Guanylation/cyclisation of amino acid esters using an imidazolin-2-iminato titanium initiator

Article abstract of DOI:10.1039/c8dt04630a

We report the catalytic hydroamination of amino acid esters with carbodiimides and isocyanates to furnish corresponding quinazolinone and urea derivatives under mild conditions using two titanium(iv) complexes [(Im^RN)₂Ti(NMe₂)₂] (R = tBu, 2a; R = Mes, 2b), which were synthesised by reacting tetrakis(dimethylamido)titanium(iv) [Ti(NMe₂)₄] with imidazolin-2-imine [Im^RNH; R = tert-butyl (tBu) (1a), mesityl (Mes) (1b)] in a 1 : 2 molar ratio in toluene. Furthermore, the reaction of titanium complex 2a with 2,6-diisopropylphenylamine (DippNH₂) resulted in the corresponding mixed ligand titanium complex [κ¹-(Im^tBuN)₂Ti(NMe₂)(HNDipp)] (3a). In contrast, the reaction of complex 2a with 2,6-dimethyl phenol afforded the mono-imidazolin-2-iminato Ti^IV phenolate complex [κ¹-(Im^tBuN)Ti(O-1,6-Me₂C₆H₃)₃] (4a). The solid-state structures of complexes 2b, 3a, and 4a, established by single crystal X-ray diffraction analyses, confirmed a very short bond between titanium and imidazolin-2-iminato nitrogen in each case. Titanium complexes 2a and 2b exhibited relatively high conversion, superior selectivity and broad functional group tolerance in both hydroamination reactions under mild conditions. We propose the most plausible mechanism for the guanylation/cyclisation of amino acid esters to carbodiimides on the basis of a number of controlled reactions.

Full text of DOI:10.1039/c8dt04630a

View Article Online
View Journal
Dalton
Transactions
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: T. K. K. Panda, S.
Das and J. Bhattacharjee, Dalton Trans., 2019, DOI: 10.1039/C8DT04630A.
This is an Accepted Manuscript, which has been through the
Volume 45 Number
1 7 January 2016 Pages 1–398
Royal Society of Chemistry peer review process and has been
accepted for publication.
Dalton
Transactions
Accepted Manuscripts are published online shortly after
An international journal of inorganic chemistry
www.rsc.org/dalton
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 1477-9226
PAPER
Joseph T. Hupp, Omar K. Farha et al.
Efficient extraction of sulfate from water using
framework
a Zr-metal–organic
rsc.li/dalton

Please do not adjust margins
Page 1 of 9
Dalton Transactions
View Article Online
DOI: 10.1039/C8DT04630A
Journal Name
ARTICLE
Guanylation/Cyclisation of Amino Acid Esters using Imidazolin-2-
iminato Titanium Initiator
Suman Das,a‡ Jayeeta Bhattacharjeea‡ and Tarun K. Panda*a
Received 00th January 20xx,
Accepted 00th January 20xx
We report the catalytic guanylation/cyclisation of amino acid esters with carbodiimides and isocyanates to
furnish corresponding quinazolinone and urea derivatives under mild conditions using two titanium(IV)
DOI: 10.1039/x0xx00000x
complexes [(ImRN)2Ti(NMe2)2] (R
= tBu, 2a; R = Mes, 2b), which were synthesised by reacting
www.rsc.org/
tetrakis(dimethylamido)titanium(IV) [Ti(NMe2)4] with imidazolin-2-imine [ImRNH; R = tert-butyl (tBu) (1a),
mesityl (Mes) (1b)] in a 1:2 molar ratio in toluene. Further, the reaction of titanium complex 2a with 2,6-
diisopropylphenylamine (DippNH2) resulted in the corresponding mixed ligand titanium complex [1-
(ImtBuN)2Ti(NMe2)(HNDipp)] (3a). In contrast, the reaction of complex 2a with 2,6-dimethyl phenol afforded
the mono-imidazolin-2-iminato TiIV phenolate complex [1-(ImtBuN)Ti(O-1,6-Me2C6H3)3] (4a). The solid-state
structures of complexes 2b, 3a, and 4a, established by single crystal X-ray diffraction analyses, confirmed a
very short bond between titanium and imidazolin-2-iminato nitrogen in each case. Titanium complexes 2a and
2b exhibited relatively high conversion, superior selectivity and broad functional group tolerance in both
guanylation and cyclisation rections under mild conditions. We propose the most plasubile mechanism for
guanylation/cyclisation of amino acid esters to carbodiimides and isocyanates on the basis of a number of
controlled reactions.
of halo benzoic acid and guanidine but the relatively narrow
substrate scope and the large requirement of additives rendered it
unfavourable.7 In 2016, Odel et al. introduced a convenient and
efficient approach for the synthesis of 2-amino quinazolinones via
domino carbonylation/cyclisation of readily available ortho-iodo
anilines with cyanamide, but the toxicity of CO gas limited this
method from being used for sustainable production.8 Pd and Mo–
Introduction
Quinazolinones, an important class of six-membered nitrogen-
containing heterocyclic compounds, have been widely used in
anticancer, antimalarial, anti-inflammatory and anti-tuberculosis
medication due to their diverse biological properties.1 Additionally,
quinazolinones are versatile and have been used as ligands for
benzodiazepine and AMPA receptors in the central nervous system
or as DNA binders.2 Quinazolinones and their derivatives have also
found considerable utility in the synthesis of natural products.3 On
the other hand, urea derivatives of amino acid esters are also used
as ligands in coordination chemistry, and synthons for challenging
organic transformations.4 Due to this, over the past decade or so, the
development of efficient synthetic methods for producing
quinazolinones and their derivatives has garnered attention from
researchers.5–6 However, until now, the efficient and economical
mediated
synthesis
of
quinazolin-4(3H)-ones
through
cyclocarbonylation using microwave irradiation, as reported by
Roberts et al., also falls in the same category.9 On the other hand, Co,
Cu, and Pd–metal catalysed aminolysis of isatoic anhydride followed
by reaction with isocyanide,10 isothiocyanate11 or cyanamide12 is a
popular method for the synthesis of miscellaneous derivatives of
quinazolinones. However, in all cases, toxic reagents are usually
required, and long and tedious procedures leading to unsatisfactory
overall yields, are both disadvantages of the above-mentioned
pathways. Hence, a novel catalytic pathway starting from earth-
abundant, environment-friendly and non-toxic metals as well as
substrates need to be developed to construct quinazolinones.13
synthesis of quinazolinones was
adequately explored. In 2015, Xi et al. reported the synthesis of
quinazolinones through CuI-catalysed intra-molecular N-arylations
a challenging task and not
Recently
Xi
and
Zhang
introduced
Zn-catalysed
a. Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi,
Sangareddy 502285, Telangana, India. Fax: + 91(40) 2301 6032; Tel: + 91(40)
2301 6036; E-mail: tpanda@iith.ac.in.
guanylation/amidation of amino acid esters with carbodiimides to
produce various quinazolines.14 In addition, Bei Zhao and his
research group developed a rare-earth metal amide as a catalyst for
the guanylation/cyclisation of amino acid esters followed by
carbodiimides.15 However, it is well known that not only are rare-
‡ Both the authors contributed equally.
Electronic Supplementary Information (ESI) available: Text giving experimental
details for the catalytic reactions, 1H, 13C{1H} and spectra of quinazolinones 5a - 5t,
and urea 6a – 6l and Ti complexes 2a, 2b, 3a, 4a. in Supporting Information. For
crystallographic details in CIF see DOI: 10.1039/b000000x/.
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
Dalton Transactions
Page 2 of 9
ARTICLE
Journal Name
earth metals less abundant and expensive, their compounds are also carbodiimides and isocyanates to afford corresponding
View Article Online
difficult to handle.16–19 With this in mind, we wanted to develop a quinazolinone and urea derivatives under mild conditions having a
DOI: 10.1039/C8DT04630A
rich catalytic chemistry using relatively inexpensive and earth- broad substrate scope.
abundant group-4 metals in the guanylation/cyclisation of amino
acid followed by carbodiimides to synthesise differently substituted
quinazolinone skeletons.20 Among the group-4 metals, titanium has
been given considerable attention in the last few years due to its
special and versatile coordination geometry,21–28 followed by its
novel chemical reactivity in numerous stoichiometric and catalytic
Results and discussion
Synthesis of titanium(IV) complexes: The bis-imidazolin-2-iminato
titanium(IV) complexes [1-(ImRN)2Ti(NMe2)2] (R = tBu, 2a; R = Mes,
2b) were prepared by the treatment of tetrakis(dimethyl-
amido)titanium(IV) [Ti(NMe2)4] with protic ligand imidazolin-2-imine
[ImRNH; R = tert-butyl (tBu) (1a), mesityl (Mes) (1b)] in a 1:2 molar
ratio in toluene in high yield (Scheme 1). Further reaction of titanium
complex 2a with 2,6-diisopropylamine (DippNH2) at 60°C gave the
reactions
such
as
hydroaminations,
hydroalkoxylations,
hydrosilylations, polymerisations, alkyne oligomerisations and
various small-molecule activations.21–28 However, the insertion of
heterocumulenes into N–H bonds of amino acid esters followed by
cyclisation to produce quinazolinones has not been explored up to
now in titanium metal chemistry. Hence, employing titanium as a
catalyst in the guanylation/cyclisation of amino acid esters with
carbodiimides would be a rational next step.
corresponding
mixed
ligand
titanium
complex
[1-
(ImtBuN)2Ti(NMe2)(HNDipp)] (3a). In contrast, the reaction of
complex 2a with 2,6-diphenyl phenol under similar reaction
conditions afforded the mono-imidazolin-2-iminato TiIV phenolate
complex [1-(ImtBuN)Ti(O-1,6-Me2C6H3)3] (4a) (Scheme 1).
Previous Work
RCH2X (X = COH, COOH, COOR)
R
N
R
N
N
Ti
N
R
Cu, Ir, Rh complex
Base, acid and ligand
N
Toluene
N
N
+
NH
Ti(NMe2)4
2
60 o C, 12 h
- 2 HNMe2
N
R
N
R
N
R
RCH2X (X = H, OH, NH2)
ImRNH [R = tBu (1a); Mes (1b)]
82%
R = tBu(2a); Mes(2b),
OH
Cu complex, Oxidant, ligand
N
H2
Toluene
O
60 o C, 12 h
Y
R1
-HNMe2
PhBr + CO
N
tBu
N
tBu
N
Toluene
tBu
O
Ti
O
N
H
X
60 o C, 12 h
R2
Pd(OAc)2, BuPAd2(ligand), DBU(Base)
N
N
N
H
X = NH2, Br, or Cl
Y = COOH, CONH2,
COOCH3, or Br
N
N
Ti
N
N
-H Me2
N
O
N
tBu
N
tBu
N
tBu
R1, R2 = alkyl, Ar
RNH2 + RC(OEt)3 + CO
74%
74%
4a
(
)
Pd(OAc)2, BuPAd2(ligand), DIPEA(Base)
3a
(
)
Scheme 1. Synthesis of TiIV complexes 2a, 2b, 3a and 4a.
Zn(OTf)2, Mo(CO)6,
Base, Solvent, lignd, Oxidant
All the new titanium complexes 2a, 2b, 3a, and 4a showed good
solubility in common organic solvents such as THF, pentane, and
toluene and were characterised using standard spectroscopic and
analytical techniques. The solid-state structures of complexes 2b, 3a
and 4a were established by single-crystal X-ray diffraction analysis.
This Work
O
O
R
N
Ti Cat 5 mol%
Neat, 60 o
Slovent free, CO free, Oxidant free, Base free,
OR1
RN=C=NR
+
R
NH2
N
N
C
H
1
The H NMR spectra of all the TiIV complexes 2a, 2b, 3a, and 4a are
consistent with their composition.
Figure 1. Reported catalysts for guanylation/cyclisation of amino acid
esters with carbodiimides.
We have recently reported the use of the imidazolin-2-iminato
titanium complex [(ImDippN)Ti(NMe2)3] (ImN = imidazolin-2-iminato,
Dipp = 2,6-iPr2C6H3) in the catalytic hydroamination of various amines
to heterocumulenes.28 We have also reported TiIV amido complex–
supported phosphinamido chalcogenide ligands as pre-catalysts for
the chemoselective hydroboration and cyanosilylation of carbonyl
compounds followed by the addition of an E–H (E = N, O, S, P, C) bond
to heterocumulenes under ambient conditions.30–32 In a continuation
of our ongoing project, we wanted to extend the applicability of TiIV
complexes as catalysts for guanylation/cyclisation of amino acid
esters with carbodiimides and isocyanates. We report here the
synthesis of bis-imidazolin-2-iminato titanium (IV) complexes [1-
(ImRN)2Ti(NMe2)2] (R = tBu, 2a; R = Mes, 2b) and their catalytic
application in hydroamination/cyclisation of amino acid esters with
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 9
Dalton Transactions
Please do not adjust margins
Journal Name
ARTICLE
Figure 2. Molecular solid-state structure of 2b. Hydrogen atoms are
omitted for clarity. Selected bond lengths (Å) and angles (°) are: Ti1–
N1 1.847(2), Ti1–N2 1.858(2), Ti1–N4 1.927(2), Ti1–N3 1.930(2), N1–
Ti1–N2 113.94(11), N1–Ti1–N4 114.02(11), N2–Ti1–N4 104.56(10),
N1–Ti1–N3 106.40(10), N2–Ti1–N3 115.12(11), N4–Ti1–N3
102.42(11), C1–N1–Ti1 157.6(2), C2–N2–Ti1 161.9(2), C44–N3–Ti1
128.8(2), C43–N3–Ti1 120.6(2), C45–N4–Ti1 123.4(2), C46–N4–Ti1
125.84(19).
2, 4-electron donation of the monoanionic imidazVoieliwn-A2rt-icimle iOnnalitnoe
DOI: 10.1039/C8DT04630A
ligands and these values are consistent with those of the previously
reported complexes [1-(ImtBuN)2TiMe2] and [1-(ImtBuN)2TiCl2] by
Tamm et al.33 In complexes 3a and 4a, the imidazolin-2-iminato
moiety coordinates with the titanium ion in an essentially linear
fashion [Ti1‒N1‒C1 = 170.85(16)° and Ti1-N2-C12 164.72(16)° for
complex 3a and Ti1‒N1‒C1 = 168.30(15)° for complex 4a]. However,
a slight deviation from linearity was observed in complex 2b
[Ti1‒N1‒C1 = 157.6(2)°, Ti1-N2-C2 161.9(2)], due perhaps to the
presence of tert-butyl groups around the titanium ion. The Ti–Namide
distances in complex 2b [1.927(2) and 1.930(2) Å] and complex 3a
[1.9355(19) Å] are very similar and consistent with those in
previously reported titanium amido complexes29 and slightly shorter
than the Ti–Nanilido bond measuring 2.0249(17) Å in complex 3a. It is
noteworthy that 2,6-diisopropylaniline replaced one dimethylamido
group to form the titanium complex 3a with three different ligand
systems keeping the titanium imidazolin-2-iminato bond
unperturbed. In contrast, complex 4a represents the imidazolin-2-
iminato titanium tris arylphenoxide complexes obtained from the
cleavage of two titanium amido bonds and one titanium imidazolin-
2-iminato bond of complex 2a.
The solid-state structure of all the complexes 2b, 3a, 4a, established
by single-crystal X-ray diffraction analysis. Details of the structural
parameters are given in Table S1 in the Supporting Information. The
solid-state structure of complex 2b is shown in Figure 2, whereas
Figures 3 and 4 represent the solid-state structures of complexes 3a
and 4a respectively. In all the titanium complexes, a 1-coordination
mode of the imidazolin-2-iminato ligand was observed. Complex 2b
crystallises in the orthorhombic space group Pccn with eight
molecules in the unit cell. In complex 2b the titanium ion is bonded
with two imidazolin-2-iminato ligands along with two dimethyl
amido groups. Complexes 3a and 4a crystallise in the monoclinic
space group C 2/c and triclinic space group P-1 respectively. In case
of 3a, titanium ion is attached with one imidazolin-2-iminato ligand,
one dimethylamido (–NMe2) group and one 2,6-diisopropylphenyl
anilido group. However, three 2,6-dimethyl phenoxide ligands are
attached to the titanium ion in complex 4a. Thus, in all the complexes
– 2a, 3a, and 4a – the titanium (IV) ion is tetra-coordinated to adopt
a distorted tetrahedral geometry around the metal ion.
Figure 4. Molecular solid-state structure of 4a. Selected bond lengths
(Å) and angles (°) are: Ti1–N1 1.7738(16), Ti1–O1 1.8128(14), Ti1–O2
1.8465(14), Ti1–O3 1.8505(13), N1–Ti1–O1 110.35(7), N1–Ti1–O2
111.73(8), O1–Ti1–O2 108.29(7), N1–Ti1–O3 111.35(7), O1–Ti1–O3
107.26(7), O2–Ti1–O3 107.70(6), C12–O1–Ti1 175.08(14), C20–O2–
Ti1 157.80(12), C28–O3–Ti1 148.25(12), C1–N1–Ti1 168.30(15).
Catalysis
Figure 3. Molecular solid-state structure of 3a. Selected bond lengths
(Å) and angles (°) are: Ti1–N1 1.8242(18), Ti1–N2 1.8334(17), Ti1–N4
1.9355(19), Ti1–N3 2.0249(17), N1–Ti1–N2 112.04(8), N1–Ti1–N4
105.32(8), N2–Ti1–N4 113.17(8), N1–Ti1–N3 105.85(7), N2–Ti1–N3
109.75(8), N4–Ti1–N3 110.40(8), C1–N1–Ti1 170.85(16), C12–N2–Ti1
164.72(16), C23–N3–Ti1 140.02(14), C36–N4–Ti1 134.80(17), C35–
N4–Ti1 115.98(16).
All the titanium complexes 2a, 2b, 3a, and 4a were first tested as pre-
catalysts for the guanylation/cyclisation of amino acid esters with
carbodiimides to afford the corresponding quinazolinones. Initial
screening of the catalytic activity of the respective titanium
complexes was performed with a catalyst loading of 5 mol% starting
with ethyl 2-aminobenzoate and N,N’ diisopropylcarbodiimide (DIC)
under solvent-free conditions.
To our satisfaction, the titanium metal compounds we used,
including amido as well as phenolato derivatives of the imidazolin-2-
iminato Ti(IV) complexes, gave the desired cyclic product in good-to-
moderate yields, whereas the corresponding cyclic quinazolinone
In all complexes, very short Ti–Niminato bond lengths – [1.847(2) Å and
1.858(2) Å for complex 2b; 1.8242(18) Å and 1.8334(17) Å for
complex 3a and 1.7738(16) Å] for 4a – are observed due to the strong
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
Dalton Transactions
Page 4 of 9
ARTICLE
Journal Name
product was obtained up to 86% when complex 2b was used as the Table 2. A linear Plot of the product concentration vs time at a
View Article Online
DOI: 10.1039/C8DT04630A
pre-catalyst at 60°C and after 12 hours of reaction time. Hence, different concentration of catalyst (2b) confirms that with the
complex 2b was chosen as the ideal catalyst. All the results are increases of catalyst ratio, the rate of the guanylation/cyclisation
summarised in Table 1. Additionally, we investigated the effect of reaction increases linearly observed in Figure FS78, 79, 80 in SI.
solvent on the guanylation/cyclisation reaction, for which various
Table 2. Substrate scope for the guanylation/cyclisation of amino
acid esters with carbodiimides catalysed by complex 2b.
solvents such as THF, hexane, and toluene, were screened. However,
in all cases, we observed sluggish reactivity even after prolonged
reaction times (Table 1, entries 7–9). Subsequent screening of
temperature of the guanylation/cyclisation reaction based on the
titanium complexes suggested that 60°C was optimal (Table 1,
entries 6). Further, catalyst loading of 2.5% or 1% substantially
lowered the reaction rate and yields of 62% and 43% respectively
were observed after 24 hours of reaction (Table 1, entries 10-11).
R2
N
O
O
R2
Cat 5 mol%
OR1
NH2
+
2
N
R3
R
C
R2
N
Neat, 60 o C, 12 h
N
N
H
R2
5a-5t
O
O
N
O
N
O
N
O
Cy
N
Cy
N
N
N
N
NH
N
NH
O
NH
Cy
NH
N
NH
Cy
5b, 95%
O
5d, 90%
5e, 85%
5a, 96%
5c, 92%
Table 1. Screening of TiIV pre-catalysts for guanylation/cyclisation of
amino acid esters with carbodiimides.
O
O
O
N
F
MeO
MeO
Cy
Cy
N
F
Cy
N
N
N
N
N
N
NH
Cy
N
NH
N
NH
Cy
N
NH
Cy
NH
Cy
O
O
5h, 92%
O
5i, 70%
O
5j, 72%
O
5f, 84%
O
5g, 94%
O
Cat x mol%
N
N
OEt
NH2
C
+
N
I
N
NH
solvent free
Br
Br
Cl
Cy
Cl
N
N
N
N
N
NH
N
NH
N
NH
Cy
N
NH
Cy
N
NH
Entry
Catalyst
Solvent
t (h)
T (°)
Yielda(%)
5o, 85%
5n, 78%
5l, 78%
5m, 80%
1
2
3
4
5
6
7
8
None
2a
2b
3a
4a
2b
2b
2b
2b
2b
2b
2b
Neat
Neat
Neat
Neat
Neat
Neat
Toluene
THF
Hexane
Neat
Neat
Neat
Neat
12
80
None
5k, 76%
O
12
12
12
12
24
24
24
24
12
12
12
24
60
60
60
60
100
80
60
60
60
60
60
60
78
86
70
65
85
68
62
58
62
43
92
30
O
N
O
O
N
O
N
I
Cy
Cy
N
Cy
N
N
N
NH
Cy
N
NH
N
NH
Cy
N
N
NH
N
NH
Cy
5p, 83%
5q, 85%
5t, 82%
5r, 84%
5s, 85%
All reactions were performed in neat conditions using the amino acid
ester (0.6060 mmol, 1 equiv.), carbodiimide (1.212 mmol, 2 equiv.),
and complex 2b (23 mg, 0.0303 mmol, 5 mol%). Yields were
calculated by isolated yield.
9
10b
11c
12d
13
A series of substituted esters was examined to observe the electronic
effect of the substituents on the outcomes. Methyl 2-
aminobenzoates, bearing the electron-donating methyl, methoxy
and naphthyl groups, gave the corresponding aminoquinazolinones
in excellent yield, up to 95% (Table 2, 5a–5h and 5s–5t). Electron-
withdrawing groups such as fluoro, chloro, bromo, iodo, and
pyridinyl were also converted to the corresponding
aminoquinazolinones in good yield, within 12 hours of reaction time
Ti(NMe2)4
aIsolated yield. b,cReaction was performed using 2.5 mol % (entry 10) and
1 mol% (entry 11) of catalyst 2b. dmolar ratio of DIC: ethyl 2-
aminobenzoate to 2:1.
At first, we carried out the reaction with ethyl 2-aminobenzoate and
N,N’ diisopropylcarbodiimide (DIC), having a molar ratio of 1:1, which
substantially lowered the product yield. From TLC detection it was
clearly observed that a certain amount of reactant amino acid ester
always remained unreacted even after the reaction was quenched,
(Table 2, 5i−5r). When we changed from DIC to
a bulkier
carbodiimide, such as DCC, we were also able to obtain excellent
while DIC was fully consumed, indicating there was some side yields from various substituted amino acid esters (Table 2, 5b−5t).
reaction occurred with DIC which prevented the other substrate
amino acid ester from the complete reaction. During this reaction,
alcohol is released as a side product which further reacts with one
molecule of carbodiimides in the presence of catalyst 2b to afford
the corresponding isourea product. This observation is already well
reported by our group using -imido titanium complexes as
catalysts.31 However, to overcome this difficulty, we increased the
molar ratio of DIC to 2:1 with respect to the amino acid ester, which
dramatically increased the yields of the product up to 92% (Table 1,
entry 12). Thus, with 60°C and solvent-free condition taken as
optimal, we set out to examine the scope of various substrates of
amino acid esters followed by carbodiimides having molar ratio of
DIC to 2:1 in the presence of 5 mol% titanium complex 2b. The results
of all catalytic guanylation/cyclisation reactions are summarised in
Furthermore, we examined the effect of the ester group of 2-
aminobenzoates, which showed that esters bearing bulky leaving
groups, such as tBu, gave the corresponding products in outstanding
yields (Table 2, entries 5s and 5t). All the products (5a–5t) were fully
characterised with the help of NMR and mass spectrum studies (Figs
FS11–FS50 in SI) and yields were calculated from isolated yields.
Table 3. Substrate scope for the hydroamination of amino acid
ester with isocyanate catalysed by catalyst 2b.
O
O
O
C
OR1
OR1
Cat 5 mol%
R3
R3
+
N
R2
NH
NH2
Neat, 12 h, rt
R2
6a-6l
O
N
H
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 9
Dalton Transactions
Please do not adjust margins
Journal Name
ARTICLE
performed some controlled reactions. The stoichiometric reaction of
View Article Online
O
catalyst 2b with amine or alcohol indeDpeOnI:d1e0n.1t0ly39/sCh8oDwTe0d463t0hAe
displacement of dimethylamido group of the titanium complexes by
either anilide or alkoxide groups respectively under mild conditions,
and we have presented their respective solid-state structures in
Figures 2 and 3 respectively (Figs FS5–FS6 and FS7–FS8 in SI). In
contrast, the same reaction of DIC, DCC or N-phenyl isocyanate with
catalyst 2b did not proceed smoothly and required harsh conditions
to displace the dimethylamido group of the relevant titanium
complexes, as we have previously reported.29,31However, we reacted
Ti complex 2b with the more reactive N-phenyl isothiocyanate in a
1:2 molar ratio to obtain a bis-insertion product [(ImMesN)2Ti{2-
SC(NMe2)NPh}2] (7) in good yield at ambient temperature (Scheme
2) (Figs FS9–FS10 in SI). Due to the high reactivity of N-phenyl
isothiocyanate, a mixture of products was always obtained when
amino acid esters were reacted with N-phenyl isothiocyanate and
catalysed by complex 2b.
O
O
O
OEt
NH
OEt
NH
OEt
NH
OMe
NH
OMe
Cl
O
N
O
N
O
N
H
H
H
O
N
H
6a, 92%
O
6b, 95%
6c, 90%
6d, 85%
O
O
OMe
NH
O
OMe
NH
F
OMe
F
OMe
OMe
Cl
OMe
NH
O
N
NH
H
O
N
H
O
N
O
N
H
6e, 93%
O
H
6f, 89%
6h, 88%
6g, 86%
O
O
F
OMe
NH
O
Br
Br
OMe
OMe
NH
Cl
Br
OMe
NH
OMe
NH
Cl
O
N
H
O
N
H
O
N
H
O
N
6i, 84%
H
6j, 88%
6k, 90%
6l, 86%
All reactions were performed in neat condition using amino acid
ester (0.6060 mmol, 1equiv) isocyanate (0.6060 mmol, 1 equiv.), and
catalyst 2b (23 mg, 0.0303 mmol, 5 mol%). Yields were calculated by
isolated yield.
N
Ph
Ph
Mes
Mes
N
N
N
Mes
Mes
N
N
N
Mes
N
N
Ti
N
S
N
N
Toluene
12 h
N
Ti
N
Further, to increase the generality of the catalytic hydroamination of
amino acid esters, the nature of the substrate scope was extended
to isocyantes to illustrate the robust nature of catalyst 2b. Using
phenyl isocyanate and its derivatives such as 4-cholro, 4-methyl or 4-
methoxy phenyl isocyanate as the heterocumulene source, the
insertion of amino acid esters was studied, and the results are
summarised in Table 3 (6a–6l in Table 3, Figs FS51–FS74 in SI). We
observed that in all cases the insertion of the relevant amino acid
ester proceeded rapidly at room temperature to give the
corresponding urea product in quantitative yields (Table 3, 6a–6l),
but it failed to form its corresponding cyclic product. Insertion of
substituted methyl 2-aminobenzoates bearing both electron-
donating and electron-withdrawing groups to isocyanates proceeded
rapidly at room temperature to give corresponding inserted products
in excellent yields – up to 98%. The enhanced reactivity of phenyl
isocyanate with various amino acid esters with respect to
carbodiimides can be explained by the stronger electrophilic
character of the isocyanate carbon atom.
2 PhNCS
+
N
N
S
Mes
Mes
Mes
N
N
Mes = 2,6-Me2C6H3
84%
(7)
Scheme 2. Reaction of TiIV complex 2b with N-phenyl-isothiocyanate
to give 7.
Ti complex 7 was characterised using spectroscopic methods (Figs
FS9–FS10 in SI) and its solid-state structure was established by single-
crystal x-ray analysis. As shown in Figure 6, the solid-state structure
of complex 7 confirmed the attachment of two thioureate fragments
to the titanium metal in 2-coordination mode through the sulphur
and nitrogen atoms. Two four-membered metallacycles
(S1‒C7‒N7‒Ti1 and S2‒C10‒N9‒Ti1) were formed by the chelation
of two thioureate building blocks, having an average bite angle of
64.48° (S‒Ti‒N).
Figure 5. Molecular structures of quinazolinones 5a (left) and 5k
(right) in the solid state.
Figure 6. Molecular solid-state structure of complex 7. Selected bond
lengths (Å) and angles (°) are: Ti1–N4 1.8377(16), Ti1–N1 1.8568(16),
Ti1–N9 2.2590(16), Ti1–N7 2.2980(17), Ti1–S1 2.4889(6), Ti1–S2
2.5141(6), N4–Ti1–N1 105.26(7), N4–Ti1–N9 153.01(7), N1–Ti1–N9
93.21(7), N4–Ti1–N7 93.16(6), N4–Ti1–N7 152.16(7), N9–Ti1–N7
78.01(8), N4–Ti1–S1 104.59(5), N1–Ti1–S1 90.38(5), N9–Ti1–S1
94.61(4), N7–Ti1–S1 64.48(5), N4–Ti1–S2 91.72(5), N1–Ti1–S2
103.50(5), N9–Ti1–S2 64.49(4), N7–Ti1–S8 96.48(5), S1–Ti1–S2
155.12(2), C7–S1–Ti1 82.07(7), C10–S2–Ti1 81.30(7), C1–N1–Ti1
In addition, to confirm the products of cyclisation, we isolated their
crystal structures by means of single-crystal x-ray analysis. The solid-
state structures of cyclisation products 5a and 5k obtained from DIC
followed by ethyl 2-aminobenzoate and 5-chloro-methyl 2-
aminobenzoate are shown in Figure 5.
Plausible mechanism
To explore the most plausible mechanism of the catalytic
guanylation/cyclisation of amino acid esters to carbodiimides, we
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 6 of 9
ARTICLE
Journal Name
169.74(15), C4–N4–Ti1 173.18(15), C7–N7–Ti1 99.34(13), C49–N7–
Ti1 136.42(13), C10–N9–Ti1 101.38(12), C55–N9–Ti1 129.56(13).
View Article Online
DOI: 10.1039/C8DT04630A
Experimental
General: All manipulations of air-sensitive materials were performed
with the rigorous exclusion of oxygen and moisture in flame-dried
Schlenk-type glassware either on a dual manifold Schlenk line,
interfaced to a high vacuum (10-4 torr) line or in an argon-filled M.
Braun glove box. Hydrocarbon solvents (toluene and n-pentane)
were distilled under nitrogen from LiAlH4 and stored in the glove box.
1H NMR (400 j) and 13C{1H} NMR (100 MHz) spectra were recorded
on a BRUKER AVANCE III-400 spectrometer. BRUKER ALPHA FT-IR
was used for FT-IR measurement. Elemental analyses were
performed on a BRUKER EURO EA at the Indian Institute of
Technology Hyderabad. Imidazolin-2-imine [ImRNH] (R = tBu, 1a; R =
Mes, 2b] were prepared according to published procedure.34 The
starting materials 2,6-disopropylaniline, 2,6-dimethylalcohol, and
phenylisocynate, phenylisothiocynate were purchased from Sigma
Aldrich and used without further purification. The NMR solvent C6D6
were purchased from Sigma Aldrich.
R
N
N
R
N
N
N
Ti
R
N
R
N
NH2
O
(2b)
N
OR
O
N
[Ti] = [ImRNTi(NMe2)]
N
HNMe2
R
N
NH
H
N
ImRN =
iPr
N
N
Ti
N
R
C
N
ROH
O
C
N
N
N
Cyclisation
iPr
iPr
OR
[2b]
(I)
OR
O
iPr
N
C
N
OR
N
N
H
H
N
N
Ti
NH
H
O
O
RO
OR
(II)
NH2
NH
insertion
N
O
Preparation of [(ImRN)2Ti(NMe2)2] (R = tBu, 2a; Mes, 2b): In a dry 25
mL Schlenk flask, compound [ImRNH; R = tBu; (200 mg, 1.024 mmol)
and 5 mL of toluene were placed together. To this solution a mixture
of tertrakis(dimethylamino)titanium (114 mg, 0.512 mmol) was
added and the resulting reaction mixture was stirred at 60°C for 12
hours. The solvent was evaporated under vacuum, and a red-
coloured residue was obtained.
N
RO
Ti
(III)
1
2a. Yield: 0.150 g, 75%. H NMR (400 MHz, C6D6, 25 ºC): δH 5.98 (s,
2H, NCH), 3.58 (s, 6H, N(CH3)3), 1.64 (s, 18H, C(CH3)3), 13C{1H} NMR
(100 MHz, C6D6): δH 140.7 (NCN), 106.5 (NCH=CHN), 54.9 (C(CH3)3),
47.2 (N(CH3)2), 28.4 (C(CH3)3), 28.1 (C(CH3)3) ppm. Elemental
Analysis: C26H52N8Ti (524.61): Calcd. C 59.53, H 9.99, N 21.36. Found
C 59.37, H 9.68, N 23.09.
Scheme 3. Proposed catalytic cycle for guanylation/cyclisation of
amino acid esters with diisopropylcarbodiimide by TiIV complex 2b.
Based on the above observations, a plausible mechanism for the
catalytic guanylation/cyclisation of amino acid esters is given in
Scheme 3. The first step is the aminolysis of bis-imidazolin-2-iminato
titanium(IV) amide complex (2b) [1-(ImRN)2Ti(NMe2)2] with the
relevant aminobenzoate, resulting in the generation of an
intermediate product (I) with the displacement of the dimethylamine
group of complex 2b. The next step is the migratory insertion of DIC
into the corresponding Ti-amide bond in rapid equilibrium, providing
the intermediate product (II). Next, intramolecular nucleophilic
amidation in product (II) occurs, yielding the active species (III) with
the release of a molecule of alcohol by-product at the same time.
Finally, intermediate product (III) follows a protonolytic cleavage,
with an additional molecule of the aminobenzoate species to
regenerate the active species (I) with the release of the target
cyclisation product under the reaction condition. The by-product
alcohol is captured by another molecule of DIC in the presence of
catalyst 2b to yield the corresponding isourea under the same
conditions which were isolated and fully characterize by NMR
2b. The method of preparation of this complex was similar to that
used to prepare 2a, but with the use of [ImMesNH (200 mg, 0.63
mmol) and tetrakis(dimethylamino)titanium (70 mg, 0.32 mmol).
1
Yield: 0.170 g, 85%. H NMR (400 MHz, C6D6, 25 ºC): δH 6.81 (s, 4H,
Ar), 5.73 (s, 2H, NCH), 2.63 (s, 6H, N(CH3)3), 2.29 (s, 12H, o-attached
CH3), 2.22 (s, 6H, p-attached CH3) ppm. 13C{1H} NMR (100 MHz, C6D6):
δC 146.9 (ipso-phenyl), 138.6 (NCN), 136.8 (o-phenyl), 134.4 (p-
phenyl), 128.7 (m-phenyl), 111.7 (NC=NC), 46.7 (NCH3), 21.0 (p-
attach CH3), 18.6 (o-attached CH3) ppm. Elemental Analysis:
C46H60N8Ti (772.89): Calcd. C 71.48, H 7.82, N 14.50. Found C 71.22,
H 7.53, N 14.37.
Preparation of [1-(ImtBuN)2Ti(NMe2)(HNDipp)] (3a): In a dry 25 mL
Schlenk flask, compound 2a (200 mg, 0.39 mmol) and 5 mL of toluene
were added. To this solution 2,6-diisopropyl aniline (67 mg, 0.39
spectroscopy (Figs FS75–FS76 in SI). Similar observation is also mmol) was added and the resulting reaction mixture was stirred at
reported in literature.29 However, in case of hydroamination of
60°C for 12 hours. The solvent was evaporated under vacuum, the
amino acid ester with isocyanate catalysed by catalyst 2b gives only
red-coloured residue was dissolved in 3 mL of n-pentane and was
un-cyclised products (Table 3).
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 9
Dalton Transactions
Please do not adjust margins
Journal Name
ARTICLE
crystallised at ‒35°C. Yellow-coloured crystals were obtained after toluene/n-pentane (3:1) in an argon-filled atmosphere at -35 °C.
View Article Online
DOI: 10.1039/C8DT04630A
three days.
However, single crystals of 5a and 5k were obtained from a solution
1
3a: Yield: 0.135 g, 68%. H NMR (400 MHz, C6D6): δH 7.28 - 7.26 (d, of ethanol at room temperature. A crystal of suitable dimensions of
1H, Ar), 7.07 - 7.05 (m, 2H, Ar), 6.91 (t, 1H, 3JHH = 7.36 Hz, Ar), 5.92 (s, complexes 2b, 3a, 4a and 7 was mounted on a CryoLoop (Hampton
2H, NCH), 3.52 (s, 6H N(CH3)2), 3.20 (s, 1H, NH), 2.65 (sept, 2H, 3JHH
=
Research Corp.) with a layer of light mineral oil and placed in a
6.84 Hz, CH(CH3)2), 1.61 (s, 18H, C(CH3)3), 1.14 (d, 12H, 3JHH = 6.84 Hz, nitrogen stream at 150(2) K. The crystals of 5a and 7k were measured
CH(CH3)2) ppm. 13C{1H} NMR (100 MHz, C6D6): δC 152.1 (ipso-Ar), at 298 K. All measurements were made on a Rigaku Supernova X-
141.7 (ipso-Ar), 140.5 (NCN), 134.5 (o-phenyl), 132.1 (o-phenyl), calibur Eos CCD detector with graphite monochromatic Cu-Kα
123.1 (m-phenyl), 118.6 (m-phenyl), 115.9 (m-phenyl), 106.9 (1.54184 Å) (2b, 4a, 7, 5a and 5k) or Mo-Kα (0.71073 Å) (3a)
(NCH=CHN), 55.4 (C(CH3)3) 47.2 (N(CH3)2), 28.8 (C(CH3)3), 28.0 radiation. Crystal data and structure refinement parameters of
(C(CH3)3) 24.6 (CH(CH3)2), 22.4 (CH(CH3)2), ppm. Elemental Analysis: complexes 2b, 3a, 4a, 7, 5a and 5k are summarized in Table TS1. The
C48H83N9Ti (3a. DippNH2 834.10): Calcd. C 69.12, H 10.03, N 15.11. structures were solved by direct methods (SIR2004)[35] and refined
Found C 68.83, H 9.86, N 15.01.
on F2 by full-matrix least-squares methods, using SHELXL-97.[36] Non-
hydrogen atoms were anisotropically refined. H-atoms were
included in the refinement on calculated positions riding on their
Preparation of [1-(ImtBuN)Ti(O-2,6-Me2C6H3)3] (4a).
In a flame-dried 25 mL Schlenk flask, compound 2a (200 mg, 0.38 carrier atoms. The function minimized was [w(Fo2- Fc2)2] (w = 1 /
[2 (Fo2) + (aP)2 + bP]), where P = (Max(Fo2,0) + 2Fc2) / 3 with 2(Fo2)
from counting statistics. The function R1 and wR2 were (||Fo| -
|Fc||) / |Fo| and [w(Fo2 - Fc2)2 / (wFo4)]1/2, respectively. The
ORTEP-3 program was used to draw the molecules of 2b, 3a, 4a, 7,
5a and 5k. Crystallographic data (excluding structure factors) for the
structures reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 1880612 (5a), 1880613 (5k), 1880614 (4a),
1880615 (3a), 1880616 (2a), and 1880617 (7). Copies of the data can
be obtained free of charge on application to CCDC, 12 Union Road,
mmol) and 5 mL of toluene were taken. To this solution, 2,6-
dimethylphenol (139.6 mg, 1.15 mmol) was added along with 5 mL
of toluene. The resulting reaction mixture was stirred at 60°C for 12
hours. The solvent was evaporated under vacuum and a red-
coloured solid was obtained. The title compound was re-crystallised
from toluene at ‒35°C. Yellow-coloured crystals were obtained after
three days.
1
Yield: 0.145 g, 72%. H NMR (400 MHz, C6D6): δH 7.14 (m, 4H, Ar),
7.11 - 7.06 (m, 6H, Ar), 7.04 - 6.90 (m, 3H, Ar), 6.76 (s, 6H, Ar), 5.67
(s, 2H, NCH), 2.56 (s, 12H, N(CH3)3), 3.22 (s, 12H, N(CH3)2), 2.23 (s,
12H, p- phenyl CH3), 2.10 (s, 12H, o-phenyl CH3), ppm. 13C{1H} NMR
(100 MHz, C6D6): 162.4 (N=CH), 149.5 (ipso-C6H3), 142.5 (NCN), 140.0
(2-pyr), 139.6 (3-pyr), 136.9 (o-C6H3), 126.0 (p-C6H3), 123.2 (m-C6H3),
118.1 (4-pyr), 113.6 (5-pyr), 107.2 (NCH=CHN), 56.1 (C(CH3)3), 50.2
(N(CH3)2), 28.3 (C(CH3)3), 26.1 (CH(CH3)2), 22.8 (CH(CH3)2) ppm.
Elemental Analysis: C35H47N3O3Ti (605.63): Calcd. C 69.41, H 7.82, N
6.94. Found C 69.19, H 7.59, N 6.84.
Cambridge CB21EZ, UK (fax:
deposit@ccdc.cam.ac.uk).
+
(44)1223-336-033; email:
General
procedure
for
catalytic
titanium-mediated
guanylation/cyclisation of amino acid esters in presence of
heterocumulene:
In a 25 mL dry Schlenk flask inside a glovebox, a solution of respective
amino acid esters (0.606 mmol) was added drop-wise into the
mixture of the relevant heterocumulene (1.212 mmol) and catalyst
2b (23 mg, 0.0303 mmol). The yellow-coloured reaction mixture was
kept under room temperature or heated to 40–60°C, depending on
the nature of nucleophiles. The progress of the reactions was
monitored by TLC. Subsequently, the reaction mixture was quenched
by adding 20 mL of ethylacetate solvent, after which the basic
workup was made by adding 5 mL of saturated sodium bicarbonate
solution to reaction mixture. The product was collected in organic
layers and finally purified by column chromatography in (5:100)
hexane/ethylacetate eluent solvent. The products were identified by
according to 1H, 13C, and DEPT NMR spectroscopy (where necessary),
as well as MS analysis.
Preparation of [(ImMesN)2Ti{2-SC(NMe2)NPh}2] (7):
In a flame-dried 25 mL Schlenk flask, compound 2b (200 mg, 0.259
mmol) and 5 mL of toluene were taken. To this solution, N-phenyl
isothiocynate (68.9 mg, 0.534 mmol) was added along with 5 mL of
toluene. The resulting reaction mixture was stirred at room
temperature for 12 hours. The solvent was evaporated under
vacuum and a red-coloured solid was obtained. The title compound
was re-crystallised from toluene at ‒35°C. Yellow-coloured crystals
were obtained after three days.
Yield: 0.160 g, 80%. 1H NMR (400 MHz, C6D6): δ 7.07-7.00 (m, 2H, Ar),
6.89-6.87 (m, 4H, Ar), 6.77 - 6.73 (m, 2H, Ar), 5.93 (s, 2H, NCH), 1.98
(s, 18H, C(CH3)3), 1.38 (s, 18H, CH3), ppm. 13C{1H} NMR (100 MHz,
C6D6): 163.1 (N=CH), 145.2 (ipso-C6H3), 140.5 (NCN), 128.7 (o-C6H3),
120.2 (p-C6H3), 107.6 (NCH=CHN), 56.7 (C(CH3)3), 29.9 (C(CH3)3), 17.7
(CH3), 17.1 (CH3) ppm. Elemental Analysis: C60H70N10S2Ti (1043.25):
Calcd. C 69.08, H 6.76, N 13.43. Found C 67.79, H 6.53, N 13.29.
Conclusion
In conclusion, the synthesis of two bis(imidazolin-2-iminato)
titanium(IV) complexes [(ImRN)2Ti(NMe2)2] (R = tBu, 2a; R = Mes,
2b) is reported, along with further reactions with 2,6-
diisopropylphenylamine and 2,6-dimethylphenol to give
titanium complexes 3a and 4a. TiIV complexes 2a and 2b acted
X-ray crystallographic analyses: Single crystals of complexes 2b, 3a,
4a and 7 were grown from a concentrated solution of toluene or
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 8 of 9
ARTICLE
Journal Name
Org. Biomol. Chem, 2012, 10, 240 – 243; h) M. Dabiri, M.
Baghbanzadeh and A. S. Delbari, J. Comb. Chem.V2ie0w0A8r,tic1le0O, 7nl0in0e
– 703; i) O. B. Pawar, F. R. Chavan, DSO. IS: .10S.1a0k3a9t/eC8aDnTd04B6.30DA.
Shinde, Chin. J. Chem, 2010, 28, 69 – 71; j) H. B. Jalani, A. N.
Pandya, D. H. Panday, J. A. Sharma, V. Sudarsanam and K. K.
Vasu, Tetrahedron Lett, 2010, 51, 4062 – 4064; k) J. Zhou, and
J. Fang, J. Org. Chem, 2011, 76, 7730 – 7736; l) H. Hikawa, Y.
Ino, H. Suzuki and Y. Yokoyama, J. Org. Chem, 2012, 77, 7046
– 7051; m) L. Xu, Y. Jiang and D. Ma, Org. Lett, 2012, 14, 1150
– 1153; n) Y. P. Zhu, Z. Fei, M. C. Liu, F. C. Jia and A. X. Wu, Org.
Lett, 2013, 15, 378 – 381; o) A. V. Lygin and A. de Meijere, Org.
Lett, 2009, 11, 389 – 392; p) B. Ma, Y. Wang, J. Peng and Q.
Zhu, J. Org. Chem, 2011, 76, 6362 – 6366; q) J. E. R. Sadig, R.
Foster, F. Wakenhut and M. C. Willis, J. Org. Chem, 2012, 77,
9473 – 9486.
as efficient pre-catalysts for catalytic guanylation/cyclisation of
amino acid esters to carbodiimides and isocyanates, resulting in
corresponding quinazolinone and urea derivatives under mild
conditions. The TiIV catalyst 2b exhibited a large substrate scope
with relatively high conversion, superior selectivity and broad
functional group tolerance in both carbodiimide and isocyanate
reactions.
Conflicts of interest
There are no conflicts to declare.
7
8
X. Huang, H. Yang, H. Fu, R. Qiao, and Y. Zhao, Synthesis, 2009,
16, 2679.
Acknowledgements
B. Roberts, D. Liptrot, T. Luker, M. J. Stocks, C. Barber, N.
Webb, R. Dods and B. Martin, Tetrahedron Lett, 2011, 52,
3793.
This work was financially supported by the Science and Engineering
Research Board (SERB), Department of Science and Technology
(DST), India, under project no. (EMR/2016/005150). We thank Dr.
Hari Pada Nayek, Indian Institute of Technology (IITISM) Dhanbad for
his help in crystallography. We also thank to reviewers for their
valuable comments to improve the manuscript.
9
L. Akerbladh and L. R. Odell, J. Org. Chem, 2016, 81, 2966.
10 (a)F. Ji, M. Lv, W. Yi and C. Cai, Org. Biomol. Chem, 2014, 12,
5766. (b)S. Vidyacharan, N. C. Chaitra, A. Sagar and D.S.
Sharada, Synth. Commun, 2015, 45, 898. (c)F. Ahmadi and A.
Bazgir, RSC Adv. 2016, 6, 61955. (d)T. Wei, P. Xu, S. Wang and
S. Ji, Eur. J. Org. Chem. 2016, 5393. (e)B. Mirza, Tetrahedron
Lett, 2016, 57, 146.
11 M. Mahdavi, M. Asadi, M. Khoshbakht, M. Saeedi, M. Bayat,
A. Foroumadi and A. Helv. Shafiee, Chim. Acta 2016, 99, 378.
12 V. N. Murthy, S. P. Nikumbh, S. P. Kumar, L. V Rao and A.
Raghunadh, Tetrahedron Lett, 2015, 56, 5767.
13 (a)W. Zeghida, J. Debray, S. Chierici, P. Dumy and M.
Demeunynck, J. Org. Chem, 2008, 73, 2473. (b) A. S.
Shestakov, I. S. Bushmarinov, O. E. Sidorenko, A. Y. Potapov,
K. S. Shikhaliev and M. Y Antipin, Chem. Heterocycl. Compd.
2011, 47, 316. (c)C. Lecoutey, C. Fossey, S. Rault and F. Fabis,
Eur. J. Org. Chem, 2011, 2785. (d)J. Li, Y. Mi, J. He, X. Luo and
E. J Fan, Heterocyclic Chem, 2013, 50, 304.
14 Y. Chi, L. Xu, S. Du, H. Yan, W. Zhang and Z. Xi, Chem. - Eur. J,
2015, 21, 10369.
15 C. Lu, C. Gong, B. Zhao, L. Hu, and Y. Yao, J. Org. Chem, 2018,
83, 1154−1159.
16 R. J. Batrice and M. S. Eisen, Chem. Sci, 2016, 7, 939–944.
17 H. Liu, N. Fridman, M. Tamm and M. S Eisen, Organometallics,
2017, 36, 3896–3903.
18 I. S. R. Karmel, M. Tamm and M. S Eisen, Angew. Chem. Int.
Ed. 2015, 127, 12599-12602.
Notes and references
1
a) S. B. Mhaske and N. P. Argade, Tetrahedron, 2006, 62, 9787
– 9826; b) S. Sinha and M. Srivastava, Prog. Drug Res, 1994,
43, 143 – 238; c) S. E. de Laszlo, C. S. Quagliato, W. J. Greenlee,
A. A. Patchett, R. S. L. Chang, V. J. Lotti, T. B. Chen, S. A. Scheck,
K. A. Faust, S. S. Kivlighn, T. S. Schorn, G. J. Zingaro and P. K. S.
Siegl, J. Med. Chem. 1993, 36, 3207 – 3210; d) N. J. Liverton,
D. J. Armstrong, D. A. Claremon, D. C. Remy, J. J. Baldwin, R. J.
Lynch, G. Zhang and R. J. Gould, Bioorg. Med. Chem. Lett.
1998, 8, 483 – 486; e) W. Zhang, J. P. Mayer, S. E. Hall and J.
A. Weigel, J. Comb. Chem, 2001, 3, 255 – 256; f) A. Gopalsamy
and H. Yang, J. Comb. Chem, 2000, 2, 378 – 381.
M. Baraldi & R. Avallone & L. Corsi & I. Venturini & C. Baraldi
& M. L. Zeneroli. a) D. Arora, H. Kumar, D. Malhotra and M.
Malhotra, Pharmacologyonline, 2011, 3, 659 – 668; b) N.
Malecki, P. Carato, G. Rigo, J. F. Goossens, R. Houssin, C. Bailly
and J. P. Henichart, Bioorg. Med. Chem, 2004, 12, 641 – 647.
(a)A.V. Gulevich, A. S. Dudnik, N. Chernyak, and V. Gevorgyan,
Chem. Rev. 2013, 113, 3084. (b)K.C. Majumdar, P. Debnath, N.
De and B. Roy, Curr. Org. Chem, 2011, 15, 1760. (c)P.W. Davies
and M. Garzon, Asian J. Org. Chem, 2015, 4, 694.
(a)W.X. Zhang, L. Xu and Z. Xi, Chem. Commun. 2015, 51, 254–
265. (b)S.G. Zarate, A.G. Santana, A. Bastida and J. Revuelta,
Curr. Org. Chem, 2014, 18, 2711–2749. (c)T. Ishikawa and T.
Kumamoto, Synthesis, 2006, 737–752.
For reviews on these topic, see: a) D. J. Connolly, D. Cusack, T.
P. O'Sullivan and P. J. Guiry, Tetrahedron, 2005, 61, 10153 –
10202; b) J. D. Hepworth, C. D. Gabbut, B. M. Heron,
Comprehensive Heterocyclic Chemistry, 2nd ed., Pergamon
Press, Oxford, 1996.
2
3
4
5
19 R.J. Batrice, C. E. Kefalidis, L. Maron and M. S. Eisen, J. Am.
Chem. Soc, 2016, 138, 2114–2117.
20 (a) M. C. Rodríguez, I. R. García, R. N. R. Maecker, L. P.
Morales, J. E. Oltra, and A. R. Martínez, Org. Process Res. Dev.
2017, 21, 911−923. (b) Z. W. Davis-Gilbert and I. A. Tonks,
Dalton Trans., 2017, 46, 11522–11528. (c) K. S. Egorova and V.
P. Ananikov, Organometallics 2017, 36, 4071−4090.
21 (a)H. Tsurugi, R. Ohnishi, H. Kaneko, T. K. Panda and K.
Mashima, Organometallics, 2009, 28, 680-687; (b) T. K. Panda,
H. Tsurugi, K. Pal, H. Kaneko and K. Mashima,
Organometallics, 2010, 29, 34-37; (c) K. Naktode, R. K.
Kottalanka and T. K. Panda, New J. Chemistry, 2012, 36, 2280-
2285.
22 L. L. Schafer, J. C. H. Yim and N. Yonson, Wiley: New York,
2014, 1135−1258.
23 (a) E. Chong, P. Garcia and L. L. Schafer, Synthesis 2014, 46,
2884−2896. (b) A. S. Ryken and L. Laurel Schafer, Acc. Chem.
Res, 2015, 48, 2576−2586.
6
For selected examples, see: a) J. Hanusek, M. Sedlak, P.
Simunek and V. Sterba, Eur. J. Org. Che, 2002, 1855 – 1863; b)
N. Tavakoli-Hoseini, A. Davoodnia, Synth. React. Inorg. Met.-
Org. Nano-Metal Chem. 2012, 42, 76 – 81; c) X. S. Wang, K.
Yang, M. M. Zhang and C. S. Yao, Synth. Commun, 2010, 40,
2633 – 2646; d) M. M. Heravi, N. TavakoliHoseini and F. F.
Bamoharram, Synth. Commun, 2011, 41, 707 – 714; e) B.
Baudoin, Y. Ribeill and N. Vicker, Synth. Commun, 1993, 23,
2833 – 2837; f) B. P. Bandgar, Synth. Commun, 1997, 27, 2065
– 2068; g) A. J. A. Watson, A. C. Maxwell and J. M. J. Williams,
24 M. J. Stanford and A. P. Dove, Chem. Soc. Rev, 2010, 39,
486−494.
25 P. Galli and G. Vecellio, Prog. Polym. Sci. 2001, 26, 1287−1336,
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 9 of 9
Dalton Transactions
Please do not adjust margins
Journal Name
ARTICLE
26 S. E. Denmark and J. Fu, Chem. Rev, 2003, 103, 2763−2794.
27 B. Schetter, B. Ziemer, Schnakenburg, and R. Mahrwald,
Tetranuclear, J. Org. Chem, 2008, 73, 813−819.
28 E. P. Talsi, D. G. Samsonenko and K. P. Bryliakov, Chem. Eur. J,
2014, 20, 14329−14335.
View Article Online
DOI: 10.1039/C8DT04630A
29 K. Naktode, S. Das, J. Bhattacharjee, H. P. Nayek and T. K.
Panda, Inorg. Chem, 2016, 55, 1142−1153.
30 J. Bhattacharjee, S. Das, R. K. Kottalankaa and T. K. Panda,
Dalton Trans, 2016, 45, 17824-17832.
31 J. Bhattacharjee, and T. K. Panda, Inorganic Chem, 2018, 57,
12610−12623.
32 A. Harinath, J. Bhattcharjee, K. R. Gorantla, B. S. Mallik and T.
K. Panda, Eur. J. Org. Chem, 2018, 3180-3192.
33 M. Tamm, S. Randoll, E. Herdtweck, N. Kleigrewe, G. Kehr, G.
Erker and B. Rieger, Dalton Trans, 2006, 459−467.
34 M. Tamm, D. Petrovic, S. Randoll, S. Beer, T. Bannenberg, P.
Jones and G. Grunenberg, J. Org. Biomol. Chem, 2007, 5,
523−530
35 Altomare, M. C. Burla, G. Camalli, G. Cascarano, C. Giacovazzo,
A. Guagliardi and G. Polidori, J. Appl. Crystallogr. 1994, 27,
435-436.
36 G. M. Sheldrick, Acta Crystallogr. Sect. A: 2008, A64, 112-122.
ORCID ID
Tarun K. Panda: http://orcid.org/0000-0003-0975-0118
Jayeeta Bhattacharjee: http://orcid.org/0000-0003-3730-
6516
Suman Das: https://orcid.org/0000-0002-3855-1348
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
Please do not adjust margins