Synthesis of alkylbismuths by regiodivergent carbobismuthination of simple alkenes

Article abstract of DOI:10.1002/chem.201302194

Switchable regioselectivity: This study represents the first carbobismuthination of alkenes achieved by the treatment of an alkene with a bismuth halide and a ketene silyl acetal. This eaction is particularly noteworthy in that a change in the type of halogen on a bismuth atom very easily switched the regioselectivity (see scheme). Copyright

Full text of DOI:10.1002/chem.201302194

COMMUNICATION
DOI: 10.1002/chem.201302194
Synthesis of Alkylbismuths by Regiodivergent Carbobismuthination of
Simple Alkenes
Yoshihiro Nishimoto, Midori Takeuchi, Makoto Yasuda, and Akio Baba*[a]
Organobismuth compounds have recently attracted much
attention because they show remarkably characteristic reac-
tivities including highly effective initiation of living radical
although many highly regioselective reactions have been de-
veloped.[8] As far as we could ascertain, this is the first ex-
ample in which the regioselectivity has been switched by the
counter anion on a metal in the carbometalation of an
alkene (Figure 1).
polymerization,[1] para C H activation of phenol deriva-
À
tives,[2] direct allyl transfer to carbonyls,[1c] a-phenylation of
carbonyls,[3] and other traditional reactions such as cross-
coupling and addition reactions to carbonyl compounds.[4]
However, most of the practical syntheses of organobismuths
involve transmetalation between a bismuth halide and an or-
ganometallic compound, which has limited the number of
compatible functional groups and constricted the develop-
ment of organobismuth chemistry.[4] Therefore,
a new
method for the synthesis of organobismuth reagents is
highly desirable. Of the options, the carbobismuthination of
alkenes represents a powerful tool for the synthesis of alkyl-
bismuth compounds because carbon–carbon and carbon–bis-
muth bonds can be simultaneously formed to easily give
a complex alkylbismuth, but this has never been reported.[5]
Recently, our group studied regio- and stereoselective car-
bometalation by activation of the carbon–carbon multiple
bond by a metal halide toward external nucleophilic attack,
in which the separate introduction of a carbon nucleophile
and a metal into the carbon–carbon unsaturated bond in an
anti-addition manner.[6] In this reaction system, carbometala-
tion is caused simply by mixing a metal salt, a carbon nucle-
ophile, and an unsaturated hydrocarbon without the prepa-
ration of organometallic nucleophiles in contrast to general
carbometalation. Under this concept, we wish to report
a novel synthetic method for alkylbismuths by the carbobis-
muthination of alkenes that directly utilizes bismuth triha-
lides and ketene silyl acetals. The present carbobismuthina-
tion is not only remarkable as a synthetic method of alkyl-
metals with an ester moiety,[6b,7] but also has the notable fea-
ture whereby a change in the type of halogen on the bis-
muth atom switches the regioselectivity, which differs from
our previously reported version of the carbometalation.[6d]
Until now, it has been difficult to realize an efficient switch-
able regioselectivity in the carbometalation of one alkene,
Figure 1. Switchable-regioselective carbobismuthination of alkenes.
First, we examined the reaction between styrene (1a,
1 mmol), BiBr3 (1.5 mmol), and dimethylketene tert-butyldi-
methylsilyl methyl acetal (2a, 1.5 mmol; Scheme 1). After
this reaction was carried out in CH2Cl2 (1 mL) at room tem-
Scheme 1. Carbobismuthination of styrene (1a) using BiBr3 and ketene
silyl acetal 2a. 1a (1 mmol), BiBr3 (1.5 mmol), 2a (1.5 mmol), CH2Cl2
(1 mL).
perature, treatment with 30 wt% HBr of a CH3COOH solu-
tion gave the corresponding a-alkylated esters 5aa and 6aa
in 77 and 5% yields, respectively. This result indicated that
carbobismuthination among 1a, BiBr3, and 2a mainly af-
forded alkylbismuth 3 along with a small amount of 4. Per-
forming the reaction in the dark exclusively gave 5aa in
94% yield. X-ray crystallographic analysis successively re-
vealed the structure of 3; the bismuth atom was bound to
the external carbon of the double bond in 1a, and the nucle-
[a] 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)
Fax : (+81)6-6879-7387
E-mail: baba@chem.eng.osaka-u.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201302194.
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ophilic carbon of 2a was bound to the internal one (Fig-
ure 2a). The dimer of 3 was formed by a bromine bridge, as
shown in Figure 2b. The geometry around the bismuth atom
in 3 was a distorted square-pyramidal, and three bromines
and a carbonyl oxygen formed a square plane. In 1H and
tyronitrile (AIBN) gave g-phenylthio ester 8aa in 74%
yield.[6d,10]
After the investigation of various bismuthACTHUNRTGNEUNG(III) salts, the
use of BiCl3 inverted the regioselectivity, affording only the
corresponding ester 6ab in 47% yield [Eq. (1)].
1
Figure 2. X-ray crystallographic analysis and selected chemical shift of H
It is noteworthy that UV irradiation increased the yield of
6ab to 71% in the presence of BiCl3. In contrast, perform-
ing the reaction in the dark retarded the reaction. These re-
and 13C NMR of alkylbismuth dibromide 3.
13C NMR spectra of 3, signals of a- and ß-pro-
tons, and the a-carbon of the bismuth atom are
significantly downfield shifted due to electron-
Table 1. Scope of alkene 1 and ketene silyl acetal 2 in carbobismuthination using BiBr3.[a]
withdrawing ability of BiBr2 group.[9]
Various types of alkenes and ketene silyl ace-
tals were investigated in the carbobismuthina-
tion using BiBr3 (Table 1). Trimethylsilyl
ketene acetal 2b as well as 2a were found to
afford the desired product 5aa in 86% yield
(Table 1, entry 1). Dialkylketene silyl acetals
2c and d were applicable to give the corre-
sponding ester products in high yields (Table 1,
entries 2 and 3). The reaction using phenylme-
thylketene silyl acetal 2e also afforded ester
5ae (Table 1, entry 4). Carbobismuthination
using monoalkylketene silyl acetal 2 f smoothly
took place (Table 1, entry 5). Optimized condi-
tions were employed with aromatic alkenes
bearing electron-donating and -withdrawing
groups, giving the desired products 5ba, ca,
and da in 99, 92 and 76% yields, respectively
(Table 1, entries 6–8). In particular, the reac-
tion of p-methoxystyrene (1b) gave an excel-
lent yield in a shorter time. Aliphatic alkene 1e
was applicable and afforded good results
(Table 1, entry 9). This carbobismuthination
was extended to a 1,1-disubstituted alkene, pro-
ducing the desired ester 5 fb in the reaction
using alkene 1 f (Table 1, entry 10). Unfortu-
nately, other types of multi-substituted alkenes
such as stilbene and cyclohexene were not ap-
plicable.
1
2
Product 5
Yield [%][b]
86
1
2
1a
1a
2b
5aa
5ac
2c
2d
90 (83)
70 (59)
3
1a
5ad
4
5
1a
1a
2e
2 f
5ae
5af
79 (55)
68 (55)
6
7
8
X=OMe
Me
Cl
1b
1c
1d
2a
2a
2a
5ba
5ca
5da
99 (98)
92 (85)
76 (72)
9
1e
2b
5eb
61 (48)
51 (36)
Next, we examined the oxidative transforma-
tion of alkylbismuth
3
(Scheme 2). N-
10[c]
1 f
2b
5 fb
bromosuccinimide (NBS) smoothly trans-
ACHTUNGTRENNUNG
formed alkylbismuth 3 to g-bromo ester 7aa in
a one-pot manner. The treatment of 3 with di-
phenyl disulfide in the presence of azobisisobu-
[a] (1) 1 (1 equiv), BiBr3 (1.5 equiv), 2 (1.5 equiv), CH2Cl2, RT. (2) 30 wt% HBr in AcOH
(1 mL). [b] Yields were determined by 1H NMR analysis using an internal standard.
Values in parentheses are isolated yields. [c] BiBr3 (1 equiv).
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Synthesis of Alkylbismuths
COMMUNICATION
sessing
electron-withdrawing
and -donating groups were
suitable substrates (Table 2,
A
A
phthalimide
moiety tolerated these condi-
tions (Table 2, entry 7). How-
ever, aliphatic alkenes, such as
1-hexene, were unsuitable for
this reaction system.
Scheme 2. Transformation of alkylbismuth 3. [a] NBS (2.5 equiv), THF, 08C to RT. [b] PhSSPh (4.5 equiv),
AIBN (2 equiv), DMF, 1008C.
After the investigation of
the oxidative transformation of
sults suggested that UV irradiation accelerates the carbobis-
muthination using BiCl3. Radical initiators such as AIBN
and Et3B were ineffective.[11] Radical scavenger, 2,2,6,6-tet-
ramethylpiperidine 1-oxyl (TEMPO) did not stop the carbo-
an alkylACTHNGUTERN(UNG dichloro)bismuth, PhIACHTUGNRTEN(NUGN OAc)2 as an oxidant in the
presence of Me3SiOAc was found to transform alkylbismuth
9 to g-acetoxy ester 10ac in a one-pot procedure [Eq. (2)].
bismuthination.[11] Other bismuth
Bi
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
flate).[10] The structure of alkylbismuth product 9 from the
reaction of styrene (1a) with diethylketene ethyl trimethyl-
silyl acetal (2c) was revealed by X-ray crystallographic anal-
ysis, and clearly showed a regioselectivity that was opposite
to carbobismuthination using BiBr3 (Scheme 3). Like alkyl-
ACHTUNGTRENNUNG(dibromo)bismuth 3, alkylbismuth 9 dimerized through
1
a chloride bridge, and a distorted square-pyramidal. In H
and 13C NMR spectra, 9 showed considerable downfield
shifts of a- and ß-protons, and the a-carbon of the bismuth
atom as in the case of alkylbismuth 3.
Table 2 shows the scope of carbobismuthination using
BiCl3. Various types of dialkylketene silyl acetals 2c, g, and
h smoothly gave the corresponding esters 6ac, ag, and ah,
respectively (Table 2, entries 1–3). Aromatic alkenes pos-
To gain insight into the carbobismuthination process, we
determined the relative configuration of the deuterated
carbon center of the alkylbismuth product given by the reac-
tion using monodeuterated styrene 1a-d. In the carbobismu-
thination using BiBr3, the corresponding alkylbismuth 3-d
was obtained stereoselectively, which indicated that the ad-
dition of BiBr3 and 2a to 1a-d occurred stereoselectively in
an anti-fashion [Eq. (3)]. BiCl3, however, showed no stereo-
selectivity [Eq. (4)].
Control experiments using isolated a-bismuthino esters 11
were performed. We previously reported that the transmeta-
lation between a bismuth trihalide and a ketene silyl acetal
occurred to afford an a-dihalobismuthino ester and a silyl
halide at room temperature: 1) The transmetalation be-
tween BiBr3 and 2b was in equilibrium [Eq. (5)], and 2) the
transmetalation between BiCl3 and 2b took place complete-
ly [Eq. (6)]. Isolated a-dibromobismuthino ester 11a did not
Scheme 3. X-ray crystallographic analysis and selected chemical shift of
1H and 13C NMR of alkylbismuth dichloride 9.
Chem. Eur. J. 2013, 19, 14411 – 14415
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A. Baba et al.
Table 2. Scope of alkene 1 and ketene silyl acetal 2 in carbobismuthination using
A plausible reaction mechanism is illustrated in
Scheme 4. Path A shows the carbobismuthination
using BiBr3. The coordination of alkene 1 to BiBr3
causes a positive charge at the internal carbon of
the double bond, which is stabilized by an R1
group.[12] Then, the nucleophilic attack of ketene
silyl acetal 2 occurs at the internal carbon atom
from the opposite side of BiBr3, and then alkylbis-
muth product 12 and Me3SiBr are generated. In
the carbobismuthination using BiCl3, the fast trans-
metalation irreversibly occurs and the resultant a-
bismuthino ester 11 is likely to be a reaction spe-
cies (Path B). Single-electron transfer from UV ir-
radiation-excited alkene 1* to bismuthino ester 11
generates radical cation 13 and anion 14. The eno-
late anion derived from radical anion 14 nucleo-
philically adds to radical cation 13 to produce 15.
Finally, the BiCl2 radical couples with radical 15,
affording alkylbismuth 16. The effect of UV irradi-
ation and no effect of both radical initiator and
scavenger support this reaction mechanism
although other radical mechanism cannot be ex-
cluded in this stage. The following factors would
determine the reaction path: 1) A soft Lewis acid,
BiBr3, sufficiently interacts with an alkene moiety
to generate a positive charge; and, 2) A hard
Lewis acid, BiCl3, does not sufficiently interact
with an alkene, and so after transmetalation the re-
action of the a-bismuthino ester 11 with alkene
1 takes place by UV irradiation.[13]
BiCl3.[a]
1
2
Product 6
Yield
[%][b]
1
2
1a 2c
1a 2g
6ac 60 (49)
6ag 63 (37)
3
4
5
6
1a 2h
1b 2b
1c 2b
1g 2b
6ah 55 (44)
6cb 45 (38)
6cb 66 (66)
6gb 71 (60)
7
1h 2b
6hb 61 (55)
[a] (1) 1 (1 mmol), BiBr3 (1.5 mmol), 2 (1.5 mmol), CH2Cl2 (2 mL), RT, 2 h. UV=
300 W high-pressure mercury lamp. (2) 30 wt% HBr in AcOH (1 mL). [b] Yields were
determined by H NMR analysis using an internal standard. Values in parentheses are
isolated yields.
In summary, we accomplished the first carbobis-
muthination of alkenes by bismuth trihalides and
ketene silyl acetals in which the regioselectivity
1
react with styrene (1a), even in the presence of equimolar
amounts of BiBr3 [Eq. (7)]. The addition of Me3SiBr
(TMSBr) promoted the carbobismuthination to furnish the
corresponding ester 5aa in 41% yield. This result indicated
that a-dibromobismuthino ester 11a is unreactive and that
BiBr3 and 2 generated by the transmetalation between 11a
and Me3SiBr caused the carbobismuthination. It is notewor-
thy that the reaction of isolated a-dichlorobismuthino ester
11b with styrene (1a) under UV irradiation occurred in the
absence of additives, which indicated that 11b is an active
intermediate in contrast to 11a [Eq. (8)].
was inverted by changing BiBr3 to BiCl3 to furnish two types
of alkylbismuth compounds possessing an ester moiety. In
addition, we found that the X2Bi groups in the resultant al-
kylbismuths could be substituted for by H, Br, SPh, and
OAc groups. Applications to other nucleophiles are current-
ly being tested.
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Synthesis of Alkylbismuths
COMMUNICATION
Keywords: alkenes · bismuth · carbobismuthination · ketene
silyl acetal · synthetic methods
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Scheme 4. Plausible reaction mechanisms.
[7] For the intramolecular carbometalation of alkenes using metal eno-
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Experimental Section
Typical procedure for carbobismuthination using BiBr3 followed by pro-
tonolysis (Table 1, Entry 4) To a suspension of BiBr3 (0.75 mmol, 0.337 g)
and methylphenylketene methyl trimethylsilyl acetal (2e; 0.76 mmol,
0.180 g) in dichloromethane (2 mL) was added styrene (1a; 0.51 mmol,
0.053 g). The mixture was stirred for 4 h at room temperature in a dark.
Then, 30 wt% HBr in CH3COOH (1 mL) was added, and the mixture
was stirred at room temperature for 30 min. The reaction was then
quenched with NaHCO3 (10 mL) and extracted with diethyl ether (3ꢁ
15 mL). The combined organic layers were dried over MgSO4. The evap-
oration of the volatiles gave the crude product which was analyzed by
1H NMR. Further purification was carried out by column chromatogra-
phy and distillation with glass tube oven under reduced pressure to give
the product 3ae (0.13 g, d.r. 1.2:1, 55%).
Typical procedure for carbobismuthination using BiCl3 followed by plo-
tonolysis (Table 2, Entry 1) To a suspension of BiCl3 (0.74 mmol, 0.234 g)
and diethylketene ethyl trimethylsilyl acetal (2c; 0.74 mmol, 0.160 g) in
dichloromethane (1 mL) was added styrene (1a; 0.53 mmol, 0.0553 g).
The mixture was stirred and was irradiated with ultraviolet (300 W high-
pressure mercury lamp). for 2 h at room temperature. Then, 30 wt%
HBr in CH3COOH (1 mL) was added, and the mixture was stirred at
room temperature for 30 min. The reaction was then quenched with
NaHCO3 (10 mL) and extracted with diethyl ether (3ꢁ15 mL). The or-
ganic layer was dried over MgSO4. The evaporation of the volatiles gave
[9] For the downfield shift of bismuth compounds, S. Shimada, M. L. N.
Rao, M. Tanaka, Organometallics 2000, 19, 931–936.
[10] The substitution of positively-charged BiPh3 group in bismuth(V)
compounds with PhSNa was reported. Y. Matano, M. Yoshimune, N.
Azuma, H. Suzuki, J. Chem. Soc. Perkin Trans. 1 1996, 1971–1977.
[11] See the Supporting Information for effects of bismuth salts and ad-
ditives.
[12] For p-electrophilic Lewis acidity, see: a) BiCl3-arene complexes, A.
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98, 742–744; Angew. Chem. Int. Ed. Engl. 1986, 25, 757–759;
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H. W. Roesky, D. Stern, C. Schulzke, D. Stalke, Angew. Chem. 2009,
121, 4587–4590; Angew. Chem. Int. Ed. 2009, 48, 4517–4520; c) a
reaction system including oxybismuthination, K. Komeyama, K. Ta-
kahashi, K. Takaki, Org. Lett. 2008, 10, 5119–5122.
1
the crude product which was analyzed by H NMR spectroscopy. Further
purification was carried out by column chromatography and distillation
with glass tube oven under reduced pressure to give the product 6ac
(0.061 g, 46%).
[13] For DFT analysis of the Lewis acidity of bismuth
ACHTUNGTREN(NUNG III) halides, see: J.
Acknowledgements
Sanderson, C. A. Bayse, Tetrahedron 2008, 64, 7685–7689.
This work was supported by the Ministry of Education, Culture, Sports,
Science and Technology (Japan).
Received: June 10, 2013
Published online: October 2, 2013
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