Cyclic Alkyne Approach to Heteroatom-Containing Polycyclic Aromatic Hydrocarbon Scaffolds

Article abstract of DOI:10.1002/anie.201903060

We report a modular synthetic strategy for accessing heteroatom-containing polycyclic aromatic hydrocarbons (PAHs). Our approach relies on the controlled generation of transient heterocyclic alkynes and arynes. The strained intermediates undergo in situ t

Full text of DOI:10.1002/anie.201903060

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Accepted Article
Title: Cyclic Alkyne Approach to Heteroatom-Containing Polycyclic
Aromatic Hydrocarbon Scaffolds
Authors: Evan Darzi, Joyann Barber, and Neil K. Garg
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201903060
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10.1002/anie.201903060
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Cyclic Alkyne Approach to Heteroatom-Containing Polycyclic
Aromatic Hydrocarbon Scaffolds
Evan R. Darzi, Joyann S. Barber, and Neil K. Garg*
Abstract: We report a modular synthetic strategy for accessing
heteroatom-containing polycyclic aromatic hydrocarbons (PAHs).
Our approach relies on the controlled generation of transient
heterocyclic alkynes and arynes. The strained intermediates
undergo in situ trapping with readily accessible oxadiazinones. Four
sequential pericyclic reactions occur, namely two Diels–Alder / retro-
Diels–Alder sequences, which can be performed in a stepwise or
one-pot fashion to assemble four new carbon–carbon (C–C) bonds.
These studies underscore how the use of heterocyclic strained
intermediates can be harnessed for the preparation of new organic
materials.
(PAHs),2,20,21,22,23 with the latter having a remarkable impact on
the materials science field.24,25 PAHs have been used in widely-
used devices, such as organic light-emitting diodes (OLEDs),
field effect transistors (OFETs), and photovoltaics (OPVs).26 An
important subset of PAHs are 9,10-diphenylanthracene
derivatives. The parent compound, 9,10-diphenylanthracene (1,
Figure 1), has been widely studied since 190427 and has been
used in blue glow sticks28 and OLEDs.29 Novel derivatives of 1
have been highly sought.30 One promising ‘analoging’ approach
is to prepare variants of 1 that bear heteroatoms in order to
modulate the properties and potential applications of PAHs.
31,32,33 Heteroatoms may be included in the anthracene ring itself
or on the C9/C10 substituents, as exemplified by 234,35,36,37 and
Alkynes contained in small rings were once considered
only intellectual curiosities. However, in recent years, strained
cyclic alkynes have resurfaced and have been widely employed
in synthetic methodology studies.1,2,3,4 Additionally, such efforts
have led to a greater understanding of aryne and cyclic alkyne
reactivity and regioselectivities, 5 , 6 , 7 and a host of synthetic
38
3,
respectively (Figure 1), which can impact material
properties.38 Compounds possessing heteroatoms on both the
anthracene ring and C9/C10 substituents, such as 4, have also
been prepared in the context of OLEDs.39 Lastly, more exotic
analogs of 1 and 2 are known where the C9/C10 substituents
are replaced with heterocycles or substituted aromatics, as
demonstrated by 534,37 and 6.40 The majority of heteroatom-
containing derivatives of 1 have been disclosed in the patent
literature over the past 6 years and reflect a rapidly growing area
of discovery.41,42
8
9
applications
impacting
catalysis,
agrochemistry,
pharmaceuticals, and academia.10 , 11 A selection of important
arynes and cyclic alkynes are shown in Figure 1.12,13,14,15,16,17,18,19
One exciting application of arynes and cyclic alkynes lies in
materials chemistry. Arynes have been employed in the
synthesis of polymers and polycyclic aromatic hydrocarbons
Cyclic Alkynes and Heterocyclic Variants
N
RN
O
N
H
N
R
O
N
3,4-oxacyclic
alkyne
benzyne
cyclohexyne
3,4-pyridyne
2,3-pyridyne
3,4-piperidyne 2,3-piperidyne
4,5-indolyne
4,5-benzofuranyne
Notable Polyaromatic Hydrocarbons
Me
Me
N
N
S
S
N
9
N
N
N
N
10
N
N
N
Me
Me
4
5
9,10-diphenylanthracene (1)
OLEDs, glow sticks
(1904)
2
3
6
OLEDs
(2010)
solar cell material
OLEDs
(2016)
OLEDs
(2015)
OLEDs
(2016)
(2017)
Figure 1. Arynes, cyclic alkynes, and heterocyclic variants, and 9,10-diphenylanthracene (1) and aza-derivatives 2–6.
Synthetic methods to rapidly generate novel heterocyclic
PAHs remain limited. For example, the assembly of non-
symmetric PAHs that possess multiple functional groups usually
requires long linear sequences.33 Additionally, approaches to
arrive at het-anthracene cores typically necessitate harsh
reaction conditions (e.g., high temperatures and strongly acidic
or basic conditions).33,13 Lastly, variation at C9 and C10 is
primarily achieved via the use of strongly basic organometallic
reagents or transition metal catalysis, and typically results in
symmetric molecules or low yields.31,43
Dr. E. R. Darzi, J. S. Barber, Prof. Dr. N. K. Garg
Department of Chemistry and Biochemistry
University of California, Los Angeles
Los Angeles, CA 90095 (USA)
E-mail: neilgarg@chem.ucla.edu
Homepage: http://garg.chem.ucla.edu
We targeted the synthesis of scaffold 7 through an
ambitious approach, whereby ring fragments A–D could be
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201903060
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united with formation of the central benzene ring (Figure 2a).
This would enable access to a range of heterocyclic PAH
scaffolds, with the possibility of accessing four quadrants of
differentiation. In practice, we questioned if highly reactive
arynes and cyclic alkynes (i.e., 8 and 10) could be used as
building blocks A and B (Figure 2b). Heterocyclic strained
intermediates (e.g. 8) would be used strategically to access the
desired heteroatom-containing PAHs.44 With regard to building
blocks C and D, oxadiazinone 9 was identified as a versatile
core scaffold. Oxadiazinones (diazapyrones) are easily prepared
from simple precursors45 and are known to readily undergo one
or more Diels–Alder (DA) cycloaddition / retro-Diels–Alder (rDA)
cycloaddition reactions (with sequential expulsion of N2 and
CO2).46 The success of this approach would hinge on uncovering
a means to allow for the controlled generation and trapping of
fragments 8 and 10 to ultimately deliver products 7 through the
We report the development of the synthetic sequence
shown in Figure 2b, which provides a modular and rapid means
to synthesize a diverse range of heteroatom-containing PAHs.
The trapping of in situ-generated strained intermediates with
oxadiazinones, demonstrated in both stepwise and one-pot
fashions, furnishes the desired structural frameworks. Small
molecule fluorophores can be accessed from this strategy.
These studies demonstrate that heterocyclic strained
intermediates can be leveraged for the preparation of new
organic materials.
With the ultimate goal of synthesizing heterocyclic PAHs
bearing four quadrants of differentiation, we first developed a
stepwise variant (Figure 3). As mentioned above, arynes are
known to undergo oxadiazinone trapping, but the intermediate
benzopyrone directly undergoes trapping with
a second
cascade of events suggested in Figure 2b. Key precedent stems
equivalent of the aryne, precluding the opportunity to introduce
two different strained alkyne fragments. When using benzyne in
our initial studies, only double addition to form 1 was observed.
We hypothesized that the intermediate benzopyrone was more
reactive than the oxadiazinone, preventing isolation or second
addition of a different aryne. We questioned if a cyclic alkyne
could be used to isolate the corresponding pyrone intermediate
based on prior studies by Sauer and co-workers using
cyclooctyne.51 Thus, we used a heterocyclic alkyne derived from
commercially available silyl triflate 11 (prepared in 3 steps from
4-methoxypyridine).13 Two key results (Figure 3) illustrate the
ability to modulate the product distribution through alteration of
the reaction stoichiometry. When silyl triflate 11 was employed in
excess, the major products were adducts 14, consistent with the
results previously seen in aryne/oxadiazinone reactions.46,47,48
However, when a 1 : 2 ratio of 11 and 12 was utilized, the
desired pyrones 13, arising from a single DA / rDA reaction,
were isolated in 74% yield under optimized conditions, without
formation of double addition products 14. Of note, pyrone 13 is
produced as a mixture of regioisomers 13a and 13b. It was
found that treatment of excess CsF under oxidative conditions
selectively decomposed 13b leaving 13a untouched. Several
points should be noted: a) our results provide the first example
of a DA cycloaddition featuring an oxadiazinone and a strained
intermediate derived from a Kobayashi silyl triflate precursor,52
b) the reactions occur under exceptionally mild reaction
conditions, c) the desired reaction produces mixtures of pyrone
isomers 13a and 13b, which may generally be viewed as both a
strength and limitation (additional analogs, yet not selective),
and d) isomer 13a, the key lynchpin to the success of our
synthetic strategy, was ultimately accessible as a single isomer
(33% yield from 11, see SI for details) and employed in
subsequent experiments.
47
from pioneering studies by Steglich in 1977,
which
demonstrated the double addition of benzyne into oxadiazinones,
in addition to the syntheses of conjugated materials by
Nuckolls48 and Wudl.49 However, a notable limitation in all cases
is the inability to introduce two different strained alkynes, instead
delivering symmetric products with respect to building blocks A
and B.50
a.
C
C
9
Desired Scaffold
+
A
B
A
B
RN
Up to Four Quadrants
of Differentiation
10
D
D
7
b.
C
9
C
D
O
O
N
N
N
N
A
8
+
+
B
A
RN
O
RN
O
10
D
9
10
C
C
retro-
Diels–Alder
N
O
Diels–Alder
N
A
O
N
O
R
A
–N2
N
O
R
D
D
O
C
C
retro-
Diels–Alder
O
O
Diels–Alder
A
7
A
N
N
R
O
B
–CO2
R
B
D
D
Figure 2. Strategy to access 7.
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Ph
Ph
Ph
Ph
Ph
Ph
Ph
OTf
O
O
O
CsF
N
N
CbzN
NCbz
+
+
+
A
A
CbzN
O
CbzN
O
O
CbzN
NCbz
CbzN
CH3CN
23 °C, 14 h
SiMe3
Ph
12
Ph
Ph
11
13a
13b
14a
14b
Ratio
Yield of 13
Yield of 14
25% yield
2 : 1
1 : 2
not observed
74% yield
not observed
Figure 3. Optimization to form pyrones 13. Cbz=benzylcarbamate, OTf=trifluoromethanesulfonate.
After establishing a suitable method to access pyrone 13a,
we turned our attention toward introducing and modulating the B
ring. Pyrone 13a readily undergoes a DA / rDA reaction
sequence, with loss of CO2, in the presence of arynes or non-
aromatic cyclic alkynes (generated from silyl triflate precursors
15) at ambient temperature (Figure 4). In each case, the
transformation proceeds with formation of two new C–C bonds
and delivers non-symmetric heterocyclic PAH skeletons 16.
Benzyne (17),52 1,2-naphthalyne (19)53 and 4,5-indolyne (21),18
performed well, giving rise to products 18, 20 and 22 in good
yields (entries 1–3). Cyclic alkynes, which offer greater sp3-
character and improved solubility of eventual products were also
tested. Cyclohexyne (23), and heterocyclic strained cyclic
alkynes 2513 and 2616 performed smoothly (entries 4–6).54 With
regard to regioselectivities (entries 2, 5, and 6), the major
product likely arises from initial bond formation occurring
between the more electron-rich carbon adjacent to the carbonyl
group of the pyrone55 and the more distorted carbon of the
strained intermediate in a concerted asynchronous fashion.6,13,16
We also sought to access products bearing differing C and
D rings. As noted earlier, in most routes to 9,10-anthracene
derivatives, the C and D rings are introduced through a double
cross-coupling or by the double addition of an organometallic
reagent, allowing for the formation of only symmetric products
with limited functional group compatibility.33,31
A series of
differentially-substituted oxadiazinones were prepared using
established chemistry45 and subjected to silyl triflate 11 under
our standard reaction conditions (Figure 5). The desired
sequence took place to deliver pyrone isomers 28–31 in yields
ranging from 66 to 84%. In all cases, it was possible to separate
the depicted pyrone isomer (42 to 72% recovery of the single
isomer from the mixture of isomers), which was then subjected
to benzyne precursor 32 under our standard
Ph
Ph
Ph
TfO
X
O
X
Y
CsF
B
+
+
B
B
CbzN
O
CbzN
CbzN
CH3CN, 23 °C
R3Si
Y
Y
X
Ph
Ph
Ph
15
(2.0 equiv)
13a
16a
Strained
16b
Strained
Intermediate
Product(s)
(Yield, Ratio)
Product(s)
(Yield, Ratio)
Entry
Entry
Intermediate
Ph
Ph
CbzN
CbzN
1
4
Ph
18
(83% yield)
Ph
24
(71% yield)
23
17
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
NCbz
+
+
CbzN
NCbz
25
NCbz
CbzN
CbzN
CbzN
2
5
14a
14b
20a
20b
19
(60% yield, 1.4:1 ratio)
(89% yield, 1.4:1 ratio)
Ph
Ph
Ph
Ph
NH
O
+
+
O
CbzN
CbzN
O
CbzN
CbzN
NH
3
6
NH
Ph
Ph
Ph
Ph
26
27a
27b
22a
22b
21
(62% yield, 1.5:1 ratio)
(70% yield, 1:1 ratio)
Figure 4. The second DA / rDA reaction using pyrone intermediate 13a. Conditions unless otherwise stated: CsF (5.0 equiv), CH3CN (0.1 M),
14 h. For entries 2, 3, 5, and 6, the mixtures of regioisomers were not separable by column chromatography. Cbz=benzylcarbamate,
OTf=trifluoromethanesulfonate.
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conditions. The desired products 33–36 were obtained in good
to excellent yields. The D ring was varied to include different
para substituents (33–35), such as a bromide (35) for use in
cross-coupling. Also, a thiophene was incorporated to give 36,
which is notable given the prevalence of thiophenes in organic
electronics.31
were not observed, suggesting high selectivity for the controlled
formation and reaction of the two strained intermediates. We
posit that silyl triflate 11 more readily undergoes fluoride-
mediated elimination to form the corresponding alkyne
compared to benzyne precursor 32 as a result of the lower strain
energy associated with 3,4-piperidyne compared to benzyne.56
The transformation proceeds by way of 4 consecutive pericyclic
reactions to create 4 new C–C bonds and deliver a heterocyclic
PAH scaffold in one-pot.
OTf
TfO
C
C
C
CbzN
SiMe3
Me3Si
O
O
N
N
11
32
CbzN
O
CbzN
O
CsF
CsF
CH3CN, 23 °C
CH3CN, 23 °C
C
C
D
D
D
OTf
TfO
O
9
28a–31a (and isomers)
33–36
CsF
N
N
A
B
A
+
+
B
CbzN
CbzN
O
CH3CN, 23 °C
(56% yield)
SiMe3
Me3Si
11
32
D
D
Three-Component
Coupling
12
18
CbzN
CbzN
CbzN
CbzN
Figure 6. Three-component coupling of 11, 12, and 32. Conditions:
silyl triflate 11 (1.0 equiv), oxadiazinone 12 (1.0 equiv), silyl triflate
32 (1.0 equiv), CsF (3.0 equiv), CH3CN (0.1 M), 14 h.
Cbz=benzylcarbamate, OTf=trifluoromethanesulfonate.
S
OMe
NO2
34
Br
.
33
35
36
62% yielda
72% recoveryb
87% yieldc
68% yielda
62% recoveryb
69% yieldc
66% yielda
43% recoveryb
92% yieldc
84% yielda
51% recoveryb
87% yieldc
We pursued several synthetic applications with a focus on
incorporating motifs commonly utilized in materials chemistry. As
shown in Figure 7, we targeted a heterocyclic PAH scaffold
reminiscent of 1. Oxadiazinone 37 was treated with silyl triflate
11 and CsF to furnish pyrone 38. Reaction with silyl triflate 39
afforded the corresponding product of the DA / rDA sequence.
Silyl protection of the indole nitrogen provided separable
isomers 40a and 40b. Removal of the Cbz-protecting group of
40a, followed by MnO2-mediated oxidation gave 41a, which
bears three heterocycles and a p-OMe-Ph motif. 41a exhibits
pH-responsive fluorescence switching properties. Neutral 41a
displays a blue fluorescence emission, whereas the protonated
version, 42a, displays an orange fluorescence emission. Stimuli
responsive materials are important for a host of materials-related
applications such as pH fluorescence sensors57 ,58 and solid-
state fluorescent switches.59
a
Figure 5. Variation of oxadiazinone.
Yield of the pyrone
intermediates 28–31 (a and b isomers). Conditions for piperidyne
cycloaddition: oxadiazinone 9 (2.0 equiv), silyl triflate 11 (1.0 equiv),
CsF (2.0 equiv), CH3CN (0.1 M), 14–18 h. b Recovery of pyrones
c
28a–31a from the mixtures of a and b isomers. See SI for details.
Yield of products 33–36. Conditions for benzyne cycloaddition:
pyrone 28a–31a (1.0 equiv), silyl triflate 32 (2.0 equiv), CsF (5.0
equiv), CH3CN (0.1 M), 18 h. Cbz=benzylcarbamate,
OTf=trifluoromethanesulfonate.
A 3-component coupling of two different silyl triflates, 11
and 32, and oxadiazinone 12 was performed (Figure 6).
Operationally, CsF was added to an equimolar solution of the
three reactants, 18 was obtained in 56% yield along with pyrone
intermediate 13 accounting for the remaining mass balance.
Notably, the products of double piperidyne or benzyne addition
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a.
S
S
S
S
NH
39
Me3Si
TfO
OTf
N
O
O
TIPS
11
N
N
CbzN
SiMe3
O
CbzN
O
CbzN
CbzN
TIPS
N
1. CsF, CH3CN, 23 °C
CsF
+
2. NaH; TIPSCl
CH3CN, 23 °C
(41% yield)
(57% yield, 2 steps)
OMe
37
OMe
OMe
OMe
38
40a
40b
b.
S
S
N
N
TIPS
TIPS
1. H2, Pd(OH)2/C
MeOH, 23 °C
CF3CO2H
Et3N
N
HN
2. MnO2, PhMe, 110 °C
(68% yield, 2 steps)
40a
41a
42a
λ(Emission)
λ(Emission)
= 469 nm
= 592 nm
OMe
OMe
Figure 7. Strategic synthesis of 40 and elaboration to pH-responsive fluorophore 41a. 40a and 41b are obtained as a 1:1 mixture of
regioisomers. Cbz=benzylcarbamate, OTf=trifluoromethanesulfonate, TIPS=triisopropylsilyl.
R
a.
Cl
We also carried out the one-pot, 3-component coupling of
silyl triflates 11 and 32 with dichlorooxadiazinone 43 (Figure 8a).
This transformation led to the controlled formation of dichloride
44 in 58% yield. 44 then underwent Pd-catalyzed borylation to
give (bis)boronic ester 45. Subsequent coupling with 46 afforded
donor–acceptor fluorophore 47, which was found to be
solvatochromic,60 indicative of a donor–acceptor system (Figure
8b).
OTf
TfO
O
CsF
N
N
+
+
CbzN
CbzN
O
CH3CN, 23 °C
(58% yield)
SiMe3
Me3Si
11
32
R
Cl
43
B2(pin)2, Pd(OAc)2, SPhos
KOAc, 1,4-dioxane, 80 °C
(93% yield)
44 (R = Cl)
45 (R = B(pin))
Bis(boronate) 45 could be employed as a building block for
polymer synthesis (Figure 8a). Suzuki–Miyaura polymerization61
between diboronic ester 45 and 4,7-dibromobenzothiadiazole
(48) provided donor–acceptor oligomer 49, which was found to
have a polydispersity index (PDI) of 1.3 and a number average
molecular weight (Mn) of 1.7 kDa. The donor–acceptor oligomer
49 displays a red-shifted absorbance and emission relative to 47
with a longest-wavelength absorption maximum of λ = 391 nm
and an emission maximum of λ = 491 nm (Figure 8c). The
chromatographic shifts can be attributed to the extended
conjugation present in oligomer 49 compared to 47. These
results demonstrate how a common adduct obtained from our
methodology (i.e. 44) can be used to rapidly access donor–
acceptor monomers and oligomers displaying differing
photophysical properties.
N
N
S
Br
N
N
N
S
N
S
CbzN
46
48
Br
Br
45
RuPhos Pd G3
K3PO4
1,4-dioxane, 80 °C
RuPhos Pd G3
K3PO4
1,4-dioxane, 80 °C
CbzN
(95% yield)
(86% yield)
N
S
N
N
N
n
47
S
Mn = 1.7 kDa
PDI = 1.3
49
b.
c.
diethyl ether
dichloromethane
dimethylsulfoxide
λ (emission)
479 nm
=
λ (emission) =
506 nm
λ (emission)
447 nm
=
1
0.8
0.6
0.4
0.2
0
47
49
215
265
315
365
415 465
Wavelength (nm)
515
565
615
665
Figure 8. a. Three-component reaction toward 47 and 49. b.
Solvatochromism of fluorophore 47. c. UV/Vis and fluorescence
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spectra in THF with oligomer 49 displaying red-shifted absorbance
(black solid line) and emission (black dashed line) relative to 47
Acknowledgements
(gray
solid
and
dashed
lines).
Cbz=benzylcarbamate,
The authors are grateful to the University of California, Los
Angeles for financial support. We are grateful to the NIH-NIGMS
(R01 GM123299 to N.K.G. and F32-GM122245 to E.R.D.),
Bristol-Myers Squibb (J.S.B.), the UCLA Graduate Division
(J.S.B.), the Trueblood Family (N.K.G), and the Chemistry-
Biology Interface training program (J.S.B., USPHS National
Research Service Award 5T32GM008496-20). We thank the
Sletten and Nelson laboratories (UCLA) for the use of their
instrumentation and Dr. Scott Virgil (Caltech) for carrying out
preparative separations. These studies were supported by
shared instrumentation grants from the NSF (CHE-1048804)
and the NCRR (S10RR025631). This work used computational
and storage services associated with the Hoffman2 Shared
Cluster provided by the UCLA Institute for Digital Research and
Education’s Research Technology Group.
OTf=trifluoromethanesulfonate, pin=pinacol ester.
We have discovered a modular synthetic platform that
leverages strained cyclic alkynes and arynes to access new
heteroatom-containing
intermediates are united with an oxadiazinone to rapidly
construct 4 new C–C bonds. An array of heterocyclic PAH
frameworks reminiscent of 1 can be accessed. These studies
demonstrate that heterocyclic strained intermediates can be
strategically harnessed for the preparation of new organic
compounds with materials-related properties.
PAH
scaffolds.
Two
strained
Keywords: cyclic alkynes • arynes • cycloadditions • polycyclic
aromatic hydrocarbons • heterocycles • materials science
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Entry for the Table of Contents
COMMUNICATION
We report
approach to access heteroatom-
rich polycyclic aromatic
a strained alkyne
Dr. E. R. Darzi, J. S. Barber, and
Prof. Dr. Neil K. Garg*
R
R
O
N
N
+
+
CbzN
CbzN
O
Page No. – Page No.
hydrocarbons. This versatile
synthetic platform allows for mild
access to non-symmetric tricyclic
cores through a sequential or
one-pot reaction between two
different strained alkynes and an
oxidiazinone. In addition, we
describe a rapid synthesis of a
small molecule and polymeric
donor–acceptor fluorophore.
4 New C–C Bonds
4 Axes of Substitution
One-Pot Variants
Cyclic Alkyne Approach to
Heteroatom-Containing
Polycyclic Aromatic
Hydrocarbon Scaffolds
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[1] R. Sanz, Org. Prep. Proced. Int. 2008, 40, 215−291.
[2] A. V. Dubrovskiy, N. A. Markina, R. C. Larock, Org. Biomol. Chem.
2013, 11, 191−218.
[45] M. L. Tîntas, A. P. Diac, A. Soran, A. Terec, I. Grosu, E. Bogdan, J.
Mol. Struct. 2014, 1058, 106–113.
[46] B. Rickborn, Org. React. 1998, 53, 223–629.
[3] S. Yoshida, T. Hosoya, Chem. Lett. 2015, 44, 1450−1460.
[4] S. S. Bhojgude, A. Bhunia, A. T. Biju, Acc. Chem. Res. 2016, 49,
1658−1670.
[5] V. Diemer, M. Begaud, F. R. Leroux, F. Colobert, Eur. J. Org. Chem
2011, 341–354.
[6] P. H.-Y. Cheong, R. S. Paton, S. M. Bronner, G.-Y. J. Im, N. K. Garg,
K. N. Houk, J. Am. Chem. Soc. 2010, 132, 1267–1269.
[7] N. F. Fine Nathel, L. A. Morrill, H. Mayr, N. K. Garg, J. Am. Chem.
Soc. 2016, 138, 10402–10405.
[47] W. Steglich, E. Buschmann, G. Gansen, L. Wilschowitz, Synthesis
1977, 252–253.
[48] Q. Miao, X. Chi, S. Xiao, R. Zeis, M. Lefenfeld, T. Siegrist, M. L.
Steigerwald, C. Nuckolls, J. Am. Chem. Soc. 2006, 128, 1340–1345.
[49] D. Chun, Y. Cheng, F. Wudl, Angew. Chem., Int. Ed. 2008, 47, 8380–
8385; Angew. Chem. 2008, 120, 8508–8513.
[50] DA reactions using substituted tetrazenes or isobenzofurans are
known, but also suffer from the inability to introduce two different strained
intermediates in a controlled fashion. For examples, see: references 2, 31,
32, 34 and S.-E. Suh, S. Chen, K. N. Houk, D. M. Chenoweth, Chem. Sci.
2018, 9, 7688–7693.
[8] C. C. Mauger, G. A. Mignani, Org. Process Res. Dev. 2004, 8,
1065−1071.
[51] J. Balcar, G. Chrisam, F. X. Huber, J. Sauer, Tetrahedron Lett. 1983,
24, 1481–1484.
[ 9 ] F. Schleth, T. Vettiger, M. Rommel, H. Tobler, World Patent
WO2011131544 A1, 2011.
[52] Y. Himeshima, T. Sonoda, H. Kobayashi, Chem. Lett. 1983, 12, 1211–
1214.
[53] D. Peña, D. Pérez, E. Guitián, L. Castedo, Org. Lett. 1999, 1, 1555–
1557.
[54] Silyl triflate precursors to 17, 19, 21, and 25 are all commercially
available from Sigma–Aldrich or TCI (see the SI for details).
[55] K. Afarinkia, V. Vinader, T. D. Nelson, G. H. Posner, Tetrahedron
1992, 48, 9111–9171.
[10] C. M. Gampe, E. M. Carreira, Angew. Chem., Int. Ed. 2012, 51,
3766−3778; Angew. Chem. 2012, 124, 3829−3842.
[11] P. M. Tadross, B. M. Stoltz, Chem. Rev. 2012, 112, 3550−3577.
[12] A. E. Goetz, N. K. Garg, Nat. Chem. 2012, 5, 54–60.
[13] T. C. McMahon, J. M. Medina, Y.-F. Yang, B. J. Simmons, K. N.
Houk, N. K. Garg, J. Am. Chem. Soc. 2015, 137, 4082–4085.
[14] C. Wentrup, R. Blanch, H. Briehl, G. Gross, J. Am. Chem. Soc. 1988,
110, 1874–1880.
[56] R. P. Johnson, K. J. Daoust, J. Am. Chem. Soc. 1995, 117, 362–367.
[57] X. Liu, J. Liu, B. Zheng, L. Yan, J. Dai, Z. Zhuang, J. Du, Y. Guo, D.
Xiao, New J. Chem. 2017, 41, 10607–10612.
[58] Q.-J. Ma, H.-P. Li, F. Yang, J. Zheng, X.-F. Wu, Y. Bai, X.-F. Li,
Sens. Actuators, B 2012, 166, 68–74.
[59] L. Tan, S. Mo, B. Fang, W. Cheng, M. Yin, J. Mater. Chem. C 2018,
6, 10270–10275.
[60] C. Reichardt, Chem. Rev. 1994, 94, 2319–2358.
[61] K.-B. Seo, I.-H. Lee, J. Lee, I. Choi, T.-L. Choi, J. Am. Chem. Soc.
2018, 140, 4335–4343.
[15] S. F. Talis, R. L. Danheiser, J. Am. Chem. Soc. 2014, 136, 15489–
15492.
[16] T. K. Shah, J. M. Medina, N. K. Garg, J. Am. Chem. Soc. 2016, 138,
4948–4954.
[17] A. E. Goetz, T. K. Shah, N. K. Garg, Chem. Commun. 2015, 51,
34−45.
[18] G.-Y. J. Im, S. M. Bronner, A. E. Goetz, R. S. Patton, P. H.-Y Cheong,
K. N. Houk, N. K. Garg, J. Am. Chem. Soc. 2010, 132, 17933–17944.
[19] M. G. Reinecke, Tetrahedron 1982, 38, 427–498.
[20] D. Pérez, D. Peña, E. Guitián, Eur. J. Org. Chem. 2013, 5981–6013.
[21] X. Xiao, T. R. Hoye, Nat. Chem. 2018, 10, 838–844.
[22] S. E. Suh, S. A. Barros, D. M. Chenoweth, Chem. Sci. 2015, 6, 5128–
5132.
[23] Y. Mizukoshi, K. Mikami, M. Uchiyama, J. Am. Chem. Soc. 2014,
137, 74–77.
[24] M. J. Allen, V. C. Tung, R. B. Kaner, Chem. Rev. 2010, 110, 132–145.
[25] A. C. Grimsdale, J. Wu, K. Müllen, Chem. Commun. 2005, 17, 2197–
2204.
[26] P. M. Beaujuge, M. J. Fréchet, J. Am. Chem. Soc. 2011, 133, 20009–
20029.
[27] A. Haller, A. Guyot, Compt. Rend. 1904, 138, 1251–1254.
[28] J. H. Carmel, J. S. Ward, M. M. Cooper, J. Chem. Educ. 2017, 94,
626–631.
[29] W. J. Jo, K. Kim, H. C. No, D. Shin, H. Oh, J. Son, Y. Kim, Y. Cho,
Q. Zhao, K. Lee, H. Oh, S. Kwon, Synth. Met. 2009, 159, 1359–1364.
[30] M. Chen, L. Yan, Y. Zhao, I. Murtaza, H. Meng, W. Huang, J. Mater.
Chem. C. 2018, 6, 7416–7444.
[31] J. T. Markiewicz, F. Wudl, ACS Appl. Mater. Interfaces 2015, 7,
28063–28085.
[32] J. E. Anthony, Chem. Rev. 2006, 106, 5028–5048.
[33] M. Stępień, E. Gońka, M. Żyła, N. Sprutta, Chem. Rev. 2017, 117,
3479–3716.
[34] F. Eiden, B. Wuensch, Arch. Pharm. 1986, 319, 886–889.
[35] C. Bozzo, M. D. Pujol, Heterocycl. Commun. 1996, 2, 163–168.
[36] J. Li, F. Yan, J. Gao, P. Li, W.-W. Xiong, Y. Zhao, X. W. Sun, Q.
Zhang, Dyes Pigm. 2014, 112, 93–98.
[37] S. J. Eum, Y. J. Cho, H. J. Kwon, B. O. Kim, S. M. Kim, S. S. Yoon,
U.S. Patent US8153279, 2012.
[38] X. Li, A. Fast, Z. Huang, D. A. Fishman, M. L. Tang, Angew. Chem.,
Int. Ed. 2017, 56, 5598–5602; Angew. Chem2017, 129, 5690–5694.
[39] C. Gao, D. Cui, Y. Wang, C. Zhang, X. Sun, Chinese Patent
CN10508599, 2018.
[40] C. Xia, C. Lin, T.-C. Wang, U.S. Patent US2016/0149139, 2016.
[ 41 ] C. Gao, D. Cui, Y. Wang, C. Zhang, X. Sun, World Patent
WO2016/192346, 2016.
[42] D.-H. Kim, J.-C. Park, H. M. Song, E.-K. Kim, Korean Patent KR10-
2010-0108120, 2010.
[43] J. L. Marshall, D. Lehnherr, B. D. Lindner, R. R. Tykwinski,
ChemPlusChem 2017, 82, 967–1001.
[44] J. B. Lin, T. K. Shah, A. E. Goetz, N. K. Garg, K. N. Houk, J. Am.
Chem. Soc. 2017, 139, 10447–10455.
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