Dichloroborane-dioxane: An exceptional reagent for the preparation of alkenyl- and alkylboronic acids

Article abstract of DOI:10.1016/j.tetlet.2003.08.086

Terminal alkynes and alkenes were conveniently hydroborated to the corresponding alkenyl- and alkyldichloroboranes using dichloroborane-dioxane in dichloromethane. These dichloroboranes were hydrolyzed by water to the corresponding alkenyl- and alkylboron

Full text of DOI:10.1016/j.tetlet.2003.08.086

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7789–7792
Dichloroborane–dioxane: an exceptional reagent for the
preparation of alkenyl- and alkylboronic acids
Kanth V. B. Josyula,* Peng Gao and Chris Hewitt
Aldrich Chemical Company, Inc., 1001 W. Saint Paul Avenue, Milwaukee, WI 53233, USA
Received 8 July 2003; revised 19 August 2003; accepted 20 August 2003
Abstract—Terminal alkynes and alkenes were conveniently hydroborated to the corresponding alkenyl- and alkyldichloroboranes
using dichloroborane–dioxane in dichloromethane. These dichloroboranes were hydrolyzed by water to the corresponding alkenyl-
and alkylboronic acids in moderate to good yields. With terminal alkenes and alkynes boron was predominantly attached to
terminal carbon. Alkynes gave exclusively trans-vinylboronic acids.
© 2003 Elsevier Ltd. All rights reserved.
Metal-mediated catalytic cross-coupling reactions con-
tinue to be widely practised in the synthesis of a broad
range of compounds having applications in pharmaceu-
tical, agrochemical, supramolecular and material sci-
due to the lesser reactivity of the alkylboronic acids in
Suzuki–Miyaura coupling conditions.4 Recently, there
has been increased interest in developing Suzuki–
Miyaura coupling conditions that can accommodate
less reactive alkylboronic acids.5,6
ence.1
Among
several
available
technologies,
Suzuki–Miyaura coupling involving aryl-, alkenyl- and
alkyl-boronic acids or esters with aryl-, heteroaryl
halides or triflates has proven to be more effective and
hence widely practised.2 In recent years, a plethora of
methodologies have been reported for the preparation
of aryl- and heteroaryl-boronic acids or esters.3 On the
contrary, not much attention has been focussed on the
preparation of alkyl- and alkenyl-boronic acids, in part
Though alkenyl- and alkyl-boronic acids or esters can
be prepared by several methods,7 hydroboration of
corresponding alkyne or alkene with catecholborane is
the widely used method.8 Unfortunately, the reaction of
catecholborane with alkynes and alkenes is sluggish at
room temperature, requiring high temperature (70°C
for alkynes and 100°C for alkenes) and in some cases,
Scheme 1.
* Corresponding author. Tel.: (414) 273-3850 ext. 5217; fax: (414) 287-4076; e-mail: kjosyula@sial.com
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.08.086

7790
K. V. B. Josyula et al. / Tetrahedron Letters 44 (2003) 7789–7792
1
addition product was noted in H NMR.
isolation of product is complicated by the presence of
catechol by-product. Though pinacolborane hydrobo-
rates alkynes to the corresponding alkenylpinacolbo-
rane esters at room temperature in 24 h, it requires two
equivalents of pinacolborane and the method is not
practical for the preparation of corresponding boronic
acids, as these pinacol esters are highly stable towards
hydrolysis and trans-esterifications.9 Dibromoborane–
methyl sulfide complex is a more practical reagent for
the preparation of corresponding boronic acids from
alkynes and alkenes. However, being a strong Lewis
acid, dibromoborane may not be compatible with acid
sensitive groups. Also, dimethyl sulfide is unpleasant to
handle in large-scale applications.10
Hydroboration of internal alkynes under these condi-
tions is sluggish. For example, the hydroboration of
3-hexyne (entry 6) with dichloroborane–dioxane gave
only 15% of the expected product. Considerable
amounts of unreacted 3-hexyne were noted in GC
analysis. Similar reactivity patterns were also observed
for olefins. More reactive cyclopentene and styrene
gave the corresponding boronic acids in good yields
(entries 7 and 8). However, moderately hindered cyclo-
hexene (entry 9) gave lower yields (52%).
The hydroboration of 3-bromo-1-propyne gave an
interesting side product. Under the reaction conditions
shown (Eq. (2)), in addition to the expected E-bro-
momethyl vinylboronic acid considerable amounts of
E-chloromethyl vinylboronic acid were also obtained.
Recently, exceptional chloroborane complexes of diox-
ane were reported with interesting regio- and stereose-
lectivities, which are devoid of problems associated with
earlier chloroborane reagents.11 These complexes were
prepared easily from simple inexpensive starting materi-
als and are stable over an extended period of time at
0°C or room temperature. In particular, dichlorobo-
rane–dioxane exhibited interesting selectivities. In reac-
tion with alkenes and alkynes, it gives the
corresponding terminal dichloroboranes, which can be
hydrolyzed to the corresponding boronic acids (Scheme
1).
(2)
To further establish the synthetic potential of this
promising reagent, we studied its reactivity towards
representative alkynes and alkenes.12 The addition of
1-octyne (0.11 mol) to a dichloromethane solution of
dichloroborane–dioxane (3 M, 0.1 mol), resulted in an
exothermic reaction and after 1 h, all 1-octyne is con-
sumed as monitored by GC analysis. The reaction
mixture was refluxed for another 4 h to ensure complete
transformation. Hydrolysis of the resulting dichlorobo-
rane intermediate provided E-1-octen-1-ylboronic acid
in 68% yield (Eq. (1)). The regio- and stereoisomeric
This is probably due to the halogen exchange resulting
from dioxane–BCl3 derived by the equilibration of
dioxane–BHCl2 under dichloromethane reflux condi-
tions (Eq. (3)).11a,13
1
purities were confirmed by H NMR, which is consis-
tent with the literature data.8
(3)
A number of alkynes and alkenes were hydroborated
and hydrolyzed to the corresponding vinyl and alkyl-
boronic acids in good yields. The results are summa-
rized in Table 1.
In conclusion, dichloroborane–dioxane shows excep-
tional reactivity in the hydroboration of terminal alky-
nes and alkenes. The corresponding dichloroboranes
are conveniently converted to akenyl- and alkylboronic
acids, which have high synthetic utility in metal medi-
ated coupling reactions. The current reagent showed
sluggish reactivity with internal alkynes. Further studies
on improving its reactivity towards the broad spectrum
of alkynes, alkenes and also utilizing its unique reactiv-
ity patterns in selective hydroboration are underway.
Dichloroborane–dioxane hydroborates terminal alkynes
conveniently to the corresponding vinyldichloroboranes
in sterio- and regioselective manner. Even in the case of
3-chloro-1-propyne (entry 5), only terminal boron-addi-
tion product was isolated after workup and no internal
(1)

K. V. B. Josyula et al. / Tetrahedron Letters 44 (2003) 7789–7792
7791
Table 1. Hydroboration-hydrolysis of alkynes and alkenes using dichloroborane–dioxane complex
Acknowledgements
Wan, T. S. M.; Chan, K. S. J. Org. Chem. 1996, 61, 3590;
(c) Kabalka, G. W.; Pagni, R. M.; Hair, C. M. Org. Lett.
1999, 1, 1423.
The authors would like to thank Dr. Clint Lane for his
support and encouragement.
5. (a) Zou, G.; Falck, J. R. Tetrahedron Lett. 2001, 42,
5817; (b) Zou, G.; Reddy, Y. K.; Falck, J. R. Tetrahedron
Lett. 2001, 42, 7213; (c) Falck, J. R.; Kumar, P. S.;
Reddy, Y. K.; Zou, G.; Capdevila, J. H. Tetrahedron
Lett. 2002, 42, 7211.
References
6. Molander, G. A.; Ito, T. Org. Lett. 2001, 3, 393.
7. (a) Matteson, D. S. Tetrahedron 1989, 45, 1859; (b)
Matteson, D. S. Chem. Rev. 1989, 89, 1535; (c) Matteson,
D. S. Acc. Chem. Res. 1988, 21, 294; (d) Roush, W. R.;
Palkowitz, A. D.; Ando, K. J. Am. Chem. Soc. 1990, 112,
6348; (e) Hoffman, R. W.; Dresely, S. Synthesis 1988, 103
and references cited therein; (f) Wuts, P. G. M.; Jung, Y.
W. J. Org. Chem. 1991, 56, 365; (g) Brown, H. C.;
Srebnik, M.; Cole, T. E. Organometallics 1986, 5, 2300;
(h) Brown, H. C.; Rangaishenvi, M. V. Tetrahedron Lett.
1990, 31, 7113 and 7115; (i) Soundararajan, R.; Mat-
teson, D. S. Organometallics 1995, 14, 4157.
1. For a review, see: Stanforth, S. P. Tetrahedron 1998, 54,
263.
2. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457;
(b) Suzuki, A. J. Organomet. Chem. 1999, 576, 147; (c)
Suzuki, A.; Brown, H. C. Organic Synthesis via Boranes,
Vol. 3. Suzuki Coupling; Aldrich Chemical Co., Inc.:
Milwaukee, 2002 (Product No. Z51,430-6).
3. Kotha, S.; Lahiri, K.; Kasinath, D. Tetrahedron 2002, 58,
9633.
4. (a) Wright, S. W.; Hageman, D. L.; McLure, L. D. J.
Org. Chem. 1994, 59, 6095; (b) Zhou, X.; Tse, M. K.;

7792
K. V. B. Josyula et al. / Tetrahedron Letters 44 (2003) 7789–7792
8. (a) Brown, H. C.; Gupta, S. K. J. Am. Chem. Soc. 1971,
water was added slowly drop wise. A vigorous reaction
occurred with hydrogen chloride gas evolution.
Dichloromethane was evaporated under reduced pressure
and more water was added. The white solid precipitated
was filtered and washed with water and cold pentane.
The solid was dried under vacuum to obtain chemically
pure boronic acid. Purity was checked using NMR and
boron estimation.
93, 1816; (b) Brown, H. C.; Gupta, S. K. J. Am. Chem.
Soc. 1972, 94, 4370; (c) Brown, H. C.; Gupta, S. K. J.
Am. Chem. Soc. 1975, 97, 5249; (d) Lane, C. F.; Kabalka,
G. W. Tetrahedron 1976, 32, 981; (e) Fend, Z.; Hellberg,
M. Tetrahedron Lett. 2000, 41, 5813.
9. (a) Tucker, C. E.; Davidson, J.; Knochel, P. J. Org.
Chem. 1992, 57, 3482; (b) Pereira, S.; Srebnik, M.
Organometallics 1995, 14, 3127.
10. (a) Brown, H. C.; Ravindran, N. J. Am. Chem. Soc. 1977,
99, 7097; (b) Brown, H. C.; Ravindran, N.; Kulkarni, S.
U. J. Org. Chem. 1980, 45, 384; (c) Brown, H. C.;
Zaidlewicz, M. Polish J. Appl. Chem. 1983, 26, 155.
11. (a) Brown, H. C. US Patent 6,008,414; (b) Kanth, J. V.
B.; Brown, H. C. J. Org. Chem. 2001, 66, 5359; (c)
Kanth, J. V. B.; Brown, H. C. Org. Lett. 1999, 1, 315.
13. To the best of our knowledge, such halogen exchange is
not reported, though it is not unexpected for allylicbro-
mides. Also, we observed similar halogen exchange for
2-bromomethylvinylboronic acid with boron trichloride
in refluxing dichloromethane conditions.
14. All starting materials and products listed in the Table 1
are available from Aldrich Chemicals. 1-Hexyne (Cat c
24,442-2), 1-octyne (24,446-5), 5-chloro-1-pentyne
(24,437-6), 3,3-dimethyl-1-butyne (24,439-2), 3-chloro-1-
propyne (38,432-1), 3-hexyne (30,689-4), cyclopentene
(34,450-8), a-styrene (24,086-9), cyclohexene (24,099-0),
E-1-hexen-1-ylboronic acid (52,101-9), E-1-octen-1-
ylboronic acid (52,102-7), E-5-chloro-1-pentenboronic
acid (56,279-3), E-tert-butyl vinyl boronic acid (55,655-6),
E-2-chloromethyl vinyl boronic acid (55,659-9),
cyclopentylboronic acid (58,841-5), phenethylboronic
acid (58,842-3), cyclohexylboronic acid (55,658-0), E-bro-
momethyl vinyl boronic acid (55,656-4).
12. Dichloroborane–dioxane complex,
3 M solution in
dichloromethane is exclusively available from Aldrich
Chemical Company (Cat c 55,595-9). General proce-
dure:
A
nitrogen-flushed flask was charged with
dichloroborane–dioxane in dichloromethane (3 M, 0.1
mol) under nitrogen pressure. Alkyne or alkene (0.11
mol) was added into the reaction flask dropwise using
addition funnel under nitrogen. A vigorous reaction
occurred and solvent started refluxing. After the addition
was complete, the contents were refluxed for additional 4
h. The reaction mixture was cooled to 0°C with ice and