Bismuth-Mediated Diastereoselective Allylation Reaction of Carbonyl Compounds with Cyclic Allylic Halides or Cinnamyl Halide

Article abstract of DOI:10.1002/adsc.201801297

An efficient diastereoselective allylation of various carbonyl compounds with cyclic allylic halides by using commercially available bismuth powder in the presence of LiI was developed. Among all the metals screened, bismuth was found to be the best mediator for the transformation. The reactions involving various cyclic allylic halides proceeded smoothly at room temperature to produce the desired homoallylic alcohols in good to excellent yields with high diastereoselectivities (>99:1 dr). Reversed diastereoselectivity was obtained when carbonyl substrate (e. g., 2-pyridinecarboxaldehyde, glyoxylic acid) containing chelating substituent was used in the allylation reaction. In addition, the reactions involving acyclic (E)-cinnamyl bromide as substrate worked equally well with high diastereocontrol. (Figure presented.).

Full text of DOI:10.1002/adsc.201801297

Title: Bismuth-Mediated Diastereoselective Allylation Reaction of
Carbonyl Compounds with Cyclic Allylic Halides or Cinnamyl
Halide
Authors: Xuan-Yu Liu, Bu-Qing Cheng, Yi-Cong Guo, Xue-Qiang Chu,
Yongxin Li, Teck-Peng Loh, and Zhi-Liang Shen
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801297
Link to VoR: http://dx.doi.org/10.1002/adsc.201801297

10.1002/adsc.201801297
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Bismuth-Mediated Diastereoselective Allylation Reaction of
Carbonyl Compounds with Cyclic Allylic Halides or Cinnamyl
Halide
Xuan-Yu Liu,a Bu-Qing Cheng,a Yi-Cong Guo,a Xue-Qiang Chu,a Yong-Xin Li,b Teck-
Peng Loh,a,b,* and Zhi-Liang Shena,*
a
Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic
Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing 211816, China
E-mail: ias_zlshen@njtech.edu.cn
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang
b
Technological University, Singapore 637371, Singapore
Phone: (+65) 6316 8899; Fax: (+65) 6791 1961; E-mail: teckpeng@ntu.edu.sg
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. An efficient diastereoselective allylation of diastereoselectivity was obtained when carbonyl substrate
various carbonyl compounds with cyclic allylic halides by (e.g., 2-pyridinecarboxaldehyde, glyoxylic acid) containing
using commercially available bismuth powder in the chelating substituent was used in the allylation reaction. In
presence of LiI was developed. Among all the metals addition, the reactions involving acyclic (E)-cinnamyl
screened, bismuth was found to be the best mediator for the bromide as substrate worked equally well with high
transformation. The reactions involving various cyclic allylic diastereocontrol.
halides proceeded smoothly at room temperature to produce
the desired homoallylic alcohols in good to excellent yields
with high diastereoselectivities (>99:1 dr). Reversed
Keywords: Bismuth; Cyclic Allylic Halide; Allylation;
Homoallylic alcohol; Diastereoselectivity
operationally
diastereoselective
simple,
allylation
and
of
highly
carbonyl
Introduction
compounds by using cyclic allylic halides as
substrates in the presence of a metal mediator is
still highly desirable, especially under relatively
loose conditions without the preclusion of air and
moisture.
Metal-mediated additions of allylic halides to
carbonyl compounds serve as an efficient method
for the synthesis of synthetically versatile
homoallylic alcohols which are important
intermediates in organic synthesis.[1,2] When γ-
substituted allylic halides were used as substrates,
normally the reactions proceeded via an SN2’-type
In recent decades, the use of bismuth(0 or III) in
organic synthesis has aroused considerable attention
from synthetic community because of its mild
reactivity, low toxicity, relatively cheap cost, and
good functional group compatibility.[4] However,
compared with other metals[5] (such as Mg, Zn, Al, Sn,
In, etc.), the use of bismuth(0) as reaction mediator in
organic synthesis has been rarely studied. In this
context, metallic bismuth, especially commercial but
unactivated bismuth powder, has not been widely
employed in allylation reaction due to its poor
reactivity and the existence of an oxide layer on the
metal surface which needs to be removed by pre-
activation.[6,7,8] In continuation of our efforts to
develop metal-mediated organic transformations,[9]
herein we describe an efficient and highly
diastereoselective allylation reaction of various
carbonyl compounds with cyclic allylic halides or
cinnamyl bromide by using commercially available
bismuth powder as reaction mediator in the presence
pathway to generate
diastereomers, having
a
mixture of two
the potential to
predominantly produce only one diastereomer,
depending on the substrates used. For typical
examples, Knochel and co-workers have
demonstrated that pre-prepared cyclic allylic
aluminium[3a] or zinc[3b] reagents, derived from the
insertion of metal into cyclic allylic halides, could
efficiently react with carbonyl compounds to
afford the corresponding homoallylic alcohols
with excellent diastereoselectivity. However, in
their cases, the reactions need to be performed
under strictly anhydrous conditions with the use
of preformed cyclic allylic metallic reagents.
Although indium could be used as reaction
mediator for the analogous allylation reactions as
well,
somewhat
erosion
of
product
diastereoselectivity (mostly 90:10 dr) was
observed.[3c] Thus, the development of a one-pot,
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801297
Advanced Synthesis & Catalysis
of LiI as reaction additive in DMF. The reactions when the reaction was performed in the absence of
proceeded smoothly at room temperature to produce any additive or catalyst (entry 1). Among the different
the desired homoallylic alcohols in good to excellent additives/catalysts (e.g., InCl3,[1b,2j,10,11] PbCl2,[10,12]
yields with high diastereoselectivities (>99:1 dr). CuCl,[13] LiCl,[3b,10,14] LiI[15]) screened (entries 2-9),
Remarkably, reversed diastereoselectivity was LiI was found to be the optimum additive for the
obtained when carbonyl substrate (e.g., 2- allylation, giving rise to the desired product 3a in
pyridinecarboxaldehyde, glyoxylic acid) containing 79% NMR yield with >99:1 dr (entry 9). In addition,
chelating substituent was used in the allylation it was found that the product yield gradually
reaction.
diminished when the reaction time was prolonged
from 12 h to 48 h (entries 9-11), indicating that the
o
product 3a might not be very stable at 120 C.
Moreover, decreasing the reaction temperature from
120 oC to room temperature led to overall
enhancement of reaction performance (96% isolated
yields; entries 12-13), a reflection of the relative
stability of the generated product at room temperature.
Further screening of reaction solvents (entries 14-18)
revealed that comparably high reaction efficiency
could also be achieved by performing the model
reaction either in THF (97% NMR yield, entry 14) or
in DMSO (98% NMR yield, entry 18).
A further study of the equivalents of substrate 2a
and bismuth powder showed that similarly high
product yield (96% NMR yield) could also be
obtained by decreasing the amount of bismuth powder
from 3 equiv to 2 equiv (Table 2, entry 2). However,
decreasing the amount of substrate 2a from 3 equiv to
2 equiv led to remarkably decreased product yield
(Table 2, entry 3).
Results and Discussion
Table 1. Optimization of reaction conditions.[a]
Yield
[%][b]
Entry
Additive or Catalyst
Conditions
1
2
--
DMF, 120 oC, 12 h
DMF, 120 oC, 12 h
DMF, 120 oC, 12 h
DMF, 120 oC, 12 h
DMF, 120 oC, 12 h
DMF, 120 oC, 12 h
DMF, 120 oC, 12 h
DMF, 120 oC, 12 h
DMF, 120 oC, 12 h
DMF, 120 oC, 24 h
DMF, 120 oC, 48 h
DMF, 60 oC, 12 h
DMF, rt, 12 h
23
32
InCl3 (0.1 equiv)
PbCl2 (0.1 equiv)
Yb(OTf)3 (0.1 equiv)
CuCl (2 equiv)
I2 (2 equiv)
3
24
4
50
5
4
6
29
7
NaI (2 equiv)
LiCl (2 equiv)
LiI (2 equiv)
LiI (2 equiv)
LiI (2 equiv)
LiI (2 equiv)
LiI (2 equiv)
LiI (2 equiv)
LiI (2 equiv)
LiI (2 equiv)
LiI (2 equiv)
LiI (2 equiv)
65
Table 2. Optimization of reaction conditions by using
different equivalents of 2a and bismuth powder.
8
70
9
79
10
11
12
13
14
15
16
17
18
72
69
82
98 (96)[c]
Entry
2a
Bi
Yield [%][a]
THF, rt, 12 h
97
1
2
3
3 equiv
3 equiv
2 equiv
3 equiv
2 equiv
3 equiv
98
96
78
CH3CN, rt, 12 h
DME, rt, 12 h
83
63
[a]
Et2O, rt, 12 h
4
Yields were determined by NMR analysis of crude
reaction mixture after work-up by using 1,4-
DMSO, rt, 12 h
98
[a] The reactions were performed at room temperature to 120
oC for 12-48 h by using 4-chlorobenzaldehyde (1a, 1 mmol),
3-bromocyclohexene (2a, 3 mmol), Bi (3 mmol), and
additive (0.1-2 equiv) in organic solvent (2 mL).
dimethoxybenzene as an internal standard.
In addition, a spectrum of metals (pre-activated by
1,2-dibromoethane and TMSCl), including In, Cr, Sm,
Zn, Fe, Mg, Al, Mn, and Pb were also investigated
(Table 3). However, under the above optimized
reaction conditions, bismuth was found to be the best
mediator for the present allylation reaction, in terms
of both product yield and diastereoselectivity (98%
NMR yield, >99:1 dr, entry 1). It should be noted that,
without the pre-activation of bismuth powder by 1,2-
dibromoethane and TMSCl, a decreaded yield of the
product 3a was obtained (82% NMR yield, entry 1).
In comparison, except indium metal which mediated
the reaction in 79% NMR yield with relatively good
diastereoselectivity (entry 2), the use of other metals
mostly led to poor product yields (entries 3-10).
[b]
Yields were determined by NMR analysis of crude
reaction mixture after work-up by using 1,4-
dimethoxybenzene as an internal standard.
[c] Isolated yield.
Initial studies were focused on optimization of
reaction conditions by using 4-chlorobenzaldehyde
(1a) and 3-bromocyclohexene (2a) as model
substrates in the presence of bismuth powder (pre-
activated by 1,2-dibromoethane and TMSCl) and
o
different additives/catalysts in DMF at 120 C for 12
h. As shown in Table 1, poor yield was obtained
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801297
Advanced Synthesis & Catalysis
Although Knochel and co-workers have reported that
pre-prepared cyclic allylic aluminium[3a] or zinc[3b]
reagents could efficiently react with carbonyl
compounds to afford the corresponding homoallylic
alcohols with excellent diastereoselectivity, Al and Zn
powder almost failed to promote the allylation
reaction under optimized reaction conditions.
Encouraged by the above results, subsequently we
continued our task to explore the substrate scope of
the reactions by using various aldehydes and cyclic
allylic halides as substrates.
Table 4. Substrate scope study by employing different
aldehydes.[a]
Table 3. Optimization of reaction conditions by
using different metals.[a]
Entry
Metal[b]
Yield [%][c]
1
2
Bi
In
98 (82)[d]
79[e]
3
Cr
0
4
Sm
Zn
Fe
0
5
<10
0
6
7
Mg
Al
35[f]
<10
0
8
9
Mn
10
Pb
<5
[a]
The reactions were performed at room
temperature for 12 h in DMF by using aldehyde 1a
(1 mmol), 3-bromocyclohexene (2a, 3 mmol),
metal (2 mmol), and LiI (2 mmol) in DMF (2 mL).
[b]
Unless otherwise noted, the metal was pre-
activated by 1,2-dibromoethane and TMSCl
[c]
Yields were determined by NMR analysis of
crude reaction mixture after work-up by using 1,4-
dimethoxybenzene as an internal standard.
[d]
Bismuth powder was not pre-activated by 1,2-
dibromoethane and TMSCl.
[e] 93:7 dr.
[f] 52:48 dr.
As listed in Table 4, under the optimized reaction
conditions, the bismuth-mediated allylation reaction
involving a wide array of aldehydes took place with
high efficiency to give the anticipated homoallylic
alcohols in moderate to good yields with excellent
diastereoselectivity (>99:1 dr). In addition to the high
performance observed with aryl aldehydes, heteroaryl
aldehydes (entries 9-10) and alkyl aldehydes (entries
12-14) were also proven to be suitable substrates for
the reaction. Moreover, the allylation reaction
occurred selectively at the formyl group of α, β-
unsaturated aldehyde 1l, rather than proceeding at the
C-C double bond via a Michael-type reaction pathway
(entry 11). Furthermore, the reaction could also be
applied to the use of ferrocenyl aldehyde as starting
[a]
The reactions were performed at room temperature for
12
h
by using aldehyde 1b-p (1 mmol), 3-
bromocyclohexene (2a, 3 mmol), Bi (2 mmol), LiI (2
mmol) in DMF (2 mL).
[b] Isolated yields.
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801297
Advanced Synthesis & Catalysis
material (entry 15). Besides, the reactions employing the reactions employing 3-chlorocyclohexene and 3-
bismuth as mild reaction mediator also allowed the iodocyclohexene as substrates worked equally well
use of aryl aldehydes bearing functional groups, such under the optimum reaction conditions to give the
as nitro, cyano, and carbonyl group (entries 1-3).
expected products with both excellent yields and
excellent diastereoselectivities (entries 1-3). Six-
membered allylic chloride 2d bearing two methyl
groups reacted with equal success under the optimal
reaction conditions (entry 4). Moreover, both seven-
membered and eight-membered allylic bromides were
demonstrated to be appropriate candidates for the
present organic transformations and reacted in an
analogous manner to afford the corresponding
homoallylic alcohols 3r-t in 71%-99% yields, with
the exclusive formation of the syn-diastereomer
(entries 5-7).
Table 5. Substrate scope study by employing different
cyclic allylic bromides.[a]
In comparison, the same reaction using less
reactive acetophenone as substrate proceeded
sluggishly under the optimized reaction conditions to
give the desired product in negligible amount. This
mildness of the present protocol allowed the selective
allylation of aldehyde in the co-existence of ketone.
For instance, when biphenyl 1q containing both
formyl and acetyl substituents were treated with
cyclic allylic bromide 2a in the presence of bismuth
and LiI under the well-established reaction conditions,
the reaction took place regioselectively at the formyl
group, leading to the expected product 3u in 96%
yield with >99:1 dr (Scheme 1). The reluctancy of
acetyl group to participate in the allylation reaction
clearly indicated that the in situ formed allylic
bismuth reagent was a mild organometallic reagent,
when compared to its allylic aluminium[3a] or zinc[3b]
counterparts which might react with both aldehyde
and ketone without regioselectivity.
Scheme 1. Selective allylation of formyl group of substrate
1q in the presence of acetyl group.
[a]
The reactions were performed at room temperature for
12 h by using aldehyde 1 (1 mmol), cyclic allylic halides
2b-f (3 mmol), Bi (2 mmol), and LiI (2 mmol) in DMF (2
mL).
[b] Isolated yields.
Next, substrate scope of the present protocol was
further surveyed by using various cyclic allylic
halides as starting materials. As outlined in Table 5,
3w
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801297
Advanced Synthesis & Catalysis
Scheme 2 Bismuth-mediated highly diastereoselective and glyoxylic acid (1v) or phenylglyoxylic acid (1w)
allylation reaction using isatin (1r or 1s) as substrate; X-ray worked with the same high performance, delivering
crystal structure of product 3w (CCDC 1858982; only one the expected products 4f-h with both excellent yields
of the two enantiomers is shown here).
and diastereoselectivities, with the anti-diastereomer
being the exclusive product. The stereochemistry of
the homoallylic alcohol 4g was unambiguously
In contrast with acetophenone which was not determined by X-ray diffraction analysis.[16]
susceptible to the present allylation, ketones 1r and 1s
containing electron-withdrawing groups at their α-
position reacted efficiently with 3-bromocyclohexene
(2a) to deliver the target products 3v and 3w in good
yields with excellent diastereoselectivities (Scheme 2).
The stereochemistry of the homoallylic alcohol 3w
was fully characterized by single crystal X-ray
diffraction analysis.[16]
It was reported that tin-mediated allylation of 2-
pyridinecarboxaldehyde with acyclic allylic halide
might lead to the generation of homoallylic alcohol
with the reversal of product stereochemistry.[2d] To
test whether the same principle could also be applied
to the present transformation using cyclic allylic
halide as substrate, we also examined the reaction of
2-pyridinecarboxaldehyde (1t and 1u) with six-,
seven-, and eight-membered cyclic allylic bromides
(2a and 2e-f). As expected, the reactions proceeded
4g
efficiently under the optimum reaction conditions to
provide the products 4a-e in good yields with
Scheme 4. Bismuth-mediated highly diastereoselective
exclusive inversion of stereochemistry, with the anti-
allylation using glyoxylic acid (1v) or phenylglyoxylic acid
(1w) as substrate; X-ray crystal structure of product 4g
diastereomer being the exclusive diastereomer
(Scheme 3). The stereochemistry of product 4a was
(CCDC 1858981; only one of the two enantiomers is
unambiguously determined with the aid of X-ray
crystal diffraction analysis. [16]
shown here).
Aside from cyclic allylic halides, exceptionally
high performance could also be accomplished by
employing acyclic allylic halides of (E)-cinnamyl
bromide as substrate. As outlined in Scheme 5, (E)-
cinnamyl bromide (2g) efficiently participated in
allylation reaction with aromatic aldehydes 1c-e to
furnish the corresponding homoallylic alcohols 4i-k
with both excellent yield and diastereoselectivity
(exclusive generation of anti-diastereomer). In
addition, the mild reaction conditions also allowed the
tolerance of cyano and carbonyl groups.
4a
Scheme 3. Bismuth-mediated highly diastereoselective
allylation using 2-pyridinecarboxaldehyde (1t and 1u) as
substrate with inversion of stereochemistry; X-ray crystal
structure of product 4a (CCDC 1858983; only one of the
two enantiomers is shown here).
Scheme 5. Bismuth-mediated highly diastereoselective
allylation using (E)-cinnamyl bromide (2g) as substrate.
Similarly, glyoxylic acid might also react in a same
manner to produce the anticipated homoallylic
In comparison, when (E)-4-bromobut-2-enoate (2h)
containing sterically less hindered methoxycarbonyl
group was employed as substrate, the allylation
alcohol
with
the
inversion
of
product
diastereoselectivity.[2d] As shown in Scheme 4, the
reactions involving cyclic allylic bromides (2a and 2f)
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801297
Advanced Synthesis & Catalysis
reaction worked with equal success (Scheme 6), but 6 h, the upper clear solution was separated from
with slightly reduced diastereoselectivity (90:10 dr).
the bottom precipitate and transferred to another
flask followed by the addition of aldehyde 1d
.
After reacting at room temperature for another 6 h,
the desired product 3d could be isolated in 62%
yield with >99:1 dr. Thus, we believed that cyclic
allylic bismuth reagent must have formed in the
transformation, otherwise the allylation reaction
would not take place.
Scheme 6. Bismuth-mediated diastereoselective allylation
using (E)-4-bromobut-2-enoate (2h) as substrate.
Mechanistically, the exclusive formation of the
syn-diastereomer by using cyclic allylic halide as
substrate (Tables 4 and 5) could be explained a
Scheme 7. Pre-formation of cyclic allylic bismuth reagent
from substrate 2a and ensuing allylation reaction with
ring aldehyde 1d.
Zimmerman-Traxler[17]
six-membered
transition state
A where the C−C double bond of
the in situ generated cyclic allylic bismuth
reagents always possesses a Z configuration and
As for the role of LiI,[15] we believed that Li+
should help to facilitate the insertion of bismuth
powder into cyclic allylic halides for the
is not susceptible to Z/E-isomerization (Figure 1).
[3]
In cases where 2-pyridinecarboxaldehyde (1t
)
was used as substrate, the adoption of a Cram- generation of the corresponding cyclic allylic
bismuth reagent, typical of the positive effects
observed in LiCl-enhanced insertion of other
metals into organohalides which were reported by
Knochel and others.[10,14] In addition, I- should
facilitate the conversion of relatively less reactive
chelated transition state
B
involving the
coordination of the nitrogen atom and carbonyl
group to the allylbismuth species forces the 2-
pyridinyl substituent to possess an axial position
in the six-membered ring transition state, which
leads to the inversion of the stereochemistry of allyl chlorides or bromides to more reactive allyl
iodides via a Felkinstein-type reaction pathway,
so that the latter might more readily undergo
bismuth insertion to in situ generate the
corresponding allylbismuth reagent.
the final product of homoallylic alcohol. A similar
Cram-chelated transition state can also be
C
applied to the use of glyoxylic acid (1v) or
phenylglyoxylic acid (1w) as substrates, where
the COOH group resides in the axial position of
the six-membered ring and coordinates with
bismuth atom.[18] When (E)-cinnamyl bromide
was used as substrate, the C-C double bond
possessed an E-configuration and sterically
hindered phenyl substituent adopted an equatorial
position in the Zimmerman-Traxler six-membered
Conclusion
In conclusion, we have developed an efficient
bismuth-mediated highly diastereoselective allylation
reaction of carbonyl compounds with cyclic allylic
halides by using commercially available bismuth
powder as reaction mediator in the presence of LiI in
DMF. The reactions proceeded smoothly at room
temperature to produce the desired homoallylic
alcohols in good to excellent yields with high
diastereoselectivities (>99:1 dr). Among all the metals
screened, bismuth was found to be the best mediator
for the reaction. A plethora of functional groups, such
as nitro, cyano, ester, and acetyl group, could be well
tolerated in the reaction. Remarkably, reversed
diastereoselectivity was obtained when carbonyl
substrate (e.g., 2-pyridinecarboxaldehyde, glyoxylic
acid) containing chelating substituent was used in the
allylation. In addition, the reactions involving acyclic
(E)-cinnamyl bromide as substrate worked equally
well, giving rise to the corresponding products with
both excellent yields and diastereoselectivities. In
contrast with the documented methods where pre-
prepared cyclic allylic aluminium[3a] or zinc[3b]
reagents were used, the present allylation reaction
using bismuth as reaction mediator, in which cyclic
ring transition state
D, thus leading to preferential
formation of the anti-diastereomer.
Figure 1. Zimmerman-Traxler six-membered ring
transition state accounted for the high diastereoselectivity
obtained.
To determine whether cyclic allylic bismuth
reagent was formed in the present allylation
reaction, we treated 3-bromocyclohexene (2a) with
bismuth powder in the presence of LiI in DMF
(Scheme 7). After stirring at room temperature for
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801297
Advanced Synthesis & Catalysis
allylic bismuth species might be in situ formed,
proceeded effectively in a simple one-pot fashion
with no exclusion of air and moisture. Further
applications of the methodology in organic synthesis
are currently underway in our laboratories.
1996, 118, 1917. j) G. Hilt, K. I. Smolko, Angew.
Chem., Int. Ed. 2001, 40, 3399. k) J.-M. Huang, X.-X.
Wang, Y. Dong, Angew. Chem., Int. Ed. 2011, 50, 924.
[3] a) Z. Peng, T. D. Blumke, P. Mayer, P. Knochel, Angew.
Chem., Int. Ed. 2010, 49, 8516; b) H. Ren, G. Dunet, P.
Mayer, P. Knochel, J. Am. Chem. Soc. 2007, 129, 5376;
c) F. A. Khan, B. Prabhudas, Tetrahedron 2000, 56,
7595.
Experimental Section
Typical procedures for the preparation of homoallylic
alcohols by the addition of allyl halides to carbonyl
compounds:
[4] For a selected review, see: a) Bismuth-mediated organic
reactions, ed. T. Ollevier, Springer, Berlin, Heidelberg,
2012. b) A. Gagnon, J. Dansereau, A. Le Roch,
Synthesis 2017, 49, 1707. For selected typical examples
of bismuth chemistry (usually Bi3+ salt functions as
Lewis acid catalysis) developed in the field of organic
synthesis, see: c) P. A. Evans, J. Cui, S. J. Gharpure, R.
J. Hinkle, J. Am. Chem. Soc. 2003, 125, 11456; d) S.
Shimada, O. Yamazaki, T. Tanaka, M. L. N. Rao, Y.
Suzuki, M. Tanaka, Angew. Chem., Int. Ed. 2003, 42,
184; e) T. Huang, Y. Meng, S. Venkatraman, D. Wang,
C.-J. Li, J. Am. Chem. Soc. 2001, 123, 7451; f) P. K.
Koech, M. J. Krische, J. Am. Chem. Soc. 2004, 126,
5350; g) Y. Matano, Chem. Commun. 2000, 2233.
To a 10 mL Schlenk flask was sequentially added bismuth
powder (418.0 mg, 2 mmol) and DMF (2 mL). Then
bismuth was activated by the addition of 1,2-
dibromoethane (18.8 mg, 5 mol%) and TMSCl (10.9 mg, 5
mol%). After stirring for 5 min, LiI (267.7 mg, 2 mmol),
allyl halides (3 mmol), and aldehyde or ketone (1 mmol)
was sequentially added to the reaction mixture. The
suspension was vigorously stirred at room temperature for
12 h before quenching with sat. NH4Cl solution (30 mL)
and extracting with ethyl acetate (20 mL×3). The combined
extracts were washed with brine (20 mL), dried over
anhydrous Na2SO4 and concentrated in vacuo. The residue
obtained was purified by silica gel column chromatography
using ethyl acetate/petroleum ether as eluent to give the
pure products.
[5] For selected reviews, see: a) Handbook of
Functionalized Organometallics, ed. P. Knochel,
Wiley-VCH, Weinheim,
Germany,
2005. b)
Acknowledgements
Comprehensive Organometallic Chemistry III, ed. R. H.
Crabtree, D. M. P. Mingos, Elsevier, Oxford, U.K.,
2007.
We gratefully acknowledge the financial support from Nanjing
Tech University (Start-up Grant No. 39837118, 39837101, and
39837146), the SICAM Fellowship from Jiangsu National
Synergetic Innovation Center for Advanced Materials,
Postgraduate Research & Practice Innovation Program of
Jiangsu Province (No. KYCX18_1075), and Nanyang
Technological University.
[6] For allylation reactions using bismuth powder as
reaction mediators, see:
a) M. Wada, K.-y. Akiba,
T
etrahedron Lett. 1985, 26, 4211; b) P. J. Bhuyan, D.
Prajapati, J. S. Sandhu, Tetrahedron Lett. 1993, 34,
7975; c) K. Smith, S. Lock, G. A. El-Hiti, M. Wada, N.
Miyoshi, Org. Biomol. Chem. 2004, 4, 935. d) M.
Wada, H. Ohki, K.-y. Akiba, Bull. Chem. Soc. Jpn.
1990, 63, 1738.
References
[1] For selected reviews regarding allylation reactions, see:
a) Z.-L. Shen, S.-Y. Wang, Y.-K. Chok, Y.-H. Xu, T.-P.
Loh, Chem. Rev. 2013, 113, 271; b) T.-P. Loh, G.-L.
Chua, Chem. Commun. 2006, 2739; c) U. K. Roy, S.
Roy, Chem. Rev. 2010, 110, 2472; d) M. Yus, J. C.
Gonzalez-Gomez, F. Foubelo, Chem. Rev. 2011, 111,
7774; e) S. E. Denmark, J. Fu, Chem. Rev. 2003, 103,
2763; f) D. Kumar, S. R. Vemula, N. Balasubramanian,
G. R. Cook, Acc. Chem. Res. 2016, 49, 2169; g) H.
Lachance, D. G. Hall, Org. React. 2008, 73, 1; h) B. W.
Gung, Org. React. 2004, 64, 1.
[7] For allylation reaction using in situ generated more
reactive bismuth as reaction mediators from the
reduction of BiX3 by reducing agent (e.g., Zn, Al,
NaBH4), see: a) S. Donnelly, E. J. Thomasa, M.
Fielding, Tetrahedron Lett. 2004, 45, 6779; b) M. Wada,
T. Fukuma, M. Morioka, T. Takahashi, N. Miyoshi,
Tetrahedron Lett. 1997, 38, 8045; c) T. Fukuma, M.
Morioka, T. Takahashi, N. Miyoshi, Tetrahedron Lett.
1993, 34, 7975; d) M. Wada, M. Honna, Y. Kuramoto,
N. Miyoshi, Bull. Chem. Soc. Jpn. 1997, 70, 2265; e)
P.-D. Ren, S.-F. Pan, T.-W. Dong, S.-H. Wu, Synth.
Commun. 1997, 27, 2569; f) X. Xu, Z. Zha, Q. Miao, Z.
Wang, Synlett 2004, 1171.
[2] For selected examples, see: a) S. Araki, H. Ito, Y.
Butsugan, J. Org. Chem. 1988, 53, 1831; b) C.-J. Li,
D.-L. Chen, Y.-Q. Lu, J. X. Haberman, J. T. Mague, J.
Am. Chem. Soc. 1996, 118, 4216. c) L. A. Paquette, T.
M. Mitzel, J. Am. Chem. Soc. 1996, 118, 1931; d) T. P.
Loh, X. R. Li, Angew. Chem., Int. Ed. 1997, 36, 980; e)
T.-P. Loh, K.-T. Tan, S.-S. Chng, H.-S. Cheng, J. Am.
Chem. Soc. 2003, 125, 2958; f) T. H. Chan, Y. Yang, J.
Am. Chem. Soc. 1999, 121, 3228. g) S. A. Babu, M.
Yasuda, A. Baba, J. Org. Chem. 2007, 72, 10264. h) K.
Lee, H. Kim, T. Miura, K. Kiyota, H. Kusama, S. Kim,
N. Iwasawa, P. H. Lee, J. Am. Chem. Soc. 2003, 125,
9682. i) L. A. Paquette, P. C. Lobben, J. Am. Chem. Soc.
[8] For two examples of allylation reaction using
allylbismuth reagent prepared from the transmetalation
of allylmagnesium with BiX3, see: a) T. Basile, A.
Bocoum, D. Savoia, A. Umani-Ronchi, J. Org. Chem.
1994, 59, 7766; b) C. Lichtenberg, F. Pan, T. P. Spaniol,
U. Englert, J. Okuda, Angew. Chem. Int. Ed. 2012, 51,
13011.
[9] For selected examples of metal-mediated organic
reactions developed in our group, see: a) Y. S. Yang, Z.
L. Shen, T. P. Loh, Org. Lett. 2009, 11, 1209; b) M. J.
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801297
Advanced Synthesis & Catalysis
Lin, T. P. Loh, J. Am. Chem. Soc. 2003, 125, 13042; c)
Y. S. Yang, Z. L. Shen, T. P. Loh, Org. Lett. 2009, 11,
2213; d) Z.-L. Shen, T.-P. Loh, Org. Lett. 2007, 9,
5413; e) Z. L. Shen, H. L. Cheong, T. P. Loh, Chem.-
Eur. J. 2008, 14, 1875; f) Z. L. Shen, Y. L. Yeo, T. P.
Loh, J. Org. Chem. 2008, 73, 3922; g) Z.-L. Shen, K. K.
K. Goh, H.-L. Cheong, C. H. A. Wong, Y.-C. Lai, Y.-S.
Yang, T.-P. Loh, J. Am. Chem. Soc. 2010, 132, 15852.
[10] T. D. Blümke, Y.-H. Chen, Z. Peng, P. Knochel, Nat.
Chem. 2010, 2, 313.
[11] a) T. D. Blümke, T. Klatt, K. Koszinowski, P. Knochel,
Angew. Chem., Int. Ed. 2012, 51, 9926. b) K. Takai, Y.
Ikawa, Org. Lett. 2002, 4, 1727.
[12] K. Takai, T. Kakiuchi, K. Utimoto, J. Org. Chem.
1994, 59, 2671.
[13] a) Z.-L. Shen, K. K. K. Goh, Y.-S. Yang, Y.-C. Lai, C.
H. A. Wong, H.-L. Cheong, T.-P. Loh, Angew. Chem.,
Int. Ed. 2011, 50, 511. b) Z.-L. Shen, K. K. K. Goh, C.
H. A. Wong, Y.-S. Yang, Y.-C. Lai, H.-L. Cheong, T.-P.
Loh, Chem. Commun. 2011, 47, 4778. c) S. Kim, C.-E.
Kim, B. Seo, P. H. Lee, Org. Lett. 2014, 16, 5552.
[14] For representative LiCl-mediated metal insertions into
organic halides, see: a) F. M. Piller, P. Appukkuttan, A.
Gavryushin, M. Helm, P. Knochel, Angew. Chem., Int.
Ed. 2008, 47, 6802; b) A. Krasovskiy, V. Malakhov, A.
Gavryushin, P. Knochel, Angew. Chem. Int. Ed. 2006,
45, 6040; c) N. Boudet, S. Sase, P. Sinha, C.-Y. Liu, A.
Krasovskiy, P. Knochel, J. Am. Chem. Soc. 2007, 129,
12358; d) Y.-H. Chen, P. Knochel, Angew. Chem., Int.
Ed. 2008, 47, 7648; e) Z.-L. Shen, P. Knochel, ACS
Catal. 2015, 5, 2324; f) P. H. Lee, K. Lee, Y. Kang, J.
Am. Chem. Soc. 2006, 128, 1139. g) P. H. Lee, K. Lee,
Angew. Chem., Int. Ed. 2005, 44, 3253. h) K. Lee, D.
Seomoon, P. H. Lee, Angew. Chem., Int. Ed. 2002, 41,
3901.
[15] B.-Z. Chen, M.-L. Zhi, C.-X. Wang, X.-Q. Chu, Z.-L.
Shen, T.-P. Loh, Org. Lett. 2018, 20, 1902.
[16] CCDC 1858982, 1858983, and 1858981 contain the
crystallographic data for compounds 3w, 4a, and 4g.
These data can be obtained free of charge from the
Cambridge Crystallographic Data Center via
www.ccdc.cam.ac.uk/ data_request/cif.
[17] a) H. E. Zimmerman, M. D. Traxler, J. Am. Chem. Soc.
1957, 79, 1920; b) C. H. Heathcock, Science 1981, 214,
395.
[18] For a chelation controlled addition of ethyl pyruvate to
cyclic allylic stannane, see: I. W. Muderawan, R. C.
Bott, D. J. Young, Synthesis 1998, 1640.
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801297
Advanced Synthesis & Catalysis
FULL PAPER
Bismuth-Mediated Diastereoselective Allylation
Reaction of Carbonyl Compounds with Cyclic
Allylic Halides or Cinnamyl Halide
Adv. Synth. Catal. Year, Volume, Page – Page
Xuan-Yu Liu, Bu-Qing Cheng, Yi-Cong Guo, Xue-
Qiang Chu, Yong-Xin Li, Teck-Peng Loh,* and
Zhi-Liang Shen*
9
This article is protected by copyright. All rights reserved.