Enantioselective synthesis of tarchonanthuslactone via iterative hydrolytic kinetic resolution

Article abstract of DOI:10.1016/j.tetlet.2005.07.056

A short and practical enantioselective synthesis of tarchonanthuslactone has been achieved in high diastereomeric excess using iterative Jacobsen's hydrolytic kinetic resolution and ring closing metathesis as the key steps.

Full text of DOI:10.1016/j.tetlet.2005.07.056

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6571–6573
Enantioselective synthesis of tarchonanthuslactone via
iterative hydrolytic kinetic resolution
Priti Gupta, S. Vasudeva Naidu and Pradeep Kumar*
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411008, India
Received 17 June 2005; revised 4 July 2005; accepted 14 July 2005
Available online 1 August 2005
Abstract—A short and practical enantioselective synthesis of tarchonanthuslactone has been achieved in high diastereomeric excess
using iterative JacobsenÕs hydrolytic kinetic resolution and ring closing metathesis as the key steps.
Ó 2005 Elsevier Ltd. All rights reserved.
Optically active syn- and anti-1,3-polyols/5,6-pyrones
are ubiquitous structural motifs in various biologically
active compounds1 (Fig. 1). Fascinated by their broad
range of biological activity and structural diversity in
compounds ranging from simple carbohydrate to com-
plex alkaloid and polyketides, synthetic chemists con-
tinue to pursue their synthesis2 and the development
of new methodologies. The lactone ring constitutes a
structural feature of many natural products, particularly
those that are Michael acceptors (a,b-unsaturated).
They display pharmacological properties of interest such
as plant growth inhibition as well as antifeedant, anti-
fungal, antibacterial, and antitumor properties.3,4 The
simplest structure isolated which possesses a syn-1,3-
diol/5,6-dihydropyran-2-one motif is the dihydrocaffeic
ester, tarchonanthuslactone 1.5a,6 Tarchonanthuslactone
was isolated by Bohlmann from Tarchonanthustrilobus
compositae.7 Caffeic acid has been established as an ac-
tive principle, which lowers plasma glucose in diabetic
rats.8 Various methods for the synthesis of tarchonan-
thuslactone 1 have been described in the literature.5
Nakata et al.5g determined the stereochemistry of 1 via
a multistep synthesis, starting with optically active
1,3-butanediol. Most of the approaches to the 1,3-diol
system are based on either enzymatic procedures5a or
asymmetric methods such as Sharpless asymmetric
dihydroxylation,5b chiral allylboration,5c use of a chiral
sulfoxide to induce the chirality,5d and 1,3-asymmetric
reduction.5e,f
HO
In continuation of our interest aimed at developing
syntheses of naturally occurring lactones,9 we became
interested in devising a simple and concise route to
tarchonanthuslactone. In this paper, we report the
stereoselective total synthesis of 1, employing hydrolytic
kinetic resolution (HKR)10 and ring closing metathesis
as the key steps. The HKR method involves the readily
accessible cobalt based chiral salen complex 5 (Fig. 2) as
catalyst and water to resolve a racemic epoxide into an
enantiomerically enriched epoxide and diol in high
enantiomeric excess.
OAc OAc
O
O
O
HO
O
O
O
Cryptocarya diacetate 2
Tarchonanthuslactone 1
OH
13
OAc OAc OAc
O
OH OH
O
O
Cryptocarya triacetate 3
Passifloricin A 4
O
Figure 1.
In designing a route to 1, we chose propylene oxide as an
appropriate starting material. Our synthesis of 1
requires two major reactions, JacobsenÕs hydrolytic
kinetic resolution to install the stereogenic centers and
ring-closing metathesis to construct the d-lactone
moiety. As shown in Scheme 1, commercially available
Keywords: Tarchonanthuslactone; JacobsenÕs hydrolytic kinetic reso-
lution; Ring closing metathesis.
*
Corresponding author. Tel.: +91 20 25893300x2050; fax: +91 20
25893614; e-mail: pk.tripathi@ncl.res.in
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.07.056

6572
P. Gupta et al. / Tetrahedron Letters 46 (2005) 6571–6573
OTBS
OTBS
OTBS OH
a
O
O
+
OH
H
H
N
N
O
9b
9a
9
Co
O
OTBS OH
OTBS
b
OAc
O
OH
9a
9b
(R,R)-SalenCo(III)OAc complex 5
Scheme 2. Reagents and conditions: (a) R,R-salen-Co-(OAc)
(0.5 mol %), dist. H2O (0.55 equiv), 0 °C, 24 h, (45% for 9a, 47% for
9b); (b) (i) PivCl, Et3N, cat. DMAP, rt; (ii) MsCl, Et3N, DMAP, 0 °C
to rt; (iii) K2CO3, MeOH, rt (61% for three steps).
Figure 2.
OH
O
O
a
+
OH
9a could easily be separated from the more polar diol 9b
through silica gel column chromatography. As the HKR
method provided the desired epoxide along with un-
wanted diol 9b in almost equal amounts, we thought it
would be appropriate to convert diol 9b into the re-
quired epoxide 9a via internal nucleophilic substitution
of a secondary mesylate.12 Accordingly chemoselective
pivalation of diol 9b with pivaloyl chloride followed
by mesylation of the secondary hydroxyl and treatment
of the crude mesylate with K2CO3 in methanol led to
deprotection of the pivaloyl ester. Concomitant ring clo-
sure via intramolecular SN2 displacement of the mesy-
late furnished the epoxide 9a in 61% overall yield
(Scheme 2).
6b
6
6a
OH
O
b
c
6a
OH
7
OTBS
O
O
d
9
8
Scheme 1. Reagents and conditions: (a) R,R-salen-Co-(OAc)
(0.5 mol %), dist. H2O (0.55 equiv), 0 °C, 14 h, (46% for 6a, 45% for
6b); (b) vinylmagnesium bromide, THF, CuI, ꢁ20 °C, 12 h, 89%; (c) m-
CPBA, CH2Cl2, 0 °C to rt, 10 h, 96%; (d) TBDMS–Cl, imidazole,
CH2Cl2, 0 °C to rt, 4 h, 95%.
With substantial amounts of 9a in hand, we proceeded
with the synthesis of 1 (Scheme 3). Thus opening of
epoxide 9a with vinylmagnesium bromide in the pres-
ence of CuI in THF at ꢁ20 °C furnished the homoallylic
alcohol 10 in 86% yield. Alcohol 10 was then esterified
with acryloyl chloride in the presence of Et3N and a
catalytic amount of DMAP to afford the acryloyl ester
11 in 89% yield. Subsequent ring closing metathesis of
the ester with commercially available GrubbsÕ 1st
propylene oxide 6 was subjected to JacobsenÕs HKR
using (R,R)-salen-Co-OAc catalyst 5 (Fig. 2) to give
25
(R)-propylene oxide 6a as a single isomer; ½aꢀD +11.4
25
(neat); lit.10d ½aꢀD ꢁ11.6 (neat) (for (S)-propylene oxide),
which was easily isolated from the more polar diol 6b by
distillation. (R)-Propylene oxide 6a was treated with
vinylmagnesium bromide in the presence of CuI to give
the homoallylic alcohol 7 in excellent yield (Scheme 1).
We then further proceeded to explore the stereoselective
outcome of the epoxidation reaction with and without
hydroxyl group protection. Toward this end the hydr-
oxyl group of homoallylic alcohol 7 was first protected as
the TBS ether, followed by epoxidation with m-CPBA.
The epoxide thus obtained was found to be a mixture
of two diastereomers (anti:syn/3:1). The desired syn iso-
mer 9a was obtained only as a minor component. How-
ever, when epoxidation was carried out on alcohol 7
followed by hydroxy protection as the TBS–ether, the
epoxide 9 was formed in favor of the desired syn isomer
9a (syn:anti/1.2:1). The two diastereoisomers could not
be differentiated on TLC.
OTBS OH
OTBS
a
O
b
10
9a
O
O
OTBS
O
OTBS
O
c
d
12
11
O
O
O
TBSO
TBSO
O
O
O
e
OH
15
13
HO
O
O
O
TBSO
TBSO
OH
In order to improve the diastereoselectivity, we at-
tempted the hydrolytic kinetic resolution method
(HKR) as depicted in Scheme 2. Thus, the HKR was
performed on 9 with (R,R)-salen-Co-OAc complex 5
(0.5 mol %) and water (0.55 equiv) in THF (0.55 equiv)
to afford the epoxide 9a as a single stereoisomer (as
O
O
f
HO
14
1
Scheme 3. Reagents and conditions: (a) vinylmagnesium bromide,
THF, CuI, ꢁ20 °C, 1 h, 86%; (b) acryloyl chloride, Et3N, CH2Cl2, 0 °C
to rt, 5 h, 89%; (c) (PCy3)2Ru(Cl)2@CH–Ph (10 mol %), CH2Cl2,
Ti(i-PrO)4, reflux, 8 h, 87%; (d) TBAF, THF, rt, overnight, 86%; (e) 14,
DCC, DMAP, CH2Cl2, 5 h, 85%; (f) TBAF, THF, 1 h, 84%.
determined from the H and 13C NMR spectral analy-
1
sis)11 in 45% yield and the diol 9b in 47% yield. Epoxide

P. Gupta et al. / Tetrahedron Letters 46 (2005) 6571–6573
6573
generation catalyst13 (10 mol %) in the presence of Ti(i-
PrO)4 (0.03 equiv) in refluxing CH2Cl2 for 8 h afforded
the a,b-unsaturated d-lactone 1214 in 87% yield. Desilyl-
ation of 12 with TBAF gave the hydroxy lactone 13 in
86% yield. Treatment of 13 with TBS protected dihydro-
caffeic acid 14 using DCC and a catalytic amount of
DMAP furnished compound 15 in 85% yield, which
was deprotected with TBAF to give tarchonanthuslac-
tone 1 in 84% yield. The physical and spectroscopic data
of 1 were in full agreement with literature data.5
Trans. 1 1990, 1809–1812; (g) Nakata, T.; Hata, N.; Iida,
K.; Oishi, T. Tetrahedron Lett. 1987, 28, 5661–5664.
6. Echeverri, F.; Arango, V.; Quinones, W.; Torres, F.;
Escobar, G.; Rosero, Y.; Archbold, R. Phytochemistry
2001, 56, 881–885.
7. Bohlmann, F.; Suwita, A. Phytochemistry 1979, 18, 677–
679.
8. Hsu, F. L.; Chen, Y. C.; Cheng, J. T. Planta Med. 2000,
66, 228–230.
9. (a) Pais, G. C. G.; Fernandes, R. A.; Kumar, P.
Tetrahedron 1999, 55, 13445–13450; (b) Fernandes, R.
A.; Kumar, P. Tetrahedron: Asymmetry 1999, 10, 4349–
4356; (c) Fernandes, R. A.; Kumar, P. Eur. J. Org. Chem.
2002, 2921–2923; (d) Kandula, S. V.; Kumar, P. Tetra-
hedron Lett. 2003, 44, 6149–6151; (e) Gupta, P.; Naidu, S.
V.; Kumar, P. Tetrahedron Lett. 2004, 45, 849–851; (f)
Naidu, S. V.; Gupta, P.; Kumar, P. Tetrahedron Lett.
2005, 46, 2129–2131; (g) Kumar, P.; Naidu, S. V.; Gupta,
P. J. Org. Chem. 2005, 70, 2843–2846; (h) Kumar, P.;
Naidu, S. V. J. Org. Chem. 2005, 70, 4207–4210.
10. (a) Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen,
E. N. Science 1997, 277, 936–938; (b) Schaus, S. E.;
Branalt, J.; Jacobson, E. N. J. Org. Chem. 1998, 63, 4876–
4877; (c) Keith, J. M.; Larrow, J. F.; Jacobsen, E. N. Adv.
Synth. Catal. 2001, 343, 5–26; (d) 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, 1307–1315.
In conclusion, a practical and enantioselective synthesis
of tarchonanthuslactone has been achieved using itera-
tive hydrolytic kinetic resolution (HKR) to generate
both the stereocenters and ruthenium catalyzed
ring closing metathesis (RCM) to construct the d-lac-
tone moiety. The synthetic strategy described here has
significant potential to synthesize a variety of other bio-
logically important substituted 1,3-polyol-5,6-dihydro-
pyran-2-one-containing natural products. Currently
studies are in progress in this direction.
Acknowledgements
P.G. and S.V.N. thank UGC and CSIR, New Delhi, for
financial assistance, respectively. We are grateful to Dr.
M. K. Gurjar for his support and encouragement.
Financial support from DST, New Delhi (Grant No.
SR/S1/OC-40/2003) is gratefully acknowledged. This is
NCL communication No. 6682.
25
11. Spectral data of compound 9a: ½aꢀD ꢁ11.4 (c 0.67,
CHCl3); IR (Chloroform): mmax 3018, 2958, 2930, 1858,
1645, 1472, 1463, 1377, 1256, 1216, 1101, 1005, 938, 878,
1
760 cmꢁ1; H NMR (CDCl3, 200 MHz): d 4.01–4.08 (m,
1H), 3.02–3.04 (m, 1H), 2.76–2.80 (m, 1H), 2.46–2.50 (m,
1H), 1.67–1.71 (m, 1H), 1.50–1.52 (m, 1H), 1.19 (d,
J = 6.3 Hz, 3H), 0.87 (s, 9H), 0.03 (s, 3H), 0.02 (s, 3H);
13C NMR (CDCl3, 125 MHz): d 66.3, 48.8, 45.8, 42.1,
25.4, 23.3, 17.6, ꢁ5.0, ꢁ5.3. Anal. Calcd for C11H24O2Si
(216.39): C, 61.05; H, 11.18; Si, 12.98. Found: C, 61.12; H,
11.08; Si, 12.96.
References and notes
1. Rychnovsky, S. D. Chem. Rev. 1995, 95, 2021–2040.
2. (a) Hunter, T. J.; OÕDoherty, G. A. Org. Lett. 2001, 3,
2777–2780; (b) Jorgensen, K. B.; Suenaga, T.; Nakata, T.
Tetrahedron Lett. 1999, 40, 8855–8858; (c) Ghosh, A. K.;
Bilcer, G. Tetrahedron Lett. 2000, 41, 1003–1006; (d)
Reddy, M. V. R.; Rearick, J. P.; Hoch, N.; Ramachan-
dran, P. V. Org. Lett. 2001, 3, 19–20; (e) Smith, A. B.;
Brandt, B. M. Org. Lett. 2001, 3, 1685–1688.
12. (a) Nicolaou, K. C.; Webber, S. E. Synthesis 1986, 453–
461; (b) Takao, K.; Ochiai, H.; Yoshida, K.; Hashizuka,
T.; Koshimura, H.; Tadano, K.; Ogawa, S. J. Org. Chem.
1995, 60, 8179–8193.
13. For reviews on ring-closing metathesis, see: (a) Grubbs, R.
H.; Chang, S. Tetrahedron 1998, 54, 4413–4450; (b)
Prunet, J. Angew. Chem., Int. Ed. 2003, 42, 2826–2830.
25
14. Spectral data of compound 12: ½aꢀD ꢁ92.6 (c 0.84,
3. Jodynis-Liebert, J.; Murias, M.; Bloszyk, E. Planta Med.
2000, 66, 199–205.
CHCl3); IR (Chloroform): mmax 3019–2857, 1718, 1472,
1445, 1424, 1380, 1255, 1216 cmꢁ1 1H NMR (CDCl3,
;
4. Drewes, S. E.; Schlapelo, B. M.; Horn, M. M.; Scott-
Shaw, R.; Sandor, O. Phytochemistry 1995, 38, 1427–1430.
5. (a) Enders, D.; Steinbusch, D. Eur. J. Org. Chem. 2003,
4450–4454; (b) Garaas, S. D.; Hunter, T. J.; OÕDoherty,
G. A. J. Org. Chem. 2002, 67, 2682–2685; (c) Reddy, M.
V. R.; Yucel, A. J.; Ramachandran, P. V. J. Org. Chem.
2001, 66, 2512–2514; (d) Solladie, G.; Gressot-Kempf, L.
Tetrahedron: Asymmetry 1996, 7, 2371–2379; (e) Mori, Y.;
Kageyama, H.; Suzuki, M. Chem. Pharm. Bull. 1990, 38,
2574–2576; (f) Mori, Y.; Suzuki, M. J. Chem. Soc., Perkin
300 MHz): d 6.90 (ddd, J = 10, 4.2, 3.9 Hz, 1H), 6.04 (ddd,
J = 10, 2.2, 2.2, 1H), 4.61 (dddd, J = 8, 8, 8, 5.1 Hz, 1H),
4.16–4.21 (m, 1H), 2.31–2.35 (m, 2H), 1.86 (ddd, J = 14.3,
8.1, 8.1 Hz, 1H), 1.62 (ddd, J = 14.8, 5.4, 4.2 Hz, 1H), 1.18
(d, J = 6 Hz, 3H), 0.88 (s, 9H), 0.09 (s, 3H), 0.07 (s, 3H);
13C NMR (CDCl3, 125 MHz): d 164.2, 144.9, 121.1, 75.2,
64.6, 43.9, 29.4, 25.5, 23.1, 17.7, ꢁ4.5, ꢁ5.1. Anal. Calcd
for C14H26O3Si (270.43): C, 62.18; H, 9.69; Si 10.39.
Found: C, 62.09; H, 9.74; Si, 10.36.