Palladium-Catalyzed Cascade Dearomative Spirocyclization and C?H Annulation of Aromatic Halides with Alkynes

DOI: 10.1021/acs.orglett.1c01736

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Organic Letters p. 5203 - 5207 (2021)

Update date:2022-08-02

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Authors:

Liao, Xingrong

Zhou, Fulin

Bin, Zhengyang

Yang, Yudong

You, Jingsong

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Article abstract of DOI:10.1021/acs.orglett.1c01736

Described herein is a palladium-catalyzed intermolecular dearomative annulation of aryl halides with alkynes, which provides a rapid approach to a class of structurally unique spiroembedded polycyclic aromatic compounds. The cascade process is accomplished by a sequential alkyne migratory insertion, Heck-type dearomatization, and C-H bond annulation. Further optoelectronic study indicated this fused spirocyclic scaffold could be a potential host material for OLEDs, as exemplified by a fabricated red PhOLED device with a maximum external quantum efficiency of 23.0%.

Full text of DOI:10.1021/acs.orglett.1c01736

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Letter

Palladium-Catalyzed Cascade Dearomative Spirocyclization and

C−H Annulation of Aromatic Halides with Alkynes

Xingrong Liao, Fulin Zhou, Zhengyang Bin, Yudong Yang,* and Jingsong You

Cite This: Org. Lett. 2021, 23, 5203 −5207

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ABSTRACT: Described herein is a palladium-catalyzed intermo-

lecular dearomative annulation of aryl halides with alkynes, which

provides a rapid approach to a class of structurally unique

spiroembedded polycyclic aromatic compounds. The cascade

process is accomplished by a sequential alkyne migratory insertion,

Heck-type dearomatization, and C−H bond annulation. Further

optoelectronic study indicated this fused spirocyclic scaﬀold could

be a potential host material for OLEDs, as exempliﬁed by a

fabricated red PhOLED device with a maximum external quantum

eﬃciency of 23.0%.

spirocyclization of alkyl bromoarenes with internal alkynes.⁷

pirocyclic scaﬀolds have attracted considerable attention in

S_{the ﬁelds of synthetic chemistry, organic functional}Although this work obviated the using of electronically

materials, and pharmaceuticals.¹The structures of spirocycles

activated aromatics as starting materials, an alkyl group is

necessary to enable a β-hydrogen elimination as the driving

force for the expected spirocyclization reaction (Scheme 1a).

Recently, the endocyclic C=C bonds of (hetero)arenes have

been regarded as nonclassic oleﬁns to enable the dearomative

difunctionalization reactions.⁸In this regard, Jia and You

reported the catalytic dearomative 1,4-difunctionalization of

naphthalenes by capturing the in situ formed π-allyl-palladium

species with a second coupling partner (Scheme 1b).^9,10

Inspired by this dearomative difunctionalization strategy, we

envisioned that the catalytic Heck-type dearomative spiroan-

nulation of polycyclic aromatic halides with diaryl acetylenes

could be achieved without the assistance of an alkyl group, by

intercepting the alkyl palladium intermediates with the

attached aryl rings on the carbon−carbon triple bonds. The

implementation of this rational design relied on the develop-

ment of a highly eﬃcient and selective catalytic system that

enables the thermodynamically unfavored dearomatization

process rather than nonspirocyclization and a following C−H

annulation process as the termination reaction of the cascade

course. Herein, we disclose a palladium-catalyzed cascade

dearomative spirocyclization and C−H annulation of aromatic

have a crucial inﬂuence on their biological activities and

photophysical properties such as HOMO−LUMO gaps, redox

potentials, carrier mobilities, molecular packing modes, and

absorption and emission properties.²Considering the wide

applications of polycyclic aromatic hydrocarbons (PAHs) as

organic semiconductors, the incorporation of the cruciform

structural feature into the PAHs could eﬀectively impact the

intermolecular π−π stacking interactions and optoelectronic

properties. Upon appropriate π-extension and/or functionali-

zation, these inherently sterically hindered spirocycles could be

evolved into advanced materials in organic optoelectronic

devices, including the host materials for organic light-emitting

diodes (OLEDs) and hole transporting materials for organic

solar cells (OSCs).^1a,3Thus, the development of concise and

eﬃcient synthetic methods enabling the rapid assembly of

structurally diverse spirofunctionalized polycyclic aromatic

hydrocarbons from simple starting materials with excellent

functional group tolerance is highly desired, which could boost

the innovation of organic functional materials and medicines.

Transition-metal-catalyzed dearomative cyclization of simple

planar arenes with alkynes has been regarded as a powerful tool

to access three-dimensional spirocyclic architectures.⁴Despite

eﬃciency, the reported methods typically require the employ-

ment of electronically activated aromatics as the substrates,

such as phenols, naphthols, indoles, and pyrroles, because of

the relatively low aromatic stabilization energy and/or

beneﬁcial keto−enol tautomerism.⁴⁻⁷In 2019, we disclosed

a palladium-catalyzed Heck-type dearomative [2 + 2 + 1]

Received: May 24, 2021

Published: June 16, 2021

https://doi.org/10.1021/acs.orglett.1c01736

Org. Lett. 2021, 23, 5203−5207

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Scheme 1. Transition-Metal-Catalyzed Dearomative

Spiroannulation of Aromatics

Table 1. Optimization of Reaction Conditions

entry

base

Pd. cat

solvent

yield (%)

Cs₂CO₃

K₂CO₃

Pd(OAc)₂

Pd₂(dba)₃

Pd(PPh₃)₄

Pd(acac)₂

toluene

o-xylene

n.d.

trace

n.d.

trace

n.d.

[Pd(allyl)Cl]₂

K₃PO₄

KO^tBu

NaO^tBu

mesitylene

THF

DCE

DMF

halides with diaryl acetylenes (Scheme 1c), which enables

streamlined synthesis of spiroembedded polycyclic aromatic

compounds and rapid assembly of a class of novel pure

hydrocarbon host materials for phosphorescent organic light-

emitting diodes (PhOLEDs).

toluene

89(81 )

cde

Reaction conditions: 1a (0.1 mmol), 2a (0.15 mmol), Pd cat. (5 mol

%), base (0.2 mmol), and solvent (1 mL) at 80 °C for 12 h under N₂.

At the beginning, the reactions of diphenyl acetylene 2a with

9-(2-iodophenyl)phenanthrene 1a, 1-bromonaphthalene, and

9-bromophenanthrene, individually, were conducted under the

previously developed catalytic system for spiroannulation of

alkyl aryl haloarenes.⁷Not suprisingly, undeﬁned complex

mixtures, which were supposed to involve [4 + 2], [3 + 2], and

[2 + 2 + 2] cyclized products (based on the GC−MS), were

generated in poor yields. Then, 1a and 2a were selected as the

model substrates for reaction optimization (Table 1). Initial

investigation indicated that the palladium source was found to

be crucial for the spirocyclization. After extensive screening of

the common palladium salts such as Pd(OAc)₂, Pd₂(dba)₃,

Pd(PPh₃)₄, [Pd(allyl)Cl]₂, and Pd(acac)₂(Table 1, entries 1−

5), it was determined that the reaction in the presence of

[Pd(allyl)Cl]₂, Cs₂CO₃, and toluene could furnish the desired

spiroembedded polycyclic product 3a in 27% yield (Table 1,

entry 5). The structure of 3a was demonstrated by single-

crystal X-ray diﬀraction. Then, the eﬀects of bases were

examined (Table 1, entries 6−9). While KO^tBu almost

terminated the reaction, NaO^tBu proved to be the most

eﬀective base, delivering 3a in 75% yield (Table 1, entry 9).

Benzene solvents such as o-xylene, mesitylene, and toluene

were the suitable solvents for this reaction (Table 1, entries 10

and 11), whereas other common solvents such as THF, DCE,

and DMF were much less eﬀective (Table 1, entries 12−14).

Prolonging the reaction time to 18 h could slightly improve the

yield to 82% (Table 1, entry 15). Finally, the reaction of 1a

(0.12 mmol), 2a (0.1 mmol), [Pd(allyl)Cl]₂(5% mmol),

NaO^tBu (0.2 mmol), and toluene (1 mL) at 80 °C for 18 h

proved to be the optimal conditions, delivering 3a in 81%

isolated yield (Table 1, entry 16) along with the formation of

trace amounts of nondearomatized annulation products. The

addition of phosphorus ligands such as X-Phos into the

catalytic system was detrimental to the reaction eﬃciency

(Table 1, entry 17; see the Supporting Information (SI), Table

S1, entries 33−36).

NMR yield using dibromomethane as an internal standard. Run for

18 h. 1a (0.12 mmol) and 2a (0.1 mmol) were used. X-Phos (20

mol %) was added. Yields of isolated products. DCE = 1,2-

dichloroethane; THF = tetrahydrofuran; DMF = N,N-dimethylfor-

mamide; n.d. = not detected.

With the optimized reaction conditions in hand, we ﬁrst

evaluated the substrate scope using diﬀerent alkynes (Table 2).

Diaryl acetylenes with either electron-donating groups

(methyl, t-butyl, methoxy) and electron-withdrawing groups

(ﬂuoro, chloro, bromo) at the para or meta position of phenyl

rings worked well under the standard conditions, giving the

spirocyclic products in 42−81% yields (3a−h). The good

functional tolerance with halo groups could provide a valuable

opportunity for further derivation (see the SI, part VII).

Generally, the electron-rich alkynes appeared to be beneﬁcial

for the reaction (3b−d vs 3e−g). Additionally, di(thiophen-3-

yl)ethyne (2i) could undergo a tandem annulation with a 69%

product yield (3i), and the terminal C−H annulation

regioselectively occurred at C2 position of thienyl, which was

identiﬁed by X-ray crystallographic analysis. To our delight,

phenyl alkyl alkynes, such as but-1-yn-1-ylbenzene (2j), could

also be suitable substrates albeit in lower yield (3j). However,

terminal alkynes such as phenylacetylene failed to undergo this

spiroannulation. Next, the substrate scope of biaryl halides was

studied. Biaryl iodides with diverse functional groups,

including triﬂuoromethyl, methoxy, methyl, chloro, cyano,

phenyl, and t-butyl, at diﬀerent positions on the iodinated aryl

rings were investigated, leading to the spirocyclic analogues in

50−91% yields (3k−u). Furthermore, biaryl halides involving

quinoxalinyl, naphthyl, and pyrenyl moieties were also suitable

substrates, giving a sterically congested spirocyclic compound

in moderate to high yields (3v−x). Unfortunately, the reaction

of 1-(2-iodophenyl)naphthalene with 2a did not provide the

desired product.

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Table 2. Scope of Biaryl Iodides and Internal Alkynes

Table 3. Scope of Bromoarenes and Internal Alkynes

Reaction conditions: 1 (0.1 mmol), 2 (0.15 mmol), Pd(dppf)Cl₂

(5.0 mol %), and CsOPiv (0.2 mmol) in 1,4-dioxane (1 mL) at 100

°C for 12 h under N₂. Yields of isolated products. Scale of 3 mmol.

At 110 °C.

Reaction conditions: 1 (0.12 mmol), 2 (0.1 mmol), [Pd(allyl)Cl]₂

Scheme 2. Plausible Mechanistic Pathway

(5.0 mol %), and NaO^tBu (0.2 mmol) in toluene (1 mL) at 80 °C for

18 h under N₂. Yields of isolated products. Scale of 3 mmol. At

100 °C. At 110 °C.

Besides the cascade [3 + 2] spirocyclization/C−H

annulation of biaryl halides with internal alkynes, condensed

aromatic bromides could also work with alkynes to undergo a

cascade [2 + 2 + 1] spirocyclization/C−H annulation to

furnish the spirocyclic scaﬀolds. After reoptimization of the

reaction conditions (see SI, Table S2), spirofeatured polycyclic

aromatic compound 4a was obtained in 67% yield accom-

panied by approximately 10% yield of the [2 + 2 + 2]

annulated byproduct (1,2,3,4-tetraphenyltriphenylene). As

exempliﬁed in Table 3, symmetrical diaryl alkynes and

bromoarenes with functional groups such as methyl, methoxy,

and carboxylic ester could be converted to the desired

spirocycles in 55−70% yields (4a−d and 4i). Of particular

note, bromo substrates with larger π-conjugated arenes such as

chrysene, benzo[g]chrysene, and pyrene could also participate

in this reaction, providing the congested spirocyclic products in

52−62% yields (4e−g).

To preliminarily investigate the reaction mechanism, an

intermolecular competitive experiment between 2a and 2a-d₁₀

with 1a was conducted (see the SI, part VIII). The kinetic

isotope eﬀect (k_H/k_D≈ 1.63) suggested that terminal C−H

cleavage of the aryl ring of alkynes might not be involved in the

rate-determining step.

subsequently participates in the C−H annulation to deliver the

palladacycle intermediate D. Finally, reductive elimination

provides the targeting spirocyclic product 3a or 4a and releases

the Pd(0) species to complete the catalytic cycle.

Recently, the development of pure hydrocarbon (PHC) host

materials has attracted much attention in the ﬁeld of OLEDs.¹¹

To evaluate the potential of the spirocyclic scaﬀolds as PHC

host materials, compound 3a was selected as the prototype

molecule for investigation. A preliminary investigation on the

photophysical properties of 3a indicated that the maximum

absorption and emission were at 331 and 438 nm in toluene

(1.0 × 10⁻⁵M), respectively. The singlet energy (E_S1) and

triplet energy (E_T1) of 3a were calculated to be 3.31 and 3.08

Based on the above results and previous reports,^7,9,10

proposed mechanism is shown in Scheme 2. Initially, oxidative

addition of Pd(0) to the C−X bond aﬀords aryl Pd(II) species

A (cycle A) or A′ (cycle B), which then undergoes migratory

insertion with diaryl acetylenes to deliver the alkenyl palladium

species B (cycle A) or 1,3-dienyl palladium speices B′ (two

migratory insertions, cycle B). Following Heck-type dearoma-

tive spiroannulation produces benzylic Pd(II) species C, which

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eV based on the ﬂuorescence emission and phosphorescence

emission spectra, respectively (see the SI, Figure S5a,b and

Table S7). The electrochemical property of 3a was studied by

cyclic voltammetry (CV) in CH₂Cl₂(see the SI, Figure S5c).

The HOMO energy was measured to be −5.71 eV, and the

LUMO was evaluated to be −2.36 eV based on the values of

E_HOMOand E_g(see the SI, Table S7 and Figure S6).

Thermogravimetric analysis (TGA) showed a high decom-

position temperature at 328 °C (5% weight loss, see the SI,

Figure S5d). Based on these results, a red phosphorescent

organic light-emitting diode (PhOLED) device was fabricated

using 3a as a host material with a device conﬁguration of ITO/

HAT-CN (5 nm)/NPB (30 nm)/TCTA (10 nm)/Ir-

(mphmq)₂(tmd):3a (5%, 25 nm)/TmPyPb (50 nm)/LiF

(0.8 nm)/Al (100 nm) (Figure 1a,b). As shown in Figure 1c,

(CCDC-2058445), 3i (CCDC-2058449), 3v (CCDC-

2082493), and 4h (CCDC-2058450) (PDF)

Accession Codes

CCDC 2058445, 2058449−2058450, and 2082493 contain the

supplementary crystallographic data for this paper. These data

can be obtained free of charge via www.ccdc.cam.ac.uk/

data_request/cif, or by emailing data_request@ccdc.cam.ac.

uk, or by contacting The Cambridge Crystallographic Data

Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44

1223 336033.

AUTHOR INFORMATION

Corresponding Author

■

Yudong Yang − Key Laboratory of Green Chemistry and