Protecting-group-free total synthesis of goniothalesdiol A

Article abstract of DOI:10.1055/s-0030-1258016

A concise asymmetric total synthesis of goniothalesdiol A was accomplished using protecting-group-free strategy, in which silyl-Prins cyclization was used as the key step. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1258016

LETTER
2283
Protecting-Group-Free Total Synthesis of Goniothalesdiol A
P
rotecting
u
-Group-Free
n
T
otal Synthe
p
sis of
G
onio
e
thalesdiol
A
ng Li,a Huaiji Zheng,a Yingpeng Su,a Xingang Xie,*a Xuegong She*a,b
a
State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences,
Lanzhou 730000, P. R. of China
b
Fax +86(931)8912582; E-mail: shexg@lzu.edu.cn
Received 7 May 2010
3,6-dihydro-2H-pyran ester 2 via stereoselective dihy-
droxylation. As for the key intermediate 2, we envisioned
that it could be constructed by an intramolecular silyl-
Prins reaction of (Z)-silyl-b-hydroxyenoate 3 which could
be prepared from (R)-2-(chloromethyl)oxirane 4 and tri-
methylsilylacetylene 5.
Abstract: A concise asymmetric total synthesis of goniothalesdiol
A was accomplished using protecting-group-free strategy, in which
silyl-Prins cyclization was used as the key step.
Key words: goniothalesdiol A, protecting-group-free, silyl-Prins
cyclization, dihydroxylation
The concept of protecting-group-free (PGF) synthesis
was not extensively explored until the twenty-first centu-
ry, although a number of protecting-group-free total syn-
theses were reported.1,2 Today, organic chemists invest
great enthusiasm to pursue the ‘ideal syntheses’;3 one area
that offers this prospect is to minimize the use of protect-
ing groups in synthesis. A protection–deprotection event
introduces at least two steps into a sequence, increasing
costs from additional reagents and waste disposal, and
generally leads to a reduced overall yield. This made the
development of PGF synthesis very attractive and urgent
in laboratory and industry.4,5
H
H
H
H
O
OMe
O
2
OMe
O
O
HO
OH
1
goniothalesdiol A
OH
O
O
Cl
TMS
+
OMe
TMS
3
4
5
Scheme 1 Retrosynthetic analysis for goniothalesdiol A
Pyrans are widely found in both natural products and
pharmaceutically active compounds, and may contribute
to a wide range of biological activities. In 2006, goniotha- Synthesis of (Z)-silyl-b-hydroxyenoate 3 was initiated
lesdiol A (Scheme 1, compound 1), a cis-2,6-disubstituted with commercially available (R)-2-(chloromethyl)oxirane
3,4-dihydroxy pyran, was isolated from the stem of a
southern Taiwan tree Goniothalamus amuyon by Wu and
4. After a regioselective ring opening of epoxide 4 with
trimethylsilylalkynyllithium,12 homopropargyl alcohol 6
co-workers.6 There were two independent synthetic ef- was obtained. DIBAL-H reduction13 of 6 gave (Z)-homo-
forts toward goniothalesdiol A reported by Yadav and allyl alcohol 7 which was transformed to (Z)-silyl-b-
Fadnavis.7,8 In the Yadav’s synthesis, goniothalesdiol A hydroxyenoate 3 by lithio orthothioformate alkylation and
was achieved in 11 steps and 35.1% overall yield by using hydrolysis.14,15
Chan alkyne reduction, Sharpless kinetic resolution and
With 3 in hand, the silyl-Prins reaction with benzaldehyde
intramolecular oxy-Michael addition as key steps.7 Fad-
was employed to afford 3,6-dihydro-2H-pyran ester 2 in
navis synthesized goniothalesdiol A in 22% overall yield
the presence of InBr3.13 It is noteworthy that aromatic al-
and ten steps via stereoselective allylation, Grignard reac-
dehydes were commonly recognized as less successful
tion, cross-metathesis and intramolecular oxy-Michael
substrates in the Prins reaction as they gave a mixture of
addition as key steps.8 As part of our ongoing program to-
cis and trans adducts in low yields in most cases.16 To our
delight, utility of InBr3 as the Lewis acid led to cis/trans
wards the syntheses of bioactive pyran- and pyranone-
type natural products,9,10 herein we report a concise and
>9:1 DHP products in a comparable yield. After a highly
protecting-group-free asymmetric total synthesis of go-
stereoselective dihydroxylation reaction,16b,c goniothales-
niothalesdiol A 1, in which silyl-Prins cyclization11 was
diol A 1 was obtained in 92% yield (Scheme 2), whose
used as the key step.
spectral data were in good agreement with those reported
in the literature.7,8,17
Retrosynthetic analysis of 1 is briefly outlined in
Scheme 1, which suggests that it could be obtained from
In summary, a concise asymmetric total synthesis of
goniothalesdiol A 1 was achieved in six steps and 30%
overall yield. The cis-2,6-disubstituted pyran moiety was
effectively constructed via silyl-Prins reaction, while C-3
and C-4 vicinal dihydroxy groups were secured by stereo-
SYNLETT 2010, No. 15, pp 2283–2284
x
x
.x
x
.2
0
1
0
Advanced online publication: 06.08.2010
DOI: 10.1055/s-0030-1258016; Art ID: W07310ST
© Georg Thieme Verlag Stuttgart · New York

2284
J. Li et al.
LETTER
TMS
OH
5, n-BuLi, BF3⋅OEt2
O
DIBAL-H
Cl
Cl
THF, –78 °C, then 4
added dropwise
–60 °C, 2 h, 96%
Et2O, r.t., 30 h , 85%
4
6
OH
SEt
SEt
OH
CuCl2, CuO
CH(SEt)3, n-BuLi
Cl
SEt
MeOH–H2O–CH2Cl2 (10:1:1)
r.t., 1.5 h, 80%
THF–HMPA (5:1)
–70 °C to –45 °C, 70%
TMS
TMS
7
8
H
H
O
OMe
O
OH
O
H
H
PhCHO, InBr3
NMO, OsO4 (cat.)
O
OMe
OMe
CH2Cl2, r.t., 2 h, 72%
THF–H2O (3:1), 0 °C to r.t.
12 h, 92%
HO
O
TMS
OH
3
2
1
goniothalesdiol A
Scheme 2 Protecting-group-free total synthesis of goniothalesdiol A
(10) (a) Zhang, J. Y.; Li, Y.; Wang, W. K.; She, X. G.; Pan, X. F.
J. Org. Chem. 2006, 71, 2918. (b) Xu, Y. F.; Huo, X.; Li, X.
Y.; Zheng, H. J.; She, X. G.; Pan, X. F. Synlett 2008, 1665.
(c) Su, Y. P.; Xu, Y. F.; Han, J. J.; Zheng, J. Y.; Qi, J.; Jiang,
T.; Pan, X. F.; She, X. G. J. Org. Chem. 2009, 74, 2743.
(d) Wang, X. L.; Wang, W. K.; Zheng, H. J.; Su, Y. P.; Jiang,
T.; He, Y. P.; She, X. G. Org. Lett. 2009, 11, 3136.
(e) Zheng, H. J.; Zheng, J. Y.; Yu, B. X.; Chen, Q.; Wang,
X. L.; He, Y. P.; Yang, Z.; She, X. G. J. Am. Chem. Soc.
2010, 132, 1788.
selective dihydroxylation. There was no protecting group
utilized in this route.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
We are grateful for the generous financial support by the MOST
(2010CB833200) and the NSFC (20872054, 20732002).
(11) Semeyn, C.; Blaauw, R. H.; Hiemstra, H.; Speckamp, W. N.
J. Org. Chem. 1997, 62, 3426.
(12) (a) Yamaguchi, M.; Hirao, I. Tetrahedron Lett. 1983, 24,
391. (b) Subburaj, K.; Okamoto, S.; Sato, F. J. Org. Chem.
2002, 67, 1024.
References and Notes
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(17) Goniothalesdiol A (1): powder; [a]D25 –21.0 (c = 0.2,
CHCl3). IR (KBr): 700, 758, 1047, 1078, 1170, 1203, 1438,
1735, 2920, 2952, 3425 cm–1. 1H NMR (400 MHz, CDCl3):
d = 1.77 (td, J = 2.4, 14.0 Hz, 1 H), 1.94 (br s, 1 H), 2.08
(ddd, J = 2.0, 3.0, 14.0 Hz, 1 H), 2.47 (dd, J = 6.0, 15.2 Hz,
1 H), 2.59 (br s, 1 H), 2.63 (dd, J = 7.2, 15.2 Hz, 1 H), 3.53
(d, J = 9.6 Hz, 1 H), 3.66 (s, 3 H), 4.22 (d, J = 3.0 Hz, 1 H),
4.41 (m, 1 H), 4.55 (d, J = 9.6 Hz, 1 H), 7.31–7.41 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 37.1, 40.5, 51.7, 67.1,
68.5, 72.7, 77.8, 127.4, 128.3, 128.6, 139.2, 171.3. HRMS
(ESI): m/z [M + NH4]+ calcd for C14H22NO5: 284.1492;
found: 284.1488.
Synlett 2010, No. 15, 2283–2284 © Thieme Stuttgart · New York

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