Tetraarylphosphonium inner-salts (TAPIS) as both Lewis base catalyst and phase tag

Article abstract of DOI:10.1016/j.tetlet.2017.06.015

Tetraarylphosphonium inner-salts (TAPIS) have been designed, synthesized and verified as recyclable and reusable Lewis base catalysts. The resulted TAPIS catalyst has been successfully applied in Michael addition, cyanation and trifluoromethylation reactions.

Full text of DOI:10.1016/j.tetlet.2017.06.015

Accepted Manuscript
Tetraarylphosphonium Inner-Salts (TAPIS) as Both Lewis Base Catalyst and
Phase Tag
Shuhui Guo, Xueling Mi
PII:
S0040-4039(17)30725-6
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.06.015
TETL 49007
Reference:
Tetrahedron Letters
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Revised Date:
Accepted Date:
28 April 2017
1 June 2017
2 June 2017
Please cite this article as: Guo, S., Mi, X., Tetraarylphosphonium Inner-Salts (TAPIS) as Both Lewis Base Catalyst
and Phase Tag, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.06.015
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Tetraarylphosphonium Inner-Salts (TAPIS)
as both Lewis Base Catalyst and Phase Tag
Leave this area blank for abstract info.
Shuhui Guo and Xueling Mi*

1
Tetrahedron Letters
jo u r n a l h o m e p a g e : w w w . e ls e v i e r . c o m
Tetraarylphosphonium Inner-Salts (TAPIS) as Both Lewis Base Catalyst and
Phase Tag
Shuhui Guoa and Xueling Mia, 
aCollege of Chemistry, Beijing Normal University, Xinjiekouwai Street 19, Beijing, 100875, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Tetraarylphosphonium inner-salts (TAPIS) have been designed, synthesized and verified as
recyclable and reusable Lewis base catalysts. The resulted TAPIS catalyst has been successfully
applied in Michael addition, cyanation and trifluoromethylation reactions.
2009 Elsevier Ltd. All rights reserved.
Available online
Keywords:
Inner Salts
Tetraarylphosphonium
Michael Addtion
Recycle and reuse
Phosphonium salts are versatile compounds that have been
used as phase transfer catalysts,1 organic reagents,2 ionic liquids3
and other applications.4 Tetraarylphosphonium salts (TAPS) with
the formular [Ar1(Ar2)3P+]X- can be readily prepared by coupling
reactions of an aryl halide (Ar1-X) and a triarylphosphine
((Ar2)3P.5 Unlike its alkyl derivatives as well as ammonium
counterparts, tetrarylphosphoniums (TAPs) are rather stable salts
that can be readily modified and functionalized. In addition, the
ionic nature also makes possible tunable solubility and hence
facile phase separation with TAPs.6 Capitalized on these
intriguing properties, we aim to explore tetrarylphosphonium
(TAP) moiety as functional building block for the design of new
organocatalysts, meanwhile as phase tags to facilitate catalyst
recovery and reuse.7 Previously, the use of teraarylphosphoniums
has been reported for supported organic synthesis and phase
transfer catalysis.8 Herein, we reported a structurally simple and
powerful tool for synthesis of functionalized organic molecules.10
Within this process, the addition of 1,3-dicarbonyl compounds to
nitroalkenes has attracted particular interest due to the reactivity
of the resulting nitrocarbonyl adducts.11 Therefore, explorative
research of catalytic activity and recyclability of TAPIS is carried
out on this type of catalytic Michael transformation.
distinctive tetraarylphosphonium inner-salt (TAPIS) as
recoverable and reusable Lewis base catalyst (Figure 1).
a
The TAPIS catalyst could be readily prepared by Ni-catalyzed
phosphonium formation from triphenylphosphine and phenols,
following by a simple treatment with NaOH (Figure 1).9 The
zwitter ionic TAPIS were obtained as viscous syrup or powder
solid. The x-ray structure of TAPIS C6 verified the zwitter ionic
structure feature. These TAPIS compounds are generally well
soluble in polar solvents, but less soluble in non-polar solvents
such as ether or hexane, which can meet the requirements of
biphasic application.
Figure 1. The TAP catalytic strategy and the synthesis of TAPIS
catalyst.
The Michael addition reaction is one of the fundamental bond-
forming process in organic chemistry and is an extremely
———
 Corresponding author. e-mail: xlmi@bnu.edu.cn

2
Tetrahedron
The biphasic properties TAPIS catalysis was then examined in
a model Michael addition reaction (Table 2). TAPIS C6 could be
readily recycled by precipitation with diethyl ether. Recycled
TAPIS C6 was directly used in the next run and demonstrated
comparable activities (Table 2, entries 1-3). Loss of activity was
observed since the fourth use of C6, but good activities could still
be achieved (Table 2, entries 4-6).
Table 1. Scope of nitroalkenes.a
Figure 2. Catalytic evaluation of TAPISs in the Michael addition.
The obtained TAPIS was then tested in the reaction of
acetoacetate and nitrostyrene (Figure 2). The reaction proceeded
smoothly in the presence of 10 mol% TAPIS to give the desired
adduct at room temperature. In comparison, the parent phenols
C1-C3 showed no activity in the reactions, verifying the Lewis
base properties of the inner salts. Among the isomeric zwitterions
examined, the para-isomer C6 showed much better activity than
its ortho-isomer C4 and meta-isomer C5. With C6, the reaction
gave 87% isolated yield in 1 h. The loading of C6 could be
reduced to 1 mol%, maintaining reasonable yield (24 h, 65%
yield). The spacing of the charge moiety seems to be critical and
the use of naphthalene bridged TAPIS C8 led to poor activity (24
h, 72% yield). The TAPIS catalysis could be further applied in
the cyanation reaction with TMSCN.12 In the presence of 10
mol% C6, the cyanation reaction with chalcone 4 occurred
selectivity to form the conjugate addition product 6 in 87% yield.
In the trifluoromethylation reaction with TMSCF3, the reaction
afforded selectively 1,2-adduct 8 in 53% yield. The cyanation
reaction with nitrostyrene has also been examined, and the
reaction afforded a dicyantion adduct 9 in 53% yield with one
equivalent of TAPIS C6. In this case, C6 also served as a base to
promote the elimination of nitro group.13
O
CN
O
C6 (10% mol)
+
TMSCN
Ph
Ph
Ph
Ph
DMF, rt, 1 d
6
5
4
87% yield
1.0 eq.
2.2 eq.
O
TMSO CF3
C6 (10% mol)
+
TMSCF3
Ph
Ph
Ph
Ph
MeCN, rt, 24 h
4
7
8
1.0 eq.
2.2 eq.
53% yield
CN
C6 (1.0 eq.)
NO2
a All reactions were carried out in a 0.2 mmol scale using C6 as catalyst at
room temperature for 1 h.
CN
+
TMSCN
Ph
Ph
MeCN, rt, 2 h
7
1a
1.0 eq.
9
2.0 eq.
56% yield
Figure 3. Lewis base catalysis of TAPIS C6 in other reactions.
Mechanistically, the TAPIS catalysis in the conjugate
additions reactions follows a typical Lewis base pathway,
wherein the TAPIS-stabilized enolate as the key intermediate.
The lower activity of ortho-TAPIS C4 over its meta- and para
isomers (C5 and C6) could be explained by its reduced basicity
as a result of a combined steric and close ion-pair effect.
The applicability of the TAPIS catalysis was further tested in
the Michael addition to nitrostyrenes using 10 mol% of C6
(Table 1). Nitrostyrenes bearing either electron-donating
substituents or electron-withdrawing substituents at the ortho,
meta or para position were tolerated with excellent yields,
although diastereoselectivities of these reactions were generally
moderate (3b-3s). The reactions proceeded very well with
Michael acceptors bearing other aromatic rings, such as
thiophene (3l) and naphthalene (3r). Alkyl nitroalkenes have also
been examined, showing unfortunately much lower activity. The
reaction also worked well with 1,3-diketone (3t), cyclic ketoester
(3u) and malononitrile (3v).
In conclusion, we have developed
a novel type of
tetraarylphosphonium inner-salts Lewis base catalyst.
Tetraarylphosphonium inner salt backbone can not only act as a

3
3. Wittig olefination: (a) Rein, T.; Pederson, T. M. Synthesis 2002, 579-
594; (b) Hoffmann, R. W. Angew. Chem. Int. Ed. 2001, 40, 1411-1416;
Lewis base catalytic moiety, but also as phase tag to facilitate
recycling and reuse of the catalyst. The explorations of chiral
tetraarylphosphonium salts in asymmetric catalysis are currently
underway in our laboratory.
(c) Cristau, H. –J. Chem. Rev. 1994, 94, 1299-1313; (d) Maryanoff, B. E.;
Reitz, A. B. Chem. Rev. 1989, 89, 863-927; (e) Maercker, A. Org. React.
1965, 14, 270. (f) Castro, B. R. Org. React. 1983, 29, 1.
4. Selected review on ionic liquid: (a) Dupont, J.; de Souza, R. F.; Suarez, P.
A. Z. Chem. Rev. 2002, 102, 3667-3692; (b) Tzschucke, C. C.; Markert,
C.; Roller, S.; Hebel, A.; Haag, R.; Bannwarth, W. Angew. Chem. Int. Ed.
2002, 41, 3964-4000; (c) Wasserscheid, P.; Keim, W. Angew. Chem. Int.
Ed. 2000, 39, 3772-3789.
5. (a) Kim Y.; Gabbaϊ, F. P. J. Am. Chem. Soc. 2009, 131, 3363-3369; (b)
Werner, T. Adv. Synth. Catal. 2009, 351, 1469-1481; (c) Moritz, R.;
Wagner, M.; Schollmeyer, D.; Baumgarten, M. Chem.-Eur. J. 2015, 21,
9119-9125; (d) Deng, Z.; Lin, J.-H.; Xiao, J.-C. Nat. Commun. 2016, 7,
10337; (e) Akutsu, H.; Yamada, J. –I.; Nakatsuji, S. Chem. Lett. 2003, 32,
1118; (f) Akutsu, H.; Yamada, J. –I.; Nakatsuji, S. Chem. Lett. 2001, 29,
208; (g) Akutsu, H.; Yamada, J. –I.; Nakatsuji, S. Synth. Met. 2001, 120,
871; (h) Beck, P. In Organic Phosphorus Compounds; Kosolapoff, G. M.;
Maier, L. Eds.; Wiley-Interscience: New York, 1972; Vol. 2, and
references cited therein.
O
O
OEt
NO2
H3CO
H3CO
O
O
H3CO
H3CO
NO2
C6 (10 mol%)
+
OEt
rt, 1 h
OCH3
OCH3
2
1s
3s
Table 2. Recycling studies for the Micheal reaction of 1s and
ethyl acetoacetate.a
6. (a) Marcoux, D.; Charette, A. B. J. Org. Chem. 2008, 73, 590-593; (b)
Marcoux, D.; Charette, A. B. Adv. Synth. Catal. 2008, 350, 2967-2974.
7. (a) Poupon, J. C.; Boezio, A. A.; Charette, A. B. Angew. Chem. Int. Ed.
2006, 45, 1415-1420. (b) Stazi, F.; Marcoux, D.; Poupon, J. C.; Latassa,
D.; Charette, A. B. Angew. Chem. Int. Ed. 2007, 46, 5011-5014.
8. (a) Zhang, L.; Luo, S. Z.; Cheng, J. P. Catal. Sci. Technol. 2011, 1, 507-
516. (b) Luo, S. Z.; Zhang, L.; Cheng, J. P. Chem. Asian. J. 2009, 4,
1184-1195.
9. (a) Hermeke, J.; Toy, P. H. Tetrahedron 2011, 67, 4103-4109. (b) Lin, Z.
H.; Chen, Z. X.; Yang, G. C.; Lu, C. F. Catal. Commun. 2013, 35, 1-5. (c)
Nie, X.; Lu, C. F.; Chen, Z. X.; Yang, G. C.; Nie, J. Q. J. Mol. Catal. A-
C. 2014, 393, 171-174. (d) Zimbron, J. M.; Dauphinais, M.; Charette, A.
B. Green Chem. 2015, 17, 3255-3259. (e) Poupon, J. C.; Boezio, A. A.;
Charette, A. B. Angew. Chem. Int. Ed. 2006, 45, 1415-1420. (f) Poupon,
J. C.; Marcoux, D.; Cloarec, J. M.; Charette, A. B. Org. Lett. 2007, 9,
3591-3594. (g) Ginisty, M.; Roy, M. N.; Charette, A. B. J. Org. Chem.
2008, 73, 590-593. (h) Werner, T.; Riahi, A. M.; Schramm, H. Synthesis,
2011, 21, 3482-3490. (i) Zhang, Q.; Zhang, S. B.; Li, S. H.
Number of Cycles
Yield (%)
1
2
3
4
5
6
97
94
91
85
84
77
a Reaction conditions: 1s (1.0 mmol), 2 (1.2 mmol), catalyst (0.10 mmol),
solvent (3.0 mL), room temperature, 1 h.
Acknowledgments
Macromolecules, 2012, 45, 2981-2988. (j) Tian, Y.; Xu, X.; Zhang, L.;
Qu, J. Org. Lett. 2016, 18, 268-271. (k) Toda, Y.; Komiyama, Y.;
Kikuchi, A.; Suga, H. ACS Catal. 2016, 6, 6906-6910.
This work was supported by NSFC (National Natural Science
Foundation of China, No. 21202009) and Beijing Normal
University.
10. Hellmut Hoffmann, Dieter Michael Chem. Ber. 1962, 523, 528-535.
11. For selected examples see: (a) Shi, X.; He, W.; Li, H.; Zhang, X.
Tetrahedron Lett. 2011, 52, 3204-3207. (b) Dong, Z.; Qiu, G.-F.; Zhou,
H.-B.; Dong, C. Tetrahedron: Asymmetry 2012, 23, 1550-1556. (c)
Hyoung, W.-M.; Dae, Y.-K. Tetrahedron Lett. 2012, 53, 6569-6572. (d)
Jia, C.-M.; Chen, D.; Zhang, C.-Y. Tetrahedron 2013, 69, 7320-7324. (e)
Liu, B.; Han, X.; Dong, Z. Tetrahedron: Asymmetry 2013, 24, 1276-1280.
12. (a) Tsogoeva, S. B. Eur. J. Org. Chem. 2007, 1701-1716. (b) Almasi, D.;
Alonso, D. A.; Najera, C. Tetrahedron: Asymmetry 2007, 18, 299-365. (c)
Vicario, J. L.; Badia, D.; Carrillo, L. Synthesis 2007, 2065-2092
13. Liu, X.; Qin, B.; Zhou, X.; He, B.; Feng, X. J. Am. Chem. Soc. 2005, 127,
12224-12225.
References and notes
1. (a) Manabe, K. Tetrahdron 1998, 54, 14465-14476; (b) Manabe, K.
Tetrahedron Lett. 1998, 39, 5807-5810. (c) Werner, T. Adv. Synth. Catal.
2009, 351, 1469; (b) Enders, D.; Nguyen, T. V. Org. Biomol. Chem.
2012, 10, 5327. (d) Liu, S.; Kumatabara, Y.; Shirakawa, S. Green Chem.
2016, 18, 331.
14. Kiyokawa, K.; Nagata, T.; Hayakawa, J.; Minakada, S. Chem. Eur. J.
2015, 21, 1280-1285.
2. Shiyao Liu, Yusuke Kumatabara and Seiji Shirakawa

4
Tetrahedron
distinctive
•
Synthesis
of
structurally
tetraarylphosphonium inner-salts (TAPIS)
•
•
TAPIS backbone could act as a Lewis base catalytic
moiety
TAPIS could act as phase tag to facilitate recycling
and reuse of the catalyst

5
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Tetraarylphosphonium Inner-Salts (TAPIS)
as both Lewis Base Catalyst and Phase Tag
Leave this area blank for abstract info.
Shuhui Guo and Xueling Mi*