Olefin-Oriented Selective Synthesis of Linear and Branched N-Alkylated Heterocycles by Hydroamination

Article abstract of DOI:10.1002/ejoc.202000373

An effective base-induced selective approach for the synthesis of linear and branched N-alkylated heterocycles by hydroamination of olefins has been described. The designed C–N bond formation method was directed through the olefin, as with styrenes only linear N-alkylated product was obtained, and acrylates gave linear as well as branched alkylated heterocycles. This protocol provided the synthesis of exclusive N-alkylated product instead of the C-3 Michael addition product. The reaction was also compatible with phenyl vinyl sulfone, thus leading to the formation of sulfone substituted heterocycles in good yield. Further, the method was utilized for the synthesis of medicinally important analogs of CB1 Cannabinoid receptor and Dimebon analogue in short reaction sequence.

Full text of DOI:10.1002/ejoc.202000373

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Olefin-Oriented Selective Synthesis of Linear and Branched N-
Alkylated Heterocycles via Hydroamination Sushmita, Trapti
Aggarwal, Kapil Mohan Saini and Akhilesh K. Verma*
Authors: Sushmita ., Trapti Aggarwal, Kapil Mohan Saini, and Akhilesh
Kumar Verma
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000373
Link to VoR: https://doi.org/10.1002/ejoc.202000373
01/2020

10.1002/ejoc.202000373
European Journal of Organic Chemistry
COMMUNICATION
Olefin-Oriented Selective Synthesis of Linear and Branched N-
Alkylated Heterocycles via Hydroamination
Sushmita, Trapti Aggarwal, Kapil Mohan Saini and Akhilesh K. Verma*
Dedication ((optional))
Abstract: An effective base-induced selective approach for the
synthesis of linear and branched N-alkylated heterocycles via
hydroamination of olefins has been described. The designed C-N
bond formation method was directed through the olefin as with
styrenes only linear N-alkylated product was obtained and acrylates
gave linear as well as branched alkylated heterocycles. This protocol
provided the synthesis of exclusive N-alkylated product instead of C-
3 Michael addition product. The reaction was also compatible with
phenyl vinyl sulfone, thus leading to the formation of sulfone
substituted heterocycles in good yield. Further, the method was
utilizied for the synthesis of medicinally important analogs of CB1
Cannabinoid receptor and Dimebon analouge in short reaction
sequence.
Tremendous advances has been gained over the past decades
with metal-catalyzed alkene hydroamination,6 however the base-
mediated synthesis of linear and branched alkylated
heterocycles remains elusive. Interestingly, heterocycles
pendant with N-alkyl group enhances the biological activity of
the molecule.7 The N-alkylated carbazoles core are present in
many drugs like AZ-5 (GAT236) CB1 Cannabinoid Receptor (I),8
latrepirdine or dimebon (II) act as antihistamine drug9 and
Ramatroban (III)10 used as DP(2) receptor antagonist (Figure 2).
The N-functionalized carbazoles are in high demand because it
increases the solubility of drug in organic solvents.
The C-N bond-forming reactions contribute as one of the most
important, versatile and practical synthetic approach for the
development
of
nitrogen-containing
compounds
that
demonstrate numerous applications in natural products and
biologically active drugs.1-2 Due to the wide applicability of N-
heterocyles, enormous effort has been devoted for the designing
of an economical and mild protocol to furnish N-alkylated indoles
and carbazoles. Hydroamination of amines with C-C unsaturated
bond using expensive metal-catalyst is among the most
preferred reaction for the N-alkylation of heterocycles because
of its high atom economy.3 Importantly, hydroamination of
alkene afforded two possible regioisomeric products, the
Markovnikov, and the anti-Markovnikov, which depends on the
formation of new C-N bond.4 Though hydroamination of alkenes
typically furnishes the Markovnikov product, however; the
participation of the lone pair available on nitrogen in the aromatic
system enhance the nucleophilicity at C-3 position of indole.
Thus, various reports are available in the literature for C-3
alkylation of indoles5 however; the challenging task was to
execute intermolecular anti-Markovnikov alkylation selectively at
nitrogen of indoles instead of C-3 position under mild reaction
conditions (Figure 1).
Figure 2. Biologically active carbazoles analogs
In 2012, Hill and co-workers reported the N-alkylation of
secondary amines with styrenes in the presence of alkaline
earth-metal catalysts (Scheme 1a).11 Later, intermolecular
hydroamination of indoles with unactivated olefins in the
presence of iridium catalyst was exploited by Hartwig and co-
workers to afford the Markonikov addition product (Scheme
1b).12 Very recently, Akai and co-workers reported the Cobalt-
catalyzed alkylation of benzotriazole with alkenes (Scheme
1c).13 Owing to the high efficacy and versatility of C-N bond
formation reaction and our ongoing research on hydroamination
with alkynes (Scheme 1d)14 herein, we wish to explore the base-
mediated hydroamination of N-heterocycles with olefins
including acrylates, olefins, and sulfones (Scheme 1e). To probe
the viability of designed protocol, we have synthesized the
analogs of CB1 cannabinoid receptors and Dimebon.
We commenced our investigation on the basis of our
previous reports on the hydroamination.14c When indole (1a) was
reacted with phenyl styrene (2a) in the presence of 1.0 equiv of
KOH in DMSO at 120 °C for 10 h, no progress in the reaction
was observed (Table 1, entry 1). Stirring the reaction for a longer
time made no significant improvement on the reaction (entry 2).
Increase in the amount of base from 2.0 equiv to 3.0 equiv,
afforded the 66% yield of N-alkylated product 3a (entries 3-5).
Altering the reaction time increases the yield of product 3a (entry
6-7). Further monitoring the reaction at different temperature
afforded the lower yield of product 3a (entry 8-9). Use of other
bases such as NaOH, CsOH provided the product 3a in lower
yield (entries 10-11). Screening of various solvents such as DMF,
NMP, DMA and toluene revealed that DMF was the only solvent
Figure 1. Overview of the Addition of Alkene on N-heterocycles
[a]
Sushmita, Dr. Trapti Aggarwal, Kapil Mohan Saini and Prof.
Akhilesh K. Verma* Department of Chemistry, University of
Delhi, Delhi 110007, India
URL: http://akvresearch.com
E-mail: : averma@acbr.du.ac.in
Supporting information for this article is given via a link at the
end of the document.
1
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000373
European Journal of Organic Chemistry
COMMUNICATION
suitable for this transformation albeit in lower yield as compared
to DMSO (entries 12-15). In the absence of base, no reaction
was observed (entry 16).
With the optimal reaction condition in hand, a diverse
library of N-alkylated product 3a–o was prepared in 60–
80% yields. The reaction of indole 1a with various styrenes
2a–e afforded the corresponding products 3a–e in good
yields (Scheme 2). A good yield of product 3b and 3c were
obtained with electron-withdrawing group substituted alkene
2b and 2c under the optimal condition. The reaction
required 40 h, when styrenes embedded with electron-
donating functional group 2d and 2e were employed under
optimized reaction condition. When methyl substituted
indole 1b-1c were subjected towards the hydroamination
reaction, the desired products 3f-g were obtained in 68%
and 70% yield, respectively. The reaction with 5-OMe
indole 1d gave the desired product 3h in 68% yield. While
good yields of product 3i_j were obtained when bromo and
Nitro substituted indole 1e_f were used as substrate.
Interestingly, the reaction proceeds smoothly with 7-
(benzyloxy)-1H-indole (1g) and afforded the N- alkylated
product 3k in 64% yield. The bromo substituted substrate,
afforded hydroaminated product over arylation in 78% yield.
The optimized reaction condition was compatible with
azaindole (1h) also to give 3l in 69% yield. The reaction
proceeded smoothly with carbazoles 1i and hydroxy
substituted carbazoles 1j provided the alkylated products
3m–n in good yield, devoid of any reaction on free hydroxyl
group present in the 1j. However, no reaction was observed
Previous Work
(a) Hill and Co-workers, J. Am. Chem.Soc. 2012
NR'R"
[M{N(SiMe3)2}2]2 (5 mol%)
M = Ca or Sr
HNR'R"
+
(b) Hartwig and Co-workers, J. Am. Chem. Soc. 2014
Ir catalyst (2.5 mol%)
+
Ralkyl
N
N
(S)-DTBM-Segphos (5 mol%)
EtOAc (1.0 equiv)
H
Me
Ralkyl
(c) Akai and Co-workers, Org. Lett. 2020
Co (20 mol%)
N
N
N
N
R2
N
PhSiH3 (4 equiv)
+
R1
N
H
H
TMFP-BF4 (2 equiv)
R1
R2
(d) Our group, Acc. Chem. Res. 2017
Hydroamination
N
R
+
KOH/ DMSO
R
N
H
H
H
(e) Present Work
R1
R1
Y
KOH(3.0 eq)
KOH
DMSO/120oC
X
X
36 h
O
N
O
O
20-42 h
N
R3
R1
R2
R3
R2
2
R3
6a-q
3a-o
4
N
H
KOH
NMe
1
KOH
Single step
4 steps X= N, C; Y = C, NH, NMe
N
R1= H, Me, OMe, NO2, COOH
N
R2
=
Ph, p-OMeC6H4, p-ClC6H4,
p-BrMeC6H4, SO2Ph
with internal alkene, i.e. trans-stilbene 2f
.
Me
N
N
R3 = OMe, OEt, OBu, OCH2Ph
Me
HN
R1
R1
13
12
Me
KOH (2.0 equiv)
S
+
Dimebon Analouge
Cannabinoid receptor
N
H
N
DMSO
120 oC, 36-42 h
R3
1
3
2
Scheme 1. Synthesis of N-Alkylated Heterocycles
Table 1. Optimization of reaction conditions.a
Cl
Styrenes =
Br
Me
N
OMe
Br
2a
2b
2e
2c
2d
Base, Solvent
Time, Temp.
Ph
+
N
N
N
Ph
N
N
H
Cl
H
1a
2a
3a
3a'
3a, 78%
3b, 75%
3c, 72%
entry
solvent
Base
(equiv)
temp
(°C)
120
t
yieldb
(%) 3a
0
Me
(h)
10
20
20
20
20
36
42
24
36
36
36
36
36
36
36
36
N
N
N
1
2
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
KOH (1.0)
KOH (1.0)
KOH (2.0)
KOH (2.5)
KOH (3.0)
KOH (3.0)
KOH (3.0)
KOH (3.0)
KOH (3.0)
NaOH (3.0)
CsOH (3.0)
KOH (3.0)
KOH (3.0)
KOH (3.0)
KOH (3.0)
-
Me
OMe
120
120
120
120
120
120
140
100
120
120
120
120
120
120
120
Traces
20
3f 68%
3e, 62%
3d, 61%
3
Me
4
40
N
N
N
5
66
Br
MeO
6
80
3i, 72%
3h, 68%
3g, 70%
7
81
N
8
65
N
N
9
63
N
O2N
10
11
12
13
14
43
O
3l 69%
3j, 70%
3k, 64%
Ph
37
OH
Ph
55
N
NMP
NR
NR
NR
NR
N
Ph
N
DMA
15c
Toluene
DMSO
3n, 71%
3m, 76%
3o, 00%
16
Scheme 2. Scope of Styrenes Reaction Conditions: The reactions were
performed using N-heterocycle 1 (0.5 mmol), 1.0 mmol of Styrenes 2, 3.0
equiv of KOH in 2.0 mL of DMSO at 120 oC.
[a]
Reactions were performed using 0.50 mmol of 1a, 0.10 mmol of
styrene 2a, 3.0 equiv of base in 2.0 mL solvent unless otherwise
noted. [b] Isolated yield. [c] Without using KOH.
2
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10.1002/ejoc.202000373
European Journal of Organic Chemistry
COMMUNICATION
Encouraged from the above results with styrenes, next
we intended to explore the hydroamination of N-
heterocycles with acrylates 4a–e in super basic medium
(Scheme 3). The reaction of indole 1a with methyl acrylate
reaction with N-methyl γ-carbolines 1p and obtained the
selective N-alkylated product 5n in 68% yield. Aza-
carbazole 1q gave the N-alkylated product 5o in good yield.
After the successful synthesis of linear alkylated products 5,
next, we intended to synthesize branched N-alkyalted
heterocycles 6a-q via hydroamination with successive Michael
(
4a) and methyl methacrylate (4b) provided the N-alkylated
product 5b_5b in 82_86% yield. Acrylonitrile 4c was well
tolerated under the screened reaction condition and
afforded the desired product in good yield. The reaction
with cyclohexyl acrylate 4d provided the N-alkylated
product 5d in 80% yield. Carboxyl and phenoxyl substituted
indole gave N-alkylated product in 72-76% yield.
addition. Using 3.0 equiv of acrylates
2 and KOH, the
hydroaminated product 5 in situ underwent sequential Michael
addition16 to afford the corresponding branched products 6a– 6q
in good to excellent yields (Scheme 4). The reaction of indole 1a
with methyl acrylate 4a, ethyl acrylate 4f and n-butyl acrylate 4g
provided the products 6a-c in 72-80% yield. Methyl methacrylate
(4b) was also found suitable, giving the desired product 6d in
good yield. Benzyloxy acrylate 4h and phenyl acrylate 4i were
well tolerated under basic medium to furnish the desired
products 6e-f in 74-78% yields.
R1
O
R1
KOH (1.0 equiv)
+
DMSO, 120 o
20 h
C
OR
N
O
N
H
1
4
5
OR
R1
KOH (3.0 equiv)
R1
O
N
O
O
DMSO, 120 o
36 h
C
+
N
N
OR
N
N
O
N
OR
H
Me
6
4
1
CN
OMe
OR
O
O
O
OMe
O
O
5a, 86%
COOH
5c, 82%
5d, 80%
O
5b, 82%
OEt
OnBu
OMe
O
N
OMe
O
N
N
N
O
N
N
N
Me
Me
N
N
OEt
O
OnBu
OMe
MeO
O
O
O
Ph
O
O
6a, 80%
6b, 78%
OMe
OMe
6d, 72%
6c, 72%
OMe
O
O
OMe
O
O
Me
Me
O
5f, 72%
5g, 77%
5h, 65%
5e, 76%
OPh
N
OMe
Ph
N
N
O
N
N
O
N
N
O
N
N
O
OPh
MeO
Br
O
OMe
MeO
O
O
Ph
O
6h, 82%
H3C
6g, 77%
6e, 74%
6f, 78%
OMe
OMe
O
5j, 00%
COOMe
O
O
OMe
OMe
5l, 75%
O
5i,78%
NH2
MeO
5k, 80%
O
OMe
O
Me
N
OMe
N
N
OMe
N
N
O
N
OMe
O
N
OMe
N
O
OMe
O
O
N
O
O
O
6k, 75%
6i, 74%
6j, 65%
O
Br
O2N
O
OMe
OMe
OMe
OMe
OMe
N
OMe
N
N
N
Br
5o, 76%
5n, 68%
5m, 51%
Scheme 3. Scope of Indole/Carbazoles with Acrylates. Reaction
Conditions: The reactions were performed using N-heterocycle (0.5
, 1.0 equiv of KOH in 2.0 mL of DMSO at
OMe
OMe
OMe
1
O
O
O
6l, 62%
6m, 52%
6n, 76%
mmol), 0.6 mmol of acrylate
120 oC for 20 h.
4
OH
O
N
O
O
N
N
O
O
The significant yield of product 5g was obtained when
azaindole 1h was employed as a substrate. Interestingly,
OMe
OMe
OMe
OMe
O
OMe
OMe
the reaction proceeds smoothly with indoline-2,3-dione (1l
)
6q, 72%
6p, 70%
6o, 75%
and afforded the N-alkylated indoline 5h in 65% yield.
Inspired from above results, we next investigated other N-
heterocycles 1m–q. When 6-bromo-1H-indazole (1m) was
used as substrate, the desired N-alkylated product 5i in
78% yield. However, no reaction was observed when indole
Scheme 4. Synthesis of N-pentanedioate substituted heterocycle. Reaction
Conditions: The reactions were performed using N-heterocycle 1 (0.5 mmol),
1.5 mmol of olefin 4, 3.0 equiv of KOH in 2.0 mL of DMSO at 120 oC for 36 h.
Substituted indoles with electron-donating groups, such as
methyl and methoxy groups, showed good reactivity in the
reaction and provide the desired products 6g–6i in 74–82%
yields. Interestingly, 7-(benzyloxy)-1H-indole (1g) also found
viable for the reaction and furnished the desired product 6j in
65% yield. The reaction of substrate 1r having free NH2 under
optimized reaction conditions, chemoselectively provided the
product 6k in 75% yield without affecting free amine group (entry
11). Electron-withdrawing group such as Br and NO2 substituted
indoles 1e-f afforded the Michael addition products 6l-m in
moderate yields. Bromo-indazole 1m gave the desired product
6n in 76% yields. Switching from indole to carbazole scaffold,
1a was reacted with internal acrylate 4e
unsubstituted carbazole 1i and
.
Similarly,
1,2,3,4
(
)
tetrahydrocarbazole (1n) on reaction with methyl acrylate
2a) in super basic medium afforded the desired N-alkylated
(
product 5k and 5l in 80 and 75% yields, respectively. To
further extend the scope of substrate, next we utilized
biologically active γ-carbolines (1o–p).15 The reaction with
substrate having two NH free i.e. γ-carboline 1o, provided
the product 5m with alkylation on both nitrogens in 51%
yield alongwith substrate 1o. After that, we preceded the
3
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10.1002/ejoc.202000373
European Journal of Organic Chemistry
COMMUNICATION
provided the fruitful yield. The reaction of carbazole 1i with
methyl acrylate 4a afforded the product 6o in 75% yield. We
next extended the substrate scope by employing substituted
carbazoles bearing hydroxy at C–2 position 1j; 70% yield of
product 6p was obtained selectively. Furthermore, tetrahydro
carbazole 1n reacted smoothly with 4a to provide the product 6q
in good yield.
Ivachtchenko group has reported that the alkyl chain present in
the products increases its affinity to 5-HT6 and H1 receptors.18
To support the selective formation of linear and branched
hydroaminated product, we conducted deuterium labeling
studies (Scheme 7). When we performed the reaction of indole
with styrene using DMSO-d6, product 3p was obtained in 72%
yield with the incorporation of two deuterium molecules at α-to
phenyl ring. Then, the formation of deuterated products 5p in
82% yield after 20 h with 70% deuterium incorporation using
DMSO-d6 supported the initial protonation on the α-carbon
adjacent to phenyl/ester group. Using excess of base in DMSO-
d6, provided 76% yield of di-deuterated product 6r after 36 h.
These experiment suggests that the reactions proceed through
hydroamination and the incoming protons were provided by the
solvent (Scheme 7A). When we performed the reaction with N-
methyl indole 1s under basic medium, the expected C-3
alkylated product 14 was not formed (Scheme 7B). Based on
the above evidence and literature14 a plausible mechanism was
proposed which shows the exchange of deuterium with
hydrogen in presence of KOH generated the DOH which
activates the styrene that leads to the formation of
hydroaminated product 3 (Scheme 7C).
Inspired from the reaction with styrenes and acrylates, next
we planned to utilize electron-deficient vinyl sulfones 7 under the
screened reaction condition and obtained the desired product
8a–b in 72-78% yield (Scheme 5). Sulfones are biologically
important synthons which on addition to any scaffold increase its
medicinal prospects.17
Scheme 5. Reaction of N-heterocycle with phenyl vinyl sulfone
After successful accomplishment with olefins, we
elaborated the protocol for the designing of new synthetic route
for the medicinally important drug analogs. Firstly, we planned to
synthesize the analog of allosteric modulators of CB1
Cannabinoid receptor in short reaction sequence (Scheme 6a).
The reaction initiates with condensation reaction between methyl
3-(9H-carbazol-9-yl)propanoate (5k) and hydrazine hydrate in
presence of methanol to give intermediate 9 in 87% yield.
Further treating the intermediate 9 with 2-isothiocyanatopropane
(10), generates thio-semicarbazides 11 in 89% yield which
subsequently cyclized in basic medium to form the targeted
analog of AZ-5 GAT236 (12) (Cannabinoid receptor) in 85%
yield. Next, we synthesize Dimebon analog 13 by treating N-
methyl γ-carboline 1p as substrate with methyl-substituted
styrene 2d under screened reaction conditions for 42 h. The
targeted product 13 was obtained in 60% yield in one-step.
Scheme 7. Control Experiments
In conclusions, we have reported the selective
hydroamination of indoles, carbazoles, aza-carbazoles and γ-
carbolines with styrenes, acrylates and sulfones in basic
medium. The designed strategy was highly specific and directed
through the olefins to furnish linear or branched N-alkylated
heterocycles. This protocol provided the N-alkylated indoles
exclusively with good to excellent yield without C-3 alkylation.
We have constructed the diverse library of substituted N-
pentandioate heterocycles through hydroamination with
sequential Michael addition under basic condition. The
KOH/DMSO strategy was also compatible with vinyl phenyl
sulfones. The developed protocol was then extended for the
construction of Dimebon analogue in one-step and AZ-5 CB1
Scheme 6. Synthesis of Allosteric Modulators of CB1 Cannabinoid Receptor
and Dimebon analogs
4
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10.1002/ejoc.202000373
European Journal of Organic Chemistry
COMMUNICATION
Cannabinoid receptor through short reaction sequence in good
yield. The method was well tolerated with variety of functional
group which can be easily elaborated through organic functional
group transformation. Further, deuterium-labelling experiments
supported the mechanistic pathway.
6
(a) E. Song, H. Y. Kim, K. Oh, Org. Lett. 2017, 19, 5264−5267; b) P.
T. Marcyk, S. P. Cook, Org. Lett. 2019, 21, 1547; c) Y. Xiong, G.
Zhang, Org. Lett. 2019, 21, 7873; d) A. J. Musacchio, B. C. Lainhart,
X. Zhang, S. G. Naguib, T. C. Sherwood, R. R. Knowles, Science
2017, 355, 727; d) M. Villa, A. J. v. Wangelin, Angew. Chem. Int. Ed.
2015, 54, 11906; e) K. D. Hesp, M. Stradiotto, ChemCatChem 2010
2, 1192.
,
Acknowledgements
7
8
(a) B. Biersack, Cancer Drug Resist, 2019, 2, 1; b) M. J. Sharma, M.
S. Kumar, M. Murahari, Y. C. Mayur, Arch Pharm Chem Life Sci
2019, 1.
.
The research work was supported by Council of Scientific and
Industrial Research (CSIR) and University of Delhi. Sushmita is
thankful to UGC for JRF, T.A. is thankful to UGC for Women
Post-doctoral fellowship and K.M.S. is thankful to CSIR for SRF
fellowship.
(a) A. V. Ranade, G. A. Thakur, Design and Synthesis of Positive
Allosteric Modulators of CB1 Cannabinoid Receptor, Master’s Thesis
Dissertation, Department of Pharmaceutical Sciences Bouvé College
of Health Sciences, Northeastern University, 2013; b) L. Daniel, Jr.
Minor, S. N. Bagriantsev, A. R. Renslo, US Pat. Appl. 9, 862, 684 B2,
2018; c) T. I. El-Emarya, H. A. K. A. El-Aala, S. K. Mohamed, Int. J.
Pharm. Sci. Rev. Res. 2018, 53, 7.
Keywords: Hydroamination • Indoles• Carbazoles • Styrenes •
9
(a) K. Ishizumi, J. Katsube, UK Pat. Appl. GB 2025932 A, 1980, 6 pp;
b) K. Ishizumi, J. Katsube, U.S. Patent US 4263304 A, 1981, 6 pp; c)
I. Okun, S. E. Tkachenko, A. Khvat, O. Mitkin, V. Kazey, A. V.
Ivachtchenko, Curr. Alzheimer Res. 2010, 7, 97
Acrylates
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10.1002/ejoc.202000373
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Hydroamination of Olefins
Sushmita, Trapti Aggarwal, Kapil
Mohan Saini and Akhilesh K.
Verma
Page No. – Page No.
Olefin-Oriented Selective
Synthesis of Linear and
Branched N-Alkylated
Heterocycles via
Hydroamination
6
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