Ring-Closing Metathesis Approach to Cage Propellanes Containing Oxepane and Tetrahydrofuran Hybrid System

Article abstract of DOI:10.1055/s-0036-1591726

The preparation of a variety of structurally interesting oxygenated cage compounds involving atom-economic processes such as Claisen rearrangement, Diels-Alder reaction, [2+2] photocycloaddition, and ring-closing metathesis (RCM) as key steps is reported.

Full text of DOI:10.1055/s-0036-1591726

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–L
paper
A
en
S. Kotha et al.
Paper
Synthesis
Ring-Closing Metathesis Approach to Cage Propellanes
Containing Oxepane and Tetrahydrofuran Hybrid System
Sambasivarao Kotha*
Subba Rao Cheekatla
Darshan S. Mhatre
OH
O
O
O
(i) O-Allylation
(ii) Claisen
Rearrangement
OH
OH
Department of Chemistry, Indian Institute
of Technology-Bombay, 400076 Powai,
India
Ring-Closing
Metathesis
4 steps
(III) MnO2 Oxidation
(iv) Diels–Alder Reaction
(v) [2+2] Cycloaddition
srk@chem.iitb.ac.in
O
O
O
O
O
O
Received: 16.09.2017
Accepted after revision: 21.10.2017
Published online: 23.11.2017
als.14 Moreover, suitably functionalized cage molecules ex-
hibit medicinal properties15 and acts as useful scaffolds for
pharmaceutical applications.16 For example, diverse cage
systems 1–6 shown in Figure 1, were assembled by employ-
ing novel synthetic strategies. These scaffolds are useful as
chiral ligands (1),17 energetic materials (2, 3),18 and they
show anti-influenza A activity (4),19 and neuroprotective
properties (5).20 Also we have included interesting cage
propellane system 621 in Figure 1.
DOI: 10.1055/s-0036-1591726; Art ID: ss-2017-t0601-op
Abstract The preparation of a variety of structurally interesting oxy-
genated cage compounds involving atom-economic processes such as
Claisen rearrangement, Diels–Alder reaction, [2+2] photocycloaddition,
and ring-closing metathesis (RCM) as key steps is reported. For the first
time, oxepane ring system is introduced in cage framework using olefin
metathesis as a key step. These cage systems assembled here are diffi-
cult to prepare by traditional methods. The synthetic sequence de-
scribed here opens up new routes to higher order polycycles containing
heteroatoms without the involvement of protecting groups. Transan-
nular cyclization observed during Grignard addition and the RCM proto-
col used here may be applicable to generate unknown oxygenated cage
systems.
Ph
N
N
N
N
N
N
N
N
I
Ph
I
Key words Claisen rearrangement, cycloaddition, alkene metathesis,
oxepane, tetrahydrofuran hybrid molecules, cage heterocycles, poly-
cycles
1
2
NH2
O
COOH
NH2
H
Cage compounds1–5 have drawn the attention of organic
chemists because of the challenges involved with the syn-
thesis as well as their applications in diverse areas of chem-
ical sciences. Synthesis of these molecules is a justifiable
task due to their rigid and strained carbon frameworks,
unique molecular architecture with symmetrical features,
and deformation of ideal C–C bond angles.6–8 Strain in-
volved in the cage systems provide the driving force to un-
usual molecular rearrangements in an unprecedented man-
ner leading to the generation of new cage systems that are
often difficult to synthesize by conventional routes.9,10
Some of these molecules hold great potential as ligands
suitable for chelation with metal ions.11 They are also useful
as synthons for natural and unnatural products,12 and core
frameworks for energetic13 and photonic/electronic materi-
N
N
H
O
O
4
3
O
O-K+
O
N
N
N
H
O
N
NH
5
6
Figure 1 Structures of various representative polycycles useful in
diverse fields
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

B
S. Kotha et al.
Paper
Synthesis
A number of approaches22–24 are available to incorpo-
rate heteroatom in cage compounds. Some of these
approaches rely on tandem cyclization,25 transannular cy-
clization,26 base-promoted rearrangement,27 dehydration of
diols,28 intramolecular alkene-oxirane photocycloaddi-
tion,29 and etherification of suitably placed alkene bond
with an organoselenium reagent.30 Additional strategies in-
clude: synthesis of acetal/ketal containing oxa-cage com-
pounds, which are derived by ozonolysis of Diels–Alder
(DA) adducts followed by treatment with a suitable acid.31
More recently, Pohmakotr and co-workers described the
synthesis of gem-difluoromethylenated oxa-cage systems
by employing PhSCF2SiMe3 as a source of fluorinating
agent.32 Gharpure and co-workers reported a tandem radi-
cal cyclization approach to assemble oxa and aza cages us-
ing Bu3SnH.33 Novel cage heterocycles 7 to 18 are reported
by intricate synthetic strategies (Figure 2).32,34 For example,
heteroatom substituted cage systems in Figure 2 show utili-
ty in supramolecular chemistry (e.g., 15) and asymmetric
catalysis (e.g., 16).34–36 They also exhibit interesting biologi-
cal activity (e.g., 17, 18).34k,l For example, pentacycloundec-
ane (PCUD)-based oxa-cage compound 8 (NGP1-01)34b,c ex-
hibits both NMDA receptor channel blocking and L-type
calcium channel antagonist activity. Oxa-cage compound
1134f was found to be suitable to study π-facial selectivity
(Figure 2).
R2
O
O
H
R2
R2
N
O
O
F
O
O
O
R1
O
O
O
R1
F
7
8
9
10
Br
Br
O
O
O
O
O
O
O
O
11
12
HN
14
13
O
O
O
O
O
N
N
N
R
R
N
O
O
NH
N
N
O
O
O
HO
OH
17
O
16
O
NO2
18
O2N
15
Figure 2 Examples of heteroatom containing cage systems
Strategy: Recently, we have established a new synthetic
strategy to a series of polycyclic cage compounds, cage pro-
pellanes, and bis-annulated cage heterocycles.37 In view of
our ongoing program aimed at designing intricate cage sys-
tems with spiro linkage,37 here we conceived a short syn-
thetic sequence to annulated cage heterocycles containing
propellane system (Scheme 1). Transannular cyclization26
that occur during Grignard addition reaction proved to be
useful to generate polycyclic cage ethers through hemiketal
formation.
The target propellanes 19a,b can be obtained from dial-
lyl cage diones 20a,b via Grignard reaction, O-allylation,
and two-fold ring-closing metathesis (RCM) protocol fol-
lowed by hydrogenation. The required hexacyclic diones
20a, b could be constructed from 2,3-diallyl-1,4-benzoqui-
none (21) through Diels–Alder sequence followed by intra-
molecular [2+2] photocycloaddition. The known diallyl qui-
none 21 may be prepared from commercially available 1,4-
hydroquinone 22 involving di-O-allylation and double
Claisen rearrangement followed by MnO2 oxidation
(Scheme 1).38–41
To realize the retrosynthetic plan shown in Scheme 1,
our journey towards the synthesis of cage heterocycles 19a
and 19b commenced with the preparation of 2,3-diallyl-
1,4-benzoquinone 21 from commercially available 1,4-hy-
droquinone 22 in three steps.42 In this regard, diallylation of
hydroquinone under basic conditions using allyl bromide
followed by ortho-Claisen rearrangement38 gave two rear-
ranged hydroquinones 24 and 25 in equimolar ratio (1:1)
and they were separated by column chromatography
(Scheme 2). Further, 2,3-diallyl compound 24 underwent
oxidation in the presence of MnO2 at room temperature to
give the required dienophile 21 suitable for Diels–Alder re-
action39 with dienes such as 2643 and 28.43
O
O
OH
O
O
OH
O
O
19a,b
20a,b
21
22
Scheme 1 Retrosynthetic approach to the target molecules 19a,b
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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S. Kotha et al.
Paper
Synthesis
O
OH
OH
OH
acetone, K2CO3,
neat, 160–165 °C
67% (1:1)
allyl bromide
55–60 °C, 85%
O
OH
OH
OH
22
23
24
25
Scheme 2 Synthesis of diallyl hydroquinones 24 and 25
Having prepared the known spirodienes 26 and 28, our
efforts were directed to generate the diallyl cage diones
such as 20a44 and 20b. Later on, [4+2] cycloaddition of qui-
none 21 with freshly generated spirodienes 26 and 28 un-
der thermal conditions afforded the Diels–Alder adducts
2744 and 29, respectively, in good yields (Scheme 3). The
stereochemistry of the cycloadducts 27 and 29 is expected
to be endo and this observation was found to be true when
the [2+2] photocycloaddition was realized by exposure to
UV light. Next, these Diels–Alder adducts 2744 and 29 un-
derwent intramolecular [2+2] photocycloaddition40 in an-
hydrous ethyl acetate by irradiation with 125 W Hg lamp
for 2 hours to deliver the cage diones 20a and 20b in excel-
lent yields (91–92%). The structure of the cage dione 20b
data. Spectral properties of the Dilels–Alder adduct 27 and
cage dione 20a were compared and found to be similar with
those of the compounds reported earlier (Scheme 3).44
After procuring diallyl cage diones 20a and 20b, we
planned to generate higher order cage ethers such as 19a
and 19b. In this regard, the diones 20a and 20b were sub-
jected to allyl Grignard addition,45 which resulted in the
formation of triallyl hemiketals 30 and 34 along with the
tetraallyl diol 31. Spectral data of these compounds 30 and
31 were found to be similar with the reported earlier
(Scheme 4 and Scheme 5).44
Hemiketal formation may be understood due to the
proximity of the two carbonyl groups in cage system.46 The
structure of hemiketal 34 was established on the basis of
high field 1H NMR spectroscopy (400 or 500 MHz) and fur-
ther supported by 13C NMR spectral data (Scheme 6).
1
was established by H NMR, 13C NMR, 13C-APT, and HRMS
O
O
OH
26
acetone
MnO2, rt, 69%
anhyd benzene
overnight reflux
O
OH
O
77%
24
21
27
anhyd toluene
overnight reflux
65%
EtOAc, hν, [2+2]
28
125 W UV lamp
2 h, 91%
125 W UV lamp
EtOAc, hν, [2+2]
O
2 h, 91%
O
O
O
O
O
20b
29
20a
Scheme 3 Synthesis of diallyl cage diones 20a and 20b
Mg, I2, anhyd Et2O
+
Br
OH
O
O
OH
OH
O
0 °C to rt, 3 h
20a
30 (50%)
31 (34%)
Scheme 4 Allyl Grignard addition to diallyl spirodione 20a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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Synthesis
The 1H NMR spectrum of the hemiketal 34 showed two
multiplets at δ = 5.98–5.79 and 5.14–5.02 for nine protons
(olefin region) of the allyl groups in oxa-cage system. Also,
13C NMR spectrum displayed two peaks at δ = 91.1, 116.9,
which resembles characteristic carbons attached to hydrox-
yl and ether hemiketal respectively. Later on, hemiketals 30
and 34, which are derived from Grignard addition se-
quence, were subjected to O-allylation under basic condi-
tions using allyl bromide in anhydrous DMF to afford the
desired tetraallyl compounds 32 (93%) and 35 (83%), re-
spectively, in excellent yields (Schemes 5 and 6). Having
tetraallyl cage systems 32 and 35 in hand, the attention was
directed towards synthesis of target compounds 33 and 36
by employing RCM41 as a key step.
Later, the tetraallyl compounds 32 and 35 upon expo-
sure to Grubbs’ second-generation catalyst (G-II)47 under-
went RCM in anhydrous dichloromethane at room tem-
perature to deliver the cage heterocycles 33 and 36 in 88 to
89% isolated yields after column chromatography. The
structures of the RCM products 33 and 36 were established
on the basis of 1H NMR, 13C NMR, 13C-APT, and further con-
firmed by HRMS data. The 1H NMR spectra of RCM products
33 and 36 clearly indicate the presence of three multiplets
at δ = 5.78–5.72 (2 H), 5.64–5.58 (1 H), and 5.43–5.38 (1 H)
for four olefinic protons of the annulated rings (Schemes 5
and 6). Moreover, the 13C NMR spectra of 33 and 36 re-
vealed two characteristic peaks at δ = 88.8, 120.4, which in-
dicate for mono-oxygenated and di-oxygenated carbon at-
oms. The structure of RCM product 33 has been established
by single-crystal X-ray diffraction studies (Figure 3).48
Br
NaH, DMF
0 °C to rt
G-II (5 mol%)
CH2Cl2
O
O
rt, 10 h, 88%
5 h, 93%
OH
O
O
O
33
30
32
Pd/C, H2 (1 atm)
rt, 4 h, 84%
N
N
Cl
Ru
Ph
Cl
P(Cy)3
G-II
O
O
19a
Scheme 5 Synthesis of bis-annulated cage ether 19a
Br
Mg, I2, anhyd Et2O
NaH, DMF
Br
0 °C to rt
5 h, 83%
OH
O
O
O
O
0 °C to rt, 5 h, 76%
O
20b
34
35
G-II (5 mol%)
CH2Cl2
rt, 15 h, 89%
Pd/C, H2 (1 atm)
rt, 5 h, 88%
O
O
O
O
19b
36
Scheme 6 Synthesis of bis-annulated nonacyclic cage ether 19b
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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Synthesis
Hydrogenation of RCM products 33 and 36 with the aid of
Pd/C under hydrogen atmosphere in anhydrous ethyl ace-
tate produced the saturated compounds 19a and 19b in ex-
cellent yields (Schemes 5 and 6).
tion of mono-annulated derivative 43 in the presence Pd/C
under hydrogen atmosphere in anhydrous ethyl acetate
gave the alkylated cage ether 44 in good yield (Scheme 9).
13C NMR values of RCM products at δ = 120–122 indicate
carbon connected with adjacent two oxygen atoms. More-
over, δ values around 86–102 ppm indicate the carbon con-
nected to oxygen atom. The 13C value at δ = 65–68 revealed
the presence of CH2 attached to oxygen atom (Figure 4).
In summary, we have established a simple synthetic se-
quence to intricate oxa-cage compounds 19a and 19b in
nine steps starting with readily available and inexpensive
starting material such as 1,4-hydroquinone using Claisen
rearrangement, Diels–Alder reaction, [2+2] photocycloaddi-
tion, and RCM as key steps. In this strategy, transannular cy-
clization during Grignard addition and RCM play a crucial
role to design annulated oxa-cage frameworks containing
oxepane and tetrahydrofuran ring system. Further exten-
sion of this strategy to novel cage molecules will be report-
ed in near future. The synthetic sequences described here
are devoid of any usage of protecting groups.49
There are two possibilities to produce RCM product
starting with tetraallyl system 32. Based on Path 1 ([a+c,
b+d]) and Path 2 ([a+b, c+d]) shown in Scheme 7, it was an-
ticipated that the four allyl groups, which are present in the
32 would undergo RCM to generate an oxa system 33 or 37.
Depending on strain energy consideration, Path 2 ([a+b,
c+d]) is not favorable to produce RCM product 37. More-
over, the separation between allyl groups (c and d) does not
allow the 2nd option. Whereas in Path 1 ([a+c, b+d]), the al-
lyl groups present in 32 are favorable for RCM to give 33.
Along similar lines, the above strategy was extended to
other annulated cage targets. To this end, cage diones 20a
and 20b were treated with vinyl Grignard reagent to pro-
duce the hemiketals 38 and 41 in good yields. Subsequently,
O-allylation of hemiketals 38 and 41 under NaH/allyl bro-
mide in anhydrous DMF for 7–10 hours at room tempera-
ture gave the compounds 39 and 42 in 76–81% yields
(Scheme 8 and Scheme 9). To synthesize bis-annulated
polycyclic caged ethers, compounds 39 and 42 were sub-
jected to the RCM sequence in the presence Grubbs’ sec-
ond-generation catalyst (G-II) in anhydrous dichlorometh-
ane at room temperature for 8–10 hours to generate the
bis-annulated product 40 and mono-annulated derivative
43 in 94% and 84% yield, respectively. The structure of the
All the required reagents, chemicals, and solvents were purchased
from commercial vendors and used as without any further purifica-
tion. Analytical TLC was performed on (10 × 5) glass plates coated
with Acme’s silica gel (GF-254) containing 13% calcium sulfate as a
binder. All the reactions were monitored by TLC using suitable solvent
system and visualization was done under UV light, exposure to iodine
vapor, and by dipping into a solution of KMnO4. Anhydrous reactions
were performed in oven-dried glassware under N2 atmosphere by us-
ing standard syringe-septum techniques. Acme’s silica gel (100–200
mesh size) was used for column chromatography and solvents were
concentrated under vacuo on rotary evaporator. Benzene, toluene,
CH2Cl2 were distilled from P2O5 or CaH2, and EtOAc was dried by using
K2CO3.
RCM product 40 was confirmed with the aid of 1H NMR, 13
C
NMR, APT, and further analyzed by HRMS data. Hydrogena-
IR spectra were recorded on a Nicolet Impact-400 FTIR spectropho-
tometer and samples were prepared as a thin film between CsCl
plates by dissolving the compound in CH2Cl2 or CHCl3 and then evapo-
rating the solvent. 1H NMR (400 and 500 MHz), 13C NMR, 13C-APT,
DEPT 135 NMR (100 and 125 MHz) spectra were recorded on Bruker
spectrometers and samples were prepared in CDCl3 solvent. The
chemical shifts are reported in parts per million (ppm) on δ scale
with TMS as an internal standard and values for the coupling con-
stants (J) are given in Hz. The standard abbreviations for 1H NMR spin
couplings are given as s, d, t, q, dd, dt, td, and m for singlet, doublet,
triplet, quartet, doublet of doublet, doublet of triplet, triplet of
Figure 3 X-ray crystal structure of 33 with thermal ellipsoids drawn at
the 50% probability level
Path 2
RCM
RCM
b
a
Path 2
Path 1
[a+c, b+d]
[a+b, c+d]
O
O
O
d
O
O
c
O
favorable
unfavorable
32
33
37
Path 2
Scheme 7 Two possible pathways for RCM of compound 32
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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Synthesis
Br
NaH, DMF
anhyd Et2O
MgBr
0 °C to rt
7 h, 81%
0 °C to rt, 3 h, 83%
O
OH
O
O
O
O
20a
38
39
G-II (5 mol%)
CH2Cl2
reflux, 10 h, 94%
O
O
40
Scheme 8 Synthesis of bis-annulated nonacyclic caged ether 40
anhyd Et2O
MgBr
Br
NaH, DMF
0 °C to rt, 5 h, 75%
0 °C to rt,
10 h, 76%
O
OH
O
O
O
O
20b
41
42
G-II (5 mol%)
CH2Cl2
rt, 8 h, 84%
Pd/C, H2 (1 atm)
rt, 5 h, 81%
O
O
Et
O
O
44
43
Scheme 9 Synthesis of polycyclic alkylated caged ether 44
O
O
O
O
O
O
O
O
86.59
122.36
65.74
88.84 120.46 65.66
86.55 122.31
68.49
88.84 120.46 68.74
O
O
O
Et
O
O
O
122.30
102.92
65.38
91.60
119.46 68.43
91.73
119.92 68.51
Figure 4 Comparison of 13C NMR value(s) of products with respect to oxygen attached carbons
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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S. Kotha et al.
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Synthesis
doublet, and multiplet, respectively. High-resolution mass spectra
(HRMS) were recorded in a positive ion electrospray ionization (ESI).
All melting points were recorded on Veego VMP-CMP melting point
apparatus and are uncorrected. All reported yields are isolated yields
of the products after column purification. X-ray data were recorded
on diffractometer equipped with graphite monochromated MoKα ra-
diation and structure was solved by direct methods shelxl-97 and re-
fined by full-matrix least-squares against F2 using shelxl-97 software.
Spirodienes 2643 and 2843 were prepared according to known litera-
ture procedures.
Diallyl Hexacyclic Cage Dione 20b
The [4+2] cycloadduct 29 (700 mg, 2.27 mmol) was dissolved in an-
hyd EtOAc (250 mL) and irradiated in a Pyrex immersion well by using
125 W UV lamp (home-made) for 2 h under N2 atmosphere at r.t. Af-
ter completion of the reaction (monitored by TLC), the solvent was
evaporated under vacuo and the crude residue was purified by silica
gel column chromatography (7% EtOAc/PE) to give 20b as a pure white
crystalline solid; yield: 640 mg (91%); mp 73–74 °C.
IR (neat): 3081, 2949, 2867, 1752, 1734, 1437, 1117, 918 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 5.49–5.59 (m, 2 H), 5.01–5.07 (m, 4 H),
2.99 (s, 2 H), 2.85 (s, 2 H), 2.51 (dd, J = 14.0, 5.6 Hz, 2 H), 2.34–2.32 (m,
2 H), 2.21 (dd, J = 14.0, 8.4 Hz, 2 H), 1.66–1.63 (m, 4 H), 1.53–1.62 (m,
4 H).
13C NMR (100 MHz, CDCl3): δ = 212.9, 132.5, 118.5, 65.4, 55.2, 53.8,
51.1, 41.3, 32.2, 30.1, 28.4, 25.5, 25.4.
Diels-Alder Adduct 2744
A solution of 2,3-diallyl-1,4-benzoquinone (21; 500 mg, 2.63 mmol)
in anhyd benzene was added to freshly prepared spiro[2.4]hepta-4,6-
diene (26; 0.5 mL, 4.73 mmol) with stirring. Then, the resulting reac-
tion mixture was refluxed overnight. At the conclusion of the reaction
(TLC analysis), the solvent was removed under vacuo and the crude
residue was directly subjected to silica gel column chromatography
without any further workup by using 7% EtOAc in PE as an eluent to
give the Diels–Alder adduct 27 as a pure viscous yellow liquid; yield:
570 mg (77%).
HRMS (ESI): m/z calcd for C21H24O2Na [M + Na]+: 331.1669; found:
331.1661.
Allyl Grignard Addition to Cage Diones 20a and 20b; General Pro-
cedure
1H NMR (400 MHz, CDCl3): δ = 6.04 (t, J = 1.9 Hz, 2 H), 5.72–5.62 (m, 2
H), 4.99–4.94 (m, 4 H), 3.36–3.35 (m, 2 H), 3.13 (td, J = 4.0, 2.0 Hz, 4
H), 2.84 (t, J = 1.8 Hz, 2 H), 0.57–0.53 (m, 2 H), 0.46–0.42 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 198.2, 149.2, 135.3, 133.5, 116.8, 53.9,
49.3, 44.7, 31.0, 8.0, 6.9.
To a freshly prepared allylmagnesium bromide solution in anhyd Et2O
was added the diallyl spiro cage dione 20a or 20b (150 mg, 0.54 mmol
for 20a or 200 mg, 0.64 mmol for 20b) in anhyd Et2O dropwise over a
period of 10 min under continuous flow of N2 at r.t. After conclusion
of the reaction (3 h for 20a and 5 h for 20b, reaction progress by TLC
monitoring), the reaction mixture was quenched with sat. aq NH4Cl at
0 °C, and the resulting aqueous layer was extracted with EtOAc. The
combined organic layers were washed with brine and dried (anhyd
Na2SO4). The solvent was evaporated under vacuo and the resulting
crude residue was subjected to silica gel column chromatography (3
to 6% EtOAc/PE ether as an eluent) to afford pure 30, 31, and 34 as col-
orless liquids.
Diallyl Hexacyclic Cage Dione 20a44
The cycloadduct 27 (400 mg, 1.42 mmol) was dissolved in anhyd EtOAc
(250 mL) and irradiated in a Pyrex immersion well by using 125 W
medium pressure UV mercury vapor lamp (home-made) for 2 h under
continuous flow of N2 at r.t. After conclusion of the reaction (TLC
monitoring), the solvent was evaporated under reduced pressure and
the crude reaction mixture was purified by silica gel column chroma-
tography using 10% EtOAc in PE as an eluent to afford the compound
20a as a white crystalline solid; yield: 178 mg ((91%); mp 81–83 °C.
Compound 30 (Triallyl Hemiketal)44
Yield: 85 mg (50%).
1H NMR (400 MHz, CDCl3): δ = 5.99–5.79 (m, 3 H), 5.15–5.02 (m, 6 H),
3.99 (s, 1 H), 2.90–2.86 (m, 1 H), 2.76–2.72 (m, 1 H), 2.58–2.53 (m, 3
H), 2.48 (dd, J = 15.2, 5.9 Hz, 1 H), 2.39–2.30 (m, 3 H), 2.25 (dd,
J = 14.4, 8.0 Hz, 1 H), 1.86 (t, J = 4.5 Hz, 1 H), 1.68 (t, J = 4.5 Hz, 1 H),
0.48–0.43 (m, 2 H), 0.34–0.27 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 136.2, 135.6, 134.4, 117.7, 117.4,
117.08, 117.04, 91.1, 58.4, 58.1, 57.2, 55.6, 49.6, 48.6, 44.7, 43.8, 40.1,
35.2, 32.4, 32.2, 5.2, 5.0.
1H NMR (400 MHz, CDCl3): δ = 5.56–5.46 (m, 2 H), 5.05–4.97 (m, 4 H),
3.05 (t, J = 1.3 Hz, 2 H), 2.89 (d, J = 1.7 Hz, 2 H), 2.47 (dd, J = 14.0, 5.7
Hz, 2 H), 2.20 (dd, J = 14.0, 8.3 Hz, 2 H), 2.10–2.07 (m, 2 H), 0.63 (m, 4
H).
13C NMR (100 MHz, CDCl3): δ = 213.0, 132.6, 118.6, 56.0, 54.7, 49.2,
41.6, 38.0, 30.2, 5.4, 4.0.
Diels-Alder Adduct 29
A solution of 2,3-diallyl-1,4-benzoquinone (21; 800 mg, 4.20 mmol)
and freshly prepared spiro[4.4]nona-1,3-diene (28; 910 mg, 7.58
mmol) in anhyd toluene (10 mL) was kept refluxed for 10 h (the reac-
tion progress monitored by TLC). Then, the solvent was evaporated
under reduced pressure and the residue was purified by silica gel col-
umn chromatography (4% EtOAc/PE) to afford pure 29 as a thick yel-
low liquid, which solidified at 0 °C; yield: 850 mg (65%); mp 47–49 °C.
Compound 31 (Tetraallyl Cage Diol)44
Yield: 67 mg (34%).
1H NMR (400 MHz, CDCl3): δ = 6.17–6.07 (m, 2 H), 5.97–5.83 (m, 2 H),
5.11–5.00 (m, 8 H), 4.93 (s, 2 H), 2.77 (dd, J = 16.1, 5.8 Hz, 2 H), 2.43–
2.33 (m, 8 H), 1.93 (dd, J = 14.0, 8.6 Hz, 2 H), 1.59 (s, 2 H), 0.47–0.43
(m, 2 H), 0.32–0.28 (m, 2 H).
IR (neat): 3016, 2954, 1662, 1354, 1271, 1216, 918 cm–1
.
13C NMR (100 MHz, CDCl3): δ = 137.8, 133.9, 117.7, 116.4, 80.1, 53.5,
1H NMR (500 MHz, CDCl3): δ = 5.96 (s, 2 H), 5.72–5.64 (m, 2 H), 4.95–
5.00 (m, 4 H), 3.28 (s, 2 H), 3.14 (d, J = 6.1 Hz, 4 H), 3.08 (s, 2 H), 1.57–
1.61 (m, 2 H), 1.50–1.42 (m, 6 H).
49.8, 49.5, 43.9, 43.0, 34.3, 30.8, 5.1, 4.6.
Compound 34 (Triallyl Hemiketal)
13C NMR (125 MHz, CDCl3): δ = 198.8, 149.2, 136.2, 133.6, 116.8, 69.0,
Yield: 173 mg (76%).
IR (neat): 3330, 2951, 2360, 1670, 1043 cm–1
.
56.6, 48.8, 32.0, 31.6, 31.0, 25.9, 25.4.
HRMS (ESI): m/z calcd for C21H24O2Na [M + Na]+: 331.1669; found:
331.1662.
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1H NMR (500 MHz, CDCl3): δ = 5.98–5.79 (m, 3 H), 5.14–5.02 (m, 6 H),
4.01 (s, 1 H), 2.78 (dd, J = 4.40, 1.80 Hz, 1 H), 2.63 (dd, J = 4.70, 1.85
Hz, 1 H), 2.57–2.53 (m, 1 H) 2.48–2.43 (m, 3 H), 2.35–2.22 (m, 3 H),
2.11 (t, J = 4.40 Hz, 1 H), 1.92 (t, J = 4.65 Hz, 1 H), 1.89 (s, 1 H), 1.55–
1.47 (m, 6 H), 1.33–1.29 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 136.2, 135.6, 134.4, 117.7, 117.3,
117.0, 116.9, 91.1, 68.6, 58.2, 57.5, 56.8, 55.0, 51.3, 50.3, 44.5, 43.7,
35.2, 32.9, 32.4, 32.2, 31.1, 25.6, 25.4.
RCM Precursors 32, 35, 39, and 42; General Procedure
To a suspension of NaH (1.4–2.6 mmol, 4 equiv) in anhyd DMF (5–10
mL) was added the required hemiketal 30, 34, 38, or 41 (0.32–0.44
mmol, 1 equiv) under N2 at 0 °C. Then the reaction mixture was
stirred for 15 min at r.t. Afterwards, allyl bromide (1.4–2.6 mmol, 4
equiv) was added and then stirring was continued for 5–10 h. At the
end of the reaction (TLC analysis), the crude reaction mixture was
quenched with sat. aq NH4Cl and the resulting aqueous layer was ex-
tracted with EtOAc. The combined organic layers were washed with
brine and dried (anhyd Na2SO4). The solvent was evaporated under
reduced pressure and the resulting crude residue was subjected to sil-
ica gel column chromatography using 1–2% EtOAc/PE as an eluent to
afford pure 32, 35, 39, and 42, respectively, as colorless liquids.
HRMS (ESI): m/z calcd for C24H30O2Na [M + Na]+: 373.2138; found:
373.2139.
Vinyl Grignard Addition to Cage Diones 20a and 20b; General
Procedure
To a solution of commercially available vinylmagnesium bromide
(1 M solution in Et2O) in anhyd Et2O was added the diallyl spiro cage
diones 20a or 20b (200 mg, 0.71 mmol for 20a or 300 mg, 0.97 mmol
for 20b) in anhyd Et2O dropwise over a period of 15 min under con-
tinuous flow of N2 at r.t. After conclusion of the reaction (5 h for 20a
and 20b, by TLC evident), the reaction mixture was quenched with
sat. aq NH4Cl at 0 °C. The aqueous layer was extracted with EtOAc and
the combined organic layers were washed with brine and dried (an-
hyd Na2SO4). The solvent was evaporated under reduced pressure and
the resulting crude residue was purified by a silica gel column chro-
matography using 5% EtOAc/PE ether as an eluent to give 38 and 41 as
pure white crystalline solids.
Compound 32
Prepared from compound 30 (120 mg, 0.37 mmol); yield: 125 mg
(93%).
IR (neat): 2994, 1605, 1229, 981 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 6.00–5.80 (m, 4 H), 5.28 (d, J = 2.35 Hz,
1 H), 5.13–4.95 (m, 7 H), 4.31 (dt, J = 4.06, 1.80 Hz, 1 H), 4.22 (dt,
J = 5.08, 1.64 Hz, 1 H), 2.99 (dd, J = 4.64, 2.68 Hz, 1 H), 2.82 (dd,
J = 4.56, 1.88 Hz, 1 H), 2.63–2.49 (m, 3 H), 2.46–2.23 (m, 5 H), 1.75 (t,
J = 4.88 Hz, 1 H), 1.69 (t, J = 4.92 Hz, 1 H), 0.48–0.44 (m, 2 H), 0.35–
0.29 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 136.7, 135.9, 135.2, 134.7, 119.9,
117.4, 116.9, 116.0, 115.4, 90.6, 66.6, 58.1, 57.5, 57.0, 51.9, 49.7, 49.0,
44.2, 43.6, 40.2, 35.3, 32.5, 31.9, 5.2, 5.0.
Compound 38
Yield: 182 mg (83%); mp 115–117 °C.
IR (neat): 3268, 2994, 1605, 1457, 1336, 1014, 918 cm–1
HRMS (ESI): m/z calcd for C25H30O2K [M + K]+: 401.1877; found:
401.1880.
.
1H NMR (400 MHz, CDCl3): δ = 6.03–5.89 (m, 2 H), 5.85–5.75 (m, 1 H),
5.27 (d, J = 1.04 Hz, 1 H), 5.16 (d, J = 12.0 Hz, 2 H), 5.09–4.99 (m, 3 H),
3.73 (s, 1 H), 2.91 (dd, J = 11.0, 4.3 Hz, 1 H), 2.81 (dd, J = 11.1, 4.56 Hz,
1 H), 2.58 (s, 2 H), 2.49 (dd, J = 15.6, 6.3 Hz, 1 H), 2.36 (dd, J = 15.6, 7.8
Hz, 1 H), 2.27 (d, J = 6.8 Hz, 2 H), 1.90 (t, J = 4.3 Hz, 1 H), 1.81 (t, J = 4.4
Hz, 1 H), 0.51–0.46 (m, 2 H), 0.37–0.30 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 136.1, 135.5, 135.1, 117.5, 117.3,
117.2, 114.8, 92.2, 60.2, 59.4, 58.3, 55.8, 50.4, 48.4, 44.8, 43.9, 40.2,
33.2, 32.3, 5.3, 5.0.
Compound 35
Prepared from compound 34 (150 mg, 0.42 mmol); yield: 138 mg
(83%).
IR (neat): 2933, 2362, 1678, 1214, 1048 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 6.00–5.80 (m, 4 H), 5.28 (dd, J = 3.79,
1.85 Hz, 1 H), 5.12–4.95 (m, 7 H), 4.31–4.27 (m, 1 H), 4.22–4.18 (m, 1
H), 2.88 (dd, J = 4.50, 2.00 Hz, 1 H), 2.70 (dd, J = 4.50, 1.90 Hz, 1 H),
2.58 (td, J = 5.65, 1.59 Hz, 1 H) 2.47–2.21 (m, 7 H), 2.00 (t, J = 4.80 Hz,
1 H), 1.92 (t, J = 4.75, 1 H), 1.56–1.47 (m, 6 H), 1.36–1.26 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 136.7, 135.8, 135.2, 134.7, 119.8,
117.3, 116.8, 116.0, 115.4, 90.6, 68.6, 66.5, 57.5, 56.8, 56.6, 51.5, 51.4,
50.6, 44.0, 43.4, 35.3, 32.9, 32.5, 31.9, 31.2, 25.7, 25.4.
HRMS (ESI): m/z calcd for C21H24O2 Na [M + Na]+: 331.1669; found:
331.1667.
Compound 41
Yield: 245 mg (75%); mp 92–94 °C.
HRMS (ESI): m/z calcd for C27H35O2 [M + H]+: 391.2637; found:
IR (neat): 3369, 3074, 2945, 2864, 1635, 1432, 1334, 1276, 1190,
391.2647.
1097, 993, 909 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 6.02–5.89 (m, 2 H), 5.83–5.73 (m, 1 H),
5.26 (d, J = 1.54 Hz, 1 H), 5.17–5.11 (m, 2 H), 5.07–4.98 (m, 3 H), 4.04
(s, 1 H), 2.82–2.70 (m, 2 H), 2.50–2.43 (m, 3 H), 2.32 (dd, J = 15.2, 7.8
Hz, 1 H), 2.25 (d, J = 6.7 Hz, 2 H), 2.13 (t, J = 4.5 Hz, 1 H), 2.04 (t, J = 4.4
Hz, 1 H), 1.56–1.48 (m, 6 H), 1.36–1.31 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 136.1, 135.5, 135.2, 117.5, 117.1,
117.0, 114.7, 92.1, 68.7, 59.5, 59.1, 57.9, 55.2, 52.0, 50.0, 44.4, 43.7,
33.2, 32.9, 32.1, 31.1, 25.6.
Compound 39
Prepared from compound 38 (100 mg, 0.32 mmol); yield: 92 mg
(81%).
IR (neat): 3020, 2966, 1608, 1325, 1215, 1027, 914 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 6.08–5.92 (m, 3 H), 5.83–5.77 (m, 1 H),
5.31–5.23 (m, 2 H), 5.19–5.11 (m, 2 H), 5.04–4.97 (m, 4 H), 4.36–4.23
(m, 2 H), 3.06 (dd, J = 4.4, 1.87 Hz, 1 H), 2.85 (dd, J = 4.48, 1.81 Hz, 1
H), 2.59–2.41 (m, 3 H), 2.35–2.24 (m, 3 H), 1.82–1.78 (m, 2 H), 0.50–
0.47 (m, 2 H), 0.37–0.31 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 136.7, 135.8, 135.7, 135.2, 120.0,
116.9, 116.1, 115.5, 114.9, 91.7, 66.7, 60.2, 59.1, 57.6, 51.7, 50.5, 48.7,
44.3, 43.4, 40.2, 33.2, 31.8, 5.3, 5.0.
HRMS (ESI): m/z calcd for C23H29O2 [M + H]+: 337.2162; found:
337.2165.
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HRMS (ESI): m/z calcd for C24H28O2Na [M + Na]+: 371.1982; found:
HRMS (ESI): m/z calcd for C23H26O2Na [M + Na]+: 357.1825; found:
371.1982.
357.1822.
Compound 42
Compound 40
Prepared from compound 41 (150 mg, 0.44 mmol); yield: 127 mg
Prepared from compound 39 (80 mg, 0.22 mmol); colorless solid;
(76%).
yield: 63 mg (94%); mp 126–128 °C.
IR (neat): 3016, 2955, 2867, 1639, 1425, 1330, 1212, 993, 919 cm–1
.
IR (neat): 3016, 2959, 1217, 1168, 1015, 949 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 6.08–5.90 (m, 3 H), 5.85–5.74 (m, 1 H),
5.33–5.25 (m, 2 H), 5.18–5.11 (m, 2 H), 5.05–4.96 (m, 4 H), 4.33 (dt,
J = 4.6, 1.7 Hz, 1 H), 4.24 (dt, J = 5.10, 1.64 Hz, 1 H), 2.96 (dd, J = 4.5,
2.0 Hz, 1 H), 2.75 (dd, J = 4.5, 1.9 Hz, 1 H), 2.50–2.40 (m, 3 H), 2.28–
2.23 (m, 3 H), 2.07–2.02 (m, 2 H), 1.55–1.48 (m, 6 H), 1.36–1.31 (m, 2
H).
1H NMR (500 MHz, CDCl3): δ = 6.05 (dt, J = 5.5, 2.1 Hz, 1 H), 5.78 (ddd,
J = 7.4, 2.86 Hz, 1 H), 5.68–5.63 (m, 1 H), 5.50–5.46 (m, 1 H), 4.46–4.26
(m, 2 H), 3.13 (dd, J = 4.3, 1.6 Hz, 1 H), 2.82 (dd, J = 4.6, 2.2 Hz, 1 H),
2.69–2.66 (m, 1 H), 2.52–2.47 (m, 3 H), 2.24–2.13 (m, 2 H), 1.91 (t,
J = 4.89 Hz, 1 H), 1.83 (t, J = 4.6 Hz, 1 H), 0.53–0.46 (m, 2 H), 0.36–0.30
(m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 136.8, 135.9, 135.3, 120.0, 117.0,
116.1, 115.5, 114.8, 91.8, 68.8, 66.7, 59.6, 58.9, 57.0, 52.2, 51.4, 50.4,
44.2, 43.3, 33.3, 33.1, 31.9, 31.2, 25.7, 25.5.
13C NMR (125 MHz, CDCl3): δ = 140.9, 129.2, 126.1, 125.8, 122.3,
102.9, 65.3, 64.1, 57.4, 57.3, 55.6, 52.0, 49.1, 47.9, 46.3, 40.4, 35.4,
27.0, 5.5, 5.1.
HRMS (ESI): m/z calcd for C26H32O2Na [M + Na]+: 399.2295; found:
HRMS (ESI): m/z calcd for C20H21O2 [M + H]+: 293.1536; found:
399.2295.
293.1536.
Compounds 33, 36, 40, and 43 via RCM Sequence; General Proce-
dure
Compound 43
Prepared from compound 42 (100 mg, 0.26 mmol); colorless liquid;
To a stirred solution of the respective RCM precursor 32, 35, 39, or 42
(0.22–0.27 mmol, 1 equiv) in anhyd CH2Cl2 (10 mL) degassed with N2
for 10 min was added G-II catalyst (5 mol%). Then the reaction mix-
ture was stirred at r.t. for 8–15 h. After completion of the reaction (re-
action progress was monitored by TLC), the solvent was removed un-
der reduced pressure and the crude reaction mixture was purified by
silica gel column chromatography using 2–5% EtOAc/PE as an eluent
to give 33, 36, 40, and 43, respectively.
yield: 78 mg (84%).
IR (neat): 2994, 2971, 2821, 2717, 1605, 1500, 1426, 1304, 1275,
1020, 918 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 6.00–5.82 (m, 4 H), 5.33–5.12 (m, 4 H),
4.34–4.20 (m, 2 H), 3.01 (dd, J = 4.6, 2.1 Hz, 1 H), 2.77 (dd, J = 4.5, 1.8
Hz, 1 H), 2.27–2.09 (m, 5 H), 1.98 (dd, J = 16.2, 6.2 Hz, 1 H), 1.86–1.85
(m, 2 H), 1.61–1.47 (m, 6 H), 1.34–1.27 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 134.9, 134.5, 127.2, 126.8, 119.7,
115.8, 114.7, 91.5, 68.3, 66.6, 58.6, 56.9, 54.2, 52.0, 51.3, 50.2, 45.3,
44.8, 32.7, 31.0, 26.1, 25.6, 25.3, 23.9.
Compound 33
Prepared from compound 32 (100 mg, 0.27 mmol); colorless solid;
yield: 75 mg (88%); mp 121–123 °C.
HRMS (ESI): m/z calcd for C24H28O2Na [M + Na]+: 371.1982; found:
371.1987.
IR (neat): 2955, 2928, 2837, 1447, 1374, 1320, 1315, 1281, 1205,
1156, 1124, 1073, 949, 861 cm–1
.
Compounds 19a, 19b, and 44 via Catalytic Hydrogenation; General
Procedure
1H NMR (400 MHz, CDCl3): δ = 5.78–5.71 (m, 2 H), 5.64–5.58 (m, 1 H),
5.43–5.38 (m, 1 H), 4.43–4.25 (m, 2 H), 2.87–2.78 (m, 2 H), 2.64–2.53
(m, 2 H), 2.47–2.33 (m, 3 H), 2.11 (d, J = 7.56 Hz, 1 H), 2.09 (t, J = 1.68
Hz, 2 H), 1.88 (t, J = 4.80 Hz, 1 H), 1.75 (t, J = 4.72 Hz, 1 H), 0.50–0.42
(m, 2 H), 0.34–0.27 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 128.9, 125.99, 125.90, 125.2, 120.4,
88.8, 65.6, 62.0, 57.9, 57.0, 55.3, 50.1, 49.6, 48.6, 45.4, 40.2, 29.1, 25.6,
25.5, 5.3, 4.9.
To a stirred solution of the respective compound 33, 36, or 43 (0.11–
0.16 mmol, 1 equiv) in anhyd EtOAc (5 mL) was added 10 mol% Pd/C
(2 to 5 mg). Then the resulting reaction mixture was stirred at r.t. for
4–5 h under H2 atmosphere (1 atm). After completion of the reaction
(TLC monitoring), the reaction mixture was filtered through a Celite
pad and washed with EtOAc (10 mL). The combined washings and fil-
trate were evaporated under vacuo and the resulting crude residue
was purified by silica gel column chromatography using 2–7%
EtOAc/PE ether as an eluent to afford the hydrogenated products 19a,
19b, and 44, respectively.
HRMS (ESI): m/z calcd for C21H22O2Na [M + Na]+: 329.1512; found:
329.1516.
Compound 36
Compound 19a
Prepared from compound 35 (100 mg, 0.25 mmol); colorless solid;
yield: 76 mg (89%); mp 135–137 °C.
Prepared from compound 33 (50 mg, 0.16 mmol); colorless solid;
yield: 43 mg (84%); mp 98–100 °C.
IR (neat): 2932, 2852, 2343, 1454, 1319, 1219, 1154, 1017, 949 cm–1
1H NMR (500 MHz, CDCl3): δ = 4.01–3.96 (m, 1 H), 3.57–3.54 (m, 1 H),
2.76–2.69 (m, 2 H), 2.64–2.61 (m, 1 H), 2.41–2.38 (m, 1 H), 2.23 (d,
J = 14.6 Hz, 1 H), 1.92 (t, J = 4.7 Hz, 1 H), 1.78–1.30 (m, 13 H), 1.10–
1.01 (m, 1 H), 0.53–0.46 (2 H), 0.37–0.31 (m, 2 H).
IR (neat): 2927, 2858, 1670, 1393, 1042, 821, 649 cm–1
.
.
1H NMR (500 MHz, CDCl3): δ = 5.76 (dd, J = 13.05, 11.90 Hz, 2 H),
5.63–5.58 (m, 1 H), 5.45–5.41 (m, 1 H), 4.42–4.29 (m, 2 H), 2.78–2.70
(m, 2 H), 2.55–2.52 (m, 2 H), 2.44–2.34 (m, 2 H), 2.29–2.26 (m, 1 H),
2.15–2.07 (m, 4 H), 2.01–1.99 (m, 1 H), 1.58–1.47 (m, 6 H), 1.35–1.24
(m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 129.0, 126.0, 125.9, 125.2, 120.4, 88.8,
68.7, 65.6, 61.7, 57.3, 56.6, 54.7, 51.8, 51.3, 48.5, 45.3, 33.1, 31.0, 29.2,
25.7, 25.6, 25.5, 25.4.
13C NMR (125 MHz, CDCl3): δ = 122.3, 86.5, 65.7, 61.8, 57.9, 56.7, 54.6,
49.7, 49.5, 47.2, 45.9, 40.1, 32.0, 29.2, 26.6, 25.7, 22.2, 21.9, 5.2, 5.0.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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S. Kotha et al.
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Synthesis
HRMS (ESI): m/z calcd for C21H26O2Na [M + Na]+: 333.1825; found:
333.1824.
J.; Priefer, R. Chem. Rev. 2015, 115, 6719. (d) Olah, G. A. Cage
Hydrocarbons; Wiley: New York, 1990. (e) Dilmaç, A. M.;
Spuling, E.; de Meijere, A.; Bräse, S. Angew. Chem. Int. Ed. 2017,
56, 5684. (f) Hopf, H. Classics in Hydrocarbon Chemistry; Wiley-
VCH: Weinheim, 2000. (g) Gharpure, S. J.; Porwal, S. K. Org. Prep.
Proced. Int. 2013, 45, 81. (h) Vogtle, F. Fascinating Molecules in
Organic Chemistry; Wiley: Chichester, 1992.
Compound 19b
Prepared from compound 36 (50 mg, 0.14 mmol); colorless solid;
yield: 45 mg (88%); mp 107–109 °C.
IR (neat): 2931, 2852, 2343, 1495, 1449, 1318, 1153, 1048, 825 cm–1
.
(2) (a) Eaton, P. E.; Or, Y. S.; Branca, S. J.; Shankar, B. K. Tetrahedron
1986, 42, 1621. (b) Lim, H. N.; Dong, G. Org. Lett. 2016, 18, 1104.
(c) Marchand, A. P. Aldrichimica Acta 1995, 28, 95. (d) Kotha, S.;
Cheekatla, S. R.; Chinnam, A. K.; Jain, T. Tetrahedron Lett. 2016,
57, 5605.
1H NMR (500 MHz, CDCl3): δ = 3.94 (ddd, J = 12.4, 7.2, 2.8 Hz, 1 H),
3.55 (ddd, J = 12.8, 6.8, 3.2 Hz, 1 H), 2.62–2.59 (m, 2 H), 2.52–2.48 (m,
1 H), 2.27 (ddd, J = 8.4, 5.6, 1.6 Hz, 1 H), 2.20–2.14 (m, 2 H), 1.99 (t,
J = 4.4 Hz, 1 H), 1.66–1.24 (m, 20 H), 1.09–0.98 (m, 1 H).
(3) (a) Ternansky, R. J.; Balogh, D. W.; Paquette, L. A. J. Am. Chem.
Soc. 1982, 104, 4503. (b) Kroto, H. W.; Heath, J. R.; O’Brien, S. C.;
Curl, R. F.; Smalley, R. E. Nature 1985, 318, 162. (c) Chow, T. J.;
Liu, L. K.; Chao, Y. S. J. Chem. Soc., Chem. Commun. 1985, 700.
(d) Fessner, W.-D.; Sedelmeier, G.; Spurr, P. R.; Rihs, G.;
Prinzbach, H. J. Am. Chem. Soc. 1987, 109, 4626.
13C NMR (100 MHz, CDCl3): δ = 122.3, 86.5, 76.8, 68.4, 65.7, 61.5, 57.6,
56.1, 53.9, 51.4, 51.2, 47.0, 45.7, 33.0, 32.0, 31.1, 29.3, 26.6, 25.8, 25.6,
25.4, 22.2, 21.9.
HRMS (ESI): m/z calcd for C23H30O2Na [M + Na]+: 361.2138; found:
361.2138.
(4) (a) Chow, T. J.; Chiu, N.-R.; Chen, H.-C.; Chen, C.-Y.; Yu, W.-S.;
Cheng, Y.-M.; Cheng, C.-C.; Chang, C.-P.; Chou, P.-T. Tetrahedron
2003, 59, 5719. (b) Melder, J.-P.; Fritz, H.; Prinzbach, H. Angew.
Chem., Int. Ed. Engl. 1989, 28, 300. (c) Sahu, B.; Gururaja, G. N.;
Kumar, T.; Chatterjee, A.; Ganguly, B.; Mobin, S. M.;
Namboothiri, I. N. N. J. Org. Chem. 2012, 77, 6998. (d) Wang, S.
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Compound 44
Prepared from compound 43 (40 mg, 0.11 mmol); colorless liquid;
yield: 33 mg (81%).
IR (neat): 2935, 2871, 2343, 1495, 1459, 1319, 1268, 1236, 1190,
1171, 1134, 1100, 1066, 1022, 980 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 3.63 (dt, J = 9.1, 6.9 Hz, 1 H), 3.53 (dt,
J = 9.0, 7.0 Hz, 1 H), 2.92 (dd, J = 4.6, 1.9 Hz, 1 H), 2.69 (dd, J = 4.5, 1.8
Hz, 1 H), 2.53–2.49 (m, 1 H), 2.46–2.42 (m, 1 H), 2.02 (t, J = 4.7 Hz, 1
H), 1.94 (t, J = 5.0 Hz, 1 H), 1.78–1.69 (m, 1 H), 1.65–1.41 (m, 15 H),
1.38–1.28 (m, 4 H), 0.89 (td, J = 7.5, 3.0 Hz, 6 H).
13C NMR (125 MHz, CDCl3): δ = 119.4, 91.6, 76.9, 68.4, 67.1, 56.9, 52.2,
51.9, 51.7, 51.5, 50.4, 44.8, 44.5, 32.9, 31.2, 25.7, 25.5, 23.5, 22.4, 20.4,
18.4, 17.9, 10.6, 9.3.
HRMS (ESI): m/z calcd for C24H34O2Na [M + Na]+: 377.2451; found:
(8) (a) Cristol, S. J.; Snell, R. L. J. Am. Chem. Soc. 1954, 76, 5000.
(b) Cole, T. W. Jr.; Mayers, C. J.; Stock, L. M. J. Am. Chem. Soc.
1974, 96, 4555.
377.2455.
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Funding Information
We thank Defence Research and Development Organisation (DRDO,
NO. ARDB/01/1041849/M/1), New Delhi-India for financial assistance.
S.K. thanks Department of Science and Technology (DST, NO.
SR/S2/JCB-33/2010) DST, New Delhi, India for the award of a J. C. Bose
fellowship and Praj industries for Chair Professorship (Green Chemis-
try). S.R.C. thanks University Grants Commission (UGC), New Delhi,
(11) (a) Mehta, G.; Rao, K. S.; Krishnamurthy, N.; Srinivas, V.;
Balasubramanian, D. Tetrahedron 1989, 45, 2743. (b) Marchand,
A. P.; Huang, Z.; Chen, Z.; Hariprakasha, H. K.; Namboothiri, I. N.
N.; Brodbelt, J. S.; Reyzer, M. L. J. Heterocycl. Chem. 2001, 38,
1361. (c) Williams, S. M.; Brodbelt, J. S.; Marchand, A. P.; Cal, D.;
Mlinarié-Majerski, K. Anal. Chem. 2002, 74, 4423. (d) Levitskaia,
T. G.; Moyer, B. A.; Bonnesen, P. V.; Marchand, A. P.; Krishnudu,
K.; Chen, Z.; Huang, Z.; Kruger, H. G.; Mckim, A. S. J. Am. Chem.
Soc. 2001, 123, 12099.
India for the award of a research fellowship.
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591726. Copies of NMR (1H, 13C &
APT) spectra for all new compounds and X-ray crystallographic data
(CIF files) for compound 33 are included.
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(12) (a) Marchand, A. P.; Suri, S. C.; Earlywine, A. D.; Powel, D. R.;
Vander Helm, D. J. Org. Chem. 1984, 49, 670. (b) Mehta, G.;
Srikrishna, A.; Reddy, A. V.; Nair, M. S. Tetrahedron 1981, 37,
4543. (c) Griesbeck, A. G. Chem. Ber. 1990, 123, 549. (d) Mehta,
G.; Murthy, A. N.; Reddy, D. S.; Reddy, A. V. J. Am. Chem. Soc.
1986, 108, 3443.
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(48) CCDC 1573495 (33) contains supplementary crystallographic
data for this paper. The data can be obtained free of charge from
The
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/getstructures. For ORTEPs of product 33,
please see the SI file.
(49) Hoffmann, R. W. Synthesis 2006, 3541.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L