Diaceno[a,e]pentalenes from homoannulations of o-alkynylaryliodides utilizing a unique Pd(OAc)2/n-Bu4NOAc catalytic combination

Article abstract of DOI:10.1021/ol502440d

A heterogeneous catalytic system, Pd(OAc)₂/n-Bu₄NOAc, for the efficient synthesis of diaceno[a,e]pentalenes via a tandem Pd catalytic cycle is reported. The catalytic partner n-Bu₄NOAc played indispensable and versatile ro

Full text of DOI:10.1021/ol502440d

Letter
pubs.acs.org/OrgLett
Diaceno[a,e]pentalenes from Homoannulations of
o‑Alkynylaryliodides Utilizing a Unique Pd(OAc)2/n‑Bu4NOAc
Catalytic Combination
Junjian Shen,†,§,∥ Dafei Yuan,†,∥ Yan Qiao,‡ Xingxing Shen,† Zhongbo Zhang,† Yuwu Zhong,§
Yuanping Yi,*,† and Xiaozhang Zhu*,†
†Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Organic Solids, Institute of Chemistry, Chinese
Academy of Sciences, Beijing 100190, P. R. China
‡State Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan, Shanxi Province
030001, P. R. China
§Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Photochemistry, Institute of Chemistry, Chinese
Academy of Sciences, Beijing, 100190, P. R. China
S
* Supporting Information
ABSTRACT: A heterogeneous catalytic system, Pd(OAc)2/n-Bu4NOAc, for the
efficient synthesis of diaceno[a,e]pentalenes via a tandem Pd catalytic cycle is
reported. The catalytic partner n-Bu4NOAc played indispensable and versatile
roles, acting as both the media for recovering active Pd(0) species and their
stabilizer. A series of new diaceno[a,e]pentalenes were obtained in moderate to
high yields, among which the octacyclic dianthracenopentalene was found to be
highly emissive.
ibenzo[a,e]pentalenes1 have been known for over 100
First, the acetate anion could act as the media for recovering
Dyears as distinctive polycyclic conjugated hydrocarbons active Pd(0) species;12 Second, the n-tetrabutylammonium
group may contribute to stabilizing Pd nanoparticles.13 In
addition, n-Bu4NOAc is neutral and a nonreductive reagent and
is thus compatible with sensitive functional groups. A series of
new diaceno[a,e]pentalenes were synthesized in moderate to
high yields, among which we found that the high-order
dianthraceno[a,e]pentalene 2t showed unusually intensive
emission, which is an exceptional example for antiaromatic
pentalene derivatives.
The synthesis of dibenzo[a,e]pentalene 2a from substrate 1a
was investigated under several catalytic combinations. Initially,
homocoupling of substrate 1a solely using 5 mol % of
Pd(OAc)2 as the catalyst in DMF at 100 °C afforded
dibenzo[a,e]pentalene 2a in a trace amount with a large
amount of unreacted starting materials, which indicated the
feasibility of the potential Pd(0, II, IV) catalytic cycle (cf. Table
1. entry 1).11 On the other hand, we ascribed low yield to the
hindered catalytic cycle at the PdI2 stage. As per our deduction,
the yield was significantly improved by addition of acetate salts
in order to recover active Pd(0) species (entries 2−6).12 In
particular, compound 2a was obtained with a good (76%) yield
using 1 equiv of n-Bu4NOAc, a neutral salt (entry 6). The yield
was further improved to excellent (94%) under higher reaction
temperature (130 °C) together with a significantly reduced
reaction time (4 h),6−9 which may partly be ascribed to the
stabilization effect of tetrabutylammonium cation upon Pd(0)
with compatibly 4n π-electrons and a stable planar structure.2
They have recently attracted considerable interest because of
intriguing properties, such as high electron affinity derived from
the aromatization tendency of cyclopentadiene by accepting
one electron.3 Although the construction of a dibenzo[a,e]-
pentalene framework comprising fused 6−5−5−6 carbocycles
was highly challenging,4 transition-metal-catalyzed synthesis of
dibenzo[a,e]pentalenes initiated by Youngs et al.5 has recently
made significant progress. The Kawase,6 Tilley7 and Itami8
groups developed tandem synthesis of dibenzo[a,e]pentalenes
by the homocoupling of o-alkynylaryl bromides or arylacety-
lenes catalyzed by Ni or Pd catalysts. Jin et al. reported the
cross annulations of o-alkynylaryl chlorides and diarylacetylenes
leading to the unsymmetrical dibenzo[a,e]pentalenes.9 How-
ever, because of the intrinsic limitations of the Pd(0, II) or
Ni(0, II) catalytic cycle, these tandem reactions only operated
with the help of the external strong reductant, oxidant, base, or
even equivalent amount of the catalyst, which narrowed
substrate scope and was thus less compatible for the synthesis
of high-order diaceno[a,e]pentalenes (pentalene-containing
acene analogues) that are very enticing for advanced
applications in organic electronics.10 Initially, we considered
that the Pd four-valence-state catalytic cycle11 might be
applicable for the synthesis of diaceno[a,e]pentalenes. We
report herein a heterogeneous catalytic system, Pd(OAc)2/n-
Bu4NOAc, for the efficient construction of diaceno[a,e]-
pentalene frameworks. The catalytic partner tetrabutylammo-
nium acetate (n-Bu4NOAc) exhibits binary effects, as follows.
Received: August 17, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ol502440d | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Effect of Additives and Temperature on the
Homocoupling of Compound 1a.
Table 2. Synthesis of Diaceno[a,e]pentalenes by Pd-
Catalyzed Homocoupling of o-Alkynylaryl Iodides
a
a
b
entry
catalytic partner
temp (°C)
yield (%)
1
2
3
4
5
6
100
100
100
100
100
100
130
130
trace
34
LiOAc (1.0 equiv)
NaOAc (1.0 equiv)
KOAc (1.0 equiv)
40
56
CsOAc (1.0 equiv)
nBu4NOAc (1.0 equiv)
nBu4NOAc (1.0 equiv)
nBu4NOAc (1.0 equiv)
54
76
c
7
c,d
94
8
75
a
Reaction conditions: 1a (0.40 mmol), Pd(OAc)2 (5 mol %), catalytic
partner, N,N-dimethylformide (DMF) (0.05 M) under N2 atmosphere
b
c
d
for 24 h. Isolated yield. Reaction time was 4 h. The reaction was
performed in air.
nanoparticles (entry 7).14 Finally, we were pleased to observe
that the reaction could even be performed under ambient
conditions, and it gave compound 2a with a good (75%) yield
(entry 8).
The scope of the tandem reaction is illustrated under the
optimized reaction conditions as shown in Table 2. Various R1
groups including sensitive chloride (entry 6), aldehyde (entry
9), and ester (entry 10) groups could be tolerated. Both the
electron-donating and the weak electron-withdrawing groups
could give the corresponding products with moderate to high
yields (entries 2−6). Substrates with electron-donating groups
smoothly gave the corresponding products with 73−94% yield
(entries 1−4). The electron-withdrawing groups slowed the
reaction rates and gave relatively low yields between 40 and
78% (entries 5, 6, and 8−10). Compound 2g with the
trifluoromethyl groups was obtained with excellent (92%) yield
using 10 mol % of Pd(OAc)2 (entry 7). The reaction was
insensitive to the steric hindrance of the substrate as compound
2k could equally be obtained at 83% yield (entry 11). The
substrate 1-iodo-2-octynylbenzene 1l can also proceed to give
hexyl-substituted dibenzo[a,e]pentalene 2l in moderate 40%
yield. Similar substituent effects were observed for substrates
with different R2 groups (entries 13−17). For the fluoride-
substituted substrate 1o, the reaction can only proceed at high
temperature, 145 °C (entry 15). The tetra-substituted
compound 2r was synthesized smoothly with 74% yield
(entry 18). The dinaphtho[a,e]pentalene and dianthraceno-
[a,e]pentalene derivatives 2s and 2t, promising organic
semiconductors,10,15 could easily be obtained with similar
80% yields (entries 19 and 20). Despite of 32 π-electrons that
are comparable to those of hepta- or octacene, dianthraceno-
[a,e]pentalene 2s is bench-stable for months. Upon UV
irradiation (360 nm, 4 W) of air-saturated solution, more
than 50% of 2t can survive after 28 h, which indicates the
considerably higher stability of 2t than that of TIPS-
pentacene.16
a
General reaction condition: 1a (0.40 mmol), Pd(OAc)2 (5 mol %), n-
Bu4NOAc (0.40 mmol), DMF (0.05 M) under N2 atmosphere at 130
°C for 4 h. Isolated yield. The reaction time was 12 h. Pd(OAc)2
b
c
d
e
f
(10 mol %) was used. The reaction temperature was 145 °C. EH: 2-
High-quality crystals of compound 2t can be readily obtained
and characterized by single-crystal X-ray analysis under ambient
conditions, which revealed a planar molecular structure with
obvious single- and double-bond alternation indicating the
absence of aromaticity (Figure 1). Because of its extended
conjugated framework, highly ordered π−π stacking inter-
actions with a distance of 3.39 Å and quite large overlapped π-
ethylhexyl. Obtained from ref 15a. Under Tilley’s conditions.7
g
h
area could be clearly observed (Figure S2, Supporing
information), which is unprecedented for the smaller dibenzo-
[a,e]pentalene (2c, 2e, 2l, see the Supporting Information) and
B
dx.doi.org/10.1021/ol502440d | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
acetate anion play complementary effects in this kind of
transformation. Thus, the Pd(0) nanoparticles were formed in
situ from Pd(OAc)2 by thermolysis and were stabilized by the
tetrabutylammonium cations. By chemical etching,
arylpalladium(II) B was formed and proceeded with inter-
and intramolecular alkyne carbopalladation to afford the
intermediate C. Intramolecular oxidative addition of aryl iodide
to Pd(II) delivered palladabenzocyclohexadiene D,11,20 which
subsequently underwent reductive elimination to afford
dibenzo[a,e]penalenes 2 and PdI2. The Pd(0) species was
further regenerated in the presence of nBu4NOAc to push
forward the catalytic cycle.21
The photophysical properties of the representative diaceno-
[a,e]pentalenes 2a, 2s, and 2t were examined in diluted
dichloromethane solution as summarized in Table 3, which
indicates disparate fluorescence property with increasing π-
conjugation. All of the compounds showed structured
absorption that bathochromically shifted from 448 to 556 nm
(Figure 2). In sharp contrast to dibenzo[a,e]pentalene 2a and
Figure 1. Single-crystal structure of compound 2t.
dinaphtho[a,e]pentalene15a congeners and is a favorable hint
for the upcoming applications in organic electronics.
A plausible reaction mechanism that involves a heteroge-
neous catalytic process via the Pd(0, II, IV) cycle11,17 was
proposed in Scheme 1. Accordingly, the key reference reactions
Scheme 1. Proposed Catalytic Cycle
Figure 2. DFT-calculated orbital energy diagram and pictorial
representation of HOMO-1, HOMO, and LUMO for diaceno[a,e]-
pentalenes 2a, 2s, and 2t. In calculations, the 2-ethylhexyloxy groups of
2t were simplied to methoxy ones. [Blue and red arrows represent the
lowest excitation and fluorescence (S0↔S1): ×, symmetry-forbidden;
√, symmetry-allowed.]
include the following (see Table S1, Supporting Information).
(1) The TEM image of the reaction mixture revealed a large
quantity of Pd nanoparticles with ∼3 nm size (Figure S1,
Supporting Information). Accordingly, adding liquid Hg to the
reaction system18 sharply decreased the yield to 15%. (2) Using
0.5 equiv of n-Bu4NOAc only gave a 38% yield that agreed well
with our assumption, i.e., an equivalent amount of n-Bu4NOAc
was necessary to continuously promote the catalytic cycle.
However, an additional 1 equiv of n-Bu4NOAc significantly
inhibited the reaction and gave a rather low yield, 10%. We
deduced that an excessive amount of tetrabutylammonium
cations would cause the surface of the Pd nanoparticles to
become overcrowded,19 which is in disfavor with the catalytic
process. (3) The changes of the acetate anion to bromide and
of tetrabutylammonium to the ammonium cation could only
give compound 2a at low yields of 17% and 3%, respectively,
which means that both the tetrabutylammonium cation and the
dinaphtho[a,e]pentalene 2s, dianthraceno[a,e]pentalene 2t
exhibited strong yellow emission at 574 nm with a promisingly
high quantum yield, 35%, and a small Stokes shift, 0.08 eV.22
To illustrate the origin of such an unusual phenomenon, we
performed calculations on the excited-state electronic proper-
ties of these compounds by means of time-dependent density
functional theory (TDDFT) at the B3LYP/6-31G* level. As
indicated previously,6,15a the longest absorption of compounds
2a and 2s originated from the second excited state (S2), and the
S1 excitation was found to be symmetry-forbidden. As shown in
Figure 2, all the compounds showed the LUMO (L, lowest
a
Table 3. Photophysical and Electrochemical Properties of the Representative Diaceno[a,e]pentalene Derivatives
b
f
g
λabs (nm) (ε, M−1
·
calcd emission wavelength (nm)
Ered
(V)
Egopt
1/2
a
b
c d
e
d
cpd.
cm−1
)
calcd excited states (nm) (origin, f )
λem (nm) (Φ)
(f)
(eV)
2a
2s
2t
424, 448 (15400)
468, 498 (19800)
516, 556 (36500)
336, 352 (13900)
568 (S1, H→L, 0.00) 440, (S2, H-1→L, 0.31)
496 (S1, H-1→L, 0.00) 493, (S2, H→L, 0.37)
h
1054 (0.00)
735 (0.00)
624 (0.51)
j
−1.68
−1.78
−1.87
h
2.61
2.32
2.13
3.40
h
543 (S1, H→L, 0.50) 513, (S2, H→L+1, 0.00) 578, 622 (0.35)
i
3
318 (S1, H→L, 0.56)
385 (0.98)
a
b
c
Measured in dichloromethane. TDDFT-calculated vertical excitation or emission wavelengths. It should be noted that except for the dominant
excitation configurations listed above, there were very small contributions (<10%) from other configurations, such as H → L+1 for S2 of 2a, H-1 → L
d
e
f
+1 for S2 of 2s, and H-1 or H-2 → L+1 for S1 of 2t. Ocillator strengths. Fluorescence quantum yield was determined by absolute method. Cyclic
g
h
i
voltammetry on a carbon electrode with nBu4NClO4 in dichloromethane (0.1 M, vs Fc+/Fc). Egopt. = 1240/λonset (eV). Not detected. Extracted
j
from ref 24 (3: indenoindene). Not examined.
C
dx.doi.org/10.1021/ol502440d | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(4) (a) Saito, M. Symmetry 2010, 2, 950. For selected recent
examples, see: (b) London, G.; von Wantoch Rekowski, M.; Dumele,
O.; Schweizer, W. B.; Gisselbrecht, J.-P.; Boudon, C.; Diederich, F.
Chem. Sci. 2014, 5, 965. (c) Chen, C.; Harhausen, M.; Liedtke, R.;
Bussmann, K.; Fukazawa, A.; Yamaguchi, S.; Petersen, J. L.; Daniliuc,
unoccupied molecular orbital) orbitals of the same centro
antisymmetry. The symmetry-allowed orbitals for the lowest
optical excitation were HOMO-1 for compound 2a and
HOMO (H, highest unoccupied molecular orbital) for
compounds 2s and 2t. Interestingly, only for compound 2t,
the S1 excitation channel was opened and attributed to the
HOMO−LUMO transition. It was shown by our calculations
that the optimal S0 and S1 geometries presented a same nature
for the molecular levels and lowest excited states. Thus, the
emission channel from S1 to S0 was switched on for compound
2t. To the best of our knowledge, compound 2t was the first
example among pentalene derivatives that showed intensive
fluorescence.23
In summary, we developed a unique catalytic system,
Pd(OAc)2/n-Bu4NOAc, for the efficient synthesis of diaceno-
[a,e]pentalenes. This catalytic combination showed good
functional group tolerance and gave a series of diaceno[a,e]-
pentalenes at moderate to excellent yields, among which the
octacyclic dianthraceno[a,e]pentalene 2t was found to be a
distinctive example of pentalene derivatives featured by the
unprecedented strong fluorescence and compact π−π stacking
in solution or solid states. The cheap catalytic partner, n-
Bu4NOAc, and the easy manipulation without need of sensitive
and expensive phosphine ligands are noteworthy, making this
catalytic combination promising for the mass preparation of
pentalene-type organic semiconductors, especially based on
high-order diaceno[a,e]pentalenes aimed at applications in
organic electronics.10,25
C. G.; Frohlich, R.; Kehr, G.; Erker, G. Angew. Chem., Int. Ed. 2013, 52,
̈
5992. (d) Hashmi, A. S. K.; Wieteck, M.; Braun, I.; Nosel, P.;
̈
Jongbloed, L.; Rudolph, M.; Rominger, F. Adv. Synth. Catal. 2012, 354,
555. (e) Li, H.; Wei, B.; Xu, L.; Zhang, W.-X.; Xi, Z. Angew. Chem., Int.
Ed. 2013, 52, 10822.
(5) Chakraborty, M.; Tessier, C. A.; Youngs, W. J. J. Org. Chem.
1999, 64, 2947.
(6) Kawase, T.; Konishi, A.; Hiro, Y.; Matsumoto, K.; Kurata, H.;
Kubo, T. Chem.Eur. J. 2009, 15, 2653.
(7) Levi, Z. U.; Tilley, T. D. J. Am. Chem. Soc. 2009, 131, 2796.
(8) Maekawa, T.; Segawa, Y.; Itami, K. Chem. Sci. 2013, 4, 2369.
(9) Zhao, J.; Oniwa, K.; Asao, N.; Yamamoto, Y.; Jin, T. J. Am. Chem.
Soc. 2013, 135, 10222.
(10) Anthony, J. E. Angew. Chem., Int. Ed. 2008, 47, 452.
(11) (a) Catellani, M.; Fagnola, M. C. Angew. Chem., Int. Ed. Engl.
1994, 33, 2421. (b) Catellani, M.; Motti, E.; Della Ca, N. Acc. Chem.
Res. 2008, 41, 1512. (c) Malacria, M.; Maestri, G. J. Org. Chem. 2013,
78, 1323. (d) Kung, Y.-H.; Cheng, Y.-S.; Tai, C.-C.; Liu, W.-S.; Shin,
C.-C.; Ma, C.-C.; Tsai, Y.-C.; Wu, T.-C.; Kuo, M.-Y.; Wu, Y.-T.
Chem.Eur. J. 2010, 16, 5909. (e) Wu, T.-C.; Chen, C.-H.; Hibi, D.;
Shimizu, A.; Tobe, Y.; Wu, Y.-T. Angew. Chem., Int. Ed. 2010, 49, 7059.
(f) Lin, Y.-D.; Cho, C.-L.; Ko, C.-W.; Pulte, A.; Wu, Y.-T. J. Org. Chem.
2012, 77, 9979.
(12) Stephenson, T. A.; Morehouse, S. M.; Powell, A. R.; Heffer, J.
P.; Wilkinson, G. J. Chem. Soc. 1965, 3632.
(13) (a) Reetz, M. T.; de Vries, J. G. Chem. Commun. 2004, 1559.
(b) Balanta, A.; Godard, C.; Claver, C. Chem. Soc. Rev. 2011, 40, 4973.
(c) Deraedt, C.; Astruc, D. Acc. Chem. Res. 2014, 47, 494.
(14) (a) Reetz, M. T.; Westermann, E. Angew. Chem., Int. Ed. 2000,
39, 165. (b) Jeffery, T. J. Chem. Soc., Chem, Commun. 1984, 1287.
(15) (a) Kawase, T.; Fujiwara, T.; Kitamura, C.; Konishi, A.; Hirao,
Y.; Matsumoto, K.; Kurata, H.; Kubo, T.; Shinamura, S.; Mori, H.;
Miyazaki, E.; Takimiya, K. Angew. Chem., Int. Ed. 2010, 49, 7728.
(b) Nakano, M.; Osaka, I.; Takimiya, K.; Koganezawa, T. J. Mater.
Chem. C 2014, 2, 64.
ASSOCIATED CONTENT
* Supporting Information
■
S
Complete experimental details, physical properties, and X-ray
data for compounds 2c,e,l,t (CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
■
(16) Maliakal, A.; Raghavachari, K.; Katz, H.; Chandross, K.; Siegrist,
T. Chem. Mater. 2004, 16, 4980.
(17) Vicente, J.; Arcas, A.; Julia-
Chem., Int. Ed. 2011, 50, 6896.
́ ́
Hernandez, F.; Bautista, D. Angew.
*E-mail: ypyi@iccas.ac.cn.
*E-mail: xzzhu@iccas.ac.cn.
Author Contributions
∥These authors contributed equally.
(18) Whitesides, G. M.; Hackett, M.; Brainard, R. L.; Lavalleye, J.-P.
P. M.; Sowinski, A. F.; Izumi, A. N.; Moore, S. S.; Brown, D. W.;
Staudt, E. M. Organometallics 1985, 4, 1819.
(19) (a) Li, Y.; Boone, E.; El-Sayed, M. A. Langmuir 2002, 18, 4921.
(b) Li, Y.; El-Sayed, M. A. J. Phys. Chem. B 2001, 105, 8938.
(20) (a) In the absence of reductant, a reductive-coupling
mechanism involving a Pd(0)/Pd(II) cycle (ref 7) unlikely operated
in our reaction.. (b) As the cross coupling between compound 1a and
di-p-tolylacetylene did not proceed under the optimized reaction
conditions, a concerted metalation deprotonation (CMD) process can
be excluded..
(21) The pyrolytic transformation from Pd(OAc)2 to Pd(0) is
elusive. (a) Reetz, M. T.; Masse, M. Adv. Mater. 1999, 11, 773.
(b) Tano, T.; Esumi, K.; Meguro, K. J. Colloid Interface Sci. 1989, 133,
530. (c) Gallagher, P. K.; Gross, M. E. J. Therm. Anal. 1986, 31, 1231.
(22) Ouchi, Y.; Sugiyasu, K.; Ogi, S.; Sato, A.; Takeuchi, M. Chem.
Asian. J. 2012, 7, 75.
(23) (a) Falchi, A.; Gellini, C.; Salvi, P. R.; Hafner, K. J. Phys. Chem. A
1998, 102, 5006. (b) Levi, Z. U.; Tilley, T. D. J. Am. Chem. Soc. 2010,
132, 11012.
(24) Zhu, X.; Tsuji, H.; Navarrete, J.; Casado, J.; Nakamura, E. J. Am.
Chem. Soc. 2012, 134, 19254.
(25) Watanabe, M.; Chang, Y. J.; Liu, S.-W.; Chao, T.-H.; Goto, K.;
Islam, Md. M.; Yuan, C.-H.; Tao, Y.-T.; Shinmyozu, T.; Chow, T. J.
Nat. Chem. 2012, 4, 574.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(91333113), the Strategic Priority Research Program of the
Chinese Academy of Sciences (XDB12010200), and the
National Basic Research Program of China (973 Program)
(No. 2014CB643500) for the financial support.
REFERENCES
(1) Brand, K. Ber. Dtsch. Chem. Ges. 1912, 45, 3071.
(2) Hopf, H. Angew. Chem., Int. Ed. 2013, 52, 12224.
■
(3) (a) Wood, J. D.; Jellison, J. L.; Finke, A. D.; Wang, L.; Plunkett,
K. N. J. Am. Chem. Soc. 2012, 134, 15783. (b) Chase, D. T.; Fix, A. G.;
Kang, S. J.; Rose, B. D.; Weber, C. D.; Zhong, Y.; Zakharov, L. N.;
Lonergan, M. C.; Nuckolls, C.; Haley, M. M. J. Am. Chem. Soc. 2012,
134, 10349. (c) Shimizu, A.; Kishi, R.; Nakano, M.; Shiomi, D.; Sato,
K.; Takui, T.; Hisaki, I.; Miyata, M.; Tobe, Y. Angew. Chem., Int. Ed.
2013, 52, 6076 and references cited therein.
D
dx.doi.org/10.1021/ol502440d | Org. Lett. XXXX, XXX, XXX−XXX