1-Alkynyl(aryl)(tetrafluoroborato)-λ3-bromanes as highly efficient Michael acceptors: Uncatalyzed conjugate addition of 1-alkynyl(trialkyl)stannanes to yield symmetrical and unsymmetrical 1,3-butadiynes

Article abstract of DOI:10.1002/anie.200461985

(Equation Presented) Symmetrical 1,3-diynes result from the oxidative homocoupling reaction of alkynylstannanes with an aryldifluoro- λ³-bromane in the presence of BF₃·Et ₂O (see scheme, Ar = p-CF₃C₆H₄). The reaction involves a Michael addition of alkynylstannanes to the initially formed alkynyl-λ³-bromanes. Cross-coupling of alkynyl-λ³-bromanes with alkynylstannanes affords unsymmetrical 1,3-diynes (see scheme).

Full text of DOI:10.1002/anie.200461985

Communications
fashion owing to the strength of the alkynyl–copper(i)
bond.[1,2] Michael addition of alkynylstannanes appears to
be a very difficult process, probably owing to the low polarity
À
of a C Sn bond, and there are no well-established precedents
for the direct reaction. Specially designed alkynylstannanes
with enhanced reactivity such as ynaminostannanes
(R2NCCSnMe3) undergo conjugated addition toward acety-
lenedicarboxylates in MeCN under heating at reflux.[3]
Palladium(0)-catalyzed Michael-type addition of alkynylstan-
nanes to conjugated ynones and alkynoates by using an
iminophosphine ligand was recently reported.[4] Herein we
report bromine(iii)-mediated homocoupling of alkynylstan-
nanes to yield symmetrical 1,3-butadiynes that involves
uncatalyzed Michael addition reactions of alkynylstannanes
to highly electron-deficient alkynyl-l3-bromanes.
Despite extensive studies on the chemistry of 1-alkynyl-
(phenyl)-l3-iodanes,[5] little is known about the closely related
group 17 1-alkynyl(aryl)-l3-bromanes 3, mostly because of
the considerable difficulty of their synthesis. Recently, we
reported the synthesis and characterization of 1-alkynyl-
(aryl)(tetrafluoroborato)-l3-bromanes
3
through ligand
exchange of a difluoro-l3-bromane with alkynylstannanes.[6]
Thus, exposure of 1-(trimethylstannyl)-1-alkyne 1 to an excess
of para-trifluoromethylphenyl(difluoro)-l3-bromane (2;
1.5 equiv; prepared from para-trifluoromethylphenyl(trime-
thyl)silane by ligand exchange with bromine trifluoride at
À78 to À258C in dichloromethane) in the presence of
BF3·Et2O at À788C in dichloromethane afforded 1-alkynyl-
(aryl)-l3-bromane 3 in high yields (Scheme 1). Use of excess
Synthetic Methods
1-Alkynyl(aryl)(tetrafluoroborato)-l3-bromanes
as Highly Efficient Michael Acceptors:
Uncatalyzed Conjugate Addition of 1-
Alkynyl(trialkyl)stannanes To Yield Symmetrical
and Unsymmetrical 1,3-Butadiynes**
Masahito Ochiai,* Yoshio Nishi, Satoru Goto, and
Hermann J. Frohn
In contrast to alkynylboron, -aluminium, and -nickel reagents,
alkynylcopper species do not efficiently transfer the alkynyl
group to electron-deficient olefins and alkynes in a conjugate
Scheme 1. TBDMS=tert-butyldimethylsilyl, TMS=trimethylsilyl.
[*] Prof. M. Ochiai, Y. Nishi, Dr. S. Goto
Faculty of Pharmaceutical Sciences
University of Tokushima
amounts of the 1-alkynylstannanes 1 (> 2 equiv) relative to
difluoro(aryl)-l3-bromane 2 dramatically changed the reac-
tion course and afforded the homocoupling products 1,3-
butadiynes 4 in good yields.
1-78 Shomachi, Tokushima 770-8505 (Japan)
Fax: (+81)88-633-9504
Rigid and sterically undemanding diacetylene moieties
are frequently embodied in many natural products and find
increasing application as key structural elements in synthetic
receptors for molecular recognition.[7] Reaction of difluoro-
l3-bromane 2 with 2.2 equivalents of 1-decynylstannane 1a in
the presence of BF3·Et2O (1.2 equiv) from À788C to room
E-mail: mochiai@ph.tokushima-u.ac.jp
Prof. H. J. Frohn
Anorganische Chemie
Universitat Duisburg-Essen
Latharstrasse 1, 47048 Duisburg (Germany)
[**] We thank Central Glass Co., Japan, for a generous gift of BrF3.
406
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DOI: 10.1002/anie.200461985
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Angewandte
Chemie
temperature in dichloromethane under argon resulted in
oxidative homocoupling with the formation of icosa-9,11-
diyne (4a) in 69% yield (Table 1, Entry 3). The use of
2 equivalents of BF3·Et2O led to a slight improvement in the
(40%; Scheme 2). Both tetrabutylstannane and phenyltrime-
thylstannane do not undergo oxidative homocoupling.
Table 1: Reaction of substituted 1-alkynes with difluoro-l3-bromane 2.[a]
Entry
1-Alkynes
BF3·Et2O [equiv]
4
Yield [%][b]
1
2
3
4
1a
1a
1a
1a
0
4a
4a
4a
4a
0
1[c]
1.2
2
49
69
72
Scheme 2.
5
6
7
1.2
1.2
1.2
4a
4a
4a
78
17
0
On the basis of our previous report[6] as well as the
observation that the oxidative homocoupling of 1-alkynyl-
stannane 1a to yield the diyne 4a does not take place in the
absence of BF3·Et2O (Table 1, Entry 1),[8] it seems reasonable
to assume that the bromine(iii)-mediated homocoupling of 1-
alkynylstannane 1 probably involves the initial formation of
[a] Unless otherwise noted, reactions were carried out by using
2.2 equivalents of an alkyne in dichloromethane in the presence of
BF3·Et2O from À788C to room temperature during 5 h under argon.
[b] Isolated yields. [c] Reaction conditions: À788C, 2.5 h.
1-alkynyl(aryl)(tetrafluoroborato)-l3-bromane
3
through
ligand exchange and its further reaction with excess 1-
alkynylstannane 1. In fact, treatment of 1-decynyl-l3-bromane
3a with 1-alkynylstannane 1a at room temperature under
argon afforded the 1,3-diyne 4a in 59% yield. The reaction
does not require activation with Lewis acids. Interestingly, in
this reaction a 4% yield of the cyclopentene 5 was also
yield (72%), whereas in the absence of BF3·Et2O no
formation of the diyne 4a was observed. 1-Decynyl(tributyl)-
stannane also afforded the diyne 4a in 78% yield. However,
the attempted dimerization of 1-decynyl(trimethyl)silane and
-germane gave poor results and large amounts of the reactants
were recovered (Table 1, Entries 6 and 7).
Our initial examination of the substrate generality for
oxidative homocoupling of 1-alkynylstannanes 1 is shown in
Table 2. Dimerization of simple primary, secondary, and
Table 2: Oxidative homocoupling of alkynylstannanes 1 by reaction with
difluoro-l3-bromane 2.[a]
produced.[9] The reaction with 1-decynyl(trimethyl)germane
provided a comparable result with formation of a small
amount of 5 (Table 3, Entry 2).
Entry
1
4
Yield [%][b]
1
2
3
4
5
6
7
8
9
1b
1c
1d
1e
1 f
1g
1h
1i
4b
4c
4d
4e
4 f
4g
4h
4i
74
83
76 (87)
80
33
69 (84)
45
47
Table 3: Uncatalyzed cross-coupling of alkynyl-l3-bromanes
alkynylstannanes 1 and -germanes.[a]
3 with
Entry
3
Alkyne
4
Yield [%][b]
1
2
3a
3a
1a
4a
4a
59
64
1j
4j
27
3
4
5
6
7
8
3a
3a
3a
3c
3c
3e
1c
1e
1 f
1a
1e
1a
4l
76
71
66
76
74
71
4m
4n
4l
4o
4m
[a] Reactions were carried out by using 2.2 equivalents of an alkyne 1 in
dichloromethane in the presence of BF3·Et2O (1.2 equiv) from À788C to
room temperature during 5 h under argon. [b] Isolated yields. Yields
obtained after GC are quoted in parentheses.
[a] Reactions were carried out by using 2.2 equivalents of an alkyne in
dichloromethane at room temperature for 5 h under argon. [b] Isolated
yields.
tertiary alkylethynyl(trimethyl)stannanes afforded the 1,3-
butadiynes 4b–e in good yields (74–83%). 1,10-Dichlorode-
cadiyne 4g was obtained in 69% yield from 5-chloropenty-
nylstannane 1g. However, phenylethynyl(trimethyl)stannane
(1 f) gave 1,4-diphenyl-1,3-butadiyne (4 f) in only 33% yield.
Ethynyl- and siloxy-substituted alkynyl(trimethyl)stannanes
1h and 1i gave 1,3-diynes in moderate yields. Selective
coupling of trimethyl(trimethylsilylethynyl)stannane (1j)
resulted in the formation of bis(trimethylsilyl)-1,3-diyne 4j,
although in a low yield (27%). The use of trimethylstannyl-
1,3-diyne 1k provided directly the conjugated octatetrayne 4k
The cross-coupling reaction makes it possible to synthe-
size unsymmetrically substituted 1,3-butadiynes 4l–o
(Scheme 3, Table 3). For instance, reaction of 3a with
alkynylstannanes 1c and 1e afforded the unsymmetrical
butadiynes 4l (76%) and 4m (71%; Table 3, Entries 3 and 4),
which were also produced by the reaction of the inverse
combinations (reaction of 1a with 3c and 3e, respectively).
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Scheme 3.
Figure 1. Mulliken atomic charges at Ca, Cb, Br, and I calculated with
the B3LYP/LanL2DZ method (Gaussian 03W).
Isolation of the byproduct cyclopentene 5 clearly indicates
that the reaction of 3a with 1a involves the intermediacy of
alkylidene carbene 6, which is produced by Michael addition
of 1-alkynylstannane 1a and the subsequent reductive
elimination of the aryl-l3-bromanyl group (Scheme 4). A
symmetrical 1,3-butadiynes. Tandem Michael addition–car-
bene rearrangements of 1-alkynyl(aryl)-l3-bromanes with 1-
alkynylstannanes provides a new route for the synthesis of
unsymmetrical 1,3-butadiynes.[7]
Scheme 4. R=n-C8H17, Ar=p-CF3C6H4.
Experimental Section
4a (Table 1, Entry 3): A solution of difluoro[4-(trifluoromethyl)-
phenyl]-l3-bromane (2; 34 mg, 0.13 mmol) in dichloromethane
(0.2 mL) followed by BF3·Et2O (22 mg, 0.16 mmol) were added
dropwise to a stirred solution of 1-decynyl(trimethyl)stannane (1a;
86 mg, 0.29 mmol) in dichloromethane (0.8 mL) at À788C under
argon. The mixture was gradually warmed to room temperature over
5 h. The reaction mixture was quenched with water and extracted
with dichloromethane. The organic layer was dried over anhydrous
sodium sulfate and concentrated under aspirator vacuum to give an
oil, which was purified by preparative TLC (SiO2, hexane/dichloro-
methane 4:1) to give a mixture (25.9 mg) of 4a and 5 (95:5; 69% and
1,2-shift of the alkynyl group in 6 produces 4a, while
competing intramolecular 1,5 carbon–hydrogen insertion
affords 5.[5,10] High migratory aptitude of alkynyl groups in
alkylidene carbenes and carbenoids are well established.[11]
The most important step in this mechanism should be an
uncatalyzed Michael addition of 1-alkynyl(trimethyl)stan-
nane 1 with rather low nucleophilicity to 1-alkynyl-l3-
bromane 3. Entry 2 in Table 3 shows that the less nucleophilic
1-decynyl(trimethyl)germane also serves as an efficient
Michael donor toward 3. The question arises why simple
alkynylstannanes and -germanes undergo uncatalyzed con-
jugate addition toward 3. We believe that the highly electron-
deficient nature of 1-alkynyl-l3-bromanes 3, evoked by a large
electron-withdrawing inductive effect of an aryl(tetrafluoro-
borato)-l3-bromanyl group with a substituent constant sI of
1.63 (for PhBr(BF4)),[12] will be responsible for this unusual
addition reaction. Actually, 1-alkynyl(aryl)-l3-iodanes asso-
ciated with a reduced inductive effect (sI = 1.35 for PhI(BF4))
do not function as Michael acceptors, and no formation of 1,3-
butadiyne 4a was observed in the attempted reaction of 1-
decynyl(para-trifluoromethylphenyl)(tetrafluoroborato)-l3-
iodane with 1-alkynylstannane 1a under the conditions
described.
1
4%, respectively). 4a: H NMR (400 MHz, CDCl3): d = 2.25 (t, J =
7.4 Hz, 4H), 1.52 (quint, J = 7.4 Hz 4H), 1.41–1.33 (m, 4H), 1.33–1.21
(m, 16H), 0.88 ppm (t, J = 6.3 Hz, 6H); 13C NMR (75 MHz, CDCl3):
d = 77.5, 65.3, 31.9, 29.2, 29.1, 28.9, 28.4, 22.7, 19.2, 14.1 ppm; IR
(neat): n˜ = 2925, 2855, 2233, 1465, 1377, 722 cmÀ1; MS (70 eV): m/z
(%): 274 (2) [M+], 245 (3), 231 (3), 217 (9), 203 (8), 189 (4), 175 (10),
161 (19), 147 (22), 133 (31), 119 (43), 105 (56), 91 (100), 79 (65);
HRMS: calcd for C20H34 [M+]: 274.2661; found: 274.2663. A pure
sample of 5 was obtained by preparative GC (20% silicon GE SF-96,
3 m). 5: 1H NMR (400 MHz, CDCl3): d = 5.89 (br s, 1H), 2.69 (m,
1H), 2.46–2.34 (m, 2H), 2.31 (t, J = 7.4 Hz 2H), 2.12–2.02 (m, 1H),
1.53 (quint, J = 7.4 Hz 2H), 1.45–1.21 (m, 19H), 0.95–0.84 ppm (6H);
IR (CHCl3): n˜ = 2928, 2856, 1465, 1265 cmÀ1; MS (70 eV): m/z (%):
274 (22) [M+], 203 (100) [M+-C5H11]; HRMS: calcd for C20H34 [M+]:
274.2661; found: 274.2651. 4l (Table 3, Entry 7): 1a (59 mg, 0.2 mmol)
was added to a stirred solution of 3,3-dimethyl-1-butynyl-l3-bromane
3c (35 mg, 0.09 mmol) in dichloromethane (2 mL) at room temper-
ature under argon. The reaction mixture was stirred for 5 h, quenched
with water, and extracted with dichloromethane. The organic layer
was dried over anhydrous sodium sulfate and concentrated under
aspirator vacuum to give an oil, which was purified by preparative
TLC (SiO2, hexane) to give 4l as a colorless oil (15 mg, 76%).
1H NMR (400 MHz, CDCl3): d = 2.25 (t, J = 7.2 Hz, 2H), 1.51 (quint,
J = 7.2 Hz, 2H), 1.42–1.33 (m, 2H), 1.32–1.25 (m, 8H), 1.24 (s, 9H),
0.88 ppm (t, J = 6.7 Hz, 3H); 13C NMR (75 MHz, CDCl3) d = 85.0,
78.8, 65.0, 63.9, 31.9, 30.6, 29.2, 29.1, 28.9, 28.4, 27.9, 22.7, 19.3,
14.1 ppm; IR (CHCl3): n˜ = 2929, 2858, 2147, 1457 cmÀ1; MS (70 eV):
m/z (%): 218 (9) [M+], 203 (24), 189 (50), 175 (22), 161 (61), 147 (58),
133 (61), 119 (96), 105 (100), 91 (60); HRMS: calcd for C16H26 [M+]:
218.2035; found: 218.2041.
To better understand these differences in reactivity in l3-
bromanes and l3-iodanes, density functional theory (DFT)
calculations on the simplified 1-propynyl derivatives 7 were
carried out (Figure 1). The acetylenic p* orbital (LUMO+4)
of 1-propynyl(phenyl)(fluoro)-l3-bromane 7a is lower in
energy than that for the l3-iodane 7b (LUMO+4;
0.04672 eV for 7a, 0.04778 eV for 7b). Mulliken atomic
charges show that the Cb carbon atom in 7a is apparently
more positive than that in 7b.
In summary, we have presented the first example of
uncatalyzed Michael addition reactions of simple 1-alkynyl-
(trimethyl)stannanes, a reaction which is involved in difluoro-
l3-bromane-mediated coupling of 1-alkynylstannanes to yield
Received: September 14, 2004
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Keywords: alkynes · carbenes · michael addition · stannanes ·
.
synthetic methods
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