Regio- and stereoselective carbobismuthination of alkynes

Article abstract of DOI:10.1002/anie.201107127

Three become one: The first carbobismuthination of alkynes has been accomplished by the simple reaction of an alkyne, BiBr₃, and a ketene silyl acetal to produce an alkenylbismuth with high stereo- and regioselectivity (see scheme). X-ray cryst

Full text of DOI:10.1002/anie.201107127

Angewandte
Chemie
DOI: 10.1002/anie.201107127
Synthetic Methods
Regio- and Stereoselective Carbobismuthination of Alkynes**
Yoshihiro Nishimoto, Midori Takeuchi, Makoto Yasuda, and Akio Baba*
The carbometalation of carbon–carbon triple bonds is of
excellent value as a synthetic method for alkenylmetal
compounds and is accompanied by the formation of both
carbon–carbon and carbon–metal bonds. Therefore, carbo-
metalations using a variety of metal elements have been
developed by many chemists.[1] As far as we could ascertain,
however, carbobismuthination has never been reported.[2–4]
Many inorganic bismuth compounds are used in various
applications, including as medicinal chemicals, because bis-
muth is a virtually nontoxic heavy element in contrast with
other heavy elements such as arsenic, antimony, lead, and
thallium.[5] However, the use of organobismuth compounds in
synthetic chemistry has been mostly limited to the introduc-
tion of aryl moieties by an arylbismuth compound,[6] perhaps
because practical synthetic methods of other organobismuth
compounds are scarce. Only transmetalation between a
bismuth halide and an organometallic compound has been
generally applied, thus limiting the number of compatible
functional groups.[7] Herein, we wish to report the first
carbobismuthination of an alkyne. In contrast with general
carbometalations, the separate introduction of a carbon
nucleophile and a metal without the preformation of organo-
metallic nucleophiles resulted in carbobismuthination
[Eq (1)]. In addition, the present study was an effort to
First, the achievement of a carbobismuthination was
confirmed by X-ray crystallographic analysis of the alkenyl-
bismuth compound. The reaction of BiBr3 with 3,5-di(tert-
butyl)phenylacetylene 1 and dimethylketene trimethylsilyl
methyl acetal 2 in CH2Cl2 at room temperature gave
monoalkenylbismuth dibromide 3 as a white solid in a
quantitative yield [Eq. (2)]. X-ray crystallographic analysis
of 3 revealed the cis conformation of bismuth and aromatic
moieties around the double bond; this conformation showed
that the carbobismuthination took place regio- and stereose-
lectively in an anti addition manner (Figure 1a). The tetramer
expand carbometalation based on this concept, which has
recently been reported for carboindation and carbogalla-
tion.[8,9] The present reaction system requires only a simple
mixture of BiBr3, an alkyne, and a ketene silyl acetal to
produce an alkenylbismuth bearing an ester moiety with high
stereo- and regioselectivity.
Figure 1. X-Ray crystallographic analysis of alkenylbismuth dibromide 3
(the thermal ellipsoids are shown at 50% probability.[17]
of 3 resulted from the formation of bromine bridges, as shown
in Figure 1b. The geometry around the bismuth atom in 3 is a
distorted trigonal bipyramidal with two bromines in axial
positions. An alkenyl group and a bromine occupied two
equatorial positions, and the other was vacant.[7] The obtained
alkenylbismuth 3 easily reacted with I2, furnishing alkenyl
iodide 4 with retention of stereochemistry [Eq. (3)].
Table 1 shows the comparison of BiBr3 with other
bismuth(III) salts in carbobismuthination/iodination using
phenylacetylene 5 and ketene silyl acetal 2. To our surprise,
[*] Dr. Y. Nishimoto, M. Takeuchi, Dr. M. Yasuda, Prof. Dr. A. Baba
Department of Applied Chemistry, Graduate School of Engineering
Osaka University, 2-1, Yamada-oka, Suita (Japan)
E-mail: baba@chem.eng.osaka-u.ac.jp
[**] This work was supported by a Grant-in-Aid for Scientific Research on
Innovative Areas (No. 22106527, “Organic Synthesis Based on
Reaction Integration. Development of New Methods and Creation
of New Substances” and No. 23105525, “Molecular Activation
Directed toward Straightforward Synthesis”) and Challenging
Exploratory Research (No. 23655083) from the Ministry of Educa-
tion, Culture, Sports, Science and Technology (Japan). We thank Dr.
Nobuko Kanehisa for valuable advice regarding X-ray crystallog-
raphy.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201107127.
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Table 1: Comparison of BiBr3 with other bismuth(III) salts.[a]
nish alkenyliodide 6 in 90% yield. In addition, monitoring the
mixture of 7 and Me3SiBr by 1H NMR spectroscopy revealed
a regeneration of the starting ketene silyl acetal 2, which
indicated that 7 is a resting state rather than an intermediate.
A plausible reaction mechanism is illustrated in Scheme 3.
It is similar to the mechanism proposed for carbometallation
Entry
BiX3
Yield of 6 [%][b]
1
2
3
4
5
BiBr3
BiF3
BiCl3
BiI3
quant.
0
0
0
0
Bi(OTf)3
[a] 1) BiX3 (1 mmol), 5 (1 mmol), 2 (1.5 mmol), CH2Cl2 (2 mL), RT, 2 h;
1
2) I2 (2 mmol). [b] Yields were determined by H NMR analysis using
1,1,2,2-tetrachloroethane as an internal standard. Tf=trifluorometha-
nesulfonyl.
Scheme 3. Plausible mechanism.
only BiBr3 characteristically gave the desired alkenyliodide 6
in a quantitative yield (Table 1, entry 1), and the other
bismuth(III) salts such as BiF3, BiCl3, BiI3, and Bi(OTf)3 gave
no product at all (Table 1, entries 2, 3, 4, and 5).
using indium and gallium trihalides, with exception of the
transmetalation between BiBr3 and ketene silyl acetal 9.[8,9]
The interaction between BiBr3 and alkyne 8 results in a
positive charge at the internal carbon of the triple bond,
which is stabilized by the R1 group.[11] Then, the internal
carbon is attacked by ketene silyl acetal 9 anti to BiBr3 to
furnish monoalkenylbismuth 11 with regio- and stereoselec-
tivity. a-Bismuthino ester 10 is not an active species, although
the reversible transmetalation between BiBr3 and 9 occurs to
generate 10 and Me3SiBr. BiCl3, which promoted no carbo-
bismuthination, irreversibly transmetalates with 9. In fact, no
formation of 9 was observed by 1H NMR in the mixture of an
isolated a-dichlorobismuthino ester and Me3SiCl.[12]
Although BiI3 does not promote the transmetalation side
reaction its Lewis acidity is too low to activate an alkyne.[13]
Some representative alkynes and ketene silyl acetals were
To examine the reaction mechanism, we monitored
CD2Cl2 solutions of bismuth trihalides and ketene silyl
1
acetal 2 by H, 13C, and 29Si NMR spectroscopy (Scheme 1).
Scheme 1. Transmetalation between a bismuth trihalide and ketene
silyl acetal 2.
Moderate transmetalation occured between BiBr3 and 2 to
give a-dibromobismuthino ester 7 and Me3SiBr. This result
indicated the involvement of 7 in the carbobismuthination. A
similar transmetalation, however, took place even in the case
of BiCl3, which promoted no production of an alkenylbismuth
(Table 1, entry 3). In contrast, BiI3, which also gave no
product (Table 1, entry 4), caused no transmetalation with
ketene silyl acetal 2. These results lend uncertainty to the
involvement of a-bismuthino esters as an intermediate.
Next, control experiments using the isolated a-bismuthino
ester 7 were performed (Scheme 2).[10] a-Bismuthino ester 7
did not react with phenylacetylene 1 at all, even in the
presence of equimolar amounts of BiBr3. In contrast, the
addition of Me3SiBr promoted carbobismuthination to fur-
examined (Scheme 4). 4-Chlorophenylacetylene gave a
slightly lower yield than phenylacetylene 5 because of the
Scheme 4. Scope of alkenes and ketene silyl acetals. Reaction condi-
tions: [a] BiBr3 (1 mmol), alkyne (1 mmol), ketene silyl acetal
(1.5 mmol), CH2Cl2 (2 mL), 2 h, RT. [b] BiBr3 (1 mmol), alkyne
(5 mmol), ketene silyl acetal (3 mmol), CH2Cl2 (2 mL), 2 h, 508C.
[c] Yields determined by 1H NMR spetroscopy. [d] Yield of the isolated
product.
lower electron density of the alkyne moiety owing to the
presence of the chloro group (12). An aliphatic alkyne also
furnished the desired alkene 13 in 50% yield at 558C. The use
of a monophenyl-substituted ketene silyl acetal led to
effective carbobismuthination at room temperature (14).
Scheme 2. Control experiments using a-bismuthino ester 7.
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We investigated the transformation of the produced
alkenylbismuth compounds. Acetic acid quantitatively
protonolyzed alkenylbismuth under mild reaction conditions
to furnish the corresponding disubstituted alkene 15 [Eq. (4)].
The substitution of a Br2Bi group was successfully performed
with p-toluenesulfonyl chloride and diphenyldisulfide in the
presence of 2,2’-azoisobutyronitrile (AIBN) to give alkenyl-
sulfone 16 and alkenylsulfide 17, respectively [Eqs. (5) and
(6); DMF = N,N’-dimethylformamide, Ts = p-toluenesul-
Scheme 5. One-pot formation of functionalized enones by coupling
reactions between alkenylbismuth compounds and acid chlorides.
Reaction conditions: 1) BiBr3, alkyne (1 equiv), ketene silyl acetal
(1.5 equiv), CH2Cl2 1 mL), RT, 2 h; 2) [Pd2(dba)3]·CHCl3 (0.1 equiv),
acid chloride (2 equiv), solvent (DMF or HMPA; 2.5 mL), RT, 7 h.
Yields of the isolated products are shown. [a] 1) BiBr3, alkyne (5 equiv),
ketene silyl acetal (3 equiv), CH2Cl2 (1 mL), 2 h, 508C; 2) [Pd2-
(dba)3]·CHCl3 (0.05 equiv), acid chloride (2 equiv), solvent (HMPA;
2.5 mL), 7 h, 508C. dba=dibenzylideneacetone, HMPA=hexamethyl-
phosphorylamide.
synthesis of regio- and stereoselectively functionalized
enones. Applications to other nucleophiles are currently
underway.
fonyl].[14] It is noteworthy that the stereochemistry of the
carbon atom attached to the bismuth atom was retained after Experimental Section
Typical Procedure (Table 1, entry 1): Ketene silyl acetal 2 (1 mmol)
the introduction of a sulfur atom. This is the first example of
the substitution of the bismuth atom in bismuth(III) com-
pounds with a sulfur atom.[15]
added to a suspension of BiBr3 (1 mmol) and alkyne 1 (1.5 mmol) in
dichloromethane (1 mL). The reaction mixture was stirred for 2 h at
room temperature and then was quenched by I2 (2 mmol). The
resultant mixture was poured into Na2S2O3 (aq) and extracted with
Et2O. The organic layer was dried over MgSO4, and volatiles were
removed under reduced pressure to afford the crude product, which
was confirmed by 1H NMR spectroscopy.
Finally, we developed a coupling reaction between the
synthesized alkenylbismuth compounds and acid chlorides; as
far as we could ascertain this reaction has been never reported
(Scheme 5).[16] After the carbobismuthination using phenyl-
acetylene 5 and ketene silyl acetal 2, the successive addition of
[Pd2(dba)3]·CHCl3, acetyl chloride, and DMF to the resultant
CH2Cl2 solution afforded coupling product 18 as a single
isomer in 61% yield. The geometry of the olefinic double
bond showed that the stereochemistry of the corresponding
alkenylbismuth was retained. The alkenylbismuth produced
from octyne gave the desired enone 19 in 35% yield.
Monophenyl-substituted ketene silyl acetal was also appli-
cable (20). Coupling reactions using isobutyryl chloride and
benzoyl chloride gave excellent results (21 and 22), although
the bulky pivaloyl chloride could not be employed (23).
In summary, we achieved the carbobismuthination of
alkynes using BiBr3 and ketene silyl acetals. X-ray crystallo-
graphic analysis of the alkenylbismuth product and control
experiments revealed the reaction mechanism whereby BiBr3
and a ketene silyl acetal add to an alkyne in an anti manner. In
addition, the Br2Bi group in the alkenylbismuth compounds
was substituted by I, Ts, and SPh groups to obtain hetero-
atom-substituted alkenes. The Pd-catalyzed cross-coupling of
alkenylbismuth compounds with acid chlorides achieved the
Received: October 8, 2011
Published online: December 8, 2011
Keywords: alkynes · bismuth · carbobismuthination ·
.
ketene silyl acetals · synthetic methods
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