Remarkable reactivity enhancement with Sb?N inter-coordination of ethynyl-1,5-azastibocines in Pd-catalyzed cross-coupling reactions with organic halides

Article abstract of DOI:10.1016/j.tetlet.2003.09.135

The reaction of 12-arylethynyl-6-methyl-5,6,7,12-tetrahydrodibenzo[c,f][1, 5]-azastibocines with organic halides such as acyl halides and aryl halides in the presence of PdCl₂(PPh₃)₂ as a catalyst led to the formation of cross-coupling products, alkynyl ketones and diaryl acetylenes, in good yields. The reactivity of the ethynyl group on the 1,5-azastibocines was far superior to that on diphenyl(phenylethynyl)stibane, which brought about marked improvement in the reaction conditions (lower temperature and shorter reaction time) and in the yields of the cross-coupling products. Single-crystal X-ray analysis of the ethynyl-1,5-azastibocine showed the presence of intramolecular Sb?N interaction which should be responsible for the remarkable reactivity enhancement of the 1,5-azastibocines for this type of reaction.

Full text of DOI:10.1016/j.tetlet.2003.09.135

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8589–8592
Remarkable reactivity enhancement with Sb···N
inter-coordination of ethynyl-1,5-azastibocines in Pd-catalyzed
cross-coupling reactions with organic halides
Naoki Kakusawa,a Yoshinori Tobiyasu,a Shuji Yasuike,a Kentaro Yamaguchi,b Hiroko Sekib and
Jyoji Kuritaa,*
aFaculty of Pharmaceutical Sciences, Hokuriku University, Kanagawa-machi, Kanazawa 920-1181, Japan
bChemical Analysis Center, Chiba University, Yayoicho, Inage-ku, Chiba 263-8322, Japan
Received 11 August 2003; revised 12 September 2003; accepted 12 September 2003
Abstract—The reaction of 12-arylethynyl-6-methyl-5,6,7,12-tetrahydrodibenzo[c,f ][1,5]-azastibocines with organic halides such as
acyl halides and aryl halides in the presence of PdCl2(PPh3)2 as a catalyst led to the formation of cross-coupling products, alkynyl
ketones and diaryl acetylenes, in good yields. The reactivity of the ethynyl group on the 1,5-azastibocines was far superior to that
on diphenyl(phenylethynyl)stibane, which brought about marked improvement in the reaction conditions (lower temperature and
shorter reaction time) and in the yields of the cross-coupling products. Single-crystal X-ray analysis of the ethynyl-1,5-azastibocine
showed the presence of intramolecular Sb···N interaction which should be responsible for the remarkable reactivity enhancement
of the 1,5-azastibocines for this type of reaction.
© 2003 Elsevier Ltd. All rights reserved.
The chemistry of organoantimony compounds has
attracted much interest over the years on account of
their widespread use for organic synthesis. For exam-
12-arylethynyl-6-methyl-5,6,7,12-tetrahydrodibenzo[c,f ]-
[1,5]azastibocines 2a–c with organic halides such as acyl
halides 3 and aryl halides 5 affords the corresponding
ethynyl derivatives 4 and 6 through the same type of
coupling reaction. In the reaction of the ethynyl-1,5-aza-
stibocines 2a–c, significant reactivity enhancement of the
ethynyl groups toward the coupling reaction was
observed, in comparison with the reaction by use of the
ethynylstibane 1 (Fig. 1).
1
ple, many organoantimony compounds have been
reported to be useful for a wide range of carbonꢀcarbon
bond-forming reactions, such as Wittig-type condensa-
tion,2 transition metal-catalyzed self-3 and cross-cou-
pling reactions,4–7 carbonylations,8 and photoreactions9
as substrates, and for transition metal-catalyzed asym-
metric reaction as chiral auxiliaries.10 However, most of
the antimony compounds substantially used are
restricted to peraryl antimony(III) and (V) derivatives
due to their easy accessibility and simple handling with
high stability. In the course of our studies on the
synthesis of new organoantimony compounds and their
utilization as synthetic reagents for organic synthe-
sis,9b,10,11 we have recently reported that the reaction of
diphenyl(phenylethynyl)stibane 1 with acid halides in the
presence of a Pd-catalyst resulted in cross-coupling
reaction to give alkynyl ketones, in good to moderate
yields.12 As a continuation of our studies on this type of
coupling reaction, we now disclose that treatment of
The key starting compounds, ethynyl-1,5-azastibocines
2a–c,13 could be easily prepared from bis(o-bromobenz-
yl)methyl amine via 12-bromo-6-methyl-5,6,7,12-tetra-
hydrodibenzo[c,f ][1,5]-azastibocine, by
a
similar
Keywords: antimony compounds; alkynyl stibane; 1,5-azastibocine;
coupling reactions; palladium catalyst.
* Corresponding author. Tel.: +00 81 76 229 1165; fax: +00 81 76 229
2781; e-mail: j-kurita@hokuriku-u.ac.jp
Figure 1.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.09.135

8590
N. Kakusawa et al. / Tetrahedron Letters 44 (2003) 8589–8592
Table 1. Palladium-catalyzed coupling reaction of 1,5-aza-
stibocines 2a–c with acyl chlorides 3a–ea
ethynyl-1,5-azastibocines 2a–c was far superior as an
alkynylation agent for this type of coupling reaction
from the standpoint of the reaction conditions; the
reaction temperature and the reaction time for 2a being
at rt for 1 h, whereas those for 1 being at 80°C for 2.5
h (entries 1–3).12 Moreover, in the reaction of 2a with
aliphatic acyl chlorides 3b–e, the reaction conditions as
well as the yields of the cross-coupling products 4 were
more satisfactory than those of 1 (entries 4–7). In all
these reactions, a catalytic amount of diaryl-1,3-
butadiynes 7 (2–3%) was isolated, and the antimony
reagent was recovered as its chloride in 40–50% yield
after chromatographic separation of the reaction mix-
ture. These coupling reactions might proceed through a
classical Stille-type coupling cycle shown previously,12
and it is likely that 2 accelerates transformation of
RCOPdL2Cl into RCOPdL2–ꢁ–Ar which is the pre-
sumed intermediate for the formation of the coupling
product RCO–ꢁ–Ar.
Entry
Sb reagent
Acid chloride
Yield of 4 (%)b
1
2
3
4
5
6
7
2a
2b
2c
2a
2a
2a
2a
3a
3a
3a
3b
3c
3d
3e
86 (87)c
81 (80)d
84 (76)d
78 (37)c
79 (47)c
63 (26)c
72 (33)c
a The reaction was carried out with Sb reagent (2: 1 mmol), 3 (1.2
mmol), and PdCl2(PPh3)2 (3 mol%) in 1,2-dichloroethane (5 ml) at
rt for 1 h under argon atmosphere.
The remarkable high ability of 2a–c as an alkynylation
agent was also disclosed by the reaction of the ethynyl-
1,5-azastibocine 2a with aryl halides 5a–f. As shown as
entry 1 in Table 2, the reaction of 1 with iodobenzene
5a at 80°C for 24 h gave cross-coupling product 6a and
homo-coupling product 7 in 16 and 47% yields, respec-
tively. On the other hand, the same reaction by use of
2a instead of 1 afforded 6a in 58% yield as a main
product under far milder reaction conditions than the
formers. It was also apparent that the yields of the
cross-coupling products 6 were highly dependent on the
electronic nature of the aryl iodides 5a–e. The aryl
iodides bearing electron-attracting substituents such as
nitro and acetyl groups on the p-position on 5
improved not only the reactivity of the iodides but also
the yields of the coupling products 6, whereas those
having electron-donating substituents showed lower
reactivity. Furthermore, the reaction of 2a with p-bromo-
b Isolated yield. The values in parentheses show the yields of 4 when
the reaction was performed at 80°C for 2–8 h using 1 instead of 2
as an alkynylation reagent.
c See ref. 12.
d At 80°C for 5 h.
procedure reported by Akiba and co-workers.14 In
order to elaborate the reaction with the 1,5-azasti-
bocines 2a–c, we first examined the transition metal-
catalyzed reaction of 2a–c with acyl chlorides 3a–e, and
the results are summarized in Table 1. The 1,5-azasti-
bocines 2a–c on treatment with benzoyl chloride 3a by
use of PdCl2(PPh3)2 as a catalyst in 1,2-dichloroethane
at room temperature brought about cross-coupling
reaction to give alkynyl ketones 4 in good yields. By
comparison with the ethynylstibane 1, the ability of the
Table 2. Palladium-catalyzed coupling reaction of 1,5-azastibocine 2a with aryl halides 5a–fa
Entry
Sb reagent
Aryl halide
Temp.
Time (min)
Yield (%)b
6
7
1
2
3
4
5
6
7
1
5a
5a
5b
5c
5d
5e
5f
80°C
rt
rt
rt
rt
24 h
5
5
5
5
16
58
95
98
57
66
43
47
7
3
<1
12
10
16
2a
2a
2a
2a
2a
2a
rt
rt
20
20
a The reaction was carried out with Sb reagent (1 or 2a: 1 mmol), aryl halide (5: 1.2 mmol), and PdCl2(PPh3)2 (3 mol%) in 1,2-dichloroethane (5
ml) under argon atmosphere.
b GC yield.

N. Kakusawa et al. / Tetrahedron Letters 44 (2003) 8589–8592
8591
19
,
,
acetophenone 5f led to the formation of cross-coup-
ling products 6c, although the reaction of 1 with the
bromide did not afford 6c under the same reaction
conditions. It is well known that aryl bromides and
chlorides are less reactive than the corresponding aryl
iodides in a variety of transition metal-catalyzed cross-
coupling reaction.15
C(a-naphthyl) [2.165 A] and SbꢀC(p-tolyl) [2.15 A]. The
coordination should arise from an effective donation of
the pair of electrons on the nitrogen atom to the s*
orbital formed in the opposite direction of the C(1)ꢀSb
bond. We consider that the activation of the ethynyl
group on the 1,5-azastibocine 2a–c for this type of
coupling reactions would be induced by the formation
of the hypervalent coordination between the nitrogen
and antimony atoms. These are comparable results to
those attained with several germanium,20 tin21 and
bismuth22 compounds having this class of coordination
which show similar high reactivity toward this type of
coupling reaction. The details including reaction mech-
anism and substituent effect on nitrogen of the 1,5-aza-
stibocines in the present reactions are under
investigation.
In order to elucidate the higher ability of the ethynyl-
1,5-azastibocines 2a–c than that of the ethynylstibane 1
as an alkynylation agent, we performed a single crystal
X-ray analysis of 2a. The results are depicted in Figure
2, along with the selected data.16 The results show the
presence of intramolecular interaction between the anti-
mony and nitrogen atoms in 2a; the distance between
,
the antimony and nitrogen atoms being 2.538(4) A
which corresponds to 68% of the sum of the van der
17
,
Waals radii of both elements (3.74 A). The central
Acknowledgements
antimony atom exhibits a pseudo-trigonal-bipyramidal
structure in the crystal, and C(1) on the ethynyl moiety
and the nitrogen lie approximately trans to each other,
the bond angle of NꢀSbꢀC(1) being 156.1(1)°. The
bond distance between antimony and C(1) [2.172(4) A]
occupying an apical position is longer than those of
This research was supported by a Grant-in Aid for
Scientific Research on Priority Areas (A) ‘Exploitation
of Multi-Element Cyclic Molecules’ from the Ministry
of Education, Sciences, Sports and Technology, Japan,
and by The Specific Research Fund of Hokuriku
University.
,
,
,
SbꢀC(1%) [2.164(4) A] and SbꢀC(1¦) [2.167(5) A]. It has
been well documented that apical bonds are slightly
longer than equatorial bonds in a large number of
Group 14, 15 and 16 hypervalent compounds.18 Never-
theless, these results imply that an elongation of the
Sb-C(1) bond would be developed by the Sb···N coordi-
nation, because single crystal X-ray analysis of
phenylethynyl(a-naphthyl)(p-tolyl)stibane lacking such
coordination shows that the bond length of SbꢀC(ethynyl)
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