A cross metathesis strategy for the synthesis of highly functionalized conjugated cyanodienes: synthesis of the C3-C17 framework of (-)-borrelidin

Article abstract of DOI:10.1016/j.tetlet.2008.01.055

A cross metathesis strategy for the synthesis of highly functionalized conjugated cyanodienes was developed and was successfully applied in the synthesis of the C3-C17 framework of (-)-borrelidin.

Full text of DOI:10.1016/j.tetlet.2008.01.055

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2013–2017
A cross metathesis strategy for the synthesis of highly
functionalized conjugated cyanodienes: synthesis of the
C3–C17 framework of (ꢀ)-borrelidin q
C. Vamsee Krishna a,b, Vasudev R. Bhonde a, A. Devendar a, Santanu Maitra a,
K. Mukkanti b, Javed Iqbal a,*
a Discovery Chemistry, Discovery Research, Dr. Reddy’s Laboratories, Ltd, Miyapur, Hyderabad 500 049, India
b Jawaharlal Nehru Technological University, Kukatpally, Hyderabad 500 072, India
Received 10 October 2007; revised 4 January 2008; accepted 10 January 2008
Available online 15 January 2008
Abstract
A cross metathesis strategy for the synthesis of highly functionalized conjugated cyanodienes was developed and was successfully
applied in the synthesis of the C3–C17 framework of (ꢀ)-borrelidin.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Borrelidin; Cross metathesis; Grubbs’ catalyst
Borrelidin (1) is a naturally occurring nitrile produced
by several Streptomycete species and was first isolated by
Jampolsky and Goldberg.1 Structure elucidation showed
it to be an 18-membered macrolide distinguished by a
1,3,5,7-‘skipped’ methylene chain (C4–C10), a cyclopen-
tane carboxylic acid fragment and a conjugated cyanodiene
unit.2,3 Borrelidin has anti-malarial,4 antiviral, and anti-
bacterial activity,5 and anti-angiogenesis effects.6 The
efforts toward the total synthesis7 of this unique macrolide
resulted in the first total synthesis by Morken and co-work-
ers.8 Subsequently, various other groups attempted the
total synthesis through synthetic9–11 and biosynthetic path-
ways.12 Wilkinson et al. prepared a set of novel borrelidin
analogs by precursor-directed biosynthesis and showed the
importance of the nitrile group at C12 for the anticancer
activity of borrelidin.13 In our endeavors14 toward the total
synthesis of borrelidin, we were interested in exploiting a
unique conjugated cyanodiene synthon to prepare simpler
and diverse analogs of borrelidin and envisioned a cross
metathesis strategy for the construction of the final macro-
lide (Fig. 1).
Although cross metathesis of conjugated diene esters
and amides has been reported,15 the cyano group, in con-
trast, has chemistry of its own and behaves differently in
metathesis reactions perhaps because of its small size and
high electronegativity.16 Hence, we chose to validate our
strategy in appropriate models and here we report the cross
metathesis of 2-bromohexa-2,4-dienenitrile with a set of
5
OH
3
9
7
HO
NC
R
11
HO
NC
O
Grignard
reaction
11
1
(E)
17
R1
17
OH
H
O
(Z)
12
15
15
H
H
COOH
1
Br
12
NC
Br
12
NC
(E)
17
Cross metathesis
OH
H
(E)
(Z)
15
q
(Z)
DRL Publication No. 660.
Corresponding author. Tel.: +91 40 23045439; fax: +91 40 23045438.
15
R1
*
Fig. 1.
E-mail address: javediqbaldrf@hotmail.com (J. Iqbal).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.055

2014
C. Vamsee Krishna et al. / Tetrahedron Letters 49 (2008) 2013–2017
diverse alkenes and further apply this strategy for the con-
struction of the C3–C17 framework of borrelidin.
and the yields were moderately good with 40–60% of the
unreacted starting material recovered from the reactions
and it is noteworthy that all the reactions proceeded with
high E selectivity in view of the small size of the nitrile
group, which is responsible for the Z selectivity observed
during the cross metathesis of acrylonitrile.16b
The cross metathesis products from both 2a and 2b were
single compounds resulting from reaction at C4 and
showed tolerance to sensitive functional groups like halo-
gen, aldehyde, and ester as evidenced by the synthesis of
compounds 4, 6, and 7, respectively. No reaction occurred
with acrylonitrile and acrolein (Scheme 1). Both com-
pounds 2a and 2b reacted with the unprotected secondary
alcohol 9 to give products 9a and 9b in 58% and 56% yield
with 6.5:1 and 4:1 selectivity allowing for recovery of the
unreacted starting material (Scheme 1; product 9). In
general the E selectivity with the E,E isomer 2a was greater
than with the Z,E isomer 2b, but the yields for the Z,E
isomer 2b were higher.
We were interested in further functionalization of these
cross metathesis products to arrive at the C11–C17 frag-
ment of borrelidin. Knochel and co-workers showed17 that
the bromo moiety in cyanodiene 13 can participate in the
reaction with isopropyl magnesium bromide and the so
formed organomagnesium species 14 can react with alde-
hydes to generate compounds of type 15 (Scheme 2).
We chose to study compound 9b18 as it contains features
very similar to those of the C11–C17 fragment of
borrelidin.
Our journey started with cyanodiene 2 synthesized as a
mixture of isomers 2a and 2b.14 Studies began with the
cyanodiene 2a (E,E) and vinyl acetate 3 (Scheme 1). A reac-
tion mixture containing 2a, vinyl acetate, and Grubbs’
catalyst I was refluxed in dichloromethane, but no reaction
occurred and the starting partners were recovered. The
more active Grubbs’ II catalyst also did not yield the
required products. Next we carried out the reaction with
methyl acrylate 4 under similar conditions. The reaction
was sluggish and the required product 4a was formed in
a low yield. Nevertheless, excellent E selectivity at the
newly formed alkene along with strict retention of the adja-
cent E alkene encouraged us to pursue this route further
(Scheme 1; 4a). The cyano and the bromo groups were
sufficiently deactivating and in combination with Grubbs’
catalyst II, the a,b-double bond was more deactivated rel-
ative to the c,d-double bond to give the single product 4a.
This finding encouraged us to perform a series of reactions
to define the scope of the cross metathesis reaction (Scheme
1; products 5a–12a). All the reactions proceeded chemose-
lectively with a series of olefins under standard reaction
conditions. With this impetus we next performed the
metathesis reactions with the same set of alkene partners
on the Z,E isomer 2b, since the double bond geometry of
the conjugated cyanodiene fragment in borrelidin is Z,E.
The required products (entries 4b–12b) were obtained again
with a high degree of E selectivity along with retention of
the spectator Z alkene. The reactions were generally clean
As outlined in Scheme 3, compound 9b after separation
by column chromatography from the minor unwanted Z,Z
isomer was reacted with TBS triflate to give the TBS ether
16 in 88% yield (Scheme 3). This was reacted with 26,
which was an advanced intermediate in our endeavors
toward the top C1–C10 part of borrelidin, as the aldehyde
component for the model Grignard reaction. The synthesis
of 26 is outlined in Scheme 4.
4
(E)
2
4
2
Grubbs ' II catalyst
CH2Cl2/ reflux
CN
1
CN
+
R
R
3
1
3
Br
Br
2a (E,E)
2b (Z,E)
3 R = OAc
3a No reaction
3b No reaction
4 R = COOCH3
5 R = Ph
4a 4%, >99% E
4b 18%, >99% E
Ketone 19 obtained from the known lactone 1719 was
subjected to a Wittig reaction with methyltriphenyl phos-
phonium bromide to afford alkene 20 (Scheme 4). The ester
group in compound 20 was reduced with lithium aluminum
5a 39%, >99% E
5b 66%, >99% E
6 R = (CH2)9Br
7 R = (CH2)8CHO
8 R = C(CH3)3
9 R = CH2CH(OH)CH3
10 R = CHO
6a 38%, >99% E
6b 61%, 12:1 E,Z
CN
CN
Br
CN
7a 41%, 8.8:1 E,Z
7b 46%, 5.2:1 E,Z
(Z)
a
b
(E)
(E)
(E)
OH
MgBr
R
R1
15
R
R
8a 16%, 4.5:1 E,Z
8b 19%, 4:1 E,Z
13
14
Scheme 2. Reagents and conditions: (a) i-PrMgBr, THF, ꢀ40 °C; (b)
9a 58%, 6.5:1 E,Z
9b 56%, 4:1 E,Z
R1–CHO, rt.
10a No reaction
10b No reaction
Br
(E)
Br
(E)
11 R = CN
11a No reaction
11b No reaction
a
HO
CN
(Z)
CN
(Z)
O
Si
16
9b
12 R =
12a 29%, >99% E
12b 29%, >99% E
O
OH
Scheme 3. Reagents and conditions: (a) TBS triflate, Hunig’s base,
Scheme 1.
CH2Cl2, 0 °C, 88%.

C. Vamsee Krishna et al. / Tetrahedron Letters 49 (2008) 2013–2017
2015
a
O
b
Ref. 18
c
O
OH
O
(R)
(S)
O
O
O
O
19
O
20
O
18
17
OH
d
N
e
f
HO
HO
I
O
23
21
22
g
h
HO
OHC
24
O
25
26
Scheme 4. Reagents and conditions: (a) CrO3, acetone, rt, 90%; (b) PPh3Br, n-BuLi, THF, 0 °C, 66%; (c) LiAlH4, THF, rt, 1 h, 94%; (d) PPh3, I2,
imidazole ACN/ether, rt, 2 h, 96%; (e) LDA, LiCl, (1R,2R)-pseudoephedrine propionamide, rt, 18 h, 88%; (f) 2 N aq NaOH/t-BuOH/MeOH, reflux, 28 h,
91%; (g) LiAlH4, THF, rt, 1 h, 94%; (h) Dess–Martin periodanane, CH2Cl2, rt, 76%.
hydride in THF to give alcohol 21, which was converted
into the corresponding iodo compound 22 using Garreg–
Samuelson’s method.20 The iodo product 22 was subjected
to a Myer’s alkylation with 1R,2R-(ꢀ)-pseudoephedrine
propionamide in the presence of LDA and LiCl to give
the alkylated product 23 in 88% yield. Compound 23 on
base hydrolysis furnished acid 24, which on reduction with
lithium aluminum hydride gave alcohol 25.21 Oxidation of
the alcohol with Dess–Martin periodanane afforded alde-
hyde 26 in 76% yield (Scheme 4). With both components
16 and 26 now available, the stage was set for the Grignard
reaction. This reaction would give the C3–C17 framework
of borrelidin and would serve as an advanced model study
and validate this strategy in our quest for the total synthe-
sis of borrelidin. Compound 16 afforded the organomagne-
sium species 27 upon treatment with i-PrMgBr in THF
(Scheme 5). In situ addition of a THF solution of aldehyde
26 to the organomagnesium species 27 afforded the de-bro-
minated cyanodiene 28 and four major compounds along
with other minor components. A careful chromatography
separation gave the two sets of diastereomers, namely
Z,E-29ab (9%, 4%) corresponding to the C3–C17 frame-
work of borrelidin and E,E-30ab (6%, 4%), respectively,
as colorless oils.22 Compound 28 accounted for 70% of
the total yield and the other minor components were not
isolated or characterized due to very low yields and may
account for the other four diastereomers possible from
the distal stereocenter in 16.
We initially attributed the formation of the de-halo-
genated product 28 to moisture in the reaction mixture,
but a recent report by Nagamitsu et al. also reported sim-
ilar observations during a samarium iodide-mediated
Reformatsky reaction on the cyanodiene.23 Lowering the
temperature to ꢀ40 °C and subsequently to ꢀ78 °C did
not provide any effective control on the formation of the
de-halogenated compound 28 (Scheme 5). No studies to
ascertain the stereochemistry at the C-11 hydroxyl center
were carried out as we envisioned a strategy wherein the
C-11 hydroxyl group would be oxidized to the ketone,
and subsequently, reduced stereoselectively back to the
hydroxyl after the final macrocyclization.
In summary we have described the first cross metathesis
study on both the isomers of a conjugated cyanodiene and
demonstrated that this reaction can be employed as a strat-
egy in the synthesis of borrelidin. Apart from excellent
chemoselectivity and diastereoselectivity, tolerance to sev-
eral functional groups such as halogen, aldehyde, and ester
was observed. We also demonstrated that the cross meta-
thesis proceeds with a high degree of E selectivity in contrast
to the Z selectivity observed during the cross metathesis of
acrylonitrile. Further, we converted the halogen into a
Grignard reagent and reacted it with an aldehyde. In this
way we have successfully installed the C3–C17 framework
of borrelidin. The future efforts of our group will focus on
completing the total synthesis of borrelidin and synthesis of
simplified analogs and to testing them for anticancer and
anti-malarial activities.
Br
MgBr
CN
(E)
(E)
a
b
CN
(Z)
O
O
Si
Si
16
27
H
(E)
(R)
(S)
(S)
CN
(R)
(S)
(S)
+
+
OH
O
OH
Si
(E)
(E)
O
NC
NC
Si
(E)
(Z)
28
Acknowledgments
29 a,b
O
Si
We thank Dr. Reddy’s Laboratories for facilities and
funding and the Analytical department, Discovery
Research, Dr. Reddy’s Laboratories for the analytical
support.
30 a,b
Scheme 5. Reagents and conditions: (a) i-PrMgBr, THF, ꢀ40 °C; (b) 26,
THF, ꢀ40 °C, 28 (70%), 29ab (9%, 4%), 30ab (6%, 4%).

2016
C. Vamsee Krishna et al. / Tetrahedron Letters 49 (2008) 2013–2017
1103, 1045, 975, 939, 802, 648, 536 cmꢀ1
;
1H NMR (400 MHz,
References and notes
DMSO-d6) d Z,E isomer distinct signals: 7.76 (d, J = 10.2 Hz, 1H),
6.58 (dt, J = 7.5 Hz, 15.0 Hz, 1H), 6.34 (dd, J = 10.2 Hz, 15.0 Hz,
1H), 4.64 (br s, 1H), 3.76–3.73 (m, 1H), 2.30–2.26 (m, 2H), 1.06 (d,
J = 6.1 Hz, 3H); 13C NMR (50 MHz, CDCl3) d 145.5, 144.5, 128.3,
114.0, 86.0, 66.8, 42.8, 23.2; ESMS m/z 214 (Mꢀ1); HRMS: (M++H)
calcd for C8H11BrNO, 216.0024; found, 216.0020.
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Yurek, D. A.; Kloosterman, D. A. J. Antibiot. 1989, 42, 1006–1007;
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978–980.
3. Anderson, B. F.; Herlt, A. J.; Rickards, R. W.; Robertson, G. B. Aust.
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21. Compound 25: (2S,4R,6S)-2,4,6,8-Tetramethyl-8-nonenol: To a sus-
pension of 0.080 g (0.00206 mol) of lithium aluminum hydride in
5 mL of dry THF and at 0 °C was added 0.175 g (0.000825 mol) of
acid 24 as a solution in THF. The contents were stirred at room
temperature for 1 h and quenched with saturated Na2SO4 and
extracted with ethyl acetate. The residue obtained on concentration
was purified by column chromatography over 100–200 mesh silica gel.
Elution of the column with 40% ether in hexanes gave on concen-
tration and drying 0.155 g (95%) of alcohol 25 as a pale yellow oil.
4. Otoguro, K.; Ui, H.; Ishiyama, A.; Kobayashi, M.; Togashi, H.;
Takahashi, Y.; Masuma, R.; Tanaka, H.; Tomoda, H.; Yamada, H.;
Omura, S. J. Antibiot. 2003, 56, 727–729.
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Nature 1965, 206, 263–265; Dickinson, L.; Griffiths, A. J.; Mason, C.
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H. Microbiol. Lett. 1993, 114, 41–46.
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Wakabayashi, T.; Littlefield, B. A. J. Antibiot. 2003, 56, 709–715.
7. Haddad, N.; Grishko, M.; Brik, A. Tetrahedron Lett. 1997, 38, 6075–
6078; Haddad, N.; Brik, A.; Grishko, M. Tetrahedron Lett. 1997, 38,
6079–6082; Zhao, C. X.; Duffey, M. O.; Taylor, S. J.; Morken, J. P.
Org. Lett. 2001, 3, 1829–1831; Herber, C.; Breit, B. Chem. Eur. J.
2006, 12, 6684–6691.
8. Duffey, M. O.; LeTiran, A.; Morken, J. P. J. Am. Chem. Soc. 2003,
125, 1458–1459 and references cited therein.
9. Hanessian, S.; Yang, Y.; Giroux, S.; Mascitti, V.; Ma, J.; Raeppel, F.
J. Am. Chem. Soc. 2003, 125, 13784–13792 and references cited
therein.
10. Nagamitsu, T.; Takano, D.; Fukuda, T.; Otoguro, K.; Kuwajima, I.;
Harigaya, Y.; Omura, S. Org. Lett. 2004, 11, 1865–1867 and
references cited therein.
11. Vong, B. G.; Kim, S. H.; Abraham, S.; Theodorakis, E. A. Angew.
Chem., Int. Ed. 2004, 43, 3947–3951 and references cited therein.
12. Olano, C.; Wilkinson, B.; Sanchez, C.; Moss, S. J.; Sheridan, R.;
Math, V.; Weston, A. J.; Brana, A. F.; Martin, C. J.; Oliynyk, M.;
Mendez, C.; Leadlay, P. F.; Salas, J. A. Chem. Biol. 2004, 11, 87–
97.
13. Wilkinson, B.; Gregory, M. A.; Moss, S. J.; Carletti, I.; Sheridan, R.
M.; Kaja, A.; Ward, M.; Olano, C.; Mendez, C.; Salas, J. A. Bioorg.
Med. Chem. Lett. 2006, 16, 5814–5817.
14. Chintakunta, V. K.; Maitra, S.; Vasu Dev, R.; Mukkanti, K.; Iqbal, J.
Tetrahedron Lett. 2006, 47, 6103–6106.
25
½aꢁD ꢀ26.4 (c 0.5 CHCl3); IR (neat) 3340, 3073, 2957, 2916, 2871,
1650, 1581, 1461, 1378, 1333, 1080, 1038, 987 cmꢀ1 1H NMR
;
(400 MHz, CDCl3) d 4.72 (br s, 1H), 4.64 (br s, 1H), 3.47–3.45 (m,
1H), 3.43–3.39 (m, 1H), 2.04–1.99 (m, 1H), 1.78–1.69 (m, 2H), 1.68 (s,
3H), 1.66–1.60 (m, 1H), 1.29–1.21 (m, 2H), 1.10–1.04 (m, 3H), 0.89 (d,
J = 6.7 Hz, 3H), 0.85 (d, J = 6.4 Hz, 3H), 0.82 (d, J = 6.4 Hz, 3H);
13C NMR (50 MHz, CDCl3) d 144.8, 111.3, 69.2, 46.0, 45.8, 40.1,
33.2, 27.7, 27.1, 22.2, 20.0, 19.7, 16.1; ESMS m/z 216 (M+ + NH4);
HRMS: (MꢀH)+ calcd for C13H25O, 197.1905; found, 197.1888.
22. Compounds 29a,b and 30a,b: 2-[5-(tert-Butyl-dimethyl-silanyloxy)-
hex-2Z,4E-diene]-3-hydroxy-4(S),6(R),8(S),10-tetramethyl-undec-
10ene nitrile: To a solution of 0.127 g (0.000369 mol) of 2-bromo-7-
(tert-butyl-dimethyl-silanyloxy)-octa-2Z,4E-diene nitrile 16 in dry
tetrahydrofuran was added 0.203 mL (0.000403 mol) of
a 2 M
solution of isopropyl magnesium bromide in THF at ꢀ40 °C. The
resulting pale red solution was stirred at ꢀ40 °C for 30 min after
which 80 mg (0.000406 mol) of aldehyde 26 in 2 mL of THF was
added at ꢀ40 °C and the contents were stirred for 1 h. Saturated brine
solution was added and the reaction mixture was extracted with ethyl
acetate. The organic layer was dried over sodium sulfate and
concentrated. The residue was purified by chromatography using a
chromatotron. Elution of the plate with 5% ether in hexanes afforded
49 mg (51%) of the debromination product 28 and further elution
with 8% ether in hexanes gave 29a,b (26 mg (9%, Z,E), 12 mg (4%,
Z,E)) and 30a,b (18 mg (6%, E,E), 12 mg (4%, E,E)), as colorless oils.
15. (a) Funk, T. W.; Efskind, J.; Grubbs, R. H. Org. Lett. 2005, 7, 187–
190; (b) Letts, G. M.; Curran, D. P. Org. Lett. 2007, 9, 5–8; (c) Ferrie,
L.; Amans, D.; Reymond, S.; Bellosta, V.; Capdevielle, P.; Cossy, J. J.
Organomet. Chem. 2006, 69, 5456–5465.
25
Compound 29a: ½aꢁD ꢀ4.4 (c 0.45, CHCl3); IR (neat) 3454, 3072, 2956,
2927, 2856, 2212, 1726, 1641, 1587, 1462, 1377, 1363, 1255, 1126,
1
1082, 1037, 1004, 975 cmꢀ1; H NMR (400 MHz, CDCl3) d 6.79 (dd,
J = 11.2 Hz, 3.2 Hz, 1H), 6.37 (dd, J = 11.2 Hz, 15.4 Hz, 1H), 6.14
(dt, J = 7.5 Hz, 15.0 Hz, 1H), 4.72 (br s, 1H), 4.63 (br s, 1H), 4.25–
4.21 (m, 1H), 3.92–3.88 (m, 1H), 2.30 (t, J = 6.58 Hz, 2H), 2.03–1.98
(m, 1H), 1.88–1.85 (m, 1H), 1.78–1.61 (m, 2H), 1.66 (s, 3H), 1.31–0.90
(m, 5H), 1.13 (d, J = 6.1 Hz, 3H), 1.03 (d, J = 6.7 Hz, 3H), 0.88 (s,
9H), 0.83 (d, J = 6.7 Hz, 3H), 0.82 (d, J = 6.1 Hz, 3H), 0.04 (s, 3H),
0.03 (s, 3H); 13C NMR (50 MHz, CDCl3) d 144.7, 143.0, 125.8, 125.7,
114.7, 111.4, 72.4, 67.8, 45.9, 45.8, 43.4, 43.3, 39.5, 39.1, 36.1, 29.6,
27.7, 27.1, 25.7, 23.7, 22.2, 19.8, 19.6, 15.3, 14.8, ꢀ4.4, ꢀ4.7; ESMS
m/z 912 (2M++NH4), 896 (2M++1), 470 (M++Na), 465 (M++NH4),
448 (M++1); HRMS: calcd for C27H49NO2SiCl, 482.3221; found,
16. (a) Basu, K.; Cabral, J. A.; Paquette, L. A. Tetrahedron Lett. 2002, 43,
5453–5456; (b) Crowe, W. E.; Goldberg, D. R. J. Am. Chem. Soc.
1995, 117, 5162–5163; (c) Dewi, P.; Randl, S.; Blechert, S. Tetrahedron
Lett. 2005, 46, 577–580; (d) Randl, S.; Gessler, S.; Wakamatsu, H.;
Blechert, S. Synlett 2001, 430–432.
17. Thibonnet, J.; Vu, V. A.; Berillon, L.; Knochel, P. Tetrahedron 2002,
58, 4787–4799.
18. Compound 9b: (2Z,4E)-2-bromo-7-hydroxy-octa-2,4-dienenitrile: To a
solution of 24.6 mg (0.000028 mol, 5 mol %) of Grubbs’ catalyst II in
1 mL of CH2Cl2 were added 100 mg (0.00058 mol) of (2Z,4E)-
2-bromo-hexa-dienenitrile (2b) and 99.9 mg (0.0011 mol) of pent-4-
en-2-ol, and the solution was stirred at 40 °C for 12 h. After 12 h
another 24.6 mg (0.000028 mol, 5 mol %) of Grubbs’ catalyst II was
added and the reaction was continued for a total of 24 h. The volatiles
were removed by rotary evaporation, and the residue was purified by
flash chromatography to give 70 mg (56%, 4:1 E,Z) of compound 9b
25
482.3210. Compound 29b: ½aꢁD ꢀ10.4 (c 0.25, CHCl3); IR (neat) 3435,
2958, 2927, 2856, 2212, 1726, 1641, 1587, 1462, 1379, 1257, 1126,
1083, 1037, 1029, 1004, 975 cmꢀ1; 1H NMR (400 MHz, CDCl3) d 6.79
(d, J = 11.2 Hz, 1H), 6.38 (dd, J = 11.5 Hz, 15.0 Hz, 1H), 6.13 (dt,
J = 7.5 Hz, 14.7 Hz, 1H), 4.72 (br s, 1H), 4.63 (br s, 1H), 4.25–4.24
(m, 1H),3.93–3.88 (m, 1H), 2.30 (t, J = 6.4 Hz, 2H), 2.03–1.99 (m,
1H), 1.89–1.84 (m, 1H), 1.77–1.60 (m, 2H), 1.66 (s, 3H), 1.34–0.94 (m,
5H), 1.13 (d, J = 6.0 Hz, 3H), 1.03 (d, J = 6.4 Hz, 3H), 0.87 (s, 9H),
25
as a colorless oil. ½aꢁD ꢀ6.8 (c 0.5, MeOH); IR (neat) 3444, 3408,
2964, 2926, 2854, 2220, 1770, 1712, 1633, 1581, 1454, 1379, 1261,

C. Vamsee Krishna et al. / Tetrahedron Letters 49 (2008) 2013–2017
2017
0.82 (d, J = 6.7 Hz, 3H), 0.81 (d, J = 6.4 Hz, 3H), 0.04 (s, 3H), 0.03 (s,
3H); 13C NMR (50 MHz, CDCl3) d 144.8, 144.6, 143.2, 125.7, 118.9,
114.7, 111.4, 72.3, 67.8, 45.9, 43.3, 39.6, 36.1, 29.6, 29.4, 27.7, 27.1,
25.8, 23.7, 22.2, 19.8, 19.6, 14.8, ꢀ4.4, ꢀ4.7; ESMS m/z 917
(2M++Na), 912 (2M++NH4), 895 (2M++1), 470 (M++Na), 465
(2M++NH4), 470 (M++Na), 465 (M++NH4), 448 (M++1); HRMS:
(2M++HCOOꢀ) calcd for C55H99N2O6Si2, 939.7042; found,
25
939.7045. Compound 30b: ½aꢁD ꢀ6.80 (c 0.25, CHCl3); IR (neat)
3431, 2958, 2927, 2856, 1641, 1587, 1460, 1379, 1255, 1128, 1083,
1
1024, 887 cmꢀ1; H NMR (400 MHz, CDCl3) d 6.77 (d, J = 11.2 Hz,
(M++NH4), 448 (M++1); HRMS: (2M++HCOOꢀ) calcd for
1H), 6.53 (dd, J = 11.0 Hz, 15.0 Hz, 1H), 6.14 (dt, J = 7.2 Hz,
14.7 Hz, 1H), 4.72 (br s, 1H), 4.64 (br s, 1H), 4.01 (t, J = 4.4 Hz,
1H), 3.93–3.89 (m, 1H), 2.32 (t, J = 6.4 Hz, 2H), 2.03–2.00 (m, 1H),
1.99–1.90 (m, 1H), 1.77–1.58 (m, 2H), 1.58 (s, 3H), 1.34–0.96 (m, 5H),
1.15 (d, J = 6.4 Hz, 3H), 0.92 (d, J = 6.4 Hz, 3H), 0.88 (m, 12H), 0.82
(d, J = 6.4 Hz, 3H), 0.04 (s, 3H), 0.03 (s, 3H); 13C NMR (50 MHz,
CDCl3) d 144.7, 144.4, 141.6, 128.3, 118.9, 114.1, 111.4, 67.9, 45.9,
45.8, 43.0, 40.1, 35.3, 29.6, 29.4, 27.7, 27.2, 25.8, 23.7, 22.2, 19.8, 19.7,
13.6, ꢀ4.4, ꢀ4.7; ESMS m/z 912 (2M++NH4), 470 (M++Na), 465
(M++NH4), 448 (M++1); HRMS: (2M++HCOOꢀ) calcd for
C55H99N2O6Si2, 939.7042; found, 939.7056.
25
C
55H99N2O6Si2, 939.7042; found, 939.7065. Compound 30a: ½aꢁD
ꢀ7.0 (c 0.6, CHCl3); IR (neat) 3469, 3074, 2958, 2927, 2856, 2214,
1726, 1641, 1598, 1462, 1377, 1255, 1128, 1082, 1039, 1002, 971,
887 cmꢀ1; 1H NMR (400 MHz, CDCl3) d 6.80–6.75 (m, 1H), 6.52 (dd,
J = 11.0 Hz, 14.9 Hz, 1H), 6.15 (dt, J = 7.5 Hz, 15.0 Hz, 1H), 4.72 (br
s, 1H), 4.64 (br s, 1H), 4.03–3.99 (m, 1H), 3.94–3.89 (m, 1H), 2.32 (t,
J = 6.7 Hz, 2H), 2.03–1.98 (m, 1H), 1.94–1.90 (m, 1H), 1.77–1.58 (m,
2H), 1.68 (s, 3H), 1.34–0.96 (m, 5H), 1.14 (d, J = 5.9 Hz, 3H), 0.91 (d,
J = 6.8 Hz, 3H), 0.88 (s, 9H), 0.86 (d, J = 6.8 Hz, 3H), 0.82 (d,
J = 6.4 Hz, 3H), 0.04 (s, 3H), 0.03 (s, 3H); 13C NMR (50 MHz,
CDCl3) d 144.6, 144.3, 141.5, 128.2, 114.7, 111.3, 67.9, 46.0, 45.9,
45.8, 43.0, 35.5, 35.3, 29.6, 27.7, 27.2, 27.1, 25.8, 23.7, 22.2, 19.8, 19.7,
18.0, 15.6, 13.5, ꢀ4.4, ꢀ4.7; ESMS m/z 917 (2M++Na), 912
23. Nagamitsu, T.; Takamo, D.; Marumoto, K.; Fukuda, T.; Furuya, K.;
Otoguru, K.; Takeda, K.; Kuwajima, I.; Harigaya, Y.; Omura, S. J.
Org. Chem. 2007, 72, 2744–2756.