Boron trihalide mediated haloallylation of aryl aldehydes: Reaction and mechanistic insight

Article abstract of DOI:10.1039/b715395c

The reaction of aryl aldehydes with allylsilanes in the presence of boron trihalides produces haloallylated products. Mechanistic details are presented. The Royal Society of Chemistry.

Full text of DOI:10.1039/b715395c

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/dalton | Dalton Transactions
Boron trihalide mediated haloallylation of aryl aldehydes: reaction and
mechanistic insight†‡
Min-Liang Yao, Scott Borella, Travis Quick and George Walter Kabalka*
Received 8th October 2007, Accepted 5th November 2007
First published as an Advance Article on the web 23rd November 2007
DOI: 10.1039/b715395c
The reaction of aryl aldehydes with allylsilanes in the presence of boron trihalides produces
haloallylated products. Mechanistic details are presented.
stereodefined alkenyl3 and alkynyl4 moieties using boron dihalides.
Very recently we found that C–O bond cleavage also occurs
smoothly in propargyloxyboron dihalides 3 (Scheme 2).5
A. Introduction
The Lewis acid mediated allylation of carbonyl compounds
leading to homoallylic alcohols constitutes one of the most
important synthetic reactions.1 Numerous allylic organometallic
reagents and Lewis acids have been investigated. In recent years,
asymmetric allylation reactions have also been studied exten-
sively due to their importance in medicinal and natural product
chemistry. Lewis acid mediated allylations have been shown to
be stepwise processes (Scheme 1). The addition of allylsilane to
an activated aldehyde forms intermediate 1. The silyl electrofuge
Scheme 2
cleavage then produces the metal homoallyloxide 2 and Me3SiX. If
the metal exchange between 2 and Me3SiX occurs smoothly, Lewis
acid MXn is regenerated and the reaction is catalytic in nature.
However, if the metal exchange does not occur, Me3SiX could
also induce further allylations (silyl cation catalyzed pathway).
To achieve high enantioselectivity in chiral Lewis acid catalyzed
allylations, minimizing the contribution from the silyl cation
catalyzed pathway is required.
In an earlier study, we reported a new method for dihalogenating
aryl aldehydes (Scheme 3).6 A NMR study revealed that the
reaction proceeds through an alkoxyboron dihalide intermediate
4. The similarity between intermediates 3 and 4 led us to investigate
the feasibility of capturing intermediate 4 with allyltrimethylsilane.
According to the postulated mechanism shown in Scheme 3, we felt
that the reaction of aryl aldehydes with allylsilane in the presence
of a stoichiometric quantity of a boron halide would lead to
haloallylated product 5 rather than the homoallylic alcohol. In
fact, during a kinetic study of the reaction between a carbocation
and allylsilane, Mayr and Gorath noted the chloroallylation of aryl
aldehydes in the presence of 2–4 equivalents of BCl3.7 A sentence
“in BCl3 promoted reaction of aldehydes with allyltrimethylsilanes
further halogeneration by excess BCl3 took place, and consecutive
products were isolated instead of the corresponding alcohols” was
used to describe the reaction mechanism. Herein we report the
results of a detailed study of this reaction, including a mechanistic
discussion.
Scheme 1
In the last decade, our group has developed a number of
novel reactions using the chemistry of boron halide derivatives.
These include, for example, the dialkenylation of aryl aldehydes
by divinylboron halides.2 A reaction that appears to occur via
an unprecedented process: C–O bond cleavage in the alkoxy-
boron monohalide intermediate. This discovery led us to develop
reactions in which the hydroxyl groups were substituted with
Scheme 3
Departments of Chemistry and Radiology, The University of Ten-
nessee, Knoxville, Tennessee, 37996-1600, USA. E-mail: kabalka@utk.edu;
Fax: +1 (865)974-2997; Tel: +1 (865)974-3269
† We would like to dedicate this paper to Professor Ken Wade on the
occasion of his 75th birthday.
B. Results and discussions
‡ Electronic supplementary information (ESI) available: Experimen-
tal details and analytical data for all new compounds. See DOI:
10.1039/b715395c
Due to its air and moisture sensitivity, 1.1 equivalents of BCl3 were
utilized for the reaction of benzaldehyde with allyltrimethylsilane.
776 | Dalton Trans., 2008, 776–778
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
Table 1 Haloallylation of aryl aldehydesa
allylation. The discovery that Me3SiX (X = Cl, Br) was not a
catalyst in non-polar solvent hexanes could be significant for
allylation reaction involving chiral Lewis catalysts. Hydrolysis
of the reaction mixture at this stage revealed products 7 and 5.
Homoallylic alcohol 7 was isolated as the major product (70%
yield) along with chloroallylated product 5c (8% yield) when BCl3
was employed. In contrast, bromoallylated product 5k was the
main product if boron tribromide was used; the yields of 7 and
5k were 26% and 41%, repectively. In a separate experiment, an
additional 0.3 equivalent of boron trihalide was added to the
substoichiometric (0.8 equivalent) mediated reactions. Both inter-
mediate 6 and the unreacted p-chlorobenzaldehyde disappeared
(no homoallylic alcohol 7 detected). Clearly the conversion of
intermediate 6 to haloallylated product 5 occured.9
The complete conversion of intermediate 6 and unreacted p-
chlorobenzaldehyde to haloallylated product 5 using only an addi-
tional 0.3 equivalent of boron trihalide (Scheme 4) was somewhat
surprising. The isolation of homoallylic alcohol 7 in 53% yield
from a modified reaction (Scheme 5) helps explain the earlier
observation. Removal of the Me3SiCl prior to addition of the
extra BCl3 inhibits the conversion of intermediate 6 to product 5c.
Entry
Z
R
X
Time/min
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
H
4-F
4-Cl
4-Br
2-Me
3,5-Br2
4-Cl
2-Me
2,3,4,5,6-F5
4-CF3
4-Cl
H
H
H
H
H
H
Me
Me
Me
Me
H
Me
Me
Me
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
30
30
20
30
20
5a
5b
5c
5d
5e
5f
5g
5h
5ic
5j
5k
5l
5m
5n
85
62
90
87
73
61
92
69
67
89
81
72
78
63
120
60
60
180
120
10
4-Cl
4-Br
3-Cl
10
10
20
a Boron halide was added at 0 ◦C and then the reaction mixture was warmed
to room temperature until complete (see ref. 8 for details). b Isolated yield
based on aldehyde. c Refluxing is required for completion
We found that the reaction proceeded readily in hexanes and gave
the expected haloallylated product 5a in 85% yield. A series of aryl
aldehydes were subjected to the reaction (Table 1). Essentially all
of the aryl aldehydes investigated were successfully converted to
the haloallylated products with the exception of p-anisaldehyde
(the cleavage of the methoxy ether by BCl3 and BBr3 is well
known). Generally, reactions with BBr3 are faster than those
using BCl3. Bromoallylated product 5k formed exclusively when
a mixture of BBr3 and BCl3 (1.1 equivalents each) was added
to the reaction with p-chlorobenzaldehyde, demonstrating a high
chemoselectivity.
Several control experiments were performed to probe the
reaction mechanism. First, the reaction of allyltrimethylsilane with
p-chlorobenzaldehyde using a substoichiometric amount of boron
trihalide (0.8 equivalent) was carried out to determine whether
the reaction was catalytic (Scheme 4). p-Chlorobenzaldehyde was
not completely consumed after 24 hours clearly indicating that
the reaction is not catalytic. Remarkably, the Me3SiX (X = Cl, Br)
generated in the reaction did not initiate a silyl cation catalyzed
Scheme 5
Based on these experiments, a tentative mechanism is proposed
to explain the boron trihalide catalyzed transformation of 6 to
5 (Scheme 6). Boron trihalide coordinates with the oxygen in
intermediate 6 to form 8. Rearrangement of 8 generates the desired
product 5 along with X2B–O–BX2 (9). Exchange between 9 and
Me3SiX regenerates boron trihalide and mixed anhydride 10.
Scheme 6
C. Conclusions
In summary, a facile haloallylation of aryl aldehydes using boron
trihalide is reported. A mechanistic study revealed the reaction
involves two-steps: i) conversion of aldehydes to homoallyloxide
Scheme 4
This journal is
The Royal Society of Chemistry 2008
Dalton Trans., 2008, 776–778 | 777
©

View Article Online
borates in the presence of a stoichiometric amount of boron
trihalides; ii) a boron trihalide catalyzed conversion of homoal-
lyloxide borates into halogenerated products in the presence of
Me3SiX (X = Br, Cl).
4 G. W. Kabalka, M.-L. Yao and S. Borella, Org. Lett., 2006, 8, 879.
5 G. W. Kabalka, M.-L. Yao and S. Borella, J. Am. Chem. Soc., 2006,
128, 11320; G. W. Kabalka, M.-L. Yao, S. Borella and L. K. Goins,
Organometallics, 2007, 26, 4112.
6 G. W. Kabalka and Z. Wu, Tetrahedron Lett., 2000, 41, 579.
7 H. Mayr and G. Gorath, J. Am. Chem. Soc., 1995, 117, 7862.
8 Typical reaction procedure: Finely ground 4-chlorobenzaldehyde
(210 mg, 1.5 mmol), allyltrimethylsilane (2.56 mg, 2.25 mmol) and dry
hexane (16 mL) were placed in a dry argon-flushed, 50 mL round-
bottomed flask equipped with a magnetic stirring bar. The solution
was cooled to 0 ◦C, and boron trichloride (1.65 mmol, 1.65 mL of a
1.0 M CH2Cl2 solution) was added via syringe. After completion of the
addition, the ice-bath was removed and the resulting solution allowed
warm to room temperature. The reaction mixture was hydrolyzed with
water and extracted with hexanes. The organic layer was separated,
dried over anhydrous MgSO4 and the product isolated by flash column
chromatography.
Acknowledgements
We wish to thank the Donors of the American Chemical Society
Petroleum Research Foundation (ACS-PRF #41768-AC1) and the
Robert H. Cole Foundation for support of this research.
Notes and references
1 S. E. Denmark and J. Fu, Chem. Rev., 2003, 103, 2763.
9 Although it is difficult to rule out the possibility of directly producing
5 from the aldehyde through a cation generated from intermediate 4 via
a C–O bond cleavage, the high electronegativity of chlorine makes this
route unlikely.
2 G. W. Kabalka, Z. Wu and Y. Ju, Org. Lett., 2002, 4, 1491.
3 G. W. Kabalka, Z. Wu and Y. Ju, Org. Lett., 2004, 6, 3929; G. W. Kabalka,
M.-L. Yao, S. Borella and Z. Wu, Chem. Commun., 2005, 2492; G. W.
Kabalka, M.-L. Yao, S. Borella and Z. Wu, Org. Lett., 2005, 7, 2865.
778 | Dalton Trans., 2008, 776–778
This journal is
The Royal Society of Chemistry 2008
©