Selective Propargylation of Diaryl Azo Compounds Using Metallic Barium

Article abstract of DOI:10.1055/s-0040-1706414

The Barbier-type propargylation of azo compounds with α,γ-disubstituted propargylic tosylates was achieved by using metallic barium as the promoter. Various propargylated hydrazines (α-adducts) were exclusively synthesized from the corresponding propargylic tosylates and azobenzenes (diaryldiazenes). The thus-obtained propargylic hydrazines were further efficiently converted into propargylic amines by reductive N-N bond cleavage. Benzidine rearrangement of the propargylic hydrazines was also attempted.

Full text of DOI:10.1055/s-0040-1706414

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© Georg Thieme Verlag Stuttgart · New York
2020, 31, A–F
letter
A
en
A. Yanagisawa et al.
Letter
Synlett
Selective Propargylation of Diaryl Azo Compounds Using Metallic
Barium
Ar2
Akira Yanagisawa*
Toshihiko Heima
Kana Watanabe
Shun Haeno
R1
Ar2
R1
HN
N
OTs
R2
γ
H
Ba
Zn
N
N
α
R1
N
+
α
Ar1
THF, r.t.
Ar1 AcOH, 80 °C
R2
up to >99% yield
Ar1
R2
up to >99% yield
R1
R3
Soft Molecular Activation Research Center, Molecular Chirality
Research Center, Department of Chemistry, Graduate School of
Science, Chiba University, Inage, Chiba 263-8522, Japan
ayanagi@faculty.chiba-u.jp
H
HCl (aq)
N
THF, 70 °C
R2
R3
up to 56% yield
NH2
Received: 17.06.2020
Accepted after revision: 13.07.2020
Published online: 17.08.2020
Ar2
Ar1
Ar2
N
R1
HN
N
OTs
R2
γ
Ba
α
R1
+
α
DOI: 10.1055/s-0040-1706414; Art ID: st-2020-u353-l
N
THF, r.t.
Ar1
R2
Abstract The Barbier-type propargylation of azo compounds with ,-
disubstituted propargylic tosylates was achieved by using metallic bari-
um as the promoter. Various propargylated hydrazines (-adducts)
were exclusively synthesized from the corresponding propargylic to-
sylates and azobenzenes (diaryldiazenes). The thus-obtained propargyl-
ic hydrazines were further efficiently converted into propargylic amines
by reductive N–N bond cleavage. Benzidine rearrangement of the prop-
argylic hydrazines was also attempted.
Scheme 1 Barbier-type propargylation of azobenzenes using metallic
barium
of such propargylic amines has captivated the interest of re-
searchers in the field of organic synthesis.
We have found that allylic barium reagents can be pre-
pared from metallic barium and allylic chlorides and show
high reactivity toward isatin imines with -selectivity.8 We
envisioned that if a propargylic or an allenylic barium re-
agent could be generated from metallic barium9 and the
corresponding propargylic halide under mild reaction con-
ditions and displayed -selectivity in the reaction with an
azo compound, the propargylation would provide a practi-
cal synthetic procedure for propargylated hydrazines. Thus,
we first selected (3-chloroprop-1-ynyl)trimethylsilane (1a)
and azobenzene (2a) as the precursor of propargylic or al-
lenylic barium reagent and the electrophile, respectively,
and attempted to perform a Barbier-type reaction due to
the simplicity of the experimental procedure. When a 3:1
mixture of propargylic chloride 1a (3 equiv) and azoben-
zene (2a, 1 equiv) was treated with metallic barium (3
equiv) in THF at room temperature for 14 h, the reaction did
not proceed and targeted propargylated hydrazine 3aa (-
adduct) was not observed at all (Table 1, entry 1). In con-
trast, -methylated trimethylsilyl-substituted propargylic
chloride 1b showed remarkable reactivity toward 2a and
the desired product was obtained in 49% yield without for-
mation of the corresponding allenylated hydrazine under
similar reaction conditions (entry 2). However, the reaction
of -dimethylated propargylic chloride 1c with 2a resulted
in a low yield (entry 3). -Methylated tert-butyl-substitut-
Key words azo compounds, barium, hydrazines, propargylation,
propargylic tosylates
Propargylic/allenylic barium compounds, which are
generated from Rieke barium1 and propargylic halides, are
useful reagents for the synthesis of organic molecules hav-
ing a carbon–carbon triple bond and high -regioselectivi-
ty.2 We have previously reported that a propargylation of
azo compounds with propargylic halides occurs via a Barbi-
er-type procedure using reactive barium as the low-valent
metal to yield propargylic hydrazines (-product).3 In addi-
tion, a Grignard-type -allylation of azo compounds with
allylic barium reagents4 and a Barbier-type benzylation of
azo compounds with benzylic chlorides5 have been
achieved. We report herein a metallic-barium-promoted
Barbier-type propargylation of azo compounds with prop-
argylic tosylates (Scheme 1). The results of reductive N–N
bond cleavage of the products, propargylic hydrazines, to
form the corresponding propargylic amines as well as ben-
zidine rearrangement of the propargylic hydrazines are also
disclosed. The propargylic amine structure is often seen as
a key framework in pharmaceutical compounds, such as
rasagiline mesylate6 and selegiline hydrochloride.7 There-
fore, the development of useful methods for the synthesis
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
A. Yanagisawa et al.
Letter
Synlett
Table 1 Optimization of Metallic-Barium-Promoted Barbier-Type Propargylation of Azobenzene (2a)a
Ph
Ph
R1
HN
N
Ph
X
γ
Ba (x equiv)
α
N
N
R1
R2
R3
+
α
solvent, r.t., 14 h
R2
Ph
R3
1a–g (x equiv)
2a
3aa–da (α/γ >99:1)
Entry
R1
Me3Si
R2
R3
X
x
Solvent
Product
Yield (%)b
1
2
H
H
H
Me
H
H
H
H
H
H
H
H
H
Cl 1a
Cl 1b
Cl 1c
Cl 1d
Cl 1d
Cl 1d
OTs 1e
3
3
3
3
3
3
3
THF
THF
THF
THF
DMF
3aa
3ba
3ca
3da
3da
3da
3da
3da
3da
3da
3da
3da
<1
49
23
46
38
60
72
46
<1
47
47
69
Me3Si
Me3Si
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
3
4
5
6
THF–DMF (4:1)
7
THF–DMF (4:1)
THF–DMF (4:1)
THF–DMF (4:1)
THF–DMF (4:1)
THF–DMF (4:1)
THF
8
OPO(OPh)2 1f
OCOCF3 1g
OTs 1e
3
3
2
4
3
9
10
11
12
OTs 1e
OTs 1e
a The Barbier-type reaction was carried out using propargylic compounds 1a–g (x equiv), metallic barium (x equiv), and azobenzene (2a, 1 equiv) in the specified
solvent at room temperature for 14 h.
b The chemical yield was determined by 1H NMR spectroscopy using 1,4-bis(trimethylsilyl)benzene as the internal standard.
ed propargylic chloride 1d showed similar reactivity to-
ward 1b and target adduct 3da was formed in 46% yield
(entry 4). Subsequently, we examined solvent effect (en-
tries 4–6) and found that a 4:1 mixture of THF and DMF
was the most suitable solvent from the point of view of
chemical yield (entry 6). We further focused on electron-
withdrawing group X of substrate 1 and when propargylic
tosylate 1e was employed, the highest chemical yield (72%)
was attained (entry 7). Diphenyl phosphate was also a
promising X group (entry 8); in contrast, trifluoroacetate
gave unsatisfactory results and desired adduct 3da was not
obtained in the reaction (entry 9). The chemical yield of
3da shown in entry 7 was not improved when the amounts
of propargylic tosylate 1e and metallic barium were de-
creased or increased (entries 10 and 11). THF was also a
suitable solvent in the reaction of 1e, and 69% yield of prod-
uct 3da was obtained under the optimized reaction condi-
tions (entry 12).
With the optimum reaction conditions in hand, we ex-
amined the propargylation of azobenzene (2a) with prop-
argylic tosylates 1e and 1h–m derived from various propar-
gylic alcohols (Table 2). Higher reactivity was observed for
the reaction of propargylic tosylate 1h, which has an ethyl
group as the R2 group (entry 2). In contrast, propargylic to-
sylate 1i, which has an isopropyl group, afforded product
3fa in a lower yield than propargylic tosylate 1e probably
due to its steric hindrance (entry 3 vs. entry 1). Employ-
ment of phenyl-substituted propargylic tosylate 1k caused
a significant decrease in the yield (31%) of its product 3ha
(entry 5). Trialkylsilyl-substituted propargylic tosylates 1l
and 1m furnished products in satisfactory yields (entries 6
and 7).
We performed the metallic-barium-promoted Barbier-
type propargylation of symmetrical azobenzenes 2b–k de-
rived from a diversely substituted aniline (Table 3). The ef-
Table 2 Metallic-Barium-Promoted Barbier-Type Propargylation of
Azobenzene (2a) with Various Propargylic Tosylates 1e and 1h–ma
Ph
R1
HN
N
Ph
OTs
R2
γ
Ba (3 equiv)
α
N
N
R1
+
α
Ph
THF, r.t., 14 h
Ph
R2
3ba, 3da, 3ea–ia (α/γ >99:1)
1e,h–m (3 equiv)
2a
Entry
R1
t-Bu
R2
Me (1e)
Product
Yield (%)b
1
2
3
4
5
6
7
3da
3ea
3fa
69
85
57
50
31
60
89
t-Bu
t-Bu
Bu
Et (1h)
i-Pr (1i)
Me (1j)
Me (1k)
Me (1l)
Me (1m)
3ga
3ha
3ba
3ia
Ph
Me3Si
t-Bu(Me)2Si
a The Barbier-type reaction was carried out using propargylic tosylates 1e
and 1h–m (3 equiv), metallic barium (3 equiv), and azobenzene (2a, 1
equiv) in THF at room temperature for 14 h.
b The chemical yield was determined by 1H NMR spectroscopy using 1,4-
bis(trimethylsilyl)benzene as the internal standard.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

C
A. Yanagisawa et al.
Letter
Synlett
fect of a substituent on the aromatic ring of azobenzenes
2b–k on the chemical yield was notable: an electron-with-
drawing group (Cl or F) at 4-position of the phenyl group
enhanced the electrophilicity of 2e and 2f relative to 2d,
which has an electron-donating MeO group (entries 4 and 5
vs. entry 3). A methyl group at 2-position reduced the reac-
tivity of 2i (entry 8), whereas 2-F substituted azobenzene
showed significant reactivity probably due to its electronic
effect rather than its steric hindrance (entry 9).
Ar2 group (entry 6). A similar site selectivity was achieved
by using 1-(2,4-difluorophenyl)-2-(3-tolyl)diazene (2r) as
the substrate: a 64:36 mixture of propargylic hydrazines A
and B was obtained in 40% combined yield (entry 7).
Table 4 Metallic-Barium-Promoted Barbier-Type Propargylation of Un-
symmetrical Azobenzenes 2l–r with Propargylic Tosylate 1ha
Ar2
Ar1
Ar1
Ar2
Ar2
t-Bu
Ba (3 equiv)
HN
N
t-Bu
HN
N
OTs
γ
α
N
N
+
α
+
α
t-Bu
Ar1
Table 3 Metallic-Barium-Promoted Barbier-Type Propargylation of
Symmetrical Azobenzenes 2b–k with Propargylic Tosylate 1ha
THF, r.t., 15 h
A
B
1h (3 equiv)
2l–r
3el–er (α/γ >99:1)
3el'–er' (α/γ >99:1)
Yield (%)b A/Bc
Ar
Entry Ar1
Ar2
4-MeC6H4 2l
Product
t-Bu
HN
N
Ar
OTs
γ
Ba (3 equiv)
α
N
N
+
α
t-Bu
Ar
THF, r.t., 14 h
1
2
3
4
5
6
7
Ph
3el + 3el′
>99
78
44:56
57:43
55:45
58:42
56:44
66:34
64:36
Ar
1h (3 equiv)
2b–k
Ph
4-FC6H4 2m
4-ClC6H4 2n
4-FC6H4 2o
4-FC6H4 2p
2-FC6H4 2q
2,4-F2C6H3 2r
3em + 3em′
3en + 3en′
3eo + 3eo′
3ep + 3ep′
3eq + 3eq′
3er + 3er′
3eb–ek (α/γ >99:1)
Ph
92
Entry
Ar
Product
Yield (%)b
4-MeC6H4
4-i-PrC6H4
2-MeC6H4
3-MeC6H4
57
1c
2
4-MeC6H4 2b
4-i-PrC6H4 2c
4-MeOC6H4 2d
4-ClC6H4 2e
4-FC6H4 2f
3eb
3ec
3ed
3ee
3ef
3eg
3eh
3ei
80
73
27
56
60
77
51
10
>99
51
39
>99
40
3
a The Barbier-type reaction was carried out using propargylic tosylate 1h (3
equiv), metallic barium (3 equiv), and azobenzenes 2l–r (1 equiv) in THF at
room temperature for 15 h.
4
5
b The chemical yield was determined by 1H NMR spectroscopy using 1,4-
bis(trimethylsilyl)benzene as the internal standard.
6d
7
3-MeC6H4 2g
3-ClC6H4 2h
2-MeC6H4 2i
2-FC6H4 2j
c The ratio was determined by 1H NMR spectroscopy or 19F NMR spectros-
copy. The structure of the major isomer was determined by N–N bond
cleavage.
8
9d
10
3ej
2,4-F2C6H3 2k
3ek
The thus-obtained propargylic hydrazines can be fur-
ther converted into propargylic amines through reductive
N–N bond cleavage.10 For example, treatment of propargylic
hydrazine derivative 3da with an excess of Zn in acetic ac-
id11 at room temperature for 15 h afforded corresponding
propargylic amine 4da in 32% yield (Table 5, entry 1). Ele-
vating the reaction temperature was effective in acquiring a
higher yield and when the reaction was performed at 80 °C,
a satisfactory isolated yield of 4da was obtained (entry 3).
Decreasing the amount of zinc (entry 4), shortening the re-
action time (entry 5), diluting the reaction solution (entries
6 and 7), and employing trifluoroacetic acid instead of ace-
tic acid (entry 8) did not improve the yield.
With the optimized reaction conditions in hand, we
then executed the N–N bond cleavage of diverse propargyl-
ic hydrazines employing Zn in AcOH. -Ethylated propar-
gylic hydrazine 3ea showed higher reactivity than 3da (Ta-
ble 6, entry 1 vs. Table 5, entry 3). Not only electron-rich
hydrazines but also electron-deficient hydrazines provided
the anticipated propargylic amines in satisfactory yields
(Table 6, entries 2–5). Regioisomeric mixtures of 3eq and
3eq′ effectively underwent the N–N bond cleavage (Table 6,
entry 6) and as a result, regioisomer 3eq was unambigu-
ously determined to be the major product of the reaction
shown in Table 4, entry 6. Similarly, regioisomer 3er was
a The Barbier-type reaction was carried out using propargylic tosylate 1h (3
equiv), metallic barium (3 equiv), and azobenzenes 2b–k (1 equiv) in THF
at room temperature for 14 h.
b The chemical yield was determined by 1H NMR spectroscopy using 1,4-
bis(trimethylsilyl)benzene as the internal standard.
c The reaction was performed for 15 h.
d The reaction was performed for 8 h.
To investigate the electronic effect on the site selectivity
of the nitrogen atoms, we carried out the propargylation of
unsymmetrical azobenzene derivatives having an electron-
deficient group on one aromatic ring and/or an electron-
rich group on the other aromatic ring. As a result, a 44:56
mixture of two regioisomers A and B was obtained as prod-
uct 3el + 3el′ in the reaction of 1-(4-tolyl)-2-phenyldiazene
(2l) with 6,6-dimethylhept-4-yn-3-yl 4-methylbenzenesul-
fonate (1h) almost quantitatively (Table 4, entry 1). In con-
trast, the reaction of unsymmetrical diaryl azo compounds
2m and 2n, which have a 4-halophenyl group as the Ar2
group, resulted in the formation of regioisomer A selective-
ly (entries 2 and 3). Similar site selectivities were observed
in the cases of 1-(4-fluorophenyl)-2-(4-tolyl)diazene (2o)
and 1-(4-fluorophenyl)-2-(4-isopropylphenyl)diazene (2p),
but with unsatisfactory isolated yields (entries 4 and 5).
The highest site selectivity was realized with a 2-tolyl
group as the Ar1 group and a 2-fluorophenyl group as the
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

D
A. Yanagisawa et al.
Letter
Synlett
Table 5 Optimization of Reductive N–N Bond Cleavage of Propargylic
Hydrazine (3da)a
posed to a 2:3 mixture of THF and 2 M HCl (aq) at 50 °C for
20 h, anticipated biphenylamine 5ea was obtained in 47%
yield (Table 7, entry 1). When the reaction temperature was
elevated to 70 °C, the yield was improved to 56% (entry 2).
Attempts to carry out the rearrangement for a shorter reac-
tion time and/or at a higher reaction temperature were not
effective in gaining better results ( entries 3 and 4).
A substituent on the aromatic ring of propargylic hydra-
zines affected the isolated yields of the products. Introduc-
tion of a methyl group to 3-position decreased the yield of
5dg because of steric repulsion between the two methyl
groups of product 5dg (Table 8, entry 2). 2-Methyl-substi-
Ph
t-Bu
HN
N
t-Bu
Zn (x equiv)
AcOH
H
N
Ph
Ph
3da
4da
Entry
x
Temp ( °C)
Time (h)
Yield (%)b
1
100
r.t.
40
80
80
80
80
120
80
15
15
15
15
4
32
57
80
70
78
46
68
33
2
100
100
50
3
4
5
100
100
100
100
Table 7 Optimization of Benzidine Rearrangement of Propargylic Hy-
drazine 3eaa
6c
7c
8d
4
4
t-Bu
Ph
4
H
t-Bu
HN
N
THF–2 M HCl aq (2:3)
N
a The reaction was carried out using propargylic hydrazine 3da (1 equiv)
and zinc dust (x equiv) in acetic acid (1.5 mL) at the specified temperature
for 4 h or 15 h.
Ph
5ea
3ea
b Isolated yield.
NH2
c Acetic acid (3 mL) was used.
d Trifluoroacetic acid was used in place of acetic acid.
Entry
Temp ( °C)
Time (h)
Yield (%)b
found to be the major product in the reaction shown in Ta-
ble 4, entry 7 from the result of the reduction of a mixture
of 3er and 3er′ (Table 6, entry 7).
Subsequently, we investigated the benzidine rearrange-
ment of propargylic hydrazine 3ea, which afforded corre-
sponding biphenylamine 5ea through the N–N bond cleav-
age of 3ea under acidic conditions.12 Optimization of the re-
action temperature and the reaction time was performed,
and the results are shown in Table 7. When 3ea was ex-
1
2
3
4
50
70
20
20
7
47
56
51
28
70
120
7
a The reaction was carried out using propargylic hydrazine 3ea in a mixture
of THF (1 mL) and 2 M HCl aq (1.5 mL) at the specified temperature for 7 h
or 20 h.
b Isolated yield.
Table 6 Reductive N–N Bond Cleavage of Various Propargylic Hydrazines 3ea, 3eb, 3ef, 3ej, 3eq+3eq′, and 3er + 3er′a
Ar2
t-Bu
HN
N
t-Bu
Zn, AcOH
H
N
Ar1
Ar1
80 °C, 15 h
3ea, 3eb, 3ef, 3ej,
3eq+3eq', and 3er+3er'
4ea, 4eb, 4ef, 4ej,
4eq+4eq', and 4er+4er'
Entry
Ar1
Ph
Ar2
Product
Yield (%)b
1
Ph 3ea
4ea
82
2c
3
4-MeC6H4
4-MeC6H4 3eb
4-MeC6H4 3eb
4-FC6H4 3ef
2-FC6H4 3ej
4eb
66
4-MeC6H4
4eb
96
4c
5
4-FC6H4
4ef
55
2-FC6H4
4ej
75
6d
7d
2-MeC6H4/2-FC6H4
3-MeC6H4/2,4-F2C6H3
2-FC6H4 3eq/2-MeC6H4 3eq′, 3eq + 3eq′ (66:34)
2,4-F2C6H3 3er/3-MeC6H4 3er′, 3er + 3er′ (64:36)
4eq + 4eq′
4er + 4er′
82 (74:26)
>99 (69:31)
a The reaction was carried out using propargylic hydrazines 3ea, 3eb, 3ef, 3ej, 3eq + 3eq′, and 3er + 3er′ (1 equiv) and zinc dust (100 equiv) in acetic acid (1.5
mL) at 80 °C for 15 h.
b Isolated yield.
c The reaction was performed for 4 h.
d The reaction was performed using zinc dust (100 equiv) and MeOH (4 equiv) in acetic acid (1.5 mL) at 80 °C for 15 h.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

E
A. Yanagisawa et al.
Letter
Synlett
tuted substrate 3di displayed comparable reactivity to 3da
(entry 3 vs. entry 1). The existence of an electron-with-
drawing group significantly decreased the yield of 5dj
probably due to suppression of protonation of the two ami-
no groups (entry 4).
OTs
γ
α
R1
1-OTs R2
r.t. Ba
TsOBa
BaOTs
R2
γ
α
γ
α
·
R1
R1
R2
N
7
6
Table 8 Benzidine Rearrangement of Various Propargylic Hydrazines
3da, 3dg, 3di, and 3dja
Ar2
N
Ar2
N
Ar2
slow
slow
fast
N
2
N
2
N
2
Ar1
t-Bu
Ar1
Ar2
Ar1
H
R
R
N
t-Bu
HN
N
Ar2
THF–2 M HCl aq (2:3)
Ar2
N
R
TsOBa
N
N
·
N
N
Ar1
R1
70 °C, 20 h
R
R1
Ar1
BaOTs
R2
TsOBa
R1
α
N
Ar1
R2
NH2
α
γ
R2
3da, 3dg, 3di, and 3dj
5da, 5dg, 5di, and 5dj
9
8
10
Entry
R
Product
Yield (%)b
Ar2
Ar1
Ar2
Ar1
R1
HN
HN
N
1
2
3
4
H 3da
5da
5dg
5di
56
30
54
9
R2
γ
α
N
·
3-Me 3dg
2-Me 3di
2-F 3dj
3
R2
α-adducts (major)
R1
γ-adducts (minor)
5dj
Scheme 2 Proposed reaction pathways to -adducts and -adducts
a The reaction was carried out using propargylic hydrazines 3da, 3dg, 3di,
and 3dj in a mixture of THF (1 mL) and 2 M HCl aq (1.5 mL) at 70 °C for 20 h.
b Isolated yield.
propargylic hydrazines in a regioselective manner.15 In ad-
dition, the site-selective propargylation of unsymmetrical
azo compounds has been realized, giving isomeric ratios of
up to 66:34. The utility of the propargylated product has
been further demonstrated by their transformation into
propargylated amines and propargylated biphenylamines
through two types of N–N bond cleavage. Further studies of
related reactions promoted by metallic barium are under
way.
A proposed reaction mechanism is illustrated in Scheme
2. Two pathways are possible for propargylic hydrazines 3
(-adducts). A barium reagent generated from propargylic
tosylate 1-OTs and metallic barium is supposed to be pres-
ent in equilibrium between propargylic isomer 6 and al-
lenylic isomer 7.13 Thus, -adducts are accessible from both
isomers 6 and 7 by treating them with azo compound 2 via
transition-state models 8 and 9, respectively, although for-
mer structure 8 is more favorable due to minimal steric re-
pulsion. Meanwhile, allenylic hydrazines (-adducts) can be
formed from 6 by an SE2′-type reaction of 6 with azo com-
pound 2 through six-membered cyclic transition state 10.
However, 10 is unstable due to steric repulsion between the
R1 group of the barium reagent and an aryl group of the azo
compound. As a consequence, propargylic barium species 6
is anticipated to react preferentially at the -carbon with
azo compound 2 via four-membered cyclic transition state
8,14 yielding the -adduct selectively. Furthermore, in the
case of unsymmetrical azobenzene (Ar1 = electron-rich Ar
group; Ar2 = electron-deficient Ar group), the propargyla-
tion occurs selectively at the nitrogen atom which bonds to
Ar1 group, because the nitrogen atom is considered to be
relatively electron-deficient probably due to resonance ef-
fect. In contrast, another relatively electron-rich nitrogen
atom is allowed to coordinate to barium atom.
Acknowledgement
We gratefully acknowledge financial support from Nippoh Chemicals
Co., Ltd.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1706414.
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References and Notes
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In conclusion, we have achieved a novel Barbier-type
propargylation of azo compounds with barium reagents
that are prepared from propargylic tosylates and metallic
barium. The employment of metallic barium as the source
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(3) Yanagisawa, A.; Koide, T.; Yoshida, K. Synlett 2010, 1515.
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© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

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Letter
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Freshly cut barium (small pieces, 103.0 mg, 0.75 mmol), propar-
gylic tosylate 1h (220.8 mg, 0.75 mmol), and azobenzene (45.6
mg, 0.25 mmol) were placed in a Schlenk tube (25 mL) under an
argon atmosphere and covered with dry THF (1 mL). The
mixture was stirred for 14 h at room temperature. The mixture
was treated with sat. aq NH4Cl (10 mL), and the aqueous layer
was extracted three times with Et2O (10 mL each). The com-
bined organic extracts were washed with brine, dried over
Na2SO4, and concentrated in vacuo after filtration. The residual
crude product was purified by column chromatography on
silica gel (hexane–MeOH, 50:1) to afford propargylic hydrazine
3ea (65.5 mg, 85% yield).
1H NMR (400 MHz, CDCl3):  = 7.25–7.15 (m, 4 H, Ar–H), 7.05–
7.03 (d, 2 H, J = 8.2 Hz, Ar–H), 6.91–6.85 (m, 3 H, Ar–H), 6.77–
6.74 (t, 1 H, J = 7.3 Hz, Ar–H), 5.67 (br, 1 H, NH), 4.43–4.39 (t, 1
H, J = 7.5 Hz, CH), 1.89–1.66 (m, 2 H, CH2), 1.16 (s, 9 H, 3 CH3),
1.04–1.00 (t, 3 H, J = 7.4 Hz, CH3). 13C NMR (99.5 MHz, CDCl3):
 = 150.8, 149.0, 129.1, 128.9, 120.7, 118.9, 116.2, 112.1, 94.9,
75.1, 58.1, 31.4, 31.1, 27.4, 11.4. IR (neat): 3311, 2965, 2359,
1600, 1496, 1362, 1308, 1239, 1170, 1092, 1025, 992, 857, 819,
745, 691, 628 cm–1. MS (ESI): m/z calcd for [C21H27N2]+ [M + H]+:
307.2169; found: 307.2170; mp 57–60 °C..
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F