An efficient total synthesis of decarestrictine D

Article abstract of DOI:10.1002/ejoc.200700868

An efficient total synthesis of decarestrictine D has been achieved using cross-metathesis or ring-closing metathesis and Yamaguchi macrolactonization as key steps. The stereogenic centres were generated by means of hydrolytic kinetic resolution (HKR) and

Full text of DOI:10.1002/ejoc.200700868

FULL PAPER
DOI: 10.1002/ejoc.200700868
An Efficient Total Synthesis of Decarestrictine D[‡]
Priti Gupta[a] and Pradeep Kumar*[a]
Keywords: Macrolides / Hydrolytic kinetic resolution / Sharpless asymmetric dihydroxylation / Cross metathesis / Ring-
closing metathesis
An efficient total synthesis of decarestrictine D has been
achieved using cross-metathesis or ring-closing metathesis
and Yamaguchi macrolactonization as key steps. The stereo-
genic centres were generated by means of hydrolytic kinetic
resolution (HKR) and Sharpless asymmetric dihydroxylation
(AD).
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
Introduction
Decarestrictine D (1a), a 10-membered ring lactone was
isolated independently from Penicillium corylophilum, P.
simplicissimum[1] and from the Canadian Tuchahoe fungi
Polyporus tuberaster.[2] It shows inhibitory activity against
cholesterol biosynthesis at 10–7 , in HEP-G2 liver cell.[1a]
The structural difference between 1a and the well known
HMG-CoA inhibitors such as mevinolin, compactin and
other synthetic cholesterol-lowering agent suggests a dif-
ferent mode of action operative with 1a. In addition, 1a is
highly selective in that it exhibits no significant antibacte-
rial, antifungal, antiprotozoal or antiviral activity.[1,2] Other
members of this 10-membered ring lactone family include
decarestrictine A (1b), decarestrictine B (1c) and decare-
strictine C (1d) (Figure 1). Considering its strong and selec-
tive biological profile, decarestrictine D has attracted a
great deal of interest among synthetic organic chemists
worldwide as an attractive synthetic target towards de-
veloping new cholesterol-lowering drugs. Consequently, the
synthesis of 1a and its seco-acid have been reported by vari-
ous research groups.[3–7] The synthetic approaches de-
scribed so far for 1a involve either a chiral building block,
asymmetric catalysis or a chiral induction to establish one
or more of stereogenic centres present in the molecule.
However, synthetic strategies that are based on 1,3-chiral
induction to establish the C7 stereocentre suffer from low
diastereoselectivity.[3,7] Similarly the Sharpless AD reaction
of a diene[3] to generate the C3 and C4 stereocentres and
stereoselective reduction of a keto group by -selectride[6]
to establish the C4 stereocentre were found to give a mix-
ture of two regioisomers and stereoisomers, respectively.
Figure 1. Examples of 10-membered ring lactones.
Pilli’s synthesis also suffers from use of excess of the toxic
Cr reagent coupled with a mixture of two diastereomers at
C7 centre. In addition, the majority of the approaches
known for decarestrictine D are based on macrolactoni-
zation for the key macrocyclization and suffer from low
yields (17–45%) for the target molecule.[3,5,6] As a part of
our research programme aimed at developing enantioselec-
tive synthesis of naturally occurring lactones[8] and amino
alcohols[9] we became interested in devising a simple and
practical route to decarestrictine D. Herein we report our
successful endeavors towards the total synthesis of 1a em-
ploying hydrolytic kinetic resolution (HKR), Sharpless
asymmetric dihydroxylation (AD), Yamaguchi coupling,
cross metathesis and ring-closing metathesis (RCM) as the
key steps.
[‡] This is NCL communication no. 6706.
[a] Division of Organic Chemistry, National Chemical Laboratory,
Pune 411008, India
Results and Discussion
Our retrosynthetic analysis is based on convergent ap-
proach as outlined in Scheme 1. We envisioned that the
Fax: +91-20-25902629
E-mail: pk.tripathi@ncl.res.in
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P. Gupta, P. Kumar
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ring-closing could be effected by Yamaguchi macrolactoni-
zation of the seco-acid 19 or by ring-closing metathesis of
diene 21. seco-Acid 19 in turn could be derived from cross-
metathesis of alcohol 10 and acid 18. Diene 21 could be
prepared by Yamaguchi coupling of the same fragments 10
and 18. Both the fragments 10 and 18 could be obtained
from olefins 4 and 13, respectively, via AD. Olefins 4 and
13 in turn could be derived from the commercially available
propylene oxide and 3-butene-1-ol, respectively.
Scheme 2. Synthesis of alcohol 10: (a) (i) vinylmagnesium bromide,
THF, CuI, –20 °C, 12 h, 89%; (ii) TBDMS-Cl, imidazole, CH2Cl2,
0 °C to room temp., 4 h, 94%; (b) Ethyl acrylate, RuCl2(=CHPh)-
(PCy3)(IEMS), benzene, room temp., 20 h, 80%; (c) (DHQ)2-
PHAL, K2CO3, K3Fe(CN)6, MeSO2NH2, OsO4 (0.1  in toluene),
tBuOH/H2O (1:1), 0 °C, 24 h, 96%; (d) pTSA, 2,2-DMP, CH2Cl2, 2
h, 89%; (e) DIBAL-H, CH2Cl2, 0 °C to room temp., 2 h, 94%; (f)
(i) TsCl, Et3N, CH2Cl2, 2 h; (ii) NaI, 2-butanone, reflux, 6 h, 87%
for both steps; (g) Zn, EtOH, reflux, 8 h, 94%; (h) (i) MEMCl,
DIPEA, CH2Cl2, 8 h; (ii) TBAF, THF, 6 h, 75% for both steps.
the allylic alcohol 9 in 94% yield. Alcohol 9 was protected
as MEM ether followed by subsequent TBS deprotection to
give the required alcohol fragment 10 in 75% yield from
both the steps.
Scheme 1. Retrosynthetic route to decarestrictine D.
Synthesis of Acid 18
The synthesis of acid fragment 18 commenced from com-
mercially available 3-butene-1-ol 11. In order to generate
the trans-olefin to execute the AD, 3-butene-1- ol was con-
Synthesis of Alcohol 10
The synthesis of alcohol 10 started from commercially verted into the enyne moiety. Thus, protection of alcohol
available propylene oxide (Scheme 2). Thus, racemic propyl- 11 with PMB bromide in the presence of NaH followed by
ene oxide was resolved by using R,R-salen-CoIIIOAc to give oxidation using mCPBA gave epoxide 12 in 96% yield. Ring
(R)-propylene oxide 2.[10]
opening of epoxide 12 with lithium acetylide in DMSO fol-
The ring opening of (R)-propylene oxide 2 with vinyl- lowed by hydroxy group protection as mesyl and subse-
magnesium bromide followed by protection of hydroxy quent elimination using DBU afforded the enyne 13 in 82%
group as TBS ether gave the olefin 3 in 94% yield. The yield. The enyne 13 was further treated with osmium tetrox-
olefin 3 on cross-metathesis[11] with ethyl acrylate using ide and potassium ferricyanide as co-oxidant in the pres-
Grubbs’ second-generation catalyst afforded the trans-ole- ence of (DHQ)2PHAL under AD conditions to give the
fin 4 in 80% yield. The olefin 4 was treated with osmium diol 14 in 94% yield with 94% ee.[14]
tetroxide and potassium ferricyanide as co-oxidant in the
presence of (DHQ)2PHAL under AD conditions[12] to give ing. Irrespective of whether catalytic quantity or several
the diol 5 in 96% yield with Ͼ95% de.[13]
molar equivalent of quinoline were present, the mixture of
The partial hydrogenation of 14 proved to be challeng-
Treatment of diol with 2,2-dimethoxypropane in the 15 and overhydrogenated product 15a was formed (Table 1).
presence of catalytic amount of pTSA (5Ǟ6) followed by However, the use of 1-octene as a co-solvent along with
reduction using DIBAL-H provided the alcohol 7 in 94% EtOAc in the presence of pyridine (EtOAc/pyridine/1-oc-
yield. Alcohol 7 was converted into iodo 8 in 87% yield, tene = 10:1:1) furnished the olefinic diol 15 as a single prod-
followed by reductive elimination using Zn/EtOH to give uct in 94% yield (Scheme 3).
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An Efficient Total Synthesis of Decarestrictine D
Table 1. Partial hydrogenation of 14.
subsequent reactions to complete the synthesis of target
molecule. We then proceeded with the synthesis initially by
cross-olefin metathesis (Scheme 5). Thus cross-metathesis
of olefin 10 (2 equiv.) and acid 18 (1 equiv.) with Grubbs’
second-generation catalyst (20 mol-%) furnished the seco
acid 19 in 54% yield with olefin ratio 5:1 in favour of E-
isomer. The required trans-isomer could easily be separated
through flash column chromatography.
Entry Base
Solvents
15:15a
1
2
3
4
quinoline (catalytic)
EtOAc
quinoline (10 equiv.) EtOAc
quinoline (10 equiv.) benzene
0:100
10:90
30:70
pyridine
octene/EtOAc (1:10) 100:0
Scheme 3. Synthesis of diol 14: (a) (i) PMBBr, NaH, TBAI, THF,
0 °C to room temp., 2 h, 93%; (ii) m-CPBA, CH2Cl2, 0 °C to room
temp., 8 h, 96%; (b) (i) LiCϵCH/ethylenediamine, DMSO, 0 °C to
room temp., overnight, 89%; (ii) MsCl, Et3N, CH2Cl2, 0 °C to room
temp., 2 h; (iii) DBU, toluene, reflux, 4 h, 82% from two steps; (c)
(DHQ)2PHAL, K2CO3, K3Fe(CN)6, MeSO2NH2, OsO4 (0.1  in
toluene), tBuOH/H2O (1:1), 0 °C, 24 h, 94%; (d) Lindlar’s catalyst,
pyridine/octene/EtOAc (1:1:10), 2 h, 94%.
Scheme 5. Synthesis of decarestrictine D through cross-metathesis
and Yamaguchi macrolactonization: (a) RuCl2(=CHPh)(PCy3)-
(IEMS), CH2Cl2, room temp., 2 days, 54%; (b) RuCl2(=CHPh)-
(PCy3)(IEMS), CH2Cl2, room temp., 2 days, 38%; (c) 2,4,6-trichloro-
benzoyl chloride, Et3N, THF, 2 h, room temp. then C6H6, DMAP,
80 °C, 1 h then reflux, 1 h, 32%; (d) TiCl4, CH2Cl2, 0 °C to room
temp., 30 min, 78%.
The treatment of diol 15 with BnBr in the presence of
NaH gave dibenzyl olefin 16 which on PMB deprotection
by using DDQ furnished the alcohol 17[15] in 93% yield.
The alcohol 17 was oxidised to aldehyde by using IBX fol-
lowed by subsequent oxidation using NaClO2 to give the
required acid fragment 18 in 80% yield (Scheme 4).
To improve the yield and E-selectivity, we further investi-
gated the cross-metathesis reaction with different function-
alities in both the fragments. Thus olefin 10 was coupled
with olefin 17 (precursor of olefin 18) in presence of
Grubbs’ second-generation catalyst to furnish the coupled
product 19a albeit in low yield and poor selectivity. Even
the use of TBS, Ac as protecting groups, could not improve
the results in terms of yield and selectivity.
With desired seco-acid 19 in hand, we turned our atten-
tion to get the macrolactone via Yamaguchi macrocycliza-
tion. However, macrolactonization of 19 under Yamaguchi
conditions[16] provided the macrocyclic lactone 20 in 32%
yield only. The low yield obtained could probably be attrib-
uted to destabilizing nonbonded, transannular interactions
and unfavourable entropic factors.[17] Compound 20 on
subsequent cleavage of the protective groups afforded the
target molecule 1a in 78% yield (Scheme 5).
Scheme 4. Synthesis of acid 18: (a) BnBr, NaH, THF, 0 °C to room
temp., 4 h, 85%; (b) DDQ, CH2Cl2/H2O, room temp., 30 min, 93%;
(c) (i) IBX, EtOAc, reflux, 3 h; (ii) NaClO2, NaH2PO4, DMSO,
overnight, 80%.
Synthesis of Decarestrictine D through Cross-Metathesis
and Yamaguchi Macrolactonization
Synthesis of Decarestrictine D through Ring-Closing
Metathesis
With substantial amounts of both the fragments in hand,
In order to circumvent the problem of low yield in the
we required to generate the trans-olefin and carry out the cross-metathesis step as well as in macrolactonization, we
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P. Gupta, P. Kumar
FULL PAPER
181 digital polarimeter. Infrared spectra were recorded on a Per-
kin–Elmer model 683 grating Infrared spectrometer. 1H NMR
(200 MHz), (500 MHz) and 13C (50 MHz), (125 MHz), NMR spec-
thought it appropriate to use Yamaguchi coupling reaction
initially for the diene ester formation and then ring-closing
metathesis[18] for macrocyclization as the last step in the
synthesis (Scheme 6). To this end the alcohol 10 was cou-
pled with acid 18 under Yamaguchi conditions to give the
diene 21 in 89% yield. The diene 21 was treated with
Grubbs’ first generation catalyst to give the α,β-unsaturated
lactone in 82% yield with olefin ratio 8:1 in favour of E-
isomer, which were separable on column chromatography.
tra were recorded in CDCl3 solution with residual CHCl3 (δH
=
7.27 ppm) and (δC = 77.00 ppm) as internal standard. Mass spectra
were obtained with an API Q STARPULSAR spectrometer using
electron spray ionization [(ESI), solvent medium: acetonitrile or
methanol] technique. Elemental analyses were carried out on a
Carlo–Erba CHNS-O analyzer. Petroleum ether of boiling range
60–80 °C was used. Column chromatography were performed on
Global deprotection of 20 using TiCl4 in CH2Cl2 gave the silica gel (60–120 and 100–200 mesh) using a mixture of petroleum
target molecule decarestrictine D (1a) in 78% yield. [α]D25
=
ether/ethyl acetate.
–63.7 (c = 0.46, EtOH) [ref.[1b] [α]D = –62.0 (c = 0.4,
EtOH)]. The physical and spectroscopic data of 1a were in
full agreement with the literature data.[3] The overall yields
and number of steps involved in our synthesis are compar-
able with those reported in the literature.
(R)-Propylene Oxide (2): The racemic propylene oxide was resolved
to (R)-propylene oxide (2) in high enantiomeric excess by the HKR
method following a literature procedure.[10a]
For (R)-propylene oxide [α]2D5 = +11.4 (neat); ref.[10a] [α]2D5 = –11.6
(neat) for (S)-propylene oxide.
(R)-4-Pentene-2-ol: This compound was prepared from (R)-propyl-
ene oxide according to ref.[8f]
(R)-tert-Butyldimethyl(pent-4-en-2-yloxy)silane (3): To a stirred sol-
uion of the above-mentioned alcohol (3.0 g, 34.83 mmol) in
CH2Cl2 (25 mL), imidazole (3.57, 52.24 mmol) was added. To this
solution tert-butylchlorodimethylsilane (5.77 g, 38.31 mmol) was
added at 0 °C and the mixture was stirred at room temperature for
4 h. The reaction mixture was quenched with a saturated aqueous
solution of NH4Cl and extracted with CH2Cl2 (3ϫ50 mL). The
extract was washed with brine, dried (Na2SO4) and concentrated.
Silica gel column chromatography of the crude product using pe-
troleum ether/EtOAc (49:1) as eluent provided 3 (6.56 g, 94%).
[α]2D5 = –14.46 (c = 1.8 in CHCl3). The spectroscopic data such as
1H NMR, 13C NMR and IR were in accord with those described
in literature.[19]
Ethyl (R,E)-5-(tert-Butyldimethylsilyloxy)hex-2-enoate (4): The ole-
fin 3 (2 g, 9.98 mmol) was diluted with benzene (20 mL) and de-
gassed for 15 minutes. Ethyl acrylate (2.5 g, 24.95 mmol, freshly
distilled) was then added to the reaction flask followed by Grubbs’
second-generation catalyst (0.169 g, 0.20 mmol). The reaction was
allowed to stir for 20 h under argon at room temperature, at which
time, it was allowed to oxidize by opening the reaction to air and
stirring overnight. The dark brown solution was then concentrated.
Silica gel column chromatography of the crude product using pe-
troleum ether/EtOAc (19:1) as eluent provided the α,β-unsaturated
ester 4 (2.18 g, 80%) as a light yellow colour liquid. [α]2D5 = –9.60
(c = 1.02 in CHCl3); ref.[20] [α]2D5 = –9.5 (c = 1 in CHCl3). The
spectroscopic data such as 1H NMR, and 13C NMR were in accord
with those described in literature.[20]
Scheme 6. Synthesis of decarestrictine D through ring-closing me-
tathesis: (a) 2,4,6-trichlorobenzoyl chloride, DMAP, Et3N, THF,
0 °C to room temp., 20 h, 89%; (b) (PCy3)2 Ru(Cl)2=CH–Ph
(20 mol-%), CH2Cl2, reflux, 14 h, 82%; (c) TiCl4, CH2Cl2, 0 °C to
room temp., 30 min, 78%.
Conclusions
In conclusion, a convergent and efficient total synthesis
of decarestrictine D, with high enantioselectivities has been
accomplished in which all the stereocentres were generated
by means of Jacobsen’s hydrolytic kinetic resolution and
asymmetric dihydroxylation, and lactone moiety was
achieved by ring closing metathesis. This approach could be
Ethyl (2R,3S,5R)-5-(tert-Butyldimethylsilyloxy)-2,3-dihydroxyhex-
anoate (5): To a mixture of K3Fe(CN)6 (7.25 g, 22.02 mmol),
K2CO3 (3.04 g, 22.02 mmol) and (DHQ)2PHAL (57 mg, 1 mol-%),
in tBuOH/H2O (1:1, 40 mL) cooled to 0 °C was added OsO4
(0.29 mL, 0.1  in toluene, 0.4 mol-%) followed by methanesulfon-
used for synthesis of other isomers of decarestrictine D for amide (0.70 g, 7.34 mmol). After stirring for 5 min at 0 °C, the ole-
fin 4 (2.0 g, 7.34 mmol) was added in one portion. The reaction
mixture was stirred at 0 °C for 24 h and then quenched with solid
sodium sulfite (11 g). The stirring was continued for 45 min and
the solution was extracted with EtOAc (3ϫ50 mL). The combined
organic phases were washed with brine, dried (Na2SO4) and con-
centrated. Silica gel column chromatography of the crude product
using petroleum ether/EtOAc (3:1) as eluent afforded diol 5 (2.16 g,
96%) in Ͼ95% de as a colorless syrup. [α]2D5 = –10.37 (c = 1.26 in
structure–activity relationship. Currently work is in pro-
gress in this direction.
Experimental Section
General: Solvents were purified and dried by standard procedures
before use. Melting points are uncorrected. Optical rotations were
measured by using the light of the sodium-D line and a JASCO-
1
CHCl3). H NMR (200 MHz, CDCl3): δ = 4.27 (q, J = 7.2 Hz, 2
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An Efficient Total Synthesis of Decarestrictine D
H), 4.20–4.05 (m, 2 H), 3.98 (d, J = 6.6 Hz, 1 H), 3.28 (br. s, 1 H), 87%) as a colorless liquid. [α]2D5 = –38.04 (c = 1.0 in CHCl3). H
1
3.11 (br. s, 1 H), 1.93 (dd, J = 10.8, 1.3 Hz, 1 H), 1.54 (dd, J = 8.2,
6.2 Hz, 1 H), 1.32 (t, J = 7.1 Hz, 3 H), 1.20 (d, J = 6.0 Hz, 3 H),
NMR (200 MHz, CDCl3): δ = 4.07–3.88 (m, 2 H), 3.55–3.51 (m, 1
H), 3.31 (d, J = 4.9 Hz, 1 H), 3.25 (d, J = 4.9 Hz, 1 H), 1.57 (t, J
0.89 (s, 9 H), 0.09 (s, 6 H) ppm. 13C NMR (50 MHz, CDCl3): δ = = 6.7 Hz, 2 H), 1.43 (s, 3 H), 1.41 (s, 3 H), 1.19 (d, J = 6.2 Hz, 3
173.2, 74.1, 69.3, 66.4, 61.5, 42.2, 25.6, 23.2, 17.8, 14.0, –4.7, –5.3
H), 0.91 (s, 9 H), 0.08 (s, 6 H) ppm. 13C NMR (50 MHz, CDCl3):
ppm. IR (CHCl ): ν = 3439, 3020, 2958, 2931, 2401, 1734, 1656, δ = 109.5, 81.9, 78.3, 68.7, 37.8, 27.3, 25.6, 25.5, 18.1, 3.8, –3.8,
˜
3
1472, 1446, 1257, 1215, 1085, 978 cm–1. C14H30O5Si (306.47): calcd.
C 54.87, H 9.87; found C 54.74, H 9.82. MS (ESI): m/z = 329 [M
+ Na]+.
–4.2 ppm. IR (CHCl ): ν = 3020, 2957, 2930, 2857, 2400, 1522,
˜
3
1472, 1382, 1299, 1215, 1035, 837 cm–1. C15H31IO3Si (414.39):
calcd. C 43.48, H 7.54; found C 43.36, H 7.48.
Ethyl
(4R,5S)-5-[(R)-2-(tert-Butyldimethylsilyloxy)propyl]-2,2-di- (3S,5R)-5-(tert-Butyldimethylsilyloxy)hex-1-en-3-ol (9): A mixture
methyl-1,3-dioxolane-4-carboxylate (6): To a solution of the diol 5
(2.0 g, 6.53 mmol), pTSA (50 mg) in CH2Cl2 (75 mL) was added
2,2-dimethoxypropane (1.02 g, 1.2 mL, 9.79 mmol) and mixture
stirred for 2 h. Solid NaHCO3 was added and stirring continued
for 1.5 h. The solution was filtered through a pad of neutral alu-
mina and concentrated. Silica gel column chromatography of the
crude product using petroleum ether/EtOAc (9:1) as eluent gave
of compound 8 (1.4 g, 3.38 mmol) and zinc (0.44 g, 6.76 mmol) in
refluxing ethanol (15 mL) under nitrogen was stirred for 8 h. The
zinc was filtered and filtrate concentrated. Silica gel column
chromatography of the crude product using petroleum ether/EtOAc
(9:1) as eluent gave 9 (0.73 g, 94%) as a light yellow liquid. [α]2D5
=
–29.18 (c = 1.0 in CHCl3). 1H NMR (200 MHz, CDCl3): δ = 6.03–
5.79 (m, 1 H), 5.36–5.06 (m, 2 H), 4.52–4.41 (m, 1 H), 4.24–4.06
(m, 1 H), 2.18 (br. s, 1 H), 1.75–1.62 (m, 2 H), 1.23 (d, J = 6.2 Hz,
acetonide ester 6 (2.01 g, 89%) as a colorless liquid. [α]2D5 = –23.05
1
(c = 1.40 in CHCl3). H NMR (200 MHz, CDCl3): δ = 4.26 (q, J 3 H), 0.92 (s, 9 H), 0.10 (s, 6 H) ppm. 13C NMR (50 MHz, CDCl3):
= 8.0 Hz, 2 H), 4.16–4.09 (m, 1 H), 4.07–4.03 (m, 2 H), 1.70–1.61 δ = 141.1, 113.7, 69.6, 66.9, 44.5, 25.7, 23.0, 17.9, –4.5, –5.0 ppm.
(m, 2 H), 1.45 (s, 3 H), 1.43 (s, 3 H), 1.29 (t, J = 7.1 Hz, 3 H), 1.19 IR (CHCl ): ν = 3451, 3081, 2955, 2936, 2856, 1642, 1472, 1456,
˜
3
(d, J = 6.4 Hz, 3 H), 0.89 (s, 9 H), 0.06 (s, 6 H) ppm. 13C NMR 1384, 1226, 1075, 940 cm–1. C12H26O2Si (230.42): calcd. C 62.55,
(50 MHz, CDCl3): δ = 170.5, 110.6, 78.9, 75.8, 65.1, 61.0, 43.3,
H
11.37; found
C 62.48, H 11.41. MS (ESI): m/z = 253
27.1, 25.6, 24.4, 17.8, 14.0, –4.5, –5.2 ppm. IR (CHCl ): ν = 3021,
[M + Na]+.
˜
3
2957, 2931, 1751, 1655, 1473, 1375, 1216, 1144, 1084, 952, 839, 758
cm–1. C17H34O5Si (346.53): calcd. C 58.92, H 9.89; found C 59.01,
H 9.86. MS (ESI): m/z = 369 [M + Na]+.
(2R,4S)-4-[(2-Methoxyethoxy)methoxy]hex-5-en-2-ol (10): A mix-
ture of compound 9 (0.5 g, 2.17 mmol), diisopropylethylamine
(0.84 g, 1.13 mL, 6.5 mmol), MEM-Cl (0.32 g, 0.30 mL,
{(4S,5S)-5-[(R)-2-(tert-Butyldimethylsilyloxy)propyl]-2,2-dimethyl- 2.60 mmol) in CH2Cl2 (20 mL) was stirred at room temperature for
1,3-dioxolan-4-yl}methanol (7): To a solution of ester 6 (2 g,
5.77 mmol) in dry CH2Cl2 (20 mL) at 0 °C was added dropwise
DIBAL-H (6.35mL, 6.35 mmol, 1  in toluene) through a syringe.
The reaction mixture was allowed to warm to room temperature
over 2 h, then re-cooled to 0 °C and treated with saturated solution
of sod./pot. tartrate. The solid material was filtered through a pad
of Celite and concentrated. Silica gel column chromatography of
the crude product using petroleum ether/EtOAc (17:3) as eluent
gave alcohol 7 (1.65 g, 94%) as a colorless liquid. [α]2D5 = –42.51 (c
= 1.20 in CHCl3). 1H NMR (200 MHz, CDCl3): δ = 4.05–4.00 (m,
2 H), 3.80–3.70 (m, 1 H), 3.63 (d, J = 4.9 Hz, 2 H), 2.18 (s, 1 H),
1.58 (t, J = 5.7 Hz, 2 H), 1.40 (s, 3 H), 1.38 (s, 3 H), 1.19 (d, J =
6.1 Hz, 3 H), 0.89 (s, 9 H), 0.07 (s, 6 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 108.6, 81.5, 73.7, 65.5, 61.9, 42.7, 27.4, 26.8, 25.8,
8 h. The reaction mixture was quenched with water and extracted
with CH2Cl2, washed with water, brine, dried (Na2SO4) and evapo-
rated to afford crude product, which was used as such for the next
step without purification. To
a solution of olefin (0.69 g,
2.17 mmol) in THF (10 mL) was added TBAF (3.25 mL,
3.25 mmol, 1.0  solution in THF) at room temperature. The reac-
tion mixture was stirred for 6 h and then diluted with water and
extracted with EtOAc. The organic layer was washed with brine,
dried (Na2SO4) and concentrated. Silica gel column chromatog-
raphy of the crude product using petroleum ether/EtOAc (7:3) as
eluent gave alcohol 10 (0.33 g, 75% from both the steps) as a color-
less liquid. [α]2D5 = –95.88 (c = 1.22 in CHCl3). 1H NMR (200 MHz,
CDCl3): δ = 5.80–5.63 (m, 1 H), 5.29–5.15 (m, 2 H), 4.83 (s, 2 H),
4.05–3.90 (m, 1 H), 3.74–3.69 (m, 1 H), 3.60–3.41 (m, 4 H), 3.39
(s, 3 H). 2.39 (br. s, 1 H), 1.71–1.57 (m, 2 H), 1.21 (d, J = 6.2 Hz,
3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 137.7, 116.7, 92.11,
24.6, 17.9, –4.5, –5.0 ppm. IR (CHCl ): ν = 3461, 3019, 2957, 2931,
˜
3
2858, 1719, 1472, 1380, 1256, 1215, 1167, 1047, 952 cm–1.
C15H32O4Si (304.5): calcd. C 59.17, H 10.59; found C 59.23, H
10.57. MS (ESI): m/z = 327 [M + Na]+.
73.9, 71.6, 66.6, 63.1, 58.8, 44.5, 23.3 ppm. IR (CHCl ): ν = 3462,
˜
3
3016, 2968, 2893, 2448, 1645, 1456, 1422, 1367, 1241, 1216, 1133,
1098, 993 cm–1. C10H20O4 (204.26): calcd. C 58.80, H 9.87; found
C 58.64, H 9.81. MS (ESI): m/z = 227 [M + Na]+.
tert-Butyl{(R)-1-[(4S,5R)-5-(iodomethyl)-2,2-dimethyl-1,3-dioxolan-
4-yl]propan-2-yloxy}dimethylsilane (8): To a stirred solution of
alcohol 7 (1.2 g, 3.94 mmol) in CH2Cl2 (40 mL) at 0 °C under ni-
trogen was added triethylamine (1.65 mL, 11.82 mmol) followed by
tosyl chloride (0.90 g, 4.73 mmol). After being stirred for 2 h at
room temperature, the reaction mixture was diluted with H2O, and
extracted with CH2Cl2 (50 mL). The combined organic layers were
washed with water, brine and dried (Na2SO4). The solvent was re-
moved under reduced pressure to give tosyl as a pale yellow oil,
which was used as such for the next step, without further purifica-
tion. Tosyl (1.8 g, 3.92 mmol) was dissolved under argon in dry 2-
butanone (20 mL) and was treated with NaI (1.76 g, 11.77 mmol).
The reaction mixture was refluxed for 6 h. After cooling to room
temperature the volatiles were removed under reduced pressure. Sil-
ica gel column chromatography of the crude product using petro-
leum ether/EtOAc (19:1) as eluent gave iodo compound 8 (1.42 g,
2-[2-(4-Methoxybenzyloxy)ethyl]oxirane (12): To a solution of 3-bu-
tene-1-ol (11) (5.0 g, 69.34 mmol) in dry THF (50 mL) was added
sodium hydride (50%, 5.0 g, 104.00 mmol) at 0 °C. The reaction
mixture was then stirred at room temperature for 30 min after
which it was again cooled to 0 °C. To this was added slowly p-
methoxybenzyl bromide (16.73 g, 83.21 mmol) and tetra-n-butyl-
ammonium iodide (2.56 g, 6.93 mmol) with further stirring for 2 h
at room temperature. The reaction mixture was quenched with ad-
dition of cold water at 0 °C. The two phases were separated and
the aqueous phase was extracted with EtOAc (3ϫ100 mL). The
combined organic layers were washed with water (3ϫ100 mL),
brine, dried (Na2SO4) and concentrated. Silica gel column
chromatography of the crude product using petroleum ether/EtOAc
(8:2) as eluent furnished the mono-PMB-protected olefin (12.40 g,
Eur. J. Org. Chem. 2008, 1195–1202
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1199

P. Gupta, P. Kumar
FULL PAPER
93%) as a colorless oil. To a stirred solution of olefin (7 g,
36.41 mmol) in CH2Cl2 (50 mL) at 0 °C was added mCPBA (50%)
(15.08 g, 43.69 mmol). The reaction mixture was stirred at room
temperature for 8 h and quenched by saturated NaHCO3 solution,
extracted with CH2Cl2, washed with sat. NaHCO3 and brine, dried
(Na2SO4) and concentrated. Silica gel column chromatography of
the crude product using petroleum ether/EtOAc (17:3) as eluent
afforded the epoxide 12 (7.28 g, 96%) as a colorless liquid. The
spectroscopic data such as 1H NMR, 13C NMR and IR were in
accord with those described in literature.[21]
8.4 Hz, 2 H), 4.46 (s, 2 H), 4.23 (dd, J = 3.7, 2.1 Hz, 1 H), 3.89–
3.84 (m, 1 H), 3.80 (s, 3 H), 3.73–3.65 (m, 2 H), 3.09 (br. s, 1 H),
2.88 (br. s, 1 H), 2.47 (s, 1 H), 1.99–1.79 (m, 2 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 159.3, 129.7, 129.4, 113.9, 82.2, 74.1, 73.8,
72.9, 67.7, 65.8, 55.2, 32.0 ppm. IR (CHCl ): ν = 3307, 3019, 2935,
˜
3
2400, 1656, 1514, 1367, 1216, 1076, 992, 858 cm–1. MS (ESI): m/z
= 273 [M + Na]+. C14H18O4 (250.29): calcd. C 67.18, H 7.25; found
C 67.21, H 7.24.
(3S,4S)-6-(4-Methoxybenzyloxy)hex-1-ene-3,4-diol (15): To a solu-
tion of 14 (2.5 g, 9.99 mmol) in 5 mL of ethyl acetate/pyridine/1-
octene (10:1:1) was added Lindlar’s catalyst (10 mg). The reaction
mixture was stirred for 2 h under a balloon of H2 at room tempera-
ture and filtered through a Celite pad. The filtrate was concentrated
and the residue was purified by silica gel column chromatography
using petroleum ether/EtOAc (3:2) as eluent to give olefin 15
(2.37 g, 94%) as a colorless liquid. [α]2D5 = +10.45 (c = 1.0 in
(E)-1-[(Hex-3-en-5-ynyloxy)methyl]-4-methoxybenzene (13): A dark
brown slurry of lithium acetylide EDA complex (7.74 g,
84.03 mmol) in dry DMSO (10 mL) was stirred with epoxide 12
(7 g, 33.61 mmol) overnight at room temperature. After the reac-
tion mixture was quenched with ice, 0.3  H2SO4 was used to neu-
tralize the resultant basic solution to pH 7, after which the product
was extracted with diethyl ether, washed with brine, dried (Na2SO4)
and concentrated. Silica gel column chromatography of the crude
product using petroleum ether/EtOAc (17:3) as eluent yielded the
acetylenic alcohol (7.0 g, 89%) as a light yellow color liquid.
1
CHCl3). H NMR (200 MHz, CDCl3): δ = 7.25 (d, J = 8.3 Hz, 2
H), 6.89 (d, J = 8.3 Hz, 2 H), 5.94–5.77 (m, 1 H), 5.38–5.19 (m, 2
H), 4.44 (s, 2 H), 3.95 (t, J = 5.7 Hz, 2 H), 3.79 (s, 3 H), 3.69–3.62
(m, 2 H), 2.75 (br. s, 2 H), 1.84–1.76 (m, 2 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 159.2, 137.40, 129.8, 129.2, 116.9, 113.7,
To a stirred solution of acetylenic alcohol (6.5 g, 27.74 mmol) in
CH2Cl2 (40 mL) at 0 °C under nitrogen was added triethylamine
(5.61 g, 7.7 mL, 55.49 mmol) followed by mesyl chloride (3.81 g,
33.29 mmol). After being stirred for 2 h at room temperature, the
reaction mixture was diluted with H2O, and extracted with CH2Cl2
(50 mL). The combined organic layers were washed with water,
brine and dried (Na2SO4). The solvent was removed under reduced
pressure and the crude product was used as such for the next step
without further purification.
75.8, 73.0, 72.7, 67.7, 55.1, 32.4 ppm. IR (CHCl ): ν = 3428, 3017,
˜
3
2957, 2935, 2868, 2401, 1612, 1586, 1513, 1464, 1422, 1249, 1216,
1083, 933, 849 cm–1. MS (ESI): m/z = 275 [M + Na]+. C14H20O4
1
(252.31): calcd. C 66.65, H 7.99; found C 66.58, H 8.04. H NMR
(200 MHz, CDCl3) of 15a: δ = 7.24 (d, J = 8.2 Hz, 2 H), 6.87 (d,
J = 8.2 Hz, 2 H), 4.47 (s, 2 H), 3.82 (s, 3 H), 3.69 (t, J = 5.6 Hz, 2
H), 3.66–3.64 (m, 1 H), 3.35 (dt, J = 4.7, 1.5 Hz, 1 H), 2.72 (br. s,
2 H), 1.89–1.74 (m, 2 H), 1.58–1.44 (m, 2 H), 0.99 (t, J = 7.4 Hz,
3 H) ppm.
To a solution of mesylate (7 g, 22.41 mmol) in toluene (50 mL)
were added DBU (3.75 g, 3.68 mL, 24.65 mmol). The reaction mix-
ture was heated to reflux for 4 h. The reaction was cooled to room
temperature and diluted with water and EtOAc. The two phases
were separated and the aqueous phase was extracted with EtOAc
(3ϫ100 mL). The combined organic phases were washed with
brine, dried (Na2SO4) and concentrated. Silica gel column
chromatography of the crude product using petroleum ether/EtOAc
(9:1) as eluent gave acetylide olefin 13 (3.97 g, 82%) as a colorless
syrup. 1H NMR (200 MHz, CDCl3): δ = 7.25 (d, J = 8.8 Hz, 2 H),
6.87 (d, J = 8.8 Hz, 2 H), 6.27 (dt, J = 7.3, 1.5 Hz, 1 H), 5.60–5.51
(m, 1 H), 4.45 (s, 2 H), 3.82 (s, 3 H), 3.50 (t, J = 6.6 Hz, 2 H), 2.81
(s, 1 H), 2.41 (q, J = 6.7 Hz 2 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 156.2, 142.9, 130.2, 129.2, 113.7, 110.3, 82.2, 76.1,
1-{[(3S,4S)-3,4-Bis(benzyloxy)hex-5-enyloxy]methyl}-4-methoxy-
benzene (16): To the above diol 15 (2 g, 7.93 mmol) in DMF
(10 mL) at 0 °C was added NaH (60% dispersion in mineral oil,
0.95 g, 23.78 mmol). After 15 min, benzyl bromide (3.25g, 2.3 Ml,
19.02 mmol) was introduced and the reaction mixture further
stirred for 4 h at room temperature. Water was carefully added to
the reaction mixture, extracted with diethyl ether, washed with
water and dried (Na2SO4). Silica gel column chromatography of
the crude product using petroleum ether/EtOAc (9:1) as eluent af-
forded dibenzyl compound 16 (2.91 g, 85%). [α]2D5 = –29.62 (c =
1
0.7 in CHCl3). H NMR (200 MHz, CDCl3): δ = 7.30–7.21 (m, 10
H), 7.13 (d, J = 8.7 Hz, 2 H), 6.79 (d, J = 8.7 Hz, 2 H), 5.84–5.67
(m, 1 H), 5.26–5.17 (m, 2 H), 4.63 (dd, J = 11.4, 8.2 Hz, 2 H),
4.44–4.35 (m, 2 H), 4.29 (s, 2 H), 3.83–3.77 (m, 1 H), 3.71 (s, 3 H),
3.67–3.47 (m, 1 H), 3.45–3.40 (m, 2 H), 1.70–1.56 (m, 2 H) ppm.
13C NMR (50 MHz, CDCl3): δ = 159.0, 138.8, 138.5, 135.3, 130.5,
129.2, 128.2, 128.1, 127.9, 127.8, 127.6, 127.4, 127.3, 118.6, 113.6,
72.6, 68.5, 55.2, 33.4 ppm. IR (CHCl ): ν = 3011, 2935, 2862, 2100,
˜
3
1719, 1612, 1586, 1514, 1465, 1422, 1363, 1249, 1173, 1095, 1035,
822, 757 cm–1. MS (ESI): m/z = 239 [M + Na]+. C14H16O2 (216.28):
calcd. C 77.75, H 7.46; found C 77.82, H 7.42.
82.6, 78.1, 73.4, 72.4, 70.4, 66.3, 55.1, 31.2 ppm. IR (CHCl ): ν =
˜
3
(3S,4S)-6-(4-Methoxybenzyloxy)hex-1-yne-3,4-diol (14): To a mix-
ture of K3Fe(CN)6 (11.42 g, 34.68 mmol), K2CO3 (4.79 g,
34.68 mmol) and (DHQ)2PHAL (90 mg, 1 mol-%), in tBuOH/H2O
(1:1, 60 mL) cooled to 0 °C was added OsO4 (0.46 mL, 0.1  in
toluene, 0.4 mol-%) followed by methane sulfonamide (1.10 g,
11.56 mmol). After stirring for 5 min at 0 °C, the olefin 13 (2.5 g,
11.56 mmol) was added. The reaction mixture was stirred at 0 °C
for 24 h and then quenched with solid sodium sulfite (17 g). The
stirring was continued for 45 min and the solution was extracted
with EtOAc (3ϫ50 mL). The combined organic phases were
washed with brine, dried (Na2SO4) and concentrated. Silica gel col-
umn chromatography of the crude product using petroleum ether/
EtOAc (3:2) as eluent gave diol 14 (2.72 g, 94%) in 94% ee as a
colorless syrup. [α]2D5 = +12.77 (c = 0.9 in CHCl3). 1H NMR
(200 MHz, CDCl3): δ = 7.23 (d, J = 8.4 Hz, 2 H), 6.86 (d, J =
3019, 2933, 2401, 1612, 1513, 1454, 1216, 1153, 1076, 992, 857, 758
cm–1. MS (ESI): m/z = 455 [M + Na]+. C28H32O4 (432.55): calcd.
C 77.75, H 7.46; found C 77.82, H 7.45.
(3S,4S)-3,4-Bis(benzyloxy)hex-5-en-1-ol (17): To a solution of 16
(2.5 g, 5.78 mmol) in CH2Cl2 (18 mL) and H2O (1 mL) at 0 °C was
added DDQ (1.57 g, 6.94 mmol) in portions. The resultant mixture
was stirred at room temperature for 0.5 h and then saturated aque-
ous NaHCO3 (10 mL) was added. The phases were separated and
the aqueous phase was extracted with CH2Cl2 (3 ϫ 50 mL). The
combined organic extracts were washed with brine, dried (Na2SO4)
and concentrated. Silica gel column chromatography of the crude
product using petroleum ether/EtOAc (7:3) as eluent afforded
alcohol 17 (1.68 g, 93%) as pale yellow oil. [α]2D5 = –19.90 (c = 1.38
in CHCl3). 1H NMR (200 MHz, CDCl3): δ = 7.26–7.20 (m, 10 H),
1200
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 1195–1202

An Efficient Total Synthesis of Decarestrictine D
5.86–5.68 (m, 1 H), 5.32–5.23 (m, 2 H), 4.70 (t, J = 11.4 Hz, 1 H),
4.57–4.51 (m, 2 H), 4.38 (d, J = 11.9 Hz, 1 H), 3.93 (t, J = 7.1 Hz,
1 H), 3.61–3.71 (m, 2 H), 1.62–1.41 (m, 2 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 138.2, 134.8, 128.4, 128.0, 127.9, 127.7,
3 H), 1.80–1.68 (m, 2 H), 1.65–1.58 (m, 2 H), 1.19 (d, J = 6.6 Hz, 3
H) ppm.
4-[(2-Methoxyethoxy)methoxy]hex-5-en-2-yl 3,4-Bis(benzyloxy)hex-5-
enoate (21): To a solution of acid 18 (500 mg, 1.53 mmol) in THF,
was added triethylamine (0.32 mL, 2.30 mmol) and 2, 4, 6-trichloro-
benzoyl chloride (0.36 mL, 2.30 mmol) under nitrogen atmosphere
at 0 °C and the reaction mixture was allowed to stir under this condi-
tion for 1 h. To this, alcohol 10 (0.31 g, 1.53 mmol) in THF (5 mL)
and catalytic amount of 4-(dimethylamino)pyridine (DMAP) were
added successively at 0 °C. Stirring was continued for additional 20
h at room temp. The reaction mixture was quenched with water and
extracted with ethyl acetate (3ϫ50 mL). The combined organic lay-
ers were thoroughly washed with saturated sodium hydrogen carbon-
ate solution, brine, dried (Na2SO4), and concentrated to afford the
crude product which was purified by silica gel column chromatog-
raphy using petroleum ether/EtOAc (9:1) to afford the ester 21
(0.70 g, 89%) as a colorless syrup. [α]D25 = –41.42 (c = 0.8 in CHCl3).
1H NMR (200 MHz, CDCl3): δ = 7.24–7.29 (m, 10 H), 5.76 (ddd, J
= 17.3, 10.0, 7.1 Hz, 1 H), 5.63 (dddd, J = 17.7, 10.0, 7.6, 5.5 Hz, 1
H), 5.35–5.12 (m, 4 H), 4.90 (s, 2 H), 4.74–4.69 (m, 1 H), 4.68–4.63
(m, 1 H), 4.60–4.54 (m, 2 H), 4.09–4.0 (m, 2 H), 3.95–3.89 (m, 2 H),
3.71–3.64 (m, 2 H), 3.51–3.44 (m, 2 H), 3.3 (s, 3 H), 2.67–2.47 (m,
2 H), 1.95–1.70 (m, 2 H), 1.19 (d, J = 6.3 Hz, 3 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 171.2, 138.5, 138.2, 137.8, 134.6, 129.5, 128.2,
127.5, 119.2, 117.5, 92.8, 81.2, 74.0, 73.3, 72.5, 71.7, 68.1, 67.1, 58.9,
119.1, 82.2, 78.6. 73.2, 70.6, 60.2, 33.2 ppm. IR (CHCl ): ν = 3377,
˜
3
3019, 2400, 1654, 1496, 1454, 1215, 1070, 993, 857, 759 cm–1. MS
(ESI): m/z = 335 [M + Na]+. C20H24O3 (312.4): calcd. C 76.89, H
7.74; found C 76.84, H 7.78.
(3S,4S)-3,4-Bis(benzyloxy)hex-5-enoic Acid (18): To a solution of
alcohol 17 (1.5 g, 4.80 mmol) in EtOAc (20 mL) was added IBX
(4.03g, 14.41 mmol) in one portion and the reaction mixture was
refluxed for 3 h. The reaction mixture was filtered through a pad
of Celite and filtrate was concentrated to give the crude aldehyde,
which was used for the next step without purification.
A solution of 79% NaClO2 (0.651 g, 7.20 mmol) in 1.0 mL of water
was added dropwise to a stirred solution of above crude aldehyde
(1.49 g, 4.80 mmol) in 0.5 mL of DMSO and NaH2PO4 (0.432 g,
3.6 mmol) in 1.0 mL of water in 5 min at room temperature. The
mixture was left overnight at room temperature, then 5% aqueous
solution of NaHCO3 was added. The aqueous phase was extracted
thrice with CH2Cl2 and washed with brine, dried (Na2SO4), and
concentrated. Silica gel column chromatography of the crude prod-
uct using petroleum ether/EtOAc (4:1) as eluent gave the acid 18
(1.25 g, 80%) as a syrup. [α]2D5 = –33.3 (c = 0.7 in CHCl3). 1H NMR
(200 MHz, CDCl3): δ = 7.33–7.28 (m, 10 H), 5.94–5.76 (m, 1 H),
5.40–5.32 (m, 2 H), 4.76 (d, J = 11.4 Hz, 2 H), 4.67 (d, J = 10.9 Hz,
1 H), 4.44 (d, J = 11.9 Hz, 1 H), 4.11–3.97 (m, 2 H), 2.70 (dd, J =
4.2 Hz, 1 H), 2.52 (dd, J = 8.2 Hz, 1 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 176.9, 138.1, 134.4, 128.3, 127.9, 127.7, 119.4, 81.01,
41.9, 36.7, 20.5 ppm. IR (CHCl ): ν = 3052, 2961, 2921, 1751, 1655,
˜
3
1478, 1373, 1216, 1144, 1097, 952, 874, 758 cm–1. MS (ESI): m/z =
535 [M + Na]+. C30H40O7 (512.63): calcd. C 70.29, H 7.86; found C
70.21, H 7.88.
(E)-4,5-Bis(benzyloxy)-8-[(2-methoxyethoxy)methoxy]-10-methyl-
4,5,9,10-tetrahydro-3H-oxecin-2(8H)-one (20). i) Yamaguchi Macro-
lactonization: To a solution of seco-acid 19 (0.150 g, 0.30 mmol) in
THF (4 mL) were added Et3N (0.10 mL, 0.75 mmol) and 2,4,6-tri-
chlorobenzoyl chloride (0.182 g, 0.75 mmol) and the reaction mix-
ture was stirred for 2 h at room temperature under argon atmosphere
and then diluted with benzene (150 mL). The resulting reaction mix-
ture was added dropwise to a solution of DMAP (0.273 g,
2.24 mmol) in benzene (20 mL) at 80 °C over 1 h and the mixture
was stirred for additional 1 h under reflux. The reaction mixture was
washed with aq. citric acid solution and brine. The organic layer was
dried (Na2SO4) and concentrated. Silica gel column chromatography
of the crude product using petroleum ether/EtOAc (3:2) as eluent
provided the lactone 20 (0.046 g, 32%) as a light yellow color thick
syrup. ii) RCM: A mixture of diene 21 (0.2 g, 0.39 mmol) and
Grubbs’ first-generation catalyst (0.065 g, 0.0078 mmol) in degassed
CH2Cl2 (50 mL) was stirred under reflux for 14 h. The reaction mix-
ture was evaporated and then purified on silica gel by eluting with
petroleum ether/EtOAc (4:1) to afford 20 (0.16 g, 82%) as a thick
syrup. [α]2D5 = –7.8 (c = 0.43 in CHCl3). 1H NMR (500 MHz,
CDCl3): δ = 7.29–7.36 (m, 10 H), 5.72 (dd, J = 15.8, 6.3 Hz, 1 H),
5.67 (dd, J = 15.8, 2.1 Hz, 1 H), 5.19–5.14 (m, 1 H), 4.81 (s, 2 H),
4.65 (d, J = 12.5 Hz, 1 H), 4.54 (d, J = 11.9 Hz, 1 H), 4.48 (d, J =
12.5 Hz, 1 H), 4.47 (d, J = 11.9 Hz, 1 H), 3.92–3.86 (m, 2 H), 3.76–
3.73 (m, 2 H), 3.72–3.69 (m, 2 H), 3.57–3.55 (m, 1 H), 3.40 (s, 3 H),
2.64 (dd, J = 15.2, 9.2 Hz, 2 H), 1.81–1.55 (m, 2 H), 1.19 (d, J =
6.4 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 178.5, 139.5,
132.8, 129.5, 128.3, 127.9, 127.5, 92.8, 81.1, 76.4, 74.1, 73.3, 70.7,
77.4, 75.9, 73.5, 36.2 ppm. IR (CHCl ): ν = 3305, 3019, 2976, 2401,
˜
3
1714, 1520, 1497, 1454, 1423, 1215, 1152, 1072, 993, 933, 854, 757
cm–1. MS (ESI): m/z = 349 [M + Na]+. C20H22O4 (326.39): calcd.
C 73.60, H 6.79; found C 73.48, H 6.74.
(3S,4S,7S,9R,E)-3,4-Bis(benzyloxy)-9-hydroxy-7-[(2-methoxyethoxy)-
methoxy]dec-5-enoic Acid (19): The acid 18 (0.100 g, 0.31 mmol)
was diluted with CH2Cl2 (20 mL) and degassed for fifteen minutes.
Alcohol 10 (0.125 g, 0.61 mmol) was then added to the reaction
flask followed by Grubbs’ second generation catalyst (26 mg,
0.03 mmol). The reaction was allowed to stir for 2 days under ar-
gon, at which time, it was allowed to oxidize by opening the reac-
tion to air and stirring overnight. The dark brown solution was
then concentrated. Silica gel column chromatography of the crude
product using petroleum ether/EtOAc (3:2) as eluent provided the
olefin 19 (0.83 g, 54%) as a light yellow color syrup. [α]2D5 = –23.05
1
(c = 1.40 in CHCl3). H NMR (200 MHz, CDCl3): δ = 7.26–7.32
(m, 10 H), 5.72 (dd, J = 16.2, 7.1 Hz, 1 H), 5.63 (dd, J = 16.2,
7.1 Hz, 1 H), 4.86 (s, 2 H), 4.67–4.74 (m, 2 H), 4.57–4.63 (m, 2 H),
3.73–3.95 (m, 1 H), 3.60–3.70 (m, 1 H), 3.47–3.55 (m, 2 H), 3.30–
3.39 (m, 4 H), 3.25 (s, 3 H), 2.46–2.68 (m, 2 H), 1.65–1.80 (m, 2
H), 1.18 (d, J = 6.6 Hz, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ
= 177.4, 138.5, 132.2, 129.5, 128.3, 127.9, 127.5, 92.8, 82.1, 74.0,
73.3, 72.5, 71.7, 70.7, 66.2, 62.3, 59.5, 47.0, 36.7, 23.8 ppm. IR
(CHCl ): ν = 3442, 3038, 2983, 2931, 1720, 1655, 1478, 1362, 1216,
˜
3
1149, 1084, 956 cm–1. C28H38O8 (502.60): calcd. C 66.91, H 7.62;
found C 66.97, H 7.64.
68.1, 60.1, 53.5, 47.4, 42.2, 29.6, 23.7 ppm. IR (CHCl ): ν = 3416,
˜
3
(5E,3S,4S,7S,9R)-7-[(2-Methoxyethoxy)methoxy]-3,4-bis(benzyloxy)-
dec-5-ene-1,9-diol (19a): Prepared by using the similar way as de-
scribed above for 19. 1H NMR (200 MHz, CDCl3): δ = 7.31–7.34
(m, 10 H), 5.70 (dd, J = 15.8, 7.0 Hz, 1 H), 5.64–5.59 (m, 1 H), 4.82
2952, 2931, 1728, 1362, 1236, 1046, 948, 869 cm–1. MS (ESI): m/z =
507 [M + Na]+. C28H36O7 (484.58): C 69.38, H 7.49; found C 69.27,
H 7.53.
(s, 2 H), 4.74–4.66 (m, 2 H), 4.59–4.52 (m, 2 H), 3.92–3.68 (m, 2 H), Decarestrictine D (1a): To a solution of 20 (0.150 g, 0.31 mmol) in
3.62–3.51 (m, 2 H), 3.48–3.39 (m, 2 H), 3.41–3.24 (m, 4 H), 3.23 (s, anhydrous CH2Cl2 (5 mL) under nitrogen at 0 °C was added TiCl4
Eur. J. Org. Chem. 2008, 1195–1202
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1201

P. Gupta, P. Kumar
FULL PAPER
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(0.587 g, 0.34 mL, 3.1 mmol). After 30 min, excess of reagent was
quenched with water, extracted with CH2Cl2, washed with water,
dried (Na2SO4), evaporated. The reaction mixture was purified on
silica gel by eluting with EtOAc to afford decarestrictine D (1a)
(52 mg, 78%) as a light yellow color solid. [α]2D5 –63.7 (c = 0.46 in
CHCl3); ref.[1b] [α]2D0 = –62.0 (c = 0.4, in CHCl3); m.p. 116–118 °C
(ref.[1b] m.p. 114–115 °C). 1H NMR (500 MHz, CDCl3): δ = 5.92
(dd, J = 15.9, 7.6 Hz, 1 H), 5.85 (dd, J = 15.9, 2.7 Hz, 1 H), 5.18–
5.14 (m, 1 H), 4.77 (br. s, 1 H), 4.43 (dd, J = 3.7, 1.6 Hz, 1 H), 4.21
(m, 1 H), 3.91 (br. s, 1 H), 2.63 (dd, J = 14.4, 1.9 Hz, 1 H) 2.42 (dd,
J = 14.4, 6.4 Hz, 1 H), 1.94–1.84 (m, 2 H), 1.55 (br. s, 2 H), 1.23 (d,
J = 6.6 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 174.9,
133.7, 129.7, 73.9, 72.5, 72.2, 66.3, 43.1, 33.2, 21.3 ppm. IR (CHCl3):
[9]
[10]
ν = 3422, 2952, 2926, 2845, 1712, 1146, 1042, 969 cm–1. MS (ESI):
˜
m/z = 239 [M + Na].
[11]
[12]
Acknowledgments
P. G. thanks the University Grants Commission (UGC), New Delhi
for financial assistance. We are grateful to Dr. Ganesh Pandey for
his support and encouragement. Financial support from the Depart-
ment of Science and Technology (DST), New Delhi (Grant No. SR/
S1/OC-40/2003) is gratefully acknowledged.
The diastereomeric excess of diol 5 was determined by its 1H
[13]
[14]
and 13C NMR spectroscopic data.
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[19]
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Received: September 13, 2007
Published Online: January 3, 2008
1202
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 1195–1202