Total syntheses of (±)-taiwaniaquinol D and (±)-taiwaniaquinone D via a key Lewis acid-catalyzed Nazarov type cyclization

Article abstract of DOI:10.1016/j.tetlet.2016.06.030

Total syntheses of structurally intriguing taiwaniaquinoids viz (±)-taiwaniaquinol D (1e) and (±)-taiwaniaquinone D (1h) have been disclosed via a key Lewis acid catalyzed Nazarov type cyclization of arylvinylcarbinols.

Full text of DOI:10.1016/j.tetlet.2016.06.030

Accepted Manuscript
Total Syntheses of ( )-Taiwaniaquinol D and ( )-Taiwaniaquinone D via a Key
Lewis Acid-Catalyzed Nazarov Type Cyclization
Badrinath N. Kakde, Amarchand Parida, Pooja Kumari, Alakesh Bisai
PII:
S0040-4039(16)30699-2
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.06.030
TETL 47757
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
31 March 2016
7 June 2016
8 June 2016
Please cite this article as: Kakde, B.N., Parida, A., Kumari, P., Bisai, A., Total Syntheses of ( )-Taiwaniaquinol D
and ( )-Taiwaniaquinone D via a Key Lewis Acid-Catalyzed Nazarov Type Cyclization, Tetrahedron Letters
(2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.06.030
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Total Syntheses of (±)-Taiwaniaquinol D and
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Badrinath N. Kakde, Amarchand Parida, Pooja Kumari,§ and Alakesh Bisai*

1
Tetrahedron Letters
Total Syntheses of (±)-Taiwaniaquinol D and (±)-Taiwaniaquinone D via a Key Lewis
Acid-Catalyzed Nazarov Type Cyclization
Badrinath N. Kakde, Amarchand Parida, Pooja Kumari, § and Alakesh Bisai*
Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal Bypass Road, Bhauri, Bhopal - 462 066, Madhya Pradesh, India
Contact: +91-755-6692374, Fax: +91-755-6692392. Address for correspondence: alakesh@iiserb.ac.in
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Total syntheses of structurally intriguing taiwaniaquinoids viz (±)-taiwaniaquinol D (1e)
and (±)-taiwaniaquinone D (1h) has been disclosed via a key Lewis acid catalyzed Nazarov
type cyclization of arylvinylcarbinols.
2012 Elsevier Ltd. All rights reserved.
Available online
Keywords:
abeo-Abietane
Total Synthesis
Nazarov Cyclization
Quaternary Stereocenter
Taiwaniaquinoids
The taiwaniaquinoids (1a-k, Figure 1)1 are a family of unusual
diterpenoids possessing a [6,5,6]-abeo-abietane skeleton sharing an
all-carbon quaternary stereocenter at the pseudobenzylic position.
Most of these diterpenoids are isolated since 1995 from Taiwania
cryptomerioides Hayata (Taxodiaceae) of central mountains of
Taiwan independently by Cheng2 and Kuo,3 Salvia dichroantha
Stapf (Lamiaceae) of a Turkish flowering sage by Kawazoe,4a Thuja
standishii (Cupressaceae) of a Japanese conifer by Tanaka.4b
Preliminary studies revealed that few members of taiwaniaquinoids
are found to exhibit potent cytotoxic activity against KB epidermoid
carcinoma cancer cells.3b Taiwaniaquinone
D (1h) possesses
antitumoral cytotoxic activity and one of the members such as
standishinal (1c) has shown aromatase inhibitory activity and,
therefore, this class of compounds may be promising candidates for
the treatment of breast cancer.5 On the other hand, few congeners of
this family are also found to be the core structure of complex
taiwaniadducts (Figure 1)6a,b such as taiwaniadduct B (2a)6c having
vicinal all-carbon quaternary sterecenters and taiwaniadduct F (2b)
sharing complex 1,3-bis all-carbon quaternary stereocenters, when
coupled with naturally occurring trans-ozic acid (3).
Because of their diverse biological profiles and uncommon
structural features, taiwaniaquinoids (1a-k) have gained extensive
attention from the synthetic community all over world leading to
numerous efficient synthetic approaches. This includes, Pd(0)-
catalyzed intramolecular reductive cyclization by Banerjee,7
a
domino intramolecular acylation carbonyltert-alkylation reaction
by Fillion,8 intramolecular Heck cyclization by Node,9a Nazarov
cyclization by Trauner,9b a tandem acylation-Nazarov cyclization
reaction by Chiu,9c acid promoted Friedel−Crafts acylation/alkylation
approach independently by She10a and Cheng,10b intramolecular
cyclization of aryldienes independently by Balme,10c Alvarez-
Manzaneda10d and Majetich,10e ring contraction reactions from
abietane diterpenoids by Li,10f including our Nazarov type
cyclization to set all-carbon quaternary center (Scheme 1).11
Figure 1: abeo-Abietane diterpenoids (1a-k) and related terpenoids sharing
all-carbon quaternary stereocenters.
The
asymmetric
syntheses
include,
enantioselective
decarboxylative allylation by Stoltz,12 enantiospecific approach via a

2
Tetrahedron Letters
thermal
6π-electrocyclization
by
Alvarez-Manzaneda,13
For this purpose, 1,2,4-trimethoxybenzene (10a) and methylether
of sesamol (11a) was reacted with acetone in presence of n-BuLi and
TMEDA at 0 ˚C to afford corresponding benzyl alcohol which on
enantioselective Heck reaction by Node,14a-b ring contraction of
abietane diterpenoids by Gademann,14c a semisynthetic approach
involving cleavage of the C7−C8 double bond of abietane diterpenes
by Alvarez-Manzaneda,14d-e an iridium catalyzed borylation and a
palladium-catalyzed asymmetric -arylation by Hartwig,15 a recent
Pd(0)-catalyzed enantioselective conjugate addition of arylboronic
acid by Stoltz.16 Recently our group has also reported total synthesis
of taiwaniaquinoids with various oxidation pattern of A-ring, such as
(±)-taiwaniaquinol F (1b), using Nazarov type cyclization of
arylvinylcarbinol (±)-6a (Scheme 1).17 Utilizing aforementioned
strategy, we have also accomplished total syntheses of (±)-
taiwaniaquinol B (1a), (±)-dichroanone (1f) and (±)-taiwaniaquinone
H (1g).17 Later, we have synthesized a variety of enantioenriched
carbotetracycle of type 9 (Scheme 1) from arylvinylcarbinol 8 via
efficient metal triflate catalyzed Nazarov-type cyclization. This
methodology provides a concise route to the marine sesquiterpene
quinol akaol A (9a).18
further
elimination
in
presence
of
Sn(OTf)2
to
furnishmethylstyrene 10b and 11b in 2 steps. The later was
hydrogenated in presence of Pd-C at 1 atm pressure followed by
reaction with N-bromosuccinimide (NBS) to afford bromoarenes 10c
and 11c over 2 steps (Scheme 2). Arylvinyl carbinols (±)-4b-c were
synthesized from bromoarenes 10c and 11c in 81% and 61% yields,
respectively.
With (±)-4b in hand, we then optimized Lewis acid catalyzed
Nazarov type cyclization of arylvinylcarbinol (±)-4b for efficient
synthesis of carbotricyclic core (±)-5b. Our optimization studies are
shown in Table 1. It was observed that, 10 mol % of Bi(OTf)3
afforded desired product (±)-5b only in 22% yield along with 73%
yield of diene 12b (Table 1). We have also found that, diene
intermediate 12b can be converted into (±)-5b under elevated
temperature.19 This clearly indicates that the reaction goes through
intermediate diene of type 12. Based on this result, we decided to
carry out cyclization of (±)-4b at elevated temperature and the results
are shown in Table 1 (entries 2-8).
Table 1: Optimization of cyclization of arylvinylcarbinol (±) 4b-c.
S.
No.
catalyst
solvent
te
m
p
time
%yielda,b
%yield
diene
of
1.
2.
3.
10 mol% Bi(OTf)3
10 mol% Bi(OTf)3
CH2Cl2
25 ˚C
12 h
5 h
22% (5b)
97% (5b)
95% (5b)
73% (12b)
00% (12b)
00% (12b)
CH2Cl2
CH2Cl2
35 ˚C
35 ˚C
10
mol%
7 h
Sn(OTf)2
4.
5.
10mol% Cu(OTf)2
CH2Cl2
CH2Cl2
35 ˚C
35 ˚C
12 h
12 h
62% (5b)
43% (5b)
31% (12b)
52% (12b)
10
mol%
Zn(OTf)2
6.
7.
8.
9.
10 mol% In(OTf)3
5 mol% Bi(OTf)3
5 mol% Sn(OTf)2
5 mol% Bi(OTf)3
CH2Cl2
CH2Cl2
CH2Cl2
(CH2Cl)
35 ˚C
35 ˚C
35 ˚C
80 ˚C
12 h
7 h
49% (5b)
95% (5b)
91% (5b)
98% (5b)
33% (12b)
00% (12b)
05% (12b)
00% (12b)
10 h
1 h
Scheme 1: Our Approches towards taiwaniaquinoids.
2
We envisioned that, highly oxygenated carbotricyclic core (±)-5b-
c could be potential advanced intermediates for unified total
synthesis of various taiwaniaquinoids viz (±)-taiwaniaquinol D (1e),
(±)-taiwaniaquinones D (1h), A (1i), and F (1j) having an additional
formyl group following synthetic elaborations (Figure 1). These
carbotricyclic cores (±)-5b-c could be obtained from a key Lewis
acid-catalyzed Nazarov type cyclization of arylvinylcarbinol (±)-4b
(Scheme 2). With above hypothesis, we have synthesized arylvinyl
carbinol (±)-4b-c from a reaction of aryllithium (prepared in situ
from bromoarene 10c) with -cyclocitral (Scheme 2).
10.
2 mol% Bi(OTf)3
(CH2Cl)
2
80 ˚C
2 h
96% (5b)
00% (12b)
11.
12.
10 mol% Bi(OTf)3
5 mol% Bi(OTf)3
CH2Cl2
25 ˚C
12 h
1 h
12% (5c)
97% (5c)
86% (12c)
00% (12c)
(CH2Cl)
2
80 ˚C
aall the reactions were performed with 0.3 mmol of (±)-4b-c. isolated yields
after column chromatography.
b
It was observed that, among various metal tiflates Bi(OTf)3, and
Sn(OTf)2 afforded (±)-5b in 95-97% yields (entries 2-3), whereas
Cu(OTf)2, Zn(OTf)2, and In(OTf)3 furnished (±)-5b in 43-62% yields
along with 31-52% yield of 12b as by product. Interestingly, 5 mol%
of Bi(OTf)3 and Sn(OTf)2 afforded (±)-5b in 95% and 91% yields
(entries 7-8). To our delight, 5 mol% and 2 mol% of Bi(OTf)3
furnished (±)-5b in 98% and 96% yields, respectively, in refluxing
dichloroethane (entries 9-10). Since total syntheses of (±)-
taiwaniaquinol B (1a), (±)-dichroanone (1f) and (±)-taiwaniaquinone
H (1g) have already reported from our group from (±)-5b, this efforts
also culminated formal total syntheses of these taiwaniaquinoids
(Scheme 3). In case of arylvinyl carbinol (±)-4c, we have isolated
aryldiene 12c in 86% yield when the reaction was carried out at
room temperature (entry 11). Interestingly, we could synthesize
carbotricyclic core (±)-5c in 97% yield under our optimized
condition (entry 12).
Scheme 2: Synthesis of arylvinylcarbinol (±)-4b-c.

3
For further synthetic elaboration, carbotricyclic core (±)-5b was
completely hydrogenated in presence of 10% Pd-C under 1 atm
pressure of H2 in MeOH to furnish (±)-13 in 98% yield (Scheme 4).
Later, (±)-13 was reacted with CrO3 in presence of 3,5-
dimethylpyrazole to affect benzylic oxidation to furnish ketone (±)-
14 in 91% yield (Scheme 4), which on subsequent reaction with
methylmagnesium bromide afforded (±)-15 as single diastereomer in
91% yield. The excellent diastereoselectivity observed in
methylmagnesium bromide addition was attributed to the approach
of the nucleophile from the less hindered convex face of substrate
(±)-14 (Scheme 4).20 In fact, the energy minimization (MM2)
calculation of diene (±)-14 (Figure 2) also supports our observed
selectivity.
We then carried out the hydrolysis of intermediate (±)-19 in KOH
in MeOH at room remperature, which simply completed total
synthesis of (±)-taiwaniaquinone D (1h). On the other hand,
reduction of p-quinone functionality was performed with Na2S2O4 to
complete total synthesis of (±)-taiwaniaquinol D (1e) in 88%
yields.24
Scheme 5: Total synthesis of (±)-taiwaniaquinone
taiwaniaquinol D (1e).
D (1h) and (±)-
In conclusion, we have demonstrated Nazarov type
cyclization of arylvinyl carbinols, is a strategic platform for
concise total synthesis of various taiwaniaquinoids. We have
completed total syntheses of (±)-taiwaniaquinol D (1e) and (±)-
taiwaniaquinone D (1h) in 15 steps from commercially available
1,2,4-trimethoxybenzene in overall yield of 13.4% and 14.0%,
respectively.25-26 We believe that (±)-1h could be further elaborated
to the expeditious approach to taiwaniaquinones A (1i) and F (1j),
which in turn could give us the opportunity for synthetic approaches
to complex taiwaniadducts B (2a) and taiwaniadduct F (2b) sharing
all-carbon quaternary centers. Importantly, enantioselective strategy
of our Nazarov type cyclization in the presence of chiral Lewis acid
complex could be an excellent platform for asymmetric total
syntheses of naturally occurring taiwaniaquinoids. Further studies
towards these directions are currently under active investigation in
our laboratory.
Scheme 3: Formal total syntheses of taiwanaquinoids.
.
Next, benzyl alcohol (±)-15 was further treated with BF3 Et2O
leading to the formation of two different regioisomers (±)-16a and
(±)-16b in 2.1:1 ratio in 71% yield (Scheme 4), which on subsequent
allylic oxidation using SeO2 in dioxane and H2O mixture exclusively
afforded (±)-17 in 83% yield.21 The later was oxidized under Swern
oxidation to furnish ,-unsaturated aldehyde (±)-18 in 94% yield
(Scheme 4). Next, compound (±)-1822-23 was treated with BBr3
followed by oxidation using ceric (IV) ammonium nitrate simply
afforded potential p-quinone intermediate (±)-19 required for
taiwaniaquinoids (±)-1h and (±)-1e.
Acknowledgments
A.B. thanks the Board of Research in Nuclear Sciences (BRNS),
Department of Atomic Energy (DAE) and Science and Engineering
Research Board (SERB), Department of Science and Technology
(DST) for research grants. B.N.K., A.P., P.K. thank the Council of
Scientific and Industrial Research (CSIR), New Delhi, for Research
Fellowship (SRF and JRF, respectively). Facilities from Department
of Chemistry, IISER Bhopal is gratefully acknowledged.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http:.....................
§Current Address:
Department of Chemistry, Indian Institute of Science Education and Research
Pune, Pashan Road, MH - 462 066, India.
Scheme 4: Synthesis of common precursor to (±)-taiwaniaquinone D (1h)
and (±)-taiwaniaquinol D (1e).
References and notes:
1. For review on taiwaniaquinoids, see; Majetich, G.; Shimkus, J.
M. J. Nat. Prod. 2010, 73, 284.
2. (a) Lin, W. H.; Fang, J. M.; Cheng, Y. S. Phytochemistry 1995
,
40, 871. (b) Kawazoe, K.; Yamamoto, M.; Takaishi, Y.; Honda, G.;
Fujita, T.; Sezik, E.; Yesilada, E. Phytochemistry 1999, 50, 493.
Figure 2: Energy minimized representation of (±)-14.

4
Tetrahedron Letters
16. (a) Kikushima, K.; Holder, J. C.; Gatti, M.; Stoltz, B. M. J. Am.
Chem. Soc. 2011, 133, 6902. (b) Shockley, S. E.; Holder, J. C.;
Stoltz, B. M. Org. Lett. 2014, 16, 6362.
3. (a) Chang, C. I.; Chien, S. C; Lee, S. M.; Kuo, Y. H. Chem.
Pharm. Bull. 2003, 51, 1420. (b) Chang, C. I.; Chang, J. Y.; Kuo,
C. C.; Pan, W. Y.; Kuo, Y. H. Planta Med. 2005, 71, 72.
17. Kakde, B. N.; Kumari, P.; Bisai, A. J. Org. Chem. 2015, 80,
9889.
4. (a) Kawazoe, K.; Yamamoto, M.; Takaishi, Y.; Honda, G.;
Fujita, T.; Sesik, E.; Yesilada, E. Phytochemistry 1999, 50, 493–
497. (b) Ohtsu, H.; Iwamoto, M.; Ohishi, H.; Matsunaga, S.;
Tanaka, R. Tetrahedron Lett. 1999, 40, 6419.
18. Our approach to the merosesquiterpenoids, see: Kakde, B. N.;
Kumar, N.; Mondal, P. K.; Bisai, A. Org. Lett. 2016, 18, 1752.
5. (a) Katoh, T.; Akagi, T.; Noguchi, C.; Kajimoto, T.; Node, M.;
Tanaka, R.; Nishizawa, M.; Ohtsu, H.; Suzuki, N.; Saito, K. Bioorg.
Med. Chem. 2007, 15, 2736. (b) Minami, T.; Iwamoto, M.; Ohtsu,
H.; Ohishi, H.; Tanaka, R.; Yoshitake, A. Planta Med. 2002, 68,
742. (c) Iwamoto, M.; Ohtsu, H.; Tokuda, H.; Nishino, H.;
Matsunaga, S.; Tanaka, R. Bioorg. Med. Chem. 2001, 9, 1911.
19. We have carried out cyclization of aryldiene 12b (0.3 mmol) in
the presence of 10 mol% Bi(OTf)3 in refluxing dichloromethane (6
mL) to afford carbotricycle (±)-5b in 85% isolated yield (10 h).
20. Energy minimization (MM2) of carbotricyclic ketone (±)-14
was performed using ChemBio 3D Ultra Version 12.0.
6. (a) Lin, W. H.; Fang, J. M.; Cheng, Y. S. Phytochemistry 1996
,
21. 2.1:1 Mixture of (±)-16a and (±)-16b afforded 45% of isolated
allylic oxidation product (±)-17 along with 41% of (±)-16a, when
the reaction was carried out for 8 h in dioxane:H2O (4:1) at 105 ˚C.
However, there were no traces of terminal olefin (±)-16b isolated
from this reaction. This probably indicates that the allylic oxidation
of (±)-16b goes through the isomerization to more substituted
olefin (±)-16a in the presence of insitu generated H2SeO3.
42, 1657. (b) Lin, W. H.; Fang, J. M.; Cheng, Y. S. Phytochemistry
1997, 46, 169. (c) Deng, J.; Zhou, S.; Zhang, W.; Li, J.; Li, R.; Li,
A. J. Am. Chem. Soc. 2014, 136, 8185.
7. (a) Banerjee, M.; Mukhopadhyay, R.; Achari, B.; Banerjee, A.
K. Org. Lett. 2003, 5, 3931. (b) Banerjee, M.; Mukhopadhyay, R.;
Achari, B.; Banerjee, A. K. J. Org. Chem. 2006, 71, 2787.
8. Fillion, E.; Fishlock, D. J. Am. Chem. Soc. 2005, 127, 13144.
9. (a) Planas, L.; Mogi, M.; Takita, H.; Kajimoto, T.; Node, M. J.
Org. Chem. 2006, 71, 2896. (b) Liang, G.; Xu, Y.; Seiple, I. B.;
Trauner, D. J. Am. Chem. Soc. 2006, 128, 11022. (c) Li, S.; Chiu, P.
Tetrahedron Lett. 2008, 49, 1741.
22. Hydrogenation of tetrasubstituted olefinic functionality of
unsaturated aldehyde (±)-18 afforded mixture of spots on thin layer
chromatography (TLC).
,-
10. (a) Tang, S.; Xu, Y.; He, J.; He, Y.; Zheng, J.; Pan, X.; She, X.
Org. Lett. 2008, 10, 1855. (b) Wang, J.; Wang, J.; Li, C.; Meng, Y.;
Wu, J.; Song, C.; Chang, J. J. Org. Chem. 2014, 79, 6354. (c)
Lomberget, T.; Bentz, E.; Bouyssi, D.; Balme, G. Org. Lett. 2003
,
23. Alcohol (±)-20 could be the advanced intermediate for the
synthesis of (±)-taiwaniaquinone A (1i), (±)-taiwaniaquinone F (1j),
and (±)-taiwaniaquinol A (1k) (Figure 1). We envisioned that,
hydrogenation of (±)-17 could efficiently afford (±)-20. However,
in an attempt to hydrogenate tetrasubstituted allylic alcohol (±)-17
using catalytic amount of 10 % Pd-C (W/W) in methanol a room
temperature for 24 h afforded carbotricyclic compound (±)-21 in
5, 2055. (d) Alvarez-Manzaneda, E.; Chahboun, R.; Cabrera, E.;
Alvarez, E.; Alvarez-Manzaneda, R.; Meneses, R.; Es-Samti, H.;
Fern ndez, A. J. Org. Chem. 2009, 74, 3384. (e) Majetich, G.;
Shimkus, J. H. Tetrahedron Lett. 2009, 50, 3311. (f) Deng, J.; Li,
R.; Luo, Y.; Li, J.; Zhou, S.; Li, Y.; Hu, J.; Li, A. Org. Lett. 2013
15, 2022.
,
71% yield, probably via the intermediacy of
16a
-methylstyrene (±)-
11. Kakde, B. N.; De, S.; Dey, D.; Bisai, A. RSC Adv. 2013, 3,
8176.
.
12. McFadden, R. M.; Stoltz, B. M. J. Am. Chem. Soc. 2006, 128,
7738.
13. (a) Alvarez-Manzaneda, E.; Chahboun, R.; Cabrera, E.;
Alvarez, E.; Haidöur, A.; Ramos, J. M.; Alvarez-Manzaneda, R.;
Hmamouchi, M.; Es-Samti, H. Chem. Commun. 2009, 592. (b)
Alvarez-Manzaneda, E.; Chahboun, R.; Cabrera, E.; Alvarez, E.;
Haidöur, A.; Ramos, J. M.; Alvarez-Manzaneda, R.; Charrah, Y.;
Es-Samti, H. Org. Biomol. Chem. 2009, 7, 5146.
14. (a) Node, M.; Ozeki, M.; Planas, L.; Nakano, M.; Takita, H.;
Mori, D.; Tamatani, S.; Kajimoto, T. J. Org. Chem. 2010, 75, 190.
(b) Ozeki, M.; Satake, M.; Toizume, T.; Fukutome, S.; Arimitsu,
K.; Hosoi, S.; Kajimoto, T.; Iwasaki, H.; Kojima, N.; Node, M.;
Yamashita, M. Tetrahedron 2013, 69, 3841. (c) Jana, C. K.;
Scopelliti, R.; Gademann, K. Chem. Eur. J. 2010, 16, 7692. (b)
Thommen, C.; Jana, C. K.; Neuburger, M.; Gademann, K. Org.
Lett. 2013, 15, 1390. (d) Alvarez-Manzaneda, E.; Chahboun, R.;
Alvarez, E.; Tapia, R.; Alvarez-Manzaneda, R. Chem. Commun.
2010, 46, 9244. (e) Tapia, R.; Guardia, J. J.; Alvarez, E.; Haidöur,
A.; Ramos, J. A.; Alvarez-Manzaneda, R.; Chahboun, R.; Alvarez-
Manzaneda, E. J. Org. Chem. 2012, 77, 573.
24. A one-pot direct conversion of (±)-18 to (±)-taiwaniaquinol D
1e) using excess amount of BBr3 solutuon (12.66 equiv), as per
Ozeki's procedure, yielded (±)-1e in only 27% yield along with
(
mixture of compounds.
25. (±)-taiwaniaquinol D ()-1e: To a stirred solution of
compound (±)-19 (60 mg, 0.175 mmol; 1.0 equiv) in acetonitrile
and water (7 mL) was added saturated aqueous solution of Na2S2O4
(2 mL) kept on stirring for 20 min. Upon completion of the reaction
(monitoring by TLC), it was diluted by water (10 mL) and extracted
with EtOAc (25 mL) by using a separatory funnel. The organic
filtrate was dried over anhydrous Na2SO4 and concentrated in a
rotary evaporator under vacuum. The crude was purified by flash
chromatography (4:1 hexanes/EtOAc) to give 53 mg (88% yield) of
15. Liao, X.; Stanley, L. M.; Hartwig, J. F. J. Am. Chem. Soc. 2011
133, 2088.
,
(

)-taiwaniaquinol
D (1e) as red color oil. Rf = 0.4 (5%
EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 10.42 (s, 1H),

5
10.41 (s, 1H), 5.26 (s, 1H), 3.78 (s, 3H), 3.40 (septet, J = 7.1 Hz,
1H), 2.73-2.68 (m, 1H), 2.01-1.93 (m, 1H), 1.90-1.86 (m, 1H),
1.69-1.63 (m, 1H), 1.60 (s, 3H), 1.56 (s, 3H), 1.54 (s, 3H), 1.53-
1.48 (m, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.44 (d, J = 7.1 Hz, 3H); 13C
NMR (125 MHz, CDCl3) δ 192.4, 185.8, 145.2, 144.6, 136.9,
135.9, 135.0, 126.3, 119.3, 62.1, 53.8, 42.5, 38.5, 35.6, 32.3, 29.1,
26.4, 23.4, 20.7, 18.1; IR (film) υmax 3387, 3175, 2951, 2869, 1633,
1454, 1426, 1369, 1335, 1211, 1115, 1059, 1015, 977,945, 899,
736-1; HRMS (ESI) m/z 345.2063 [(M + H)]+; calculated for
[C21H28O4 + H]+: 345.2060.
slowly and the mixture was diluted with dichloromethane (15
mL). The combined organic phase washed with brine and dried
over Na2SO4 and concentrated using rotator evaporator under
vaccum. The crude products were purified by flash chromatography
(20:1 hexanes/EtOAc) to give 39 mg (92% yield) of
()-
taiwaniaquinone D )-1h as a red syrup. Rf = 0.4 (5% EtOAc in
(

hexane); 1H NMR (500 MHz, CDCl3) δ 10.44(s, 1H), 3.20 (septet,
J = 7.1 Hz, 1H), 2.47-2.43 (m, 1H), 1.93 (qt, J = 13.7, 3.7 Hz, 1H),
1.71-1.65 (m, 1H), 1.49 (s, 3H), 1.34 (s, 3H), 1.27 (m, 2H), 1.25 (d,
J = 7.1 Hz, 3H), 1.24 (d, J = 7.1 Hz, 3H), 1.19 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 194.1, 185.2, 177.3, 176.7, 152.2, 147.7,
147.2, 134.5, 123.3, 55.9, 43.4, 38.1, 35.2, 33.7, 25.7, 24.0, 21.3,
19.94, 19.91, 18.3; IR (film) υmax 3359, 2930, 2872, 1698, 1633,
1593, 1531, 1463, 1366, 1316, 1224, 1165, 1104, 969, 924, 790,
737 cm-1; HRMS (ESI) m/z 329.1761 [(M + H)]+; calculated for
[C20H24O4 + H]+: 329.1747.
26.
(±
)-taiwaniaquinone D (
)-1h: Oven dried round-bottom flask
was charged with (

)-19 (45 mg, 0.13 mmol, 1.0 equiv) in MeOH
(3 mL). To this solution was added a solution of 2M KOH solution
in MeOH (3 mL) at room temprature. Reaction mixture was stirred
at room temperature for 24 h. Then 2N HCL (1.5 mL) was added