Toward a modular, bidirectional synthesis of (-)-mucocin

Article abstract of DOI:10.1016/j.tet.2011.07.079

A convergent stereoselective synthesis of the C13-C34 fragment of (-)-mucocin is described. The salient features include (a) the bidirectional synthesis of the C-2 symmetric C13-C21 subunit, (b) regio- and stereoselective preparation of a 1,3-diol derivative from a diene activated by NBS via intramolecular nucleophilic sulfinyl group participation, (c) utilizing the self-metathesis reaction to prepare a functionalized C10 alkene, and (d) regio- and stereoselective intermolecular epoxide opening to construct the ether bond between C20 and C24. An organocatalytic α-hydoxylation has been employed to create the C4 stereogenic center of C1-C12 subunit. Attempted union of the two subunits utilizing the B-alkyl Suzuki coupling did not succeed.

Full text of DOI:10.1016/j.tet.2011.07.079

Tetrahedron 67 (2011) 7529e7539
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Toward a modular, bidirectional synthesis of (ꢀ)-mucocin
*
Sadagopan Raghavan , S. Ganapathy Subramanian
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A convergent stereoselective synthesis of the C13eC34 fragment of (ꢀ)-mucocin is described. The salient
features include (a) the bidirectional synthesis of the C-2 symmetric C13eC21 subunit, (b) regio- and
stereoselective preparation of a 1,3-diol derivative from a diene activated by NBS via intramolecular
nucleophilic sulfinyl group participation, (c) utilizing the self-metathesis reaction to prepare a func-
tionalized C10 alkene, and (d) regio- and stereoselective intermolecular epoxide opening to construct the
Received 22 April 2011
Received in revised form 25 July 2011
Accepted 26 July 2011
Available online 31 July 2011
ether bond between C20 and C24. An organocatalytic a-hydoxylation has been employed to create the C4
stereogenic center of C1eC12 subunit. Attempted union of the two subunits utilizing the B-alkyl Suzuki
coupling did not succeed.
Keywords:
Sulfoxide
Mucocin
Asymmetric synthesis
Antitomor agent
Neighboring group participation
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
to functionalize a 1,3-diene activated by NBS as the electrophile.
Mucocin was envisioned to be obtained by a B-alkyl Suzuki cross-
(ꢀ)-Mucocin 1, an annonaceous acetogenin, was isolated by
McLaughlin and co-workers from the leaves of Rollinia mucosa.1
Annonaceous acetogenins are polyketide derived fatty acid natural
coupling reaction between a vinyl iodide 3 and the trialkylborane
derived from terminal alkene 2. Compound 2 can be secured by
a selective ring-closing metathesis (RCM) reaction of triene 4,
which in turn can be visualized to be obtained by the union, via
ether formation (C20eOeC24), of epoxy tosylate 5 (C22eC34
subunit) and a tetrol derivative 6 (C13eC21 fragment). The diene 6
was envisioned to be obtained from diene sulfoxide 7, Scheme 1.
Construction of the THP ring system by the similar ring-closing
metathesis reaction was reported by Crimmins and co-workers.5g
The synthesis began from diene 7, which was readily prepared in
two steps from (S)-methyl-p-tolyl sulfoxide 8.6 Thus the lithio an-
products characterized by a long chain with a terminal
g-lactone
subunit, one to three tetrahydrofuran (THF) rings and carbinol chiral
centers. Based on the number and the position of the THF rings the
acetogenins have been classified into three subgroups: the mono-THF,
the adjacent bis-THF and the non adjacent bis-THF acetogenins. No-
tably, mucocin was the first acetogenin shown to possess tetrahy-
dropyran ring (THP) along with a THF ring.2 Mucocin shows selective
inhibition against A-549 (lung cancer) and PACA-2 (pancreatic cancer)
solid tumor cell lines with a potency 10,000 greater than the known
antitumor agent adriamycin.3 The mode of action is through blockage
of the mitochondrial complex I (NADH-ubiquinone oxidoreductase)
and inhibition of the plasma membrane NADH oxidase resulting in
ATP depletion and consequent apoptosis in malignant cells.4
ion of 8 on reaction with ethyl sorbate7 9 furnished the
b-keto
sulfoxide 10 that on diastereoselective reduction8 using Dibal-H in
the presence of anhydrous zinc chloride yielded diene alcohol 7 (dr
>95:<5). The hydroxy group in 7 was protected as its tert-butyl-
dimethylsilyl ether 11 and further subjected to reaction with freshly
recrystallized N-bromosuccinimide to furnish the bromohydrin 12
as the sole product regio- and stereoselectively,9 Scheme 2. The
2. Results and discussion
reaction probably proceeds via initial
p-complex formation be-
tween the bromonium ion and the alkene followed by intra-
molecular 6-endo nucleophilic attack10 by the sulfinyl group as
depicted in the putative transition state TS1, to yield the sulfoxo-
nium salt that on hydrolysis by attack of water at sulfur in SN2
fashion would afford bromohydrin 12. The alternate transition
state, TS2, that would afford the stereoisomer of 12, is probably not
preferred for both steric and stereoelectronic reasons. 1,3-Diaxial
interactions would be observed between the bulky p-Tol and hy-
drogen atoms in TS2, while in TS1 diaxial interactions would be
The unique structure and potent antitumor activity of mucocin
make it an inviting target for total synthesis; seven total syntheses
have been published till date.5 Herein, we describe a convergent,
stereoselective synthesis of the C13eC34 subunit (2) of mucocin by
taking advantage of the nucleophilic potential of the sulfinyl group
* Corresponding author. E-mail addresses: purush101@yahoo.com, sraghavan@
iict.res.in (S. Raghavan).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.07.079

7530
S. Raghavan, S.G. Subramanian / Tetrahedron 67 (2011) 7529e7539
Compound 12 serves as the key intermediate in our proposed
HO
21
19
HO
O
bidirectional synthesis of the C13eC34 subunit. Subjecting 12 to
self metathesis13 using HoveydaeGrubbs catalyst12 14 in refluxing
dichloromethane afforded the alkene 15. It is noteworthy that al-
kene 15 is densely substituted with functional groups including the
olefinic group which provide opportunities for further trans-
formations. Reduction of the double bond in 15 using PtO2/C under
an atmosphere of hydrogen yielded the diol 16. Oxidation of the
sulfinyl group using m-CPBA afforded the sulfone 17 cleanly. Pro-
tection of the hydroxy groups as their benzyl ethers using benzyl
trichloroacetamidate14 in the presence of catalytic amounts of tri-
fluoromethanesulfonic acid afforded 18. It remained to displace the
bromine atoms at C15, C20 and introduce hydroxy groups in its
place with inversion of configuration and install terminal double
bonds at C14 and C21. This was envisioned to be accomplished by
a three step sequence involving, (a) desilylation of TBS ethers, (b)
1 O
H
H
24
9
5
O
16
O
9
H
OH
13
OH
(-)-Mucocin 1
HO
O
OP
1 O
OH
24
I
O
12
+
9
H
OP
OP
13
3
2
OTs
C9H19
24
HO
OP
O
5
24
20
OH
O
+
9
H
epoxide formation, and (c) reductive b-elimination of the resulting
OP
13
OP
4
20
epoxy sulfones. In the event, treatment of 18 with TBAF furnished
the vinyl sulfone 21 and none of the expected diol 19. The formation
of 21 can be rationalized by the formation of epoxide 20 from diol
OH
HO
H
13
OP
6
O
S
19, which suffers b-elimination due to the basicity of TBAF. Pro-
OH
ceeding ahead, desulfonylation of 21 was attempted using Mg in
ethanol15 to yield the diene 6. A C-2 symmetric ten carbon chain
possessing four of the nine stereogenic centers corresponding to
C13eC21 fragment of mucocin was thus obtained by a straightfor-
ward sequence of ten reactions from ethyl sorbate, Scheme 3.
The synthon corresponding to C22eC34 fragment of mucocin
was prepared starting from commercially available 1-undecanal 22.
Wittig olefination with the stable ylide Ph3PCHCO2Et afforded the
unsaturated ester 23 that on chemoselective reduction using
alane16 furnished allylic alcohol 24. Sharpless asymmetric epoxi-
P = Protecting group
p-Tol
14/21
17/18
7
Scheme 1. Retrosynthetic analysis of (ꢀ)-mucocin.
only between OTBS and hydrogen atom. Also in TS2, with the OTBS
group in the equatorial orientation, the antibonding orbitals of CeO
bond are parallel to the p-orbitals of the double bond which would
decrease the electron density by overlap and therefore the nucle-
ophilicity of the alkene.11 The structure of 12 was unambiguously
proven by conversion to the acetonide 13, obtained by deprotection
of the TBS group followed by reaction with 2,2-dimethoxypropane.
The CHBr resonated as a doublet of doublet (J¼10.3, 9.5 Hz) in-
dicating its axial orientation. Also Ha and Hb in 13 mutually show
NOE with each other and also with the axial methyl group.
dation17 using (
)-DET afforded compound 25, which was con-
D
verted following standard conditions into tosylate 5, Scheme 4.
With both the coupling partners becoming available, opening of 5
by 6 was attempted in the presence of BF3$Et2O as the catalyst using
slightly modified conditions known in the literature,18 to afford the
coupled product 26 regioselectively. Epoxide formation using an-
hydrous potassium carbonate in a mixture of acetonitrile and
methanol yielded 27. The triene precursor 4 for the RCM reaction,
was obtained by treatment of 27 with an excess of ylide generated
from trimethylsulfonium iodide and n-BuLi.19 The RCM reaction
proceeded cleanly in the presence of Grubbs’ catalyst 2820 to yield
dihydropyran 2 (38%) and cyclooctene derivative 29 (38%) resulting
from the metathesis of C13eC21 alkenes,21 Scheme 4. The un-
desired product 29 was avoided by protection of the hydroxy group
in 27 as its TES ether 30 using standard reaction conditions.
Opening of the epoxide with the sulfur ylide furnished triene 31.
RCM reaction using 28 proceeded cleanly to afford the dihy-
dropyran 32. Protection of the hydroxy group using TBS/OTf and
2,6-lutidine furnished the TBS ether 33, Scheme 4. Thus, the
C13eC34 subunit of mucocin was synthesized in 16 steps by the
longest linear sequence.
O
O
O
b
a
S
S
p-Tol
Me
p-Tol
8
10
O
S
TBSO
H2O
H
OP
Br
d
p-Tol
S
O
7, P = H
p-Tol
TS1
c
11, P = TBS
O
H
OTBS
OH
The synthesis of the C1eC12 subunit 3, commenced from the
e
O
S
Br
S
O
known22 acetylenic alcohol 34. Swern oxidation23 afforded the al-
p-Tol
p-Tol
Ha
dehyde 35 that was subjected to
a-hydroxylation using Zhong’s
Br
12
Hb
protocol24 in the presence of
L-proline to yield diol 36 after in situ
O
reduction and subsequent NeO bond cleavage.25 Selective trans-
formation of the primary hydroxy group to a triflate and the sec-
ondary hydroxy group as its TBS ether was achieved in an one-pot
operation by treatment with triflic anhydride followed by TBS/OTf
in the presence of 2,6-lutidine to afford compound 38. Alkylation26
of the lithio anion of lactone27 39 with 38 furnished a di-
astereomeric mixture of sulfides 40.28 Oxidation of the sulfide to
sulfoxide and thermal elimination of phenyl sulfenic acid yielded
butenolide 41. The terminal alkyne 41 was converted to bromo al-
kyne 42 by reaction with N-bromosuccinimide in the presence of
13
p-Tol
H
H
EtO
H2O
S
O
Br
O
9
TBSO
TS2
Scheme 2. Synthesis of bromohydrin 12. Reagents and conditions: (a) LDA, THF,
ꢀ40 ꢁC, 30 min, warm to 0 ꢁC, add 9, 52%. (b) Dibal-H, ZnCl2, THF, ꢀ78 ꢁC, 82%. (c) TBS-
Cl, imidazole, CH2Cl2, 0 ꢁC to rt, 90%. (d) NBS, H2O, toluene, rt, 76%. (e) (i) TBAF/AcOH,
THF, 0 ꢁC to rt; (ii) 2,2-dimethoxypropane, cat CSA, CH2Cl2, rt, 70% for two steps.

S. Raghavan, S.G. Subramanian / Tetrahedron 67 (2011) 7529e7539
7531
O
S
OTBS
OTBS
Br
O
S
Br
OH
X
OP
O
S
c
a
Y
p-Tol
p-Tol
12
p-Tol
p-Tol
S
O
OP
HO
Br
Br
O
TBSO
TBSO
15, X,Y = double bond
16, X, Y = Single bond
O
b
17, P = H
d
18, P = Bn
O
S
O
Br
OBn
OH OBn
O
O
O
S
O
e
p-Tol
S
p-Tol
p-Tol
S
p-Tol
O
O
O
H
BnO
20
O
Br
BnO
19
OH
OH
OBn
N
N
Cl
Mes
Mes
X
Ru
O
X
Cl
OH
OBn
21, X = SO2Tol-p
6, X = H
14
f
Scheme 3. Synthesis of C13eC21 fragment. Reagents and conditions: (a) 3 mol % 14, CH2Cl2, reflux, 95% (based on recovered sm, 80% conversion). (b) PtO2, H2, 10 bar, MeOH/PhH
(1:1), rt, 80%. (c) m-CPBA, CH2Cl2, 0 ꢁC to rt, 80%. (d) Cl3C(NH)OBn, cat TfOH, CH2Cl2/cyclohexane, 0 ꢁC to rt, 70%. (e) TBAF, THF, 0 ꢁC to rt, 72%. (f) Mg, cat HgCl2, EtOH, 0 ꢁC to rt, 70%.
AgNO3.29 Compound 42 on treatment30 with n-Bu3SnH and
PdCl2(PPh3)2 furnished31 an intermediate vinyl stannane that on
treatment with iodine furnished regioselectively the iodo alkene 3,
Scheme 5. With both the coupling partners 3 and 33 becoming
available, their union using B-alkyl Suzuki reaction was attempted.
Thus, treatment of 33 with 9-BBN dimer afforded the tri-
organoborane 43 that was subjected to reaction with compound 3
in the presence of Pd(PPh3)4 and K3PO4.32 A complex mixture of
products resulted. Attempted Suzuki coupling using PdCl2(dppf)33
and Cs2CO3 also did not yield any desired product34 44, Scheme 5.
a
d
O
c
C9H19
23, X = CO2Et
OH
C9H19
C9H19
X
O
22
25
b
24, X = CH2OH
OTs
HO
OBn
OBn
OH
OH
OBn
e
OH
OTs
C9H19
+
O
H
O
5
OBn
26
C9H19
6
O
HO
OBn
P'O
OBn
OBn
OP
f
g
OP
OP
h
O
O
O
H
H
H
OBn
C9H19
OBn
4, P = H
OBn
C9H19
C9H19
27, P = H
i
2, P = P' = H
30, P = TES
31, P = TES
32, P = TES, P' = H
j
+
33, P = TES, P' = TBS
OH
HO
N
OBn
N
Mes
Mes
Cl
Ru
O
H
Cl
(Cy)3P
OBn
29
C9H19
28
Scheme 4. Selective RCM reaction of triene 32. Reagents and conditions: (a) Ph3PCHCO2Et, PhH, 80 ꢁC, 80%. (b) AlH3, Et2O, 0 ꢁC to rt, 75%. (c) (D)-DET, Ti(OiPr)4, t-BuOOH, CH2Cl2,
ꢀ20 ꢁC, 80%. (d) Ts-Cl, Et3N, cat DMAP, CH2Cl2, 0 ꢁC to rt, 90%. (e) BF3$Et2O, CH2Cl2, 0 ꢁC to rt, 70%. (f) K2CO3, EtOH/AcCN (1:1), rt, 90%. (g) Me3SI, n-BuLi, THF, ꢀ10 ꢁC to rt, 70%. (h) 5
Mole % 28, CH2Cl2, reflux, 76% of 2 and 29 from 4, 85% of 32 from 31. (i) TES-Cl, Imidazole, CH2Cl2, 0 ꢁC to rt, 90%. (j) TBSOTf, 2,6-lutidine, CH2Cl2, ꢀ78 ꢁC, 85%.

7532
S. Raghavan, S.G. Subramanian / Tetrahedron 67 (2011) 7529e7539
a
b
O
OH
OP
6
7
7
34
OP1
35
36, P = P1 = H
c(i)
37, P = OTf, P1 = H
38, P = OTf, P1 = TBS
c(ii)
O
O
O
I
d
e
PhS
g
X
O
O
O
6
6
6
OTBS
OTBS
OTBS
3
40
41, X = H
42, X = Br
f
TBSO
TBSO
OBn
OBn
h or
OTES
OTES
C10H21
O
C10H21
O
H
i
H
OBn
33
OBn
43
BBN
BBN
O
TBSO
O
O
OBn
O
PhS
OTES
C10H21
O
H
OBn
OTBS
39
44
Not obtained
Scheme 5. Synthesis of iodo alkene 3 and its attempted coupling with alkene 33. Reagents and conditions: (a) (COCl)2, DMSO, CH2Cl2, ꢀ78 ꢁC, 30 min then add Et3N, ꢀ78 ꢁC to rt, 90%.
(b) (i) PhNO, 20 mol % L-proline, DMSO, rt; (ii) NaBH4, EtOH, 0 ꢁC; (iii) CuSO4$5H2O, MeOH, rt, 53% overall. (c) (i) Tf2O, 2,6-lutidine, CH2Cl2, ꢀ50 ꢁC; (ii) TBSOTf, ꢀ50 ꢁC to 0 ꢁC, 93% overall.
(d) LiHMDS, THF, HMPA, add 39, ꢀ78 ꢁC to rt, 65%. (e) (i) m-CPBA, CH2Cl2, 0 ꢁC; (ii) Na2CO3, toluene, 80 ꢁC, 76% overall. (f) NBS, 10 mol % AgNO3, acetone, rt, 75%. (g) n-Bu3SnH,
PdCl2(PPh3)2, 0 ꢁC, cool to e78 ꢁC add I2, 70% overall. (h) (i) 9-BBN dimer, THF; (ii) 3, Pd(PPh3)4, K3PO4, Dioxane, 85 ꢁC (i) (i) 9-BBN dimer, THF; (ii) 3, PdCl2(dppf), Cs2CO3, Ph3As, rt.
3. Conclusion
P2O5 for toluene. Commercially available reagents were used
without purification. Thin layer chromatography was performed on
precoated silica gel plates. Column chromatography was carried out
using silica gel (60e120 mesh). NMR spectra were recorded on
a 200, 300 or 400 MHz spectrometer. 1H and 13C NMR samples were
internally referenced to TMS (0.00 ppm). Melting points are
uncorrected.
In summary, we have described a highly stereoselective con-
vergent route to the C13eC34 subunit 33, of mucocin. An organo-
catalytic aminoxylation reaction was employed to create the C4
stereogenic center in iodo alkene 3. The coupling of subunits 3 and
33 envisioned by utilizing the B-alkyl Suzuki reaction, failed. The
key steps in the synthesis of the C13eC34 fragment include the
regio- and stereoselective 1,3-diol formation by intramolecular
sulfinyl group participation from 1,3-diene via 1,2-functionalization
without any complication arising due to competing 1,4-
functionalization, self metathesis reaction to prepare a highly
functionalized C2-symmetric molecule, which has the 1,4-diol
moiety, a common structural feature of acetogenins, regiose-
lective intermolecular opening of an epoxy tosylate and a selective
RCM reaction for the formation of the THP ring. The key steps in the
synthesis of compound 3 include alkylation using the triflate and
regioselective stannation of the bromo alkyne 41. A revised syn-
thetic plan is being explored to unite subunits related to 33 and 3 to
complete the synthesis of mucocin.
4.1.1. (3E,5E)-(1Ss)-(p-Tolylsulfinyl)hepta-3,5-dien-2-one
[10]. To
a solution of diisopropyl amine (7 mL, 55 mmol) in dry THF
(275 mL) cooled at 0 ꢁC under nitrogen atmosphere was added n-
BuLi (23 mL, 2.4 M in hexanes, 55 mmol) dropwise and the mixture
stirred for 15 min. The solution of LDA thus generated was cooled to
ꢀ40 ꢁC and a solution of (S)-methyl-p-tolyl sulfoxide 8 (3.85 g,
25 mmol) in anhydrous THF (200 mL) was added dropwise over
5 min. The reaction mixture was stirred for 30 min and warmed to
0 ꢁC. After 5 min the solution of ester 9 (3.86 g, 27.5 mmol) in THF
(25 mL) was added dropwise over 5 min and the reaction mixture
stirred for 15 min. The reaction was then quenched by the addition
of saturated aq NH4Cl solution and diluted with EtOAc (250 mL).
The layers were separated and the organic layer was washed with
water, brine, and dried over Na2SO4. The solvent was evaporated
under reduced pressure to afford the crude product, which was
purified by column chromatography using 30% EtOAc/hexane (v/v)
as the eluent give pure keto sulfoxide 10 (3.22 g, 13 mmol) in 52%
4. Experimental
4.1. General remarks
All air or moisture sensitive reactions were carried out under
nitrogen atmosphere. Solvents were distilled over Na/benzophe-
none ketyl for THF, over P2O5 followed by CaH2 for DCM, and over
yield as a gummy oil. TLC, Rf (40% EtOAc/hexane) 0.3. ½a D25
ꢂ
ꢀ53.0 (c
3.0, CHCl3); nmax (KBr) 2924, 2854, 1631, 1040, 810 cmꢀ1
;
dH
(400 MHz, CDCl3): 7.51 (d, J¼8.8 Hz, 2H), 7.30 (d, J¼8.8 Hz, 2H), 7.09

S. Raghavan, S.G. Subramanian / Tetrahedron 67 (2011) 7529e7539
7533
(dd, J¼15.4, 9.6 Hz, 1H), 6.27e6.03 (m, 3H), 4.02 (d, J¼12.5 Hz, 1H),
a gummy oil. TLC, Rf 0.25 (20% EtOAc/hexane). ½a D25
ꢂ
þ66.8 (c 0.5,
3.83 (d, J¼12.5 Hz, 1H), 2.42 (s, 3H), 1.90 (d, J¼5.1 Hz, 3H); dC
(75 MHz, CDCl3): 190.8, 146.3, 143.0, 142.1, 139.2, 130.1, 130.0, 127.2,
124.2, 66.9, 21.4, 18.9; m/z (MS-ESI) 271 [MþNa]þ; HRMS (ESI) calcd
for C14H16O2SNa: 271.0768. Found: 271.0768.
MeOH); nmax (KBr) 3360, 2928, 2856, 1631, 1255, 1085, 776 cmꢀ1
; dH
(400 MHz, CDCl3) 7.51 (d, J¼8.3 Hz, 2H), 7.31 (d, J¼8.3 Hz, 2H),
5.81e5.67 (m, 1H), 5.56 (ddd, J¼16.1, 7.5, 1.5 Hz, 1H), 4.69 (dt, J¼9.0,
1.5 Hz, 1H), 4.23 (br s, 1H), 4.10 (dd, J¼7.5, 2.3 Hz, 1H), 3.99 (dd,
J¼9.0, 2.3 Hz, 1H), 3.10 (dd, J¼12.8, 1.5 Hz, 1H), 2.86 (dd, J¼12.8,
9.8 Hz, 1H), 2.45 (s, 3H), 1.76 (d, J¼6.0 Hz, 3H), 0.99 (s, 9H), 0.28 (s,
3H), 0.22 (s, 3H); dC (75 MHz, CDCl3) 141.5, 140.7, 130.5, 129.9, 123.9,
73.5, 66.2, 64.8, 64.1, 25.7, 21.3, 18.0, 17.6, ꢀ4.5; m/z (MS-ESI) 483
[MþNa]þ. HRMS (ESI) calcd for C20H33O3NaSiSBr: 483.1000. Found:
483.0999.
4.1.2. (2S,3E,5E)-1-(p-Tolylsulfinyl)hepta-3,5-dien-2-ol [7]. To a so-
lution of anhydrous ZnCl2 (2.92 g, 40 mmol) in anhydrous THF
(150 mL) was added a solution of keto sulfoxide 10 (4.96 g,
20 mmol) in THF (50 mL) dropwise over 5 min. The reaction mix-
ture was stirred at rt for 30 min and then cooled to ꢀ78 ꢁC. After
5 min Dibal-H (21.4 mL, 1.4 M in toluene, 30 mmol) was added
dropwise over 5 min. After 30 min, MeOH (5 mL) was added slowly
to the reaction mixture and allowed to warm to rt. The volatiles
were evaporated under reduced pressure and the residue was
dissolved by adding aq 5% HCl (100 mL) at 0 ꢁC. Then EtOAc
(100 mL) was added, the layers were separated and the aqueous
layer extracted with EtOAc (2ꢃ100 mL). The combined organic
layers were washed with water, brine and dried over Na2SO4. The
solvent was evaporated under reduced pressure to afford the crude
product, which was purified by column chromatography using 40%
EtOAc/hexane as the eluent to give pure hydroxy sulfoxide 7 (4.1 g,
16.4 mmol) in 82% yield as a gummy oil. TLC, Rf 0.25 (40% EtOAc/
4.1.5. (4S,5S,6R)-5-Bromo-2,2-dimethyl-4-((E)-prop-1-enyl)-(6Rs)-
(p-tolylsulfinylmethyl)-1,3-dioxane [13]. To a solution of the bro-
mohydrin 12 (230 mg, 0.5 mmol) in THF (2 mL) were added a pre-
mixed solution of TBAF (1.5 mL, 1 M/THF, 1.5 mmol) and acetic acid
(0.08 mL, 1.5 mmol) and the reaction mixture was stirred at rt for
12 h. The reaction was quenched by adding saturated aq NaHCO3
(2 mL). The organic layer was separated and the aqueous layer was
extracted with EtOAc. The combined organic layers were washed
with water, brine, and dried over Na2SO4. The solvent was evapo-
rated under reduced pressure to afford the crude diol as a gummy
oil which was taken ahead to the next step without purification. To
the crude diol in DCM (5 mL) was added 2,2-dimethoxypropane
(0.18 mL, 1.5 mmol) and catalytic camphor sulfonic acid. The re-
action mixture was stirred for 4 h. The solvent was evaporated
under reduced pressure to afford the crude product, which was
purified by column chromatography using 10% EtOAc/petroleum
ether (v/v) as the eluent to give the pure product 13 (135 mg,
0.35 mmol) in 70% yield as a gummy oil. TLC, Rf 0.5 (15% EtOAc/
hexane). ½a 2D5
ꢂ
ꢀ194.0 (c 1.02, CHCl3); nmax (KBr) 3417, 2925, 2856,
1727, 1085, 994, 810 cmꢀ1
;
dH (400 MHz, CDCl3) 7.53 (d, J¼8.1 Hz,
2H), 7.31 (d, J¼8.1 Hz, 2H), 6.20 (dd, J¼15.1, 10.4 Hz, 1H), 5.98 (dd,
14.9, 10.4 Hz, 1H), 5.75e5.63 (m, 1H), 5.51 (dd, J¼15.1, 6.4 Hz, 1H),
4.73e4.66 (m, 1H), 3.04 (dd, J¼13.0, 8.9 Hz, 1H), 2.77 (dd, J¼13.0,
3.6 Hz, 1H), 2.41 (s, 3H), 1.74 (d, J¼6.8 Hz, 3H); dC (75 MHz, CDCl3)
141.6, 140.7, 131.8, 130.8, 130.6, 130.0, 129.9, 124.1, 68.9, 63.1, 21.5,
18.2; m/z (MS-ESI) 273 [MþNa]þ. HRMS (ESI) calcd for
C14H18O2SNa: 273.0925. Found: 273.0921.
hexane). ½a 2D5
ꢂ
þ86.8 (c 0.5, MeOH); nmax (KBr) 2923, 2854, 1740,
1459, 785 cmꢀ1
;
dH (400 MHz, CDCl3) 7.54 (d, J¼8.0 Hz, 2H), 7.30 (d,
J¼8.0 Hz, 2H), 5.89e5.81 (m, 1H), 5.39 (ddq, J¼15.4, 7.3, 1.5 Hz, 1H),
4.51 (td, J¼10.3, 1.5 Hz, 1H), 4.35 (dd, J¼9.5, 7.3 Hz, 1H), 3.41e3.34
(m, 2H), 2.65 (dd, J¼13.2, 10.3 Hz, 1H), 2.39 (s, 3H), 1.71 (dd, J¼6.6,
1.5 Hz, 3H), 1.61 (s, 3H), 1.46 (s, 3H); dC (75 MHz, CDCl3) 141.5,
141.2132.0, 129.9, 127.7, 123.8, 100.1, 75.3, 68.7, 62.4, 51.3, 29.3, 21.3,
19.4, 17.7. m/z (MS-ESI) 409 [MþNa]þ. HRMS (ESI) calcd for
C17H23O3BrSNa: 409.0448. Found: 409.0434.
4.1.3. tert-Butyldimethyl((2S,3E,5E)-(1Ss)-(p-tolylsulfinyl)hepta-3,5-
dien-2-yloxy) silane [11]. To a solution of the hydroxy sulfoxide 7
(8.0 g, 32 mmol) in DCM (128 mL) cooled at 0 ꢁC was added im-
idazole (5.2 g, 76.8 mmol) and then TBS-Cl (5.77 g, 38.4 mmol). The
reaction mixture was allowed to warm to rt and stirred overnight.
The reaction mixture was quenched by the addition of saturated aq
NH4Cl solution, diluted with DCM (100 mL). The layers were sep-
arated and the organic layer was washed with water, brine and
dried over Na2SO4. The solvent was evaporated under reduced
pressure to afford the crude product, which was purified by column
chromatography using 10% EtOAc/hexane (v/v) as the eluent to give
pure TBS ether 11 (10.48 g, 28.8 mmol) in 90% yield as a gummy oil.
4.1.6. (5R,6S,7S,10S,11S,12R,E)-6,11-Dibromo-2,2,3,3,14,14,15,15-
octamethyl-5(Rs),12(Rs)-bis(p-tolylsulfinylmethyl)-4,13-dioxa-3,14-
disilahexadec-8-ene-7,10-diol [15]. To a solution of bromohydrin 12
(3.29 g, 7.15 mmol) in DCM (35 mL) was added HoveydaeGrubbs
catalyst 14 (90 mg, 0.143 mmol) and the reaction mixture was
refluxed for 2 days. To this a second portion of the catalyst (45 mg,
0.071 mmol) was added and the reaction was continued for another
2 days when TLC revealed 80% conversion. The solvent was evap-
orated and the residue was purified by column chromatography
using 40% EtOAc/hexane (v/v) as the eluent to give pure 15 (2.5 g,
2.86 mmol) and recovered starting material 12 (552 mg, 1.2 mmol)
in 95% yield (based on recovered starting material) as a gummy oil.
TLC, Rf 0.5 (20% EtOAc/hexane). ½a D25
ꢂ
ꢀ41.5 (c 1.05, MeOH); 2929,
nmax (KBr) 2368, 1466, 1253,1046, 990, 836, 776 cmꢀ1
;
dH (400 MHz,
CDCl3) 7.50 (d, J¼8.3 Hz, 2H), 7.30 (d, J¼8.3 Hz, 2H), 6.21 (dd, J¼15.1,
10.4 Hz,1H), 6.05 (dd,15.1,10.6 Hz,1H), 5.79e5.68 (m,1H), 5.59 (dd,
J¼15.1, 6.4 Hz, 1H), 4.52e4.46 (m, 1H), 3.07 (dd, J¼12.8, 5.3 Hz, 1H),
2.72 (dd, J¼12.8, 8.3 Hz, 1H), 2.43 (s, 3H), 1.80 (d, J¼6.8 Hz, 3H), 0.88
(s, 9H), 0.05 (s, 3H), 0.04 (s, 3H); dC (75 MHz, CDCl3) 141.4, 141.3,
132.3, 131.0, 130.4, 129.9, 124.1, 69.4, 66.7, 25.7, 21.3, 18.1, ꢀ4.1, ꢀ4.9;
m/z (MS-ESI) 387 [MþNa]þ. HRMS (ESI) calcd for C20H32O2SiSNa:
387.1790. Found: 387.1780.
TLC, Rf 0.25 (50% EtOAc/hexane). ½a D25
ꢂ
þ105.1 (c 1.17, MeOH); nmax
(KBr) 3353, 2929, 2856, 1725, 1255, 1088, 676, 514 cmꢀ1
;
dH
(400 MHz, CDCl3) 7.43 (d, J¼7.9 Hz, 4H), 7.20 (d, J¼7.9 Hz, 4H),
5.90e5.76 (m, 2H), 4.56 (d, J¼9.8 Hz, 2H), 4.19e4.09 (m, 2H),
4.01e3.97 (m, 2H), 3.04 (dd, J¼12.6, 2.5 Hz, 2H), 2.74 (dd, J¼12.6,
10.0 Hz, 2H), 2.33 (s, 6H), 0.88 (s, 18H), 0.15 (s, 6H), 0.09 (s, 6H); dC
(75 MHz, CDCl3) 141.5, 140.5, 132.5, 130.0, 123.9, 72.4, 66.0, 63.9,
63.7, 25.8, 21.2, 18.0, ꢀ4.5, ꢀ4.6; m/z (MS-ESI) 889 [MþNa]þ. HRMS
(ESI) calcd for C36H58O6 NaS2Si2Br2: 887.1477. Found: 887.1462.
4.1.4. (4S,5S,6R,E)-5-Bromo-6-(tert-butyldimethylsilyloxy)-(7Rs)-(p-
tolylsulfinyl) hept-2-en-4-ol [12]. To a solution of the TBS ether 11
(4.36 g, 12 mmol) in toluene (60 mL) was added water (0.32 mL,
17.7 mmol) and the mixture stirred at rt for 5 min. To the above
solution freshly recrystallised NBS (2.03 g, 11.4 mmol) was added
portionwise over a period of 2 h. TLC examination revealed con-
sumption of most of the starting material. The solvent was evapo-
rated under reduced pressure and the residue was purified by
column chromatography using 15% EtOAc/hexane (v/v) as the elu-
ent to give pure bromohydrin 12(4.2 g, 9.12 mmol) in 76% yield as
4.1.7. (5R,6S,7S,10S,11S,12R)-6,11-Dibromo-2,2,3,3,14,14,15,15-
octamethyl-5(Rs),12(Rs)-bis(p-tolylsulfinylmethyl)-4,13-dioxa-3,14-
disilahexadecane-7,10-diol [16]. To a solution of the cross metath-
esis product 15 (2.5 g, 2.86 mmol) in MeOH/benzene (1:1, 28 mL)

7534
S. Raghavan, S.G. Subramanian / Tetrahedron 67 (2011) 7529e7539
was added Adams catalyst (100 mg) and the reaction mixture was
stirred at rt under hydrogen pressure (10 bar) for 24 h. The reaction
mixture was filtered through a pad of Celite and washed with
MeOH. Volatiles were evaporated and the residue was purified by
column chromatography using 40% EtOAc/hexane (v/v) as the el-
uent to give the pure reduced product 16 (1.98 g, 2.23 mmol) in 80%
warm to rt and stirred further for 30 min. The solvent was evapo-
rated under reduced pressure and the residue was purified by
column chromatography using 40% EtOAc/hexane (v/v) as the el-
uent to give the vinyl sulfone 21 (1.20 g, 1.74 mmol) in 72% yield as
a gummy oil. TLC, Rf 0.2 (40% EtOAc/hexane). ½a D25
ꢂ
ꢀ24.2 (c 0.8,
MeOH); nmax (KBr) 3444, 2925, 2855, 1456, 1068, 924, 737 cmꢀ1
;
dH
yield as a gummy oil. TLC, Rf 0.30 (50% EtOAc/hexane). ½a D25
ꢂ
þ83.0 (c
(400 MHz, CDCl3) 7.67 (d, J¼8.3 Hz, 4H), 7.27e7.14 (m, 14H), 6.86
(dd, J¼15.1, 3.4 Hz, 2H), 6.57 (dd, J¼15.1, 1.9 Hz, 2H), 4.43e4.35 (m,
4H), 4.22e4.17 (m, 2H), 3.31e3.27 (m, 2H), 2.35 (s, 6H), 1.61e1.46
(m, 4H); dC (75 MHz, CDCl3) 144.8, 144.3, 137.4, 137.3, 131.8, 129.9,
128.7, 128.2, 128.1, 127.8, 80.3, 72.9, 71.5, 26.4, 21.7; m/z (MS-ESI)
713 [MþNa]þ. HRMS (ESI) calcd for C38H42O8NaS2: 713.2218.
Found: 713.2238.
2.5, CHCl3); nmax (KBr) 3427, 1714, 1309, 1147, 814, 639 cmꢀ1
;
dH 7.52
(d, J¼7.7 Hz, 4H), 7.32 (d, J¼7.7 Hz, 4H), 4.74 (td, J¼8.6, 1.9 Hz, 2H),
3.99 (dd, J¼8.6, 2.9 Hz, 2H), 3.68 (t, J¼8.6 Hz, 2H), 3.12 (dd, J¼13.4,
1.9 Hz, 2H), 2.86 (dd, J¼13.4, 8.6 Hz, 2H), 2.41 (s, 3H), 2.17e2.12 (m,
2H), 1.71e1.61 (m, 2H), 0.96 (s, 18H), 0.24 (s, 6H), 0.18 (s, 6H); dC
(75 MHz, CDCl3) 141.6, 140.3, 130.1, 123.9, 72.1, 66.3, 64.7, 63.8, 30.9,
25.7, 21.4, 18.0, ꢀ4.5, ꢀ4.6; m/z (MS-ESI) 891 [MþNa]þ. HRMS (ESI)
calcd for C36H60O6NaS2Si2Br2: 889.1634. Found: 889.1652.
4.1.11. (3S,4S,7S,8S)-4,7-Bis(benzyloxy)deca-1,9-diene-3,8-diol
[6]. To a solution of vinyl sulfone 21 (1.20 g, 1.74 mmol) in ethanol
(17 mL) was added magnesium turnings (250 mg, 10.44 mmol)
followed by HgCl2 (few crystals) at 0 ꢁC. The reaction mixture was
stirred for 4 h, while gradually allowing the temperature to rise to
rt. The residue was filtered and washed with ethanol. The combined
filtrates were concentrated under reduced pressure to afford the
crude product, which was purified by column chromatography
using 15% EtOAc/hexane (v/v) as the eluent to afford the diol 6
(0.47 g, 1.22 mmol) in 70% yield as a gummy oil. TLC, Rf 0.3 (20%
4.1.8. (5R,6S,7S,10S,11S,12R)-6,11-Dibromo-2,2,3,3,14,14,15,15-
octamethyl-5,12-bis(tosylmethyl)-4,13-dioxa-3,14-disilahexadecane-
7,10-diol [17]. To a solution of the compound 16 (3.0 g, 3.45 mmol)
in DCM (17 mL) was added m-CPBA (1.43 g, 8.3 mmol) at 0 ꢁC. After
20 min the reaction was quenched by adding 10% aq NaHSO3
(20 mL) and the mixture stirred for 5 min. The reaction mixture was
diluted by adding DCM (20 mL). The organic layer was separated,
washed with saturated NaHCO3 (20 mL), water, brine, and dried
over Na2SO4. The solvent was evaporated under reduced pressure
to afford the crude product, which was purified by column chro-
matography using 20% EtOAc/hexane (v/v) as the eluent to give the
sulfone 17 (2.48 g, 2.76 mmol) in 80% yield as a gummy oil. TLC, Rf
EtOAc/hexane). ½a D25
ꢂ
ꢀ35.8 (c 0.6, MeOH); nmax (KBr) 3427, 2922,
2856, 1639, 1452, 1065, 923, 698 cmꢀ1
;
dH (400 MHz, CDCl3)
7.32e7.28 (m, 10H), 5.85 (ddd, J¼17.4, 10.6, 6.0 Hz 2H), 5.33 (dt,
J¼17.4, 1.5 Hz, 2H), 5.21e5.20 (dt, J¼10.6, 1.5 Hz, 2H), 4.59 (d,
J¼11.3 Hz, 2H), 4.53 (d, J¼11.3 Hz, 2H), 4.05 (t, J¼6.0 Hz, 2H), 3.34
(dt, J¼10.6, 6.0 Hz, 2H), 1.75e1.56 (m, 4H); dC NMR (75 MHz, CDCl3)
138.1, 137.3, 128.5, 127.8, 117.0, 81.9, 74.2, 72.5, 25.4; m/z (MS-ESI)
405 [MþNa]þ. HRMS (ESI) calcd for C24H30O4Na: 405.2041. Found:
405.2052.
0.5 (40% EtOAc/hexane). ½a D25
ꢂ
þ4.4 (c 1.25, CHCl3); nmax (KBr) 3427,
1714, 1309, 1147, 814, 639 cmꢀ1
;
dH (400 MHz, CDCl3) 7.80 (d,
J¼8.1 Hz, 4H), 7.37 (d, J¼8.1 Hz, 4H), 4.74 (ddd, J¼6.7, 4.4, 2.2 Hz,
2H), 4.0 (dd, J¼9.5, 2.2 Hz, 2H), 3.81e3.71 (m, 4H), 3.24 (dd, J¼15.4,
4.4 Hz, 2H), 2.45 (s, 6H), 2.19e2.11 (m, 2H), 1.73e1.59 (m, 2H), 0.83
(s, 18H), 0.11 (s, 6H), 0.01 (s, 6H); dC (75 MHz, CDCl3) 145.1, 136.4,
130.1,127.9, 72.2, 67.1, 63.2, 62.0, 30.5, 25.6, 21.6,17.8, ꢀ4.8, ꢀ4.9; m/
z (MS-ESI) 923 [MþNa]þ. HRMS (ESI) calcd for C36H60O8 NaS2Si2Br2:
921.1532. Found: 921.1511.
4.1.12. (E)-Ethyl tridec-2-enoate [23]. To a solution of 1-undecanal
22 (3.4 g, 20 mmol) in benzene (80 mL) was added ethyl-
(triphenylphosphoranylidene)acetate (8.35 g, 24 mmol) and the
reaction mixture was heated to reflux for 15 h. The reaction mixture
was cooled to rt and benzene was evaporated under reduced
pressure. The residue was cooled to 0 ꢁC diluted with ether and the
mixture filtered through a sintered funnel to remove the triphe-
nylphosphineoxide. The ether layer was evaporated under reduced
pressure to afford the crude product, which was purified by column
chromatography using 5% EtOAc/hexane (v/v) as the eluent to give
23 (3.84 g, 16.0 mmol) in 80% yield as a colorless liquid. TLC, Rf 0.5
4.1.9. (5R,6S,7S,10S,11S,12R)-7,10-Bis(benzyloxy)-6,11-dibromo-
2,2,3,3,14,14,15,15-octamethyl-5,12-bis(tosylmethyl)-4,13-dioxa-3,14-
disilahexadecane [18]. To
a solution of sulfone 17 (2.48 g,
3.45 mmol) and benzyl trichloroacetimidate (8.71 g, 34.5 mmol) in
DCM/cyclohexane (1:1, 17 mL) was added triflic acid (0.03 mL,
0.35 mmol) dropwise at 0 ꢁC and the reaction mixture was stirred at
rt overnight. The reaction was quenched by adding aq saturated
NaHCO3 (2 mL). The reaction mixture was filtered through a pad of
Celite and washed with DCM/cyclohexane (1:1, 30 mL). The com-
bined organic layers were washed with water, brine and dried over
Na2SO4. The solvent was evaporated under reduced pressure to
afford the crude product, which was purified by column chroma-
tography using 15% EtOAc/hexane (v/v) as the eluent to give the
benzyl ether 18 (2.60 g, 2.41 mmol) in 70% yield as a gummy oil.
(5% EtOAc/hexane). nmax (KBr) 2926, 2855,1723,1181,1042 cmꢀ1
; dH
(400 MHz, CDCl3) 6.89 (dt, J¼15.5, 7.0 Hz, 1H), 5.75 (d, J¼15.5 Hz,
1H), 4.14 (q, J¼7.2 Hz, 2H), 2.17 (q, J¼7.0 Hz, 2H), 1.45e1.19 (m, 19H),
0.86 (t, J¼6.8 Hz, 3H); dC (75 MHz, CDCl3) 166.5, 149.2, 121.3, 60.0,
32.2, 31.9, 29.6, 29.5, 29.4, 29.3, 29.2, 28.1, 22.7, 14.3, 14.1; m/z (MS-
ESI) 263 [MþNa]þ. HRMS (ESI) calcd for C15H28O2Na: 263.1987.
Found: 263.1994.
TLC, Rf 0.25 (20% EtOAc/hexane). ½a D25
ꢂ
þ37.3 (c 0.8, CHCl3); nmax
(KBr) 2925, 2855, 1456, 1068, 924, 737 cmꢀ1
;
dH (400 MHz, CDCl3)
4.1.13. (E)-Tridec-2-en-1-ol [24]. To a suspension of LiAlH4 (570 mg,
15 mmol) in ether (12 mL) cooled at 0 ꢁC was added a solution of
AlCl3 (670 mg, 5 mmol) in ether (8 mL). The reaction mixture was
stirred at the same temperature for 1 h. To the alane so generated,
a solution of the ester 23 (2.4 g, 10 mmol) in ether (15 mL) was
added dropwise over 2 min. The reaction temperature was gradu-
ally allowed to rise to rt and the reaction mixture stirred for 2 h. The
reaction mixture was diluted with ether (30 mL), and quenched by
careful addition of ice pieces until the reaction ceased. The reaction
mass was filtered through a pad of Celite and washed with hot ethyl
acetate. The combined organic layers were washed with water,
brine, and dried over Na2SO4. The solvent was evaporated under
reduced pressure to afford the crude product, which was purified
7.86 (dd, J¼8.3 Hz, 4H), 7.53e7.38 (m, 14H), 4.93 (td, J¼5.3, 1.7 Hz,
2H), 4.73e4.63 (m, 4H), 4.31 (dd, J¼9.3, 1.9 Hz, 2H), 3.97e3.80 (m,
4H), 3.39 (dd, J¼14.2, 4.9 Hz, 2H), 2.60 (s, 6H), 2.12e1.97 (m, 4H),
1.07 (s, 18H), 0.29 (s, 6H), 0.25 (s, 6H); dC (75 MHz, CDCl3) 144.3,
137.8, 137.7, 129.9, 128.5, 128.0, 127.9, 78.6, 72.2, 68.7, 62.1, 58.9,
29.8, 26.0, 21.7, 18.2, ꢀ4.4, ꢀ4.5; m/z (MS-ESI) 1103 [MþNa]þ. HRMS
(ESI) calcd for C50H72O8NaS2Si2Br2: 1101.2471. Found: 1101.2476.
4.1.10. (1E,3S,4S,7S,8S,9E)-4,7-Bis(benzyloxy)-1,10-ditosyldeca-1,9-
diene-3,8-diol [21]. To a solution of the benzyl ether 18 (2.85 g,
2.42 mmol) in THF (25 mL) was added TBAF (9.7 mL, 1 M in THF) at
0
ꢁC dropwise over 5 min. The reaction mixture was allowed to

S. Raghavan, S.G. Subramanian / Tetrahedron 67 (2011) 7529e7539
7535
by column chromatography using 15% EtOAc/hexane (v/v) as the
eluent to afford the pure compound 24 (1.49 g, 7.5 mmol) in 75%
yield as a colorless liquid. TLC: Rf 0.2 (20% EtOAc/hexane). nmax (KBr)
gradually warm to rt and stirred further for 24 h. The reaction
mixture was recooled to 0 ꢁC and another portion of BF3$Et2O
(19 mL, 0.15 mmol) was added and stirring continued for another
3329, 2924, 2853, 1631, 1461, 1089, 969 cmꢀ1
;
dH (400 MHz, CDCl3)
15 h at rt. The reaction was quenched by adding few pieces of ice
and the mixture was stirred for 10 min. The reaction mixture was
filtered through a pad of Celite and the residue was washed with
DCM. The organic layer was washed with water, brine and dried
over Na2SO4. The solvent was evaporated under reduced pressure
to afford the crude product, which was purified by column chro-
matography using 15% EtOAc/hexane (v/v) as the eluent to give
pure product 26 (1.58 g, 2.1 mmol) in 70% yield as a gummy oil. TLC,
5.65e5.51 (m, 2H), 4.67 (br s, 1H), 4.05 (d, J¼3.9 Hz, 2H), 2.04 (q,
J¼6.3 Hz, 2H), 1.56e1.07 (m, 16H), 0.88 (t, J¼7.0 Hz, 3H); dC NMR
(75 MHz, CDCl3) 136.6, 123.9, 65.3, 32.4, 32.0, 29.7, 29.6, 29.4, 29.3,
29.0, 22.8, 14.2. m/z (MS-ESI) 221 [MþNa]þ. HRMS (ESI) calcd for
C13H26ONa: 221.1881. Found: 221.1886.
4.1.14. ((2R,3R)-3-Decyloxiran-2-yl)methanol [25]. To a stirred sus-
pension of activated 4 A molecular sieves (660 mg) in DCM (28 mL)
Rf 0.25 (20% EtOAc/hexane). ½a D25
ꢂ
ꢀ19.0 (c 1.0, MeOH); nmax (KBr)
ꢀ
was added (ꢀ)DET (0.34 mL, 2 mmol) and Ti(OiPr)4 (0.6 mL,
2 mmol) and the resulting mixture was stirred for 30 min at rt. The
reaction mixture was then cooled to ꢀ20 ꢁC and a solution of the
allylic alcohol 24 (1.98 g, 10 mmol) in DCM (4 mL) was added
dropwise into it. The resulting mixture was stirred for another
30 min at ꢀ20 ꢁC. TBHP (6.1 mL, 3.6 M in toluene, 22 mmol) was
added dropwise and the resulting mixture stirred at the same
temperature for 12 h. The reaction mixture was allowed to warm to
0 ꢁC, quenched with water (11.2 mL) and stirred for 2 h at rt. Then
aq NaOH (30%) saturated with NaCl (4 mL) was added and the
resulting mixture was stirred vigorously for another 30 min at rt.
The mixture was filtered through Celite and the filter cake was
washed well with DCM. The organic layers were separated and the
aqueous layer was extracted with DCM (3ꢃ25 mL). The combined
extracts were washed with water, brine and dried over Na2SO4. The
solvent was evaporated under reduced pressure to afford the crude
product, which was purified by column chromatography using 20%
EtOAc/hexane (v/v) as the eluent to give the pure product 25 (1.71 g,
8.0 mmol) in 80% yield as a gummy solid. TLC, Rf 0.2 (30% EtOAc/
3445, 2923, 2855, 1725, 1457, 1074, 742 cmꢀ1
; dH (400 MHz, CDCl3)
7.77 (d, J¼8.5 Hz, 2H), 7.36e7.24 (m, 12H), 5.88e5.74 (m, 1H),
5.67e5.56 (m, 1H), 5.35e5.17 (m, 4H), 4.65e4.47 (m, 4H), 4.19e3.98
(m, 3H), 3.90e3.74 (m, 2H), 3.43 (dd, J¼6.9, 5.3 Hz, 1H), 3.30 (m,
2H), 2.43 (s, 3H), 1.72e1.17 (m, 22H), 0.88 (t, J¼6.4 Hz, 3H); dC
(75 MHz, CDCl3) 144.9, 138.5, 138.1, 137.4, 135.1, 129.8, 128.4, 128.3,
127.9, 127.8, 127.7, 127.6, 119.7, 116.7, 81.7, 81.6, 80.7, 76.4, 74.0, 73.1,
72.3, 71.3, 70.5, 31.9, 29.8, 29.6, 29.5, 29.3, 25.9, 25.8, 24.5, 22.6, 21.6,
14.1; m/z (MS-ESI) 768 [MþNH4]þ, 773 [MþNa]þ. HRMS (ESI) calcd
for C44H62O8NaS: 773.4063. Found: 773.4089.
4.1.17. (3S,4S,7S,8S)-4,7-Bis(benzyloxy)-8-((S)-1-((R)-oxiran-2-yl)
undecyloxy)deca-1,9-dien-3-ol [27]. To a solution of the tosylate 26
(1.58 g, 2.1 mmol) in a mixture of acetonitrile/ethanol (1:1, 20 mL)
was added anhydrous K2CO3 (1.18 g, 4.4 mmol) and the reaction
mixture was stirred at rt for 12 h. The reaction mixture was passed
through a pad of Celite and the Celite pad was washed with aceto-
nitrile (15 mL). The combined organic layers were evaporated under
reduced pressure to afford the crude product, which was purified by
column chromatography using 10% EtOAc/hexane (v/v) as the elu-
ent to give the epoxide 27 (1.09 g, 1.89 mmol) in 90% yield as
hexane). ½a 2D5
ꢂ
þ47.3 (c 3.0, CHCl3); nmax (KBr) 3287, 2923, 2852,
1460, 1250, 872, 719 cmꢀ1
;
dH (400 MHz, CDCl3) 3.87 (ddd, J¼12.5,
5.5, 2.3 Hz, 1H), 3.59 (ddd, J¼12.5, 7.8, 3.9 Hz, 1H), 2.94e2.83 (m,
2H), 1.60e1.23 (m, 18H), 0.90 (t, J¼6.2 Hz, 3H); dC (75 MHz, CDCl3)
61.7, 58.4, 56.0, 31.8, 31.5, 29.5, 29.4, 29.3, 25.9, 22.6, 14.0; m/z (MS-
ESI) 215 [MþH]þ. HRMS (ESI) calcd for C13H26O2Na: 237.1830.
Found: 237.1835.
a gummy oil. TLC, Rf 0.3 (20% EtOAc/hexane). ½a D25
ꢀ17.2 (c 2.52,
ꢂ
MeOH); nmax (KBr) 3432, 2924, 2854, 1763, 1457, 1243, 1058, 923,
699 cmꢀ1
; dH (400 MHz, CDCl3) 7.33e7.17 (m, 10H), 5.83e5.66 (m,
2H), 5.31e5.11 (m, 4H), 4.74e4.42 (m, 4H), 3.97 (t, J¼5.5 Hz,1H), 3.81
(t, J¼6.6 Hz, 1H), 3.34e3.21 (m, 2H), 3.08 (dd, J¼11.3, 5.5 Hz, 1H),
2.77e2.72 (m, 1H), 2.63 (dd, J¼5.5, 4.0 Hz, 1H), 2.50 (dd, J¼5.3,
2.6 Hz, 1H), 1.66e1.14 (m, 22H), 0.85 (t, J¼6.0 Hz, 3H); dC (75 MHz,
CDCl3) 138.7,138.2,137.7,136.4,128.4,128.3,127.8,127.7,127.6,127.5,
117.7, 116.4, 82.0, 81.9, 80.9, 77.8, 73.9, 73.0, 72.3, 53.4, 46.1, 32.9,
32.0, 30.0, 29.7, 29.6, 29.5, 29.4, 26.0, 25.8, 25.0, 22.7, 14.2; m/z (MS-
ESI) 601 [MþNa]þ. HRMS (ESI) calcd for C37H54O5Na: 601.3868.
Found: 601.3858.
4.1.15. ((2R,3R)-3-Decyloxiran-2-yl)methyl 4-methylbenzene-
sulfonate [5]. To a solution of the epoxy alcohol 25 (1.71 g,
8.0 mmol) in DCM (40 mL) were added Et3N (2.24 mL,16 mmol) and
catalytic amounts of DMAP. The reaction mixture was cooled to 0 ꢁC
and tosyl chloride (1.85 g, 9.6 mmol) was added. The reaction was
stirred gradually allowing the temperature to rise to rt for 3 h. The
reaction mixture was diluted with DCM (50 mL). The organic layer
was washed with water, brine, and dried over Na2SO4. The solvent
was evaporated under reduced pressure to afford the crude prod-
uct, which was purified by column chromatography using 10%
EtOAc/hexane (v/v) as the eluent to give the pure tosylate 5 (2.65 g,
7.2 mmol) in 90% yield as a gummy solid. TLC, Rf 0.2 (10% EtOAc/
4.1.18. (3R,4S)-4-((3S,4S,7S,8S)-4,7-Bis(benzyloxy)-8-hydroxydeca-
1,9-dien-3-yloxy)tetradec-1-en-3-ol [4]. To a suspension of trime-
thylsulfonium iodide (184 mg, 0.9 mmol) in anhydrous THF
(2.8 mL) cooled at ꢀ10 ꢁC was added n-BuLi (0.3 mL, 2.4 M in
hexanes, 0.72 mmol) and the reaction mixture stirred for 1 h. To
this a solution of the epoxide 27 (110 mg, 0.18 mmol) in THF
(1.8 mL) was added dropwise. The reaction mixture was gradually
allowed to warm to rt and stirred for 4 h. The reaction was
quenched by adding saturated aq NH4Cl, it was then filtered
through a pad of Celite and the residue was washed with EtOAc. The
combined organic layers were washed with water, brine and dried
over Na2SO4. The solvent was evaporated under reduced pressure
to afford the crude product, which was purified by column chro-
matography using 15% EtOAc/hexane (v/v) as the eluent to give
pure 4 (79 mg, 0.13 mmol) in 70% yield as a gummy oil. TLC: Rf 0.3
hexane). ½a 2D5
ꢂ
þ37.3 (c 2.0, CHCl3); nmax (KBr) 3445, 2920, 2850,
1640, 1250, 870, 570 cmꢀ1
;
dH (400 MHz, CDCl3) 7.78 (d, J¼8.3 Hz,
2H), 7.33 (d, J¼8.3 Hz, 2H), 4.10 (dd, J¼11.3, 4.5 Hz, 1H), 3.95 (dd,
J¼11.3, 6.0 Hz, 1H), 2.90e2.87 (m, 1H), 2.75e2.71 (m, 1H), 2.46 (s,
3H), 1.55e1.20 (m, 18H), 0.89 (t, J¼6.8 Hz, 3H); dC (75 MHz, CDCl3)
144.5, 133.5, 129.8, 128.1, 69.9, 56.7, 54.4, 31.9, 31.4, 29.7, 29.6, 29.5,
29.4, 25.8, 22.7, 21.7, 14.3; m/z (MS-ESI) 391 [MþNa]þ. HRMS (ESI)
calcd for C20H32O4SNa: 391.1919. Found: 391.1916.
4.1.16. (2R,3S)-3-((3S,4S,7S,8S)-4,7-Bis(benzyloxy)-8-hydroxydeca-
1,9-dien-3-yloxy)-2-hydroxytridecyl 4-methylbenzenesulfonate
[26]. To a solution of the mixture of diol 6 (1.14 g, 3 mmol), ep-
(30% EtOAc/hexane). ½a D25
ꢂ
ꢀ37.3 (c 1.0, MeOH); nmax (KBr) 3540,
2925, 2362, 1638, 1147, 772 cmꢀ1
;
dH (400 MHz, CDCl3) 7.33e7.21
ꢀ
oxy tosylate 5 (1.32 g, 3.6 mmol) and activated powdered 4 A MS
(m, 10H), 5.88e5.69 (m, 3H), 5.34e5.13 (m, 6H), 4.69e4.45 (m, 4H),
4.08e4.05 (m, 1H), 4.00 (t, J¼5.9 Hz, 1H), 3.90 (t, J¼6.0 Hz, 1H),
3.41e3.33 (m, 2H), 3.27 (dd, J¼10.6, 4.7 Hz, 1H), 1.70e1.18 (m, 22H),
(100 mg) in DCM (6.6 mL) cooled at 0 ꢁC was added freshly distilled
BF3$Et2O (38 mL, 0.3 mmol). The reaction mixture was allowed to

7536
S. Raghavan, S.G. Subramanian / Tetrahedron 67 (2011) 7529e7539
0.9 (t, J¼6.6 Hz, 3H), m/z (MS-ESI) 615 [MþNa]þ. HRMS (ESI) calcd
to warm to rt and stirred for 4 h. The reaction was quenched by
adding saturated aq NH4Cl, it was then filtered through a pad of
Celite and the residue was washed with EtOAc. The combined or-
ganic layers were washed with water, brine, and dried over Na2SO4.
The solvent was evaporated under reduced pressure to afford the
crude product, which was purified by column chromatography
using 15% EtOAc/hexane (v/v) as the eluent to give pure 31 (0.95g,
1.35 mmol) in 70% yield. As a gummy oil. TLC, Rf 0.2 (20% EtOAc/
for C38H56O5Na: 615.4025. Found: 615.4035.
4.1.19. (2S,3R,6S)-6-((1S,4S,5S)-1,4-Bis(benzyloxy)-5-hydroxyhept-6-
enyl)-2-decyl-3,6-dihydro-2H-pyran-3-ol [2] and (1S,4S,5S,8S,Z)-5,8-
bis(benzyloxy)-4-((3R,4S)-3-hydroxytetradec-1-en-4-yloxy)cyclooct-
2-enol [29]. To a solution of the allylic alcohol 4 (79 mg, 0.13 mmol)
in DCM (27 mL) was added Grubbs second generation catalyst 28
(6 mg, 0.007 mmol) and the mixture refluxed for 12 h. The solvent
was evaporated under reduced pressure to afford the crude prod-
uct, which was purified by column chromatography using 30%
EtOAc/hexane (v/v) as the eluent, the product 2 eluted initially
(30 mg, 0.05 mmol) in 38% yield and the cyclooctene derivative 29
eluted next (30 mg, 0.05 mmol) in 38% yield.
hexane). ½a 2D5
ꢂ
ꢀ17.3 (c 1.0, MeOH); nmax (KBr) 3452, 2934, 2862,
1739, 1451,1070, 742 cmꢀ1
;
dH (400 MHz, CDCl3) 7.24e7.19 (m,10H),
5.93e5.68 (m, 3H), 5.26e5.11 (m, 6H), 4.67e4.50 (m, 4H), 4.22 (t,
J¼5.5 Hz, 1H), 4.09e4.03 (m, 1H), 3.85 (dd, J¼7.4, 6.2 Hz, 1H),
3.43e3.24 (m, 3H), 1.68e1.16 (m, 22H), 0.96e0.87 (m, 12H), 0.56 (q,
J¼7.7 Hz, 6H); dC (75 MHz, CDCl3) 138.9, 138.8, 137.7, 136.7, 136.3,
128.2, 127.8, 127.5, 118.7, 116.2, 115.5, 82.4, 81.1, 80.3, 74.7, 74.1, 73.1,
72.7, 32.0, 30.0, 29.8, 29.7, 29.6, 29.4, 26.9, 25.8, 25.7, 22.8, 14.2, 7.0,
5.0; m/z (MS-ESI) 729 [MþNa]þ. HRMS (ESI) calcd for C44H70O5N-
aSi: 729.4890. Found: 729.4908.
Compound 2: Gummy oil. TLC, Rf 0.2 (30% EtOAc/hexane). ½a D25
ꢂ
ꢀ72.0 (c 2.0, MeOH); nmax (KBr) 3428, 2923, 2855, 1455, 1069,
739 cmꢀ1
; dH (400 MHz, CDCl3) 7.34e7.23 (m, 10H), 5.87e5.75 (m,
3H), 5.32 ( dt, J¼15.6, 1.5 Hz, 1H), 5.17 (dt, J¼10.4, 1.5 Hz, 1H),
4.69e4.47 (m, 4H), 4.29e4.25 (m, 1H), 4.0 (t, J¼5.8 Hz, 1H),
3.89e3.84 (m, 1H), 3.45e3.37 (m, 1H), 3.28 (dd, J¼10.6, 5.9 Hz, 1H),
3.14 (dt, J¼8.3, 2.6 Hz, 1H), 1.68e1.20 (m, 22H), 0.89 (t, J¼7.0 Hz,
3H). m/z (MS-ESI) 587 [MþNa]þ. HRMS (ESI) calcd for C36H52O5Na:
587.3712 Found: 587.3733.
4.1.22. (2S,3R,6S)-6-((1S,4S,5S)-1,4-Bis(benzyloxy)-5-(triethylsily-
loxy)hept-6-enyl)-2-decyl-3,6-dihydro-2H-pyran-3-ol [32]. To a so-
lution of the allylic alcohol 31 (0.953 g, 1.35 mmol) in DCM (270 mL)
was added Grubbs second generation catalyst 28 (58 mg,
0.067 mmol) and refluxed for 12 h. The solvent was evaporated
under reduced pressure to afford the crude product, which was
purified by column chromatography using 20% EtOAc/hexane (v/v)
as the eluent to give the pure product 32 (0.79 g, 1.16 mmol) in 85%
Compound 29: Gummy oil. TLC, Rf 0.1 (30% EtOAc/hexane). ½a D25
ꢂ
ꢀ82.0 (c 2.2, MeOH); nmax (KBr) 3422, 2920, 2850, 1440, 1071,
739 cmꢀ1
; dH (400 MHz, CDCl3) 7.35e7.22 (m, 10H), 6.13e6.07 (m,
1H), 5.87e5.78 (m, 2H), 5.3 (dt, J¼15.2, 1.5 Hz, 1H), 5.2 (dt, J¼10.5,
1.5 Hz, 1H), 4.63e4.46 (m, 4H), 4.16e4.11 (m, 1H), 4.04 (t, J¼5.5 Hz,
1H), 3.90 (td, J¼8.7, 2.6 Hz, 1H), 3.73e3.69 (m, 1H), 3.42 (dd, J¼10.6,
5.9 Hz, 1H), 3.32 (t, J¼5.9 Hz, 1H), 2.3 (dd, J¼14.6, 7.9 Hz, 1H),
2.07e1.96 (m, 1H), 1.71e1.08 (m, 20H), 0.88 (t, J¼6.8 Hz, 3H). m/z
(MS-ESI) 587 [MþNa]þ. HRMS (ESI) calcd for C36H52O5Na: 587.3712.
Found: 587.3703.
yield as a gummy oil. TLC, Rf 0.2 (25% EtOAc/hexane). ½a D25
ꢀ89.0 (c
ꢂ
2.25 MeOH); nmax (KBr) 3448, 2926, 2855, 1728, 1635, 1255, 1023,
613 cmꢀ1
; dH (400 MHz, CDCl3) 7.32e7.16 (m, 10H), 5.92e5.74 (m,
3H), 5.16 (dt, J¼17.2, 1.7 Hz, 1H), 5.10 (dt, J¼10.6, 1.7 Hz, 1H), 4.65 (d,
J¼8.9 Hz, 1H), 4.61 (d, J¼8.9 Hz, 1H), 4.53 (d, J¼5.9 Hz, 1H), 4.50 (d,
J¼5.9 Hz, 1H), 4.24e4.17 (m, 2H), 3.86e3.82 (m, 1H), 3.37 (dd,
J¼11.1, 6.0 Hz, 1H), 3.29e3.23 (m, 1H), 3.11 (td, J¼8.5, 2.5 Hz, 1H),
1.78e1.20 (m, 22H), 0.96e0.86 (m, 12H), 0.55 (q, J¼7.7 Hz, 6H); dC
(75 MHz, CDCl3) 138.9, 138.8, 137.8, 130.5, 128.8, 128.2, 127.9, 127.7,
127.4, 115.5, 82.3, 80.4, 79.6, 75.7, 74.8, 72.9, 72.5, 68.1, 32.5, 32.0,
29.9, 29.8, 29.7, 29.6, 26.4, 26.2, 26.0, 22.8, 14.3, 7.0, 4.9; m/z (MS-
ESI) 696 [MþNH4þ]þ. HRMS (ESI) calcd for C42H66O5NaSi: 701.4577.
Found: 701.4567.
4.1.20. ((3S,4S,7S,8S)-4,7-Bis(benzyloxy)-8-((S)-1-((R)-oxiran-2-yl)
undecyloxy)deca-1,9-dien-3-yloxy)triethylsilane [30]. To a solution
of the carbinol 27 (1.15 g, 2.0 mmol) in DCM (10 mL) cooled at 0 ꢁC
was added imidazole (0.27 g, 4 mmol) followed by TES-Cl (0.5 mL,
3 mmol) dropwise. The reaction mixture was gradually allowed to
warm to rt and stirred for 2 h. The reaction was quenched by adding
saturated aq NH4Cl solution. The organic layer was separated and
the aqueous layer was extracted with DCM. The combined organic
layers were washed with water, brine and dried over Na2SO4. The
solvent was evaporated under reduced pressure to afford the crude
product, which was purified by column chromatography using 10%
EtOAc/hexane (v/v) as the eluent to give the product 30 (1.25 g,
1.8 mmol) in 90% yield as the gummy oil. TLC, Rf 0.5 (15% EtOAc/
4.1.23. ((2S,3R,6S)-6-((1S,4S,5S)-1,4-Bis(benzyloxy)-5-(triethylsily-
loxy)hept-6-enyl)-2-decyl-3,6-dihydro-2H-pyran-3-yloxy)(tert-bu-
tyl)dimethylsilane [33]. To a solution of the pyran derivative 32
(0.79 g, 1.16 mmol) in DCM (12 mL) was added 2,6-lutidine
(0.32 mL, 2.78 mmol) and the reaction mixture was cooled to
ꢀ78 ꢁC. TBSOTf (0.32 mL, 1.39 mmol) was added dropwise and the
reaction mixture was stirred at the same temperature for 15 min.
The reaction was quenched by adding saturated aq NH4Cl solution
(5 mL). The layers were separated and the layer was extracted with
DCM (10 mL). The combined organic layers were washed with
water, brine and dried over anhydrous Na2SO4. The solvent was
evaporated under reduced pressure to afford the crude product,
which was purified by column chromatography using 5% EtOAc/
hexane (v/v) as the eluent to give the pure product 33 (0.78 g,
0.98 mmol) in 85% yield as a gummy oil. TLC, Rf 0.2 (25% EtOAc/
hexane). ½a 2D5
ꢂ
ꢀ2.0 (c 1.0, MeOH); nmax (KBr) 2925, 2859, 1727, 1458,
1078, 736 cmꢀ1
;
dH (400 MHz, CDCl3) 7.27e7.12 (m,10H), 5.85e5.54
(m, 2H), 5.19e5.03 (m, 4H), 4.67e4.42 (m, 4H), 4.14 (t, J¼5.5 Hz,1H),
3.73 (t, J¼6.6 Hz, 1H), 3.28e3.15 (m, 2H), 3.00 (dd, J¼11.3, 6.0 Hz,
1H), 2.71e2.67 (m, 1H), 2.56 (dd, J¼5.3, 3.8 Hz, 1H), 2.44 (dd, J¼5.3,
2.6 Hz, 1H), 1.57e1.13 (m, 22H), 0.88e0.81 (m, 12H), 0.48 (q,
J¼7.9 Hz, 6H); dC (75 MHz, CDCl3) 139.0, 138.9, 137.6, 136.6, 128.1,
127.7, 127.6, 127.4, 117.3, 115.4, 82.5, 82.3, 81.2, 78.0, 74.6, 73.0, 72.7,
53.4, 46.2, 33.0, 32.0, 30.0, 29.7, 29.6, 29.5, 29.4, 26.8, 25.8, 24.9,
22.7, 14.2, 6.9, 5.0; m/z (MS-ESI) 715 [MþNa]þ. HRMS (ESI) calcd for
C43H68O5NaSi: 715.4734. Found: 715.4744.
hexane). ½a 2D5
ꢂ
ꢀ104.0 (c 2.5, CHCl3); nmax (KBr) 2923, 2853, 1461,
1088, 836, 733 cmꢀ1
;
dH (400 MHz, CDCl3) 7.30e7.19 (m, 10H),
5.92e5.66 (m, 3H), 5.22 (dt, J¼17.2, 1.3 Hz, 1H), 5.11 (dt, J¼10.4,
1.3 Hz, 1H), 4.65 (d, J¼8.7 Hz, 1H), 4.61 (d, J¼8.7 Hz, 1H), 4.54 (d,
J¼9.6 Hz, 1H), 4.50 (d, J¼9.6 Hz, 1H), 4.24e4.17 (m, 2H), 3.88 (dd,
J¼8.1, 2.6 Hz, 1H), 3.39e3.13 (m, 3H), 1.76e1.16 (m, 22H), 0.99e0.85
(m, 21 H), 0.55 (q, J¼7.7 Hz, 6H), 0.08 (s, 3H), 0.06 (s, 3H). dC
(75 MHz, CDCl3) 139.0, 138.8, 137.9, 131.4, 128.2, 127.9, 127.8, 127.7,
127.4, 115.5, 82.3, 80.5, 79.1, 75.9, 74.8, 72.8, 72.5, 68.6, 32.2,
32.0, 29.7, 29.6, 29.4, 26.4, 26.2, 25.9, 25.4, 22.7, 18.1, 14.2, 7.0, 4.9,
4.1.21. (3R,4S)-4-((3S,4S,7S,8S)-4,7-Bis(benzyloxy)-8-(triethylsily-
loxy)deca-1,9-dien-3-yloxy)tetradec-1-en-3-ol [31]. To a suspension
of trimethylsulfonium iodide (1.84 g, 9 mmol) in anhydrous THF
(28 mL) cooled at ꢀ10 ꢁC was added n-BuLi (3.6 mL, 2.5 M in
hexanes, 9 mmol) and the reaction mixture was stirred for 1 h. To
this a solution of the epoxide 30 (1.25g, 1.8 mmol) in THF (2.5 mL)
was added dropwise. The reaction mixture was gradually allowed

S. Raghavan, S.G. Subramanian / Tetrahedron 67 (2011) 7529e7539
7537
ꢀ4.0, ꢀ4.6. m/z (MS-ESI) 816 [MþNa]þ. HRMS (ESI) calcd for
(550 mg, 3.23 mmol) and 2,6-lutidine (1.88 mL,16.15 mmol) in DCM
(30 mL) at ꢀ50 ꢁC. After 15 min, TBSOTf (1.11 mL, 4.84 mmol) was
added and the mixture was stirred for 5 min at 0 ꢁC. The reaction
was quenched by adding saturated aq NH4Cl (10 mL) and the
mixture was extracted with Et2O. The extract was washed with
saturated aq NH4Cl, water, and brine prior to drying and solvent
evaporation. The residue was purified by column chromatography
using 10% EtOAc/hexane (v/v) as the eluent to give pure triflate 38
(1.24 g, 3.0 mmol) in 93% yield, which was used immediately for the
next step. To a solution of LHMDS (1.0 M in THF, 6.0 mL, 6.0 mmol)
in THF (15 mL) cooled at ꢀ78 ꢁC was added lactone 39 (1.24 g,
6 mmol) in THF (18 mL). The mixture was stirred for 10 min, then at
0 ꢁC for 10 min and again cooled to ꢀ78 ꢁC. After 10 min of stirring,
HMPA (19 mL) was added and then after 5 min, the solution of
triflate 38 (1.24 g, 3.0 mmol) in THF (44 mL), precooled to ꢀ78 ꢁC
was canulated into it. After 10 min, the mixture was allowed to
warm to 0 ꢁC over a period of 15 min, then stirred at rt for 10 min
and quenched with aq NH4Cl extracted with ether (3ꢃ50 mL) and
the combined organic layers were washed with saturated NH4Cl
(30 mL). The organic layer was separated and washed with brine
(30 mL), dried over anhydrous Na2SO4. The solvent was evaporated
under reduced pressure to afford the crude product, which was
purified by column chromatography using 20% EtOAc/hexane (v/v)
as the eluent to give the alkylated product 40 as a diastereomeric
mixture (924 mg, 1.95 mmol) in 65% yield as a gummy oil. TLC, Rf
C48H80O5NaSi2: 815.5442. Found: 815.5440.
4.1.24. Dec-9-ynal [35]. To a solution of oxalyl chloride (8.2 mL,
93.45 mmol) in DCM (200 mL) cooled at ꢀ78 ꢁC under nitrogen
atmosphere was added a solution of DMSO (8.7 mL, 124.6 mmol)
in DCM (15 mL) dropwise and stirred for 5 min at this tempera-
ture. To the above, a solution of the alcohol 34 (9.6 g, 62.3 mmol)
in DCM (15 mL) was added dropwise. The reaction mixture was
stirred for 30 min at this temperature, Et3N (43.7 mL, 311.5 mmol)
was added dropwise at ꢀ78 ꢁC and the reaction mixture was
allowed to warm to rt. Water (200 mL) was added and the organic
layer was separated. The aq layer was extracted with DCM
(2ꢃ100 mL). The combined organic layers were washed succes-
sively with 1 M HCl (100 mL), water, brine, dried over anhydrous
Na2SO4 and evaporated under reduced pressure to afford the
crude aldehyde which was purified by column chromatography
using 10% EtOAc/hexane (v/v) as the eluent to give pure aldehyde
35 (8.52 g, 56.07 mmol) in 90% yield as a gummy oil. TLC, Rf 0.3
(15% EtOAc/hexane); nmax (KBr) 2930, 1725, 1636, 769 cmꢀ1
; dH
(400 MHz, CDCl3) 9.75 (s, 1H), 2.33 (t, J¼7.4 Hz, 2H), 2.16 (td, J¼6.6,
2.2 Hz, 2H), 1.84 (t, J¼2.2 Hz, 1H), 1.70e1.31 (m, 10H). dC (75 MHz,
CDCl3) 180.1, 84.5, 68.1, 33.9, 28.8, 28.6, 28.4, 28.3, 24.5, 18.2; m/z
(MS -EI) 175 [MþNa]þ. HRMS (ESI) calcd for C10H16ONa: 175.1098.
Found: 175.1093.
0.25 (25% EtOAc/hexane). ½a D25
ꢂ
ꢀ89.0 (c 2.25 MeOH); nmax (KBr)
4.1.25. (R)-Dec-9-yne-1,2-diol [36]. DMSO (4 mL) was added to
L-
2931, 2857, 1766, 1465, 1184, 834 cmꢀ1
; dH (400 MHz, CDCl3)
proline (55.2 mg, 0.48 mmol), and DMSO (4 mL) at rt under ni-
trogen atmosphere and the suspension was stirred for 10 min.
Nitrosobenzene (257 mg, 2.4 mmol) was added in one portion at
which time the solution became green. Aldehyde 35 (400 mg,
2.63 mmol) in DMSO (11 mL) was added in one portion to the above
greenish suspension and stirring continued at rt until the reaction
was determined to be complete by TLC (the change of color of the
green colour solution to a yellow homogeneous solution was ob-
served). The reaction mixture was then transferred to a suspension
of NaBH4 (365 mg, 9.6 mmol) in ethanol (5 mL) at 0 ꢁC. After 20 min
of stirring, the reaction mixture was treated with saturated aq
NaHCO3 (15 mL) and extracted with dichloromethane (3ꢃ10 mL).
The combined organic layers were washed with brine (15 mL),
dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to
afford the crude anilinoxy compound (470 mg, 1.8 mmol) in 75%
yield, which was used immediately for the next reaction. (b) To
a solution of the above anilinoxy compound (470 mg, 1.8 mmol) in
methanol (8 mL), was added CuSO4$5H20 (174 mg, 0.61 mmol). The
reaction mixture was stirred at rt overnight and then quenched
with a cold saturated NH4Cl solution (5 mL). The mixture was fil-
tered on a Celite pad and washed thoroughly with ethyl acetate
(15 mL). The volatiles were removed under reduced pressure. The
residue was extracted with ethyl acetate (3ꢃ15 mL). The combined
organic layers were washed with brine (10 mL), dried over anhy-
drous Na2SO4. The solvent was evaporated under reduced pressure
to afford the crude product, which was purified by column chro-
matography using 30% EtOAc/hexane (v/v) as the eluent to give
pure diol 36 (214 mg, 1.26 mmol) in 70% yield as a gummy oil. TLC,
7.53e7.24 (m, 10H), 4.63e4.42 (m, 2H), 4.26e4.16 (m, 1H),
3.82e3.73 (m, 1H), 2.98 (dd, J¼14.4, 7.6 Hz, 1H), 2.43 (dd, J¼14.4,
10.6 Hz, 1H), 2.24 (J¼14.4, 7.6 Hz, 1H), 2.16e2.06 (m, 4H), 2.0e1.76
(m, 7H), 1.56e1.09 (m, 26H), 0.88 (s, 9H), 0.85 (s, 9H), 0.14 (s, 3H),
0.10 (s, 3H), 0.01 (s, 3H), 0.00 (s, 3H). dC (75 MHz, CDCl3) 176.7, 174.3,
137.1, 136.7, 130.5, 129.9, 129.5, 128.9, 84.3, 84.2, 73.2, 72.9, 70.2,
69.4, 68.5, 55.0, 54.8, 42.5, 41.5, 41.2, 39.8, 38.5, 38.0, 29.3, 29.1, 28.7,
28.3, 26.1, 24.4, 21.6, 20.5, 18.4, 18.1, ꢀ3.6, ꢀ3.7, ꢀ4.0. m/z (MS-ESI)
497 [MþNa]þ. HRMS (ESI) calcd for C27H42O3SiSNa: 497.2521.
Found: 497.2511.
4.1.27. (S)-3-((R)-2-(tert-Butyldimethylsilyloxy)dec-9-ynyl)-5-
methylfuran-2(5H)-one [41]. To a solution of the alkylated product
40 (924 mg, 1.95 mmol) in DCM (5 mL) cooled to 0 ꢁC was added
m-CPBA (370 mg, 2.14 mmol) portionwise over 30 min. The reaction
was quenched by adding saturated aq Na2SO3 (5 mL). The layers
were separated, the aqueous layer was extracted with DCM (10 mL).
The combined organic layers were washed with saturated aq
NaHCO3 (10 mL), water, brine and dried over anhydrous Na2SO4.
The solvent was evaporated under reduced pressure to afford the
crude sulfoxides (860 mg, 1.75 mmol) as a diastereomeric mixture
in 90% yield. The crude compound was taken ahead to the next step
without purification. To a solution of the sulfoxides (860 mg,
1.75 mmol) in toluene (17.5 mL) was added solid Na2CO3 (372 mg,
3.5 mmol) and the mixture heated to reflux for 6 h. The reaction
mixture was cooled to rt, filtered through a pad of Celite and
washed with ethyl acetate. The combined organic layers were
evaporated under reduced pressure to afford the crude compound,
which was purified by column chromatography using 10% EtOAc/
hexane (v/v) as the eluent to give the pure enone 41 (541 mg,
1.48 mmol) in 85% yield as a gummy oil. TLC, Rf 0.25 (15% EtOAc/
Rf 0.25 (40% EtOAc/hexane). ½a D25
ꢂ
þ8.6 (c 1.02, CHCl3); nmax (KBr)
3405, 2933, 2858, 1639, 1460, 1061, 770 cmꢀ1
;
dH (400 MHz, CDCl3)
4.07 (br s, 1H), 3.64e3.49 (m, 3H), 3.3 (dd, J¼11.3, 8.3 Hz, 1H), 2.14
(td, J¼6.8, 2.3 Hz, 2H), 1.84 (t, J¼2.3 Hz, 1H), 1.53e1.23 (m, 10H). dC
(75 MHz, CDCl3) 84.6, 72.2, 68.2, 66.7, 33.0, 29.0, 28.5, 28.3, 25.4,
18.3. m/z (MS-EI) 193 [MþNa]þ. HRMS (ESI) calcd for C10H18O2Na:
193.1204. Found: 193.1211.
hexane). ½a 2D5
ꢂ
þ26.8 (c 2.25 CHCl3); nmax (KBr) 2928, 2857, 1755,
1073, 836, 775 cmꢀ1
;
dH (400 MHz, CDCl3) 7.10 (d, J¼1.5 Hz, 1H), 5.0
(q, J¼6.8 Hz, 1H), 4.0e3.94 (m, 1H), 2.44 (d, J¼6.0 Hz, 2H), 2.18 (td,
J¼6.8, 3.0 Hz, 2H), 1.86 (t, J¼3.0 Hz, 1H), 1.59e1.26 (m, 13 H), 0.90
(s, 9H), 0.08 (s, 3H), 0.05 (s, 3H). dC (75 MHz, CDCl3) 173.1, 150.9,
131.0, 84.2, 77.0, 70.0, 68.5, 36.9, 32.9, 29.2, 28.6, 28.3, 26.0, 25.0,
19.1, 18.1, ꢀ4.4. m/z (MS-ESI) 387 [MþNa]þ. HRMS (ESI) calcd for
C21H36O3SiNa: 387.2331. Found: 387.2331.
4.1.26. (S)-3-((R)-2-(tert-Butyldimethylsilyloxy)dec-9-ynyl)-5-
methyl-3-(phenylthio)dihydrofuran-2(3H)-one [40]. Freshly distilled
Tf2O (0.6 mL, 3.62 mmol) was added to a mixture of diol 36

7538
S. Raghavan, S.G. Subramanian / Tetrahedron 67 (2011) 7529e7539
4.1.28. (S)-3-((R)-10-Bromo-2-(tert-butyldimethylsilyloxy)dec-9-
ynyl)-5-methylfuran-2(5H)-one [42]. A solution of the enone 41
(900 mg, 2.47 mmol) in acetone (25 mL) was treated at rt with
AgNO3 (42 mg, 0.247 mmol) and N-bromosuccinimide (528 mg,
2.96 mmol). After 1h, ether (30 mL) was added, and the mixture
was filtered through a plug of Celite. The plug was rinsed with ether
(20 mL) and the combined organic layers were evaporated under
reduced pressure to afford the crude compound which was purified
by column chromatography using 10% EtOAc/hexane (v/v) as the
eluent to give the pure bromo alkyne 42 (820 mg, 1.85 mmol) in
0.105 mmol) in THF (0.5 mL), and the resultant solution was stirred
at rt for 70 min. In a separate flask, a solution of (E)-vinyl iodide 3
(45 mg, 0.09 mmol) in DMF (0.7 mL) was prepared. To this solution
were added PdCl2(dppf)$CH2Cl2 (6.5 mg, 0.009 mmol), Ph3As
(3.0 mg, 0.009 mmol), and 3 M aq Cs2CO3 solution (0.045 mL,
0.13 mmol). The resultant mixture was stirred at rt for 15 min be-
fore it was treated with the above trialkylborane solution. After
being stirred at rt overnight, the resultant mixture was diluted with
diethyl ether and washed with H2O. The aqueous layer was
extracted with diethyl ether. The combined organic layer was
washed with brine, dried over Na2SO4, filtered, and concentrated
under reduced pressure. A complex product mixture was obtained.
75% yield as a gummy oil. TLC, Rf 0.25 (15% EtOAc/hexane). ½a D25
ꢂ
þ15.9 (c 1.5, CHCl3); nmax (KBr) 3449, 2925, 2854, 1747, 1257,
1032 cmꢀ1
;
dH (400 MHz, CDCl3) 7.08 (d, J¼1.3 Hz, 1H), 5.0 (q,
J¼6.8 Hz, 1H), 4.01e3.93 (m, 1H), 2.42 (d, J¼5.7 Hz, 2H), 2.22 (t,
J¼6.8 Hz, 2H), 1.58e1.28 (m, 13H), 0.9 (s, 9H), 0.08 (s, 3H), 0.05 (s,
3H). dC (75 MHz, CDCl3) 173.4,151.1,131.0, 77.2, 70.0, 36.9, 32.9, 29.2,
28.7, 28.2, 26.0, 25.0, 19.7, 19.1, ꢀ4.3. m/z (MS-ESI) 466 [MþNa]þ.
HRMS (ESI) calcd for C21H36O3SiNaBr: 465.1436. Found: 465.1431.
Acknowledgements
S.R. is thankful to Dr. J.M. Rao, Head, Org. Div. I & Dr. J.S. Yadav,
Director, I.I.C.T, for constant support and encouragement. S.G.S is
thankful to CSIR, New Delhi for a fellowship. Financial assistance
from DST (New Delhi) is gratefully acknowledged. We thank Dr. A.C.
Kunwar for the NMR spectra and Dr. R. Srinivas for the mass spectra.
4.1.29. (S)-3-((R,E)-2-(tert-Butyldimethylsilyloxy)-10-iododec-9-
enyl)-5-methylfuran-2(5H)-one [3]. A solution of the bromo alkyne
42 (775 mg, 1.75 mmol) and PdCl2(PPh3)2 (246 mg, 0.35 mmol) in
THF (3.0 mL) was cooled under N2 to 0 ꢁC. The flask was evacuated,
flushed with N2 and n-Bu3SnH (0.93 mL, 3.5 mmol) was added in
one portion. The reaction mixture was stirred at 0 ꢁC for 30 min
where TLC examination showed complete disappearance of the
starting bromo alkyne. The reaction mixture was cooled to ꢀ78 ꢁC
and a solution of I2 (577 mg, 2.28 mmol) in DCM (30 mL) was added
dropwise over 20 min, such that a dark brown color persisted. The
mixture was quenched with saturated aq NaHCO3 (10 mL) and
saturated aq Na2S2O3 (10 mL) solutions. Ethyl acetate (10 mL) was
added and the mixture was stirred for 30 min at rt and extracted
with ethyl acetate. The combined organic layers were dried over
anhydrous Na2SO4, filtered, and concentrated. Purification by silica
gel chromatography using 10% EtOAc/hexane (v/v) as the eluent
furnished the vinyl iodide 3 (602 mg, 1.23 mmol) in 70% yield as
Supplementary data
Experimental procedure for the preparation of the mono
benzoate-mono mandelate ester of diol 36 and its enantiomer
prepared using D
-proline is detailed. Copies of 1H and 13C NMR
spectra are available. Supplementary data associated with this ar-
ticle can be found, in the online version, at doi:10.1016/
j.tet.2011.07.079.
References and notes
1. Shi, G.; Alfonso, D.; Fatope, M. O.; Zeng, L.; Gu, Z.-M.; Zhao, G.-x.; He, K.;
MacDougal, J. M.; McLaughlin, J. L. J. Am. Chem. Soc. 1995, 117, 10409.
2. (a) Rupprecht, J. K.; Hui, Y. H.; McLaughlin, J. L. J. Nat. Prod. 1990, 53, 237; (b)
Zeng, L.; Ye, Q.; Oberlies, N. H.; Shi, G.; Gu, Z. M.; He, K.; McLaughlin, J. L. Nat.
Prod. Rep. 1996, 13, 275; (c) Alali, F. Q.; Liu, X.-X.; McLaughlin, J. L. J. Nat. Prod.
1999, 62, 504.
a clear, colorless syrup. TLC, Rf 0.2 (15% ethyl acetate/hexanes); ½a D25
ꢂ
þ12.8 (c 2.0, CHCl3); nmax (KBr) 2922, 2852, 1759, 1461, 1070 cmꢀ1
;
3. McLaughlin, J. L. In Methods in Plant Biochemistry; Hostettmann, K., Ed.; Aca-
dH (400 MHz, CDCl3) 7.13 (d, J¼1.3 Hz, 1H), 6.56e6.45 (m, 1H), 5.97
(dd, J¼14.4, 1.3 Hz), 5.01 (q, J¼6.6 Hz, 1H), 4.02e3.93, (m, 1H), 2.43
(d, J¼5.3 Hz, 2H), 2.08 (q, J¼7.2 Hz, 2H), 1.49e1.26 (m, 13H), 0.90 (s,
9H), 0.07 (s, 3H), 0.05 (s, 3H). dC (75 MHz, CDCl3) 173.9, 151.3, 146.5,
130.8, 77.3, 74.4, 70.3, 36.8, 35.9, 32.7, 29.4, 28.8, 28.2, 25.9, 24.9,
19.0, ꢀ4.4. m/z (MS-ESI) 515 [MþNa]þ. HRMS (ESI) calcd for
C21H37IO3SiNa: 515.1454. Found: 515.1451.
demic: London, UK, 1991; Vol. 6, p 1.
4. (a) Ahammadsahib, K. I.; Hollingworth, R. M.; McGovren, J. P.; Hui, Y. H.;
McLaughlin, J. L. Life Sci. 1993, 53, 1113; (b) Morre, D. J.; de Cabo, R.; Farley, C.;
Oberlies, N. H.; McLaughlin, J. L. Life Sci. 1995, 56, 343.
5. (a) Neogi, P.; Doundoulakis, T.; Yazbak, A.; Sinha, S. C.; Sinha, S. C.; Keinan, E. J.
Am. Chem. Soc. 1998, 120, 11279; (b) Hoppen, S.; Baurle, S.; Koert, U. Chem.dEur.
J. 2000, 6, 2906; (c) Takahashi, S.; Kubota, A.; Nakata, T. Angew. Chem., Int. Ed.
2002, 41, 4751; (d) Takahashi, S.; Nakata, T. J. Org. Chem. 2002, 67, 5739 and
references therein; (e) Evans, P. A.; Cui, J.; Gharpure, S. J.; Polosukhin, A.; Zhang,
H. J. Am. Chem. Soc. 2003, 125, 14702; (f) Zhu, L.; Mootoo, D. R. Org. Biomol.
Chem. 2005, 3, 2750; (g) Crimmins, M. T.; Zhang, Y.; Dias, F. A. Org. Lett. 2006, 8,
2369.
6. Drago, C.; Caggiano, L.; Jackson, R. F. W. Angew. Chem., Int. Ed. 2005, 44, 7221.
7. Solladie, G.; Frechou, C.; Hutt, J.; Demailly, G. Bull. Soc. Chim. Fr. 1987, 827.
8. (a) Solladie, G.; Demailly, G.; Greck, C. Tetrahedron Lett. 1985, 26, 435; (b) Sol-
ladie, G.; Frechou, C.; Demailly, G.; Greck, C. J. Org. Chem. 1986, 51, 1912; (c)
Carreno, M. C.; Garcia Ruano, J. L.; Martin, A. M.; Pedregal, C.; Rodriguez, J. H.;
Rubio, A.; Sanchez, J.; Solladie, G. J. Org. Chem. 1990, 55, 2120.
9. For the oxidative functionalization of alkenes activated by electrophiles via
intramolecular participation of the sulfinyl group see: (a) Raghavan, S.;
Rasheed, M. A.; Joseph, S. C.; Rajender, A. Chem. Commun. 1999, 1845; (b) Ra-
ghavan, S.; Ramakrishna Reddy, S.; Tony, K. A.; Naveen Kumar, C. H.; Varma, A.
K.; Nangia, A. J. Org. Chem. 2002, 67, 5838; (c) Raghavan, S.; Rajender, A.; Joseph,
S. C.; Rasheed, M. A.; Ravi Kumar, K. Tetrahedron: Asymmetry 2004, 15, 365; (d)
Raghavan, S.; Sreekanth, T. Tetrahedron Lett. 2008, 49, 1169.
10. The 6-endo nucleophilic attack is expected based on Markonikov’s rule, see: (a)
Markovnikov, V. Liebigs Ann. Chem. 1870, 153, 256; (b) For a modern in-
terpretation, see: Isenberg, N.; Grdinic, M. J. Chem. Educ. 1969, 46, 601 No trace
of other regio- and stereisomers resulting from 1,2- and 1,4-addition across the
diene could be detected.
4.1.30. Attempted synthesis of compound 44. (a) To a solution of
compound 33 (56 mg, 0.07 mmol) in anhydrous THF (1 mL) cooled
at 0 ꢁC was added dropwise a solution of 9-BBN dimer (0.105 mmol
in 1 mL THF). The solution was stirred at 0 ꢁC until complete con-
version of the starting alkene (approximately 2 h, followed by TLC).
In another round bottomed flask, a suspension of K3PO4 (22 mg,
0.105 mmol) and iodo compound 3 (45 mg, 0.09 mmol) in freshly
distilled dioxane (1.5 mL) was degassed for 30 min by bubbling
nitrogen. The solution of trialkylborane and Pd(PPh3)4 (4 mg,
0.0035 mmol) was then added to the iodide solution and the re-
action mixture was heated for 8 h at 85 ꢁC. After cooling to rt, the
unreacted borane was oxidized by addition of an aqueous solution
of sodium acetate (0.01 mL, 3 M) and hydrogen peroxide (30%,
0.01 mL). After 1 h of stirring at rt, the red solution was diluted with
diethyl ether and washed with a saturated aq NH4Cl and brine. The
combined organic extracts were dried over Na2SO4. The organic
layer was evaporated under reduced pressure to afford the crude
product, which was found to be a complex product mixture.
(b) To a solution of 33 (56 mg, 0.07 mmol) in THF (0.9 mL) cooled
to 0 ꢁC was added a solution of 9-BBNeH dimer (25 mg,
11. Chamberlin, A. R.; Mulholland, R. L., Jr.; Kahn, S. D.; Hehre, W. J. J. Am. Chem. Soc.
1987, 109, 672.
12. Cossy, J.; BouzBouz, S.; Hoveyda, A. H. J. Organomet. Chem. 2001, 624, 327.
13. The metathesis reaction did not proceed under a variety of conditions using
Grubbs’ first generation catalyst while the yield was moderate using Grubbs’
second generation catalyst.

S. Raghavan, S.G. Subramanian / Tetrahedron 67 (2011) 7529e7539
7539
14. The hydroxy groups in compound 16 could not be protected as its benzyl ether
using benzyl imidate due to competitive binding of triflic acid to the more basic
oxygen of the sulfinyl moiety rather than the imine of the imidate. The starting
material was recovered unreacted after prolonged reaction period.
15. Lee, G. H.; Choi, E. B.; Lee, E.; Pak, C. S. Tetrahedron Lett. 1993, 34, 4541
Attempted reductive elimination of the sulfone using NaeHg afforded the
saturated sulfone in addition to the desired olefin 22.
16. Brown, H. C.; Yoon, N. M. J. Am. Chem. Soc. 1966, 88, 1464.
17. Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974.
18. Hoffmanm, H. M. R.; Pohlmann, J. Tetrahedron Lett. 1998, 39, 7085.
19. Alcaraz, L.; Harnett, J. J.; Mioskowski, C.; Martel, J. P.; Le Gall, T.; Shin, D.-S.;
Falck, J. R. Tetrahedron Lett. 1994, 35, 5449.
benzoate-mono mandelate ester with that of its enantiomer prepared using
-proline as the organocatalyst. See supplementary data for details.
D
26. Attempted alkylation using the iodo compound instead of the triflate afforded
S-alkylated product along with the unsaturated lactone as the major products.
27. Lactone 39 was prepared following the procedure of White and coworkers, see:
White, J. D.; Somers, T. C.; Reddy, G. N. J. Org. Chem. 1992, 57, 4991.
28. Yoshimitsu, T.; Makino, T.; Nagaoka, H. J. Org. Chem. 2004, 69, 1993.
29. Hofmeister, H.; Annen, K.; Laurent, H.; Weichert, R. Angew. Chem., Int. Ed. Engl.
1984, 23, 720.
30. Hydrostannation of terminal alkyne 40 afforded a regioisomeric mixture of
vinyl stannanes.
ꢁ
31. Zhang, H. X.; Guibe, F.; Balavoine, G. J. Org. Chem. 1990, 55, 1857.
20. Scholl, S.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953; (b) Sanford,
M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 1232, 6543.
21. The structure was assigned to compound 29 based on the NOE observed for the
methine protons at C14 and C22.
32. (a) Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Satoh, M.; Suzuki, A. J.
Am. Chem. Soc. 1989, 111, 314; (b) Oh-e, T.; Miyaura, N.; Suzuki, A. Synlett 1990,
221; (c) Watanabe, T.; Miyaura, N.; Suzuki, A. Synlett 1992, 207; (d) Miyaura, N.;
Suzuki, A. Chem. Rev. 1995, 95, 2457.
22. Macaulay, S. R. J. Org. Chem. 1980, 45, 734.
23. Mancuso, A. J.; Swern, D. Synthesis 1981, 165.
24. Zhong, G. Angew. Chem., Int. Ed. 2003, 42, 4247.
33. Johnson, C. R.; Braun, M. P. J. Am. Chem. Soc. 1993, 115, 11014.
34. The reason for the failure of the reaction is unclear, though the reaction
of 3 with an allylic alcohol protected as its triethylsilyl ether possessing
a long alkyl chain, a substrate much simpler to 33, afforded the desired
coupling product.
25. The enantiomeric purity (>95%) and absolute configuration (‘R’) of diol
36 was determined by comparison of the 1H NMR spectrum of its mono