Stereoselective approaches to the total synthesis of (6R,4′S, 6′R)-cryptofolione

Article abstract of DOI:10.1055/s-0030-1258215

Total syntheses of cryptofolione were accomplished by two different routes via a common intermediate that underwent a cross-metathesis (CM) reaction with a vinyl lactone. The intermediate was prepared by coupling of an acyl anion equivalent with a chiral allyl epoxide synthon, or by Prins cyclization of a trans-cinnamaldehyde with a chiral homoallylic alcohol. Goniothalamin was obtained as a cross-metathesis product of the diacetate and vinyl lactone. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1258215

PAPER
3453
Stereoselective Approaches to the Total Synthesis of
(6R,4¢S,6¢R)-Cryptofolione
Total
S
yntheses of
o
C
ryptofolion
w
e
ravaram Sabitha,* S. Siva Sankara Reddy, D. Vasudeva Reddy, Vangala Bhaskar, Jhillu S. Yadav
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)27160512; E-mail: gowravaramsr@yahoo.com; E-mail: sabitha@iict.res.in
Received 4 June 2010; revised 23 June 2010
O
Abstract: Total syntheses of cryptofolione were accomplished by
two different routes via a common intermediate that underwent a
cross-metathesis (CM) reaction with a vinyl lactone. The intermedi-
ate was prepared by coupling of an acyl anion equivalent with a
chiral allyl epoxide synthon, or by Prins cyclization of a trans-cin-
namaldehyde with a chiral homoallylic alcohol. Goniothalamin was
obtained as a cross-metathesis product of the diacetate and vinyl
lactone.
OH OH
O
6
6'
4'
7'
1'
cryptofolione (6R,4'S,6'R)-1
O
OH OH
O
Key words: lactones, total synthesis, heterocycles, cyclizations,
cryptofolione
(6S,4'S,6'R)-2
O
The a,b-unsaturated d-lactone core unit (or 5,6-dihydro-
2H-pyran-2-one moiety] is present in a variety of natural
products.1,2 Some of these compounds display important
biological activities including antitumor activity.3 One
such lactone is cryptofolione, a 6-(w-aralkenyl)-5,6-dihy-
dro-a-pyrone isolated from the branches, leaves, and stem
bark of two species of Cryptocarya (Lauraceae), C. myr-
tifolia and C. moschata, which are indigenous to South
Africa and Brazil, respectively.4,5 The structure of crypto-
folione was elucidated on the basis of its circular dichro-
ism and 13C NMR spectra. C. moschata is an important
food plant for primates such as the wooly spider monkey
(Brachyteles arachnoids). Later, cryptofolione was also
isolated from the fruits of C. alba, and its structure was
confirmed by spectroscopic methods.6 Cryptofolione is
active against the trypomastigotes of Trypanosoma cruzi,
reducing their number by 77% at 250 mg/mL; it is also
moderately cytotoxic to both macrophages and T. cruzi
amastigotes, and it displays a mild inhibitory effect on the
promastigote form of Leishmania species.
OH OH
O
(6R,4'R,6'S)-3
Figure 1 The absolute stereochemistry of cryptofolione
The main structural features of cryptofolione 1 are an anti
1,3-diol, two double bonds in the 1¢- and 7¢- positions, and
a 6-substituted 5,6-dihydro-a-pyrone subunit. In the re-
ported method for the synthesis of cryptofolione, the three
chiral centers in 1 were fixed by means of two successive
asymmetric hetero-Diels–Alder reactions of a Danishefsky
diene with aldehydes by using second-generation salen
complexes of chromium as catalysts.7
As a continuation of our interest on the synthesis of bioac-
tive lactones,8 we report two different strategies for the to-
tal synthesis of cryptofolione 1 that involve fewer steps
than the original method. A retrosynthetic analysis
(Scheme 1) suggested that the key intermediate 4 in route
a might be synthesized by coupling of the acyl anion
equivalent 7 with the chiral allyl epoxide 8, whereas for
route b, the analysis suggested that compound 4 might be
prepared by a Prins cyclization of trans-cinnamaldehyde
(10) with the homoallylic alcohol 11. Finally, the target
molecule 1 should be obtainable by a cross-metathesis re-
action of 4 with the vinyl lactone 5.8p,t
Cryptofolione could be one of two possible stereoisomers
(1 and 2; Figure 1). To determine the absolute configura-
tion of cryptofolione, compounds 1 and 3 (an enantiomer
of 2) were synthesized in an enantioselective manner by
using an asymmetric hetero-Diels–Alder reaction as the
key step.7 A comparison of the 1H and 13C NMR spectra,
CD spectra, and specific rotations of the synthetic com-
pounds with those reported in the literature established
unequivocally that cryptofolione has the absolute config-
uration 1 (6R,4¢S,6¢R).
We began our synthesis of intermediate 4 by route a
(Scheme 2) from commercially available trans-cinnamal-
dehyde (10). The aldehyde 10 was transformed into the
thioacetal 7 in 85% yield by treatment with propane-1,3-
dithiol in the presence of boron trifluoride etherate as a
catalyst in dichloromethane.9 Coupling of the known allyl
epoxide 8 [prepared in one-step from (S)-epichlorohy-
SYNTHESIS 2010, No. 20, pp 3453–3460
x
x.
x
x
.
2
0
1
0
Advanced online publication: 17.08.2010
DOI: 10.1055/s-0030-1258215; Art ID: Z14410SS
© Georg Thieme Verlag Stuttgart · New York

3454
G. Sabitha et al.
PAPER
O
O
OH OH
O
O
O
O
+
4
5
cryptofolione (1)
OH
O
O
OMOM
I
6
9
route b
route a
S
CHO
CHO
O
OH
S
+
HO
+
10
7
8
10
11
Scheme 1 Retrosynthetic analysis for cryptofolione (1)
drin]10 with the acyl anion equivalent 7 through metala- dane, potassium carbonate/iodomethane, mercury(II)
tion at –78 °C with one equivalent of butyllithium in the chloride/calcium carbonate, or cerium(IV) ammonium ni-
presence of boron trifluoride etherate gave the dithioketal trate/aqueous acetonitrile, failed to give the hydroxy ke-
12 in 75% yield. Attempts to deprotect the dithioketal 12 tone 13; however, by using mercury(II) perchlorate
under various conditions,11 such as diacetyl(phenyl)-l3-io- hydrate/calcium carbonate,12 the thioketal was deprotect-
OH
S
S
S
a
O
b
+
S
7
8
12
O
O
OH
H
H
O
13
14
O
OMOM
OMOM
S
S
c
b
12
15
6
OH OH
OH OMOM
e
d
16
17
O
O
f
4
Scheme 2 Reagents and conditions: (a) BuLi, BF3·OEt2, anhyd THF, –78 °C, 1 h, 75%; (b) Hg(ClO4)2·×H2O), THF–H2O (5:1), CaCO3, 0 °C,
0.5 h, 85%; (c) MOMCl, DIPEA, CH2Cl2, 0 °C to r.t. 0.5 h, 92%; (d) S-CBS catalyst, toluene, BH3·DMS, 0 °C, 0.5 h, 78%, 98% de; (e)
CeCl3·7H2O, MeCN–MeOH (1:1), reflux, 6 h, 91%; (f) Me2C(OMe)2, PPTS, CH2Cl2, 0 °C, 20 min, 89%.
Synthesis 2010, No. 20, 3453–3460 © Thieme Stuttgart · New York

PAPER
Total Syntheses of Cryptofolione
3455
OH
O
ed to give 13. This hydroxy ketone underwent cyclization
onto the double bond in situ to give the pyranone 14,
which was characterized by means of 1H NMR and mass
spectroscopy (further studies on this core unit will be re-
ported in a separate publication). The free hydroxy group
in dithioketal 12 was therefore protected by formation of
its methoxymethyl ether 15, and this was subjected to
deprotection of the thioketal with mercury(II) perchlorate
hydrate to give the required ketone 6 in 85% yield. Dia-
stereoselective reduction13 of the ketone group was
achieved by using the S-form of the Corey–Bakshi–Shibata
catalyst (S-CBS) with borane–dimethyl sulfide adduct at
CHO
OH
a
+
OH
HO
18
10
11
OH
OH
I
OTs
c
b
O
O
19
9
1
0 °C to give the protected anti-diol 16 in 78% yield. H
NMR analysis showed that the diastereomeric purity of
the product (de) was >95%. Removal of the methoxy-
methyl group by using cerium(III) chloride heptahydrate
in acetonitrile–methanol (1:1) gave the diol 17. The rela-
tive stereochemistry of the 1,3-diol system in 17 was de-
termined by using Rychnovsky’s acetonide method.14
Thus, treatment of diol 17 with 2,2-dimethoxypropane
and pyridinium p-toluenesulfonate in dichloromethane
gave the anti-acetonide 4. The anti relationship of the two
hydroxy groups in 4 was confirmed by the appearance in
the 13C NMR spectrum of the resonances for methyl car-
bons at d = 24.8 and 25.5 ppm and for the acetal carbon at
d = 100.4 ppm.
OH OH
d
17
Scheme 3 Reagents and conditions: (a) (i) TFA, CH2Cl2, 0 °C to
r.t., 4 h; (ii) K2CO3, MeOH, r.t., 0.5 h, 55% (two steps); (b) TsCl,
Et3N, CH2Cl2, Bu2SnO (cat.), DMAP (cat.), 0 °C to r.t., 4 h, 90%;
(c) NaI, acetone, reflux, 7 h, 89%; (d) Zn dust, EtOH, reflux, 2 h, 85%.
firmed from its mass spectrum. However, to our surprise,
the cross-metathesis reaction of the diacetate 2017 with vi-
nyl lactone 5 gave (R)-(+)-goniothalamin (21) in 80%
yield, along with traces of the vinyl lactone homodimer-
ized product (1–2%). The structure of 21 was established
by spectroscopy and by comparison with an authentic
sample that we had previously prepared.8d
In route b, cryptofolione was synthesized stereoselective-
ly by means of a Prins cyclization (Scheme 3). Prins cy-
clization of the chiral homoallylic alcohol 118r,s with
trans-cinnamaldehyde (10) in the presence of trifluoro-
acetic acid, followed by hydrolysis of the resulting tri-
fluoroacetate, gave trisubstituted pyran 18. The
stereochemistry was assumed to be that shown in the
scheme, as this has been well examined and previously es-
tablished.8r,s,15 (This was later proved to be the case by the
conversion of the compound 18 into the target molecule 1,
which was identical to the reported compound in all re-
spects.) Tosylation of 18 with 1.1 equivalents of tosyl
chloride in the presence of triethylamine and catalytic
amounts of dibutyltin(IV) oxide and 4-(N,N-dimethylami-
no)pyridine in dichloromethane gave the corresponding
primary tosylate 19 in 90% yield. Treatment of tosylate 19
with sodium iodide in refluxing acetone gave the corre-
sponding iodomethyl derivative 9, which on treatment
with nonactivated zinc in refluxing ethanol gave the open-
chain key intermediate 17 with the anti-1,3-diol system in
85% yield. The properties of 17 exactly matched those of
the sample of 17 prepared by route a, and both were dia-
stereomerically pure (<95% de) and could be carried over
to the next reaction.
However, the cross-metathesis reaction of acetonide-
protected compound 4 with vinyl lactone 5 in the presence
of Grubbs’ second-generation catalyst in refluxing dichlo-
romethane gave the desired cross-coupled product 22 in
good yield (87%), along with a small amount of the vinyl
lactone homodimerized product (4%) (Scheme 5).
Several attempts to remove the acetonide group from the
cross-coupled product 22 failed to give the target mole-
cule 1, as shown in Table 1.
Table 1 Attempts to Remove the Acetonide Group from Compound
22 under Various Conditions
Catalyst
PTSA
PPTS
Solvent
MeOH
MeOH
CH2Cl2
Temp (°C) Remarks
0
0
0
decomposed
decomposed
decomposed
PTSA
Fortunately, however, treatment with aqueous 4% hydro-
gen chloride at 0 °C did give cryptofolione (1) in 93%
yield. The spectral and analytical data for the synthetic
sample of 1 agreed well with the reported data for natural
cryptofolione.
The stage was now set to prepare cryptofolione (1) by an
olefin cross-metathesis reaction. However, the cross-
metathesis reaction16 between the homoallylic alcohol 17
and the known vinyl lactone 58p,t in the presence of
Grubbs’ second-generation catalyst or Hoveyda’s catalyst
in dichloromethane gave only the product from ho-
modimerization of the vinyl lactone in 90% yield within
15 min (Scheme 4); the nature of the product was con-
In conclusion, a convergent synthesis of cryptofolione (1)
was devised by utilizing two different strategies. These
protocols represent a second synthesis of cryptofolione
Synthesis 2010, No. 20, 3453–3460 © Thieme Stuttgart · New York

3456
G. Sabitha et al.
PAPER
O
O
OH OH
O
O
a
+
2
17
5
homodimer
O
O
OAc OAc
O
b
O
+
21
20
5
N
N
N
N
Cl
Cl
Ru
Ru
Cl
Cl
Ph
P
O
Hoveyda catalyst
Grubbs II catalyst
Scheme 4 Reagents and conditions: (a) Grubbs II catalyst or Hoveyda catalyst (10 mol%), CH2Cl2, reflux, 15 min, 90%; (b) Grubbs II catalyst
(10 mol%), CH2Cl2, reflux, 4 h, 80%.
O
O
O
O
O
O
O
O
a
+
22
4
5
O
OH OH
O
b
1
Scheme 5 Reagents and conditions: (a) Grubbs II catalyst (10 mol%), CH2Cl2, reflux, 6 h, 87%; (b) aq 4% HCl, MeCN, 0 °C, 0.5 h, 93%.
(2S)-1-{2-[(E)-2-Phenylvinyl]-1,3-dithian-2-yl}pent-4-en-2-ol
(12)
(1) by a short route that also provides access to the natural
product goniothalamin (21).
A 2.5 M soln of BuLi in hexane (2.85 mL, 7.13 mmol) was added
to a soln of dithiane 7 (300 mg, 3.57 mmol) and epoxide 8 (1.03 g,
4.63 mmol) in anhyd THF (20 mL) at –78 °C under N2, and the mix-
ture was stirred for 25 min. A soln of BF3·OEt2 (0.23 mL) in anhyd
THF (2 mL) was then added dropwise. After 1 h, the reaction was
quenched by slow addition of MeOH (0.2 mL) followed by sat. aq
NH4Cl (2 mL). The mixture was then extracted with CH2Cl2 (3 × 10
mL). The extracts were washed with brine, dried (Na2SO4), filtered,
and concentrated. The residue was purified by flash column chro-
matography [silica gel, PE–EtOAc (8:2)] to give a colorless oil;
Reactions were conducted under N2 in anhyd solvents such as
CH2Cl2, THF, or toluene. All reactions were monitored by TLC us-
ing silica-coated plates that were visualized under UV radiation. PE
(bp 60–80 °C) was used. Yields refer to chromatographically and
spectroscopically (1H and 13C NMR) homogeneous material. Air-
sensitive reagents were transferred by syringe or double-ended nee-
dle. Evaporation of solvents was performed at reduced pressure on
a Buchi rotary evaporator. 1H and 13C NMR spectra of samples in
CDCl3 were recorded on Varian FT-200MHz (Gemini) and Bruker
UXNMR FT-300MHz (Avance) spectrometers. Chemical shifts (d)
are reported relative to TMS (d = 0.0) as an internal standard. Mass
spectra were recorded EI conditions at 70 eV on an LC-MSD (Agi-
lent Technologies) spectrometer. Column chromatography was per-
formed on silica gel (60–120 mesh; Acme Chemical Co., India).
TLC was performed on Merck 60 F-254 silica gel plates. Optical ro-
tations were measured with a Jasco DIP-370 polarimeter at 20 °C.
25
yield: 817 mg (75%); [a]D +12.0 (c 0.25, CHCl3); Rf = 0.6 (PE–
EtOAc, 8:2).
IR (neat): 3449, 3071, 2920, 1639, 1421, 1275, 1062, 972, 913, 748,
694 cm–1.
1H NMR (CDCl3, 400 MHz): d = 7.43–7.18 (m, 5 H), 6.81 (d, J =
15.8 Hz, 1 H), 6.24 (d, J = 15.8 Hz, 1 H), 5.86–5.75 (m, 1 H), 5.12–
Synthesis 2010, No. 20, 3453–3460 © Thieme Stuttgart · New York

PAPER
Total Syntheses of Cryptofolione
ESIMS: m/z = 283 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C16H20NaO3: 283.1310; found:
283.1307.
3457
5.06 (m, 2 H), 4.11–4.01 (m, 1 H), 2.98–2.89 (m, 2 H), 2.81–2.72
(m, 2 H), 2.48–2.45 (br s, 1 H, OH), 2.28–1.90 (m, 6 H).
13C NMR (CDCl3, 75 MHz): d = 136.1, 134.4, 133.1, 132.5, 128.7,
128.0, 126.6, 117.9, 67.7, 48.4, 42.1, 29.7, 27.4, 27.1, 24.9.
(1E,3R,5S)-5-(Methoxymethoxy)-1-phenylocta-1,7-dien-3-ol
(16)
LCMS: m/z = 329 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C17H22NaOS2: 329.1009; found:
A soln of BH3·DMS (2 M in THF; 0.76 mL, 1.52 mmol) was added
to a soln of S-CBS catalyst (1 M in toluene; 0.15 mL, 0.15 mmol) in
toluene (2 mL) at 0 °C, and the mixture was stirred for 0.5 h. A con-
cd soln of dienone 6 (400 mg, 1.53 mmol) in toluene (0.5 mL) was
added, and the mixture was stirred for 0.5 h at 0 °C. The reaction
was then quenched with MeOH (1 mL) and the mixture was allowed
to warm to r.t. The solvent was then removed under reduced pres-
sure and the residue was purified by column chromatography [silica
gel, PE–EtOAc (7:3)] to give a colorless liquid; yield: 314 mg
(78%); [a]D25 +31.7 (c 0.5, CHCl3); Rf = 0.6 (PE–EtOAc, 7:3).
329.1002.
(2S)-2-Allyl-6-phenyltetrahydro-4H-pyran-4-one (14)
A soln of enol 12 (70 mg, 0.22 mmol) and CaCO3 (45 mg, 0.45
mmol) in 5:1 THF–H2O (5 mL) was treated with Hg(ClO4)2·×H2O
(9 mg, 0.02 mmol) for 0.5 h at 0 °C. The mixture was then diluted
with Et2O (20 mL) and filtered through Celite. Concentration of the
filtrate followed by flash chromatography [silica gel, PE–EtOAc
(8:2)] gave a colorless liquid; yield: 41 mg (85%); Rf = 0.4 (PE–
EtOAc, 8:2).
IR (neat): 3446, 2926, 1641, 1445, 1147, 1036, 969, 916, 749, 694
cm–1.
IR (neat): 2923, 2853, 1734, 1453, 1229, 1055, 918, 757, 698 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.36–7.12 (m, 5 H), 5.97–5.72 (m,
1 H), 5.22–5.08 (m, 2 H), 4.50–4.35 (m, 1 H), 3.40–3.08 (m, 1 H),
2.94–2.65 (m, 2 H), 2.61–2.32 (m, 2 H), 2.18–1.95 (m, 2 H).
LCMS: m/z = 239 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C14H16NaO2: 239.1047; found:
1H NMR (CDCl3, 300 MHz): d = 7.36–7.14 (m, 5 H), 6.58 (d, J =
15.8 Hz, 1 H), 6.16 (dd, J = 15.8, 6.0 Hz, 1 H), 5.85–5.70 (m, 1 H),
5.13–5.04 (m, 2 H), 4.75 (d, J = 6.7 Hz, 1 H), 4.64 (d, J = 6.7 Hz, 1
H), 4.48–4.39 (m, 1 H), 3.94–3.83 (m, 1 H), 3.41 (s, 3 H), 2.40–2.32
(m, 2 H), 1.88–1.65 (m, 2 H).
13C NMR (CDCl3, 75 MHz): 136.8, 134.1, 132.1, 129.4, 128.5,
127.4, 126.3, 117.7, 96.3, 74.9, 68.8, 55.8, 41.4, 39.4.
239.1039.
LCMS: m/z = 285 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C16H22NaO3: 285.1466; found:
2-[(2S)-2-(Methoxymethoxy)pent-4-en-1-yl]-2-[(E)-2-phenylvi-
nyl]-1,3-dithiane (15)
DIPEA (1.18 mL, 9.14 mmol) and MOMCl (0.36 mL, 4.5 mmol)
were added sequentially to a cooled (0 °C) soln of enol 12 (700 mg,
2.28 mmol) in CH2Cl2 (10 mL), and the mixture was stirred at r.t.
for 0.5 h. The solvent was evaporated and the residue was purified
by column chromatography [silica gel, PE–EtOAc (8:2)] to give a
colorless liquid; yield: 736 mg (92%); [a]D25 +19.4 (c 0.5, CHCl3);
Rf = 0.75 (PE–EtOAc, 8:2).
285.1479.
(1E,3R,5S)-1-Phenylocta-1,7-diene-3,5-diol (17)
CeCl3·7H2O (3.98 g, 10.68 mmol) was added to a stirred soln of di-
enol 16 (280 mg, 1.06 mmol) in a mixture of MeOH (5 mL) and
MeCN (5 mL) under N2, and the mixture was stirred for 6 h at the
reflux temperature. The reaction was quenched with solid NaHCO3
(4.0 g) and the mixture was filtered. The solvent was removed under
reduced pressure, and the residue was purified by column chroma-
tography [silica gel, PE–EtOAc (7:3)] to give a colorless oil; yield:
211 mg (91%); [a]D25 +32.0 (c 0.25, CHCl3); Rf = 0.4 (PE–EtOAc,
7:3).
IR (neat): 2925, 1443, 1151, 1038, 915, 747, 694 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.42–7.17 (m, 5 H), 6.77 (d, J =
15.8 Hz, 1 H), 6.19 (d, J = 15.8 Hz, 1 H), 5.88–5.70 (m, 1 H), 5.10–
5.02 (m, 2 H), 4.65 (d, J = 6.8 Hz, 1 H), 4.49 (d, J = 6.8 Hz, 1 H),
3.91–3.81 (m, 1 H), 3.30 (s, 3 H), 3.00–2.83 (m, 2 H), 2.73–2.59 (m,
2 H), 2.40–2.27 (m, 2 H), 2.18–1.81 (m, 4 H).
IR: 3370, 3075, 2924, 1641, 1443, 1066, 968, 917, 748, 694 cm–1.
13C NMR (CDCl3, 75 MHz): d = 136.4, 134.1, 132.9, 132.5, 128.6,
127.7, 126.5, 117.8, 96.5, 74.5, 55.7, 53.7, 47.2, 40.9, 27.2 (d, 2 C),
25.1.
1H NMR (CDCl3, 300 MHz): d = 7.36–7.16 (m, 5 H), 6.61 (d, J =
15.8 Hz, 1 H), 6.24 (dd, J = 15.8, 6.0 Hz, 1 H), 5.88–5.72 (m, 1 H),
5.18–5.09 (m, 2 H), 4.65–4.57 (m, 1 H), 4.06–3.95 (m, 1 H), 2.32–
2.19 (m, 2 H), 1.81–1.70 (m, 2 H).
LCMS: m/z = 373 [M + Na]+.
13C NMR (CDCl3, 75 MHz): d = 136.6, 134.3, 131.9, 129.8, 128.5,
HRMS: m/z [M + Na]+ calcd for C19H26NaO2S2: 373.1271; found:
373.1286.
127.6, 126.4, 118.4, 70.3, 68.1, 42.1 (2 C).
LCMS: m/z = 241 [M + Na]+.
(1E,5S)-5-(Methoxymethoxy)-1-phenylocta-1,7-dien-3-one (6)
A soln of the dithiane 15 (700 mg, 1.99 mmol) and CaCO3 (399 mg,
3.99 mmol) in 5:1 THF–H2O (10 mL) was treated with
Hg(ClO4)2·×H2O (79 mg, 0.19 mmol) for 0.5 h at 0 °C. The mixture
was then diluted with Et2O (70 mL) and filtered through Celite.
Concentration of the filtrate followed by flash chromatography [sil-
ica gel, PE–EtOAc (7:3)] gave a colorless liquid; yield: 441 mg,
(85%); [a]D25 –14.5 (c 0.55, CHCl3); Rf = 0.7 (PE–EtOAc, 7:3).
HRMS: m/z [M + Na]+ calcd for C14H18NaO2: 241.1204; found:
241.1206.
(4S,6R)-4-Allyl-2,2-dimethyl-6-[(E)-2-phenylvinyl]-1,3-diox-
ane (4)
Me2C(OMe)2 (0.07 mL, 0.48 mmol) and a catalytic amount of PPTS
were added to a soln of diol 17 (60 mg, 0.27 mmol) in anhyd CH2Cl2
(3 mL), and the mixture was stirred at r.t. for 20 min. Aq NaHCO3
was then added to neutralize the PPTS and the mixture was filtered
and concentrated. The residue was purified by column chromatog-
raphy [silica gel, PE–EtOAc (9:1)] to give a clear liquid; yield: 63
mg (89%); [a]D25 +45.5 (c 0.85, CHCl3); Rf = 0.6 (PE–EtOAc, 9:1).
IR: 2926, 1642, 1376, 1223, 1072, 968, 747 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.35–7.14 (m, 5 H), 6.51 (d, J =
15.8 Hz, 1 H), 6.17 (dd, J = 15.8, 6.0 Hz, 1 H), 5.87–5.71 (m, 1 H),
IR (neat): 2926, 1659, 1610, 1448, 1331, 1038, 917, 751 cm–1.
1H NMR (CDCl3, 500 MHz): d = 7.55–7.34 (m, 6 H), 6.71 (d, J =
16.0 Hz, 1 H), 5.88–5.78 (m, 1 H), 5.16–5.06 (m, 2 H), 4.63 (q, J =
6.7 Hz, 2 H), 4.25–4.18 (m, 1 H), 3.32 (s, 3 H), 2.94 (dd, J = 16.0,
7.5 Hz, 1 H), 2.68 (dd, J = 16.0, 5.0 Hz, 1 H), 2.37 (t, J = 6.7 Hz, 2
H).
13C NMR (CDCl3, 75 MHz): d = 198.4, 142.9, 134.4, 134.0, 130.5,
128.9, 128.3, 126.6, 117.9, 95.9, 73.6, 55.6, 45.5, 39.3.
Synthesis 2010, No. 20, 3453–3460 © Thieme Stuttgart · New York

3458
G. Sabitha et al.
PAPER
(2S,4R,6R)-2-(Iodomethyl)-6-[(E)-2-phenylvinyl]tetrahydro-
5.13–5.00 (m, 2 H), 4.52–4.41 (m, 1 H), 3.97–3.86 (m, 1 H), 2.38–
2.14 (m, 2 H), 1.88–1.69 (m, 2 H), 1.37 (d, J = 7.5 Hz, 6 H).
2H-pyran-4-ol (9)
NaI (463 mg, 3.08 mmol) was added to a soln of tosylate 19 (120
mg, 0.30 mmol) in acetone (20 mL), and the mixture was refluxed
for 7 h. The acetone was evaporated H2O (8 mL) and EtOAc (20
mL) were added to the residue. The organic layer was dried
(Na2SO4) and concentrated, and the residue was purified by column
chromatography [silica gel, PE–EtOAc (1:1)] to give a white solid;
yield: 94 mg (89%); mp 105–107 °C; [a]D25 +49.3 (c 0.8, CHCl3);
Rf = 0.8 (PE–EtOAc, 1:1).
13C NMR (CDCl3, 75 MHz): d = 136.7, 134.2, 130.4, 129.8, 128.5,
127.6, 126.4, 117.1, 100.4, 67.8, 66.0, 25.5, 24.8, 40.2, 37.4.
LCMS: m/z = 281 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C17H22NaO2: 281.1517; found:
281.1521.
(2S,4R,6R)-2-(Hydroxymethyl)-6-[(E)-2-phenylvinyl]tetrahy-
dro-2H-pyran-4-ol (18)
IR (KBr): 3357, 2946, 1653, 1455, 1364, 1187, 1043, 965, 748, 693
cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.38–7.15 (m, 5 H), 6.59 (d, J =
15.8 Hz, 1 H), 6.16 (dd, J = 15.8, 6.0 Hz, 1 H), 4.09–3.98 (m, 1 H),
3.97–3.80 (m, 1 H), 3.50–3.38 (m, 1 H), 3.32–3.17 (m, 2 H), 2.30–
2.21 (m, 1 H), 2.08–1.98 (m, 1 H), 1.42–1.14 (m, 2 H).
13C NMR (CDCl3, 75 MHz): d = 136.5, 130.8, 128.7, 128.5, 127.7,
126.5, 76.2, 74.9, 67.6, 40.7, 40.5, 8.6.
LCMS: m/z = 367 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C14H17IO2Na: 367.0171; found:
TFA (1.5 mL, 19.56 mmol) was added slowly to a soln of dioxane
11 (100 mg, 0.98 mmol) and trans-cinnamaldehyde (10; 323 mg,
2.44 mmol) in CH2Cl2 (20 mL) at r.t. under N2. The mixture was
stirred for 4 h before sat. aq NaHCO3 (20 mL) was added and the
pH was adjusted to >7 by addition of Et3N. The aqueous layer was
extracted with CH2Cl2 (4 × 10 mL) and the combined organic phase
was concentrated. The residue was dissolved in MeOH (15 mL) and
stirred with K2CO3 (3.2 g) for 0.5 h. The MeOH was then evaporat-
ed and H2O (5 mL) was added. The mixture was extracted with
CH2Cl2 (3 × 20 mL) and the combined organic phase was dried
(Na2SO4) and concentrated. The residue was purified by column
chromatography [silica gel, PE–EtOAc (1:1)] to give a gummy liq-
367.0157.
25
uid; yield: 125 mg (55%); [a]D +25.5 (c 0.35, CHCl3); Rf = 0.2
(1E,3R,5S)-1-Phenylocta-1,7-diene-3,5-diol (17)
(PE–EtOAc, 1:1).
Commercial Zn dust (133 mg, 2.03 mmol) was added to a soln of
iodide 9 (70 mg, 0.20 mmol) in EtOH (10 mL), and the mixture was
refluxed for 2 h then cooled to 25 °C. Addition of solid NH4Cl (150
mg) and Et2O (30 mL) followed by stirring for 5 min gave a gray
suspension. The suspension was filtered through Celite, and the fil-
trate was concentrated. The residue was purified by column chro-
matography [silica gel, PE–EtOAc (7:3)] to give a colorless oil;
yield: 37 mg (85%); Rf = 0.4 (PE–EtOAc, 7:3).
IR (neat): 3373, 2936, 1649, 1354, 1061, 970, 748, 693 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.36–7.17 (m, 5 H), 6.55 (d, J =
15.8 Hz, 1 H), 6.16 (dd, J = 15.8, 6.0 Hz, 1 H), 4.07–3.98 (m, 1 H),
3.96–3.80 (m, 1 H), 3.70–3.49 (m, 3 H), 1.73–1.54 (br s, 2 H, 2 ×
OH), 1.50–1.20 (m, 4 H).
13C NMR (CDCl3, 75 MHz): d = 136.4, 130.8, 129.1, 128.5, 127.7,
126.4, 76.2, 76.1, 67.5, 65.7, 41.0, 36.5.
The physical data for 17 exactly matched those of the sample of 17
prepared by route a.
LCMS: m/z = 257 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C14H18NaO3: 257.1153; found:
257.1157.
(1S,3R,4E)-3-(Acetyloxy)-1-allyl-5-phenylpent-4-en-1-yl Ace-
tate (20)
{(2S,4R,6R)-4-Hydroxy-6-[(E)-2-phenylvinyl]tetrahydro-2H-
pyran-2-yl}methyl Tosylate (19)
Pyridine (0.08 mL, 1.0 mmol) and Ac2O (0.05 mL, 0.54 mmol)
were added sequentially to a stirred soln of diol 17 (60 mg, 0.27
mmol) in anhyd CH2Cl2 (3 mL) at 0 °C. The mixture was stirred for
1 h and then diluted with CH2Cl2 (10 mL). The organic layer was
washed sequentially with 5% aq NaHCO3 (2 × 3 mL) and brine
(2 × 3 mL) then dried (Na2SO4) and concentrated under reduced
pressure. The residue was purified by column chromatography [sil-
ica gel, PE–EtOAc (8:2)] to give a colorless liquid; yield: 52 mg,
65%); [a]D25 +49.6 (c 0.95, CHCl3); Rf = 0.8 (PE–EtOAc, 8:2).
Et3N (0.09 mL, 0.59 mmol), Bu2SnO (cat.) and DMAP (cat.) were
added to a soln of diol 18 (100 mg, 0.42 mmol) in anhyd CH2Cl2
(5.0 mL) at 0 °C. TsCl (81 mg, 0.42 mmol) was then added over 1
h. The resulting mixture was allowed to warm to r.t., stirred for 3 h,
then treated with 1 M aq HCl (3 mL) and extracted with CH2Cl2
(3 × 30 mL). The organic layer was washed sequentially with sat. aq
NaHCO3 (5 mL) and H2O (5 mL), and the the combined organic
phase was dried (Na2SO4) and concentrated. The residue was puri-
fied by column chromatography [silica gel, PE–EtOAc (1:1)] to
IR (neat): 2922, 1738, 1371, 1240, 1022, 967, 749, 694 cm–1.
25
give a clear liquid; yield: 148 mg (90%); [a]D –2.0 (c 1.25,
CHCl3); Rf = 0.5 (PE–EtOAc, 1:1).
1H NMR (CDCl3, 300 MHz): d = 7.36–7.17, (m, 5 H), 6.59 (d, J =
15.8 Hz, 1 H), 6.06 (dd, J = 15.8, 7.1 Hz, 1 H), 5.82–5.65 (m, 1 H),
5.50–5.40 (m, 1 H), 5.14–4.98 (m, 3 H), 2.32 (t, J = 6.6 Hz, 2 H),
2.05 (s, 3 H), 2.0 (s, 3 H), 1.97–1.80 (m, 2 H).
13C NMR (CDCl3, 75 MHz): d = 170.5, 170.2, 136.1, 133.0, 132.6,
128.5, 128.0, 127.1, 126.5, 118.2, 70.7, 68.9, 39.1, 38.4, 21.2, 21.0.
LCMS: m/z = 325 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C18H22NaO4: 325.1415; found:
IR (neat): 3411, 2924, 1722, 1598, 1358, 1176, 975, 818, 753, 668
cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.79 (d, J = 8.1 Hz, 2 H), 7.35–
7.15 (m, 7 H), 6.47 (d, J = 15.8 Hz, 1 H), 6.06 (dd, J = 15.8, 5.6 Hz,
1 H), 4.16–3.75 (m, 4 H), 3.73–3.58 (m, 1 H), 2.41 (s, 3 H), 2.09–
1.89 (m, 2 H), 1.61 (br s, 1 H, OH), 1.40–1.11 (m, 2 H).
13C NMR (CDCl3, 75 MHz): d = 144.8, 136.5, 132.8, 130.6, 129.8,
128.7, 128.5, 128.0, 127.7, 126.4, 76.0, 72.9, 71.8, 67.4, 40.7, 36.6,
21.6.
325.1401.
(6R)-6-[(E)-2-Phenylvinyl]-5,6-dihydro-2H-pyran-2-one (21;
Goniothalamin)
A soln of Grubbs II catalyst (8 mg, 0.01 mmol) in CH2Cl2 (0.5 mL)
was added dropwise to a soln of diacetate 20 (30 mg, 0.09 mmol)
and lactone 5 (18 mg, 0.14 mmol) in CH2Cl2 (0.5 mL) at r.t. The
mixture was refluxed for 4 h, then the solvent was removed under
reduced pressure and the crude product was purified by column
LCMS: m/z = 411 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C21H24NaO5S: 411.1242; found:
411.1236.
Synthesis 2010, No. 20, 3453–3460 © Thieme Stuttgart · New York

PAPER
Total Syntheses of Cryptofolione
3459
chromatography [silica gel, PE–EtOAc (8:2)] to give a white solid;
yield: 15 mg (80%); mp 81–83 °C; [a]D +161.3 (c 1.7, CHCl3);
Rf = 0.3 (PE–EtOAc, 8:2).
Acknowledgment
25
S.S.S.R and D.V.R thank CSIR and V.B. thanks UGC, New Delhi,
for awards of fellowships.
IR (KBr): 2923, 1720, 1382, 1245, 1024, 966, 814, 750.
1H NMR (CDCl3, 300 MHz): d = 7.40–7.22 (m, 5 H), 6.94–6.86 (m,
1 H), 6.71 (d, J = 15.8 Hz, 1 H), 6.25 (dd, J = 15.8, 6.0 Hz, 1 H),
6.11–6.05 (m, 1 H), 5.12–5.04 (m, 1 H), 2.56–2.50 (m, 2 H).
13C NMR (CDCl3, 75 MHz): d = 163.8, 144.6, 135.7, 133.1, 128.6,
128.3, 126.6, 125.6, 121.6, 77.9, 29.8.
LCMS: m/z = 201 [M + H]+.
HRMS: m/z [M + H]+ calcd for C13H13O2: 201.0915; found:
References
(1) (a) Negishi, E.; Kotora, M. Tetrahedron 1997, 53, 6707.
For a review, see: (b) Collins, I. J. Chem. Soc., Perkin
Trans. 1 1999, 1377. (c) Boucard, V.; Broustal, G.;
Campagne, J. M. Eur. J. Org. Chem. 2007, 225. (d) Marco,
J. A.; Carda, M.; Murga, J.; Falomir, E. Tetrahedron 2007,
63, 2929 . For recent examples, see: (e) Pospíšil, J.; Markó,
I. E. Tetrahedron Lett. 2006, 47, 5933. (f) Gobbini, M.;
Cerri, A. Curr. Med. Chem. 2005, 12, 2343. (g) de Fátima,
Â.; Pilli, R. A. Tetrahedron Lett. 2003, 44, 8721. (h) de
Fátima, Â.; Pilli, R. A. ARKIVOC 2003, (x), 118.
(i) Bruckner, R. Curr. Org. Chem. 2001, 5, 679. (j) Job, A.;
Wolberg, M.; Muller, M.; Enders, D. Synlett 2001, 1796.
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Org. Chem. 2005, 2, 333. (b) Yet, L. Chem. Rev. 2003, 103,
4283. (c) Mereyala, H. B.; Joe, M. Curr. Med. Chem.: Anti-
Cancer Agents 2001, 1, 293.
201.0921.
(6R)-6-((1E)-3-{(4S,6R)-2,2-Dimethyl-6-[(E)-2-phenylvinyl]-
1,3-dioxan-4-yl}prop-1-en-1-yl)-5,6-dihydro-2H-pyran-2-one
(22)
A soln of Grubbs II catalyst (13 mg, 0.01 mmol) in CH2Cl2 (1 mL)
was added dropwise to a soln of the ketal 4 (42 mg, 0.16 mmol) and
lactone 5 (30 mg, 0.24 mmol) in CH2Cl2 (1 mL) at r.t., and the mix-
ture was refluxed for 1 h. The solvent was removed under reduced
pressure and the crude product was purified by column chromatog-
raphy [silica gel, PE–EtOAc (7:3)] to give a semi-solid; yield: 49
mg (87%); [a]D25 +51.3 (c 0.9, CHCl3); Rf = 0.4 (PE–EtOAc, 7:3).
(3) Hoffmann, H. M. R.; Rabe, J. Angew. Chem. Int. Ed. 1985,
24, 94.
IR (neat): 2924, 2856, 1718, 1378, 1242, 1020, 968, 816, 748 cm–1.
(4) Sehlapelo, B. M.; Drewes, S. E.; Scott-Shaw, R.
Phytochemistry 1994, 37, 847.
(5) Cavalheiro, A. J.; Yoshida, M. Phytochemistry 2000, 53,
811.
(6) Schmeda-Hirschmann, G.; Astudillo, L.; Bastida, J.; Codina,
C.; Rojas de Arias, A.; Ferreira, M. E.; Inchaustti, A.;
Yaluff, G. J. Pharm. Pharmacol. 2001, 53, 563.
1H NMR (CDCl3, 300 MHz): d = 7.39–7.17 (m, 5 H), 6.90–6.82 (m,
1 H), 6.54 (d, J = 15.8 Hz, 1 H), 6.19 (dd, J = 15.8, 6.0 Hz, 1 H),
6.04 (dt, J = 9.8, 1.5 Hz, 1 H), 5.92–5.79 (m, 1 H), 5.68 (dd, J = 15.8,
6.0 Hz, 1 H), 4.89 (q, J = 6.7 Hz, 1 H), 4.49 (q, J = 6.7 Hz, 1 H),
4.01–3.87 (m, 1 H), 2.49–2.19 (m, 4 H), 1.92–1.47 (m, 2 H), 1.40
(d, J = 3.0 Hz, 6 H).
13C NMR (CDCl3, 75 MHz): d = 164.0, 144.7, 130.9, 129.9, 129.6,
129.3, 128.9, 128.4, 127.6, 126.4, 121.5, 100.5, 77.9, 67.7, 65.8,
39.2, 38.5, 37.4, 25.5, 24.8.
(7) Matsuoka, Y.; Aikawa, K.; Irie, R.; Katsuki, T. Heterocycles
2005, 66, 187.
(8) (a) Sabitha, G.; Sudhakar, K.; Reddy, N. M.; Rajkumar, M.;
Yadav, J. S. Tetrahedron Lett. 2005, 46, 6567. (b) Sabitha,
G.; Narjis, F.; Swapna, R.; Yadav, J. S. Synthesis 2006,
2879. (c) Sabitha, G.; Reddy, E. V.; Yadagiri, K.; Yadav, J.
S. Synthesis 2006, 3270. (d) Sabitha, G.; Sudhakar, K.;
Yadav, J. S. Tetrahedron Lett. 2006, 47, 8599. (e) Sabitha,
G.; Bhaskar, V.; Yadav, J. S. Tetrahedron Lett. 2006, 47,
8179. (f) Sabitha, G.; Swapna, R.; Reddy, E. V.; Yadav, J. S.
Synthesis 2006, 4242. (g) Sabitha, G.; Bhikshapathi, M.;
Yadav, J. S. Synth. Commun. 2007, 37, 561. (h)Sabitha, G.;
Gopal, P.; Yadav, J. S. Synth. Commun. 2007, 37, 1495.
(i) Sabitha, G.; Yadagiri, K.; Yadav, J. S. Tetrahedron Lett.
2007, 48, 1651. (j) Sabitha, G.; Yadagiri, K.; Yadav, J. S.
Tetrahedron Lett. 2007, 48, 8065. (k) Sabitha, G.; Bhaskar,
V.; Yadav, J. S. Synth. Commun. 2008, 38, 1. (l) Sabitha,
G.; Bhaskar, V.; Reddy, S. S. S.; Yadav, J. S. Tetrahedron
2008, 64, 10207. (m) Sabitha, G.; Bhaskar, V.; Reddy, S. S.
S.; Yadav, J. S. Synthesis 2009, 3285. (n) Sabitha, G.;
Gopal, P.; Reddy, C. N.; Yadav, J. S. Tetrahedron Lett.
2009, 46, 6298. (o) Sabitha, G.; Gopal, P.; Reddy, C. N.;
Yadav, J. S. Synthesis 2009, 3301. (p) Sabitha, G.; Fatima,
N.; Gopal, P.; Reddy, C. N.; Yadav, J. S. Tetrahedron:
Asymmetry 2009, 20, 184. (q) Sabitha, G.; Fatima, N.;
Reddy, E. V.; Yadav, J. S. Tetrahedron Lett. 2008, 49, 6087.
(r) Sabitha, G.; Prasad, M. N.; Shankaraiah, K. S.; Jadav, J.
S. Synthesis 2010, 1171. (s) Sabitha, G.; Reddy, N. M.;
Prasad, M. N.; Yadav, J. S. Helv. Chim. Acta 2009, 92, 967.
(t) Sabitha, G.; Bhaskar, V.; Reddy, S. S. S.; Yadav, J. S.
Helv. Chim. Acta 2010, 93, 329.
LCMS: m/z = 377 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C22H26NaO4: 377.1728; found:
377.1734.
6-[(1E,4R,6S,7E)-4,6-Dihydroxy-8-phenylocta-1,7-dien-1-yl]-
5,6-dihydro-2H-pyran-2-one (1; Cryptofolione)
An aq 4% soln of HCl (0.5 mL) was added to a stirred soln of lac-
tone 22 (28 mg, 0.07 mmol) in MeCN (5 mL) at 0 °C, and the mix-
ture was stirred at 0 °C for 0.5 h. The reaction was quenched with
solid NaHCO3 (100 mg) and the mixture was filtered. The filtrate
was concentrated under reduced pressure, and the crude product
was purified by column chromatography [silica gel, PE–EtOAc
25
(1:1)] to give an oil; yield: 22 mg (93%); [a]D +44.3 (c 0.011,
CH2Cl2); Rf = 0.25 (PE–EtOAc, 1:1).
IR (neat): 3406, 2924, 1707, 1385, 1253, 1051, 969, 818, 751, 696
cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.37–7.14 (m, 5 H), 6.88–6.77 (m,
1 H), 6.59 (d, J = 15.8 Hz, 1 H), 6.23 (dd, J = 15.8, 6.0 Hz, 1 H),
5.98 (dt, J = 9.8, 1.5 Hz, 1 H), 5.94–5.81 (m, 1 H), 5.64 (dd, J = 15.8,
6.0 Hz, 1 H), 4.85 (q, J = 6.7 Hz, 1 H), 4.60 (q, J = 6.0 Hz, 1 H),
4.10–3.91 (m, 1 H), 3.51–3.01 (br s, 2 H, 2 × OH), 2.44–2.34 (m, 2
H), 2.31–2.20 (m, 2 H), 1.83–1.56 (m, 2 H).
13C NMR (CDCl3, 75 MHz): d = 164.1, 144.9, 136.5, 131.7, 131.1,
129.9, 129.8, 128.5, 127.6, 126.4, 121.4, 77.8, 70.3, 68.1, 42.2,
40.3, 29.7.
LCMS: m/z = 337 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C19H22NaO4: 337.1415; found:
(9) Mandal, P.; Roy, S. C. Tetrahedron 1995, 51, 7823.
(10) (a) Burova, S. A.; McDonald, F. E. J. Am. Chem. Soc. 2004,
126, 2495. (b) De Camp Schuda, A.; Mazzocchi, P. H.;
Fritz, G.; Morgan, T. Synthesis 1986, 309.
337.1418.
Synthesis 2010, No. 20, 3453–3460 © Thieme Stuttgart · New York

3460
G. Sabitha et al.
PAPER
(11) (F3CCO2)2IPh: (a) Smith, A. B. III; Beauchamp, T. J.;
LaMarche, M. J.; Kaufman, M. D.; Qiu, Y.; Arimoto, H.;
Jones, D. R.; Kobayashi, K. J. Am. Chem. Soc. 2000, 122,
8654. MeI/K2CO3: (b) Liu, J.-H.; Long, Y.-Q. Tetrahedron
Lett. 2009, 50, 4592. HgCl2/CaCO3: (c) Corey, E. J.; Bock,
M. G. Tetrahedron Lett. 1975, 16, 2643. CAN/aq MeCN:
(d) Solladié, G.; Hutt, J. Tetrahedron Lett. 1987, 28, 797.
(12) HgClO4/CaCO3: Jiang, B.; Chen, Z. Tetrahedron:
Asymmetry 2001, 12, 2835.
Garber, S. B.; Kingsbury, J. S.; Harrity, J. P. A. Org. Biomol.
Chem. 2004, 2, 8. (e) Marsh, G. P.; Parsons, P. J.;
McCarthy, C.; Corniquet, X. G. Org. Lett. 2007, 9, 2613.
(f) Moura-Letts, G.; Curran, D. P. Org. Lett. 2007, 9, 5.
(g) Bieniek, M.; Bujok, R.; Cabaj, M.; Lugan, N.; Lavigne,
G.; Arlt, D.; Grela, K. J. Am. Chem. Soc. 2006, 128, 13652.
(17) Diacetate 20 was prepared from the diol 17 by acetylation
(Scheme 6).
(13) Corey, E. J.; Helal, C. J. Angew. Chem. Int. Ed. 1998, 37,
1986.
OH OH
(14) Rychnovsky, S. D.; Skalitzky, D. J. Tetrahedron Lett. 1990,
31, 945.
(15) (a) Bonini, C.; Chiummiento, L.; Lopardo, M. T.; Pullex,
M.; Colobert, F.; Solladié, G. Tetrahedron Lett. 2003, 44,
2695. (b) Yadav, J. S.; Reddy, M. S.; Rao, P. P.; Prasad, A.
R. Tetrahedron Lett. 2006, 47, 4397.
(16) For a recent review on cross-metathesis, see: (a)BouzBouz,
S.; Simmons, R.; Cossy, J. Org. Lett. 2004, 6, 3465.
(b) Comin, M. J.; Parrish, D. A.; Deschamps, J. R.; Marquez,
V. E. Org. Lett. 2006, 8, 705. (c) Connon, S. J.; Blechert, S.
Angew. Chem., Int. Ed. 2003, 42, 1900. (d) Hoveyda, A. H.;
Gillingham, D. G.; Van Veldhuizen, J. J.; Kataoka, O.;
17
Ac2O, Py,
CH2Cl2
0 °C to r.t.,
1 h, 65%
OAc OAc
20
Scheme 6
Synthesis 2010, No. 20, 3453–3460 © Thieme Stuttgart · New York