Boron trihalide mediated alkyne-aldehyde coupling reactions: A mechanistic investigation

Article abstract of DOI:10.1021/jo702493j

(Chemical Equation Presented) A boron trihalide mediated alkyne-aldehyde coupling reaction leading to stereodefined 1,3,5-triaryl-1,5-dihalo-1,4- pentadienes is described. The study led to the discovery of a direct substitution of hydroxyl groups by stere

Full text of DOI:10.1021/jo702493j

Boron Trihalide Mediated Alkyne-Aldehyde Coupling Reactions:
A Mechanistic Investigation
George W. Kabalka,* Min-Liang Yao, Scott Borella, Zhongzhi Wu, Yu-Hong Ju, and
Travis Quick
Departments of Chemistry and Radiology, The UniVersity of Tennessee, KnoxVille, Tennessee 37996-1600
kabalka@utk.edu
ReceiVed December 17, 2007
A boron trihalide mediated alkyne-aldehyde coupling reaction leading to stereodefined 1,3,5-triaryl-1,5-
dihalo-1,4-pentadienes is described. The study led to the discovery of a direct substitution of hydroxyl
groups by stereodefined alkenyl moieties using alkenylboron dihalides. During the investigation, it was
also discovered that, at low temperatures, the reaction of BCl3 with alkynes produces monovinylboron
dichloride rather than the reported divinylboron chloride. A modified reaction mechanism for the boron
trichloride mediated alkyne-aldehyde coupling reaction is now proposed. The reaction temperature and
mode of addition have been found to have dramatic affects on the stereochemistry of the diene products.
Introduction
kanones,7 and cycloalkenones.8 Using transition metal com-
plexes, additional products can be generated through either
carbon-carbon triple bond cleavage in alkynes9 or decarbony-
lation of aldehydes.10
Efficient one-pot syntheses of complex molecules from
readily available starting materials are always desirable. Espe-
cially attractive are reactions affording multifunctionalized
molecules.1 The alkyne-aldehyde coupling reaction is a prime
example. A variety of molecules can be generated from this
coupling reaction by varying the Lewis acids and transition metal
complexes employed. Synthons afforded by this coupling
reaction include propargylic alcohols,2 R,â-unsaturated ketones,3
allylic alcohols,4 stereodefined enynols,5 and naphthalene
derivatives.6 When carried out in an intramolecular fashion, the
reaction provides an efficient route to R-alkylidenecycloal-
(3) (a) Bu¨chi, G.; Kofron, J. T.; Koller, E.; Rosenthal, D. J. Am. Chem.
Soc. 1956, 78, 876. (b) Tsuda, T.; Kiyoi, T.; Saegusa, T. J. Org. Chem.
1990, 55, 2554. (c) Hayashi, A.; Yamaguchi, M.; Hirama, M. Synlett 1995,
195. (d) Jun, C.-H.; Lee, H.; Hong, J.-B.; Kwon, B.-I. Angew. Chem., Int.
Ed. 2002, 41, 2146. (e) Viswanathan, G. S.; Li, C.-J. Tetrahedron Lett.
2002, 43, 1613. (f) Curini, M.; Epifano, F.; Maltese, F.; Rosati, O. Synlett
2003, 552. (g) Willis, M. C.; Randell-Sly, H. E.; Woodward, R. L.; Currie,
G. S. Org. Lett. 2005, 7, 2249. (h) Willis, M. C.; Randell-Sly, H. E.;
Woodward, R. L.; McNally, S. J.; Currie, G. S. J. Org. Chem. 2006, 71,
5291.
(4) (a) Oblinger, E.; Montgomery, J. J. Am. Chem. Soc. 1997, 119, 9065.
(b) Huang, W.-S.; Chan, J.; Jamison, T. F. Org. Lett. 2000, 2, 4221. (c)
Wei, H.-X.; Gao, J. J.; Li, G. Tetrahedron Lett. 2001, 42, 9119. (d) Takai,
K.; Sakamoto, S.; Isshiki, T. Org. Lett. 2003, 5, 653. (e) Colby, E.; Jamison,
T. F. J. Org. Chem. 2003, 68, 156. (f) Huddleston, R. R.; Jang, H.-Y.;
Krische, M. J. J. Am. Chem. Soc. 2003, 125, 11488.
(5) (a) Wang, S.-H.; Tu, Y.-Q.; Chen, P.; Hu, X.-D.; Zhang, F.-M.; Wang,
A.-X. J. Org. Chem. 2006, 71, 4343. (b) Wang, S.-H.; Tu, Y.-Q.; Wang,
M. Tetrahedron Lett. 2006, 47, 8621.
(6) (a) Viswanathan, G. S.; Wang, M.; Li, C.-J. Angew. Chem., Int. Ed.
2002, 41, 2138. (b) Kabalka, G. W.; Ju, Y.; Wu, Z. J. Org. Chem. 2003,
68, 7915.
(7) Takeshi, K.; Sugishima, K.; Sasaki, K.; Tanaka, K. Chem. Eur. J.
2004, 10, 5681.
(8) Tanka, K.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 11492.
(1) Review: (a) Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown,
S. D.; Keating, T. A. Acc. Chem. Res. 1996, 29, 123. (b) Do¨mling, A.;
Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168. (c) Hulme, C.; Gore, V.
Curr. Med. Chem. 2003, 10, 51. (d) Vugts, D. J.; Jansen, H.; Schmitz, R.
F.; de Kanter, F. J. J.; Orru, R. V. A. Chem. Commun. 2003, 2594. (e)
Stru¨bing, D.; von Wangelin, A. J.; Neumann, H.; Go¨rdes, D.; Hu¨bner, S.;
Klaus, S.; Spannenberg, A.; Beller, M. Eur. J. Org. Chem. 2005, 107. (f).
Gommermann, N.; Knochel, P. Chemistry 2006, 12, 4380.
(2) (a) Takita, R.; Yakura, K.; Ohshima, T.; Shibasaki, M. J. Am. Chem.
Soc. 2005, 127, 13760. (b) Yao, X.; Li, C.-J. Org. Lett. 2005, 7, 4395. (c)
Jiang, B.; Si, Y. -G. Tetrahedron Lett. 2002, 43, 8323. (d) Anand, N. K.;
Carreira, E. M. J. Am. Chem. Soc. 2001, 123, 9687. (e) Yamaguchi, M.;
Hayashi, A.; Minami, T. J. Org. Chem. 1991, 56, 4091.
10.1021/jo702493j CCC: $40.75 © 2008 American Chemical Society
Published on Web 03/05/2008
2668
J. Org. Chem. 2008, 73, 2668-2673

Boron Trihalide Mediated Alkyne-Aldehyde Coupling
TABLE 1. Boron Trichloride Mediated Coupling of Aryl
Aldehydes and Alkynesa
SCHEME 1. Boron Halide Mediated Coupling of Aryl
Aldehydes and Alkynes
entry
Z
R
product
yield (%)b
1
2
3
4
5
6
7
8
9
H
4-F
4-Br
4-Me
4-CN
H
4-F
4-Me
4-F
Ph
Ph
Ph
Ph
Ph
4-Me-Ph
4-Me-Ph
4-Me-Ph
4-F-Ph
1a
1b
1c
1d
1e
1f
1g
1h
1i
65
73
68
65
27c,d
67
63
62
76
62
A new alkyne-aldehyde coupling reaction was recently
discovered.11 In the presence of a stoichiometric amount of
boron trihalide, aryl aldehydes were found to couple with 2
equiv of aryl alkynes to provide stereodefined 1,3,5-triaryl-1,5-
dihalo-1,4-pentadienes (Scheme 1). Interestingly, the stereo-
chemistry of the diene products is dependent on the boron halide
employed. If boron trichloride is used, the reactions afford (Z,E)-
1,4-pentadienes as major products along with minor quantities
of the (Z,Z)-1,4-pentadienes. However (Z,Z)-1,4-pentadienes are
the products formed if boron tribromide is used. In view of the
potential value of these dihalodiene products in organic syn-
thesis, the study led to the use of other Lewis acids, including
10
4-Me
4-F-Ph
1j
a Reaction carried out at 0 °C for 2 h and then maintained at room
temperature (see Experimental Section for details). b Isolated yields based
on the starting aldehyde. c (Z,Z)-Isomer (41%) was isolated as the major
product. d (Z,E)-Isomer was obtained in 66% isolated yield when the reaction
was kept at 0 °C for 5 h while using excess alkyne (3.0 equiv).
13
TiX4,12 FeCl3 and GaX3.14 A tentative reaction mechanism
for these coupling reactions was proposed.11-13 In this paper,
we describe an investigation initially designed to validate the
originally proposed mechanism. A modified reaction mechanism
was subsequently put forward and led to the discovery of the
dramatic influence of temperature on the stereochemistry of the
boron trichloride mediated alkyne-aldehyde coupling reaction.
In addition, it was found that the mode of reagent addition
greatly affects the stereochemistry of the products formed in
these three-component reactions (allyloxide, boron trihalide and
alkyne).
the 9-BBN ring prohibits reduction of the aldehyde via a
â-hydride transfer.18 The low reactivity of B-alkenyl-9-BBN
derivatives and the limited availability of functionally substituted
B-alkenyl-9-BBN derivatives restrict the scope of the 9-BBN
reactions. Alkenylboron dihalides exhibit high reactivity and
are not prone to â-hydride transfer; these chemical features led
us to investigate the reaction of aldehydes with (Z)-2-halo-1-
alkenylboron dihalides.
The reaction of benzaldehyde with preformed (Z)-2-chloro-
2-phenylvinylboron dichloride was first examined in dichlo-
romethane at room temperature. Surprisingly, the reaction
afforded (Z,Z)-1,5-dichloro-1,3,5-triphenyl-1,4-pentadiene along
with the expected allylic alcohol (Z)-3-chloro-1,3-diphenylprop-
2-en-1-ol. It has been reported that boron trihalides add to
terminal alkynes readily at -78 °C.19 Therefore, we examined
the possibility of a one-pot reaction by mixing boron trichloride,
phenylacetylene and benzaldehyde at 0 °C. The diene product
formed. However, the (Z,E)-1,4-pentadiene was isolated as the
major product along with minor amounts of the expected (Z,Z)-
1,4-pentadiene. None of the (E,E)-1,4-pentadiene isomer was
detected. A series of aldehydes and alkynes were then subjected
to the new reaction. The results are presented in Table 1.
Generally, reactions involving aryl aldehydes bearing electron-
Results and Discussions
Boron Trihalide Mediated Alkyne-Aldehyde Coupling
Reaction. We have been investigating the chemistry of boron
halide derivatives for many years, and a number of novel
reactions have been developed.15 In a continuation of a study
focused on the Grignard-like alkylation of aryl aldehydes using
dialkylboron halides,15e we investigated the addition of alk-
enylboron dihalide reagents to aldehydes. Brown16 and Soder-
quist17 had earlier reported the successful 1,2-addition of
B-alkenyl-9-BBN derivatives to aldehydes. The rigid nature of
(9) Lee, D.-Y.; Hong, B.-S.; Cho, E.-G.; Lee, H.; Jun, C.-H. J. Am. Chem.
Soc. 2003, 125, 6372.
(10) Varela, J. A.; Gonza´lez-Rodr´ıguez, C.; Rub´ın, S. G.; Castedo, L.;
Saa´, C. J. Am. Chem. Soc. 2006, 128, 9576.
(11) Kabalka, G. W.; Wu, Z.; Ju, Y. Org. Lett. 2002, 4, 1491.
(12) Kabalka, G. W.; Wu, Z.; Ju, Y. Org. Lett. 2002, 4, 3415.
(13) Miranda, P. O.; Diaz, D. D.; Padron, J. I.; Ramirez, M. A.; Martin,
V. S. J. Org. Chem. 2005, 70, 57.
(14) Yadav, J. S.; Reddy, B. V. S.; Eeshwaraiah, B.; Gupta, M. K;
Biswas, S. K. Tetrahedron Lett. 2005, 46, 1161.
(15) (a) Kabalka, G. W.; Tejedor, D.; Li, N. -S.; Malladi, R. R.; Trotman,
S. J. Org. Chem. 1998, 63, 6438. (b) Kabalka, G. W.; Tejedor, D.; Li, N.
-S.; Malladi, R. R.; Trotman, S. Tetrahedron Lett. 1998, 39, 8071. (c).
Kabalka, G. W.; Wu, Z. Tetrahedron Lett. 2000, 41, 579. (d) Kabalka, G.
W.; Wu, Z.; Ju. Y. Tetrahedron Lett. 2000, 41, 5161. (e) Kabalka, G. W.;
Wu, Z.; Trotman, S.; Gao, X. Org. Lett. 2000, 2, 255. (f) Kabalka, G. W.;
Wu, Z.; Ju, Y. Tetrahedron 2001, 57, 1663. (g) Kabalka, G. W.; Wu, Z.;
Ju, Y. Tetrahedron Lett. 2001, 41, 5793. (h) Kabalka, G. W.; Wu, Z.; Ju,
Y. Synthesis 2004, 2927. (i) Kabalka, G. W.; Wu, Z.; Ju, Y. Tetrahedron
Lett. 2003, 44, 1187. (j) Kabalka, G. W.; Wu, Z.; Ju, Y.; Yao, M.-L. J.
Org. Chem. 2005, 70, 10285.
1
withdrawing groups tend to proceed more slowly. The H and
13C NMR spectra of each 1,5-dichloro-1,4-diene derivative
displayed two sets of vinyl hydrogen resonances, indicating that
all were (Z,E)-1,4-pentadienes.20
(Z,Z)-1,5-Dibromo-1,4-pentadienes (rather than (Z,E)-1,5-
dibromo-1,4-pentadienes) were obtained as the major products
from the one-pot BBr3-mediated alkyne-aldehyde coupling
reaction. Since the bromination of aryl aldehydes by boron
(18) Grignard-like addition of 9-BBN derivatives to aldehydes and
ketones, see: (a) Brown, H. C.; Molander, G. A.; Singh, S. M.; Racherla,
U. S. J. Org. Chem. 1985, 50, 1577. (b) Evans, J. C.; Goralski, C. T.; Hasha,
D. L. J. Org. Chem. 1992, 57, 2941. (c) Maddess, M. L.; Lautens, M. Org.
Lett. 2005, 7, 3557. (d) Gonzalez, A. Z.; Canales, E.; Soderquist, J. A.
Org. Lett. 2006, 8, 3331.
(19) Lappert, M. F.; Prokai, B. J. Organomet. Chem. 1964, 1, 384.
(20) The X-ray molecular structure was reported earlier and supported
the NMR assignment; see ref 11. A crystal structure of a closely related
E,E isomer, 10b, is reported in this summary. See Supporting Information.
(16) Jacob, P.; Brown, H. C. J. Org. Chem. 1977, 42, 579.
(17) Rane, A. M.; Vaquer, J.; Colberg, J. C.; Soderquist, J. A.
Tetrahedron Lett. 1995, 36, 987.
J. Org. Chem, Vol. 73, No. 7, 2008 2669

Kabalka et al.
SCHEME 3. Direct Evidence Supporting Alkenyl Group
TABLE 2. Boron Tribromide Mediated Coupling of Aryl
Aldehydes and Alkynesa
Migration
entry
Z
R
product
yield (%)b
1
2
3
4
5
6
7
8
9
4-F
Ph
Ph
Ph
Ph
Ph
4-Me-Ph
4-Me-Ph
4-Cl-Ph
4-Cl-Ph
4-Cl-Ph
2a
2b
2c
2d
2e
2f
2g
2h
2i
91
95
80
83
80
80
70
83
74
89
4-Cl
4-Me
2-Me
4-NO2
4-F
4-Br
4-F
4-Br
2-Me
SCHEME 4. Competitive Reaction Designed To Distinguish
Concerted and Cationic Mechanisms
10
2j
a Reaction carried out at -40 °C (see experimental section for detail).
b Isolated yields based on the starting aldehydes.
SCHEME 2. Tentative Reaction Mechanism for Boron
Halides Mediated Coupling Reaction
migration outlined in Scheme 2 occurred, intermediate 7 would
be expected to rearrange to the desired product 8. Indeed,
reactions of allyloxides with alkenylboron dihalides proceed
efficiently at room temperature and generate 8 in good yields.
Thus, the proposed migration appeared reasonable since the
stereochemistry of the vinyl group was also retained. These
preliminary results were communicated.21 From the viewpoint
of organic synthesis, the reaction shown in Scheme 3 provides
a formal, transition-metal-free Suzuki reaction.22
Upon confirmation of vinyl group migration, we attempted
to ascertain whether the vinyl group migration proceeded via a
cationic or concerted pathway. It is known that allyltrimethyl-
silane readily captures cationic intermediates.23 Therefore, a
competition reaction involving vinylboron dihalide, allylsilane
and an allyloxide was designed to probe the vinyl group
migration (Scheme 4). To a mixture of preformed alkenylboron
dichloride 6a and allyltrimethylsilane, 1 equiv of allyloxide 5
was added to generate intermediate 7a. If the vinyl group
migration proceeds in a concerted fashion, only product 8a
should form. In contrast, if the vinyl group migration proceeds
via a cationic route, allyltrimethylsilane should capture a
percentage of the cation intermediate, generating 9 in addition
to the desired product 8a. When the reaction was carried out, a
mixture of allylated product 9 and 8a formed in a ratio of 5:2
tribromide has been reported to be quite facile,15c the boron
tribromide mediated reactions were carried out at -40 °C.
Consistent with the fact that the haloboration of alkynes is faster
with boron tribromide than boron trichloride, coupling reactions
involving boron tribromide are also faster than those using boron
trichloride. The results are summarized in Table 2. As antici-
1
pated, the H and 13C NMR spectra of the symmetrical (Z,Z)-
1,5-dibromide-1,4-pentadiene derivatives exhibited only one set
of vinyl resonances.
Tentative Reaction Mechanism. Due to the facile nature of
the haloboration reaction, the boron trihalide mediated alkyne-
aldehyde coupling reactions were initially postulated to occur
as outlined in Scheme 2. Haloboration of the alkyne first
generates di(halovinyl)boron halide 3, which then adds to the
aldehyde in a Grignard-like fashion to form 4. The migration
of the second halovinyl group from boron to carbon center then
affords the final product. The retention of the vinyl group
configuration during migration leads to high stereoselectivity.
(The E,Z stereochemistry of the vinyl groups was believed to
have been established during the formation of the divinylboron
halide intermediate; a postulation that was later shown to be
incorrect.) This tentative mechanism was based on the following
two factors: isolation of the anticipated 1,4-pentadiene from
the reaction of preformed dialkenylboron bromides with alde-
hydes and isolation of (Z)-3-halo-1,3-diarylprop-2-en-1-ol, the
expected product from intermediate 4, when the reactions were
quenched with water prior to completion.
(21) Kabalka, G. W.; Yao, M.-L.; Borella, S.; Wu, Z. Chem. Commun.
2005, 2492.
(22) For transition-metal-free Suzuki-coupling reaction, see: (a) Lead-
beater, N. E.; Marco, M. Angew. Chem., Int. Ed., 2003, 42, 1407. (b) Li,
C. J. Angew. Chem., Int. Ed., 2003, 42, 4856. (c) Leadbeater, N. E.; Marco,
M. J. Org. Chem. 2003, 68, 5660. (d) Arvela, R. K.; Leadbeater, N. E.;
Sangi, M. S.; Williams, V. A.; Granados, P.; Singer, R. D. J. Org. Chem.
2005, 70, 161.
(23) (a) Okajima, M.; Suga, S.; Itami, K.; Yoshida, J.-I. J. Am. Chem.
Soc. 2005, 127, 6930. (b) Barry, C.S.; Bushby, N.; Harding, J. R.; Hughes,
R. A.; Parker, G. D.; Roe, R.; Willis, C. L. Chem. Commun. 2005, 3727.
To examine the feasibility of a halovinyl group migration
from boron to carbon, the reaction shown in Scheme 3 was
carried out. The reaction of allyloxide 5 and alkenylboron
dihalide 6 would be expected to generate intermediate 7, which
is similar to the proposed reaction intermediate 4. If the
2670 J. Org. Chem., Vol. 73, No. 7, 2008

Boron Trihalide Mediated Alkyne-Aldehyde Coupling
TABLE 3. Reaction of Preformed (Z,Z)-Dialkenylboron Chloride
SCHEME 5. Reaction of (Z,Z)-Dialkenylboron Chloride
with 4-Chlorobenzylaldehyde
with Aryl Aldehydesa
entry
Z
R
product
yield (%)b
1
2
3
4
5
6
7
8
9
4-Cl
4-Br
4-CN
2-Me
H
Ph
Ph
Ph
Ph
Ph
4-MePh
4-MePh
4-MePh
4-BrPh
3-OMePh
3-FPh
10a
10b
10c
10d
10e
10f
10g
10h
10i
78
83
82
76
60
81
82
34
75
48
76
(isolated yields of 9 and 8a are 62% and 25%, respectively,
based on 5).
4-Cl
4-NO2
3,4-di-OMe
4-Cl
4-CF3
4-Cl
The identification of a cationic intermediate24 raises questions
relating to the stereochemistry of products isolated from the
boron trichloride mediated alkyne-aldehyde coupling reaction.
The intermediacy of the (Z,E)-di(chlorovinyl)boron chloride,
postulated earlier to explain the predominant formation of (Z,E)-
diene products, is probably not correct. Therefore, we reinves-
tigated the boron trichloride mediated alkyne-aldehyde coupling
reaction.
Reinvestigation of the Boron Trichloride Mediated Alkyne-
Aldehyde Coupling Reaction. The intermediacy of a (Z,E)-
di(chlorovinyl)boron chloride was initially postulated to explain
the Z,E-stereochemistry of the product dienes. However, the
reaction of boron halides with 2 equiv of alkyne has been
reported to afford only (Z,Z)-di(halovinyl)boron halides.19 Upon
reexamining the initial report, we noted that the (Z,Z)-di(2-
chloro-2-phenylvinyl)boron chloride used for product charac-
terization was obtained by distillation and in relatively low yield
(the reaction of alkynes with BBr3 gives quantitative yields).
Therefore, it is reasonable to postulate that, at low temperatures,
the reaction of 2 equiv of phenylacetylene with 1 equiv of boron
trichloride might produce the monovinylboron dichloride prod-
uct and that the divinylboron chloride product would be formed
only during distillation.
10
11
10j
10k
a Reaction carried out at 0 °C and then maintained at room temperature
(see Experimental Section for details). b Isolated yields based on the starting
aldehyde.
SCHEME 6. Dialkenylation of Aliphatic Aldehydes Using
Preformed Divinylboron Halides
prepared from the same starting materials (alkynes, aldehydes
and boron trichloride).
We also investigated the reactions of preformed divinylboron
halides with aliphatic aldehydes. The reactions afforded the
desired dialkenylation products 11 in moderate yields (Scheme
6). The use of preformed divinylboron halide reagents minimizes
enolization reactions leading to aldol products.
To summarize, the formation of (Z,Z)-1,5-dihalo-1,4-penta-
dienes from mixtures of alkynes with boron tribromide at -40
°C and from mixtures of alkynes refluxed with boron trichloride,
both involve the (Z,Z)-di(halovinyl)boron halide intermediates.
Grignard-like addition of the divinylboron halide intermediate
to the aryl aldehyde, followed by migration of the second vinyl
group proceeds with retention of olefin configuration, leads to
high stereoselectivity in the alkyne-aldehyde coupling.
A Modified Reaction Mechanism for the Boron Trichlo-
ride Mediated Alkyne-Aldehyde Coupling Reaction at 0 °C.
Since the reaction of boron trichloride with alkynes at 0 °C
generates only the (Z)-chlorovinylboron dichloride species, a
modified reaction mechanism is now proposed for the boron
trichloride mediated reaction at 0 °C (Scheme 7). The Grignard-
like addition of (Z)-halovinylboron dichloride to the aldehyde
forms intermediate 12. The subsequent cleavage of the carbon-
oxygen bond affords carbocation intermediate 13. Addition of
cation 13 to the second alkyne then generates the more
thermodynamically stable (Z,E)-diene product 1 with high
stereoselectivity.26 The isolation of pure (Z)-3-chloro-1,3-
diarylprop-2-en-1-ol from experiments in which incomplete
reactions were quenched with water is thus readily explained.
The modified mechanism (Scheme 7) involves an unusual
carbon-oxygen bond cleavage to generate a cation intermediate
To support the postulation that (Z,Z)-di(vinylchlorophenyl)-
boron chloride formed only during distillation, phenylacetylene
and boron trichloride (2:1) were refluxed in dichloromethane
for 3 h and the reaction mixture then allowed to cool to 0 °C.
Addition of p-chlorobenzaldehyde to the mixture produced
(Z,Z)-diene 10a in 78% isolated yield (Scheme 5). This strongly
supports the postulation that the observed (Z,Z)-diene products
arise from divinylboron halide intermediates (the reaction of
aldehyde with preformed dialkenylboron bromide also produces
(Z,Z)-dienes).
Reactions of preformed (Z,Z)-di(chlorovinyl)boron chlorides
with various aryl aldehydes were then carried out. The results
1
are summarized in Table 3. The H and 13C NMR spectra of
each product revealed only one set of vinyl group resonances
due to a single vinyl group, supporting the formation of (Z,Z)-
1,5-dichloro-1,4-pentadienes. In addition, a single crystal of
compound 10b was analyzed by X-ray crystallography.25 The
X-ray molecular structure confirmed the NMR assignment.
Thus, by changing the reaction sequence, and the temperature
at which the reaction is conducted, either (Z,E)-dichloro-1,4-
pentadienes 1 or (Z,Z)-dichloro-1,4-pentadienes 10 can be
(24) Other evidence supporting a cationic mechanism includes the ring
opening of a cyclopropyl group and the racemization of a chiral center in
benzyloxide derivatives in the coupling reaction of benzyloxides and
vinylboron dihalides. See: Kabalka, G. W.; Yao, M.-L.; Borella, S.; Wu,
Z. Org. Lett. 2005, 7, 2865.
(26) It is reported that the addition of benzylic carbocation to terminal
alkynes stereoselectively gives (Z)-alkenyl halides. See: Marcuzzi, F.;
Melloni, G.; Modena, G. J. Org. Chem. 1979, 44, 3022.
(25) See Supporting Information.
J. Org. Chem, Vol. 73, No. 7, 2008 2671

Kabalka et al.
SCHEME 9. Reaction of Z-Chlorovinylboron Dichloride
SCHEME 7. Modified Mechanism for BCl3-Mediated
Coupling of Aryl Aldehydes and Alkynes at 0 °C
with Aldehyde
triaryl-1,4-pentadiene products from preformed (Z)-2-chloro-
2-phenylvinylboron dichloride (vide supra). It is well-known
that electrophiles can add to vinylboron reagents stereoselec-
tively with retention of configuration of the vinyl group.31 Thus
an intermediate cation would add to a second equivalent of the
monovinylboron dihalide to generate the observed Z,Z-diene
product as illustrated for the formation of (Z,Z)-1,5-dichloro-
1,3,5-triphenyl-1,4-pentadiene (Scheme 9).
SCHEME 8. Evidence Supporting the Cleavage of the C-O
Bond via BCl3
Conclusion
The effects of reactant addition and temperature on the boron
trihalide mediated alkyne-aldehyde coupling reaction is de-
scribed. It is now possible, by controlling the sequence of
reactant addition and the reaction temperature, to generate either
(Z,Z)-1,5-dichloro-1,4-pentadienes or the corresponding (Z,E)-
isomers. The (Z,Z)-1,5-dibromo-1,4-pentadienes are the primary
products under all reaction conditions. It was discovered that,
at room temperature, the reaction of boron trichloride with 2
equiv of alkynes actually generates only the monovinylboron
dichloride products and not the originally reported divinylboron
chloride! Several novel carbon-carbon bond-forming reactions
were developed, including a direct substitution of a hydroxyl
group with a stereodefined alkenyl moiety.
13.27 To validate the formation of 13, the reaction of allyloxide
5 with phenylacetylene in the presence of boron trichloride was
examined at room temperature (Scheme 8). The (E,E)-1-chloro-
1,3,5-triphenyl-1,4-pentadiene (14) was isolated in 78% yield,
only 4% of (Z,E)-1-chloro-1,3,5-triphenyl-1,4-pentadiene was
formed. The isolation of diene 9 when allyltrimethylsilane is
present in the reaction mixture provides further support for the
intermediacy of a carbocation. The generation of cations from
alkoxides with the assistance of a Lewis acid is unprecedented.
This unusual carbon-oxygen cleavage reaction led to the
discovery of straightforward allylation of propargyl alcohols.28
Significantly, the stereochemistry of the 1,4-diene product
obtained (Scheme 8) is opposite to that of the products from
the reaction shown in Scheme 3. Thus, by changing the mode
of addition of the reactants, both (Z,E)-1-halo-1,3,5-triphenyl-
1,4-pentadienes 8 and (E,E)-1-halo-1,3,5-triphenyl-1,4-penta-
dienes 14 can be prepared from the same starting materials
(alkynes, boron trihalide and allyloxides)!
Experimental Section
All glassware was dried in an oven heated to 100 °C for at least
12 h and then cooled prior to use. Dichloromethane was distilled
from appropriate drying agents prior to use. Reactions were
magnetically stirred and monitored by TLC. Products were purified
by flash chromatography, using silica gel (230-400 mesh, 60 Å).
Boron trichloride (1.0 M methylene chloride solution) and boron
tribromide were used as received. All aldehydes and alkynes were
used as received.
Synthesis of (Z,E)-1,5-dichloro-1,3,5-triphenyl-1,4-pentadiene
(1a). Representative Procedure for the Synthesis of (Z,E)-1,5-
Dichloro-1,4-pentadienes (1a-j). Benzaldehyde (0.42 g, 4.0
mmol) and phenylacetylene (0.82 g, 8.0 mmol) were placed in a
dry argon-flushed, 50 mL round-bottomed flask equipped with a
stirring bar and containing 20 mL of dry CH2Cl2. The solution was
cooled to 0 °C in an ice bath, and boron trichloride (4.4 mmol, 4.4
mL of a 1.0 M CH2Cl2 solution) was added via syringe. The solution
was allowed to stir for 2 h at 0 °C and then for 4 h at room
temperature. The reaction solution gradually turned dark purple.
The resulting mixture was hydrolyzed with water (20 mL) and
29
13,30
Since the syn-additions of TiX4 and FeCl3
to terminal
alkynes are known, the TiX4- and FeCl3-mediated alkyne-
aldehyde coupling reactions to form (Z,E)-dienes most likely
proceed through the pathway similar to that in Scheme 7.
The intermediacy of a carbocation intermediate such as 13
could also explain the formation of (Z,Z)-1,5-dichloro-1,3,5-
(27) A similar cleavage has been proposed recently in the TiCl4/R3N-
mediated conversion of propargyl alcohols to chloroallenes; see: Karunakar,
G. V.; Periasamy, M. J. Org. Chem. 2006, 71, 7463.
(28) (a) Kabalka, G. W.; Yao, M.-L.; Borella, S. J. Am. Chem. Soc. 2006,
128, 11320. (b) Kabalka, G. W.; Yao, M.-L.; Borella, S.; Goins, L. K.
Organometallics, 2007, 26, 4112.
(29) Lemarchand, D.; M’Baye, N.; Braun, J. J. Organomet. Chem. 1972,
39, C69.
(31) (a) Hara, S.; Dojo, H.; Takinami, S.; Suzuki, A. Tetrahedron Lett.
1983, 24, 731. (b) Stewart, S. K.; Whiting, A. Tetrahedron Lett. 1995, 36,
3925. (c) Lightfoot, A. P.; Maw, G.; Thirsk, C.; Twiddle, S. J. R.; Whiting,
A. Tetrahedron Lett. 2003, 44, 7645. (d) Kabalka, G. W.; Mereddy, A. R.
Organometallics 2004, 23, 4519. (e) Batsanov, A. S.; Knowles, J. P.;
Whiting, A. J. Org. Chem. 2007, 72, 2525.
(30) Cassagne, D.; Gillet, M.; Braun, J. Bull. Soc. Chim. Fr. 1979, 140.
2672 J. Org. Chem., Vol. 73, No. 7, 2008

Boron Trihalide Mediated Alkyne-Aldehyde Coupling
extracted with hexanes (3 × 30 mL). The organic layer was
separated and dried over anhydrous MgSO4. Product 1a (0.95 g,
65% yield) was isolated by flash column chromatography. 1H NMR
(250 MHz): δ 7.57-7.21 (m, 15H), 6.26 (d, J ) 9.2 Hz, 1H),
(20 mL) was added, the reaction mixture extracted with ethyl acetate
(3 × 20 mL) and dried over anhydrous MgSO4. The products 8a
(125 mg, 25% yield) and 9 (218 mg, 62% yield) were isolated by
flash column chromatography using hexane as an eluent.
6.19 (d, J ) 10.6 Hz, 1H), 4.88 (dd, J ) 10.6 and 9.2 Hz, 1H). 13
C
Synthesis of (Z,Z)-1,5-dichloro-3-(4-chlorophenyl)-1,5-diphe-
nyl-1,4-pentadiene (10a). Representative Procedure for the
Synthesis of (Z,Z)-1,5-Dichloro-1,4-pentadienes (10a-k and
11a,b). Phenylacetylene (306 mg, 3.0 mmol) and boron trichloride
(1.5 mmol, 1.5 mL of a 1.0 M CH2Cl2 solution) were placed in a
dry argon-flushed, 50 mL round-bottomed flask equipped with a
stirring bar and containing 20 mL of dry CH2Cl2. The solution was
refluxed for 3 h and then cooled down to 0 °C using an ice-bath.
To this solution, 4-chlorobenzaldehyde (210 mg, 1.5 mmol) was
added. The solution was allowed to stir for 2 h at 0 °C and then 6
h at room temperature. The resulting mixture was hydrolyzed with
water (20 mL) and extracted with hexanes (3 × 20 mL). The organic
layer was separated and dried over anhydrous MgSO4. Product 10a
(471 mg, 78% yield) was isolated by flash column chromatography.
1H NMR (300 MHz): δ 7.62-7.58 (m, 4H), 7.37-7.29 (m, 10H),
6.29 (dd, J ) 9.0 and 0.9 Hz, 2H), 5.42 (t, J ) 9.0 Hz, 1H). 13C
NMR: δ 139.8, 137.5, 134.8, 132.6, 128.9, 128.8, 128.4, 126.8,
126.6, 45.2. IR (Neat, νmax/cm-1): 3032, 1596, 1491, 1445, 1093,
827, 759, 693. Anal. Calcd for C23H17Cl3: C, 69.11; H, 4.29.
Found: C, 69.27; H, 4.31.
BCl3-Mediated Coupling Reaction of Allyloxide 5 with
Phenylacetylene. (Evidence supporting the C-O bond cleavage
in alkoxide.) Alkoxide 5 (generated in situ by treating 315 mg, 1.5
mmol of (Z)-1,3-diphenylprop-2-en-1-ol with 1 mL of 1.6 M
n-BuLi), phenylacetylene (153 mg, 1.5 mmol) and dry dichlo-
romethane (8 mL) were combined in a 50 mL round-bottomed flask
under a nitrogen atmosphere at 0 °C. Boron trihalide (1.5 mmol,
1.5 mL of a 1.0 M CH2Cl2 solution) was added and the mixture
stirred at room temperature overnight. Water (20 mL) was added,
the reaction mixture extracted with ethyl acetate (3 × 20 mL) and
dried over anhydrous MgSO4. Product 14 (275 mg, 78% yield) was
isolated by flash column chromatography using hexane as an eluent.
Spectra for diene 14. 1H NMR (250 MHz): δ 7.44-7.12 (m, 15H),
6.47-6.20 (m, 3H), 4.32 (dd, J ) 10.6 and 10.5 Hz, 1H). 13C
NMR: δ 142.2, 136.9, 131.6, 131.2, 130.7, 130.3, 128.8, 128.7,
128.5, 128.3, 127.6, 127.5, 126.8, 126.3, 48.4. Anal. Calcd for
C23H19Cl: C, 83.50; H, 5.79. Found: C, 83.44; H, 5.82.
NMR: δ 141.5, 137.6, 136.7, 133.7, 129.0, 128.9, 128.8, 128.3,
127.6, 127.2, 126.9, 126.5, 45.6. Anal. Calcd for C23H18Cl2: C,
75.62; H, 4.97. Found: C, 75.48; H, 4.88.
Synthesis of (Z,Z)-1,5-dibromo-3-(4-fluorophenyl)-1,5-diphe-
nyl-1,4-pentadiene (2a). Representative Procedure for the
Synthesis of (Z,Z)-1,5-Dibromo-1,4-pentadienes (2a-j). 4-Fluo-
robenzaldehyde (0.52 g, 4.2 mmol) and phenylacetylene (0.86 g,
8.4 mmol) were placed in a dry argon-flushed, 50 mL round-
bottomed flask equipped with a stirring bar and containing 20 mL
of dry CH2Cl2. The solution was cooled to -40 °C, and boron
tribromide (4.5 mmol, 4.5 mL of a 1.0 M CH2Cl2 solution) was
added via syringe. The reaction solution turned purple immediately.
The solution was allowed to stir at -40 °C for 4 h. The resulting
mixture was hydrolyzed with water (20 mL) and extracted with
hexanes (3 × 25 mL). The organic layer was separated and dried
over anhydrous MgSO4. Product 2a (1.8 g, 91% yield) was isolated
1
by flash column chromatography. H NMR (250 MHz): δ 7.58-
7.00 (m, 14H), 6.40 (d, J ) 8.9 Hz, 2H), 5.31 (t, J ) 8.9 Hz, 1H).
13C NMR: δ 163.8, 159.8, 139.4, 136.5, 130.7, 129.0, 128.9, 128.3,
127.7, 127.3, 115.8, 115.5, 50.7. Anal. Calcd for C23H17Br2F: C,
58.50; H, 3.63. Found: C, 58.41; H, 3.73.
Coupling of Alkoxides with Vinylboron Dihalides To Afford
Dienes 8. (Evidence supporting the migration of the halovinyl group
from boron to the carbon center.) Boron trihalide (1.5 mmol, 1.5
mL of a 1.0 M CH2Cl2 solution), phenylacetylene (153 mg, 1.5
mmol) and dry dichloromethane (8 mL) were combined in a 50
mL flask and stirred for 1 h under a nitrogen atmosphere. Alkoxide
5 (generated in situ by treating 315 mg, 1.5 mmol of (Z)-1,3-
diphenylprop-2-en-1-ol with 1 mL of 1.6 M n-BuLi) was added at
0 °C and allowed to stir at room temperature overnight. Water (20
mL) was added, the reaction mixture extracted with ethyl acetate
(3 × 20 mL), and then dried over anhydrous MgSO4. Product 8a
(412 mg, 83% yield) was isolated by flash column chromatography
1
using hexane as an eluent. Spectra for diene 8a. H NMR (250
MHz): δ 7.60-7.57 (m, 2H), 7.37-7.15 (m, 13H), 6.58-6.34 (m,
3H), 4.94 (dd, J ) 9.0 and 8.9 Hz, 1H). 13C NMR: δ 142.1, 137.9,
137.1, 133.4, 130.9, 130.3, 128.7, 128.5, 128.3, 127.8, 127.4, 126.9,
126.6, 126.3, 48.5. Anal. Calcd for C23H19Cl: C, 83.50; H, 5.79.
Found: C, 83.57; H, 5.65.
Competition Reaction between Vinylboron Dihalides and
Allyltrimethylsilane. (Evidence supporting a cationic mechanism.)
Boron trihalide (1.5 mmol, 1.5 mL of a 1.0 M CH2Cl2 solution),
phenylacetylene (153 mg, 1.5 mmol) and dry dichloromethane (8
mL) were combined in a 50 mL flask and stirred for 1 h under a
nitrogen atmosphere. The reaction mixture was cooled to 0 °C,
allyltrimethylsilane (171 mg, 1.5 mmol) and alkoxide 5 (generated
in situ by treating 315 mg, 1.5 mmol of (Z)-1,3-diphenylprop-2-
en-1-ol with 1 mL of 1.6 M n-BuLi) were then added. The resulted
reaction mixture was stirred at room temperature overnight. Water
Acknowledgment. Acknowledgment is made to the Donors
of the Petroleum Research Fund for support of this research.
We also wish to thank the U.S. Department of Energy and the
Robert H. Cole Foundation for partial support of this research.
Supporting Information Available: 1H and 13C NMR data for
all compounds reported, IR data for 10a and 10i, elemental analysis
for all new compounds, and X-ray file in CIF format for Compound
10b. This material is available free of charge via the Internet at
http://pubs.acs.org.
JO702493J
J. Org. Chem, Vol. 73, No. 7, 2008 2673