Ligand-free Iron(II)-Catalyzed N-Alkylation of Hindered Secondary Arylamines with Non-activated Secondary and Primary Alcohols via a Carbocationic Pathway

Article abstract of DOI:10.1002/adsc.201701183

Secondary benzylic alcohols represent a challenging class of substrates for N-alkylation of amines. Herein, we describe an iron(II)-catalyzed eco-friendly protocol for N-alkylation of secondary arylamines with secondary benzyl alcohols through a carbocationic pathway instead of the known borrowing hydrogen transfer (BHT) approach. Transiently generated carbocations, produced from alcohols via self-condensation, were coupled with arylamines to provide highly functionalized amine products. The scope of this methodology involves N-alkylation of primary, secondary and heterocyclic amines with primary/secondary benzylic, allylic and heterocyclic alcohols, which are common key structures in numerous pharmaceuticals drugs. The method can also be easily adopted for the amination of various natural products. (Figure presented.).

Full text of DOI:10.1002/adsc.201701183

Title: Ligand-free Iron(II)-catalyzed N-Alkylation of Hindered Secondary
Arylamines with Non-activated Secondary and Primary Alcohols
via a Carbocationic Pathway
Authors: Onkar S. Nayal, Maheshwar S. Thakur, Manoranjan Kumar,
Neeraj Kumar, and Sushil Maurya
This manuscript has been accepted after peer review and appears as an
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201701183
Link to VoR: http://dx.doi.org/10.1002/adsc.201701183

10.1002/adsc.201701183
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Ligand-free Iron(II)-Catalyzed N-Alkylation of Hindered
Secondary Arylamines with Non-activated Secondary and
Primary Alcohols via a Carbocationic Pathway
Onkar S. Nayal,a,b Maheshwar S. Thakur,a,b Manoranjan Kumar,a,b Neeraj Kumar‡ and
Sushil K. Maurya*,a,b
a Natural Product Chemistry and Process Development Division, CSIR-Institute of Himalayan Bioresource Technology,
Palampur, Himachal Pradesh 176 061, India. E-mail: sushilncl@gmail.com, skmaurya@ihbt.res.in
b Academy of Scientific and Innovative Research, CSIR-IHBT, India.
‡ Dedicated to the late Dr. Neeraj Kumar who deceased on 28th March 2016.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201
Abstract. Secondary benzylic alcohols represent
a
The scope of this methodology involves N-alkylation of
challenging class of substrates for N-alkylation of amines. primary, secondary and heterocyclic amines with
Herein, we describe an iron(II)-catalyzed eco-friendly primary/secondary benzylic, allylic and heterocyclic
protocol for N-alkylation of secondary arylamines with alcohols, which are common key structures in numerous
secondary benzyl alcohols through a carbocationic pathway pharmaceuticals drugs. The method can also be easily
instead of the known borrowing hydrogen transfer (BHT) adopted for the amination of various natural products.
approach. Transiently generated carbocations, produced
from alcohols via self-condensation, were coupled with
arylamines to provide highly functionalized amine products.
Keywords: Iron(II) bromide; Tertiary amine; Heterocyclic
amine; Secondary alcohol; Carbocation
Introduction
Nature produces more than 200 billion tons of
biomass per year through photosynthesis; however,
only 4% is utilized in various sectors.[1] In the area of
bio-based chemistry, the conversion of biomass into a
great variety of valuable chemicals is a major thrust
area. Intense efforts and progress have been realized
through the development of an attractive
methodology for the transformation of feedstocks
into basic chemicals. In this context, bio-based
chemicals such as alcohols can be easily used for
various transformations such as alkylation of amines.
Amines are important building blocks often used in
the synthesis of a wide range of pharmaceuticals,
agrochemicals, surfactants and bioactive molecules
(Scheme 1a).[2] The alkylation of amines with
alcohols to produce higher amines is an attractive and
eco-friendly alternative to conventional methods,
such as Buchwald-Hartwig amination,[3] reductive
amination of carbonyl compounds,[4] hydroamination
of alkynes/alkenes[5] and C-H nitrogen insertion.[6] N-
Alkylation of amines with alcohols is usually redox-
type reaction involving “hydrogen auto transfer”
mechanism (alcohol oxidation/imine formation/imine
hydrogenation). Recently, precious transition metal
catalysts such as Ru,[7] Pt,[8] Pd[9] and Ir[10] were
shown to be highly effective for this strategy,
However, these methods have some limitations, for
Scheme 1. a) Some tertiary amine containing drug motifs.
b) Amination rate of alcohols. c) Previous work. d) Our
work.
instance, the low abundance of catalyst, high cost and
need of stabilizing ligands.
1
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10.1002/adsc.201701183
Advanced Synthesis & Catalysis
Despite the recent progress, the development of an
efficient catalytic system using widely abundant,
inexpensive and eco-friendly metals remains elusive.
Noteworthy, highly abundant and bio-relevant
homogeneous transition metal catalysts such as Fe,
Co and Mn which were used in the mono alkylation
of primary amines with primary as well as secondary
alcohols.[11,12] For example, Zeng,[13] Shimizu,[14]
Saito,[15] Feringa[16] and other groups[17] reported
metal catalyzed mono-N-alkylation of primary
amines with alcohols by a borrowing hydrogen
transfer (BHT) methodology. Moreover, Saito
group[15] reported N-alkylation of primary amines
with primary benzyl alcohol using ligand assisted
iron as a catalyst. Additionally, few examples of
tertiary amines were also synthesized by this method
using primary benzyl alcohol as an alkylating agent.
However, the major disadvantages of these protocol
involved required prolonged reaction time and high
catalyst loading, ligand and elevated temperature for
the N-alkylation of secondary amine. However, N-
alkylation of secondary arylamines with secondary
benzyl alcohols is still a challenge due to the
following reasons: (a) the larger size of secondary
arylamines; they are generally considered more
difficult coupling partners than primary anilines for
N-arylation reactions,[18,19] (b) as an alkylating agent,
secondary alcohols are less reactive substrates as
compared to primary alcohols in borrowing hydrogen
transfer strategy because of the difficulty in its in situ
dehydrogenation to the corresponding ketones,[20, 21]
(c) the hydrogenation of the iminium or enamine
intermediates is also challenging (Scheme 1b).[22, 4a, 4c]
So far, only few methods are known for N-alkylation
of secondary amines by using precious transition
metal based catalyst such as Ru[7a] and Ir[10b]. For
example, Williams’s group reported Ru-catalyzed N-
alkylation of secondary aliphatic cyclic amines with
primary alcohols.[11a] Earlier, Beller’s group also
reported Ru-catalyzed N-alkylation of secondary
aliphatic amines with secondary alcohols (Scheme
1c).[23] To the best of our knowledge, there have been
no report on iron catalyzed N-alkylation of secondary
arylamines with secondary benzyl alcohols for the
synthesis of tertiary arylamines. The present work
overcomes the immanent challenges of N-alkylation
of secondary arylamines with secondary benzyl
alcohols via a carbocationic pathway. Previously, we
introduced a new catalytic approach for N-alkylation
of amines with ketones; wherein mechanistic
pathway completely relies on in situ generated
electrophilic carbon from ketone (Scheme 2b).[4c]
Keeping this in mind, we hypothesized that it can
also be possible to generate electrophilic carbon
(carbocation) from alcohols and use it as an
alkylating agent for N-alkylation of amines.
For the optimization of reaction conditions, N-
methylaniline (b) and 1-phenylethanol (a) were
selected as the model substrates. A small sampling of
control experiments and key results are shown in
Table 1. Various Lewis acidic salts and additives
were tested for the alkylation of N-methylaniline with
1-phenylethanol (Table 1, for details, see SI Table
S1). Copper and cobalt based catalyst gave lower
yield of desired product (Table 1, entries 1 & 2).
Table 1. Optimization of Reaction Conditions.[a]
S.
No
Catalyst
Additive
Solvent
Yield
(%)[b]
1
2
Cu(OAc)2
CoCl2
FeSO4. 7H2O
FeBr2
FeBr2
FeBr2
---
KHSO4
KHSO4
KHSO4
KHSO4
KHSO4
KHSO4
KHSO4
----
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
----
28
26
3
30
4
77
5[c]
6[d]
7
55
51
NR
NR
47
8
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
9
KHSO4
KHSO4
KHSO4
KHSO4
KHSO4
KHSO4
KHSO4
KHSO4
NaOtBu
KH2PO4
K2S2O8
KHSO4
KHSO4
10[e]
11
12
13
14
15
16
17
18
19
20 [f]
21[g]
Toluene
Dioxane
n-BuOH
DMSO
DMF
89
NR
NR
NR
NR
7
ACN
Benzene
Toluene
Toluene
Toluene
Toluene
Toluene
33
NR
47
NR
51
33
[a]
General reaction conditions: a (0.25 mmol), b (0.14
mmol), catalyst (5 mol%), additive (0.14 mmol) and
solvent (1.0 mL) at 120 °C for 24 h.
[b]
Yield was determined by GC-FID using hexadecane as
the internal standard.
[c] 3 mol% FeBr2 was used.
[d] 7 mol% FeBr2 was used.
[e] Dry toluene was used.
[f] 0.09 mmol KHSO4 was used.
[g] 0.21 mmol KHSO4 was used.
Results and Discussion
Iron salts were found to be more efficient catalysts as
compared to other Lewis acidic salts (Table 1, entries
3-4 and see SI, Table S1, entries 6-13). Further the
catalyst loading were optimized. It was observed that
Optimization of Reaction Conditions
2
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10.1002/adsc.201701183
Advanced Synthesis & Catalysis
5 mol% of catalyst afforded highest yield of product,
while decreasing or increasing the catalyst loading
resulted in decreased yield of desired product (Table
1, entries 5-6 and see SI, Table S2, entries 1-6).
Interstingly, 5 mol % iron(II) bromide was found be
more efficient catalyst as compared to other iron salts
(Table 1, entry 4). As expected, in the absence of iron
catalyst and additive KHSO4, no reaction was
observed (Table 1, entries 7-8). The effect of solvent
was also investigated for this transformation. Under
neat reaction conditions, the product yield decreased
significantly (Table 1, entry 9). Dry toluene gave an
optimum yield of the product as compared to other
solvents (Table 1, entries 10-16 and see SI, Table S4,
entries 1-12). Different additives were also tested for
this transformation and 1.0 equivalent of KHSO4 was
found to be the most effective as compared to other
additives (Table 1, entries 17-21 and see SI, Table S3,
entries 1-8).
agent for this amination reaction (Scheme 3c1). The
reaction most likely proceeded via the SN1
substitution pathway.[24b] Interestingly, when 2-
phenyl-2-propanol was used as an alkylating agent
with sterically hindered N-methylaniline, lower yield
of desired product was observed (Scheme 3c2).
Moreover, these results also excluded the BHT
pathway. In order to verify this pathway, (R)-1-
phenylethanol (>98% ee) (a1) was treated with N-
methylaniline (b). After 24 hour, the product aa was
isolated in 84% yield in racemic mixture (Scheme 3d
& see SI, page no-S11). These results clearly
suggested
Experimental Mechanistic Study
To establish this hypothetical strategy, different
control experiments were carried out. Initially, during
the optimization, we found that ether was formed
from secondary alcohol instead of oxidized carbonyl
compound (ketone) (see SI, page no-S7). This ether
was timely consumed and converted into the desired
amine (Scheme 3a). To further understand the exact
role of ether in the catalytic cycle, ether was isolated
from the reaction mixture and subjected to reaction
with b to obtained moderate yield of desired amine
(Scheme 3b). These preliminary control experiments
completely ruled out the known BHT pathway
(Scheme 2a).
Scheme 3. Preliminary Mechanistic Studies.
Scheme 2. a) Known BHT pathway. b) Carbocationic
pathway for N-alkylation of amine with ketone.
On the basis of results of preliminary control
]
experiments and previous studies,[24 we thought that
Scheme 4. N-Alkylation of 4-Cyano-N-methylaniline with
α-Cyclopropylbenzyl alcohols.
the reaction might be proceeding through the
unimolecular nucleophilic substitution (SN1) pathway.
Further, to elucidate the involvement of SN1 pathway
in our catalytic cycle, other control experiments were
performed under standard reaction conditions. We
choose sterically hindered alcohols as an alkylating
the involvement of carbocation intermediate in the
catalytic cycle which is generated through in situ
24d]
formed Csp3–O etheric bond cleavage.[24b,
Additionally, to support this carbocationic pathway
mechanism, we carried out the reaction of 4-cyano-N-
agent
for
the
N-alkylation
of
amines.
Diphenylmethanol served as a suitable alkylating
3
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10.1002/adsc.201701183
Advanced Synthesis & Catalysis
methylaniline with α-cyclopropylbenzyl alcohol and
87% yield of the ring opening product (3p) was
obtained (Scheme 4). It is due to the dynamic
behavior and rearrangement of cyclopropyl methyl
carbocation, which is established in carbocation
chemistry.[25] Moreover, the transient carbocation
species was also trapped by various nucleophiles such
as thiol, tert-butylammonium bromide and
phenylacetylene (Scheme 5). Results of the above
control experiments clearly indicated that the reaction
goes through a carbocationic pathway.
a regenerated through the protonation of iron(III)
alkoxide (e) for another catalytic cycle. However, the
generation of d cannot be excluded from a.
Reactions of Secondary Benzylic Alcohols with
Secondary Arylamines
After exploring the mechanistic pathway and optimal
reaction conditions in hand, we explored the scope of
secondary benzylic alcohols that can be employed as
alkylating agents for the synthesis of diverse tertiary
arylamines (Scheme 7). α-Methylbenzyl alcohol
reacted smoothly with N-methylaniline to afford the
excellent yield of the desired amine (Scheme 7, 3a).
N-Alkylation of N-methylaniline with electron
deficient secondary benzylic alcohols afforded
Scheme 7. N-Alkylation of Secondary Arylamines with
Secondary Benzylic Alcohols.[a]
Scheme 5. Transient Carbocation Species Trapping
Experiments.
On the basis of control experiments and previous
literature, a complete depiction of the putative
mechanism for the N-alkylation of amines with
benzylic alcohol is shown in scheme 6 (see SI, page
no. S7-S14 for complete mechanistic study). Initially,
benzylic alcohol undergoes condensation in the
presence of iron(II) bromide to afford intermediate
ether (b), which readily reacts with iron(II) bromide
to generate transient carbocationic species (d) and
iron(III) alkoxide (e) via the formation of iron(III)
benzyloxonium species (c).[24b, 24c] Subsequently, the
[a] General reaction conditions: 1 (1.8 mmol), 2 (1 mmol),
FeBr2 (0.5 mmol), KHSO4 (1.0 mmol), dry toluene (1.0
mL) at 120 °C for 24 h.
corresponding product in good to excellent yields
(Scheme 7, 3b-3d). Unlikely, the reaction did not
proceed with p-nitro-1-phenylethanol (Scheme 7, 3e).
When the electron-rich secondary benzylic alcohol
was employed as an alkylating agent, N-
methylaniline afforded the corresponding amine in
good yield (Scheme 7, 3f). Electron deficient
secondary anilines except 4-(methylamino)-benzoic
acid also underwent N-alkylation with 1-
phenylethanol to give moderate to good yields of the
desired amines (Scheme 7, 3g-3k). However, an
electron-rich secondary aniline displayed less
reactivity with 1-phenylethanol, which resulted in
poor yield of desired amine (Scheme 7, 3l).
Interestingly, up to 70% yield was obtained for
tertiary amines when alkylation of N-ethylaniline was
carried out using 1-phenylethanol and 1-(4-
bromo)phenylethanol (Scheme 7, 3m-3n). Sterically
hindered alcohol such as benzhydrol coupled
Scheme 6. Proposed mechanistic pathway.
nucleophilic amine (f) attacks on the benzylic
carbocation (d), giving the desired product (h)
followed by deprotonation of g. Finally, the complex
4
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10.1002/adsc.201701183
Advanced Synthesis & Catalysis
smoothly with N-methylaniline and afforded good
yield of corresponding amine (Scheme 7, 3o).
Surprisingly, when α-cyclopropylbenzyl alcohol was
reacted with 4-cyano-N-methylaniline, 87% yield of
ring opening product 3p was obtained (Scheme 7, 3p
& for details see SI, Scheme S4).
butylbenzyl alcohol to give good yield of the
corresponding amine, which is generally considered
as a challenging substrate[26] (Scheme 9, 9f).
Interestingly, α-cyclopropylbenzyl alcohol delivered
the alkylated product of p-bromoaniline in good yield,
without the formation of rearrangement product
(Scheme 9, 9g).
N-Alkylation of Secondary Arylamines with
Primary Benzyl Alcohols
Scheme 9. N-Alkylation of Primary Amines with
Primary/Secondary Benzylic Alcohols.[a]
We next investigated the behaivour of primary benzyl
alcohols as alkylating agents. A broad array of
primary alcohols effectively served as alkylating
agents in N-alkylation reaction (Scheme 8). The
reaction was successful for the N-alkylation of N-
methylaniline with benzyl alcohol to give an
excellent yield of the desired product (Scheme 8, 6a).
Substituted benzyl alcohols such as 3, 4-dimethoxy
benzyl alcohol and piperonyl alcohol also readily
reacted with N-methylaniline to give good yields of
corresponding amines (Scheme 8, 6b-6c).
Interestingly, electron deficient amines easily
underwent alkylation with sterically hindered as well
as para substituted benzylic alcohols to give excellent
yields of corresponding amines (Scheme 8, 6d-6e).
Allylic alcohols were smoothly coupled with 4-
chloro-N-methylaniline and gave the excellent yields
of desired amines (Scheme 8, 6f-6g). 4-
Methylbenzylic alcohol reacted smoothly with 3-
methyl-N-methylaniline to afford good yield of
respective amine (Scheme 8, 6h).
a General reaction conditions: 7 (1.8 mmol), 8 (1 mmol),
FeBr2 (0.5 mmol), KHSO4 (1.0 mmol), dry toluene (1.0
mL) at 120 °C for 24 h.
N-Alkylation of Heterocyclic Amines with Benzylic
Alcohols
One more advantage of this developed methodology
was further demonstrated through the N-alkylation of
heterocyclic amines with benzylic alcohols for the
synthesis of higher amines (Scheme 10). Heterocyclic
Scheme 8. N-Alkylation of Secondary Arylamines with
Primary Benzyl Alcohols.[a]
Scheme 10. N-Alkylation of Heterocyclic Amines with
Benzylic Alcohols.[a]
[a] General reaction conditions: 4 (1.8 mmol), 5 (1.0 mmol),
FeBr2 (0.5 mmol), KHSO4 (1.0 mmol), dry toluene (1.0
mL) at 120 °C for 24 h.
N-Alkylation of Primary Amines with Primary
and Secondary Benzylic Alcohols
Further, we explored the established iron(II)
catalyzed protocol for the N-alkylation of primary
amines with primary/secondary alcohols for the
synthesis of secondary arylamines (Scheme 9).
Electron deficient anilines reacted smoothly with α-
methylbenzyl alcohol, afforded 73%-83% yield of
corresponding amines (Scheme 9, 9a-9c). However,
when the electron-rich anilines were employed, lower
reactivity was observed (Scheme 9, 9d & 9e). An
electron-deficient aniline was also well tolerated with
electron rich alkylating agent such as p-tert-
[a] General reaction conditions: 10 (1.8 mmol), 11 (1 mmol),
FeBr2 (0.5 mmol), KHSO4 (1.0 mmol), dry toluene (1.0
mL) at 120 °C for 24 h.
amines are most common motifs in various
pharmaceuticals and biologically active natural
products.[27] Substituted amino pyridines reacted
smoothly with primary and secondary benzylic
alcohols to afford good to excellent yields of the
5
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10.1002/adsc.201701183
Advanced Synthesis & Catalysis
desired
amines
(Scheme
10,
12a-12c).
Friedel-Crafts Alkylation of Anilines with
Secondary Benzylic Alcohols
Aminoquinolines reacted smoothly with benzyl
alcohol and afforded up to 83% yield of N-alkylated
products (Scheme 10, 12d & 12e). Moreover,
polysubstituted alcohol further demonstrated the
versatility of this amination reaction (Scheme 10,
12f). Notably, a wide range of alcohols having
heteroaromatic skeletons were readily executed for
the alkylation of heteroamines under these reaction
conditions (Scheme 10, 12g-12j). Benzyl alcohol also
When we were exploring the substrate scope of
secondary benzylic alcohol with N-methyl aniline for
the synthesis of tertiary amines, an unexpected
Friedel-Craft alkylated product was formed with
secondary benzylic alcohols and benzhydrols both
bearing electron donating groups (Scheme 13).
Interestingly, up to 90% yield of o- & p-substituted
Friedel-Craft alkylated products (21a-21c) were
isolated instead of desired N-alkylated product of p-
coupled
smoothly
with
6-ethoxy-2-
aminobenzothiazole and gave good yield of desired
methoxy substituted benzylic
alcohol
and
amine (Scheme 10, 12k).
benzhydrols. It might be due to the higher stability of
carbocation via positive mesomeric effect.[28]
Surprisingly, p-amine substituted benzyl and
benzhydrol selectively gave only p-substituted
Friedel-Craft alkylated products (21d-21e).
Amination of Naturally Occuring Alcohols
Next, we sought to demonstrate the utility of the
developed methodology for the amination of natural
products (Scheme 11). Intriguingly, naturally
occurring alcohols such as acyclic mono/diterpenes
(nerol, geraniol and phytol) delivered the N-
alkylated products of 8-aminoquinoline as well as 5-
amino-2-chloropyridine in high yields (Scheme 11,
15a-15e).
Scheme 13. Friedel-Crafts Alkylation of Anilines with
Secondary Benzylic Alcohols.[a]
Scheme 11. N-Alkylation of Heterocyclic/Arylamines with
Natural Alcohols.[a]
[a]
General reaction conditions: 13 (1.8 mmol), 14 (1.0 mmol),
FeBr2 (0.05 mmol), KHSO4 (1.0 mmol), dry toluene (1.0 mL) at
120 °C for 24 h.
[a]
General reaction conditions: 20 (1.8 mmol), b (1.0
mmol), FeBr2 (0.05 mmol), KHSO4 (1.0 mmol), dry
toluene (1.0 mL) at 120 °C for 24 h.
Interestingly, when natural alcohol bearing pyrone
skeleton such as maltol (16) was used as an alkylating
agent for N-alkylation of 17, an unexpected
rearranged product 19 was obtained instead of desired
product 18 (Scheme 12). In future, we will explore
the surprising reactivity pattern of this type of
moieties with amines via specific structural
rearrangement.
Conclusion
In conclusion, we have developed a conceptually
novel strategy for the N-alkylation of arylamines with
readily available alcohols via
a carbocationic
pathway. The salient feature of the proposed
mechanism is the generation of carbocation from
ether, through the cleavage of in situ generated sp3C-
O bond. Further, this carbocation intermediate was
trapped with arylamines to provide functionalized
Scheme 12. Amination of Maltol.[a]
arylamines.
This
environmentally
amiable,
economical catalytic method exhibits a wide substrate
scope for the synthesis of various higher arylamines
in good to excellent yields.
[a]
General reaction conditions: 16 (1.8 mmol), 17 (1.0
mmol), FeBr2 (0.05 mmol), KHSO4 (1.0 mmol), dry
toluene (1.0 mL) at 120 °C for 24 h.
6
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10.1002/adsc.201701183
Advanced Synthesis & Catalysis
Experimental Section
2010, 14, 1046–1049; b) R. Kawahara, K. Fujita, R.
Yamaguchi, J. Am. Chem. Soc. 2010, 132, 15108–15111.
To an oven dried 10 mL screw cap reaction tube was
added 0.05 mmol of FeBr2, 1.0 mmol of KHSO4, 1.0
mmol of aniline, 1.8 mmol of secondary benzyl
alcohol or primary alcohol and 1.0 ml of toluene. The
reaction tube was capped and the mixture was then
heated to 120 °C in an oil bath and under air. After
completion of reaction (monitored by TLC), the
reaction mixture was allowed to cool, ethyl acetate (3
× 7 mL) was added, and the mixture was filtered and
passed through anhydrous sodium sulfate. The crude
product was purified by column chromatography over
silica gel (60-120 and 230-400 mesh) with an
appropriate mixture of n-hexane and ethyl acetate.
[11] a) M. Haniti, 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, 1766–1774; b) U.
Jana, S. Maiti, S. Biswas, Tet. Lett. 2008, 49 858–862; c)
Y. Du, S. Oishi, S. Saito, Chem. Eur. J. 2011, 17, 12262–
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C. Darcel, M. Beller, Angew. Chem. Int. Ed. 2015, 54,
14483–14486.
[12] a) Y. Zhang, C. Lim, D. S. B. Sim, H. Pan, Y. Zhao,
Angew. Chem. 2014, 126, 1423–1427; b) G. Guillena, D. J.
Ramon, M. Yus, Chem. Rev. 2010, 110, 1611–1641; c) D.
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Acknowledgements
The authors are grateful to the Director, CSIR-IHBT, for
financial support (MLP 0066). M. S. T. and M. K. thank UGC for
research fellowship. The authors also thank Dr. Upendra Sharma
and Dr. Bikram Singh for valuable discussions. CSIR-IHBT
communication no 4149.
[13] G. Zhang, Z. Yin, S. Zheng, Org. Lett. 2016, 18, 300–
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Ligand-free Iron(II)-catalyzed N-Alkylation of Hindered Secondary Arylamines with
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