mg, 91%): 1H
E isomer), 1.60 (d, J = 7.1 Hz, 0.57H, Z isomer).
3.78–3.64 (m, 1H), 2.41–2.34 (m, 2H), 2.20–2.00 (m, 3H),
1.81–1.64 (m, 2H), 1.60 (s, 1H), 1.47–1.35 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 134.8, 125.9, 69.1, 40.8, 37.3, 28.3, 23.2.
1-(Phenylethynyl)cyclohept-3-enol (4g). Slight yellow oil
General procedure for rearrangements of cyclopropyl carbinols
in Table 3
1-Phenylcyclohept-3-enol (4a). To a 50 mL round-bottom (156 mg, 74%): 1H NMR (400 MHz, CDCl3) δ 7.47–7.38 (m,
flask containing the substrate 3a (188 mg, 1.0 mmol) was 2H), 7.34–7.26 (m, 3H), 6.08–5.98 (m, 1H), 5.73–5.62 (m, 1H),
added 1,4-dioxane (2.5 mL), and then to the solution was 2.74–2.58 (m, 2H), 2.32–2.02 (m, 5H), 1.75–1.64 (m, 2H); 13C
added H2O (22.5 mL). The flask was fitted with a condenser, NMR (100 MHz, CDCl3) δ 135.2, 131.6, 128.2, 125.4, 122.8,
stirred vigorously under reflux conditions. After completion 92.6, 84.2, 68.6, 46.2, 41.8, 28.2, 23.0; HRMS (EI) for C15H16O
confirmed by TLC, the resulting solution was cooled to room calcd for [M]+ m/z 212.1201, found 212.1198.
temperature. The mixture was extracted with EtOAc (3 ×
1,6,6-Trimethylcyclohept-3-enol (4h). Slight yellow oil
1
50 mL), washed with brine, dried over MgSO4 and evaporated (137 mg, 89%): H NMR (400 MHz, CDCl3) δ 5.90 (dt, J = 10.5,
under reduced pressure. The residue was purified by silica gel 6.8 Hz, 1H), 5.74 (dt, J = 10.4, 6.4 Hz, 1H), 2.40–2.27 (m, 2H),
column chromatography (MTBE–hexane = 1 : 5) to afford the 2.15–2.00 (m, 2H), 1.77–1.57 (m, 2H), 1.23 (s, 3H), 1.03 (s, 3H),
desired product 4a (150 mg, 80%). Colorless oil: 1H NMR 0.94 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 132.9, 127.9, 71.4,
(400 MHz, CDCl3) δ 7.55–7.47 (m, 2H), 7.39–7.29 (m, 2H), 58.2, 40.5, 40.2, 32.8, 32.1, 31.7, 29.6; HRMS (EI) for C10H18O
7.27–7.20 (m, 1H), 6.19–6.09 (m, 1H), 5.71–5.62 (m, 1H), calcd for [M]+ m/z 154.1358, found 154.1353.
2.91–2.83 (m, 1H), 2.46 (ddd, J = 14.8, 8.1, 1.9 Hz, 1H),
3-Methylcyclohept-3-enol (4i). Colorless oil (89 mg, 71%):
2.37–2.27 (m, 2H), 2.26–2.00 (m, 3H), 1.71–1.61 (m, 2H); 13C 1H NMR (400 MHz, CDCl3) δ 5.67 (s, 1H), 3.77–3.62 (m, 1H),
NMR (100 MHz, CDCl3) δ 149.5, 136.1, 128.1, 126.4, 126.1, 2.47 (t, J = 11.8 Hz, 1H), 2.24 (d, J = 14.1 Hz, 1H), 2.12–1.92 (m,
124.1, 72.4, 45.7, 41.4, 28.7, 21.8; HRMS (EI) for C13H16O calcd 3H), 1.82–1.53 (m, 3H), 1.75 (s, 3H), 1.45–1.31 (m, 1H); 13C
for [M]+ m/z 188.1201, found 188.1210.
NMR (100 MHz, CDCl3) δ 134.5, 127.8, 68.3, 42.5, 41.1, 27.6,
1-(p-Tolyl)cyclohept-3-enol (4b). White solid (151 mg, 75%): 26.7, 23.7; HRMS (EI) for C8H14O calcd for [M]+ m/z 126.1045,
mp = 39–41 °C; 1H NMR (400 MHz, CDCl3) δ 7.40 (d, J = found 126.1048.
8.2 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 6.16–6.08 (m, 1H),
5.70–5.62 (m, 1H), 2.89–2.81 (m, 1H), 2.45 (ddd, J = 14.8, 8.1, NMR (400 MHz, CDCl3) δ 5.65 (t, J = 6.4 Hz, 1H), 3.64 (br s,
3-Butylcyclohept-3-enol (4j). Colorless oil (136 mg, 81%): 1H
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1H), 2.52–2.39 (m, 1H), 2.24 (d, J = 14.1 Hz, 1H), 2.11–1.91 (m, 5.71–5.50 (m, 2H), 5.06 (dd, J = 6.9, 4.1 Hz, 1H), 2.86–2.67 (m,
5H), 1.77–1.67 (m, 2H), 1.50 (s, 1H), 1.43–1.21 (m, 5H), 0.89 (t, 2H), 2.66–2.55 (m, 1H), 2.55–2.43 (m, 1H), 1.90 (s, 1H); 13C
J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 138.6, 127.5, NMR (100 MHz, CDCl3) δ 143.7, 134.6, 129.6, 129.0, 128.7,
68.8, 41.4, 41.3, 40.0, 30.0, 27.5, 24.0, 22.4, 12.0; HRMS (EI) for 128.2, 128.1, 127.7, 126.5, 124.9, 72.4, 37.1, 29.5; HRMS (EI)
C11H20O calcd for [M]+ m/z 168.1514, found 168.1521.
3-Phenylcyclohept-3-enol (4k-1). White solid (145 mg, 77%):
for C13H14O calcd for [M]+ m/z 186.1045, found 186.1038.
Compound 4p. White solid (73%): mp = 124–126 °C; 1H
mp = 79–80 °C; 1H NMR (400 MHz, CDCl3) δ 7.39–7.34 (m, NMR (400 MHz, CDCl3) δ 5.69–5.60 (m, 1H), 5.59–5.51 (m, 1H),
2H), 7.33–7.27 (m, 2H), 7.25–7.18 (m, 1H), 6.22 (t, J = 6.9 Hz, 5.36 (d, J = 4.0 Hz, 1H), 4.61 (dd, J = 9.0, 7.9 Hz, 1H), 3.04 (d,
1H), 3.91–3.80 (m, 1H), 2.92 (dd, J = 14.3, 9.2 Hz, 1H), 2.82 (dt, J = 16.6 Hz, 1H), 2.48 (dd, J = 16.4, 7.8 Hz, 1H), 2.24–2.13 (m,
J = 14.3, 1.7 Hz, 1H), 2.34–2.19 (m, 2H), 2.18–2.09 (m, 1H), 1H), 2.08–1.96 (m, 2H), 2.05 (s, 3H), 1.95–1.85 (m, 1H),
1.90–1.78 (m, 1H), 1.78–1.68 (m, 1H), 1.68–1.56 (br s, 1H), 1.81–1.72 (m, 2H), 1.71–1.56 (m, 5H), 1.56–1.46 (m, 1H),
1.55–1.43 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 144.3, 138.8, 1.42–1.27 (m, 3H), 1.26–1.06 (m, 2H), 0.99 (s, 3H), 0.82 (s, 3H);
131.9, 128.2, 126.6, 125.8, 68.4, 41.3, 41.1, 28.1, 23.3; HRMS 13C NMR (100 MHz, CDCl3) δ 171.2, 144.9, 130.1, 129.3, 122.2,
(EI) for C13H16O calcd for [M]+ m/z 188.1201, found 188.1203.
82.8, 51.4, 43.0, 42.4, 40.5, 36.9, 35.2, 34.2, 31.8, 31.0, 27.6,
6-Phenylbicyclo[3.2.0]heptan-6-ol (4k-2).24 Slight yellow oil 24.0, 23.5, 22.9, 21.2, 20.9, 12.0; HRMS (EI) for C22H32O calcd
1
(20 mg, 11%): H NMR (400 MHz, CDCl3) δ 7.59–7.51 (m, 2H), for [M]+ m/z 328.2402, found 328.2410.
7.38 (t, J = 7.6 Hz, 2H), 7.29–7.22 (m, 1H), 3.02–2.92 (m, 1H),
Compound 4q-1.33 1H NMR (400 MHz, CDCl3) δ 4.01–3.88
2.75–2.66 (m, 1H), 2.66–2.56 (m, 1H), 2.10 (dd, J = 13.4, 6.6 Hz, (m, 1H), 2.25–2.13 (m, 1H), 2.03–1.95 (m, 2H), 1.92–1.80 (m, 6H),
1H), 2.00–1.79 (m, 3H), 1.75 (br s, 1H), 1.64 (dd, J = 12.5, 1.65–1.50 (m, 5H), 1.25 (br s, 1H); 13C NMR (100 MHz, CDCl3)
6.2 Hz, 1H), 1.59–1.49 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 127.6, 125.1, 67.5, 39.4, 31.3, 30.2, 29.8, 28.4, 23.0, 22.9.
δ 148.9, 128.3, 126.6, 124.2, 72.7, 50.9, 41.6, 32.7, 31.1, 26.6,
25.9.
Compound 4q-2.33 1H NMR (400 MHz, CDCl3) δ 5.66 (t, J =
5.0 Hz, 1H), 2.39–2.29 (m, 1H), 2.23–2.05 (m, 4H), 2.03–1.93
(1S,6R)-6-Isopropenyl-3-methyl-3-cyclohepten-1-ol (4l-1).3h (m, 1H), 1.88–1.71 (m, 3H), 1.64–1.43 (m, 3H), 1.42–1.33 (m,
Colorless oil (90 mg, 54%): 1H NMR (400 MHz, CDCl3) 2H), 1.22–1.09 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 140.0,
δ 5.74–5.66 (m, 1H), 4.71–4.65 (m, 2H), 4.09 (d, J = 4.1 Hz, 1H), 126.9, 75.0, 48.3, 40.7, 39.1, 33.4, 26.2, 23.2, 22.0.
2.47 (d, J = 14.7 Hz, 1H), 2.38 (dd, J = 14.8, 7.4 Hz, 1H),
2.34–2.24 (m, 1H), 2.15–2.06 (m, 2H), 2.06–1.98 (m, 1H),
1.84–1.79 (m, 1H), 1.77 (s, 3H), 1.71 (s, 3H), 1.68–1.60 (m, 1H);
Acknowledgements
13C NMR (100 MHz, CDCl3) δ 150.5, 134.8, 126.0, 108.9, 66.6,
44.1, 40.3, 38.9, 33.1, 27.1, 20.5.
This work was financially supported by grants from the NSFC
(1R,3S,5R,6S)-3-Isopropenyl-6-methyl-bicyclo[3.2.0]heptan- (21072098, 21372119), the National Natural Science Foun-
6-ol (4l-2).3h Colorless oil (15 mg, 15%): 1H NMR (400 MHz, dation of China Innovation Group (21121002), and Tianjin
CDCl3) δ 4.76 (s, 1H), 4.72 (s, 1H), 2.84 (tt, J = 12.1, 6.1 Hz, Natural Science Foundation (14JCYBJC20200).
1H), 2.58 (t, J = 7.7 Hz, 1H), 2.51–2.40 (m, 1H), 2.23–2.12 (m,
1H), 2.01 (dd, J = 13.4, 6.6 Hz, 1H), 1.78 (s, 3H), 1.70–1.57 (m,
2H), 1.49–1.39 (m, 3H), 1.36 (d, J = 6.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 148.1, 108.4, 69.5, 50.2, 45.7, 41.2, 37.3,
Notes and references
31.0, 30.6, 29.8, 21.6.
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NMR (400 MHz, CDCl3) δ 5.78–5.57 (m, 2H), 3.87–3.75 (m, 1H),
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11.6, 1.5 Hz, 1H), 5.81 (ddd, J = 11.6, 9.8, 4.5 Hz, 1H),
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