Synthesis of chryseno[1,2-b]heteroarenes and phenanthro[1,2-b:8,7-b']diheteroarenes by an SNAr-anionic cyclization cascade reaction strategy

Article abstract of DOI:10.1016/j.tetlet.2020.152663

The synthesis of [5]heterophenacenes bearing one or two indole, furan, or thiophene rings is described using an S_NAr-anionic cyclization cascade strategy. The convergent reaction sequences furnish chryseno[1,2-b]heteroarenes and phenanthro[1,2-

Full text of DOI:10.1016/j.tetlet.2020.152663

Tetrahedron Letters 61 (2020) 152663
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Tetrahedron Letters
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Synthesis of chryseno[1,2-b]heteroarenes and phenanthro[1,2-b:8,7-b’]
diheteroarenes by an SNAr-anionic cyclization cascade reaction strategy
⇑
James Gilmore, Daeseong Hwang, Jack M. Crissy, James M. Mercado-Rodríguez, Jeffrey L. Katz
Department of Chemistry, Colby College, 5754 Mayflower Hill, Waterville, ME 04901, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of [5]heterophenacenes bearing one or two indole, furan, or thiophene rings is described
using an SNAr-anionic cyclization cascade strategy. The convergent reaction sequences furnish chry-
seno[1,2-b]heteroarenes and phenanthro[1,2-b:8,7-b’]diheteroarenes in only four synthetic steps. The
heteroaromatic functionality is selected and installed in the final step of the syntheses from common
ortho-fluoro-ethynylarene precursors.
Received 30 October 2020
Accepted 11 November 2020
Available online 16 November 2020
Keywords:
Ó 2020 Elsevier Ltd. All rights reserved.
Phenacene
Heteroarene
SNAr
Cascade
Nucleophilc substitution
[n]Phenacenes, W-shaped fused aromatic molecules, have
emerged as promising compounds for the next-generation of
organic electronics (Fig. 1) [1]. In contrast to the linearly fused
[n]acenes, [n]phenacenes exhibit significantly higher stability to
air and light owing to lower HOMO energy levels that are main-
tained even for extended aromatic systems [2]. Modification of
the phenacene core by installation of heteroaromatic rings at inte-
rior [3] and terminal [4] positions has been explored as a means to
alter and optimize molecular properties for electronic applications.
For example, the thiophene-containing systems phenanthro[2,1-
b:7,8-b’]dithiophene (PDT) [4a,b] and piceno[4,3-b:9,10-b0]dithio-
phene (PiDT) [4] have shown promise as organic field effect tran-
sistors and as polymer-based semiconductors in organic solar
cells. However, the syntheses of these compounds are not readily
adapted for incorporation of heterocycles beyond thiophene, and
have thus far been limited to systems with symmetrically disposed
thiophene rings. Therefore, there remains an urgent need for gen-
eral and efficient methods to access diverse [n]heterophenacenes,
especially those containing terminal heteroaromatic rings, to fur-
ther applications development.
or selenophene rings [6]. The cascade reaction proceeds without
the use of transition metals and allows installation of diverse
heteroaromatic systems from a common synthetic precursor. Fur-
thermore, the functionality present on the ethynyl group is incor-
porated at the 2-position of the resulting heterocycle, allowing
facile installation of 2-aryl and 2-tert-butyl groups. We now report
the synthesis of chryseno-systems 1 and phenanthro-systems 2
using SNAr-anionic cyclization reactions (Fig. 1). The synthetic
sequences are short and convergent, allowing the formation of
heteroaromatic rings with X = N—H, N-Ar, O, or S in the final step
of the synthesis from common ortho-fluoro-ethynylarene
precursors.
Our route to common cyclization precursor 7 toward the syn-
thesis of chryseno[1,2-b]heteroarenes 1 is shown in Scheme 2.
Mizoroki-Heck coupling of 1-bromo-2-fluoro-3-iodobenzene
3
Our group has developed tandem nucleophilic aromatic substi-
tution (SNAr)-anionic cyclization cascades of ortho-fluoro-ethynyl-
benzenes with N- and O- nucleophiles to produce indoles and
benzofurans (Scheme 1) [5]. These methods have also been inves-
tigated with S-, and Se-nucleophiles, for the formation of thiophene
⇑
Corresponding author.
E-mail address: jlkatz@colby.edu (J.L. Katz).
Fig. 1. Representative phenacenes and heterophenacenes.
https://doi.org/10.1016/j.tetlet.2020.152663
0040-4039/Ó 2020 Elsevier Ltd. All rights reserved.

J. Gilmore, D. Hwang, J.M. Crissy et al.
Tetrahedron Letters 61 (2020) 152663
Scheme 1. General Scheme of SNAr-Anionic Cyclization Reactions of ortho-fluoro-
ethynylarenes.
Scheme 4. Synthesis of common cyclization precursor 2-(tert-butylethynyl)-1-
fluorochrysene 10.
which was isolated in 76% yield (KOtBu, DMSO, 145 °C, 18 h). It is
notable that post-cyclization arylation of the indole nitrogen atom
on 1a to yield 1b would be challenging due to the adjacent tert-
butyl substituent. Reaction of 2-(tert-butylethynyl)-1-fluorochry-
sene
7 was also investigated using chalcogen nucleophiles.
Hydroxide reacted smoothly with 7 (DMSO, 150 °C, 3 d), furnishing
chryseno[1,2-b]furan 1c in 87% yield. Surprisingly, sodium sulfide
reacted rather sluggishly with chrysene 7 in comparison to our
observations on related systems for the formation of thiahelicenes
[6]. Nonetheless, reaction completion was observed at 120 °C for
18 h, providing chryseno[1,2-b]thiophene 1d in 67% yield (Na2-
Sꢀ9H2O, DMSO, 120 °C, 18 h).
Scheme 2. Synthesis of common cyclization precursor 2-(tert-butylethynyl)-1-
fluorochrysene 7.
With our successful generation of chryseno[1,2-b]heteroarenes
1a-d, we next turned to investigating the synthesis of symmetrical
phenanthro[1,2-b:8,7-b’]diheteroarenes 2. Our synthetic sequence
to the requisite bisethynylphenanthrene 10 again utilized 1-
bromo-2-fluoro-3-iodobenzene 3, which was subjected to Stille
coupling using 1,2-bis(tributylstannyl)ethene (Pd(PPh3)4, toluene,
110 °C, 18 h), furnishing stilbene 8 (Scheme 4). Photocyclization
of 8 to form the desired phenanthrene core then proceeded
smoothly to produce dibromophenanthrene 9 in 70% yield (I2,
cyclohexane, propylene oxide, 300 nm, 24 h). Finally, Sonogashira
coupling (tert-butylacetylene, PdCl2(PPh3)2, CuI, NEt3, 80 °C, 18 h)
provided tert-butylethynyl-substituted phenanthrene 10, function-
alized for entry into SNAr-anionic cyclization cascades.
with 1-vinylnaphthalene (4) was carried out under aqueous condi-
tions using our recently developed heterogenous Pd@poly(mPO)
catalyst [7] at a Pd catalyst loading of 0.1 mol % (Pd@poly(mPO),
K3PO4, H2O, 95 °C, 48 h). The resulting stilbene 5 was then sub-
jected to Mallory photocyclization to furnish 2-bromo-1-fluo-
rochrysene 6 in 84% yield (I2, cyclohexane, propylene oxide,
300 nm, 24 h) [8]. Installation of the requisite ortho-ethynyl group
was accomplished via Sonogashira coupling of tert-butylacetylene
to yield cyclization precursor 7 (PdCl2(PPh3)2, CuI, NEt3, 80 °C,
18 h). Our previous investigations [5] revealed that arylethynyl
groups were most activating for substitution of aryl fluorides, lead-
ing to SNAr-anionic cyclization cascades that proceeded at lower
temperatures and in the highest yields. However, for this study
we chose to utilize tert-butylethynyl systems to both maximize
organic solubility and to generate a substitution pattern that is
otherwise difficult to install by metalation or cross-coupling
methods.
With a common precursor in hand, formation of chryseno[1,2-
b]heteroarenes 1 was then investigated by reaction of 2-(tert-buty-
lethynyl)-1-fluorochrysene 7 with N-, O-, and S- nucleophiles
(Scheme 3). As we have previously reported on simple ortho-flu-
oro-ethynylarenes, use of acetamide as the nucleophile in these
cascade processes proceeds with in situ acetate cleavage, leading
to N—H indole products [5]. Indeed, reaction of 7 with acetamide
furnished N—H—phenanthro[1,2-g]indole 1a in 68% yield (KOtBu,
DMSO, 145 °C, 18 h). Changing to a p-toluidine nucleophile allowed
for facile formation of N-p-tolyl-phenanthro[1,2-g]indole target 1b,
Reaction of 2,7-bisethynyl-1,8-difluorophenanthrene 10 with
N-, O-, and S- nucleophiles successfully furnished the desired
targets, phenanthro[1,2-b:8,7-b’]diheteroarenes
2 (Scheme 5).
N—H—benzodiindole 2a was formed by reaction with acetamide
(KOtBu, DMSO, 145 °C, 18 h), while analogous reaction using p-
toluidine led to formation of N-p-tolyl-benzodiindole 2b. Likewise,
reaction of phenanthrene 10 with potassium hydroxide provided
phenanthro-difuran 2c (DMSO, 150 °C, 3 d), while sodium sulfide
generated phenanthro-dithiophene 2d (Na2Sꢀ9H2O, DMSO,
120 °C, 18 h).
Single crystals of phenanthro[1,2-g]indole 1b were obtained by
slow evaporation from chloroform, and the solid-state structure is
shown in Fig. 2 [9]. Due to steric buttressing by the 2-position tert-
butyl group, the N-p-tolyl substituent on 1b is held nearly orthog-
Scheme 3. Synthesis of chryseno[1,2-b]heteroarenes 1 from common precursor 7
via SNAr-anionic cyclization reactions.
Scheme 5. Synthesis of phenanthro[1,2-b:8,7-b’]diheteroarenes 2 from common
precursor 10 via SNAr-anionic cyclization reactions.
2

J. Gilmore, D. Hwang, J.M. Crissy et al.
Tetrahedron Letters 61 (2020) 152663
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3

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Tetrahedron Letters 61 (2020) 152663
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[9] Crystallographic data for 1b: M = 413.53, monoclinic space group P21/c, a =
23.6799(7) Å, b = 9.5379(3) Å, c = 22.9830(7) Å, b = 115.465(3)°, V = 4686.6(3)
Å3, Z = 8, R1 = 0.0460, Rw = 0.1082, GOF = 1.036. CCDC 2016643 contains the
data_request@ccdc.cam.ac.uk,
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
+44 1223 336033.
or
by
contacting
The
Cambridge
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