Highly chemo- and regioselective C-P cross-coupling reaction of quinone imine ketals with Ar2P(O)H to construct: Ortho -amino triarylphosphine derivatives

Article abstract of DOI:10.1039/c9gc00989b

A highly chemo- and regioselective approach for the construction of ortho-amino triarylphosphine oxides has been achieved through a C-P cross-coupling reaction involving quinone imine ketals (QIKs) with Ar₂P(O)H and catalyzed via a Lewis base. This alternative protocol provided a wide substrate scope with excellent yields (82-95%), and a variety of ortho-amino triarylphosphines were obtained with high yields (87-95%) via further reductive reaction. Furthermore, this reaction could be scaled-up and several synthetic transformations were accomplished for the construction of functionalized organophosphorus.

Full text of DOI:10.1039/c9gc00989b

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DOI: 10.1039/C9GC00989B
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Highly Chemo- and Regioselective C-P Cross-coupling reaction of
Quinone Imine Ketals with Ar2P(O)H to Construct Ortho-amino
Triarylphosphine Derivatives
Received 00th January 20xx,
Accepted 00th January 20xx
Teng Liu,†* Yongqin Li,† Feixiang Cheng,† Xianfu Shen,† Jianjun Liu,† Jun Lin‡*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A highly chemo- and regioselective approach for the construction of ortho-amino triarylphosphine oxides has been
achieved through a C-P cross-coupling reaction involving quinone imine ketals (QIKs) with Ar2P(O)H and catalyzed via Lewis
base. The alternative protocol provided a wide substrate scope with excellent yields (82-95%), and a variety of ortho-
amino triarylphosphines were obtained with high yields (87-95%) via further reductive reaction. Furthermore, the reaction
could be scaled-up and several synthetic transformations were accomplished for the construction of functionalized
organophosphorus.
synthesis of structurally diverse ortho-amino substituted
triaryphosphine oxides and their derivatives is still highly
desired. In addition, the development of such a strategy will
significantly expand the site-selectivity of quinone imine ketals
(QIKs), yet remains a formidable challenge.
Introduction
Triarylphosphine oxides and their derivatives are one of the
most important classes of phosphorus-containing compounds
due to their widespread application in organic synthesis1 and
materials science.2 Because of their unique intrinsic properties,
ortho-amino substituted triaryphosphine oxides and their
derivatives play an important role in organic transformation as
catalysts or ligands.3 In recent years, the general strategies to
access such molecular architectures involved: (i) P-arylation of
diarylphosphine with ortho-haloanilides via C-X (X = Cl, Br, I)
cleavage (Scheme 1. Route 1);4 (ii) C-H amidation of
arylphosphoryl catalyzed by transition metals (Scheme 1.
Route 2);5 (iii) Pd-catalyzed Buchwald-Hartwig amination of
ortho-bromofluorobenzene, and subsequent phosphorylative
reaction (Scheme 1. Route 3);6 (iv) benzyne-inserting reaction,
which synchronously constructs C-P and C-N bonds (Scheme 1.
Route 4).7 However, despite these advances, the afore-
mentioned methods frequently require transition-metal
catalysis,4d,5,6 toxic and hazardous reagents,4a-4c and rigorous
reaction conditions.7 To the best of our knowledge, the direct
R1
R2
P(O)Ar2
(ii) Route 2
N
(i) Route 1
R1
R2
X
N
C-N Coupling
C-X Cleavage
P(O)Ar2
X = Cl, Br, I
F
OTf
(iv) Route 4
(iii) Route 3
ortho-amino triary
phosphine oxides
Benzyne-Inserting
reaction
Buchwald-Hartwig
reaction
TMS
Br
Scheme 1 The general strategies to construct ortho-amino
triaryphosphine oxides.
Quinone imine ketals (QIKs),9 are versatile and powerful
synthons, which are always utilized as electrophilic aryl group
surrogates in organic synthesis due to their intrinsic properties
of multiple reactive sites (N, C1, C2 and C3) (Scheme 2, a).10
Until now, the pioneering works to control the chemo- and
regioselective of QIKs have proved to be challenging.9c Indeed,
the C3-site9h-9j,9l of the QIKs as a nucleophile has been well
developed compared to the C1-site9a,9e and C2-site9c,9d,9j of the
QIKs, including our recent work9n (Scheme 2, b). To our
C-P cross-coupling reaction is one of the most important knowledge, the site-selectivity of C-P cross-coupling procedure
approaches for the preparation of arylphosphines.8 A new
version of C-P cross-coupling strategies that allow the efficient
of QIKs with Ar2P(O)H has not been realized, which would
enable the construction of a bidentate ligand containing
simultaneously a soft (phosphorus) and a hard (nitrogen)
coordination centers, holding promising potential for creation
on the basis of unique complexes with Pt, Pd, Rh, and other
metals.11 Additionally, to continue our interest in studying the
chemo- and regioselectivity of QIKs9n and the reaction of C-X (X
= N, O, S, and P) bond formation,12 this study describes a
†
Center for Yunnan-Guizhou Plateau Chemical Functional Materials and Pollution
Control, Qujing Normal University, Qujing, 655011, P. R. China.
E-mail:15288404381@163.com
‡
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of
Education and Yunnan Province, School of Chemical Science and Technology, Lewis-base promoted highly selective C-P cross-coupling
Yunnan University, Kunming, 650091, P. R. China. Fax: +86 871 65031633; Tel: +86
871 65031633;
E-mail:linjun@ynu.edu.cn
†Electronic Supplementary Information (ESI) available: CCDC 1903624, 1903625,
1903626.For ESIand crystallographic data in CIF or other electronic format see
DOI: 10.1039/x0xx00000x
reaction of QIKs with Ar2P(O)H that assembled the ortho-
amino substituted triaryphosphine oxides or triaryphosphines
(Scheme 2, c).
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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(a) Structural features substrate 1a and computed electrostatic potential map (EPM)
View Article Online
Ts
O
O
Ts
DOI: 10.1039/CN9HGC00989B
NH
O
P
S
MeO
MeO
O
N
Me
P
C1
C3 C2
Model substrate 1a
OMe
OMe
3aa
4
Energy= -366.17041684 eV
Energy= -366.38113289 eV
Negative
-5e-2
C2-site Favored
C3-site Unfavored
Scheme 3 Computational-aided analysis of the product energy
satisfactory yield. Notably, the C3-site product 4 was not detected
in any of the cases (Table 1, entries 1-5). The relative configuration
of 3aa was determined by X-ray crystal analysis in Scheme 4 (CCDC
1903624). Furthermore, computational-aided analysis showed that
the energy for the formation of product 3aa was lower than that for
product 4, which indicated that the reaction was more beneficial to
occur on C2-site of QIKs (Scheme 3)13. Additionally, the reaction
could proceed smoothly without any catalyst, and produced the
desired product 3aa with 65% yield. Furthermore, the reductive
product 5 of the raw material 1a was obtained at 22% yield (Table 1,
entry 6). Subsequently, several other solvents were tested. Even
though H2O could be used as solvent to promote this reaction, poor
solubility led to an unsatisfactory yield of the product 3aa. To
improve the solubility of reactants, mixed solvents (EtOH/H2O)
were further investigated. The mixed solvents (EtOH/H2O, 2:1, v-v)
as medium could offer the same excellent yield (Table 1, entry 13).
Increasing or lowering the temperature did not improve the yield of
3aa (Table 1, entries 15-16). Ultimately, it was determined that the
optimal conditions of this reaction were 20 mol% Cs2CO3 at 50 °C in
mixed solvents (EtOH/H2O, 2:1, v-v), affording 3aa with a 89% yield
(Table 1, entry 13).
5e-2 Positive
(b) Challenges of QIKs: chemo- and regioselective
R1
NHR1
NHR1
R1HN
R2
N
C1
Nu
Nu
R2
R2
C2
C3
R2
conditions
+
+
NuH
+
Nu
R3O OR3
R3O OR3
OR3
OR3
QIKs
C2-site
C1-site
C3-site
(c) This work:
R1
R1
R1
N
NH
NH
Ar(Het)
O
O
P
P
Ar(Het)
P
R2
Lewis-Base
R2
R2
R3O OR3
+
H
(Het)Ar
Ar(Het)
Ar(Het)
Mild condtions
Ar(Het)
OR3
OR3
16 examples
C2-site
30 examples
82-95% yields
87-95% yields
Mild reaction conditions
Excellent substrate scope
High chemo- and regioselective
High yields and gram scales
Scheme
regioselectivity.
2 Selective challenges of QIKs: chemo- and
Results and discussion
Having established the optimal reaction conditions, the substrate
scope of quinone imine ketals (QIKs) 1 were investigated to
examine the feasibility of this method. Firstly, the N-protected
group could be altered from Ts to Bz with 83% yield (Scheme 4,
3ab). Substitution the para-position of the aromatic ring with either
an electron-donating group (MeO, Ph) or an electron-withdrawing
Initially, the C-P cross-coupling reaction is commenced with
quinone imine ketal (QIK) 1a and secondary phosphine oxide 2a as
coupling partners in EtOH. Both acid and base catalysts could
promote this reaction, and provided the C2-site product 3aa at
Table 1 Optimization of the reaction conditionsa
Ts
Ts
Ts
Ts
NH
N
NH
Scheme 4 Substrate scope of the reaction 3aa-3ava
O
P
NH
O
P
H
C2
C3
O
P
Catalyst (20 mol%)
Solvent, 50 oC, 10 h
+
R1
+
R1
NH
O
P
N
O
P
MeO OMe
OMe
OMe
H
OMe
5
Cs2CO3 (20 mol%)
R2
+
R2
R3
1a
2a
3aa
4
EtOH/H2O (2:1, v-v)
50 oC, 8-12 h
OR3
OR3
O
Entry
Catalystb
Solvent
3aa (%)b 5 (%)b
2a
3aa-3av
1
O
O
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15c
16d
HOAc
PPh3
Na2CO3
K2CO3
Cs2CO3
─
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
MeOH
EtOAc
THF
75
70
S
NHTs
OMe
NHBz
OMe
3ac
3ad
3ae
3af
3ag
3ah
, R = OMe, 90%
, R = Ph, 84%
, R = Cl, 85%
, R = Br, 87%
, R = CF3, 82%
, R = NO2, 91%
NH
O
P
O
O
P
R
P
65
86
89
65
89
85
40
82
35
75
89
89
72
88
─
OMe
3aa
3ab
3ac-3ah
, 89%
3aa
, 83%
(CCDC 1903624)
─
22
O
S
O
NH
O
O
O
O
S
S
Alkyl
NH
NH
O
P
O
O
P
S
P
3ak
3al
3am
, Alkyl = Et, 89%
, Alkyl = n-Bu, 92%
, Alkyl = Bn, 87%
─
─
─
─
─
─
─
─
─
OMe
OMe
OMe
3ai
3aj
3ak-3am
, 88%
, 91%
Toluene
H2O
EtOH/H2O (1:1,v-v)
EtOH/H2O (2:1,v-v)
EtOH/H2O (3:1,v-v)
EtOH/H2O (2:1,v-v)
EtOH/H2O (2:1,v-v)
NHTs
NHTs
NHTs
OMe
O
P
O
P
O
Me
P
Me
MeO
OMe
OMe
3an
3ao
3ap
, 95%
, 91%
, 94%
3ap (CCDC 1903625)
NHTs
OMe
NHTs
NHTs
O
NHTs
O
P
O
P
O
P
P
3aq
3ar
3as
, R = Cl, 90%
, R = Br, 88%
, R = I, 85%
R
OEt
3au
OiPr
OMe
aThe reaction was performed with 1a (0.1 mmol), 2a (0.11 mmol),
and catalyst (20 mol%) in the solvent (2.0 mL). bIsolated yield based
on 1a. cThe reaction temperature was 30 oC. dThe reaction
temperature was 70 oC.
3aq-3as
3at
3av
, 94%
, 92%
,
91%
aAll reactions were performed with QIKs 1 (0.1 mmol), 2a (0.11
mmol), and Cs2CO3 (20 mol%) in EtOH/H2O (2:1, v-v) 2.0 mL, and
isolated yield based on 1.
2 | J. Name., 2012, 00, 1-3
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group (Cl, Br, CF3, and NO2), offered the desired products in 82-91%
yields (Scheme 4, 3ac-3ah). In addition, -naphthylsulfonyl, 2-
thienylsulfonyl, and aliphaticsulfonyl substituted of R1 proved to be
suitable substrates in the transformation, and delivered the
corresponding products with satisfactorily yields 87-92% (Scheme 4,
3ai-3am). Furthermore, the substrate scope of quinone imine ketals
(QIKs) was broadened, bearing electron–rich or –poor substituents
of R2 (2-Me, 3-Me, 3-OMe, 3-Cl, 3-Br, 3-I), which led to an increase
of the yield of corresponding products of up to 95% (Scheme 4, 3an-
3at). When the alkoxyl group OR3 was elongated to OEt and OiPr,
the desired products were obtained with 91% and 94% yields,
respectively (Scheme 4, 3au-3av).
Scheme 6 Synthesis of ortho-amino triarylphosphines
View Article Online
DOI: 10.1039/C9GC00989B
R3
Ts
Ts
Het
NH
NH
R3
O
P
Het
R3
R1
P
HSiCl3/Et3N
R1
toluene, 100 oC, N2
2-6 h
Het
Het
OR2
OR2
R3
3
6a-6p
Ts
Ts
Ts
NH
NH
NH
, R1 = Me, 93%
6e
6f
, R2 = Me, 92%
Me
, R1 = OMe, 95%
6a
6b
6c
P
P
P
, R2 = Et, 90%
2
, R1 = Cl, 91%
6g
R1
iPr, 91%
6h, R1 = I, 88%
, R
=
OR2
6a 6c
OMe
6d
, 94%
OMe
6e 6h
-
-
Me
Me
Ts
Me
Ts
Ts
Ts
NH
Me
NH
NH
NH
Then, the compatibility of this reaction protocol with various
secondary phosphine oxides 2 were examined (Scheme 5). The
substitution of the para/meta-position of the aromatic ring with the
electron-donating group (3-Me, 4-Me) or the electron-with drawing
group (4-F, 4-Cl, 4-CF3), and even the sterically hindered group in
aromatic ring (3,5-(Me)2, 3-F-5-Me), could provide the
corresponding products at 83-93% yields, respectively (Scheme 5,
3ba-3bg). Notably, diheteroarylphosphine oxide was also well
tolerated during this transformation, providing a desired product
3bh with satisfactory yield.
P
P
P
P
Me
Me
OMe
OMe
OMe
OMe
Me
6l
, 87%
Me
F
6i
, 90%
6j
6k
, 92%
, 93%
Me
Cl
Ts
Ts
Ts
Ts
F
NH
NH
NH
S
NH
P
P
P
P
S
Me
OMe
OMe
OMe
6n
OMe
F
Cl
F
6m
, 92%
6o
, 91%
, 90%
6p
, 85%
aAll reactions were performed with 3 (0.05 mmol), HSiCl3 (0.5
mmol), and Et3N (1.0 mmol) in toluene 2.0 mL, and isolated yield
based on 3.
Scheme 5. Substrate scope of the reaction 3ba-3bha
Ts
Ts
NH
R
N
O
P
R
O
P
assembled ortho-amino and meta-hydroxyl in the aromatic ring
with 72% yield. Subsequently, trifluoromethanesulfonylation of
compound 7 gained the intermediate 8, which was then well
tolerated with Pd/C-Mg reduction at a 92% yield and produced
product 9. Finally, compound 9 was reduced to ortho-amino
triphenylphosphine 10 at 88% yield under HSiCl3/Et3N in toluene at
100 oC.
H
Het
Cs2CO3 (20 mol%)
+
EtOH/H2O (2:1, v-v)
50 oC, 8-12 h
R
R
Het
MeO OMe
OMe
1a
2
3ba-3bh
Ts
Ts
Ts
Ts
NH
Me
Me
NH
NH
NH
O
P
O
P
O
P
O
P
R
Me
3bd
3be
3bf
, R = F, 93%
, R = Cl, 91%
, R = CF3, 90%
Me
OMe
OMe
OMe
Me
OMe
3bb
Me
Me
R
Me
3ba
Ts
3bc
3bd-3bf
Ts
, 91%
Ts
, 86%
, 92%
Ts
N
NH
O
P
NH
O
P
H
HSiCl3/Et3N
toluene, 100 oC, N2
Cs2CO3 (20 mol%)
Ts
(a)
P
F
+
NH
NH
O
P
EtOH/H2O (2:1, v-v)
50 oC, 8 h
O
P
S
MeO OMe
1a
OMe
OMe
2a
2.2 mmol, 0.445 g
3aa
6a
Me
S
OMe
Me
2.0 mmol, 0.614 g
0.840 g, 88% yield
0.738 g, 91% yield
OMe
F
3bg
3bh,
3bh (CCDC 1903626)
83%
90%
Ts
Ts
Ts
NH
NH
OH
NH
aAll reactions were performed with QIKs 1a (0.1 mmol), 2 (0.11
mmol), and Cs2CO3 (20 mol%) in EtOH/H2O (2:1, v-v) 2.0 mL, and
isolated yield based on 1a.
O
O
P
O
P
(b)
P
BBr3, Bu4NBr
Tf2O, Pyridine
DCM, 0 oC-r.t.
72% yield
DCM, r.t.
81% yield
OMe
3aa
OTf
7
8
Considering the importance of triarylphosphines and ortho-
amino triarylphosphines in organic synthesis,3 compound 3 could be
easily converted to ortho-amino triarylphosphines via the reductive
Ts
Ts
NH
NH
O
P
P
HSiCl3/Et3
N
Mg, 10% Pd/C
toluene, 100 oC, N2
88% yield
MeOH,r.t.
92% yield
o
reaction under HSiCl3/Et3N in toluene at 100 C. A variety of ortho-
10
9
amino triarylphosphines with the potential to be bidentate ortho-
amino phosphine ligands have been achieved with 85-95% yields,
including the electron-donating/electron-withdrawing group, the
sterically hindered group in aromatic ring, and even the heterocyclic
group (Scheme 6, 6a-6p).
Scheme 7 Gram-scale reaction and further synthetic transformation.
H
O
Ts
Ts
Ts
P
Ph
Ts
N
N
N
NH
O
P
O
P
Ph
2a'
tautemerization
Cs+
2a
imine-enamine
Ph
Ph
tautemerization
binding
and
activiation
-Cs+, -MeOH
Ph
Ph
To further evaluate the utility of this approach, the gram-scale
reaction was conducted by the C-P cross-coupling procedure with
1a and 2a. The yield of 3aa remained reasonable, and the reductive
product 6a was obtained with almost identical yield (Scheme 7, a).
In addition, several synthetic transformations for the construction
of functionalized organophosphorus were achieved according to a
similar route (Scheme 7, b).7a,9l Firstly, the compound 3aa
underwent demethylation to form compound 7, which was
MeO OMe
MeO OMe
OMe
Int-B
OMe
1a
Cs+
3aa
Int-A
Scheme 8 The proposed mechanism.
Finally,
a
proposed mechanism of the reaction has been
described in Scheme 8.8j Firstly, the binding of the Cs(I) species to
1a may form an Int A to activate the C–O bond. Then, the
phosphorus atom of 2a’ (tautomer of 2a) attack the C2-site of 1a
may give an Int B with the formation of the C–P bond and the loss
This journal is © The Royal Society of Chemistry 20xx
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of one molecule of methanol. Finally, the imine-enamine
tautomerization of Int B takes place to give the product 3aa
(Scheme 8).
Acknowledgements
View Article Online
This work was supported by theDOIP: 1r0o.1g0r3a9m/C9GfCo0r098th9Be
application fundamental research of Yunnan Province (No.
2018FB019) and the National Natural Science Foundation of
China (No. 21861032).
Computational Methods ： First-principle calculations were
performed by the density functional theory (DFT) using the Vienna
Ab-initio Simulation Package (VASP) package. The generalized
gradient approximation (GGA) with the Perdew- Burke-Ernzerhof
(PBE) functional were used to describe the electronic exchange and
correlation effects. Uniform G-centered k-points meshes with a
resolution of 2π*0.03 Å-1 and Methfessel-Paxton electronic
smearing were adopted for the integration in the Brillouin zone for
geometric optimization. The simulation was run with a cutoff
energy of 500 eV throughout the computations. These settings
ensure convergence of the total energies to within 1 meV per atom.
Structure relaxation proceeded until all forces on atoms were less
than 1 meV Å -1 and the total stress tensor was within 0.01 GPa of
the target value. In addition, for the product 3aa and possible
product 4, they were formed by the same reactants (QIK 1a and
SPO 2a) and we could find that the geometries of QIK 1a and SPO
2a are basically the same before and after the reaction.
Furthermore, when SPO 2a was added to the C-site of QIK 1a, only
one phosphorus-carbon bond was formed. The bond length is 1.821
Å for C2-P bond, while 1.837 Å for C3-P bond. The shorter the bond
length, the stronger the chemical bond, resulting in the more stable
the structure and the lower energy (-366.38113289 eV VS -
366.17041684 eV). Beside, we could find the difference of degree of
spatial distortion was very small (Scheme 9).
Notes and references
1
(a) C. Bolm, F. Bienewald, A. Seger, Angew. Chem. Int. Ed.,
1996, 35, 1657; (b) J.-J. Cao, F. Zhou, J. Zhou, Angew. Chem.
Int. Ed., 2010, 49, 4976; (c) V. V. Grushin, Chem. Rev., 2004,
104, 1629; (c) L. Hong, W. Sun, D. Yang, G. Li, R. Wang, Chem.
Rev., 2016, 116, 4006; (d) X.-P. Zeng, Z.-Y. Cao, X. Wang, L.
Chen, F. Zhou, F. Zhu, C.-H. Wang, J. Zhou, J. Am. Chem. Soc.,
2016, 138, 416; (e) G. Storch, O. Trapp, Nat. Chem., 2017, 9,
179; (f) L. Wang, D. Yang, D. Li, X. Liu, P. Wang, K. Wang, H.
Zhu, L. Bai, R. Wang, Angew. Chem. Int. Ed., 2018, 57, 9088.
(a) V. Maraval, R. Laurent, P. Marchand, A.-M. Caminade, J.-P.
Majoral, J. Organomet. Chem., 2005, 690, 2458; (b) T.
Baumgartner, R. Réau, Chem. Rev., 2006, 106, 4681; (c) J. I.
Bates, J. Dugal-Tessier, D. P. Gates, Dalton Trans., 2010, 39,
3151; (d) A. M. Caminade, J. P. Majoral, J. Mater. Chem., 2005,
15, 3643; (e) M. Hissler, P. W. Dyer, R. Reau, Top. Curr. Chem.,
2005, 250, 127; (f) M. G. Hobbs, T. Baumgartner, Eur. J. Inorg.
Chem., 2007, 3611.
2
3
(a) T. Mino, Y. Tanaka, Y. Sato, A. Saito, M. Sakamoto, T. Fujita,
Tetrahedron Lett., 2003, 44, 4677; (b) T. Mino, Y. Tanaka, T.
Yabusaki, D. Okumura, M. Sakamoto, T. Fujita, Tetrahedron:
Asymmetry 2003, 14, 2503; (c) B. Jiang, Z.-G. Huang, K.-J.
Cheng, Tetrahedron: Asymmetry 2006, 17, 942; (d) T. Mino, Y.
Tanaka, Y. Hattori, T. Yabusaki, H. Saotome, M. Sakamoto, T.
Fujita, J. Org. Chem., 2006, 71, 7346; (e) M. Eggenstein, A.
Thomas, J. Theuerkauf, G. Franciò, Walter Leitnera, Adv.
Synth. Catal., 2009, 351, 725; (f) T. Mino, A. Omura, Y. Uda, K.
Wakui, Y. Haga, M. Sakamoto, T. Fujita, Tetrahedron:
Asymmetry 2011, 22, 2024; (g) N. Liu, L. Wang, Z.-X. Wang,
Chem. Commun., 2011, 47, 1598; (h) T. Mino, M. Asakawa, Y.
Shima, H. Yamada, F. Yagishita, M. Sakamoto, Tetrahedron
2015, 71, 5985; (i) I. Neogi, S. Jhulki, A. Ghosh, T. J. Chow, J. N.
Moorthy, ACS Appl. Mater. Interfaces 2015, 7, 3298; (j) T.
Mino, K. Nishikawa, M. Asano, Y. Shima, T. Ebisawa, Y.
Yoshidaa, M. Sakamoto, Org. Biomol. Chem., 2016, 14, 7509.
(a) A. Bruch, A. Ambrosius, R. Fröhlich, A. Studer, D. B.
Guthrie, H. Zhang, D. P. Curran, J. Am. Chem. Soc., 2010, 132,
11452; (b) K. Liu, X. Wu, S. B. J. Kan, S. Shirakawa, K. Maruoka,
Chem. Asian J., 2013, 8, 3214; (c) S. Shirakawa, K. Liu, K.
Maruoka, J. Am. Chem. Soc., 2012, 134, 916; (d) D. Jiang, Q.
Jiang, H. Fu, Y. Jiang, Y. Zhao, Syntheis 2008, 21, 3473; (e) Y.
Zhang, H. He, Q. Wang, Q. Cai, Tetrahedron Lett., 2016, 57,
5308.
(a) Y. Hwang, Y. Park, S. Chang, Chem. –Eur. J.,2017, 23, 11147;
(b) D. Gwon, D. Lee, J. Kim, S. Park, S. Chang, Chem. –Eur. J.,
2014, 20, 12421; (c) D. Gwon, S. Park, S. Chang, Tetrahedron
2015, 71, 4504.
(a) L.-C. Liang, W.-Y. Lee, C.-H. Hung, Inorg. Chem., 2003, 42,
5471; (b) L.-C. Liang, M.-H. Huang, C.-H. Hung, Inorg. Chem.,
2004, 43, 2166; (c) L.-C. Liang, F.-Y. Chen, M.-H. Huang, L.-C.
Cheng, C.-W. Lia, H. M. Lee, Dalton Trans., 2010, 39, 9941; (d)
M. Eggenstein, A. Thomas, J. Theuerkauf, G. Franciò, W.
Leitner, Adv. Synth. Catal., 2009, 351, 725; (e) R. Lindner, B.
van den Bosch, M. Lutz, J. N. H. Reek,J. I. van der Vlugt,
Organometallics 2011, 30, 499.
4
3aa
Scheme 9
Conclusions
In summary, a highly chemo- and regioselective approach was
established to construct ortho-amino triarylphosphine oxides
through C-P cross-coupling reaction, which involved quinone imine
ketals (QIKs) with Ar2P(O)H catalyzed by Cs2CO3. This protocol
provided an array of diverse substrates at excellent yields (82-95%),
and a variety of ortho-amino triarylphosphines were synthesized at
high yields (87-95%) via further reductive reaction. In addition, the
reaction was suitable for gram-scale and several synthetic
transformations were achieved for the construction of
functionalized organophosphorus, which would enable the
construction of bidentate ligands containing phosphorus and
nitrogen coordination centers simultaneously, thus offering
promising potential for complexes with transition metals. Further
applications of these functionalized organophosphorus are still
under investigation in our laboratory.
4
5
6
Conflicts of interest
There are no conflicts to declare.
7
(a) C. Shen, G. Yang, W. Zhang, Org. Lett., 2013, 15, 5722; (b)
C. Lopez-Leonardo, R. Raja, F. López-Ortiz, M. Á. del Águila-
Sánchez, M. Alajarin, Eur. J. Org. Chem., 2014, 1084; (c) M. Á.
4 | J. Name., 2012, 00, 1-3
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Green Chemistry
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Journal Name
COMMUNICATION
del Águila-Sánchez, Y. Navarro, J. G. López, G. P. Guedes, F. L.
Ortiz, Dalton Trans., 2016, 45, 2008.
View Article Online
DOI: 10.1039/C9GC00989B
8
(a) A. L. Schwan, Chem. Soc. Rev., 2004, 33, 218; (b) Q. Xu, L.-
B. Han, J. Organomet. Chem., 2011, 696, 130; (c) J. L.
Montchamp, Acc. Chem. Res., 2014, 47, 77; (d) J. Genet, I.
Wauters, W. Debrouwer, C. V. Stevens, Beilstein J. Org.
Chem., 2014, 10, 1064; (f) M. Dutartre, J. Bayardon, S. Jugé,
Chem. Soc. Rev., 2016, 45, 5771; (g) C. A. Bange and R.
Waterman, Chem. – Eur. J., 2016, 22, 12598; (h) R. Shen, M.
Zhang, J. Xiao, C. Dong, L.-B. Han, Green Chem., 2018, 20,
5111; (i) F. M. J. Tappe, V. T. Trepohl, M. Oestreich, Synthesis
2010, 18, 3037; (j) M. Zhang, X. Jia, H. Zhu, X. Fang, C. Ji, S.
Zhao, L.-B. Han, R. Shen, Org. Biomol. Chem., 2019, 17, 2972.
(a) C.-P. Chen, C.-T. Chou, J. S. Swenton, J. Am. Chem. Soc.,
1987, 109, 946; (b) J. S. Swenton, B. R. Bonke, W. M. Clark, C.-
P. Chen, K. V. Martin, J. Org. Chem., 1990, 55, 2027; (c) P.
Dalidowicz, J. S. Swenton, J. Org. Chem., 1993, 58, 4802; (d) S.
C. Banfield, D. B.; England, M. A. Kerr, Org. Lett., 2001, 3,
3325; (e) K. V. Chuang, R. Navarro, S. E. Reisman, Chem. Sci.,
2011, 2, 1086; (f) T. Dohi, Y. Hu, T. Kamitanaka, N. Washimi, Y.
Kita, Org. Lett., 2011, 13, 4814; (g) Y. Hu, T. Kamitanaka, Y.
Mishima, T. Dohi, Y. Kita, J. Org. Chem., 2013, 78, 5530; (h) T.
Hashimoto, H. Nakatsu, Y. Takiguchi, K. Maruoka, J. Am. Chem.
Soc., 2013, 135, 16010; (i) Y.-C. Zhang, F. Jiang, S.-L. Wang, F.
Shi, S.-J. Tu, J. Org. Chem., 2014, 79, 6143; (j) Y.-C. Zhang, J.-J.
Zhao, F. Jiang, S.-B. Sun, F. Shi, Angew. Chem. Int. Ed., 2014,
53, 13912; (k) C. Shu, L.-H. Liao, Y.-J. Liao, X.-Y. Hu, Y.-H.
Zhang, W.-C. Yuan, X.-M. Zhang, Eur. J. Org. Chem., 2014,
4467; (l) F. Jiang, Y.-C. Zhang, S.-B. Sun, L.-J. Zhou, F. Shi, Adv.
Synth. Catal., 2015, 357, 1283; (m) Liu, L.; Chen, K.; Wu, W.-Z.;
Wang, P.-F.; Song, H.-Y.; Sun, H.; Wen, X.; Xu, Q.-L. Org. Lett.,
2017, 19, 3823; (n) T. Liu, J. Liu, X. Shen, J. Xu, B. Nian, N. He,
S. Zeng, F. Cheng, Synthesis 2019, 51, 1365.
9
10 Computational Methods ： Geometry optimizations and ESP
calculations on the ground-state potential energy surfaces
have been performed by density functional theory (DFT)
approach with the 6-31G basis set. The Becke’s three-
parameter hybrid exchange functional and the Lee-Yang-Parr
correlation functional (B3LYP) implemented in the GAUSSIAN
03 package have been used in the DFT calculation.
11 For some selected examples (a) N. J. S. Costa, P. K. Kiyohara,
A. L. Monteiro, Y. Coppel, K. Philippot, L. M. Rossi, J. Catal.,
2010, 276, 382; (b) F. Lorenzini, B. O. Patrick, B. R. James,
Inorg. Chim. Acta 2008, 361, 3199; (c) L.-C. Liang, F.-Y. Chen,
M.-H. Huang, L.-C. Cheng, C.-W. Li, H. M. Lee, Dalton Trans.,
2010, 39, 9941; (d) N. Liu, L. Wang, Z.-X. Wang, Chem.
Commun., 2011, 47, 1598; (e) R. Lindner, B. van den Bosch, M.
Lutz, J. N. H. Reek, J. I. van der Vlugt, Organometallics 2011,
30, 499; (f) A. O. Tolpygin, T. A. Glukhova, A. V. Cherkasov, G.
K. Fukin, D. V. Aleksanyan, D. Cui, A. A. Trifonov, Dalton Trans.,
2015, 44, 16465; (g) A. O. Tolpygin, O. A. Linnikova, T. A.
Glukhova, A. V. Cherkasov, G. K. Fukin, A. A. Trifonov, RSC
Adv., 2016, 6, 17913; (h) N. Y. Rad’kova, A. O. Tolpygin, V. Y.
Rad’kov, N. M. Khamaletdinova, A. V. Cherkasov, G. K. Fukin,
A. A. Trifonov, Dalton Trans., 2016, 45, 18572.
12 T. Liu, J. Liu, S. Xia, J. Meng, X. Shen, X. Zhu, W. Chen, C. Sun, F.
Cheng, ACS Omega 2018, 3, 1409.
This journal is © The Royal Society of Chemistry 20xx
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Green Chemistry
Page 6 of 6
View Article Online
DOI: 10.1039/C9GC00989B
TOC Graphic
Highly Chemo- and Regioselective C-P Cross-coupling
reaction of Quinone Imine Ketals with Ar2P(O)H to
Construct Ortho-amino Triarylphosphine Derivatives
Teng Liu,†* Yongqin Li,† Feixiang Cheng,† Xianfu Shen,† Jianjun Liu,† Jun Lin‡*
The first highly chemo- and regioselective C-P cross-coupling reaction of
quinoneimine
ketals
with
Ar2P(O)H
to
construct
ortho-amino
triarylphosphinederivatives strategy has been developed. The reaction could be
scaled-up and several synthetic transformations were accomplished for the
construction of functionalized organophosphorus.
R1
R1
R1
NH
NH
N
Ar(Het)
Ar(Het)
O
P
O
P
Cs2CO3 (20 mol%), 50 o
C
HSiCl3/Et3N
Ar(Het)
P
R2
R2
R2
R3O OR3
(Het)Ar
H
+
EtOH/H2O (2:1, v-v)
Toluene, 100 oC, N2
Ar(Het)
Ar(Het)
OR3
C2-site
OR3
30 examples
16 examples
82-95% yields
87-95% yields
Mild reaction conditions
High yields and gram scales
Excellent substrate scope
High chemo- and regioselective