Synthesis of a model compound of corydendramine a via a julia coupling

Article abstract of DOI:10.1080/00397910902788208

The synthesis of the tetraenylpiperidine 12, which has the same core structure as the natural product corydendramine A, has been completed in eight steps starting from 2-piperidinemethanol 3 and trans,trans-2,6-nonadienal 6. The key step of the synthesis was a Julia coupling of sulfone (10) with aldehyde (5) to form a conjugated triene.

Full text of DOI:10.1080/00397910902788208

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Synthesis of a Model Compound
of Corydendramine A via a
Julia Coupling
a
a
Maddy McCrea-Hendrick & Christopher J. Nichols
a
Department of Chemistry and Biochemistry ,
California State University , Chico, Chico, California,
USA
Published online: 08 Sep 2009.
To cite this article: Maddy McCrea-Hendrick & Christopher J. Nichols (2009)
Synthesis of a Model Compound of Corydendramine A via a Julia Coupling, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:20, 3611-3620, DOI: 10.1080/00397910902788208
To link to this article: http://dx.doi.org/10.1080/00397910902788208
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1
Synthetic Communications , 39: 3611–3620, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902788208
Synthesis of a Model Compound
of Corydendramine A via a Julia Coupling
Maddy McCrea-Hendrick and Christopher J. Nichols
Department of Chemistry and Biochemistry, California State University,
Chico, Chico, California, USA
Abstract: The synthesis of the tetraenylpiperidine 12, which has the same core
structure as the natural product corydendramine A, has been completed in eight
steps starting from 2-piperidinemethanol 3 and trans,trans-2,6-nonadienal 6. The
key step of the synthesis was a Julia coupling of sulfone (10) with aldehyde (5) to
form a conjugated triene.
Keywords: Julia coupling, piperidine, triene
INTRODUCTION
[1]
In 2000, Lindquist, Shigematsu, and Pannell reported the isolation and
structural characterization of the natural products named corydendra-
mine A and B (1 and 2, Fig. 1) from the marine hydroid Corydendrium
parasiticum. C. parasiticum does not possess penetrating nematocysts like
some other members of the hydroid family. Instead, these lipophilic sec-
ondary metabolites serve as fish-feeding deterrents. Other piperidine
[
2]
alkaloids with a similar structural motif, such as prosopinine and
[
3]
micropine,
show interesting biological activity: prosopinine has
anesthetic, antibiotic, and antihypertensive properties, and micropine
has antibiotic properties. Evaluation of corydendramines A and B for
Received December 19, 2008.
Address correspondence to Christopher J. Nichols, Department of Chemistry
and Biochemistry, California State University, Chico, 400 W. 1st Street, Chico,
CA 95929-0210, USA. E-mail: cjnichols@csuchico.edu
3
611

3612
M. McCrea-Hendrick and C. J. Nichols
Figure 1. Corydendramines A (1) and B (2).
similar biological activity would require a large supply, and so a synthetic
project was initiated with these compounds as the target.
Several other methods of affixing the lipophilic ‘‘tail’’ to the piperi-
dine ‘‘head’’ were attempted without success, including a Negishi-style
[
coupling of a vinylzinc species with a vinyl iodide, and addition of a
4]
[
5]
vinyl boronate to an N-acyliminium ion. A reference that showed
success in the stereoselective formation of an all-trans triene using a Julia
[
coupling led us to adopt that same route in our synthesis.
6]
RESULTS AND DISCUSSION
Preparation of the aldehyde coupling partner was achieved in two steps
[
7]
from the commercially available 2-piperidinemethanol (Scheme 1).
After protection with a tert-butoxycarbamate group, the N-Boc-
[
piperidine-2-methanol 4 was converted to the carbaldehyde 5 by using
a Swern oxidation.
The synthesis of the lipophilic tail (Scheme 2) began with trans, trans-
8]
[9]
[
10]
2
,6-nonadienal 6 and use of a Horner–Wadsworth–Emmons
to afford the ethyl ester 7. This ester was subsequently reduced
.2 equivalents of diisobutyl aluminum hydride (DIBAL-H) in toluene
reaction
[
11]
with
2
to afford the alcohol 8 after workup.
The alcohol 8 was then transformed into the aromatic sulfide 9 using
[6]
a Mitsunobu reaction with 2-mercaptobenzothiazole and diisopropyl
1
azodicarboxylate (DIAD). In our first attempt at this reaction, the H
NMR spectrum of the product after chromatographic purification
Scheme 1. Reagents and conditions: (a) Boc
ꢁ
2
O, Et
ꢁ
3
N, CH
2
Cl
2
, rt, 1 h, 84%; and
(
b) (COCl) , DMSO, Et N, CH Cl , ꢀ78 C to 0 C, 2.25 h, 68%.
2
3
2
2

Corydendramine A Model
3613
Scheme 2. Reagents and conditions: (a) (EtO) POCH COOEt, NaH, THF,
2
2
ꢁ
ꢁ
ꢀ
30 C to rt, overnight, 83%; (b) DIBAL-H, toluene, 0 C to rt, overnight, 91%;
ꢁ
(
c) 2-mercaptobenzothiazole, Ph
3
P, DIAD, THF, 0 C to rt, overnight, 90%; (d)
(
NH ) Mo O , H O , EtOH, rt, 8 h, 98%; (e) (i) KHMDS, 18-crown-6, THF,
4 6 7 24 2 2
ꢁ
ꢁ
ꢁ
ꢀ
80 C, 1 h, (ii) 5, THF, ꢀ80 C, 2.5 h, then ꢀ80 C to rt, overnight, 98%; and
(
f) TMSOTf, CH
Cl , 2,6-lutidine, 40%.
2 2
indicated the presence of two additional compounds (extra doublets in
the 4.0–4.5 ppm region) that were not present in the NMR spectrum of
the crude reaction mixture. These extra compounds were likely formed
by acid-catalyzed rearrangement of the polyene system during purifica-
tion with silica gel. To avoid this rearrangement in subsequent runs of
this reaction, the silica gel was doped with 1% triethylamine.
Oxidation of the sulfide 9 to the sulfone 10 was completed with fresh
[6]
hydrogen peroxide and a molybdenum catalyst. In most cases, a sulfox-
ide side product was present in the crude reaction product, but it could be
removed using column chromatography. The key step, the Julia coupling,
proceeded in very good yield, with no indication of the presence of other
1
13
stereoisomers in the H NMR of the coupled product 11 or the C NMR
1
of 11 or the deprotected product 12. Assignment of the H NMR signals
to the hydrogen atoms in the molecule (listed in the experimental section)
were based on the splitting patterns observed in the spectra and estimated
chemical shifts calculated for a triene system. Removal of the Boc group
proved problematic: the best yield obtained was only 40% despite
attempting a variety of conditions.
EXPERIMENTAL
General
Unless otherwise specified, starting materials were obtained from com-
mercial suppliers and used without purification. Tetrahydrofuran
(
THF) was distilled over Na=benzophenone, and CH Cl and toluene
2 2

3614
M. McCrea-Hendrick and C. J. Nichols
were distilled over CaH . NMR spectra were recorded on a Varian
2
Mercury VX300. Fourier transform–infrared (FT-IR) spectra were
recorded on a Mattson Galaxy Series 3000 or a Nicolet 4700 instrument.
Electron impact (EI) mass spectra were recorded on an HP 5973 mass
selective detector attached to an HP 6890 GC instrument. Electrospray
ionization (ESI) mass spectra were recorded on a ThermoFinnigan
LCQ-Advantage instrument. Thin-layer chromatography (TLC) was
run on aluminum-backed plates of SiO with 0.2 mm thick. All reactions
2
were run under an inert atmosphere of argon, and all glassware was dried
in an oven overnight prior to use.
[9]
N-Boc-piperidine-2-methanol (4)
Triethylamine (23.34 mL, 156.42 mmol) was added to a solution of
-piperidinemethanol (5.00 g, 43.45 mmol) in dichloromethane (150 mL)
dropwise, and the solution was stirred for an hour upon complete
2
addition. Then a solution of di-tert-butyl dicarbonate (Boc O, 11.38 g,
2
5
2.14 mmol) in dichloromethane (20 mL) was added dropwise to the
solution, and it was stirred for an additional hour upon complete addi-
tion. The reaction was poured into 50 mL water. The organic phase
was extracted with water, and the aqueous phases were extracted with
dichloromethane (2 ꢂ 20 mL). The combined organic phases were washed
with brine, dried over MgSO , and filtered, and the solvent was removed
4
in vacuo. The crude product was purified via column chromatography
using silica gel and hexanes=EtOAc (1:1) to afford alcohol 4 (7.865 g,
1
4%) as a white solid. Several peaks in the H NMR experienced broad-
8
ening as a result of the presence of rotamers associated with the
ꢁ
ꢁ
[12] 1
carbamate. Mp 75–77 C (lit. Mp 74–78 C).
H NMR (300 MHz,
CDCl ) d: 4.29 (1H, m), 3.94 (1H, 2x br s), 3.81 (1H, dd, J ¼ 10.8,
3
9
apparent br t), 2.12 (1H, br s), 1.53–1.73 (6H, m), 1.46 (9H, s, Bu).
.1 Hz, CH OH), 3.61 (1H, dd, J ¼ 10.5, 5.9 Hz, CH OH), 2.87 (1H,
2
2
t
1
3
C NMR (75 MHz, CDCl ): 156.6, 80.0, 61.9, 52.7, 40.1, 28.6, 25.5,
3
ꢀ
1
5.4, 19.8. IR (film): 3418, 2934, 1668 cm . M=S (EI) m=z: 215 (M ),
þ
2
1
84, 142, 128 (100%), 84, 57.
[9]
N-Boc-piperidine-2-carbaldehyde (5)
DMSO (7.15 mL, 101.6 mmol) was added dropwise to a solution of
freshly distilled oxalyl chloride (4.56 mL, 50.8 mmol) in dichloromethane
ꢁ
(
100 mL) at ꢀ78 C, and the solution was stirred for 45 min. A solution of
the alcohol 4 (7.29 g, 33.9 mmol) in dichloromethane (20 mL) was added

Corydendramine A Model
3615
ꢁ
dropwise, and the solution was stirred for 1 h at ꢀ78 C. Triethylamine
(
38.22 mL, 254.0 mmol) was added to the solution, which was warmed
ꢁ
to 0 C upon complete addition of the base and was allowed to stir an
additional 30 min. The reaction was poured into 50 mL water, the layers
were separated, and the aqueous phase was extracted with dichloro-
methane (4 ꢂ 20 mL). The combined organic phases were washed with
1
% HCl (10 mL), water, saturated sodium bicarbonate, and brine. The
organic phase was then dried over MgSO and filtered, and the solvent
4
was removed in vacuo. The crude product was purified via column chro-
matography using silica gel and EtOAc=hexanes (20=80) to afford the
aldehyde 5 (4.8992 g, 68%) as a colorless oil. Several peaks in the
1
H NMR experienced broadening as a result of the presence of rotamers
associated with the carbamate. Pairs of peaks from rotameric carbons in
1
the C NMR spectrum are enclosed within parentheses. H NMR
3
1
(
300 MHz, CDCl ): 9.58 (1H, s, CHO), 4.54 (1H, apparent br d), 3.92
3
(
1H, apparent br d), 2.90 (1H, br s), 2.15 (1H, apparent br d),
t
.58–1.73 (5H, m), 1.46 (9H, s, Bu). C NMR (75 MHz, CDCl3):
13
1
2
2
01.6, 158.0, 80.6, 77.5, (61.6, 60.8), (43.3, 42.1), 28.5, (24.9, 23.8),
1.1. IR (thin film): 2940, 1734, 1693, 1405, 1164 cm
ꢀ1
.
Ethyl (2E,4E,8E)-Undeca-2,4,8-trienoate (7)
Solid sodium hydride (900 mg, 22 mmol) was washed with hexanes
(
3 ꢂ 10 mL). THF (40 mL), was then added to the hydride and the solu-
ꢁ
tion was cooled to ꢀ30 C. Triethyl phosphonoacetate (4.36 mL,
2
2 mmol) was added dropwise, and the solution was stirred for 30 min.
The silvery solution became clear upon completion of the reaction.
2E,6E)-Nonadienal 6 (2.0 mL, 12.6 mmol) was added dropwise to the
(
ꢁ
ꢁ
clear solution, stirred for 30 min at ꢀ30 C, allowed to warm to 10 C
overnight, and then brought to room temperature and stirred for 1 h.
The reaction was poured into a separatory funnel with saturated ammo-
nium chloride and diethyl ether. The layers were separated, and the aqu-
eous phase was extracted with diethyl ether (3 ꢂ 15 mL). The combined
organic phases were washed with 10% sodium carbonate (2 ꢂ 10 mL)
and brine (2 ꢂ 10 mL), dried over MgSO , and filtered, and the solvent
4
was removed in vacuo. The crude product was purified via column chro-
matography on silica gel using EtOAc–hexanes (15=85) to afford the ester
1
(2.1908 g, 83%) as a yellow oil. H NMR (300 MHz, CDCl ): 7.26 (1H,
7
3
dd, J ¼ 15.5, 10.0 Hz, H3), 6.07–6.23 (2H, m, H4 and H5), 5.79 (1H, d,
J ¼ 15.2 Hz, H2), 5.50 (1H, dt, J ¼ 15.2, 6.0 Hz, H8 or H9), 5.37 (1H,
dt, J ¼ 15.2, 6.3, 1.3 Hz, H8 or H9), 4.21 (2H, q, J ¼ 7.1 Hz, Et), 2.24
(
2H, q, J ¼ 6.2 Hz, H6 or H7), 2.13 (2H, q, J ¼ 6.9 Hz, H6 or H7), 2.01

3616
M. McCrea-Hendrick and C. J. Nichols
(
2H, quin t, J ¼ 7.0, 1.2 Hz, H10), 1.30 (3H, t, J ¼ 7.2 Hz, Et), 0.97 (3H, t,
1
3
J ¼ 7.5 Hz, H11). C NMR (75 MHz, CDCl ): 167.5, 145.2, 144.2, 133.3,
3
1
1
28.8, 127.9, 119.5, 60.4, 33.2, 31.9, 25.8, 14.5, 14.1. IR (film): 1715, 1643,
ꢀ
1
617 cm . MS (EI) m=z: 208 (M ), 140, 69 (100%), 67.
þ
(2E,4E,8E)-Undeca-2,4,8-trien-1-ol (8)
DIBAL-H (1 M in hexanes, 20.0 mL, 20 mmol) was added dropwise to a
solution of ethyl undeca-2,4,8-trienoate 7 (2.0355 g, 9.77 mmol) in toluene
ꢁ
(
40 mL) at 0 C. The solution was warmed to room temperature and
ꢁ
allowed to stir overnight. The solution was again cooled to 0 C, and
HCl (6 M, 3.5 mL, 21.0 mmol) was added dropwise to the solution. The
reaction was warmed to room temperature and stirred for 2 h, whereupon
it was poured into brine (20 mL), diethyl ether (30 mL), and solid sodium
chloride (10 g). The layers were separated, and the aqueous phase was
washed with diethyl ether (3 ꢂ 15 mL). The combined organic phases
were washed with brine, dried over MgSO , and filtered, and the solvent
4
was removed in vacuo. The crude product was flushed with ethyl acetate
through a small column consisting of a layer of silica gel on top of a layer
of Celite, and the solvent was again removed in vacuo. The product was
kept under high vacuum for 2 h to completely remove traces of isobutyl
alcohol, producing the pure alcohol 8 (1.4785 g, 91%) as a colorless oil.
1
H NMR (300 MHz, CDCl ): 6.23 (1H, dd, J ¼ 14.9, 10.0 Hz, H3), 6.06
3
(
1H, dd, J ¼ 15.0, 10.5 Hz, H4), 5.75 (1H, dq, J ¼ 14.9, 5.9 Hz, H2 or
H5), 5.71 (1H, dq, J ¼ 14.9, 5.9 Hz, H2 or H5), 5.48 (1H, dt, J ¼ 15.5,
.7 Hz, H8 or H9), 5.38 (1H, dt, J ¼ 15.2, 5.6 Hz, H8 or H9), 4.17 (2H,
d, J ¼ 5.9 Hz, H1), 1.95–2.20 (6H, m, H6, H7, and H10), 1.46 (1H, br
5
1
3
s, OH), 0.97 (3H, t, J ¼ 7.3 Hz, H11). C NMR (75 MHz, CDCl ):
3
1
35.3, 132.9, 132.3, 129.8, 129.7, 128.4, 63.8, 32.9, 32.4, 25.8, 14.2. IR
film): 3347, 2962, 1660, 1441 cm . MS (EI) (m=z): 166 (M ), 122, 79
ꢀ1
þ
(
(100%), 69, 67.
2
-[(2E,4E,8E)-Undeca-2,4,8-trienylsulfanyl]-benzothiazole (9)
(2E,4E,8E)-Undeca-2,4,8-trien-1-ol 8 (1.134 g, 6.82 mmol) was added to a
solution of 2-mercaptobenzothiazole (1.71 g, 10.23 mmol) in THF
(
(
20 mL) at room temperature. In a separate flask, triphenylphosphine
3.13 g, 120 mmol) was dissolved in THF (80 mL) and was cooled to
ꢁ
0 C. DIAD (2.23 mL, 11.2 mmol) was added dropwise to the triphenyl-
phosphine solution. The solution turned from colorless to opaque white
before complete addition. Then the alcohol=benzothiazole solution was

Corydendramine A Model
3617
transferred into the triphenylphosphine=DIAD solution dropwise via
syringe. The reaction was allowed to warm to room temperature and
stirred overnight. The solvent was removed in vacuo, and the residue
was purified by column chromatography using silica gel and
EtOAc=Et N=hexanes (10=1=89), affording the sulfide 9 (1.95 g, 90%)
3
1
as a yellow oil. H NMR (300 MHz, CDCl ): 7.86 (1H, ddd, J ¼ 8.2,
3
1
.1, 0.6 Hz, Ar), 7.76 (1H, ddd, J ¼ 7.9, 1.2, 0.6 Hz, Ar), 7.43 (1H, ddd,
J ¼ 8.5, 7.3, 1.3 Hz, Ar), 7.30 (1H, ddd, J ¼ 8.2, 7.6, 1.1 Hz, Ar), 6.33
(
5
5
1H, dd, J ¼ 14.7, 10.0 Hz, H3), 6.04 (1H, dd, J ¼ 15.2, 10.2 Hz, H4),
.76 (1H, dt, J ¼ 15.0, 7.5 Hz, H2), 5.72 (1H, dt, J ¼ 15.5, 6.4 Hz, H5),
.48 (1H, dt, J ¼ 15.5, 6.4 Hz, H8 or H9), 5.38 (1H, dt, J ¼ 15.5, 5.7 Hz,
H8 or H9), 4.04 (2H, d, J ¼ 7.3 Hz, H1), 1.94–2.19 (6H, m, H6, H7,
1
3
H10), 0.96 (3H, t, J ¼ 7.5 Hz, H11). C NMR (75 MHz, CDCl ):
3
1
1
1
66.7, 153.4, 135.7, 135.5, 135.2, 132.9, 129.5, 128.4, 126.2, 124.5,
24.4, 121.7, 121.2, 35.1, 33.0, 32.4, 25.8, 14.1. IR (film): 3020, 2960,
ꢀ
1
460, 1427, 1309, 1238, 991 cm
.
2
-[(2E,4E,8E)-Undeca-2,4,8-triene-1-sulfonyl]-benzothiazole (10)
Ammonium molybdate tetrahydrate (764 mg, 0.618 mmol) was added to
a solution of hydrogen peroxide (30% aq., 1.89 mL, 61.8 mmol), and the
mixture was stirred for 10 min. In a separate flask with a stir bar, the sul-
fide 9 (1.95 g, 6.18 mmol) was dissolved in absolute ethanol (25 mL). The
peroxide solution was transferred into the sulfide solution dropwise with
a pipet, and the color changed from clear yellow to an opaque yellow.
The reaction was stirred for 8 h and was then poured into water
(
(
30 mL) and ether (20 mL). The aqueous phase was washed with ether
2 ꢂ 20 mL). The combined organic phases were washed with 20 mL each
of 10% thiosulfate, saturated sodium bicarbonate, and brine, then dried
over MgSO , filtered, and concentrated in vacuo. The product was
4
purified via column chromatography on silica gel using EtOAc=
Et N=hexanes (20=2=78) to afford the sulfone 10 (2.10 g, 98%) as a yellow
3
1
oil. H NMR (300 MHz, CDCl ): 8.24 (1H, ddd, J ¼ 8.5, 1.5, 0.8 Hz, Ar),
3
8
.01 (1H, ddd, J ¼ 7.6, 2.0, 0.9 Hz, Ar), 7.63 (2H, m, Ar), 6.24 (1H, dd,
J ¼ 15.2, 10.3 Hz, H3), 6.01 (1H, dd, J ¼ 15.0, 10.6 Hz, H4), 5.68 (1H,
dt, J ¼ 15.2, 6.4 Hz, H5), 5.53 (1H, dt, J ¼ 15.2, 7.6 Hz, H2), 5.28–5.48
(
2H, m, H8 and H9), 4.24 (2H, d, J ¼ 7.6 Hz, H1), 1.92–2.14 (6H, m,
1
3
H6, H7, and H10), 0.95 (3H, t, J ¼ 7.5 Hz, H11). C NMR (75 MHz,
CDCl ): 165.7, 152.9, 141.3, 138.4, 137.1, 133.0, 129.0, 128.2, 128.1,
3
1
3
27.8, 125.7, 122.5, 113.7, 59.0, 32.9, 32.1, 25.8, 18.7, 14.1. IR (film):
ꢀ
1
026, 2996, 2921, 2846, 1654, 1554, 1471 1332, 1146 cm
.

3618
M. McCrea-Hendrick and C. J. Nichols
2-((1E,3E,5E,9E)-Dodeca-1,3,5,9-tetraenyl)piperidine-1-carboxylic Acid
tert-Butyl Ester (11)
Potassium bis(trimethylsilyl)amide or potassium hexamethyldisilazide
KHMDS) (0.5 M in THF, 1.41 mL, 0.705 mmol) was added dropwise to
a solution of the sulfone 10 (238.5 mg, 0.677mmol) and 18-crown-6
(
ꢁ
(
193 mg, 0.732 mmol) in THF (5 mL) at ꢀ80 C. The solution was stirred
for 1 h. N-Boc-piperidine-2-carbaldehyde 5 (115mg, 0.542mmol) in THF
(10 mL) was added dropwise, and the reaction was stirred for 2.5 h at
80 C. The reaction was allowed to warm to room temperature overnight
and then poured into saturated ammonium chloride (20 mL). The layers
were separated, and the aqueous phase was extracted with EtOAc
ꢁ
ꢀ
(
3 ꢂ 10 mL). The combined organic phases were washed with brine, dried
over Na SO , and filtered, and the solvent was removed in vacuo. The crude
2
4
product was purified via column chromatography on silica gel using
EtOAc=Et N=hexanes (10=1=89) to afford the tetraene 11 (183.6mg, 98%)
3
1
as a yellow oil. H NMR (300MHz, CDCl ): 6.00–6.18 (4H, m, H2 , H3 ,
0
0
3
0
0
0
H4 , H5 ), 5.71 (1H, dt, J ¼ 14.6, 6.2 Hz, H6 ), 5.62 (1H, dd, J¼ 14.6,
0
0
0
5
.0 Hz, H1 ), 5.48 (1H, dt, J¼ 15.3, 5.7Hz, H9 or H10 ), 5.39 (1H, dt,
0
0
J¼ 15.2, 5.7 Hz, H9 or H10 ), 4.84 (1H, br s, H2), 3.93 (1H, apparent br
0
0
d, H6a), 2.82 (1H, apparent br d, H6b), 1.95–2.21 (6H, m, H7 , H8 ,
0
t
H11 ), 1.45–1.75 (6H, m, H3, H4, H5), 1.46 (9H, s, Bu), 0.97 (3H, t,
0
13
J¼ 7.3 Hz, H12 ). C NMR (75 MHz, CDCl ): 155.5, 135.0, 132.8, 132.7,
3
1
2
32.0, 131.5, 130.7, 130.4, 128.5, 79.6, 52.2, 40.0, 33.2, 32.5, 29.6, 28.73,
ꢀ
1
8.68, 25.8, 19.8, 14.2. IR (film): 3014, 2855, 1693, 1453, 1409, 1163 cm
.
2
-((1E,3E,5E,9E)-Dodeca-1,3,5,9-tetraenyl)piperidine (12)
2
piperidine 11 (134.7 mg, 0.390 mmol) in CH Cl (5 mL) at 0 C. The
,6-Lutidine (178 mL, 1.53 mmol) was added to a solution of the protected
ꢁ
2
2
solution was stirred for several minutes, and then trimethylsilyl tri-
fluoromethanesulfonate or trimethylsilyl triflate (TMSOTf) (92 mL,
0
.508 mmol) was added dropwise to the solution, which was then stirred
for 3 h at room temperature. The reaction mixture was poured into satu-
rated aq. NaHCO and extracted twice with CH Cl . The combined
organic extracts were washed with brine, dried over MgSO , and filtered,
3
2
2
4
and the solvent was removed in vacuo. The crude product was purified
via column chromatography on silica gel using methanol=CH Cl
2
2
(15=85) to afford the deprotected tetraene 12 (38 mg, 40%) as a yellow
solid. Mp 48–51 C. H NMR (300 MHz, CDCl ): 6.01–6.22 (4H, m,
ꢁ
1
3
0
0
0
0
0
0
0
H2 , H3 , H4 , H5 ), 5.62–5.74 (2H, m, H1 , H6 ), 5.48 (1H, dt,
0
0
J ¼ 14.9, 5.7 Hz, H9 or H10 ), 5.39 (1H, dt, J ¼ 15.4, 5.7 Hz, H9 or

Corydendramine A Model
3619
0
H10 ), 3.06–3.16 (2H, m, H2 and H6a), 2.67 (1H, td, J ¼ 11.7, 3.0 Hz, H6b),
13
0 0 0
1
.95–2.20 (6H, m, H7 , H8 , H11 ), 1.81 (1H, m, ring H), 1.20–1.72 (6H, m,
0
ring H’sþ NH), 0.96 (3H, t, J ¼ 7.3 Hz, H12 ). C NMR (75 MHz,
CDCl ): 132.0, 130.0, 128.1, 128.0, 126.0, 125.9, 125.1, 123.8, 54.4, 42.3,
3
2
8.42, 28.37, 27.8, 21.4, 21.1, 20.1, 9.4. IR (KBr) 3013, 2924, 2848, 1448,
þ
ꢀ1
1002, 964, 892 cm . MS (ESI) m=z: 246 [M þ H] . High-resolution MS
(EI, m=z): 245.2141, calcd. for C H N 245.2143.
17 27
CONCLUSION
A tetraenyl piperidine compound (12), whose structure is analogous to
corydendramine A, was successfully synthesized in eight steps. The
results from the completion of the model study are currently being used
in a synthesis of the complete natural product 1.
ACKNOWLEDGMENTS
Funding for this project was made possible by a Cottrell College Science
Award from the Research Foundation, grant number CC-5918. Thanks
to Prof. Bruce Lipshutz at UC Santa Barbara for help in obtaining
HRMS of compound 12. Thanks are also given to the CSU, Chico,
Department of Chemistry and Biochemistry, and to Prof. David B. Ball
for helpful discussions.
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