Hydroquinone-pyrrole dyads with varied linkers

Article abstract of DOI:10.3762/bjoc.12.10

A series of pyrroles functionalized in the 3-position with p-dimethoxy benzene via various linkers (CH₂, CH₂CH₂, CH=CH, C=C) has been synthesized. Their electronic properties have been deduced from ¹H NMR, ¹³C NMR, and UV-vis spectra to detect possible interactions between the two aromatic subunits. The extent of conjugation between the subunits is largely controlled by the nature of the linker, with the largest conjugation found with the tmns-ethene linker and the weakest with the aliphatic linkers. DFT calculations revealed substantial changes in the HOMO-LUMO gap that correlated with the extent of conjugation found experimentally. The results of this work are expected to open up for use of the investigated compounds as components of redox-active materials in sustainable, organic electrical energy storage devices.

Full text of DOI:10.3762/bjoc.12.10

Hydroquinone–pyrrole dyads with varied linkers
Hao Huang1, Christoffer Karlsson1, Maria Strømme1, Martin Sjödin1 and Adolf Gogoll*2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2016, 12, 89–96.
1Nanotechnology and Functional Materials, Department of
doi:10.3762/bjoc.12.10
Engineering Sciences, The Ångström Laboratory, Uppsala University,
Box 534, SE-751 21 Uppsala, Sweden and 2Department of Chemistry
Received: 22 October 2015
Accepted: 29 December 2015
Published: 18 January 2016
-
BMC, Biomedical Centre, Uppsala University, Box 576, SE-751 23
Uppsala, Sweden
Email:
Associate Editor: J. A. Murphy
Adolf Gogoll* - adolf.gogoll@kemi.uu.se
©
2016 Huang et al; licensee Beilstein-Institut.
*
Corresponding author
License and terms: see end of document.
Keywords:
conjugation; heterocycles; hydroquinone; linker effect; pyrrole
Abstract
A series of pyrroles functionalized in the 3-position with p-dimethoxybenzene via various linkers (CH2, CH2CH2, CH=CH, C≡C)
has been synthesized. Their electronic properties have been deduced from 1H NMR, 13C NMR, and UV–vis spectra to detect
possible interactions between the two aromatic subunits. The extent of conjugation between the subunits is largely controlled by the
nature of the linker, with the largest conjugation found with the trans-ethene linker and the weakest with the aliphatic linkers. DFT
calculations revealed substantial changes in the HOMO–LUMO gap that correlated with the extent of conjugation found experi-
mentally. The results of this work are expected to open up for use of the investigated compounds as components of redox-active
materials in sustainable, organic electrical energy storage devices.
Introduction
Quinone–pyrrole dyads have attracted interest in various appli-
cations due to the possibility of modulating the electronic inter-
action between the two subunits, with porphyrin–quinone dyads
being well-known examples [1-3]. Recently, we have shown the
suitability of the quinone–hydroquinone redox couple
(
Figure 1) as the redox active and capacity carrying component
in conducting redox polymers (CRPs) [4,5]. To further investi-
gate the interaction between the molecular components in these
systems, a series of compounds with different linkers between
the pyrrole and hydroquinone subunits was designed [6].
Although it is known that N-protected pyrrole (Py) can be selec-
tively functionalized at the β-position [7], we found the
Figure 1: Structure of pyrrole/hydroquinone derivatives 3-(2,5-
dimethoxyphenyl)-1H-pyrrole (1) and 3-(1,4-dihydroxyphenyl)-1H-
pyrrole (2) [5].
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Beilstein J. Org. Chem. 2016, 12, 89–96.
published procedures to be unsuitable for our purpose (vide tical in countries where the use of hydrazine has been restricted
infra). Therefore, we have developed improved procedures for by law [12]. As an alternative, the Suzuki–Miyaura reaction can
the synthesis of quinone–pyrrole dyads with a variety of linkers be utilized for C–C cross coupling of benzyl halides with
between the two subunits.
heteroarylboronic acids. However, in contrast to its use for the
synthesis of thiophene and furane derivatives, it has rarely been
The target compounds thus consist of a pyrrole unit as well as a employed for the coupling of pyrrolylboronic acids with benzyl
hydroquinone group (protected as dimethyl ether, i.e., halides [13-17]. We applied the Suzuki–Miyaura cross-coupling
dimethoxybenzene, DMB), connected by different linkers, as shown in Scheme 1, with a total yield of nearly 50% (from
resulting in varying distance and degree of conjugation be- 2,5-dimethoxybenzyl bromide (5)).
tween the two subunits (Figure 2). DMB was chosen due to its
superior stability compared to the hydroquinone counterpart Starting material 5 was prepared from 2,5-dimethoxybenzyl-
during the synthesis. The corresponding hydroquinone ana- alcohol by a reported procedure [18] in 95% yield. Using
logue can be achieved by straightforward demethylation with typical conditions, the yield of the coupling reaction was 56%,
BBr3 [8-10]. The electronic properties of the monomers were which was considered satisfactory because of the ready avail-
investigated by NMR and UV–vis spectroscopy as well as den- ability of starting materials and the modest reaction time of
sity functional theory (DFT) calculations.
4 hours. Since the starting materials in the Suzuki–Miyaura
cross-coupling tolerate a wide variety of functional groups,
facile and versatile combination of different dihydroxybenzyl
halide derivatives and pyrrolylboronic acids should be possible.
Ethylene linker: Synthesis of 3-(2,5-
dimethoxystyryl)-1H-pyrrole (3c)
Our initial approach of synthesizing vinyl linker dyad 3c was to
use a Heck reaction, coupling 3-iodo-1-(triisopropylsilyl)-1H-
pyrrole and dimethoxystyrene. A variation of reaction parame-
ters was investigated, involving the selection of base and sol-
vent. However, none of the attempted conditions gave the
desired product. Instead, desilylation of 3-iodo-1-(triisopropyl-
silyl)-1H-pyrrole was observed during the reaction, and some of
the dimethoxystyrene could be recovered (for details, see
Supporting Information File 2).
Figure 2: Hydroquinone dimethyl ether functionalized pyrroles with
linkers L discussed in this study.
Results and Discussion
Synthesis
Methyl linker: Synthesis of 3-(2,5-dimethoxybenzyl)-
1
H-pyrrole (3a)
For our target compound 3-(2,5-dimethoxybenzyl)-1H-pyrrole
3a), we initially considered some published procedures, but According to a study by Liu et al. [19], the protecting group for
(
none of them were deemed adequate for our requirements. For 3-iodo pyrrole is essential in the Heck reaction involving
example, Foos et al. have devised a synthetic route using alkyl- pyrrole. Based on this suggestion, 3-iodo-1-tosyl-1H-pyrrole
ation of pyrrylmagnesium bromide with the benzyl bromide 5 was also tested but did not result in any product. It is worth to
[
10], but yielding only 3.1% after a tedious work-up. Aquino- mention that in their study, ten equivalents of styrene were used
Binag et al. achieved a total yield of 70% [11], however, their to obtain 28% yield, indicating that the reaction conditions were
procedure relies on a Wolff–Kishner reduction of the corre- not optimal, and therefore cannot be applied to other vinyl
sponding acylpyrrole with hydrazine hydrate, making it imprac- substrates such as dimethoxystyrene directly. A synthetic route
Scheme 1: Synthetic route for 3-(2,5-dimethoxybenzyl)-1H-pyrrole (3a). Conditions: i) Pd(PPh3)4, Na2CO3 (2 M aq), MeOH/toluene, microwave
heating, 110 °C, 4 h, 56%; ii) TBAF, THF, rt, 0.5 h, 88%.
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Beilstein J. Org. Chem. 2016, 12, 89–96.
via hydrogenation of the ethynyl linker compound 4d was also Acetylene linker: Synthesis of 3-((2,5-dimethoxy-
investigated (vide infra), but did not produce satisfactory phenyl)ethynyl)-1H-pyrrole (3d)
results.
The synthesis strategy for the ethynyl-linked compound 3d was
straightforward, using a Sonogashira coupling reaction
Settambolo et al. [20] reported a synthetic route starting from (Scheme 3). Thus, 2,5-dimethoxyphenyl bromide (8) was con-
an acylation of pyrrole by phenylacetyl chloride via a verted to ((2,5-dimethoxyphenyl)ethynyl)trimethylsilane (9),
Friedel–Crafts reaction, followed by reduction by NaBH4, and which was desilylated by addition of NaOH (aq) to give
elimination to give the vinylpyrrole product. When this strategy 2-ethynyl-1,4-dimethoxybenzene (10). Sonogashira conditions
was applied to the reaction of (2,5-dimethoxyphenyl)acetyl were as described by Erdélyi et al. using microwave heating
chloride with 1-(triisopropylsilyl)-1H-pyrrole, nearly 50% yield [22], allowing the reaction to be completed in half an hour with
was achieved in the first step, but requiring a reaction time of 95% yield. A second Sonogashira reaction of 10 with 3-iodo-1-
more than one day. Therefore, considering the total reaction (triisopropylsilyl)-1H-pyrrole afforded the protected pyrrole
time and availability of starting material, a Wittig reaction was derivative 4d. For this second Sonogashira reaction, these
chosen as an alternative.
conditions, when attempting to couple 10 to 3-bromo-1-(triiso-
propylsilyl)-1H-pyrrole resulted in low yield (20%) and also
The Wittig reaction approach is shown in Scheme 2. In this homocoupling. Considering that desilylation of triisopropyl-
reaction, phosphonium salt 7 was prepared in quantitative yield
from 5 and triphenylphosphine by reflux in toluene, according
to a procedure reported for dimethoxybenzyl chloride [21]. The
work-up involved simple filtration and washing with toluene.
Use of t-BuOK as a base to deprotonate the phosphonium salt
resulted in a dark red phosphorous ylide, to which 1-(triiso-
propylsilyl)-1H-pyrrole-3-carbaldehyde was added, followed by
heating at 80 °C. The desired product 4c was obtained in
4
0% yield after 3 h. When the reaction was performed at room
temperature, only 20% yield was obtained after 48 h. Close to
equal quantities of cis-4c and trans-4c were formed in this reac-
tion, and were separated chromatographically. Having access to
both isomers was desirable, since the stereoisomers are
expected to have different electronic properties. After desilyl-
ation, compound 3c was obtained in a combined total yield of
3
5% (sum of cis-3c and trans-3c) from the pyrrole-3-carbalde-
hyde. To obtain trans-4c selectively, a Wittig–Horner reaction
was investigated, with dimethoxybenzyl bromide as starting
material for the corresponding phosphonate. However, neither
n-BuLi nor t-BuOK used as base succeeded to give the desired
product.
Scheme 3: Synthesis of 3-((2,5-dimethoxyphenyl)ethynyl)-1H-pyrrole
3d). Conditions: i) Ethynyltrimethylsilane, Pd(PPh3)2Cl2, CuI, PPh3,
diethylamine, DMF, microwave heating, 120 °C, 30 min, 95%; ii) NaOH
1 M, aq), MeOH/CHCl3, rt, 0.5 h, 90%; iii) Pd(PPh3)2Cl2, CuI, triethyl-
amine, 3-iodo-1-(triisopropylsilyl)-1H-pyrrole, THF, rt, overnight, 50%;
iv) TBAF, THF, rt, 0.5 h, 85%.
(
(
Scheme 2: Synthetic route for 3-(2,5-dimethoxystyryl)-1H-pyrrole (3c); cis-4c and trans-4c were separated chromatographically to achieve the syn-
thesis of both isomers of 3c separately. Conditions: i) PPh3, toluene, reflux, overnight, quantitative; ii) t-BuOK, THF, 0.5 h, not isolated; iii) 1-(triiso-
propylsilyl)-1H-pyrrole-3-carbaldehyde, 80 °C, 3 h, 40%; iv) TBAF, THF, rt, 0.5 h, 86%.
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Beilstein J. Org. Chem. 2016, 12, 89–96.
silyl protected pyrrole might occur at high temperature in DMF, shifts are closely matched by those derived from the DFT calcu-
an overnight reaction at room temperature was performed, lations (see Supporting Information File 2 for details) [26,27],
resulting in a yield for 4d of 50%. In summary, after a four step with average errors of 0.13 ppm for 1H (RMS error = 0.17), and
synthesis route, the total yield of 3d from 8 was 36%. Attempts 1.9 ppm for 13C (RMS error = 2.6). The above mentioned
were made to convert alkyne 4d into the corresponding alkene pattern of δpyrrole H-2 > δpyrrole H-5 for the conjugated com-
4
c. However, partial hydrogenations with a Lindlar catalyst [23] pounds, with reversal for the non-conjugated compounds, was
or with trimethylsilane using a palladium catalyst [24] were also present in the calculated chemical shifts, except for 3a and
either unsuccessful or produced low yields (for details, see trans-3c. We notice that in these two compounds, the deviation
Supporting Information File 2).
between observed and calculated chemical shift is untypically
high at 0.23 ppm for both Py-5 in 3a and Py-2 in trans-3c. This
illustrates the well-known caveat for chemical shift predictions
[26].
Ethyl linker: Synthesis of 3-(2,5-
dimethoxyphenethyl)-1H-pyrrole (3b)
Compound 3b was prepared by reduction of 4d with H2 over
Pd/C catalyst (Scheme 4). The N-protected 4d was used instead To assess the electronic properties as indicated in UV–vis
of 3d to minimize the risk of decomposition during the hydro- spectra, reference spectra of pyrrole, DMB, 1,4-dimethoxy-2-
genation reaction, since unprotected pyrrole is known to be vinylbenzene (DMB-VI), and 1,4-dimethoxy-2-ethynylbenzene
far less stable [25]. After desilylation by TBAF, 3-(2,5- (DMB-EN) were recorded. The UV–vis spectra of non-conju-
dimethoxyphenethyl)-1H-pyrrole (3b) was obtained in a total gated 3a and 3b closely resemble the sum of absorptions from
yield of 36% over five steps from 8.
the individual DMB and pyrrole spectra, indicating the absence
of substantial electronic effects from the substituent. On the
other hand, for the conjugated 3c, 3d and 1, a red shift is ob-
served when compared to the individual reference compound
spectra (Figure 5).
Electronic properties: Evidence from NMR
spectroscopy, UV–vis spectroscopy and
DFT calculations
In the NMR spectra, conjugation between the DMB and the
pyrrole units is indicated by increased chemical shifts for DMB- According to DFT calculations (see Supporting Information
H-6 (7.13–7.03 for 1, 3c and 3d) as compared to the non-conju- File 2 for details), the HOMO–LUMO transition is allowed for
gated compounds (6.83–6.76 for 3a and 3b) (Figure 3). In par- all compounds and has π–π* character. The HOMO of DMB
ticular, the chemical shift of the pyrrole H-2 (Pyr-2) is lower couples strongly to the pyrrole HOMO, resulting in increased
than that of the pyrrole H-5 (Pyr-5) in the non-conjugated com- HOMO energy in 1, cis-3c, trans-3c, and 3d. Additionally, the
pounds 3a and 3b, whereas pyrrole H-2 has considerably higher corresponding coupling between the DMB and pyrrole LUMOs
chemical shift than H-5 in the conjugated compounds 1, 3c and results in a lowering of the LUMO level in the combined mole-
3
d. This proton might therefore be used as an indicator of cular systems, since they are anti-bonding. The perturbation of
conjugation. Also, in the 13C NMR spectra, DMB C-1 (Ph-1) the HOMOs and LUMOs depends on the degree of interaction
has a lower chemical shift in the conjugated compounds between the two subunits, and is therefore a measure of the
(
128.7–113.9 for 1, 3c and 3d) as compared to the non-conju- charge delocalization in the molecule. This effect can be viewed
gated ones (132.3 for 3a and 3b) (Figure 4).
as an increased delocalized system that results in a lowering of
the HOMO–LUMO gap, which can be traced by the red shifts
To rationalize these chemical shift patterns, DFT calculations of the highest wavelength absorption in UV–vis spectra
were performed. The observed 1H and 13C NMR chemical (Table 1).
Scheme 4: Synthesis of 3-(2,5-dimethoxyphenethyl)-1H-pyrrole (3b). Conditions: i) Pd/C, MeOH/acetone, rt, 1.5 h, 98%; ii) TBAF, THF, rt, 0.5 h,
85%.
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Beilstein J. Org. Chem. 2016, 12, 89–96.
Figure 3: 1H NMR spectra (400 MHz, CDCl3 solution) of the DMB-pyrrole dyads (aliphatic signals not shown).
Figure 4: 13C NMR spectra (100.6 MHz, CDCl3 solution) of the DMB-pyrrole dyads (aliphatic signals not shown).
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Beilstein J. Org. Chem. 2016, 12, 89–96.
Figure 5: UV–vis absorption spectra of 1, 3a–d, (full lines) and the reference compounds DMB, DMB-VI, DMB-EN (dotted lines). The calculated
wavelengths for absorption maxima from DFT calculations for each linker compound are indicated by vertical red lines.
pounds such as 3d, the HOMO is distributed over both rings
Table 1: Calculated and experimental values (nm) for the absorption
maxima corresponding to the HOMO–LUMO transition in DMB, 1 and
a–d.
(Figure 6b).
3
DMB
1
3a 3b trans-3c cis-3c 3d
Among the conjugated compounds, 1 has the largest
HOMO–LUMO gap. This may be explained by the smaller
overall conjugated π system as compared to cis-3c, 3d and
trans-3c. The vinyl-linker structures (cis- and trans-3c) have
more extended π systems, which yield lower energy
Calculation
270 297 270 272 337
314
325
328
322
Experimental 290 308 290 290 336
The extent of conjugation among the series of linker com- HOMO–LUMO transitions. However, a significant difference is
pounds can be assessed by the HOMO–LUMO transition observed between trans-3c and cis-3c, which arises from the
(
Table 1). Since there is no conjugation between the two difference in their geometry: Whereas trans-3c has a planar
subunits in 3a and 3b, the HOMO and LUMO levels do not structure, for cis-3c the pyrrole and DMB substituents on the
shift with respect to the reference compound DMB. This is also vinyl linker were found to be twisted due to steric hindrance
revealed by the electron distribution on both of the rings at the between them, which might also explain the low chemical shift
HOMO level. For both 3a and 3b, the HOMO is entirely local- of the pyrrole-H-4 in cis-3c as the result of being exposed to an
ized at the DMB unit (Figure 6a), whereas for conjugated com- anisotropy effect of the DMB ring.
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Beilstein J. Org. Chem. 2016, 12, 89–96.
Figure 6: Calculated HOMO for 3a (a) and 3d (b).
Conclusion
Foundation as well as the Olle Byggmästare Foundation are
In summary, synthesis protocols for a series of methyl-protected acknowledged for their financial support of this work. We thank
hydroquinone-pyrrole dyads with good overall yields have been Bo Ek for HRMS measurements as well as Julien Andrès for
devised. DFT calculations allow insight into the electronic invaluable discussions and proofreading of the manuscript.
properties and conjugation within these compounds, with good
agreement between calculations and experimental spectro- References
scopic data. The extent of conjugation was found to vary with
the linker, with trans-3c (trans-3-(2,5-dimethoxystyryl)-1H-
pyrrole) having the strongest conjugation, as judged by the
HOMO–LUMO gap, while 3a (3-(2,5-dimethoxybenzyl)-1H-
pyrrole) and 3b (3-(2,5-dimethoxyphenethyl)-1H-pyrrole) have
no conjugation, with HOMO–LUMO gaps similar to DMB
1. Tsue, H.; Imahori, H.; Kaneda, T.; Tanaka, Y.; Okada, T.; Tamaki, K.;
Sakata, Y. J. Am. Chem. Soc. 2000, 122, 2279–2288.
doi:10.1021/ja9900454
2.
Kacprzak, S.; Kaupp, M. J. Phys. Chem. B 2006, 110, 8158–8165.
doi:10.1021/jp061105c
3.
Karr, P. A.; Zandler, M. E.; Beck, M.; Jaeger, J. D.; McCarty, A. L.;
Smith, P. M.; D'Souza, F. J. Mol. Struct.: THEOCHEM 2006, 765,
91–103. doi:10.1016/j.theochem.2006.03.012
(
p-dimethoxybenzene). These compounds should be interesting
4.
5.
6.
7.
Karlsson, C.; Huang, H.; Strømme, M.; Gogoll, A.; Sjödin, M.
J. Phys. Chem. C 2013, 117, 23558–23567. doi:10.1021/jp408567h
Karlsson, C.; Huang, H.; Strømme, M.; Gogoll, A.; Sjödin, M.
J. Phys. Chem. C 2014, 118, 23499–23508. doi:10.1021/jp506821z
Karlsson, C.; Huang, H.; Strømme, M.; Gogoll, A.; Sjödin, M. RSC Adv.
as components of redox active materials, as we have recently
shown in the synthesis of conducting redox polymers for use as
the active material in organic electrical energy storage [6].
2015, 5, 11309–11316. doi:10.1039/C4RA15708G
Supporting Information
Bray, B. L.; Mathies, P. H.; Naef, R.; Solas, D. R.; Tidwell, T. T.;
Artis, D. R.; Muchowski, J. M. J. Org. Chem. 1990, 55, 6317–6328.
doi:10.1021/jo00313a019
Supporting Information File 1
Synthetic details.
8
.
.
Kon, A. B.; Foos, J. S.; Rose, T. L. Chem. Mater. 1992, 4, 416–424.
doi:10.1021/cm00020a034
[http://www.beilstein-journals.org/bjoc/content/
9
Weissman, S. A.; Zewge, D. Tetrahedron 2005, 61, 7833–7863.
doi:10.1016/j.tet.2005.05.041
supplementary/1860-5397-12-10-S1.pdf]
Supporting Information File 2
10.Foos, J. S.; Degnan, S. M.; Glennon, D. G.; Beebe, X.
J. Electrochem. Soc. 1990, 137, 2530–2533. doi:10.1149/1.2086982
Optimization of experimental conditions, computated
electron distributions, UV–vis, IR, and NMR spectral data.
1
1
1
1
1
1.Aquino-Binag, C.; Kumar, N.; Pigram, P. Org. Prep. Proced. Int. 1995,
27, 700–703. doi:10.1080/00304949509458537
[http://www.beilstein-journals.org/bjoc/content/
2.Swedish Regulation, "Förordning (2008:245) om kemiska produkter
och biotekniska organismer".
supplementary/1860-5397-12-10-S2.pdf]
3.Alvarez, A.; Guzman, A.; Ruiz, A.; Velarde, E.; Muchowski, J. M.
J. Org. Chem. 1992, 57, 1653–1656. doi:10.1021/jo00032a011
4.Molander, G. A.; Eliac, M. D. J. Org. Chem. 2006, 71, 9198–9202.
doi:10.1021/jo061699f
Acknowledgements
The Swedish Foundation for Strategic Research (SSF), The
5.Burns, M. J.; Fairlamb, I. J. S.; Kapdi, A. R.; Sehnal, P.; Taylor, R. J. K.
Org. Lett. 2007, 9, 5397–5400. doi:10.1021/ol702291r
Swedish Energy Agency (Project SweGRIDS), the Carl Trygger
95

Beilstein J. Org. Chem. 2016, 12, 89–96.
1
1
1
1
2
2
2
2
2
2
2
2
6.Molander, G. A.; Canturk, B.; Kennedy, L. E. J. Org. Chem. 2009, 74,
73–980. doi:10.1021/jo802590b
7.Chen, X.; Zhou, L.; Li, Y.; Xie, T.; Zhou, S. J. Org. Chem. 2014, 79,
30–239. doi:10.1021/jo4024123
9
2
8.Kostikov, A. P.; Popik, V. V. J. Org. Chem. 2007, 72, 9190–9194.
doi:10.1021/jo701426j
9.Liu, J.-H.; Chan, H.-W.; Wong, H. N. C. J. Org. Chem. 2000, 65,
3274–3283. doi:10.1021/jo991531c
0.Settambolo, R.; Lazzaroni, R.; Messeri, T.; Mazzetti, M.; Salvadori, P.
J. Org. Chem. 1993, 58, 7899–7902. doi:10.1021/jo00079a040
1.Rosowsky, A.; Papoulis, A. T.; Forsch, R. A.; Queener, S. F.
J. Med. Chem. 1999, 42, 1007–1017. doi:10.1021/jm980572i
2.Erdélyi, M.; Gogoll, A. J. Org. Chem. 2001, 66, 4165–4169.
doi:10.1021/jo0057250
3.Beccalli, E. M.; Marchesini, A.; Pilati, T. Tetrahedron 1994, 50,
1
2697–12712. doi:10.1016/S0040-4020(01)89402-3
4.Luo, F.; Pan, C.; Wang, W.; Ye, Z.; Cheng, J. Tetrahedron 2010, 66,
399–1403. doi:10.1016/j.tet.2009.11.098
1
5.Jolicoeur, B.; Chapman, E. E.; Thompson, A.; Lubell, W. D.
Tetrahedron 2006, 62, 11531–11563. doi:10.1016/j.tet.2006.08.071
6.Lodewyk, M. W.; Siebert, M. R.; Tantillo, D. J. Chem. Rev. 2012, 112,
1
839–1862. doi:10.1021/cr200106v
7.Willoughby, P. H.; Jansma, M. J.; Hoye, T. R. Nat. Protoc. 2014, 9,
43–660. doi:10.1038/nprot.2014.042
6
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