Synthesis of bench-stable solid triorganoindium reagents and reactivity in palladium-catalyzed cross-coupling reactions

Article abstract of DOI:10.1039/c7cc09344f

Bench-stable solid triorganoindium compounds have been prepared by coordination with 4-(dimethylamino)pyridine (DMAP). The solid R₃In(DMAP) complexes are obtained from the corresponding solution of R₃In in quantitative yield and can

Full text of DOI:10.1039/c7cc09344f

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: J. M. Gil-Negrete,
J. Pérez Sestelo and L. Sarandeses, Chem. Commun., 2018, DOI: 10.1039/C7CC09344F.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Please do not adjust margins
ChemComm
Page 1 of 5
View Article Online
DOI: 10.1039/C7CC09344F
Journal Name
COMMUNICATION
Synthesis of Bench-Stable Solid Triorganoindium Reagents and
Reactivity in Palladium-Catalyzed Cross-Coupling Reactions
Received 00th January 20xx,
Accepted 00th January 20xx
José M. Gil-Negrete, José Pérez Sestelo,* and Luis A. Sarandeses*
DOI: 10.1039/x0xx00000x
www.rsc.org/
Bench-stable solid triorganoindium compounds have been using nitrogen or phosphorus atoms.11 The isolation and
prepared by coordination with 4-(dimethylamino)pyridine characterization of allyl and 1-butenylindium halides stabilized
(DMAP). The solid R3In(DMAP) complexes are obtained from the by complexation with phosphine and pyridine ligands were
corresponding solution of R3In in quantitative yield and can be also reported by Baba.6,12 Trimethylindium complexes have
stored for up to several weeks. These reagents show excellent also been characterized but their reactivity and synthetic
reactivity in palladium-catalyzed cross-coupling reactions with utility remains unknown.11,13 Herein, we report the
organic electrophiles.
preparation of stable solid triorganoindium compounds
stabilized by coordination with 4-(dimethylamino)pyridine
(DMAP) and their reactivity in palladium-catalyzed cross-
coupling reactions.
In recent years, indium(III) organometallics have become an
attractive alternative to classical organometallic species in
organic synthesis.1 In 1999, we discovered the palladium-
catalyzed cross-coupling reactions of triorganoindium reagents
R3In,2 which is probably their most relevant reaction and
whose utility in organic synthesis is continuously increasing.3 In
this reaction the R3In species show a high atom efficiency as all
three organic groups are transferred from indium to the
electrophile with excellent selectivity, high versatility and, in
general, low toxicity.4 Triorganoindium reagents are commonly
prepared by transmetallation from the corresponding
organolithium or organomagnesium reagents, although other
protocols have also been developed.5 A significant limitation
for the use of these organometallic species is associated with
their preparation and use as solutions, since attempts to
isolate and store these reagents led to decomposition.6
Bearing in mind the stabilization of Group 13 derivatives by
nitrogen ligands, our research started with the preparation of
stable solid triphenylindium complexes by addition of different
pyridines L1–L5 to Ph3In in THF solution and removal of the
solvent. In general, this procedure afforded a solid material
that could be manipulated in air and whose reactivity was
tested in a Pd-catalyzed cross-coupling reaction with 4-
bromoacetophenone (1a, Table 1). Initial studies using a 1:2
ratio of Ph3In and DMAP as ligand gave the coupling product
(
2a) in moderate yield (Table 1, entries 2–6). Interestingly, on
using the 1:1 complex (Ph3In/DMAP) 2a was obtained in 73%
yield with 40 mol% of the complex and PdCl2(PPh3)2 (5 mol%)
as catalyst (Table 1, entry 7), while the use of a 50 mol% of the
complex led to an excellent 91% yield of 2a (Table 1, entry 8).
The use of lower amounts (<50 mol%) of Ph3In(DMAP)
afforded lower yields, probably due to some decomposition of
the complex during the process. The stoichiometry of the
complex was studied by NMR spectroscopy and a 1:1 ratio of
Ph3In/DMAP was found, whereas the use of larger amounts of
DMAP gave rise to an equilibrium between ligated and non-
ligated DMAP. Additionally, the use of a substoichiometric
amount of DMAP (ratio Ph3In/DMAP 1:0.8) resulted in the
appearance of benzene due to the decomposition of non-
ligated organometallic complex (Figure 1).
The preparation of solid-salt stabilized reagents is an
interesting research topic that allows the use of
organometallic and other nucleophilic species as solid
reagents. Organotrifluoroborates,7 MIDA-boronates8 and
stable siloxanes9 are useful examples of solid-salt stabilized
reagents, whereas among the main-group metal derivatives,
organozinc pivalates have emerged as interesting reactive solid
species.10
In the field of indium chemistry, Schumann and co-workers
reported an extensive study on the characterization of indium
organometallics stabilized by intramolecular coordination
Accordingly, the addition of DMAP (1 equiv.) to a THF solution
of Ph3In at room temperature for one hour followed by
evaporation of the solvent in vacuo gave a white solid with the
tentative formula Ph3In(DMAP)·3LiCl
(3, Scheme 1). This
compound showed bench-stable, and was handled in air and
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 5
View Article Online
DOI: 10.1039/C7CC09344F
COMMUNICATION
Journal Name
Table 1. Ligand optimization studies.a
Entry
L
mol% Lb
–
80
80
mol% Ph3Inb
Yield (%)c
1
2
3
4
5
6
7
8
–
40
40
40
40
40
40
40
50
–
L1
L2
L3
L4
L5
L4
L4
23
15
5
80
80
80
55
Scheme 1. Preparation of Ph3In(DMAP) (3') and ORTEP drawing (showing 40%
probability displacement ellipsoids) of the crystal structure of Ph3In(DMAP). The
hydrogen atoms are omitted for clarity.a a CCDC-1579360.
11
73
91
40
50
of complexes R3In(DMAP)·3LiCl abbreviated as R3In(DMAP) for
clarity was prepared (Table 2) including aromatic and
heteroaromatic indium reagents (
3–8), a trialkynylindium
complex (9) and the tribenzylindium complex (10).
a For experimental details, see the ESI. b mol% of L and Ph3In with respect to 1a. c
The reactivity of the solid triorganoindium reagents was tested
in palladium-catalyzed cross-coupling reactions using common
electrophiles under the established conditions reported for
R3In prepared in situ in THF solution. The reaction of the
Isolated yields of reaction product after column chromatography.
used as a solid reagent. In order to characterize this solid, the
LiCl was removed by filtration after boiling in dry toluene. This
process afforded a compound that was crystallized from
toluene/hexane (3:1). X-ray diffraction studies on the pure
crystals (3') showed a trigonal pyramidal structure in which the
ideal plane formed by the phenyl groups and the indium atom
is distorted by the ligand (DMAP) to give an N–In–C dihedral
angle of around 100° (Scheme 1). The In–N distance was 2.27 Å
and the In–C distance was 2.17 Å. Interestingly, the cross-
coupling reaction with 4-bromoacetophenone carried out
using the purified crystals (3') afforded the coupling product in
excellent yield (90%) on using only 34 mol% of the solid
organometallic reagent and showing the efficient transference
of all three organic groups attached to the indium to the
electrophile.
Ph3In(DMAP) complex (
bromide 11 proceeded efficiently (92–94%, Table 3). The
coupling with other electrophiles such as -bromostyrene and
benzyl bromide also gave the corresponding products 2c in
3) with the aryl triflate 1b or the aryl
β
–d
good yields (81–88%). Additionally, the Pd-catalyzed allylic
substitution14 with cinnamyl bromide gave regioselectively the
α
-substitution product 2e in excellent yield (87%).
To our delight, other solid derivatives of triarylindium
reagents, such as the tri(2-methoxyphenyl)indium(DMAP) (
4
)
and tris(4-trifluoromethylphenyl)indium(DMAP)
(
3
)
also
reacted efficiently with the electrophiles 1a and 11
–14 to give
the corresponding cross-coupling products in good to excellent
yields (81–96%, Table 3). In all cases the reaction proceeded
under mild reaction conditions and in short reaction times
using 50 mol% of the solid indium reagents, thus showing the
feasibility of using these compounds in cross-coupling
Having successfully prepared the complex Ph3In(DMAP), the
protocol was applied to other triorganoindium species and the
reactivity of the resulting complexes was studied in palladium-
catalyzed cross-coupling reactions. With this purpose, a series
Table 2. Preparation of solid triorganoindium complexes.a
a
b
LiCl in complexes is omitted for clarity. Prepared from benzylmagnesium
bromide.
• DMAP. ◊ Ph3In. × Benzene (resulting from Ph3In decomposition).
Figure 1. Ph3In(DMAP) stoichiometry experiments.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 3 of 5
View Article Online
DOI: 10.1039/C7CC09344F
Journal Name
COMMUNICATION
Table 3. Palladium-catalyzed cross-coupling reactions of solid triarylindium and
Table 4. Palladium-catalyzed cross-coupling reactions of solid alkynylindium complex 9
triheteroarylindium complexes 3–8 with organic electrophiles.a
with organic electrophiles.
indium reagents. Furthermore, the efficient coupling achieved
using the pyridylindium complex
6 showed that the nitrogen
lone pair does not interfere in the complexation process with
DMAP and the reactivity remains similar to that of the
tripyridylindium in solution.
The reactivity of the solid alkynylindium complex
9 was also
studied with aryl and alkenyl halides 1a, 11 and 12 under
standard reaction conditions. These coupling reactions also
proceeded efficiently to give excellent yields (80–93%, Table
4). Finally, the reactivity of the tribenzylindium(DMAP)
complex (10) was tested. In this case, it was found that the
coupling reactions with aryl bromide 1a, β-bromostyrene (12)
and 2-bromobenzonitrile (21) gave satisfactory yields (58–71%,
Table 5). In this case, 10 was prepared from benzylmagnesium
bromide.
The synthetic utility of the novel solid triorganoindium species
was demonstrated not only in terms of their reactivity but also
due to their integrity against decomposition over time. In this
respect, Ph3In(DMAP)·3LiCl (3) was stored on the laboratory
bench at room temperature under Ar and the stability of the
complex evaluated by means of palladium-catalyzed cross-
coupling reactions over time. The results are presented in
Table 6 and it can be seen that one month after preparation of
the complex, the solid reagent remained highly reactive (78%
yield of 2a, Table 6, entry 6). Interestingly, the use of purified
Ph3In(DMAP) (3', without LiCl) gave compound 2a in 95% yield
after 45 days. The other organoindium complexes prepared in
this study generally show high stabilities under Ar at room
temperature. The stability ranges from weeks for
in the case of and 10, and >6 h for the nitrogen
and (tested by studying a Pd-
4 and 7, days
5, 9
a
1a: 4-Bromoacetophenone; 1b: 4-acetylphenyl trifluoromethanesulfonate; 11: heterocyclic derivatives
4-bromotoluene; 12: β-bromostyrene; 13: benzyl bromide; 14: cinnamyl bromide.
6
8
Table 5. Palladium-catalyzed cross-coupling reactions of solid tribenzylindium(DMAP)
complex (10) with organic electrophiles.
reactions. The presence of DMAP as a ligand does not interfere
with the reactivity of the organoindium compound since the
yields are comparable to those obtained in reactions in which
the R3In was generated in situ in solution.
Then, we proceeded to study the reactivity of the solid
heteroaryl indium compounds
results in Table 3, coupling reactions between these
compounds and electrophiles 1a and 11 14 also proceeded in
6–8. As can be seen from the
–
good yields (71–95%, Table 3) under the same experimental
conditions as before. Interestingly, the reactions involving aryl
halides and also a vinyl halide, benzyl bromide and an allylic
bromide as electrophiles, showed the versatility of the solid
a 1H NMR yield.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 5
View Article Online
DOI: 10.1039/C7CC09344F
COMMUNICATION
Journal Name
Table 6. Reactivity of complex 1 over time.
J. Pérez Sestelo and L. A. Sarandeses, Org. Lett., 2006, 8, 1403;
(d) Á. Mosquera, M. A. Pena, J. Pérez Sestelo and L. A.
Sarandeses, Eur. J. Org. Chem., 2013, 2013, 2555; (e) M. Mato,
C. Pérez-Caaveiro, L. A. Sarandeses and J. Pérez Sestelo, Adv.
Synth. Catal., 2017, 359, 1388, and references therein.
(a) K. Takami, H. Yorimitsu, H. Shinokubo, S. Matsubara and K.
Oshima, Org. Lett., 2001, 3, 1997; (b) P. H. Lee, S.-Y. Sung and K.
Lee, Org. Lett., 2001, 3, 3201; (c) K. Lee, D. Seomoon and P. H.
Lee, Angew. Chem. Int. Ed., 2002, 41, 3901; (d) U. Lehmann, S.
Awasthi and T. Minehan, Org. Lett., 2003, 5, 2405; (e) Y.-H.
Chen, M. Sun and P. Knochel, Angew. Chem. Int. Ed., 2009, 48,
2236; (f) Z.-L. Shen, K. K. K. Goh, H.-L. Cheong, C. H. A. Wong, Y.-
C. Lai, Y.-S. Yang and T.-P. Loh, J. Am. Chem. Soc., 2010, 132,
15852; (g) D. Lee, T. Ryu, Y. Park and P. H. Lee, Org. Lett., 2014,
16, 1144; (h) S. Kim, C.-E. Kim, B. Seo and P. H. Lee, Org. Lett.,
2014, 16, 5552; (i) S. Thapa, S. K. Gurung, D. A. Dickie and R.
Giri, Angew. Chem. Int. Ed., 2014, 53, 11620; (j) Y. Park, J. Min,
D. Eom and P. H. Lee, Org. Lett., 2015, 17, 3934.
3
Entry Days after preparation of Ph3In(DMAP) Yield (%)
1
2
3
4
5
6
7
3
5
91a
88a
93a
84a
82a
78a
95b
7
14
21
28
45
a
b
Reactions with non-purified Ph3In(DMAP)·3LiCl (3). Reaction with purified
Ph3In(DMAP) (3').
4
5
J. Burgess, Chem. Soc. Rev., 1996, 25, 85.
catalyzed cross-coupling reaction, Table S1).
(a) J. L. W. Pohlmann, F. E. Brinckman, G. Tesi and R. E. Donadio,
Z. Naturforsch., 1965, 20b, 5; (b) H. C. Clark and A. L. Pickard, J.
Organomet. Chem., 1967, 8, 427; (c) E. Font-Sanchis, Á. Sastre-
Santos and F. Fernández-Lázaro, Dalton Trans, 2009, 2470; (d)
Z.-L. Shen, K. K. K. Goh, Y.-S. Yang, Y.-C. Lai, C. H. A. Wong, H.-L.
Cheong and T.-P. Loh, Angew. Chem. Int. Ed., 2011, 50, 511; (e)
L. Adak and N. Yoshikai, J. Org. Chem., 2011, 76, 7563; (f) S.
Bernhardt, Z.-L. Shen and P. Knochel, Chem. Eur. J., 2013, 19,
828.
M. Yasuda, M. Haga and A. Baba, Organometallics, 2009, 28,
1998.
(a) G. A. Molander and N. Ellis, Acc. Chem. Res., 2007, 40, 275;
(b) G. A. Molander, J. Org. Chem., 2015, 80, 7837.
In general, the use of organoindium species is limited to ethers
as solvents, and to their preparation from the corresponding
organolithium or organomagnesium reagents. For this reason,
we studied the reactivity of the solid-stable R3In complexes in
non-ethereal solvents. The palladium-catalyzed coupling
reaction of Ph3In(DMAP) with 1a in various solvents, such as
toluene, chloroalkanes or DMF, generally afforded good yields
of the coupling product 2a (45–93%, Table S3, entries 2–6).
In conclusion, a variety of bench-stable solid triorganoindium
reagents have been prepared by complexation with DMAP in a
1:1 stoichiometry. The stability of the R3In complexes ranges
from days to weeks depending on the nature of the R groups.
These reagents reacted with organic electrophiles under
palladium catalysis to afford the coupling products in good
yields. Interestingly, only 50 mol% of the solid organometallic
reagent is necessary to complete the reactions. Other solvents
can be used in the coupling reactions and this demonstrates
the versatility and utility of these solid reagents. Further
studies on the isolation of new complexes and their
applications in synthesis are underway and will be published in
due course.
6
7
8
9
J. Li, A. S. Grillo and M. D. Burke, Acc. Chem. Res., 2015, 48,
2297.
D. Martinez-Solorio, B. Melillo, L. Sanchez, Y. Liang, E. Lam, K. N.
Houk and A. B. Smith III, J. Am. Chem. Soc., 2016, 138, 1836.
10 Selected references: (a) S. Bernhardt, G. Manolikakes, T. Kunz
and P. Knochel, Angew. Chem. Int. Ed., 2011, 50, 9205; (b) J. R.
Colombe, S. Bernhardt, C. Stathakis, S. L. Buchwald and P.
Knochel, Org. Lett., 2013, 15, 5754; (c) M. Ellwart and P.
Knochel, Angew. Chem. Int. Ed., 2015, 54, 10662; (d) Y.-H. Chen,
C.-P. Tüllmann, M. Ellwart and P. Knochel, Angew. Chem. Int.
Ed., 2017, 56, 9236–9239.
11 Representative references: (a) H. Schumann, U. Hartmann, W.
Wassermann, A. Dietrich, F. H. Görlitz, L. Pohl and M. Hostalek,
Chem. Ber., 1990, 123, 2093; (b) H. Schumann, J. Kaufmann, B.
C. Wassermann, F. Girgsdies, N. Jaber and J. Blum, Z. Anorg.
Allg. Chem., 2002, 628, 971; (c) H. Schumann, F. Girgsdies, B.
Heymer, J. Kaufmann, C. Marschall and W. Wassermann, Z.
Anorg. Allg. Chem., 2007, 633, 2268.
Conflicts of interest
There are no conflicts to declare.
12 (a) M. Yasuda, M. Haga and A. Baba, Eur. J. Org. Chem., 2009,
2009, 5513; (b) M. Yasuda, M. Haga, Y. Nagaoka and A. Baba,
Eur. J. Org. Chem., 2010, 2010, 5359; (c) K. Kiyokawa, M. Yasuda
and A. Baba, Organometallics, 2011, 30, 2039.
13 (a) D. C. Bradley, H. Dawes, D. M. Frigo, M. B. Hursthouse and B.
Hussain, J. Organomet. Chem., 1987, 325, 55; (b) K. M. Coward,
A. C. Jones, A. Steiner, J. F. Bickley, L. M. Smith and M. E.
Pemble, J. Chem. Soc., Dalton Trans., 2001, 41; (c) F. Thomas, T.
Bauer, S. Schulz and M. Nieger, Z. Anorg. Allg. Chem., 2003, 629,
2018; (d) X. Tian, R. Fröhlich, T. Pape and N. W Mitzel,
Organometallics, 2005, 24, 5294.
Acknowledgements
We are grateful to the Spanish Ministerio de Economía y
Competitividad (CTQ2015-68369-P), Xunta de Galicia
(GRC2014/042) and EDRF funds for financial support. We also
thank Dr. Antonio L. Llamas-Díaz (RIAIDT, Universidade de
Santiago de Compostela, Spain) for the X Ray structure
analysis.
Notes and references
14 (a) L. Baker and T. Minehan, J. Org. Chem., 2004, 69, 3957; (b)
D. Rodríguez, J. Pérez Sestelo and L. A. Sarandeses, J. Org.
Chem., 2004, 69, 8136; (c) R. Riveiros, R. Tato, J. Pérez Sestelo
and L. A. Sarandeses, Eur. J. Org. Chem., 2012, 2012, 3018.
1
(a) Z.-L. Shen, S.-Y. Wang, Y.-K. Chok, Y.-H. Xu and T.-P. Loh,
Chem. Rev., 2013, 113, 271; (b) K. Zhao, L. Shen, Z.-L. Shen and
T.-P. Loh, Chem. Soc. Rev., 2017, 46, 586.
2
(a) I. Pérez, J. Pérez Sestelo and L. A. Sarandeses, Org. Lett.,
1999, 1, 1267; (b) I. Pérez, J. Pérez Sestelo and L. A. Sarandeses,
J. Am. Chem. Soc., 2001, 123, 4155; (c) R. Riveiros, D. Rodríguez,
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 5
ChemComm
View Article Online
DOI: 10.1039/C7CC09344F
Table of Contents Entry
Manuscript title: Synthesis of Bench-Stable Solid Triorganoindium Reagents and Reactivity in
Palladium-Catalyzed Cross-Coupling Reactions
Authors: José M. Gil-Negrete, José Pérez Sestelo, and Luis A. Sarandeses
Triorganoindium reagents can be isolated as bench-stable solid R3In(DMAP) complexes and show
excellent reactivity in palladium-catalyzed cross-coupling reactions.