Iridium-Catalyzed Sustainable Access to Functionalized Julolidines through Hydrogen Autotransfer

Article abstract of DOI:10.1002/cctc.201500051

The straightforward and ecofriendly preparation of functionalized julolidines starting from tetrahydroquinoline, diols, and aldehydes, for which water is produced as the only side product was investigated. To achieve this task, several well-defined ruthenium and iridium complexes including three new complexes were prepared from the corresponding phosphine-sulfonates, phosphine-carboxylates, and phosphine-phosphonates. The first transformation involved in situ generation of enaminoiminium intermediates, which allowed the formation of the julolidines through formal N,C(sp²)-cyclization of tetrahydroquinoline and the propane-1,3-diols. The influence of the chelate acidity points out that [Cp?Ir^III]-based catalysts (Cp?=C₅Me₅) featuring phosphine-carboxylate and phosphine-sulfonate ligands were suitable for the cyclization, whereas the acidic phosphinophosphonate-containing complex favored the formation of reduced N-alkylated tetrahydroquinoline. We found that substitution of the propane-1,3-diols was crucial for the generation of enaminoiminium ions, which accounts for the efficiency and selectivity of the reaction. Applying another hydrogen autotransfer process, the prepared julolidines were easily functionalized at the C2 position.

Full text of DOI:10.1002/cctc.201500051

DOI: 10.1002/cctc.201500051
Communications
Iridium-Catalyzed Sustainable Access to Functionalized
Julolidines through Hydrogen Autotransfer
Amira Labed,[b] Fan Jiang,[a] Ilhem Labed,[a] Alexis Lator,[a] Marius Peters,[a] Mathieu Achard,*[a]
Ahmed Kabouche,[b] Zahia Kabouche,[b] Gangavaram V. M. Sharma,[c] and Christian Bruneau[a]
The straightforward and ecofriendly preparation of functional-
ized julolidines starting from tetrahydroquinoline, diols, and al-
dehydes, for which water is produced as the only side product
was investigated. To achieve this task, several well-defined
ruthenium and iridium complexes including three new com-
plexes were prepared from the corresponding phosphine–sul-
fonates, phosphine–carboxylates, and phosphine–phospho-
nates. The first transformation involved in situ generation of
enaminoiminium intermediates, which allowed the formation
of the julolidines through formal N,C(sp2)-cyclization of tetrahy-
droquinoline and the propane-1,3-diols. The influence of the
chelate acidity points out that [Cp*IrIII]-based catalysts (Cp*=
C5Me5) featuring phosphine–carboxylate and phosphine–sulfo-
nate ligands were suitable for the cyclization, whereas the
acidic phosphinophosphonate-containing complex favored the
formation of reduced N-alkylated tetrahydroquinoline. We
found that substitution of the propane-1,3-diols was crucial for
the generation of enaminoiminium ions, which accounts for
the efficiency and selectivity of the reaction. Applying another
hydrogen autotransfer process, the prepared julolidines were
easily functionalized at the C2 position.
followed by condensation then reduction of the resulting un-
saturated intermediates with the in situ generated metal hy-
dride species. Since the seminal results of Shvo and Laine on
the dealkylation/alkylation of tertiary amines involving iminium
intermediates[2] in the presence of Ru3(CO)12 followed by the
works of Griggs[3] and Watanabe[4], who independently devel-
oped ruthenium complexes to achieve N-alkylation with alco-
hols, recent examples adopting these strategies have been
documented to allow more selective and milder reaction con-
ditions,[5] water-soluble or reusable/immobilized catalysts,[6]
and asymmetric approaches.[7] Recently, a- and b-alkylation of
cyclic amines broadened the scope of this transformation.[8] By
suppressing the final hydrogenation step, acceptorless dehy-
drogenative condensation represents another elegant sustaina-
ble approach for the preparation of pyrroles, pyridines, and,
more recently, quinolines through dual or multicomponent
cascades.[9–13]
Owing to their strong electron-releasing and fluorescent
properties, julolidine derivatives have found broad applications
as photosensitizers in material sciences, including in organic
light-emitting diodes and solar cells (Figure 1).[14] Surprisingly,
traditional approaches to julolidines usually involve the reac-
tion of anilines or tetrahydroquinolines with 1,3-dihalogenated
Redox-neutral processes involving hydrogen transfers known
as “borrowing hydrogen”, “hydrogen autotransfer”, and “hydro-
gen shuttling” represent ecofriendly approaches for the devel-
opment of benign and atom-efficient protocols that allow the
formation of carbon–heteroatom and carbon–carbon bonds.[1]
In these reactions, the cascade transformation involves the ac-
tivation of the alcohols or amines through dehydrogenation
Figure 1. Some examples and applications of julolidines.
[a] F. Jiang, I. Labed, A. Lator, M. Peters, Dr. M. Achard, Dr. C. Bruneau
UMR6226 CNRS, Institut des Sciences Chimiques de Rennes
UniversitØ de Rennes1
propanes such as harmful 3-chloro-1-bromopropane followed
by functionalization of the C9 atom through bromination with
N-bromosuccinimide (NBS) or Vilsmeier–Haack formylation to
allow the introduction of the electron acceptor.[14,15]
OMC: Organometallics: Materials and Catalysis
Campus de Beaulieu, 35042 Rennes Cedex (France)
Fax: (+33)223236939
E-mail: mathieu.achard@univ-rennes1.fr
[b] A. Labed, Dr. A. Kabouche, Prof. Z. Kabouche
University of Constantine 1
In 1985, Watanabe and co-workers pioneered the prepara-
tion of quinoline through dehydrogenative condensation from
1,3-propanediol and aniline in the presence of a ruthenium tri-
chloride/tributylphosphine catalytic system along with a stoi-
chiometric amount of nitrobenzene acting as a hydrogen ac-
ceptor.[16] Since then, several reports have dealt with N,C(sp2)-
cyclization through either acceptor-mediated dehydrogenative
coupling or, more recently, acceptorless dehydrogenative cou-
pling in the presence of a base.[10,16] However, a catalytic
system allowing the reduction of the final unsaturated inter-
Department of Chemistry
Laboratory of Therapeutic Substances Obtention (LOST)
Chaabet Ersas Campus, 25000 Constantine (Algeria)
Fax: (+213)31811100
[c] Dr. G. V. M. Sharma
Organic and Biomolecular Chemistry Division
CSIR-Indian Institute of Chemical Technology
Tarnaka, Hyderabad-500 607 (India)
Supporting Information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201500051.
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mediates through hydrogen au-
totransfer is so far unknown. The
development of such a transfor-
mation is highly desirable and
could lead to ecofriendly, halo-
genated reagent-free syntheses
of functionalized julolidines with
the generation of water as the
only side product; this could
provide new insight into immo-
bilization, matrix incorporation,
and cell-permeation enhance-
ment (Scheme 1).
Herein, we report the develop-
ment of
a
straightforward
method for the preparation of
julolidines by cyclization of 1,3-
propanediols with tetrahydroqui-
noline involving borrowing-hy-
Scheme 2. Preparation of the iridium and ruthenium complexes.
after crystallization with solvent-diffusion techniques (CH2Cl2/n-
hexane), expected complex cat. D along with 2(H3O+; ClÀ);
1H2O molecules with a signal at d=9.5 ppm in the 31P NMR
spectrum (Figure 2).[20] Further neutralization by careful treat-
ment with water finally afforded cat. D in 21% yield
(Scheme 2). Recently, Rieger and co-workers reported the syn-
thesis of phosphinophosphonic prochelates from diethyl phos-
phonates for the preparation of various palladium(II) com-
plexes.[21] Following this methodology, we thus decided to pre-
pare corresponding new IrIII complex cat. E. Treatment of this
phosphonic acid with 1 equivalent of potassium tert-butoxide
followed by the addition of [Cp*IrCl2]2 gave two complexes.
Analysis by 31P NMR spectroscopy confirmed the formation of
one major species with resonances at d=16.3 and 4.3 ppm
corresponding to the phosphonate and phosphine groups, re-
spectively, which after purification gave expected iridium(III)
cat. E in 70% yield (Scheme 2).[22,23]
Scheme 1. Direct access to julolidines from tetrahydroquinoline and pro-
pane-1,3-diol.
drogen processes. Particularly, the preparations of various
ruthenium and iridium complexes featuring phosphine–sulfo-
nate/carboxylate/phosphonate chelates allow the influence of
the acidic moiety on the chelating ligands towards the com-
petitive side dehydration/reduction to be tackled. The diversi-
ty-oriented synthesis of functionalized julolidines is achieved
through selective b-alkylation involving borrowing-hydrogen
processes on the resulting challenging substrates.
Having prepared the well-defined complexes, we next inves-
tigated the target transformation to access to the correspond-
ing julolidines (Table 1). Thus, tetrahydroquinoline (1a) was
first treated with 1,3-propanediol (2a) for 20 h at 1308C by
using toluene as the solvent without any base or acid additive.
[IrIII(Cp*)]-based catalyst A was found to be active in this novel
N,C(sp2)-dialkylation of 1a with 2a to give 3a. However,
a modest yield of 43% was obtained during our initial at-
tempts (Table 1, entry 1). Analysis of the reaction mixture high-
lighted the side formation of N-propyltetrahydroquinoline
(4a); a 61:39 ratio of 3a/4a was reached.[16,24] Modification of
the temperature and concentration had only a limited impact
on this ratio. Gratifyingly, increasing the amine 1a/diol 2a ratio
from 1:1.2 to 2:1 minimized the formation of N-alkylated prod-
uct 4a and afforded julolidine 3a in 72% yield with a 3a/4a
ratio of 87:13 (Table 1, entry 2). As expected, the corresponding
in situ generated complex obtained by treatment of
[Ir(Cp*)Cl2]2 with DPPBSA afforded a similar conversion, ratio,
and yield (Table 1, compare entries 7 and 2). Lowering the con-
centration of 2a resulted in a higher conversion, but the ratio
of 3a/4a decreased (Table 1, entries 7–9). We next investigated
the influence of the chelate toward selectivity and yield. Com-
With this idea in mind, we first focused our attention on the
preparation of various ruthenium and iridium complexes con-
taining an acidic chelating ligand to further evaluate the
impact of the carboxylate, sulfonate, and phosphonate moiet-
ies toward the targeted cyclization. The phosphinosulfonate-
containing either Cp*-iridium(III) (Cp*=C5Me5) cat. A or arene
ruthenium(II) cat. B complexes were prepared from deproton-
ated diphenylphosphinobenzenesulfonic acid (DPPBSA) and
the [Cp*IrCl2]2 and [Ru(p-cymene)Cl2]2 metal precursors, respec-
tively (Scheme 2).[17] New square-planar iridium(I) complex
cat. C was similarly synthesized starting from [Ir(cod]Cl]2 (cod=
1,5-cyclooctadiene) in 83% yield; it was characterized by NMR
spectroscopy and its structure was confirmed by X-ray crystal-
lography (Figure 2).[18,19] We next investigated the use of the
less acidic diphenylphosphinobenzoic acid (DPPBA). By using
methodology similar to that used for the preparation of cat. A,
the reaction led to the formation of the expected, but surpris-
ingly sensitive, complex cat. D characterized by a resonance at
d=4.7 ppm in its 31P NMR spectrum along with two distinct
undesired species. Therefore, slight modification to the reac-
tion conditions by performing the reaction with DPPBA gave,
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served in the presence of iridium(I) precatalyst C, but an equi-
molar ratio of 3a/4a was obtained (Table 1, entry 6). Optimiza-
tion of the promising result obtained with D led us to use
DPPBA as a proligand for further investigations. A similar result
and a similar conversion were obtained by mixing DPPBA with
[Ir(Cp*)Cl2]2 (Table 1, entry 10 vs. 3); therefore, in situ genera-
tion of the active species was next used for convenience. In-
creasing the reaction time to 36 h led to complete conversion
and 91% yield (Table 1, entry 11). The tedious separation of re-
maining 1a with formed 3a along with trace amounts of 4a
by column chromatography over silica gel led to isolation of
pure 3a in 80% yield (Table 1, entry 11). Notably, the reactions
were also performed on gram scale, and similar ratios and
yields were observed.[25]
With our best reaction conditions in hand, we next investi-
gated the scope of the transformation with substituted 1,3-
propanediols (Table 2) The reaction of 2-methylpropane-1,3-
diol (2b) with [Ir(Cp*)Cl2]2 in the presence of DPPBA cleanly af-
forded expected julolidine 3b in 78% yield with 5% yield of N-
isobutyltetrahydroquinoline. Butane-1,3-diol (2c) was a more
challenging substrate. In this case, competitive formation of
the iminium and ketiminium ions resulting from condensation
of the in situ generated aldehyde and ketone, respectively, led
to julolidines 3c and 3d in yields of 5 and 23%, respectively.
However, dehydration processes became the major pathway,
and undesired N-alkylation products were obtained in 40%
yield. The favored formation of 3d+4d relative to that of
3c+4c revealed the selective formation of the iminium ion.
Rationalization of the formation of 3 and 4 was next under-
taken (Figure 3). In the presence of the catalytic species, activa-
tion of the propane-1,3-diol substrate through dehydrogena-
tion followed by condensation in the presence of amine 1a
gives iminium intermediate I. Deprotonation affords key enam-
ino alcohol intermediate II. According to path I and depending
on the acidity of the ligand held by iridium, intermediate II can
undergo protonation in the presence of an acidic catalytic spe-
cies to form a,b-unsaturated exocyclic iminium ion IV after loss
of a molecule of water. Then, reduction with the generated
metal hydride species followed by protonation gives side prod-
uct 4a. On the other hand, in the presence of the required
extra amount of amine 1a and with the less acidic softer spe-
cies arising from cat. A and cat. D following path II, key inter-
mediate II after dehydrogenation and condensation could
afford enaminoiminium ion V as a formal Povarov key inter-
mediate.[26–28] Therefore, electrocyclization followed by proto-
nation and the release of amine 1a might lead to a,b-unsatu-
rated endocyclic iminium ion VI. Finally, reduction/protona-
tion/reduction affords expected julolidine 3a. This pathway
tends to explain the competitive formation of 3c and 3d
during the reaction with 2c. However, we cannot totally ex-
clude the formation of 3a from sequential alkylations through
hydrogen autotransfer (path III). The formation of 4a could
also arise from prior dehydration/isomerization processes of
starting diol 1a to afford propanal, which might also account
for the formation of 4a.[29] To distinguish between the postu-
lated pathways, we decided to perform the reaction with 2,2-
dimethylpropane-1,3-diol, which cannot lead to key enamino
Figure 2. X-ray structures of new complexes cat. C (top), cat. D (middle), and
cat. E (bottom), and comparison of the relevant bond lengths. Hydrogen
atoms and solvents are omitted for clarity.
plex D featuring the softer phosphinocarboxylate chelate di-
minished the side reductive dehydration process to afford
a similar conversion but an improved 92:08 ratio of 3a/4a and
3a was obtained in 77% yield (Table 1, entry 3). In contrast, IrIII
complex E even with a 2:1 ratio of 1a/2a, which favored the
formation of expected julolidine with A and D, enhanced the
formation of N-propyltetrahydroquinoline with complete con-
version with a 60:40 ratio of 3a/4a, which demonstrates the in-
fluence of the second acidic dissociation constant (P-OH) on
this complex toward the side dehydration/reduction reaction
(Table 1, entry 4 vs. entries 2 and 3).
The use of arene ruthenium(II) complex B afforded a ratio of
products similar to that provided by A but with a modest 53%
conversion (Table 1, entry 5). Low conversion was also ob-
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At this first stage, considering
the importance of the substitu-
tion patterns to ensure selective
cyclization and the limited
number of commercially avail-
able propane-1,3-diol derivatives,
the diversity of julolidines arising
from hydrogen autotransfer
could appear quite limited. How-
ever, we considered that the pre-
pared julolidines would be suita-
ble candidates for post-function-
alization through hydrogen au-
totransfer in the presence of
electrophiles such as aldehydes
to access b-alkylated julolidines.
Noteworthy, the chromophoric
properties of julolidines are in-
herent to their strong electron-
donating properties. Therefore,
the highly nucleophilic site at C9
adds another challenge to the
target transformation (Figure 4).
To our delight, the use of
Table 1. Reaction of tetrahydroquinoline (1a) with propan-1,3-diol (2a).[a]
Entry
Catalyst
([mol%])
Ligand
([mol%])
t
[h]
Ratio 1a/2a
[2a]
[m]
Ratio 3a/4a
Conv.
[%][b]
Yield of
3a [%][c]
1
2
3
4
5
6
7
8
A (2.5)
A (2)
D (2)
E (2)
B (2.5)
C (2)
[Cp*IrCl2]2 (1)
[Cp*IrCl2]2 (1)
[Cp*IrCl2]2 (1)
[Cp*IrCl2]2 (1)
[Cp*IrCl2]2 (1)
–
–
–
–
–
–
20
20
20
20
20
20
20
20
20
20
36
1:1.2
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
1.3
1.3
1.3
1.3
1.3
1.3
1.3
0.8
0.4
1.3
1.3
61:39
87:13
92:08
60:40
85:15
50:50
85:15
85:15
75:25
91:9
87
84
85
99
53
25
82
95
99
82
99
43
72
77
52
25
15
67
80
DPPBSA (2)
DPPBSA (2)
DPPBSA (2)
DPPBA (2)
DPPBA (2)
9
10
11
70
71
91 (80)
95:5
[a] All reactions were performed in dry and degassed toluene under an inert atmosphere of argon. [b] Conver-
sion was calculated based on GC analysis of the limiting substrate. [c] Yield of 3a was determined by GC analy-
sis by using dodecane as an internal standard, and the number in parentheses is the yield of the isolated prod-
uct after purification by column chromatography on SiO2.
phosphinocarboxylate
DPPBA
and phosphinosulfonate DPPBSA
chelates allowed the formation
of the expected Cb-functional-
ized julolidines from various al-
dehydes acting as electrophiles
(Table 3). Under conditions that
we previously used for Cb-alkyla-
tion,[8b] for example, in the pres-
ence of formic acid to achieve
final reduction, reaction of ben-
zaldehyde with 3a afforded 5a
in 67% yield. Similarly, p-methyl-
benzaldehyde reacted cleanly to
give 5d in 43% yield. ortho- and
para-Bromobenzaldehyde gave
halogenated julolidines 5b and
5c in yields of 65 and 64%, re-
spectively; this opens new per-
spectives of transformations of
julolidines through catalyzed
cross-coupling reactions. Thio-
phene carboxaldehydes were
compatible with the transforma-
Figure 3. Proposed intermediates accounting for the formation of 3a and 4a.
alcohol of type II. In this case, the corresponding uncyclized
amino alcohol product was predominantly formed, whereas
2,2-dimethyljulolidine was only detected by GC–MS analysis,
that is, it was formed in <1% (Scheme 3). This result tends to
suggest the requirement of enaminoiminium intermediate V
to ensure cyclization and might confirm that path II mainly ac-
counts for the formation of julolidine 3. This overall transfor-
mation complements traditional Povarov cyclizations that re-
quire specific dienophiles.[27]
Scheme 3. Importance of a,b-unsaturated intermediates II to ensure juloli-
dine formation.
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which afforded the disubstituted
products in 34–60% yields. Nota-
bly, with the aldehydes em-
ployed above, no C9-alkylation
products were detected during
the transformation. However,
during our attempts to react 2-
furfural with julolidine 3a, a tem-
perature-dependent mixture of
products was observed. Analyses
revealed the formation of C9-al-
kylated julolidine 6b in 20%
yield (Scheme 4). The use of
ethyl glyoxylate completely sup-
pressed the b-alkylation and
only 6a was formed during the
reaction, which highlights that
aldehydes featuring a coordinat-
ing oxygen atom in the a-posi-
tion favor Friedel–Crafts-type
products. Taken together, these
results provide new insight into
accessing julolidines through
borrowing-hydrogen processes
and the C9 position is kept
intact for the introduction of an
electron acceptor.
Table 2. Yields of isolated julolidines 3a–d, and product distributions from propanediol derivatives 2.
Table 3. Yields of isolated products from the b-alkylation of julolidines 3.
In conclusion we have demon-
strated that the preparation of
various julolidines can be easily
achieved through hydrogen au-
totransfer involving consecutive
N,C-dialkylation of tetrahydroqui-
noline and b-alkylation under
green conditions with formation
of water as the sole byproduct.
Phosphinosulfonate and phos-
phinocarboxylate were found to
be efficient ligands for these
transformations, whereas more
acidic
phosphinophosphonate
favored dehydration/reduction
pathways. The efficiency of the
same iridium catalysts in both
synthesis and functionalization
reactions
suggests
that
a
tandem protocol might be
possible for the overall transformation. Modification of the op-
tical properties during b-alkylation of the julolidines by sup-
pressing the final reduction with formic acid would afford in-
teresting results. Extension of this methodology to N-substitut-
ed anilines is currently underway.
Figure 4. Competitive alkylation pathways.
tion, as they yielded products 5e and 5 f in up to 72% yield. In
each case, the use of methyl-substituted julolidine 3b led to
the formation of two isomers without diastereoselectivity,
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Tse, S. Zhou, M. M. Pohl, J. Radnik,
S. Hübner, K. Jähnisch, A. Brückner,
M. Beller, J. Am. Chem. Soc. 2009,
131, 1775; h) S. Bähn, S. Imm, K.
Mevius, L. Neubert, A. Tillack,
J. M. J. Williams, M. Beller, Chem.
Eur. J. 2010, 16, 3590; i) S. Agrawal,
M. Lenormand, B. Martín-Matute,
Org. Lett. 2012, 14, 1456; j) D.
Scheme 4. C9-Alkylation of julolidine 3a.
Weickmann, B. Plietker, Chem-
CatChem 2013, 5, 2170; k) D.
Weickmann, W. Frey, B. Plietker,
Experimental Section
Chem. Eur. J. 2013, 19, 2741. For selected recent contributions concern-
ing iridium, see: l) R. Yamaguchi, S. Kawagoe, C. Asai, K. I. Fujita, Org.
Lett. 2008, 10, 181; m) B. Blank, S. Michlik, R. Kempe, Chem. Eur. J. 2009,
15, 3790; n) D. Gnanamgari, E. L. Sauer, N. D. Schley, C. Butler, C. D. In-
carvito, R. H. Crabtree, Organometallics 2009, 28, 321; o) O. Saidi, A. J.
Blacker, M. M. Farah, S. P. Marsden, J. M. J. Williams, Chem. Commun.
2010, 46, 1541; p) N. Andrushko, V. Andrushko, P. Roose, K. Moonen, A.
Bçrner, ChemCatChem 2010, 2, 640; q) M. A. Berliner, S. P. A. Dubant, T.
Makowski, K. Ng, B. Sitter, C. Wagger, Y. Zhang, Org. Process Res. Dev.
2011, 15, 1052; r) J. Q. Li, P. G. Andersson, Chem. Commun. 2013, 49,
6131; s) S. Ogawa, Y. Obora, Chem. Commun. 2014, 50, 2491. For
a recent contribution concerning rhenium, see: t) H. Jin, J. Xie, C. Pan,
X. Zhu, Y. Cheng, C. Zhu, ACS Catal. 2013, 3, 2195. For a recent contri-
bution concerning osmium, see: u) M. L. Buil, M. A. Esteruelas, J. Her-
rero, S. Izquierdo, I. M. Pastor, M. Yus, ACS Catal. 2013, 3, 2072. For
a recent contribution concerning metal-free catalysis, see: v) X. Han, J.
Wu, Angew. Chem. Int. Ed. 2013, 52, 4637; Angew. Chem. 2013, 125,
4735.
General Procedure for the preparation of the julolidines 3
A 25 mL, flame-dried Schlenk tube was charged with 1,3-propane-
diol (2; 0.67 mmol, 1.0 equiv.), 1,2,3,4-tetrahydroquinoline (1a,
2.0 equiv.), toluene (0.5 mL), well-defined cat. D (2.5 mol%) or
in situ [Ir(C5Me5)Cl2]2 (1 mol%), and 2-(diphenylphosphino)benzoic
acid (DPPBA, 2 mol%). The mixture was evacuated by vacuum–
argon cycles (5”) and stirred at 1308C (oil bath temperature) for
20–36 h. After cooling the mixture to room temperature, the crude
material was suspended on silica and purified by column chroma-
tography (Et2O/petroleum ether) to isolate expected julolidine 3.
Acknowledgements
The authors thank Dr. Thierry Roisnel and Dr. Vincent Dorcet for
X-ray analyses. F.J. thanks the European Union (FP-7 integrated
project Synflow, NMP-2009-3.2-1 no. 246461; http://synflow.eu)
for a fellowship. Thanks are also due to CEFIPRA/IFCPAR (Indo
French Centre for the Promotion of Advanced Research) (IFC/A/
5105-4/2014/777) for support.
[6] a) G. W. Lamb, F. A. Al Badran, J. M. J. Williams, Chem. Eng. Res. Des.
2010, 88, 1533; b) K. Yamaguchi, J. He, T. Oishi, N. Mizuno, Chem. Eur. J.
2010, 16, 7199; c) R. Kawahara, K. I. Fujita, R. Yamaguchi, J. Am. Chem.
Soc. 2010, 132, 15108; d) H. Ohta, Y. Yuyama, Y. Uozumi, Y. M. A.
Yamada, Org. Lett. 2011, 13, 3892; e) R. Kawahara, K. I. Fujita, R. Yamagu-
chi, Adv. Synth. Catal. 2011, 353, 1161; f) S. Pei Shan, T. T. Dang, A. M.
Seayad, B. Ramalingam, ChemCatChem 2014, 6, 808.
[7] a) A. Eka Putra, Y. Oe, T. Ohta, Eur. J. Org. Chem. 2013, 6146; b) Y. Zhang,
C. S. Lim, D. S. B. Sim, H. J. Pan, Y. Zhao, Angew. Chem. Int. Ed. 2014, 53,
1399; Angew. Chem. 2014, 126, 1423.
[8] a) I. Jovel, S. Prateeptongkum, R. Jackstell, N. Vogl, C. Weckbecker, M.
Beller, Chem. Commun. 2010, 46, 1956; b) K. Yuan, F. Jiang, Z. Sahli, M.
Achard, T. Roisnel, C. Bruneau, Angew. Chem. Int. Ed. 2012, 51, 8876;
Angew. Chem. 2012, 124, 9006; c) Z. Sahli, B. Sundararaju, M. Achard, C.
Bruneau, Green Chem. 2013, 15, 775.
[9] Pyrroles: a) S. Michlik, R. Kempe, Nat. Chem. 2013, 5, 140; b) M. Zhang,
H. Neumann, M. Beller, Angew. Chem. Int. Ed. 2013, 52, 597; Angew.
Chem. 2013, 125, 625; c) K. Iida, T. Miura, J. Ando, S. Saito, Org. Lett.
2013, 15, 1436; d) D. Srimani, Y. Ben-David, D. Milstein, Angew. Chem.
Int. Ed. 2013, 52, 4012; Angew. Chem. 2013, 125, 4104; e) M. Zhang, X.
Fang, H. Neumann, M. Beller, J. Am. Chem. Soc. 2013, 135, 11384; f) S.
Chandrasekhar, V. Patro, L. N. Chavan, R. Chegondi, R. GrØe, Tetrahedron
Lett. 2014, 55, 5932.
[10] Pyridines and quinolines: a) D. Srimani, Y. Ben-David, D. Milstein, Chem.
Commun. 2013, 49, 6632; b) S. Michlik, R. Kempe, Angew. Chem. Int. Ed.
2013, 52, 6326; Angew. Chem. 2013, 125, 6450; c) S. Ruch, T. Irrgang, R.
Kempe, Chem. Eur. J. 2014, 20, 13279.
Keywords: borrowing hydrogen · chelates · cyclization · green
chemistry · iridium
[1] For reviews, see: a) K. I. Fujita, R. Yamaguchi, Synlett 2005, 560; b) G.
Guillena, D. J. Ramón, M. Yus, Angew. Chem. Int. Ed. 2007, 46, 2358;
Angew. Chem. 2007, 119, 2410; c) M. H. S. A. Hamid, P. A. Slatford, J. M. J.
Williams, Adv. Synth. Catal. 2007, 349, 1555; d) G. W. Lamb, J. M. J. Wil-
liams, Chim. Oggi 2008, 26, 17; e) T. D. Dixon, M. K. Whittlesey, J. M. J.
Williams, Dalton Trans. 2009, 753; f) G. E. Dobereiner, R. H. Crabtree,
Chem. Rev. 2010, 110, 681; g) G. Guillena, D. J. Ramón, M. Yus, Chem.
Rev. 2010, 110, 1611; h) R. Yamaguchi, K. I. Fujita, M. Zhu, Heterocycles
2010, 81, 1093; i) Y. Obora, Y. Ishii, Synlett 2011, 30; j) S. Bähn, S. Imm, L.
Neubert, M. Zhang, H. Neumann, M. Beller, ChemCatChem 2011, 3,
1853; k) J. Moran, M. J. Krische, Pure Appl. Chem. 2012, 84, 1729; l) C.
Gunanathan, D. Milstein, Science 2013, 341, 249.
[2] Y. Shvo, R. M. Laine, J. Chem. Soc. Chem. Commun. 1980, 753.
[3] a) R. Grigg, T. R. B. Mitchell, S. Sutthivaiyakit, N. Tongpenyai, J. Chem.
Soc. Chem. Commun. 1981, 611; b) R. Grigg, T. R. B. Mitchell, S. Sutthi-
vaiyakit, N. Tongpenyai, Tetrahedron Lett. 1981, 22, 4107.
[4] a) Y. Watanabe, Y. Tsuji, Y. Oshugi, Tetrahedron Lett. 1981, 22, 2667; b) Y.
Watanabe, Y. Tsuji, H. Ige, Y. Ohsugi, T. Ohta, J. Org. Chem. 1984, 49,
3359.
[5] For selected recent contributions concerning ruthenium, see: a) M.
Haniti, S. A. Hamid, J. M. J. Williams, Chem. Commun. 2007, 725; b) A.
Tillack, D. Hollmann, D. Michalik, M. Beller, Eur. J. Org. Chem. 2008,
4745; c) M. H. S. A. Hamid, C. L. Allen, G. W. Lamb, A. C. Maxwell, H. C.
Maytum, A. J. A. Watson, J. M. J. Williams, J. Am. Chem. Soc. 2009, 131,
1766; d) A. J. Blacker, M. M. Farah, M. I. Hall, S. P. Marsden, O. Saidi,
J. M. J. Williams, Org. Lett. 2009, 11, 2039; e) J. He, J. W. Kim, K. Yamagu-
chi, N. Mizuno, Angew. Chem. Int. Ed. 2009, 48, 9888; Angew. Chem.
2009, 121, 10072; f) G. W. Lamb, A. J. A. Watson, K. E. Jolley, A. C. Max-
well, J. M. J. Williams, Tetrahedron Lett. 2009, 50, 3374; g) F. Shi, M. K.
[11] Imidazoles: a) C. Crotti, E. Farnetti, S. Licen, P. Barbieri, G. Pitacco, J. Mol.
Catal. A 2014, 382, 64; b) T. Hille, T. Irrgang, R. Kempe, Chem. Eur. J.
2014, 20, 5569.
[12] Amide from amine: J. R. Khusnutdinova, Y. Ben-David, D. Milstein, J. Am.
Chem. Soc. 2014, 136, 2998.
[13] Indoles: M. PeÇa-López, H. Neumann, M. Beller, Chem. Eur. J. 2014, 20,
1818.
[14] a) R. W. Castelino, G. Hallas, J. Chem. Soc. B 1971, 793; b) H. Wang, Z. Lu,
S. J. Lord, K. A. Willets, J. A. Bertke, S. D. Bunge, W. E. Moerner, R. J.
Twieg, Tetrahedron 2007, 63, 103; c) A. Srivastava, P. K. Singh, M. Kumb-
hakar, T. Mukherjee, S. Chattopadyay, H. Pal, S. Nath, Chem. Eur. J. 2010,
16, 9257; d) L. Zhu, C. Zhong, Z. Liu, C. Yang, J. Qin, Chem. Commun.
2010, 46, 6666; e) J. Shao, S. Ji, X. Li, J. Zhao, F. Zhou, H. Guo, Eur. J.
Org. Chem. 2011, 6100; f) N. Hebbar, C. Fiol-Pettit, Y. Ramondenc, G. PlØ,
ChemCatChem 2015, 7, 1090 – 1096
www.chemcatchem.org
1095
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
N. PlØ, Tetrahedron 2011, 67, 2287; g) A. M. Piloto, G. Hungerford, S. P. G.
Costa, M. S. T. Goncalves, Eur. J. Org. Chem. 2013, 7715; h) G. Wu, F.
Kong, J. Li, W. Chen, X. Fang, C. Zhang, Q. Chen, X. Zhang, S. Dai, Dyes
Pigm. 2013, 99, 653; i) S. Kamino, M. Murakami, M. Tanioka, Y. Shirasaki,
K. Watanabe, J. Horigome, Y. Ooyama, S. Enomoto, Org. Lett. 2014, 16,
258; j) T. N. Murakami, N. Koumura, M. Kimura, S. Mori, Langmuir 2014,
30, 2274; k) G. J. Park, Y. J. Na, H. Y. Jo, S. A. Lee, C. Kim, Dalton Trans.
2014, 43, 6618. l) S. Lucas, M. Negri, R. Heim, C. Zimmer, R. W. Hart-
mann, J. Med. Chem. 2011, 54, 2307.
[23] CCDC 1049270 contains the supplementary crystallographic data for
the protonated cat. E demonstrating the proton responsive ability of
such complex.
[24] For the formation of reduced N-alkylated products from aniline and
propane-1,3-diol, see: S. D. Lacroix, A. Pennycook, S. Liu, T. T. Eisenhart,
A. Marr, Catal. Sci. Technol. 2012, 2, 288.
[25] It should be noted that on large scale reactions, the use of 1.3 equiv. of
1a is sufficient to ensure similar yields.
[26] For, reviews, see: a) G. Masson, C. Lalli, M. Benohoud, G. Dagousset,
Chem. Soc. Rev. 2013, 42, 902; b) X. X. Jiang, R. Wang, Chem. Rev. 2013,
113, 5515.
[15] S. Liu, W. H. Wang, Y. L. Dang, Y. Fu, R. Sang, Tetrahedron Lett. 2012, 53,
4235.
[16] Y. Tsuji, H. Nishimura, K. T. Huh, Y. Watanabe, J. Organomet. Chem. 1985,
286, c44.
[17] B. Sundararaju, Z. Tang, M. Achard, G. V. M. Sharma, C. Bruneau, Adv.
Synth. Catal. 2010, 352, 3141.
[18] N. G. Leonard, G. V. Parker, P. G. Williard, W. H. Bernskoetter, J. Inorg. Or-
ganomet. Polym. 2014, 24, 157.
[19] CCDC 1044096 contains the supplementary crystallographic data for
cat. C.
[27] For julolidines with electron-rich dienophile or styrene by the Povarov
reaction, see: a) J. Legros, B. Crousse, M. OurØvitch, D. Bonnet-Delpon,
Synthesis 2006, 1899; b) J. Baptista Simðes, A. de Fµtima, A. A. Sabino,
F. T. de Aquino, D. L. da Silva, L. C. A. Barbosa, S. A. Fernandes, Org.
Biomol. Chem. 2013, 11, 5069.
[28] For a selected recent application, see: a) C. Min, A. Sanchawala, D.
Seidel, Org. Lett. 2014, 16, 2756, and references cited therein.
[29] Z. Sahli, B. Sundararaju, M. Achard, C. Bruneau, Org. Lett. 2011, 13, 3964.
[20] CCDC 1044095 contains the supplementary crystallographic data for
cat. D.
[21] C. M. Reisinger, R. J. Nowack, D. Volkmer, B. Rieger, Dalton Trans. 2007,
272.
Received: January 20, 2015
[22] CCDC 1044356 contains the supplementary crystallographic data for
cat. E.
Published online on March 10, 2015
ChemCatChem 2015, 7, 1090 – 1096
www.chemcatchem.org
1096
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim