One-Step Synthesis of Benzophosphole Derivatives from Arylalkynes by Phosphenium-Dication-Mediated Sequential C-P/C-C Bond Forming Reaction

概要

Title

One-Step Synthesis of Benzophosphole Derivatives
from Arylalkynes by Phosphenium-DicationMediated Sequential C-P/C-C Bond Forming
Reaction

Author(s)

Nishimura, Kazutoshi; Xu, Shibo; Nishii, Yuji et
al.

Citation

Organic Letters. 2023, 25(9), p. 1503-1508

Version Type AM
URL

https://hdl.handle.net/11094/92684

rights

© 2023 American Chemical Society.

Note

Osaka University Knowledge Archive : OUKA
https://ir.library.osaka-u.ac.jp/
Osaka University

One-Step Synthesis of Benzophosphole Derivatives from Arylalkynes by Phosphenium-Dication-Mediated Sequential C–
P/C–C Bond Forming Reaction
Kazutoshi Nishimura,†,§ Shibo Xu,‡,§ Yuji Nishii,† and Koji Hirano*,†,‡
†

Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871,
Japan
‡
Innovative Catalysis Science Division, Institute for Open and Transdisciplinary Research Initiatives (ICS-OTRI),
Osaka University, Suita, Osaka 565-0871, Japan
Supporting Information Placeholder

O
OH
P
R
H

Tf2O/base

+
X

δ+

via

R

Y

P

O Ar
P
O
Ph

δ+

O
R

X
Y
two C–P and one C–C
formations in one-step

O
Ph

P
Ar

P
O

double cyclization

P

P
N
Me

fully intermolecular version

ABSTRACT: A metal-free, phosphenium-dication-mediated sequential C–P and C–C bond forming reaction has been
developed. This protocol can provide concise access to the (di)benzophosphole derivatives in one synthetic operation
from the readily available and simple arylalkynes and phosphinic acids. Application to the multiple cyclization reaction
and the fully intermolecular three-component-coupling-type reaction are also described.

Phosphole derivatives have recently received significant attention in fields of phosphorus-based organic functional materials because of their unique optoelectronic
and physical properties.1 Accordingly, numerous strategies for the preparation and decoration of phosphole nuclei have been developed so far. While most traditional
protocols largely relied on the transition-metal-mediated
multistep sequence with some toxic and sensitive reagents,1,2 P-radical,3 -cation,4 and -dication5-promoted
methods recently appeared to streamline the synthesis of
targeted phosphole cores via efficient C–P bond formation. In particular, our previous work using the
phosphenium dication equivalent5a enabled the rapid construction of the dibenzophospholes from the corresponding simple biaryls and phosphinic acids (Scheme 1a).
However, electron-rich (hetero)aromatics such as indole,
thiophene, and phenoxy moieties were generally essential to trigger the reaction, which apparently limited the
versatility of the phosphole product. Herein, we repot a
more flexible approach to the benzophospholes from the
arylalkynes and phosphinic acids: the phosphenium-dication-mediated sequential C–P/C–C bond forming reaction
is developed (Scheme 1b). By using the alkyne moiety as
the reaction trigger, this strategy easily accesses the nonheteroaromatic benzene-fused phosphole derivatives

with high efficiency. The starting arylalkynes are also
readily available by the Sonogashira coupling, same as in
the preparation of biaryls via the Suzuki-Miyaura coupling.
Thus, this protocol significantly expands the applicability
of the P-cation-based strategy in the phosphole synthesis.
Additionally, the multiple phosphole-constructing cyclization and application to the fully intermolecular three-component-coupling reaction of alkynes, phosphinic acids,
and external nucleophiles are achieved. We note that
during the course of this study, Huang and Xiao reported
the related reaction of ortho-MeO- and MeS-substituted
diarylalkynes,5b but the products were restricted to the furan- and thiophene-fused dibenzophospholes, which are
more readily synthesized by our previous double C–P
bond forming reaction of heterobiaryls.5a In addition, the
intermolecular process was not mentioned at all.
Scheme 1. Phosphenium-Dication-Mediated Approaches to (Di)Benzophospholes

sive screening, the targeted benzophosphole oxide derivative 3aa was found to be isolated in 90% yield by using
one Ar is generally limited to
the combination of Tf2O and 2,6-lutidine in heated DCE
O
+
P
–
P
e -rich (hetero)arene
R
δ+
R
(Scheme 3). Some observations are to be noted: the cor= heteroatom
responding P(III) phosphole derivative was not detected
at all, and 3aa was only formed even without any addib) Sequential C–P/C–C bond formation from arylalkynes (this work)
tional oxidative treatment.9 Tf2O was the critical dehydrating reagent as far as we tested. No reaction occurred unO
δ+
alkyne-triggered more flexible
der Lewis-base-free conditions. Some other pyridine-type
P
+
P
approach to nonheteroaromatic
R
R
δ+
benzene-fused systems
Lewis bases also promoted the reaction, whereas slugX
X
Y
Y
gish conversion of 1a was observed in the presence of
alkylamines and inorganic bases (see the Supporting
Our reaction design is shown in Scheme 2. The active
Information for details).
phosphenium dication equivalent A is initially generated
With optimal conditions in hand, we first investigated
from the phosphinic acid 1 by the action of 2 equiv of dethe scope of the arylalkynes 2. In addition to the model
hydrating reagent Tf2O and Lewis base (L) via P(V)/P(III)
substrate 2a, electron-donating and -withdrawing substittautomerization.6 Subsequent [1+2] cycloaddition with
uents both were well compatible under the reaction conthe alkyne moiety of 2 generates the corresponding threeditions (3ab and 3ac). The sterically congested ortho-Me
7
membered phosphirenium species B. The ring-opening
group (3ad) and more condensed naphthalene (3ae) and
process is induced by the intramolecular attack of the tethphenanthrene (3af) substitutions were also accommoered Ar group to form C. The intermediate C has still one
dated. The alkyne containing the heteroaromatic thiopositive charge on the phosphorus and thus undergoes
phene moiety underwent the reaction without any difficulty
8
the intramolecular phospha-Friedel-Crafts-type reaction
(3ag). The ethylene tether could also be replaced with
to furnish the benzophosphole derivative 3. Overall, two
the oxygen-, nitrogen-, and ester-based linkers, and the
C–P bonds and one C–C bond are constructed in one
corresponding heteroatom-incorporated benzophosphole
synthetic operation.
derivatives 3ah–ak were isolated in synthetically acceptaScheme 2. Working Hypothesis
ble yields. In the case of 3ai, the regioisomeric 3ai’ was
also formed probably because of the competitive steric
and electronic effects. Notably, in the reaction of the NTsL
O
OH
type substrate 2j, the additional treatment with KOH in
+
OH
δ
Tf2O/L
P
P
P +
MeOH promoted the elimination of TsH to selectively form
R
δ
R
R
–
2TfOH
X
H tautomerization
OH
2
Y
the aromatized pyridine-fused phosphole 3aj. The benA L
1
zene ring also worked well as the two-carbon tether, and
δ+
the targeted highly condensed 3al, 3am, and 3an were
δ+
P
P
R P
R
R
obtained in good yields. The electronically diverse ar+
+
–
H
–
H
+
δ
X
X
X
ylphosphinic acids 1b and 1c could also be coupled with
Y
C
3
B
Y
Y
2a to deliver the corresponding 3ba and 3ca in 69% and
72% yields, respectively. Moreover, the aliphatic phosWe selected phenylphosphinic acid (1a) and the arphinic acid was employed with good efficiency (3da). On
ylalkyne 2a as model substrates and started optimization
the other hand, the alkene substrate instead of the alkyne
studies to identify the suitable conditions including the dedid not provide the targeted cyclization product (see the
hydrating reagent, Lewis base, and solvent. After extenSupporting Information for details).
Scheme 3. Phosphenium-Dication-Mediated Sequential C–C/C–P Bond Formation of Arylalkynes 2 with Phosphinic Acids 1a
a) Double C–P bond formation from (hetero)biaryls
δ+

O
OH
P
R
H
1
• scope of arylalkynes

O

Tf2O/2,6-lutidine

+
X

R

DCE, 60 or 90 ˚C, 16 h

X

2

Y

MeO

P
3

Y

F3C
Me

O
Ph

O
O

P

Ph

O

P

Ph

Ph

P

O

P

3ad 90%

3aa 90% (70%)b

3ab 67%

Me

O

P

Ph

Ph

P

3ae 66%

3ac 74%

3af 81%

S
O
Ph

O
P

Ph

O

P

Ph
O
3ah 79%

3ag 66%

O

P

+ Ph
O

O
P

O
3ai + 3ai’ 81% (7:3)c

MeO

O
Ph

O
P
O

Ph

O

P

Ph

O

P

Ph

3am 52%

from
N
Ts

N

O

P

O
n-C8H17

R
3al 53%

P

3aj 52%d
• scope of phosphinic acids

P

O
3ak 35%

Ph

3an 53%e

a

R = MeO: 3ba 69%
R = CF3: 3ca 72%

2j

P

3da 70%

Reaction conditions: 1 (0.20 mmol), 2 (0.10 mmol), Tf2O (0.48 mmol), 2,6-lutidine (0.48 mmol), DCE (1.5 mL), 60 or
90 ˚C, 16 h. Isolated yields are shown. b On a 1.0 mmol scale. c Obtained as a 7:3 mixture of regioisomers. d With
additional treatment with KOH in MeOH. See the Supporting Information for details. e On a 0.20 mmol scale in toluene.
Additionally notable is that the conjugated 1,3-diyne 2o
cyclization product 3cs (Scheme 4e). This is probably bewas readily converted to the phosphole derivative 3ao by
cause of the acid-mediated aryl ring 1,2-migration after
the sequential two C–P and two C–C bond formations in
the first cyclization event, a similar process of which is freone synthetic operation (Scheme 4a). The phospheniumquently found in the acid-promoted Scholl reaction of the
dication-promoted strategy was also applied to the double
condensed aromatic compounds.10 The structure was ficyclization reaction of the dialkynylnaphthalenes 2p and
nally determined by the crystallographic analysis after the
2q (Scheme 4b and c). In these cases, four C–P and two
conversion of P=O to P=S (anti-3cs-S; CCDC 2231651).
C–C bonds were successively formed to deliver the corNotably, in Schemes 4b–e, the use of CF3-containing
responding octa- and decacyclic systems 3cp and 3cq
phosphinic acid 1c was critical to success: with simple
with two phosphole rings. The structure of syn-3cq was
phenyl-substituted 1a, the reaction stopped after the sinconfirmed by X-ray analysis (CCDC 2210187). Moreover,
gle cyclization. ...

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