Synthetic studies toward nortriterpenoids of schisandraceae family. Approach to the construction of functionalized C/D and A/B ring units of micrandilactone C and rubrifloradilactone B

Article abstract of DOI:10.1016/j.tetlet.2011.09.104

Construction of 6/7 fused bicycles featuring C/D rings of micrandilactone C and rubrifloradilactone B is reported through IMDA reaction of properly designed substrates. Also a route to the construction of a tricycle having A/B ring of nortriterpenoids of

Full text of DOI:10.1016/j.tetlet.2011.09.104

Tetrahedron Letters 52 (2011) 6473–6476
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthetic studies toward nortriterpenoids of schisandraceae family. Approach
to the construction of functionalized C/D and A/B ring units
of micrandilactone C and rubrifloradilactone B
⇑
Md. Firoj Hossain, Kiran Matcha, Subrata Ghosh
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Construction of 6/7 fused bicycles featuring C/D rings of micrandilactone C and rubrifloradilactone B is
reported through IMDA reaction of properly designed substrates. Also a route to the construction of a tri-
cycle having A/B ring of nortriterpenoids of schisandra family is reported using RCM and a bromonium ion
initiated cycloetherification reaction as the key steps.
Received 30 August 2011
Revised 20 September 2011
Accepted 22 September 2011
Available online 2 October 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Diels–Alder reaction
Metathesis
Terpenoids
Lactone
Plants of the Schisandraceae family continue to be a rich
source of highly bioactive nortriterpenoids.1 Extracts of the
leaves and bark of these plants are extensively used as folk med-
icines in China for thousands of years. Over the years a large
number of compounds belonging to the family of triterpenoids
with densely oxygenated novel polycyclic skeletons have been
isolated from the plants of this family. Biosynthetically these
compounds are proposed to be derived from cycloartane.
Depending on the structural pattern, they have been classified
into six different types such as schisanartane (e.g. micrandilac-
tone A 1), schiartane (e.g. micrandilactone C 2), 18-nor schiar-
tane (e.g. rubrifloradilactone B 3), 18 (13?14)-abeo-schiartane
(wuweizidilactone C 4), pre-schisanartane (e.g. pre-schisanarta-
nin A 5 and wuweiziartane (e.g. schintrilactone A 6). Many of
these compounds exhibit promising medicinal properties. For
example, micrandilactone C 2,2 isolated from the leaves and
O
OH
O
H
O
OH
O
H
O
O
H
OH
H
H
H
H
O
O
O
O
O
H
A
B
O
D
O
O
H
O
H
H
OH
H
O
O
C
H
H
O
O
O
H
O
OH
H
H
OH
H
2
OH
H
1
3
O
O
H
O
O
O
O
O
H
OH
H
OH
OH
O
O
OAc
O
O
H
O
O
O
H
H
O
O
H
H
OH
H
O
H
O
O
O
H
OH
OAc
H
H
5
6
4
⇑
Corresponding author. Tel.: +91 33 2473 4971; fax: +91 33 2473 2805.
E-mail address: ocsg@iacs.res.in (S. Ghosh).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.09.104

6474
Md. Firoj Hossain et al. / Tetrahedron Letters 52 (2011) 6473–6476
O
O
O
A
B
2
3
H
O
O
H
O
O
7
8
A
O
O
H
B
O
O
O
O
A
B
H
H
O
9
H
Scheme 1. Retrosynthesis.
stems of Schisandra micrantha, possesses anti-HIV activity with
an EC50 value of 7.71
g mLꢀ1. Rubrifloradilactone B 3,3 isolated
from the leaves and stems of Schisandra Rubriflora, exhibits
anti-HIV activity with an EC50 value of 9.75
g mLꢀ1. The unique
l
l
architectural features combined with the remarkable medicinal
properties, schisandra terpenoids have elicited considerable inter-
est4 among synthetic organic chemists. Examination of the struc-
tures reveals the presence of the A/B/C ring as the common
structural unit. Thus synthetic efforts have so far remained re-
stricted to the development of strategies for the construction
of A/B4j,k,d or A/B/C4b,g,l,n fragments. There are also few reports
on the construction of the central carbocyclic4a,e,f,h,i,m,o core of
some of these compounds. However there is no report aimed
at the synthesis of micrandilactone C 2, and there is only a sin-
gle report5 on the construction of a tricyclic core structure of
rubrifloradilactones.
Figure 1. X-ray structure of compound 18b.
We initially focussed on determining the feasibility of the IMDA
reaction to construct 6/7 fused ring system as it is present in a large
number of terpenes other than schisandra nortriterpenes. Intramo-
lecular Diels–Alder reaction has been extensively explored to con-
struct hydrindane and decalin systems. However, there are only
few reports6 on IMDA reactions of undecatrienones to produce 6/
7 fused bicycles due to their significantly reduced reactivity toward
cycloaddition. Successful construction of 6/7 fused rings7 by IMDA
reaction requires high temperature,7a–c long reaction time7d and
even in some cases high pressure.8 During this investigation we
observed that intramolecular Diels–Alder reaction of the undecat-
rienones 17 and 20 in which the dienes and the dienophiles were
tethered through a furanosugar unit is very facile.
The precursor 17a for the IMDA reaction was prepared as delin-
eated in Scheme 2. Reaction of the glucose derivative 10 with the
Grignard reagent prepared from 4-bromo-1-butene led to the
known carbinol 119 in 50% isolable yield. Protection of the hydro-
xyl group as benzyl ether 12 followed by cleavage of the terminal
alkene unit produced the aldehyde 13 in over all excellent yield.
The aldehyde 1310 was then subjected to Wittig reaction with
the ylide generated from allyl triphenylphosphonium bromide to
produce the diene 14a in good yield. Selective deprotection of
the 5,6-acetonide moiety followed by periodate cleavage of the
resulting vicinal diol provided the aldehyde 15a. Addition of vinyl
magnesium bromide to the aldehyde 15a produced the carbinol
16a. When the carbinol 16a was subjected to Dess–Martin period-
inane (DMP) oxidation at rt, to our delight the tricyclic ketone 18a
Remarkable inhibitory activity of these two terpenoids against
HIV-1 replication stimulated our interest in developing routes to
the total synthesis of these natural products. We initially embarked
on developing a flexible route that could be employed to construct
functionalized tetracyclic A/B/C/D fragments present in both 2 and
3. Retrosynthetically, an intramolecular Diels–Alder (IMDA) reac-
tion in an appropriately designed substrate having the diene–
dienophilic component stitched together through the pre-built A/B
ring was envisaged as the key step (Scheme 1). To this end an IMDA
reaction in 7 was considered for the construction of the C/D ring
present in 2 while an IMDA reaction in 8 having a conjugated acety-
lenic ketone as the dienophilic component could be employed for
the synthesis of the C/D ring aromatic analogue present in 3. Precur-
sors 7 and 8 could in principle be available from 9. Herein we report
the preliminary results of our investigation on IMDA reaction for the
construction of C/D rings of 2 and 3 and a route to the synthesis of the
projected intermediate 9 featuring A/B ring present in a large num-
ber of schisandra nortriterpenoids.
O
O
O
O
O
O
CHO
O
O
H
H
H
H
H
H
H
H
O
O
O
O
v
O
O
iii
O
O
i
iv
O
O
O
O
O
R
H
H
H OR
H OBn
H OBn
11
, R = H
13
10
ii
14 a
b
, R = H
, R = Me
12, R = Bn
O
O
H
OH
H
O
H
H
H
H
H
H
O
H
O
O
O
CHO
vii
vi
O
O
O
R
O
O
O
H
O
R
R
H OBn
R
HOBn
17 a, R = H
H OBn
OBn
15 a
16 a
, R = H
, R = H
18 a, R = H
b, R = Me
b, R = Me
b
b
, R = Me
, R = Me
Scheme 2. Reagents and conditions: (i) 4-Bromo-1-butene, Mg, Et2O, 0 °C, 2 h, 50%; (ii) NaH, THF, 0 °C, HMPA, BnBr, 4 h, 95%; (iii) OsO4, THF–H2O (3:2), NaIO4, 0 °C, 12 h, 80%;
(iv) (a) nBuLi, allyltriphenylphosphonium bromide, THF, 0 °C, 1 h, 62%; (b) nBuLi, (2-methyl-2-propenyl)triphenylphosphonium bromide, THF, 0 °C, 1 h, 60%; (v) (a) 70% aq
AcOH, rt, 12 h, 80% (R = H) and 70% (R = Me); (b) NaIO4, THF–H2O (3:2), 0 °C, 2 h, 75% (R = H) and 70% (R = Me); (vi) CH2–CHMgBr, THF, ꢀ78 °C to rt, 55% (R = H) and 60%
(R = Me); (vii) DMP, CH2Cl2, 0 °C to rt, 9 h, 85% (R = H) and 80% (R = Me).

Md. F. Hossain et al. / Tetrahedron Letters 52 (2011) 6473–6476
6475
R
R
O
O
OH
O
H
H
H
H
H
O
H
H
H
O
O
O
O
O
R
O
R
O
i
ii
15a
O
O
H
O
O
H
H
H
OBn
OBn
OBn
21 a, R = H
OBn
22 a, R = H
19 a, R = H
20 a, R = H
b
b
b
b
, R = TMS
, R = TMS
, R = TMS
, R = TMS
Scheme 3. Reagents and conditions: (i) (a) Ethynylmagnesium bromide, THF, ꢀ78 °C to rt, 60%; (b) ethynyltrimethylsilane, nBuLi, THF, ꢀ78 °C to rt, 65%; (ii) DMP, CH2Cl2, 0 °C
to rt, 9 h, 45% (R = H) and 50% (R = TMS).
OH H
O
OH
O
O H
O
O
O
OH
O
O
i
iv
ii
iii
10
O
O
O
O
O
O
O
O
H
H
H
O
H
H
H
H
H
O
O
O
O
26
23
24
25
R
O
O H
O
H
O
OH
H
O
H
H
O
O
O
O
viii
v
vi
O
OH
HO
O
O
O
O
H
O
O
H
H
H
H
H
O
28
29
, R= Br
, R = H
9
27
vii
30
Scheme 4. Reagents and conditions: (i) CH2@CHMgBr, THF, ꢀ78 °C to rt, 2 h, 80%; (ii) NaH, CH2@CHCH2Br, THF, rt, 92%; (iii) [(PCy3)2Cl2Ru@CHPh], CH2Cl2, rt, 6 h, 95%; (iv) (a)
60% aq AcOH, rt, 12 h, 88%; (b) NaIO4, MeOH–H2O (2:1), 0.5 h, 84%; (c) MeMgl, Et2O; (d) DMP, CH2Cl2, 68% (two steps); (v) MeMgl, Et2O, 0 °C, 1 h, 80%; (vi) NBS, DMF, rt, 1 h,
95%; (vii) TBTH, AIBN, toluene, reflux, 2 h, 90%; (viii) RuCl3, NaIO4, rt, 5 h, 75%.
was obtained directly in excellent yield through IMDA reaction of
the in situ generated trienone 17a.
Intrigued by facile IMDA reaction of 17a during its generation,
we extended this protocol to make 18b. The aldehyde 13 was trea-
ted with the ylide generated from (2-methyl-2-propenyl) triphen-
ylphosphonium bromide to produce the diene 14b. The diene 14b
was then transformed to the carbinol 16b following the protocol
described for the transformation of 14a to 16a. Treatment of 16b
with DMP at rt similarly produced the tricyclic ketone 18b arising
through facile IMDA reaction of the in situ generated trienone 17b.
The structure of the adduct 18b was determined through X-ray
(Fig. 1).11 This led to assignment of structure to the adduct 18a.
The facile intramolecular Diels–Alder reaction of 17a and 17b to
form fused 6/7 bicyclic systems prompted us to examine the reac-
tivity with acetylenic dienophiles in order to make benzosuberone
Figure 2. X-ray structure of compound 28.
derivatives present in rubrifloradilactone B 3. Toward this direction
the aldehyde 15a was allowed to react with ethynylmagnesium
bromide to produce the carbinol 19a in excellent yield. Attempted
oxidation of this carbinol with DMP led directly to the benzosuber-
one derivative 22a in overall very good yield through IMDA reac-
tion of the in situ generated ketone 20a to the diene 21a (could
not be isolated) followed by its in situ dehydrogenation. It may
be noted that aromatization of 3,6-cyclohexadiene generally re-
quires7b treatment with DDQ. In the present case it occurred spon-
Grubbs’ 1st generation catalyst [(PCy3)2Cl2Ru@CHPh] afforded
the dihydrofuran derivative 25 in near quantitative yield. The dihy-
drofuran derivative 25 was then converted to the methyl ketone 26
as delineated in Scheme 4 in over all good yield. Addition of meth-
ylmagnesium iodide to 26 afforded the carbinol 27. The dihydrofu-
ran derivative 27 when treated with NBS-DMF underwent smooth
bromonium ion initiated cycloetherification to produce the tricy-
clic bromide 28 in 95% yield. The structure of this compound was
established through X-ray (Fig. 2). Reductive elimination of bro-
mine from 28 was achieved on treatment with tributyltin hydride
(TBTH) to afford the tricycle 29. The tricycle 29 was then smoothly
converted to the lactone 9 on oxidation with RuCl3–NaIO4. The su-
gar residue in the lactone 9 can in principle be elaborated to IMDA
precursor analogous to 17 and 20 through the keto-lactone 30 for
annulation of the C/D rings toward the synthesis of the nortriterp-
enoids 2 and 3.
taneously. In
a
similar fashion, the trimethyl silylated
benzosuberone derivative 22b was obtained as delineated in
Scheme 3. Thus by using IMDA reaction, C/D fused ring present
in micrandilactone C and rubrifloradilactone B can be made. The
facile IMDA reaction observed above suggests that appropriately
constructed undecatrienones on a prebuilt A/B ring can provide
the A/B/C/D rings present in 1 and 2.
After successfully demonstrating the feasibility of IMDA reac-
tion to construct 6/7 bicyclic system, we next focused on the con-
struction of the ring system 9 featuring the A/B ring of the
schisandra terpenoids. Reaction of the ketone 1012 with vinylmag-
nesium bromide produced the known carbinol 23 in excellent
yield. The carbinol was then transformed to the allyl ether 24 in
92% yield. Ring closing metathesis (RCM)13 of the diene 24 with
In conclusion, we have developed an IMDA reaction based route
to construct fused 6/7 bicycle featuring C/D ring systems present in
the nortriterpenoids 2 and 3. We have also developed a route for
the construction of the A/B ring present in schisandra terpenoids

6476
Md. Firoj Hossain et al. / Tetrahedron Letters 52 (2011) 6473–6476
21.5 (CH2); HRMS (ESI) calcd for C23H28O5Na (M+Na)+, 407.1834; found,
using RCM and a bromonium ion initiated cycloetherification reac-
tions as the key steps.
407.1834. Compound 18b. Mp 137–138 °C; ½a D26
ꢀ26.48 (c 0.33, CHCl3); IR mmax
ꢁ
(liquid film) 1715 cmꢀ1 1H NMR (300 MHz, CDCl3) d 7.45–7.29 (5H, m), 5.9
;
(1H, d, J = 3.6 Hz),5.08 (1H, s), 4.65 (1H, d, J = 10.8 Hz), 4.53 (1H, d, J = 10.7 Hz),
4.52 (1H, s), 4.36 (1H, d, J = 3.5 Hz), 3.39–3.33 (1H, m), 2.51 (1H, m), 2.35–2.31
(1H, m), 2.17–2.10 (2H, m), 1.87–1.70 (3H, m), 1.67 (3H, s), 1.59 (3H, s), 1.53–
1.41 (1H, m), 1.37 (3H, s), 1.32–1.26 (1H, m); 13C NMR (75 MHz, CDCl3) d 209.4
(CO), 138.4 (C), 135.0 (C), 128.4 (CH), 128.3 (CH), 127.6 (2CH), 127.5 (CH),
122.9 (CH), 113.9 (C), 105.5 (OCHO), 86.8 (OCH), 84.5 (C), 83.5 (OCH), 66.6
(OCH2), 41.6 (CH), 35.3 (CH), 30.1 (CH2), 27.9 (CH3), 27.1 (CH3), 27.0 (CH3), 26.4
(CH2), 23.9 (CH2), 22.1 (CH2); HRMS (ESI) calcd for C24H30O5Na (M+Na)+,
Acknowledgments
S.G. thanks the Department of Science and Technology, Govern-
ment of India for the financial support through Grant No. SR/S1/
OC-19/2011. M.F.H. and K.M. thank CSIR, New Delhi for Research
Fellowships. Financial support from DST for National Single Crystal
X-ray Diffractometer facility at the Department of Inorganic Chem-
istry is gratefully acknowledged.
421.1991; found, 421.1992. Compound 22a. Mp 197–198 °C; ½a D26
ꢀ15.7 (c
ꢁ
0.59, CHCl3); IR m ;
max (liquid film) 1697 cmꢀ1 1H NMR (300 MHz, CDCl3) d 7.60
(1H, d, J = 7.5 Hz), 7.41–7.24 (7H, m), 7.17 (1H, d, J = 7.5 Hz), 5.98 (1H, d,
J = 3.8 Hz), 4.84 (1H, br s), 4.76 (1H, d, J = 10.9 Hz), 4.67 (1H, d, J = 10.9 Hz), 4.57
(1H, d, J = 3.84 Hz), 3.16–3.08 (1H, m), 2.92–2.83 (1H, m), 2.33–2.18 (2H, m),
1.63 (3H, s), 1.39 (3H, s); 13C NMR (75 MHz, CDCl3) d 201.1 (CO), 140.5 (C),
138.4 (C), 136.8 (C), 131.6 (CH), 129.6 (CH), 129.4 (CH), 128.3 (2CH), 127.6
(2CH), 127.3 (CH), 126.8 (CH), 113.7 (C), 106.2 (OCHO), 88.3 (OCH), 85.7 (C),
83.8 (OCH), 67.1 (CH2), 32.7 (CH2), 29.0 (CH2), 27.1 (CH3), 26.9 (CH3); HRMS
(ESI) calcd for C23H24O5Na (M+Na)+, 403.1521; found, 403.1524. Compound
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.09.104.
22b. ½ ꢁ ;
a 2D6 56.0 (c 3.5, CHCl3); IR mmax (liquid film) 1680 cmꢀ1 1H NMR
(300 MHz, CDCl3) d 7.48 (1H, d, J= 7.5 Hz), 7.40–7.23 (6H, m), 7.09 (1H, d,
J = 7.5 Hz), 5.83 (1H, d, J = 3.6 Hz),4.78 (1H, d, J = 10.2 Hz), 4.76 (1H, s), 4.69 (1H,
d, J = 10.2 Hz), 4.39 (1H, d, J = 3.6 Hz), 3.10 (1H, dd, J = 15.6, 10.5 Hz), 2.61 (1H,
dd, J = 15.8, 8.8 Hz), 2.26 (1H, dd, J = 14.8, 8.8 Hz), 1.85 (1H, dd, J = 14.2,
11.2 Hz), 1.61 (3H, s), 1.33 (3H, s), 0.27 (9H, s); 13C NMR (75 MHz, CDCl3) d
206.5 (CO), 144.5 (C), 140.2 (C),138.4 (C), 136.8 (C), 133.5 (CH), 129.5 (CH),
129.4 (CH), 128. (CH), 128.4 (CH), 127.5 (3CH), 113.6 (C), 105.6 (OCH), 86.3 (C),
85.9 (OCH), 83.1 (OCH), 67.0 (OCH2), 30.4 (CH2), 28.7 (CH2), 26.9 (2CH3), 0.47
(3CH3); HRMS (ESI) calcd for C26H32O5SiNa (M+Na)+, 475.1917; found,
References and notes
1. For a review on Schisandra nortritepinoids see: (a) Xiao, W. L.; Li, R. T.; Huang,
S. X.; Pu, J. X.; Sun, H. D. Nat. Prod. Rep. 2008, 25, 871–891; For some recently
isolated compounds see: (b) Cheng, Y.-B.; Liao, T.-C.; Lo, I.-W.; Chen, Y.-C.; Kuo,
Y.-C.; Chen, S.-Y.; Chien, C.-T.; Shen, Y.-C. Org. Lett. 2010, 12, 1016–1019; (c)
Meng, F.-Y.; Sun, J.-X.; Li, X.; Yu, H.-Y.; Li, S.-M.; Ruan, H.-L. Org. Lett. 2011, 13,
1502–1505; (d) Shi, Y.-M.; Li, X.-Y.; Li, X.-N.; Luo, X.; Xue, Y.-B.; Liang, C.-Q.;
Zou, J.; kong, L.-M.; Li, Y.; Pu, J.-X.; Xiao, W.-L.; Sun, H.-D. Org. Lett. 2011, 13,
3848–3851.
2. Li, R. T.; Han, Q. B.; Zheng, Y. T.; Wang, R. R.; Yang, L. M.; Lu, Y.; Sang, S. Q.;
Zheng, Q. T.; Zhao, Q. S.; Sun, H. D. Chem. Commun. 2005, 2936–2938.
3. Li, R. T.; Li, S. H.; Zhao, Q. S.; Lin, Z. W.; Sun, H. D.; Lu, Y.; Wang, C.; Zheng, Q. T.
Tetrahedron Lett. 2003, 44, 3531–3534.
4. (a) Tang, Y.; Zhang, Y.; Dai, M.; Luo, T.; Deng, L.; Chen, J.; Yang, Z. Org. Lett. 2005,
7, 885–888; (b) Zhang, Y. D.; Tang, Y. F.; Luo, T. P.; Shen, J.; Chen, J. H.; Yang, Z.
Org. Lett. 2006, 8, 107–110; (c) Krishnan, K. S.; Smitha, M.; Suresh, E.;
Radhakrishnan, K. V. Tetrahedron 2006, 62, 12345–12350; (d) Fischer, D.;
Theodorakis, E. A. Eur. J. Org. Chem. 2007, 4193–4196; (e) Zhang, Y. D.; Ren, W.
W.; Lan, Y.; Xiao, Q.; Wang, K.; Xu, J.; Chen, J. H.; Yang, Z. Org. Lett. 2008, 10,
665–668; (f) Wang, Q.; Chen, C. Org. Lett. 2008, 10, 1223–1226; (g) Paquette, L.
A.; Lai, K. W. Org. Lett. 2008, 10, 2111–2113; (h) Lai, K. W.; Paquette, L. A. Org.
Lett. 2008, 10, 2115–2118; (i) Paquette, L. A.; Lai, K. W. Org. Lett. 2008, 10,
3781–3784; (j) Mehta, G.; Bhat, B. A. Tetrahedron Lett. 2009, 50, 2474–2477; (k)
Mehta, G.; Bhat, B. A.; Kumara, T. H. S. Tetrahedron Lett. 2009, 50, 6597–6600;
(l) Mehta, G.; Bhat, B. A.; Kumara, T. H. S. Tetrahedron Lett. 2010, 51, 4069–
4072; (m) Matcha, K.; Maity, S.; Malik, C. K.; Ghosh, S. Tetrahedron Lett. 2010,
51, 2754–2757; (n) Maity, S.; Matcha, K.; Ghosh, S. J. Org. Chem. 2010, 75, 4192–
4200; (o) Mehta, G.; Yaragorla, S. Tetrahedron Lett. 2011, 52, 4485–4489.
5. Cordonnier, M.-C. A.; Kan, S. B. J.; Anderson, E. A. Chem. Commun. 2008, 5818–
5820.
475.1917. Compound 25. ½a D27
ꢁ
68.7 (c 1.8, CHCl3); 1H NMR (300 MHz, CDCl3)
d 6.14 (1H, d, J = 6.3 Hz), 5.74 (1H, d, J = 3.5 Hz), 5.70 (1H, dt, J = 6.3, 2.3 Hz),
4.71 (2H, t, J = 2.1 Hz), 4.24 (1H, d, J = 3.5 Hz), 4.14 (1H, d, J = 6.6 Hz), 3.98–3.89
(3H, m), 1.60 (3H, s), 1.40 (3H, s), 1.33 (3H, s), 1.28 (3H, s); 13C NMR (75 MHz,
CDCl3) d 130.8 (CH), 124.9 (CH), 113.3 (C), 109.3 (C), 103.2 (CH), 95.9 (C), 83.2
(CH), 79.3 (CH), 75.9 (CH2), 74.4 (CH2), 67.0 (CH2), 27.0 (CH3), 26.7 (CH3), 26.4
(CH3), 25.6 (CH3); HRMS (ESI) calcd for C15H22O6Na (M+Na)+, 321.1314; found,
321.1314. Compound 9.
½ ꢁ 65.1 (c 0.53, CHCl3); IR (liquid film) mmax
a 2D6
1784 cmꢀ1 1H NMR (500 MHz, CDCl3) d 5.97 (1H, d, J = 3.5 Hz), 4.51 (1H, d,
;
J = 6.5 Hz), 4.49 (1H, d, J = 3.6 Hz), 4.46 (1H, s), 2.75 (2H, m), 1.61 (3H, s), 1.37
(3H, s), 1.31 (3H, s), 1.26 (3H, s); 13C NMR (125 MHz, CDCl3) d 174.0 (CO), 114.3
(C), 105.3 (CH), 98.9 (C), 87.0 (CH), 86.0 (CH), 79.9 (CH), 78.5 (CH), 36.9 (CH2),
27.2 (2CH3), 27.0 (CH3), 23.2 (CH3); HRMS (ESI) calcd for C13H18O6Na (M+Na)+,
293.1001; found, 293.1005.
11. Crystal
data:
Compound
18b.
Colorless
block
shaped
crystal
(0.32 ꢂ 0.27 ꢂ 0.14 mm) of 18b was analyzed. Empirical formula C24H30O5,
Mr = 398.48, orthorhombic space group P212121 (No. 19), a = 5.6717(7),
b = 12.6924(16),
calcd = 1.270 g cmꢀ3
mmꢀ1 = 0.088, 2hmax = 50.0°, 19771 total reflections, 3672 unique reflections,
3428 observed (I > 2 (I)) 265 parameters; Rint = 0.0332, R1 = 0.0317;
wR2 = 0.0790 (I > 2 (I)), R1 = 0.0346; wR2 = 0.0813 (all data) with GOF = 1.025.
c = 28.958(4) Å,
V = 2084.6(4) Å3,
T = 100 K,
Z = 4.
q
.
F(000) = 856, k(Mo-K
a
) = 0.71073 Å, Mo
l
Ka/
r
r
Compound 28. C13H19BrO5, M = 335.19, orthorhombic, space group P212121,
a = 5.6969(5), b = 10.2560(9), c = 24.299(2) Å, V = 1419.7(2) Å3, T = 298 K, Z = 4.
6. For reviews on intramolecular Diels–Alder reaction see: (a) Oppolzer, W.
Angew. Chem., Int. Ed. 1977, 16, 10–23; (b) Brieger, G.; Bennett, J. N. Chem. Rev.
1980, 80, 63–97; (c) Fallis, A. G. Can. J. Chem. 1984, 62, 183–234; (d) Sing, V.;
Iyer, S. R.; Pal, S. Tetrahedron 2005, 61, 9197–9231; (e) Juhl, M.; Tanner, D.
Chem. Soc. Rev. 2009, 38, 2983–2992.
F(000) = 688,
collected, 2345 observed (I > 2
R1 = 0.0254; wR2 = 0.0608 (I > 2 (I)), R1 = 0.0288; wR2 = 0.0622 (all data) with
GOF = 1.014. X-ray single crystal data were collected using MoK
l
= 2.909 mmꢀ1
,
2hmax = 49.98°, 13110 reflections were
r(I)) 176 parameters; Rint = 0.0287,
r
a
7. (a) Wenkert, E.; Naemura, K. Synth. Commun. 1973, 3, 45–48; (b) Tuckett, M.
W.; Watkins, W. J.; Whitby, R. J. Tetrahedron Lett. 1998, 39, 123–126; (c) Li, C.-
C.; Liang, S.; Zhang, X.-H.; Xie, Z.-X.; Chen, J.-H.; Wu, Y.-D.; Yang, Z. Org. Lett.
2005, 7, 3709–3712; (d) Page, P. C. B.; Jennens, D. C.; Farland, H. M. Tetrahedron
Lett. 1997, 38, 6913–6916.
(k = 0.7107 Å) radiation on a SMART APEX II diffractometer equipped with
CCD area detector. Data collection, data reduction, structure solution/
refinement were carried out using the software package of SMART APEX. The
structures were solved by direct method and refined in a routine manner. Non
hydrogen atoms were treated anisotropically. The hydrogen atoms were
geometrically fixed. CCDC (CCDC Nos. 830899 for 18b and 835934 for 28)
contain the supplementary crystallographic data for this paper. These data can
be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or
from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge
CB21EZ, UK; fax: (+44) 1223 336 033; or deposit@ccdc.cam.ac.uk.
8. Harwood, L. M.; Ishikawa, T.; Phillips, H.; Watkin, D. Chem. Commun. 1991,
527–530.
9. Malik, C. K.; Yadav, R. N.; Drew, M. G. B.; Ghosh, S. J. Org. Chem. 2009, 74, 1957–
1963.
10. All new compounds were characterized on the basis of IR, 1H, 13C NMR and
HRMS data. Spectral data for selected compounds: Compound 18a. Mp 124–
12. Saito, Y.; Zevaco, T. A.; Agrofolio, L. A. Tetrahedron 2002, 58, 9593–9603.
13. For reviews on RCM reactions see: (a) Schuster, M.; Blechert, S. Angew. Chem.,
Int. Ed. 1997, 36, 2036–2056; (b) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54,
4413–4450; (c) Fürstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012–3043; (d)
Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104, 2199–2238; (e) Nicolaou, K. C.;
Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed. 2005, 44, 4490–4527; (f) Ghosh,
S.; Ghosh, S.; Sarkar, N. J. Chem. Sci. 2006, 118, 223–235; (g) Chattopadhyay, S.
K.; Karmakar, S.; Biswas, T.; Majumdar, K. C.; Rahaman, H.; Roy, B. Tetrahedron
2007, 63, 3919–3952.
125 °C; ½a 2D4
ꢁ
ꢀ48.41 (c 1.5, CHCl3); IR mmax (liquid film) 1711 cmꢀ1
;
1H NMR
(300 MHz, CDCl3) d 7.36–7.18 (5H, m), 5.88 (1H, d, J = 3.5 Hz), 5.71 (1H, ddd,
J = 10.0, 6.3, 3.8 Hz), 5.30 (1H, dd, J = 10.0, 2.2 Hz), 4.58 (1H, d, J = 10.8 Hz), 4.48
(1H, d, J = 12.2 Hz), 4.46 (1H, br s), 4.29 (1H, d, J = 3.5 Hz), 3.42–3.31 (1H, m),
2.47–2.33 (2H, m), 2.08 (1H, dd, J = 12.3, 8.0 Hz), 1.91–1.85 (1H, m), 1.73–1.52
(3H, m), 1.51(3H, s), 1.47–1.34 (2H, m), 1.30 (3H, s); 13C NMR (75 MHz, CDCl3) d
209.4 (CO), 138.4 (C), 128.6 (CH), 128.3 (2CH), 127.8 (CH), 127.6 (CH), 127.5
(2CH), 113.9 (C), 105.4 (OCHO), 86.6 (OCH), 84.2 (C), 83.5 (OCH), 66.6 (OCH2),
41.9 (CH), 34.8 (CH), 30.1 (CH2), 27.1 (CH3), 29.0 (CH3), 26.2 (CH2), 23.0 (CH2),