Ir-Catalyzed Intramolecular Transannulation/C(sp2)-H Amination of 1,2,3,4-Tetrazoles by Electrocyclization

Article abstract of DOI:10.1021/jacs.8b05343

An efficient strategy for the intramolecular denitrogenative transannulation/C(sp²)-H amination of 1,2,3,4-tetrazoles bearing C8-substituted arenes, heteroarenes, and alkenes is described. The process involves the generation of the metal-nitrene intermediate from tetrazole by the combination of [CpIrCl₂]₂ and AgSbF₆. It has been shown that the reaction proceeds via an unprecedented electrocyclization process. The method has been successfully applied for the synthesis of a diverse array of α-carbolines and 7-azaindoles.

Full text of DOI:10.1021/jacs.8b05343

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Communication
Ir-Catalyzed Intramolecular Transannulation/C(sp2)–
H Amination of 1,2,3,4-Tetrazoles by Electrocyclization
Sandip Kumar Das, Satyajit Roy, Hillol Khatua, and Buddhadeb Chattopadhyay
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b05343 • Publication Date (Web): 28 Jun 2018
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Ir-Catalyzed Intramolecular Transannulation/C(sp2)–H Amination
of 1,2,3,4-Tetrazoles by Electrocyclization
Sandip Kumar Das,† Satyajit Roy,† Hillol Khatua,† and Buddhadeb Chattopadhyay†,*
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†Center of Bio-Medical Research, Division of Molecular Synthesis & Drug Discovery, SGPGIMS Campus, Raebareli Road,
Lucknow 226014, Uttar Pradesh, India
Supporting Information Placeholder
On the other hand, owing to the presence in molecules with a
ABSTRACT: An efficient strategy for the intramolecular
denitrogenative transannulation/C(sp2)–H amination of
1,2,3,4-tetrazoles bearing C8-substituted arenes, heteroarenes
and alkenes is described. The process involves the generation
of the metal-nitrene intermediate from tetrazole by the combi-
nation of [Cp*IrCl2]2 and AgSbF6. It has been shown that the
reaction proceeds via an unprecedented electrocyclization
process. The method has been successfully applied for the
synthesis of a diverse array of a-carbolines and 7-azaindoles.
wide range of biological activity, a-carboline ring system has
been branded as one of the privileged frameworks9 for drug
discovery (Chart 1, C). Numerous methods10 exist for the
assembly of various a-carboline, however, every method is
associated with their own restrictions (e.g. selectivity issues,
poor yield, requirement of particular classes of substrate etc.).
Thus, it is highly desirable to develop new methods to over-
come the existing shortcomings. Herein, we report a new con-
cept11 for the intramolecular denitrogenative transannulati-
on/C(sp2)–H amination of 1,2,3,4-tetrazoles by iridium cataly-
sis, which undergo likely via the TS-IV (Chart 1, B) for the
synthesis of diverse a-carbolines, 7-azaindoles and other im-
portant classes of heterocycles.
Transition metal-catalyzed denitrogenative transannulation1 is
one of the most efficient methods to construct nitrogen-
containing heterocycles. It has been reported that while 1,2,3-
triazoles readily undergo denitrogenative transannulation with
transition metal catalysts via either an ionic1,2 or a radical acti-
vation mechanism,3 1,2,3,4-tetrazoles remain completely inac-
tive for the transannulation.4 In this context, Wentrup’s pio-
neering denitrogenative thermal and photochemical nitrene-
nitrene rearrangement of tetrazoles is remarkable, which pro-
vide various nitrogen heterocycles.5 Usually, 1,2,3,4-tetrazoles
exist in equilibrium between closed and open form, the posi-
tion of this equilibrium depends on (Chart 1, A) several pa-
rameters6 (e.g. temperature, solvents and substituents). Alt-
hough, Driver group7 has studied well on metal-nitrene com-
plexes derived from ortho-substituted aryl azides, however,
the denitrogenative transannulation of 1,2,3,4-tetrazole via
metal-nitrene is entirely underdeveloped to date. Thus, it
would be highly intriguing to develop this transannulation/C–
H amination8 chemistry via metal-nitrene formation.
Table 1. Evaluation and Reaction Optimizationsa
2-20 mol% [M]-cat.
0-20 mol% AgSbF6, solvent
130 oC, 24 h
+
N
N
N
N
N
NH2
H
N
N
– N2 gas
2a’
1a
2a
solvent
PhMe
DCE
PhH
2a/2a’
cat.
Cu-cat.
additive
#
1
2
3
4
5
6
7
8
9
0
–
0
Zn-cat.
–
0
Co-cat.
–
PhH
0
Fe-cat.
–
PhH
0
Mn-cat.
–
dioxane
DCE
PhH
0
Ru-cat.
–
0
0/40
100 (96)
0
Rh-cat.
–
[Ir(cod)(Cl)]2
[Cp*IrCl2]2
[Cp*IrCl2]2
AgSbF6
AgSbF6
–
PhH
Chart 1. Concept for the Transannulation/C–H Amination
PhH
10
Cu-cat. = Cu(MeCN)4•PF6, CuI, CuBr, CuBr•Me2S, Cu(acac)2, Cu(OTf)•C6H6;
Zn-cat. = ZnI2; Co-cat. = Co(TPP), Fe-cat. = FeBr2, Fe(TPP)Cl; Mn-cat. =
Mn(TPP)Cl, Ru-cat. = [Ru(p-cymene)Cl]2; Rh-cat. = Rh2(OAc)4, Rh2(oct)4,
Rh2(O2CC3F7)4, Rh2(esp)4, Rh2(s-dosp)4
(A) Proposed hypothesis for the metal-nitrene
unknown
7
known
FG
[M]
metal-carbene
N
FG
8
6
[M]-cat.
[M]
[M]-cat.
N
N
5
N1
4N
3N
N
N3
N
N
N2
N
aReactions were conducted with 0.25 mmol scale and NMR
conversions were determined using 1,3,5-trimethoxybenzene as
internal standard; in parenthesis, isolated yield is given.
N2
metal-nitrene
via
N
2
(B) Proposed hypothesis and designed work plan
X = SbF6
N
N
Ir(III)
SbF6
[M]-cat.
X
Thus, we started our initial investigations with substrate 1a
using a variety of transition metal catalysts (Table 1, entries 1-
7, see: SI, for detail optimization) based on the proposed hy-
pothesis that in presence of metal catalysts tetrazole would
first generate the metal-nitrene intermediate and subsequently
undergo intramolecular transannulation/C(sp2)–H amination.12
To our surprise, none of the metal catalysts afforded desired
product and the tetrazole remain completely unreacted under
the employed reaction conditions. For this extreme inertness13
of the tetrazole, we reasoned that metal catalysts such as Cu,
Zn, Co, Fe, Mn, Ru and Rh might be strongly coordinating
N
N
Me
Me
Me
H
H
H
N
N
N3
N
Me
TS-IV
N2
α-carboline
N
N
Me
(C) Selected examples for bioactive molecules
Me
COMe
HOHN
N
N
HO
N
N
O
N
H
OH
N
Me
Neocryptolepin
OMe
OMe
O
Food-derived carcinogen
Cl
O
O
O
N
O
S
HO
OMe
N
N
N
N
H
N
H
Me
Cytotoxicity against
CH3
HO
Mescengricin
Antioxidant
HL-60AceCllSlinPearagon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
with both the nitrogen atoms of the tetrazole (i.e. pyridine and
Table 2. Scope of Reaction with Diverse Substrates
1
2
3
4
5
6
7
8
azide nitrogen) and inhibiting the catalytic process for the
generation of the metal-nitrene intermediate.14 Next, consider-
ing the unique reactivity of Chang’s amidation,15 we turned
our attention towards iridium-based catalytic systems. Thus,
transannulation was carried out by the combination of
[Ir(cod)Cl]2 and AgSbF6, which gave 40% reduced product
R1
5.0 mol% [Cp*IrCl2]2
20 mol% AgSbF6, PhH
R1
R
R
130 oC, 12-24 h
N
N
N
N
H
– N2 gas
2b-v
1b-v
N
N
(A) scope of C-8 arene with diverse substitutions
Me
F
OMe
Ph
¢
(2a , entry 8). Remarkably, when the same reaction was per-
N
N
N
N
N
N
N
N
H
formed in presence of [Cp*IrCl2]2 and AgSbF6 in benzene
solution, we observed quantitative conversion of the starting
tetrazole into the desired transannulation product (2a) in 96%
isolated yield (entry 9). In order to verify the role of the
AgSbF6, same reaction was carried out without AgSbF6, which
resulted in no reaction (entry 10). Moreover, conducting the
reaction with only AgSbF6, no product formation observed.
With these encouraging results, transannulations/C(sp2)–H
aminations were performed for a series of 1,2,3,4-tetrazoles
(Table 2). Irrespective of the substituents present in the C8
arene, for example, alkyl, alkoxy, phenyl, vinyl, ester, trifluo-
romethyl, and ketone were well tolerated under the reaction
conditions (Table 2, A). Remarkably, in case of the meta-
substituted C8-arene, the reaction produced exclusively one
regioisomer out of the possible two regioisomers (entries 2h-
2l, 2v). Moreover, various disubstituted arenes at C8 position
(2q-2t) including a bulky naphthyl group (2u) led to the a-
carbolines in good yield. For further elaboration, we examined
various substitutions at the pyridine moiety of the 1,2,3,4-
tetrazoles (Table 2, B). Thus, 1,2,3,4-tetrazoles with different
substituents at pyridine such as, 5-methyl (2w), 6-phenyl-7-
methyl (2x), 6-methyl (2y) and 6-phenyl (2z) were found to be
compatible. Moreover, 5-hexenyl (2ab) and 5-pentenyl (2ac)
also tolerated in the reaction conditions delivering a-
carbolines in excellent yield.16
H
H
2b: 85%
2c: 90%
2d: 93%
9
Cl
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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60
N
H
N
H
N
H
2f: 90%
2e: 80%
2g: 83%
Me
OMe
CF3
N
N
N
N
N
N
N
N
H
H
H
2j: 69%
2h: 80%
2i: 89%
Me
CHO
CO2Et
N
N
H
N
H
N
H
2m: 77%
2l: 82%
2k: 76%
MeO
Ph
F
N
N
N
N
N
N
N
N
H
N
H
H
2n: 96%
2p: 83%
2o: 67%
Me
OMe
OMe
CF3
N
N
H
N
H
N
H
Me
CF3
2q: 91%
2r: 92%
2s: 74%
F
COMe
F
N
N
N
N
H
N
H
H
2t: 71%
2u: 84%
2v: 88%
(B) scope of pyridine ring of the tetrazoles
Me
Next, we explored the substrate scope with respect to the
different types of heteroaromatic systems for C8 substituted
1,2,3,4-tetrazoles (Table 2, C). A range of heterocyclic
systems smoothly underwent transannulation/amination to
afford the desired multiple-nitrogen-containing molecules in
excellent yields. For example, variously substituted pyridines
(2ad-2ag), quinoline (2ah) and N-methylindole (2ai) gave the
corresponding products in excellent yields. In this context, it
deserves mentioning that in case of C8-substituted heterocycle
(2ae), out of two possible regioisomers, we observed only the
aforementioned isomer as the sole products. For further appli-
cation of this newly developed strategy, we have demonstrated
that the alkaloid Neocryptolepin (4) and an important mole-
cule, which exhibits cytotoxicity against HL-60 cell line (5)
can be synthesized efficiently with excellent yields from the
corresponding tetrazoles (Chart 2).
Towards this end, we were interested in the further develop-
ment of this method with respect to the C8-substituted alkenes.
Pleasingly, the developed method was found to be equally
efficient with numerous alkenes and the results are summa-
rized in Table 3. Performing the reactions with electronically
neutral alkene (6a), electron-deficient alkenes (6b-c) and
electron-rich alkenes (6d-e) provided the corresponding 7-
azaindoles (7a-e) with excellent yields. Moreover, transannu-
lations of cyclic alkenes-bearing 1,2,3,4-tetrazoles were also
found to be compatible delivering consistently in good yields
(7f-g). Furthermore, substitution at the pyridine ring of the
tetrazole-bearing styrene type of alkenes smoothly underwent
denitrogenative transannulation/C(sp2)–H amination to give
the substituted 7-azaindole derivatives.
Ph
Me
Me
N
N
N
N
N
N
H
H
H
2w: 82%b
2x: 71%
2y: 86%
Ph
N
N
N
N
N
H
N
H
H
2z: 85%
2ac: 83%b
2ab: 80%b
(C) scope of C-8 heteroarene with various substitutions
N
N
Me
N
N
N
N
N
N
H
N
N
H
H
2af: 89%
2ad: 95%
2ae: 76%
N
N
N
N
N
N
N
H
N
H
Me
Me
2ag: 92%
H
2ah: 89%
2ai: 66%
aReactions were conducted with 0.5 mmol scale; isolated yields
were reported after purification. bReaction completed within 12 h.
Chart 2. Short Synthesis of Important Molecules
– N2 gas
i) 5.0 mol% [Cp*IrCl2]2, 20 mol%
AgSbF6, PhH, 130 oC, 24 h
ii) 3.0 equiv. MeI, THF, 80 oC, 12 h
N
N
N
N
Me
3
4, 96%
N
N
Neocryptolepin
COMe
– N2 gas
H
i) 5.0 mol% [Cp*IrCl2]2, 20 mol%
AgSbF6, PhH, 130 oC, 24 h
O
ii) 1.1 equiv. FG–Br, 2.0 equiv KOH,
THF, 70 oC, 30 min
FG = 3,4,5-trimethoxybenzyl
N
H
Me
N
N
N
5, 80%
FG
N
N
1v
Cytotoxicity against
HL-60 cell line
2
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Table 3. Scope of Transannulation with Alkenesa
with substrate 11 and observed no reaction, which clearly in-
1
2
3
4
5
6
7
8
dicates that conjugation is essential for the reaction.
R/Ar
5.0 mol% [Cp*IrCl2]2
20 mol% AgSbF6, PhH
130 oC, 24 h
R1
Chart 4. Mechanistic Studies/Control Experiments
R1
N
N
R/Ar
N
N
H
A) control experiments with nonconjugated alkene and conjugated Z-alkene:
– N2 gas
N
6a-i
N
developed
conditions
7a-i
developed
Ph conditions
H
N
N
N
N
Ph
N
N
N
N
N
N
H
H
N
N
8
9, 0%, no reaction
B) measurement of KIE value (intermolecular & intramolecular):
7b, conv. 69%
10, Z-isomer
N
N
N
CO2Me
Ph
N
N
N
H
D/H
Me
H
7c: 79%
H
Me
H
7a: 86%
D/H
D/H
7b: 89%
developed
conditions
9
developed
conditions
Me
OMe
Me
D/H
D
N
N
N
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
N
N
N
N
N
N
N
N
KH/KD = 1.034
KH/KD = 1.01
H
N
H
N
H
N
H
D/
N
D/H
2b/2b-d2
N
1b–d
OMe
Me
1b/1b-d2
2b–d
7f: 96%
7e: 90%
7d: 93%
C) control reaction with non-conjugated 1,2,3,4-tetrazole:
OMe
developed conditions
Me
N
N
N
N
N
N
N
N
Ph
Ph
H
N
N
H
N
N
11
12, 0%, no reaction
H
7h: 88%
H
7g: 87%
D) effects of substituents at C3 and C4 position of arene:
7i: 91%
OMe
OMe
aReactions were conducted with 0.5 mmol scale; isolated yields
were reported after purification.
OMe
developed
+
OMe
+
N
N
conditions
N
N
N
N
N
N
N
H
2c: conv. 38% @4 h
H
2i: conv. 6% @4 h
N
N
N
1c
1:1 ratio
same vessel
Next, we studied the mechanism and the product formation
might be explained by the following four mechanisms, which
are depicted in Chart 3, such as: i) C–H activation15 via TS-I,
ii) C–H insertion via TS-II, iii) electrophilic aromatic substitu-
tion (EAS) via TS-III and iv) electrocyclization via TS-IV.17
1i
Chart 5. Proposed Electrocyclization Mechanism
[Cp*IrCl2]2
2AgSbF6
2AgCl
Ph
N3
Ph
SbF6
N
X
N
H
(III) Me
Ir
Me
Me
Chart 3. Possible Four Mechanistic Pathways
product
N
N
N
1a
Me
N
N
Me
X = SbF6
AC-1
N
N
N
N
N
N
H
N
N
N2
H
X
H
N
N
N
N
SbF6
SbF6
H
SbF6
Me
Me
X
X
Ir(III)
X
Ir(III)
X
SbF6
X
SbF6
Me
Ir(III)
Ir(v)
Ir(v)
Ir(III)
Me
Me
Me
Me
Me
SbF6
N2
Me
Me
Me
N
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
(E)
Me
Me
Me
N
Me
SbF6
Me
(A)
X
Me
Me
Me
TS-I: C-H Activation
Me
Ir(III)
Me
TS-II: C-H Insertion
TS-IV: Electrocyclization
TS-III: EAS
Me
Me
1,5 H-shift
Me
Thus, to shed light on the mechanistic aspects of the proposed
pathways, we executed several control experiments (Chart 4).
According to the literature report, since the [Cp*IrCl2]2 is
known15 to catalyze the reaction via direct C-H activation
mechanism, we thus decided to verify whether our transannu-
lation/C(sp2)–H amination would follow the same C-H activa-
tion or π-electron participation. For that reason, we conducted
a control experiment with substrate 8, where conjugation was
disturbed by one methylene group. We observed that substrate
8 does not give even a trace amount of the desired product,
which indicates that the present transannulation/amination
strategy might not follow neither C–H activation mechanism
(TS-I) nor C–H insertion mechanism (TS-II). For further
studies, we performed another control experiment with sub-
strate 10 (Z-isomer),18 where C-H bond is away from the reac-
tion center. We anticipated that due to the geometric constrain,
transannulation should not occur with the Z-isomer (10). But,
to our surprise, substrate 10 smoothly underwent the transan-
nulation affording 69% product conversion, which also oppose
the C-H activation and C–H insertion mechanism (TS-I & TS-
II). Finally, determining the KIE value (intermolecular and
intramolecular), we observed a secondary kinetic isotope ef-
fect (~1.0), which is again ruling out the possibility of TS-I
and TS-II.
N
Me
TS-IV
4-electron
5-atom
SbF6
N
N
N
Ir(v)
N
electro-
cyclization
X
X
(B)
Ir(v)
N
Me
Me
Me
Me
SbF6
N
Me
H
X
SbF6
Me
Ir(III)
Me
Me
Me
N
Me
Me
SbF6
H
X
Me
Me
Ir(III)
Me
(D)
(B’) disfavored
Me
Me
Me
Me
steric between lp of
N & Me grs of Cp*
Me
(C)
Me
To gain more insight, we conducted another competitive ex-
periment using a 1/1 mixture of 3-OMe and 4-OMe-
substituted substrates (1i/1c), hypothesizing that the EAS (TS-
III) and electrocyclization process (TS-IV) would be more
favored with 1i and 1c respectively, producing more product
conversion due to the electronic effects (Chart 4, D).19 How-
ever, we virtually observed that whereas, substrate 1i gave
only 6% conversion, substrate 1c afforded 38% conversion,
which is evidencing the proof-of-concept for the electrocy-
clization process (TS-IV).
Thus, based on the experimental evidences, we proposed the
following electrocyclization mechanism (Chart 5). Treating
with AgSbF6, dimeric [Cp*IrCl2]2 generates the active catalyt-
ic species (AC-1),15a,20 which coordinates with the N1 atom of
the tetrazole (1a) to form the species (A). Then, the species
(A), might produce the sterically favored (B)21 by the loss of
dinitrogen. Next, the metal-nitrene (B) upon rearrangement of
its π-electron generates the TS-IV, which undergoes 4-
electron-5-atom electrocyclization to form the C–N bond in
species (C). Subsequently, by a routine 1,5-H shift from the
Next, we hypothesized that if the reaction goes via electro-
philic aromatic substitution (EAS, TS-III), then substrate 11
should furnish the corresponding transannulation product 12,
because continuous conjugation is not essential for the EAS
process. Following this hypothesis, reaction was performed
3
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Wentrup, C. J. Am. Chem. Soc. 2011, 133, 5413 (l) Messmer, A.;
resonating structure (D) of (C) led to the product formation
with the regeneration of the active catalytic species (AC-1).
In conclusion, we have developed an efficient intramolecular
denitrogenative transannulation/C(sp2)–H amination method
for the synthesis of a wide number of carbolines and 7-
azaindoles by Ir(III)-catalyzed electrocyclization process. The
essential requirement of this approach is the employment of
[Cp*IrCl2]2 and AgSbF6 to generate the active catalytic species
that help to form the metal-nitrene intermediate for the
transannulation/amination. This is the first report for the deni-
trogenative transannulation/amination via metal-nitrene for-
mation, which undergoes via an unprecedented electrocycliza-
tion process. The developed method shows very broad sub-
strate scope and functional group tolerance. The synthetic
benefits of the developed approach are showcased with a short
synthesis of important bioactive molecules. More efforts are
underway in our laboratory.
Hajos, G.; Juhasz-Riedl, Z.; Sohar, P. J. Org. Chem. 1988, 53, 973.
(m) For click reaction, see: Chattopadhyay, B.; Rivera Vera, C. I.;
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47
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(8) For a leading review of C–H aminations by metal-nitrene for-
mation, see: Davies, H. M. L.; Manning, J. R. Nature 2008, 451, 417.
(9) For selected examples, see: (a) Helbecque, N.; Moquin, C.;
Bernier, J. L.; Morel, E.; Guyot, M.; Henichart, J. P. Cancer Biochem.
Biophys. 1987, 9, 271. (b) Yeung, B. K. S.; Nakao, Y.; Kinnel, R. B.;
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Metab. Dispos. 1996, 24, 395.
(10) For selected examples, see: (a) He, L.; Allwein, S. P.; Dugan,
B.; Knouse, K. W.; Ott, G. R.; Zificsak, C. A. Org. Synth. 2016, 93,
271. (b) Wadsworth, A. D.; Naysmith, B. J.; Brimble, M. A. Eur. J.
Med. Chem. 2015, 97, 816.
(11) This is the first report for the intramolecular denitrogenative
transannulation/C(sp2)–H amination of fused 1,2,3,4-tetrazoles via
metal-nitrene. Attempted transannulation of 1,2,3,4-tetrazoles with
alkynes and nitriles failed under the developed reaction conditions.
(12) Extensive screenings were carried out by the different combi-
nations of solvents, catalysts and additives, for details, see: SI.
(13) Based on the NMR studies at room temperature, we observed
that 1,2,3,4-tetrazole always exits in closed form, there is no effect of
substituent at C8 position. However, halogen substituent at C5 posi-
tion gives appreciable amount of open form. For details, see ref. 6.
(14) For lower reactivity of 2-pyridyl diazo-compounds in Rh-
catalyzed reactions, see: Davies, H. M. L.; Townsend, R. J. J. Org.
Chem. 2001, 66, 6595.
(15) For selected examples, see: (a) Ryu, J.; Kwak, J.; Shin, K.;
Lee, D.; Chang, S. J. Am. Chem. Soc. 2013, 135, 12861. (b) Park, Y.;
Heo, J.; Baik, M.-H.; Chang, S. J. Am. Chem. Soc. 2016, 138, 14020.
(c) Hong, S. Y.; Park, Y.; Hwang, Y.; Kim, Y. B.; Baik, M.-H.;
Chang, S. Science 2018, 359, 1016. (d) Shin, K.; Park, Y.; Baik, M.
H.; Chang, S. Nat. Chem. 2018, 10, 218. (e) Park, Y.; Kim, Y.;
Chang, S. Chem. Rev. 2017, 117, 9247.
ASSOCIATED CONTENT
Supporting Information Available: Full characterization, copies
of all spectral data, experimental procedures. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
buddhadeb.c@cbmr.res.in, buddhachem12@gmail.com
Author Contributions
SKD and SR contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by CSIR-EMR-II grant (Sanction No.
02(0259)/16/EMR-II), Ramanujan grant and DST-Young Scien-
tist Grant. SKD thanks CSIR for JRF, SR and HK thanks CSIR
for SRF and JRF. We thank the NMR and mass spectrometry
facility at CBMR, and the Director, for the research facilities.
REFERENCES
(1) For leading reviews on transannulations of 1,2,3-triazoles, see:
(a) Chattopadhyay, B.; Gevorgyan, V. Angew. Chem. Int. Ed. 2012,
51, 862. (b) Gulevich, A. V.; Gevorgyan, V. Angew. Chem. Int. Ed.
2013, 52, 1371. (c) Davies, H. M. L.; Alford, J. S. Chem. Soc. Rev.
2014, 43, 5151.
(16) Notably, for C5-substituted pyridine, reaction completed
within short period of time, which might be due to more open azide
form of the tetrazole.
(17) Selected examples of electrocyclization of other types of azi-
des: (a) Shen, M.; Leslie, B. E.; Driver, T. G. Angew. Chem. Int. Ed.
2008, 47, 5056. (b) Stokes, B. J.; Jovanovic, B.; Dong, H.; Richert, K.
J.; Riell, R. D.; Driver, T. G. J. Org. Chem. 2009, 74, 3225. (c)
Stokes, B. J.; Richert, K. J.; Driver, T. G. J. Org. Chem. 2009, 74,
6442. (d) Driver, T. G. Org. Biomol. Chem. 2010, 8, 3831. (e)
Pumphrey, A. L.; Dong, H.; Driver, T. G. Angew. Chem. Int. Ed.
2012, 51, 5920. (f) Nguyen, Q.; Nguyen, T.; Driver, T. G. J. Am.
Chem. Soc. 2013, 135, 620. (g) Harrison, J. G.; Gutierrez, O.; Jana,
N.; Driver, T. G.; Tantillo, D. J. Am. Chem. Soc. 2016, 138, 487. (h)
Mazumdar, W.; Jana, N.; Thurman, B. T.; Wink, D. J.; Driver, T. G.
J. Am. Chem. Soc. 2017, 139, 5031. (i) Alford, J. S.; Spangler, J. E.;
Davies, H. M. L. J. Am. Chem. Soc. 2013, 135, 11712.
(18) To verify the isomerization during the reaction, Z-isomer (10)
was heated at 130 oC for several hours and found no interconversion.
(19) For detailed mechanistic studies via electrocyclization path-
way of nonpyridyl azide substrates, see: ref. 17c.
(20) Wang, L.; Yang, Z.; Yang, M.; Zhang, R.; Kuaia, C.; Cui, X.
Org. Biomol. Chem. 2017, 15, 8302.
(2) For the first report of denitrogenative transannulation via ionic
mechanism, see: (a) Chuprakov, S.; Hwang, F. W.; Gevorgyan, V.
Angew. Chem. Int. Ed. 2007, 46, 4757. (b) Horneff, T.; Chuprakov,
S.; Chernyak, N.; Gevorgyan, V.; Fokin, V. V. J. Am. Chem. Soc.
2008, 130, 14972.
(3) For the first report of denitrogenative transannulation by radical
activation mechanism, see: Roy, S.; Das, S. K.; Chattopadhyay, B.
Angew. Chem. Int. Ed. 2018, 57, 2238.
(4) During preparation of our manuscript, one report appeared for
the denitrogenative transannulation with monocyclic 1,2,3,4-
tetrazoles via metal-carbene intermediate, Nakamuro, T.; Hagiwara,
K.; Miura, T.; Murakami, M. Angew. Chem. Int. Ed. 2018, 57, 5497.
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Wentrup, C. Org. Biomol. Chem. 2004, 2, 1227. (h) Reisinger, A.;
Koch, R.; Wentrup, C. J. Chem. Soc., Perkin Trans. I 1998, 2247. (i)
Reisinger, A.; Wentrup, C. Chem. Commun. 1996, 813. (j) Wentrup,
C. Tetrahedron 1970, 27, 367. (k) Kvaskoff, D.; Vosswinkel, M.;
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Intramolecular Transannulation/C(sp2)–H Amination of 1,2,3,4-Tetrazoles
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[Cp*Ir]-cat.
[Cp*Ir]-cat.
H
N
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N
N
N
H
N
H
N2
N2
N
N
7-azaindole
derivatives
9 examples
α-carboline
36 examples
66-95% yields
N
79-96% yields
N
Ir(III)
SbF6
X
Me
Me
Me
Me
Me X = SbF6
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via Metal-Nitrene/
Electrocyclization
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