Stereoselective total synthesis of (-)-(6 R,11 R,14 R)-colletallol via RCM protocol

Article abstract of DOI:10.1055/s-0029-1218270

The total synthesis of (-)-colletallol via a ring-closing metathesis protocol is reported. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218270

2924
LETTER
Stereoselective Total Synthesis of (–)-(6R,11R,14R)-Colletallol via RCM
Protocol
S
ynthesisof (–
a
)-(6
R
,11
R
,
l
14
R
)-C
a
olletallol kodety Radha Krishna,* D. Venkata Ramana, B. Karunakar Reddy
D-211, Discovery Laboratory, Organic Chemistry Division-III, Indian Institute of Chemical Technology, Hyderabad 500607, India
Fax +91(40)27193158; E-mail: prkgenius@iict.res.in
Received 21 August 2009
kinetic resolution8/epoxide ring-opening reaction with al-
Abstract: The total synthesis of (–)-colletallol via a ring-closing
lyl magnesium chloride and protection of the ensuing hy-
metathesis protocol is reported.
droxyl group as its silyl ether afforded 6. The terminal
Key words: (–)-colletallol, ring-closing metathesis (RCM), Grubbs
olefin was used in two ways, firstly Sharpless asymmetric
II catalyst, Jacobsen’s hydrolytic kinetic resolution (HKR)
dihydroxylation (AD-mix-b, t-BuOH–H2O (1:1), 48 h)
furnished diol 7 (84%) albeit in 63% de. Further purifica-
tion of 7 led to diminished yields. Consequently, an alter-
Colletallol (1), a diolide belonging to a series of structur-
nate Jacobsen’s hydrolytic kinetic resolution (HKR)
based strategy was adopted and the loss in chemical yield
ally related macrolides, was isolated from plant pathogen
Colletrichum capsici.1 This diolide and its congeners at-
was circumvented by a two-step recycling of the resoluted
tracted the attention of many synthetic organic chemists
worldwide since isolation, but only two syntheses of 1
were reported so far, out of which one was an enantio-
diol 7a into the requisite epoxide 8.9 Thus both enhanced
chemical and optical yields were met through this strate-
gy. Epoxide 8 obtained by both methods was found to
selective total synthesis by Zwanenburg et al.2 using ep-
have comparable spectral data. Later, ring-opening
oxy diazomethyl ketone as the starting material and its
photo-induced rearrangement to 4-hydroxy-2-alkenoate
reaction10 (Me3S+I–, THF, –20 °C to r.t., 3 h) of epoxide 8
gave allylic alcohol 9 (85%) which was protected as its
MOM ether 10 under conventional conditions. TBS
deprotection (TBAF, THF, r.t., 2 h) in 10 furnished the
as the useful intermediate en route and the other one being
a racemic synthesis way back in 1985.3 Subsequently, a
14-epimer was synthesized by Floćh et al.4 using two con-
corresponding alcohol 5 (85%) as the suitable intermedi-
secutive Wittig olefination reactions as an alternative
ate for the next reaction.
methodology to classical macrolactonization strategy. As
a part of our ongoing program on the metathesis-based
O
synthesis of natural products,5 herein we describe a stere-
O
O
O
oselective total synthesis of natural (–)-colletallol (1) via
Grubbs catalyst assisted ring-closing metathesis protocol
of the corresponding diester derivative 2 (Scheme 1).
2
6
O
O
O
11
14
O
The retrosynthetic analysis envisioned for 1 is depicted in
Scheme 1, using a ring-closing metathesis (RCM) of the
corresponding diester derivative 2 followed by the depro-
tection of the MOM protecting group. Compound 2 in turn
could be synthesized from 3 on PMB deprotection and
acryloylation. Compound 3 should be accessible through
the esterification of acid 4 with alcohol 5 that were inde-
pendently synthesized from the commercially available
propylene oxide as starting material.
OH
1
OMOM
2
O
OPMB
OH
OPMB
O
O
+
OH
OMOM
3
4
5
OMOM
Thus, the synthesis began in the direction of accessing
both the acid 4 and the alcohol 5 components indepen-
dently. Firstly, acid 4 was accessed based on the literature
procedure6 wherein the synthesis of its enantiomer was re-
ported.
O
Subsequently, alcohol 5 was also prepared from propy-
lene oxide (Scheme 2) using a literature-inspired route.7
Accordingly, propylene oxide upon Jacobsen’s hydrolytic
propylene oxide
Scheme 1 Retrosynthetic analysis
SYNLETT 2009, No. 18, pp 2924–2926
x
x
.x
x
.2
0
0
9
Advanced online publication: 02.10.2009
DOI: 10.1055/s-0029-1218270; Art ID: G27209ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of (–)-(6R,11R,14R)-Colletallol
2925
the a,b-unsaturated esters marked the formation of the
product. The HRMS spectrum displayed the m/z [M +
Na]+ 335.1475, calculated 335.1470 for the molecular for-
mula C16H24O6Na. Later, deprotection of MOM ether in
11 under Hannessian conditions12 resulted in the natural
product 1 (95%). The physical and spectroscopic data of
synthetic 1 is consistent with the reported values.1,2,13
O
OTBS
ref. 7
propylene
oxide
6
route B
route A
a
a'
OTBS
OTBS
OH
OH
7a
7
O
OPMB
OH
O
+
OH
b'
b
ref. 9
b
a
O
4
5
+
OTBS
OTBS
c
3
OMOM
8
9
OH
d
O
OH
OTBS
d
c
O
O
e
1
2
OMOM
5
10
O
OMOM
OMOM
11
Scheme 2 Reagents and conditions: route A: (a) AD-mix-b,
t-BuOH–H2O (1:1), 48 h, 84%, 63% de; (b) i) TsCl, Et3N, CH2Cl2,
r.t.; ii) K2CO3, MeoH, r.t., 1 h, 72% (over two steps); route B: (a¢) (i)
MCPBA, CHCl3, 0 °C to r.t., 2 h, 90%; (ii) (R,R)-(salen)CoIII(OAc),
0.55 equiv H2O, r.t., 18 h,; (b¢) ref. 9; (c) n-BuLi, Me3S+I–, THF,
–20 °C to r.t., 3 h, 85%; (d) MOMCl, DIPEA, DMAP (cat.) CH2Cl2,
0 °C to r.t., 8 h, 98%; (e) TBAF, THF, r.t., 2 h, 85%.
Scheme 3 Reagents and conditions. a) DCC, DMAP, CH2Cl2, r.t.,
80%; b) (i) DDQ, CH2Cl2, 0 °C to r.t., 95%; (ii) acryloyl chloride,
DIPEA, CH2Cl2, 4 h, r.t., 95%; c) Grubbs II (10 mol%), toluene, ref-
lux, 4 h, 80%; d) TMSCl, n-Bu4N+Br–, CH2Cl2, –10 °C to 0 °C, 2 h,
95%.
In summary, synthesis of (–)-colletallol was accom-
plished via the RCM of the highly substituted diester 2
with Grubbs II catalyst in good yields and selectivity. The
key intermediates 4 and 5 were accessed from a common,
inexpensive starting material viz. ( )-propylene oxide
through simple transformations using Jacobsen’s HKR
protocol as the means of introducing chirality.
Having both the intermediates 4 and 5 in hand, the next
task was to couple them as an ester (Scheme 3). Accord-
ingly, esterification (DCC, DMAP, CH2Cl2, r.t.) of 4 and
5 afforded 3 (80%) which was characterized by its spec-
1
tral data. For instance, H NMR spectrum of ester 3 re-
vealed the characteristic signals due to the ester-linked
proton shifting downfield to d = 4.90–4.98 ppm as a mul-
tiplet while the rest of the protons resonated at their ex-
pected chemical shifts. Also, the characteristic olefinic
protons present in conjugation with the a,b-unsaturated
ester revealed the a-proton at d = 5.57–5.67 ppm integrat-
ing for 1 H, while the b-proton appeared at d = 6.85–6.94
ppm. The terminal olefinic protons integrating for 3 H re-
tained their expected chemical shifts. The HRMS was in
good agreement {m/z calcd for C23H34O6Na [M + Na]+:
429.2253; found: 429.2263} with the expected structure.
Next, the PMB group was deblocked under DDQ condi-
tions; the corresponding hydroxyl group was acryloylated
(acryloyl chloride, DIPEA, CH2Cl2, r.t.) to furnish the
crucial intermediate 2 (95%). Diester 2 was then subjected
to ring-closing metathesis reaction (Grubbs II, toluene, re-
flux, 4 h) to afford diolide 11 in good yields albeit as an E/
Z mixture in a 85:15 ratio.11 The required E-isomer was
purified by column chromatography and characterized by
Acknowledgment
Two of the authors (D. V. R. and B. K. R.) thank the CSIR, New
Delhi for the financial support in the form of fellowships.
References and Notes
(1) (a) MacMillan, J.; Pryce, R. J. Tetrahedron Lett. 1968,
5497. (b) MacMillan, J.; Simpson, T. J. J. Chem. Soc.,
Perkin Trans. 1 1973, 1487.
(2) Dommerholt, F. J.; Thijs, L.; Zwanenburg, B. Tetrahedron
Lett. 1991, 32, 1495.
(3) Wakamatsu, T.; Yamada, S.; Ozaki, Y.; Ban, Y.
Tetrahedron Lett. 1985, 26, 1989.
(4) Amigoni, S. J.; Toupet, L. J.; Le Floćh, Y. J. J. Org. Chem.
1997, 62, 6374.
(5) (a) Radha Krishna, P.; Narsingam, M. Tetrahedron Lett.
2004, 45, 4773. (b) Radha Krishna, P.; Srinivas, P. R.
Tetrahedron 2007, 63, 3995. (c) Radha Krishna, P.;
Krishnarao, L. Synlett 2007, 1742. (d) Radha Krishna, P.;
Srinivas, R. Tetrahedron: Asymmetry 2007, 18, 2197.
(e) Radha Krishna, P.; Dayaker, G. Tetrahedron Lett. 2007,
48, 7279. (f) Radha Krishna, P.; Narsingam, M.
Tetrahedron Lett. 2007, 48, 8721. (g) Radha Krishna, P.;
Srinivas, R. Tetrahedron: Asymmetry 2008, 19, 1160.
(h) Radha Krishna, P.; Srinivas, P. R. Synlett 2009, 209.
(6) Sharma, G. V. M.; Babu, K. V. Tetrahedron: Aymmetry
2007, 18, 2175.
1
its spectral data. For instance, the H NMR spectrum of
(E)-11 displayed the absence of chemical shifts due to ter-
minal olefinic protons, the emergence of two nonequiva-
lent a-protons: one at d = 5.79 ppm as a doublet (J = 15.1
Hz) and the other at d = 5.87 ppm as a double doublet
(J = 16.1, 1.4 Hz); while one of the two b-protons appear-
ing at d = 6.68–6.75 ppm as a multiplet and the other one
at d = 6.81 ppm as a double doublet (J = 15.6, 4.3 Hz) of
Synlett 2009, No. 18, 2924–2926 © Thieme Stuttgart · New York

2926
P. Radha Krishna et al.
LETTER
(7) Liu, J.; Zhang, L.; He, L.; Ma, B.; Pan, X.; She, X.
Tetrahedron: Aymmetry 2008, 19, 906.
(8) (a) Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen,
E. N. Science 1997, 277, 936. (b) Schaus, S. E.; Brandes,
B. D.; Larrow, J. F.; Tokunaga, M.; Hansen, K. B.; Gould,
A. E.; Furrow, M. E.; Jacobsen, E. N. J. Am. Chem. Soc.
2002, 124, 1307.
(9) Radha Krishna, P.; Srinivas, R. Tetrahedron Lett. 2007, 48,
2013.
(10) Alcaraz, L.; Harnett, J. J.; Mioskowski, C.; Martel, J. P.;
Legall, T.; Shin, D.-S.; Falck, J. R. Tetrahedron Lett. 1994,
35, 5449.
(11) (a) Lee, C. W.; Grubbs, R. H. J. Org. Chem. 2001, 66, 7155.
(b) Chatterjee, A. K.; Grubbs, R. H. Angew. Chem. Int. Ed.
2002, 41, 3171. (c) Deiters, A.; Martin, S. Chem. Rev. 2004,
104, 2199.
(12) Hanessian, S.; Delorme, D.; Dufresne, Y. Tetrahedron Lett.
1984, 25, 2515.
73.1, 70.6, 70.1, 55.3, 55.2, 39.2, 31.7, 31.1, 19.9, 19.6.
HRMS: m/z calcd for C23H34O6Na [M + Na]+: 429.2253;
found: 429.2263.
Compound 2: colorless liquid; [a]D25 +155.9 (c 0.5, CHCl3).
1H NMR (500 MHz, CDCl3): d = 6.92–6.84 (m, 1 H), 6.39
(d, J = 17.0 Hz, 1 H), 6.09 (d, J = 17.0, 10.2 Hz, 1 H), 5.90–
5.80 (m, 2 H), 5.70–5.61 (m, 1 H), 5.24–5.17 (m, 2 H), 5.12–
5.06 (m, 1 H), 4.99–4.93 (m, 1 H), 4.68 (d, J = 6.8 Hz, 1 H),
4.52 (d, J = 6.8 Hz, 1 H), 4.00–3.94 (m, 1 H), 3.36 (s, 3 H),
2.55–2.44 (m, 2 H), 1.69–1.55 (m, 4 H), 1.28 (d, J = 6.3 Hz,
3 H), 1.24 (d, J = 6.3 Hz, 3 H). 13C NMR (75 MHz, CDCl3):
d = 165.7, 165.5, 143.2, 137.9, 130.7, 128.5, 124.5, 117.5,
93.7, 77.0, 71.4, 69.3, 55.4, 38.3, 31.7, 31.2, 20.3, 19.6.
HRMS: m/z calcd for C18H28O6Na [M + Na]+: 363.1783;
found: 363.1773.
Compound 11: brown colored liquid; [a]D25 +123.8 (c 0.06,
CHCl3). 1H NMR (500 MHz, CDCl3): d = 6.75–6.71 (dd,
J = 16.1, 5.4 Hz, 1 H), 6.70–6.63 (m, 1 H), 5.82 (d, J = 16.1
Hz, 1 H), 5.71 (d, J = 15.6 Hz, 1 H), 5.28–5.22 (m, 1 H),
5.16–5.11 (m, 1 H), 4.56 (s, 2 H), 4.44–4.40 (m, 1 H), 3.32
(s, 3 H), 2.54–2.48 (m, 2 H), 2.05–1.97 (m, 2 H), 1.81–1.74
(m, 1 H), 1.67–1.61 (m, 1 H), 1.45 (d, J = 6.3 Hz, 3 H), 1.17
(d, J = 6.8 Hz, 3 H). 13C NMR (75 MHz, CDCl3): d = 168.3,
165.5, 149.2, 143.6, 126.2, 122.1, 94.5, 74.0, 69.1, 68.3,
55.4, 40.6, 27.7, 26.5, 20.7, 17.5. HRMS: m/z calcd for
C16H24O6Na [M + Na]+: 335.1470; found: 335.1475.
Compound 1: colorless syrup; [a]D25 –85.5 (c 0.1 CHCl3). 1H
NMR (500 MHz, CDCl3): d = 6.81 (dd, J = 15.6, 4.3 Hz, 1
H), 6.75–6.68 (m, 1 H), 5.87 (dd, J = 16.1, 1.4 Hz, 1 H), 5.79
(d, J = 15.1 Hz, 1 H), 5.26–5.16 (m, 2 H), 4.60 (s, 1 H), 2.53
(m, 1 H), 2.38–2.24 (m, 2 H), 2.17 (d, J = 2.9 Hz, 1 H), 1.79–
1.67 (m, 2 H), 1.36 (d, J = 6.3 Hz, 3 H), 1.19 (d, J = 6.8 Hz,
3 H). 13C NMR (75 MHz, CDCl3): d = 170.0, 165.6, 150.9,
143.5, 126.2, 121.3, 70.4, 69.1, 68.4, 40.6, 32.2, 29.1, 20.6,
17.4. HRMS: m/z calcd for C14H20O5Na [M + Na]+:
291.1208; found: 291.1210.
(13) Spectral Data for Selected Compounds
Compound 5: colorless liquid; [a]D25 +243.0 (c 0.15,
CHCl3). 1H NMR (500 MHz, CDCl3): d = 5.73–5.58 (m, 1
H), 5.24–5.13 (m, 2 H), 4.64 (d, J = 6.8 Hz, 1 H), 4.48 (d,
J = 6.8 Hz, 1 H), 4.04–3.96 (m, 1 H), 3.83–3.73 (m, 1 H),
3.35 (s, 3 H), 1.68–1.39 (m, 4 H), 1.17 (d, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 138.0, 117.2, 93.7, 77.4,
67.8, 55.4, 34.7, 31.7, 23.4. MS (EI): m/z = 113 [M –
OMOM].
Compound 3: colorless liquid; [a]D25 +90.0 (c 0.25, CHCl3).
1H NMR (500 MHz, CDCl3): d = 7.19 (d, J = 8.3 Hz, 2 H),
6.94–6.85 (m, 1 H), 6.80 (d, J = 8.3 Hz, 2 H), 5.80 (d,
J = 15.6 Hz, 1 H), 5.67–5.57 (m, 1 H), 5.23–5.13 (m, 2 H),
4.98–4.90 (m, 1 H), 4.67–4.61 (m, 1 H), 4.49–4.24 (m, 2 H),
4.37 (d, J = 11.2 Hz, 1 H), 3.98–3.90 (m, 1 H), 3.78 (s, 3 H),
3.63–3.56 (m, 1 H), 3.3 (s, 3 H), 2.49–2.4 (m, 1 H), 2.37–
2.27 (m, 1 H), 1.67–1.54 (m, 4 H), 1.24 (d, J = 5.8 Hz, 3 H),
1.18 (d, J = 6.3 Hz, 3 H). 13C NMR (75 MHz, CDCl3): d =
165.9, 145.1, 137.9, 129.0, 123.5, 117.4, 113.7, 93.6, 77.0,
Synlett 2009, No. 18, 2924–2926 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.