One-pot synthesis and functionalization of polyynes via alkylidene carbenoids

Article abstract of DOI:10.1055/s-2007-1000937

A one-pot, two-step method for the synthesis of diynes and triynes is reported. The reaction of a dibromoolefinic precursor with BuLi effects a Fritsch-Buttenberg-Wiechell rearrangement and generates a lithium acetylide intermediate, which is then trapped

Full text of DOI:10.1055/s-2007-1000937

1
158
PRACTICAL SYNTHETIC PROCEDURES
One-Pot Synthesis and Functionalization of Polyynes via Alkylidene
Carbenoids
1
S
T
ynthesis and F
h
unctionaliz
a
a
tion of Poly
n
ynes h Luu, Yasuhiro Morisaki, Rik R. Tykwinski*
Department of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada
Fax +1(780)4928231; E-mail: rik.tykwinski@ualberta.ca
PSP
Received 7 March 2007; revised 11 April 2007
No120
Abstract: A one-pot, two-step method for the synthesis of diynes and triynes is reported. The reaction of a dibromoolefinic precursor with
BuLi effects a Fritsch–Buttenberg–Wiechell rearrangement and generates a lithium acetylide intermediate, which is then trapped with a
variety of electrophiles to produce substituted diynes and triynes. Alternatively, transmetalation from the lithium acetylide to give a zinc
acetylide provides a nucleophilic coupling partner for aryl iodides in the presence of palladium to form symmetrical or unsymmetrical
diynes and triynes via the Negishi coupling.
Key words: carbenoid rearrangement, rearrangement deprotonation, polyyne, lithium acetylide, zinc acetylide
Br
Br
BuLi
(
2.2 equiv)
R
Li
n
hexanes
and/or
toluene
n
R
H
4
a–f
diynes
a–j
1
a–f
2
ZnCl2
(1.2 equiv)
or
a R = Ph (n = 0)
b R = Ph (n = 1)
c R = t-BuPh (n = 1)
d R = Me (n = 1)
e R = Bu (n = 1)
triynes
3a–k
R
ZnCl
n
f
R = TIPS (n = 1)
5
a–f
Scheme 1 General scheme for the transformation of dibromoolefins into diynes and triynes
Acetylene chemistry has played an important role in both situ with numerous electrophiles. Alternatively, aryl
organic synthesis and materials chemistry. Many alcohols polyynes can result from the conversion of the intermedi-
bearing a polyyne framework have been isolated from ate lithium acetylide to a zinc acetylide, followed by pal-
species of plants, fungi, or sponges, and they often show ladium-catalyzed Negishi coupling.10 The current scope
2
important biological activity. Moreover, conjugated of this reaction is described herein.
polyynes are widely used as carbon-rich building blocks,3
The direct precursors, terminal enynes 1a–f, are produced
and extended polyynes themselves show interesting opti-
from the corresponding trimethylsilyl protected deriva-
4
cal properties. Over the years, a variety of methods have
been developed to form diynes via a one-pot reaction; that
is, transformations that accomplish both the generation
and subsequent substitution of a metal acetylide all in a
single step. Typical examples for the formation and trap-
ping of diynes include (a) the elimination of 1-halobut-1-
10,11
tives, which are either known or easily prepared.
The
general transformation to the desired products, diynes 2
and triynes 3, is shown in Scheme 1. Precursor 1 is dis-
solved in toluene or a mixture of toluene and hexanes
(
(
1:5), depending on solubility, and cooled to –20 °C. BuLi
2.2 equiv) is added dropwise to this solution via a syringe
5
,6
en-3-ynes, (b) monodesilylation of 1,4-bis(trimethyl-
and the temperature is raised to 0 °C giving the intermedi-
ate lithium acetylide 4. The solution is then recooled to
7
silylbuta)-1,3-diyne with MeLi/LiBr, and (c) the elimina-
8
tion of (Z)-1-methoxybut-1-en-3-ynes.
–
20 °C and an equal amount of anhydrous Et O (10 mL)
2
We have recently developed a divergent approach that has added, followed by an electrophile dissolved in Et O. The
2
been successful for the formation of functionalized diynes reaction temperature is then slowly raised to room temper-
and triynes. In this process, a lithitated diyne or triyne is ature and quenched. Aqueous workup and purification by
generated from a dibromoolefin with BuLi via a carbenoid column chromatography gives the desired products. Key
9
rearrangement. This intermediate can then be trapped in to the success of this protocol is absolutely anhydrous re-
action conditions, because both the carbenoid and acetyl-
ide intermediates are rapidly quenched by adventitious
water, resulting in lower yields and more difficult chro-
matographic separations.
SYNTHESIS 2008, No. 7, pp 1158–1162
x
x
.
x
x
.2
0
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8
Advanced online publication: 10.01.2008
DOI: 10.1055/s-2007-1000937; Art ID: Z06807SS
Georg Thieme Verlag Stuttgart · New York
©

PRACTICAL SYNTHETIC PROCEDURES
Synthesis and Functionalization of Polyynes
1159
A slightly different procedure is employed to achieve the iodide coupling partner and Pd(PPh ) (5 mol%) are
3
4
1
3
Negishi coupling. Terminal alkyne 1 is dissolved in introduced and the reaction mixture heated to 70 °C for
toluene and the temperature is lowered to –40 °C. BuLi ca. 20 hours. Workup and purification gives the diynes
2.2 equiv) is added, and the reaction temperature is raised and triynes in reasonable to excellent yield.
1
2
(
to –20 °C to ensure complete rearrangement of the alkyl-
idene carbenoid to the lithiated polyyne. The reaction
Dibromoenyne 1a has been used as a model system to ex-
plore the potential of this one-pot reaction. Under the con-
ditions described above, lithium acetylide 4a reacted with
mixture is again cooled to –40 °C and ZnCl (1.2 equiv)
2
added to give the zinc acetylide 5. Subsequently, the aryl
14
methyl iodide to form diyne 2a in good yield, whereas
Table 1 Diynes 2a–j Formed from Dibromoolefin 1a
Electrophile
Product
Yield (%)a
67
Me
Et
MeI
2
2
2
a
b
c
EtI
<5
CO2
COOH
OH
64
O
H
7
5
5
2
d
e
TIPS
TIPS
OH
O
H
7
0
OTBDMS
OTBDMS
2
HO
HO
HO
O
O
2
3
2
(
(
+)-2f
–)-2g
0
O
2b
OTBDMS
OTBDMS
Me
2
2
h
i
90
I
Me
6
4
I
I
2
j
a
Isolated yield.
HMPA (2.6 equiv) added.
b
Synthesis 2008, No. 7, 1158–1162 © Thieme Stuttgart · New York

1
160
T. Luu et al.
PRACTICAL SYNTHETIC PROCEDURES
the analogous reaction with ethyl iodide to produce 2b +6, c 0.55, MeOH), shows analogous spectral data and op-
was unsuccessful. The formation of diyne carboxylic acid tical rotation as pilosol A, a diyne isolated from Bidens pi-
1
5
16
2
c was achieved in good yield by trapping the interme- losa. Thus, both the structure and R-stereochemistry for
diate lithium acetylide with carbon dioxide, and the de- this natural product were confirmed. The use of HMPA
sired product was purified by an acid-base extraction. used as an additive did not improve the yield of the ep-
Secondary alcohols 2d and 2e were produced when either oxide addition reactions (e.g., compound 2h).
an alkynyl or alkyl aldehyde was used as the electrophile,
although the yield was lower in the case of 2e due presum-
ably to the acidic a-protons of the alkyl aldehyde.
Formation of the zinc acetylide 5a provided a nucleophilic
coupling partner necessary for the Negishi reaction, via
reaction with aryl iodides. Diyne 2i was produced in ex-
Epoxides were used as electrophiles in reactions with 4a, cellent yield, and using a double Negishi coupling, 5a was
giving optically active homopropargylic alcohols 2f and reacted with 1,3-diiodobenzene to form compound 2j in
2
g, albeit the yields were consistently low. The product 64% yield (80% yield per coupling event).
2
0
from the reaction of (R)-propylene oxide, (+)-2f ([a]D
Table 2 Triynes 3a–k Formed from Dibromoolefins 1b–f
Dibromoolefin
Electrophile
Product
Yield (%)a
59
O
OH
1
d
d
Me
H
H
3
a
OH
Me
1
O
58b
65
Me
3
3
3
b
1
b
b
MeI
CO2
c
1
COOH
OH
65
54
d
O
H
1
1
b
e
3
e
OH
O
Bu
82
3
f
TIPS
TIPS
I
TIPS
TIPS
1
1
e
Bu
NMe2
24
80
NMe2
3
g
OMe
b
I
I
OMe
Me
3
h
t-Bu
Me
1
c
60
3
i
1
1
f
TIPS
Me
CN
69
78
I
I
Me
CN
3
j
f
TIPS
3
k
a
Isolated yield.
Oxirane was dissolved in NH3.
b
Synthesis 2008, No. 7, 1158–1162 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Synthesis and Functionalization of Polyynes
1161
Because of the inherent challenges that have faced triyne the stability of a dibromoolefinic precursors limits the
syntheses in the past, both the ability to form the polyyne success of the one-pot procedure, providing lower overall
skeleton and functionalize one terminus in a single step yields of the desired product.
was quite desirable. Gratifyingly, the protocol optimized
for the synthesis of 2a–j has been equally applicable for
triynes (Table 2), and the scope of the reaction has been
demonstrated over a broader range of dibromoolefinic distilled from sodium/benzophenone ketyl, and hexanes and
Reagents were purchased reagent grade from commercial suppliers
and used without further purification. Et O, toluene, and THF were
2
substrates 1b–f. For example, reaction of the methyl-ter- CH Cl were distilled from CaH , immediately prior to use. Evapo-
2
2
2
ration and concentration in vacuo was done at water-aspirator pres-
sure. All reactions were performed in standard, dry glassware under
minated lithium acetylide 4d with paraformaldehyde gave
the propargylic alcohol 3a in reasonable yield, a natural
product identified from the fungi Kuehneromyces mutabi-
lis, Psilocybe merdaria, and Ramaria flava. The corre-
sponding homopropargylic alcohol 3b was derived from
an inert atmosphere of Ar or N . Column chromatography: silica
2
gel-60 (230–400 mesh) from General Intermediates of Canada.
TLC: aluminum sheets covered with silica gel-60 F254 from
1
7
Macherey-Nagel; visualization by UV light or KMnO stain. Melt-
4
–
1
the reaction of 4d with oxirane in a reaction mixture dilut- ing points: Gallenkamp apparatus. IR spectra (cm ): Nic-Plan IR
1
13
ed with NH . The product, 3,5,7-nonatriyn-1-ol, was iso- Microscope. H NMR and C NMR spectra: Varian Inova 300, 400
3
1
or 500 instruments, at r.t. in CDCl ; solvent peaks (7.24 ppm for H
lated as a white solid that turned pink when exposed to
light. This compound has been isolated from a number of
3
1
3
and 77.0 ppm for C) were used as reference. EI MS (m/z): Kratos
MS50 instrument. Elemental analyses were conducted by Spectral
Services at the University of Alberta. Spectral data for compounds
not provided below or referenced in the text can be found in refer-
ence 10b.
1
8
natural sources including Collybia peronata, Lentinus
1
9
20
edodes (shiitake mushroom), and Tridax trilobata. Us-
ing the phenyl-substituted dibromoolefin 1b, rearrange-
ment and reaction with MeI and CO gave the known
2
2
1
22
natural products 3c and 3d in respectable yields, while Enynes 1; General Procedure
To a solution of the appropriate trimethylsilyl-protected precursor
of 1 (1 mmol) in THF (10 mL) and MeOH (10 mL) was added pul-
using benzaldehyde as the electrophile gave secondary al-
cohol 3e. Generation of the butyl derivative 4e from 1e
and reaction with a diynone produced compound 3f in ex-
cellent yield as a stable brown oil.
1
1
verized K CO (0.1 g, 0.75 mmol) at r.t. TLC analysis was used to
2
3
monitor the reaction until desilylation was complete (typically ca. 1
h; the R of the product is always slightly less than that of the starting
f
material). Sat. aq NH Cl (10 mL) and Et O (10 mL) were then add-
The synthesis of aryl triynes through Negishi coupling
was explored via the generation of intermediate triyne
acetylides 4b,c,e,f and subsequent transmetalation to give
the zinc acetylide intermediates 5b,c,e,f. The palladium-
catalyzed cross-coupling of butyl acetylide 5e with 4-
4
2
ed, the organic layer was separated, washed with H O (2 × 50 mL),
2
and dried (MgSO ). After filtration, the solvent was reduced to ca.
4
1
–2 mL, and this solution was passed through a short silica gel col-
umn to afford the terminal alkyne 1. The product was dried under
vacuum. Care must be taken to ensure that the desilylated product
(
N,N-dimethyl)iodoaniline gave triyne 3g in low yield, is absolutely anhydrous to prevent quenching of the carbenoid inter-
which is not unexpected for an electron-rich coupling mediate during the subsequent step. In some cases, products 1 slow-
ly discolor over time (e.g., 1b,d,e), and are therefore either best used
immediately or stored in solution under refrigeration.
partner. Coupling with p-iodoanisole was more successful
and gave 3h in good yield (80%). p-Iodotoluene reacted
with tert-butyl derivative 5c and TIPS derivative 5f to
give 3i and 3j, respectively. Completing the series, zinc
acetylide 5f was coupled with the electron-deficient 4-cy-
anoiodobenzene to produce 3k as a stable, light yellow toluene (10 mL) at –40 °C under argon was added BuLi (2.5 M in
crystalline solid in 78% yield.
1
,3-Bis(3-phenylbuta-1,3-diynyl)benzene (2j); Typical Proce-
dure 1
To a stirred solution of dibromoolefin 1a (215 mg, 0.752 mmol) in
hexanes, 0.66 mL, 1.7 mmol) by a syringe over a period of ca. 5
min. The mixture was allowed to warm slowly to –20 °C and then
recooled to –40 °C. ZnCl (0.5 M in THF, 1.8 mL, 0.9 mmol) was
In conclusion, a one-pot protocol has been developed for
synthesis of diynes and triynes in reasonable to excellent
2
added by a syringe over a period of ca. 5 min. The mixture was then
yield. Overall, this method shows several advantages, but allowed to warm slowly to 0 °C over ca. 10 min. 1,3-Diiodobenzene
also some limitations. Advantages of this method include: (110 mg, 0.333 mmol) and Pd(PPh ) (60 mg, 0.052 mmol) were
3 4
added, and this mixture was heated to reflux under a positive pres-
sure of argon. After 20 h, the mixture was cooled and filtered
through a pad of Celite. The resulting solution was concentrated un-
der reduced pressure and the residue purified by column chromatog-
raphy (silica gel, hexanes–CH Cl , 6:1), giving 2j as a yellow solid;
(
a) it is divergent and assembles and functionalizes the
polyyne framework in a single step, (b) it does not require
kinetically unstable polyyne precursors that can be diffi-
cult to obtain neat, and (c) it readily provides unsymmet-
rical substituted diynes and triynes, including both
polyyne natural products and carbon-rich scaffolds. Un- 6:1).
fortunately, this method is not suitable for use in all cases,
2
2
yield: 71.1 mg (64%); mp 115–117 °C; R = 0.3 (hexanes–CH Cl ,
f
2
2
–1
IR (mscope, neat solid): 3062 (w), 2220 (m), 1589 cm (m).
including (a) situations where a polar ethereal solvent
such as THF or Et O is needed to solubilize the precursor
1
H NMR (500 MHz, CDCl ): d = 7.66–7.64 (m, 1 H), 7.54–7.48 (m,
3
2
6
H), 7.39–7.29 (m, 7 H).
dibromoolefin 1; even small amounts of such solvents ef-
fectively prevent the carbenoid rearrangement step, (b)
cases where an acidic or electrophilic substrate would be
desired as a substituent on the dibromoolefin; that is,
groups that will not tolerate BuLi, and (c) in some cases,
1
3
C NMR (125 MHz, CDCl ): d = 136.1, 133.0, 132.6, 129.4, 128.7,
3
1
28.5, 122.5, 121.6, 82.1, 80.2, 74.8, 73.7.
MS (EI, 70 eV): m/z (%) = 326.1 (100, [M]+).
+
HRMS (EI): m/z [M] calcd for C H : 326.1096; found: 326.1099.
26 14
Synthesis 2008, No. 7, 1158–1162 © Thieme Stuttgart · New York

1
162
T. Luu et al.
PRACTICAL SYNTHETIC PROCEDURES
References
Nona-3,5,7-triyn-1-ol (3b); Typical Procedure 2
Dibromoolefin 1d (451 mg, 1.82 mmol) was disssolved in toluene
(
(
(
1) Current address: Department of Polymer Chemistry,
Graduate School of Engineering, Kyoto University, Japan.
2) Shi Shun, A. L. K.; Tykwinski, R. R. Angew. Chem. Int. Ed.
(
(
10 mL) and cooled to –20 °C under argon. To this solution, BuLi
2.5 M in hexanes, 1.6 mL, 4.0 mmol) was added via a syringe over
a period of ca. 1 min. The mixture was allowed to warm slowly to
°C, recooled to –20 °C, and Et O (10 mL) was added. To this so-
2006, 45, 1034.
0
2
3) Acetylene Chemistry: Chemistry, Biology, and Material
Science; Diederich, F.; Stang, P. J.; Tykwinski, R. R., Eds.;
Wiley-VCH: Weinheim, 2005.
lution was added, via a cannula, a mixture of oxirane (2 mL, 40
mmol) in NH (5 mL) cooled to –20 °C. The solution was allowed
to warm to r.t., stirred overnight, and quenched with sat. aq NH Cl
3
4
(
4) (a) Luu, T.; Elliott, E.; Slepkov, A. D.; Eisler, S.; McDonald,
R.; Hegmann, F. A.; Tykwinski, R. R. Org. Lett. 2005, 7,
(10 mL) and Et O (10 mL). The organic phase was separated,
2
washed with brine (2 × 10 mL), and dried (MgSO ). Solvent remov-
al and purification by column chromatography (silica gel, CH Cl )
gave compound 3b as a white crystalline solid that turned pink
when exposed to light; yield: 140 mg (58%); mp 54–56 °C; R = 0.3
4
51. (b) Eisler, S.; Slepkov, A. D.; Elliott, E.; Luu, T.;
2
2
McDonald, R.; Hegmann, F. A.; Tykwinski, R. R. J. Am.
Chem. Soc. 2005, 127, 2666.
5) (a) Himbert, G.; Umbach, H.; Barz, M. Z. Naturforsch., B
f
(
(
CH Cl ).
2 2
1
984, 39, 661. (b) Negishi, E.; Okukado, N.; Lovich, S. F.;
IR (mscope, neat solid): 3262 (vs), 2946 (s), 2876 (s), 2219 (s), 2036
Luo, F.-T. J. Org. Chem. 1984, 49, 2629. (c) Kende, A. S.;
Smith, C. A. J. Org. Chem. 1988, 53, 2655. (d) Alami, M.;
Crousse, B.; Linstrumelle, G. Tetrahedron Lett. 1995, 36,
3687.
(
w), 1054 cm–1 (m).
1
H NMR (500 MHz, CDCl ): d = 3.74 (t, J = 6.0 Hz, 2 H), 2.55 (t,
3
J = 6.0 Hz, 2 H), 1.94 (s, 3 H), 1.64 (br s, 1 H).
1
3
(6) This general approach has very recently been extended to tri-
and tetra- and pentaynes, see: Métay, E.; Hu, Q.; Negishi, E.
Org. Lett. 2006, 8, 5773.
C NMR (125 MHz, CDCl ): d = 75.4, 75.3, 67.5, 64.8, 61.2, 60.6,
3
5
9.3, 23.8, 4.5.
+
MS (EI, 70 eV): m/z (%) = 132.1 (72, [M] ), 102.0 (100, [M –
CH O] ).
(
7) (a) Holmes, A. B.; Jennings-White, C. L. D.; Schulthess, A.
H.; Akinde, B.; Walton, D. R. M. J. Chem. Soc., Chem.
Commun. 1979, 840. (b) Fiandanese, V.; Bottalico, D.;
Marchese, G.; Punzi, A. Tetrahedron 2006, 62, 5126.
8) (a) Stracker, E. C.; Zweifel, G. Tetrahedron Lett. 1990, 31,
+
2
+
HRMS (EI): m/z [M] calcd for C H O: 132.0575; found: 132.0577.
9
8
Anal. Calcd for C H O (132.16): C, 81.79; H, 6.10. Found: C,
8
Spectral data were consistent with those reported.17a
9
8
(
(
1.58; H, 6.26.
6815. (b) Kwon, J. H.; Lee, S. T.; Shim, S. C. J. Org. Chem.
1994, 59, 1108.
9) For a review, see: Chalifoux, W. A.; Tykwinski, R. R. Chem.
Rec. 2006, 6, 169.
3
-(3-Triisopropylsilylethynyl)-1-triisopropylsilyl-1,4,6,8-tri-
decatetrayn-3-ol (3f); Typical Procedure 3
Dibromoolefin 1e (273 mg, 0.947 mmol) was dissolved in toluene
(10) For a more thorough description of this process, see:
(a) Morisaki, Y.; Luu, T.; Tykwinksi, R. R. Org. Lett. 2006,
8, 689. (b) Luu, T.; Morisaki, Y.; Cunningham, N.;
Tykwinksi, R. R. J. Org. Chem. 2007, 72, 9622.
(11) (a) Shi Shun, A. L. K.; Chernick, E. T.; Eisler, S.;
Tykwinski, R. R. J. Org. Chem. 2003, 68, 1339. (b) Eisler,
S.; Tykwinski, R. R. J. Am. Chem. Soc. 2000, 122, 10736.
(c) Eisler, S.; Chahal, N.; McDonald, R.; Tykwinski, R. R.
Chem. Eur. J. 2003, 9, 2542.
(
2 mL) and this solution was diluted with hexanes (10 mL). To this
stirred mixture at –20 °C was added BuLi (2.5 M in hexanes, 0.83
mL, 2.1 mmol) and the reaction was warmed to 0 °C. 1,5-Bis(triiso-
propylsilyl)penta-1,4-diyn-3-one (321 mg, 0.822 mmol) dissolved
in Et O (10 mL) was added, and the reaction was allowed overnight
2
to warm to r.t. Workup and purification as described above for 3b
gave compound 3f as a brown oil; yield: 370 mg (82%); R = 0.44
f
(
hexanes–CH Cl , 6:1).
(12) Toluene was used instead of hexanes to achieve a higher
temperature for reflux in the Negishi cross-coupling.
(13) Negishi, E. In Handbook of Organopalladium Chemistry for
Organic Synthesis; Negishi, E., Ed.; Wiley-VCH: New
York, 2002, 229.
2
2
IR (CHCl , cast): 3435 (w), 2943 (vs), 2866 (vs), 2219 (m), 2155
(
3
–1
w), 1463 cm (m).
1
H NMR (500 MHz, CDCl ): d = 2.75 (br s, 1 H), 2.30 (t, J = 7.0
3
Hz, 2 H), 1.54–1.48 (m, 2 H), 1.44–1.36 (m, 2 H), 1.06 (s, 42 H),
(
14) Reisch, J.; Walker, H. Arch. Pharm. (Weinheim, Ger.) 1964,
97, 628.
(15) Fleming, I.; Ramarao, C. Org. Biomol. Chem. 2004, 2, 1504.
0
1
.89 (t, J = 7.0 Hz, 3 H).
2
3
C NMR (125 MHz, CDCl ): d = 102.7, 85.9, 82.3, 72.6, 67.8,
3
(
16) Chang, M.-H.; Wang, G.-J.; Kuo, Y.-H.; Lee, C.-K. J. Chin.
Chem. Soc. 2000, 47, 1131.
6
6.1, 65.3, 58.6, 54.8, 29.9, 21.9, 19.1, 18.5, 13.4, 11.1.
MS (EI, 70 eV): m/z (%) = 477.3 (17, [M – i-Pr]+).
(
17) (a) Luu, T.; Tykwinski, R. R. J. Org. Chem. 2006, 71, 8982.
(b) Luu, T.; Wei, S.; Lowary, T. L.; Tykwinski, R. R.
Synthesis 2005, 3167.
+
HRMS (EI): m/z [M – i-Pr] calcd for C H OSi : 477.3009; found:
4
3
0
45
2
77.3019.
(
(
(
(
(
18) Higham, C. A.; Jones, E. R. H.; Keeping, J. W.; Thaller, V.
J. Chem. Soc., Perkin Trans. 1 1974, 1991.
19) Tokimoto, K.; Fujita, T.; Takeda, Y.; Takaishi, Y. Proc. Jpn.
Acad., B 1987, 63, 277.
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Chem. 1970, 739, 135.
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Aranda, E.; Delgado, G. Planta Med. 1996, 62, 355.
22) Bohlmann, F.; Sucrow, W.; Queck, I. Chem. Ber. 1964, 97,
Acknowledgment
We thank the University of Alberta and the Natural Sciences and
Engineering Research Council of Canada (NSERC) for the financi-
al support through the Discovery and Nano Innovation Platform
(NanoIP) grant programs. T.L. thanks the University of Alberta for
a Dissertation Fellowship.
2586.
Synthesis 2008, No. 7, 1158–1162 © Thieme Stuttgart · New York