Dioxane-monochloroborane: A new and highly reactive hydroborating reagent with exceptional properties

Article abstract of DOI:10.1021/ol990639b

(equation presented) Dioxane-monochloroborane was prepared by the reaction of dioxane and dioxane-BCl₃ with diborane or NaBH₄ in 98% purity. The adduct thus obtained is a liquid, 6.2 M in BH₂Cl, stable indefinitely at either 0 or 25°C. The adduct hydroborates simple unhindered olefins to the corresponding dialkylchloroboranes within 0.5 h, while moderately hindered olefins take 1-4 h at room temperature. Hindered tetrasubstituted olefins rapidly hydroborate to the monoalkylchloroborane stage with further hydroboration slow. Regioselectivity studies of representative olefins reveal that this new reagent possesses selectivities similar to those from the monochloroborane-diethyl ether adduct. Consequently, dioxane-monochloroborane can readily substitute for the older hydroborating agents, BH₃:THF and BH₃:DMS.

Full text of DOI:10.1021/ol990639b

ORGANIC
LETTERS
1
999
Vol. 1, No. 2
15-317
Dioxane−Monochloroborane: A New
and Highly Reactive Hydroborating
Reagent with Exceptional Properties
3
Josyula V. B. Kanth and Herbert C. Brown*
H. C. Brown and R. B. Wetherill Laboratories of Chemistry, Purdue UniVersity,
West Lafayette, Indiana 47907-1393
hcbrown@chem.purdue.edu
Received May 6, 1999
ABSTRACT
3 4
Dioxane−monochloroborane was prepared by the reaction of dioxane and dioxane−BCl with diborane or NaBH in 98% purity. The adduct
thus obtained is a liquid, 6.2 M in BH Cl, stable indefinitely at either 0 or 25 °C. The adduct hydroborates simple unhindered olefins to the
2
corresponding dialkylchloroboranes within 0.5 h, while moderately hindered olefins take 1−4 h at room temperature. Hindered tetrasubstituted
olefins rapidly hydroborate to the monoalkylchloroborane stage with further hydroboration slow. Regioselectivity studies of representative
olefins reveal that this new reagent possesses selectivities similar to those from the monochloroborane−diethyl ether adduct. Consequently,
3 3
dioxane−monochloroborane can readily substitute for the older hydroborating agents, BH :THF and BH :DMS.
Hydroboration of alkenes using monochloroborane provides
sulfide:BH
equilibrium with dimethyl sulfide-BH
methyl sulfide-BHCl (12.5%). Also, the unpleasant odor
of dimethyl sulfide poses significant environmental problems
in large-scale operations. The diethyl ether:BH Cl adduct is
2
Cl is a stable reactive adduct, but exists in
anti-Markovnikov hydroboration products in >99.5% iso-
3
(12.5%) and di-
1
meric purity, unlike the simple borane reagents, such as BH
3
:
2
2
THF and BMS, which give a mixture of regioisomers. These
product dialkylchloroboranes are widely used for many
synthetic transformations. For example, dicyclohexylchlo-
2
free from these problems but can be obtained only in
approximately 90% purity. Moreover, this reagent is unstable
roborane has been used as an enolizing agent for aldol type
3
5
reactions, while (+)- or (-)-Ipc
2
BCl and Eap
2
BCl reveal
and must be freshly prepared before utilization. The adduct,
4
promising characteristics as chiral reducing agents. The
current monochloroborane adducts, such as dimethyl sulfide-
monochloroborane and diethyl ether-monochloroborane,
serve major needs in these applications. However, these
reagents do suffer from some disadvantages. The dimethyl
2
tetrahydrofuran-BH Cl, can be obtained in 98% purity;
however, its slow reactivity and relatively rapid ring opening
5
limits its applications.
The increasing use of these monochloroborane reagents
and the diverse applications of the product dialkylchloro-
(
1) (a) Brown, H. C.; Ravindran, N. J. Org. Chem. 1973, 38, 182. (b)
(4) (a) Brown, H. C.; Chandrasekharan, J.; Ramachandran, P. V. J. Am.
Chem. Soc. 1988, 110, 1539. DIP chlorode is a trademark of Adrich
Chemical Company, USA. (b) Brown, H. C.; Ramachandran, P. V.;
Teodorovic, A. V.; Swaminathan, S. Tetrahedron Lett. 1991, 32, 6691. (c)
Ramachandran, P. V.; Brown, H. C. In Reductions in Organic Synthesis;
Abdel-Magid, A.F., Ed.; American Chemical Soceity: Washington, DC,
1996; Chapter 5.
Brown, H. C.; Ravindran, N. J. Am. Chem. Soc. 1972, 94, 2112. (c) Brown,
H. C.; Ravindran, N. J. Org. Chem. 1977, 42, 2533.
(
2) (a) Brown, H. C.; Subba Rao, B. C. J. Am. Chem. Soc. 1959, 81,
428. (b) Brown, H. C.; Zweifel, G. J. Am. Chem. Soc. 1960, 82, 4708. (c)
Brown, H. C. Organic Synthesis Via Boranes: Wiley: New York, 1975.
3) Brown, H. C.; Dhar, R. K.; Ganesan, K.; Singaram, B. J. Org. Chem.
992, 57, 499.
6
(
1
(5) Brown, H. C.; Zaidlewicz, M. Polish J. Appl.Chem. 1983, 26, 155.
1
0.1021/ol990639b CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/15/1999

boranes in organic synthesis prompted us to investigate the
possibilities of providing a more convenient reagent for these
applications. Herein we report a new, highly pure, reactive
monochloroborane:dioxane adduct for such applications.
Moreover, dioxane-monochloroborane can readily substitute
Scheme 3
for the older hydroborating agents BH
3
:THF and BMS.
Dioxane-BCl was prepared by passing BCl
3
3
gas slowly
into dioxane at 0 °C. The adduct thus obtained is a solid
which melts at 56 °C (with decomposition), but is stable at
0
°C for several weeks. Reaction of this adduct with diborane
is 6.3 M in BH
and at room temperature.
Hydroboration of Representative Olefins with Diox-
2
Cl and is stable indefinitely both at 0 °C
in dioxane produces dioxane-BH Cl, as outlined in Scheme
2
1.
ane-BH
toward representative olefins, hydroboration studies using
dioxane:BH Cl were carried out in dioxane and in dichlo-
2
Cl. To examine the reactivity of this new adduct
Scheme 1
2
romethane solvents. The hydroborations were carried out by
the addition of an olefin in dioxane or dichloromethane to
dioxane:BH
reaction mixture was brought to room temperature. The final
solution was 0.5 M in BH Cl and 1 M in the olefin.
2
Cl at 0 °C, followed by further stirring as the
2
Representative olefins such as 1-decene, 2-methyl-1-pentene,
cis-4-methyl-2-pentene, 2-methyl-2-butene, â-pinene, cyclo-
hexene, R-pinene, 3-carene, 1-phenyl-2-methyl-1-propene,
2,3-dimethyl-2-butene, and 1,2-dimethylcyclopentene were
utilized. The progress of these hydroboration reactions was
monitored by B NMR and hydride analysis of the residual
active hydride present by removing aliquots at intervals and
measuring the hydrogen evolved by injecting them into a
The dioxane-BH
2
Cl adduct thus obtained was 98% pure
by B NMR (+7.9, triplet). The adduct is a liquid, 6.2 M
in BH Cl, with a hydrogen-to-chlorine ratio of 2.00:1.00.
The stability of this adduct at 0 °C and room temperature
1
1
2
1
1
25 °C) was monitored using 1 B NMR examination of a
1
(
sealed sample (2 M dioxane-BH Cl in dioxane) in an NMR
2
11
tube, recording the B NMR at intervals. It was also checked
using active hydride analysis. Both of these studies did not
show any detectable change over a period of one year.
To make the synthesis more convenient, the possibility
Table 1. Hydroboration of Representative Olefins Using
2
Dioxane-BH Cl in Dioxane and Dichloromethane at Room
was explored of synthesizing the dioxane-BH
using NaBH and dioxane:BCl . However, the formation of
dioxane-BH Cl was not achieved, as indicated by B NMR,
even after 3 days of stirring at room temperature (Scheme
).
2
Cl complex
Temperaturea
4
3
reaction
time (h) hydride time (h) hydride
in in
usedb usedb
dioxane (equiv) CH2Cl2 (equiv)
reaction
11
2
2
olefin
1
2
-decene
-methyl-1-pentene
0.25
0.25
0.25
0.50
0.25
0.50
0.50
0.50
2.00
2.00
2.00
2.00
2.00
2.00
2.00
1.92
2.00
1.00
0.25
0.25
0.25
0.50
0.25
0.50
1.0
0.50
1.50
0.50
2.00
2.00
2.00
2.00
2.00
2.00
2.00
1.82
2.00
1.00
Scheme 2
cis-4-methyl-2-pentene
-methyl-2-butene
2
â-pinene
cyclohexene
3
-carene
R-pinene
1
.0
2
-methyl-1-phenyl-1-
propene
0.25
4
0.25
8.0
0.50
48.0
.0
1.82
1.18
1.76
1.00
1.62
4.0
0.50
48.0
0.50
48.0
1.76
1.18
1.68
1.00
1.54
Fortunately, addition of small catalytic amounts of triglyme
changed the course of reaction dramatically, so that dioxane:
BH Cl was conveniently prepared by taking appropriate
amounts of NaBH (10% excess), dioxane, dioxane:BCl
and 3 mol % of triglyme (Scheme 3).
Decantation of the clear supernatant layer provided
2
1
,3-dimethyl-2-butene
4
2
,2-dimethylcyclopentene
4
3
,
a
All reactions were carried out in solutions of dioxane or dichlo-
romethane which were 1.00 M in olefin and 0.50 M in BH2Cl (the olefin
was used in small excess (5%)). b Hydride analysis was carried out by
hydrolyzing an aliquot with a 1:1 mixture of glycerol-water and measuring
the hydrogen evolved.
1
dioxane:BH
spectrum in CDCl
2
Cl of 98% purity. Interestingly, the H NMR
of dioxane:BH Cl thus obtained did not
3
2
show the presence of triglyme. It is apparently absorbed by
the precipitated sodium chloride. The adduct thus obtained
316
Org. Lett., Vol. 1, No. 2, 1999

Table 2. Products from Hydroboration-Oxidation of Representative Olefins with Dioxane-BH
2
Cl in Dioxane
relative yield (%) of products
relative yield (%) of products
olefin
productsa
1-octanol
-octanol
2-methyl-1-butanol
-methyl-2-butanol
3-methyl-2-butanol
-methyl-2-butanol
2-phenyl-ethanol
-phenyl-ethanol
2-phenyl-1-propanol
-phenyl-2-propanol
4-methyl-2-pentanol
-methyl-3-pentanol
with dioxane:BH2Clb
with (C2H5)2O: BH2Cl
1
2
2
-octene
100
0.0
99.5
0.5
99.1
0.9
95.0
5.0
99.6
0.4
59.0
41.0
99.5
0.5
99.9
0.1
99.7
0.3
96.0
4.0
100
0.0
60.0
40.0
2
-methyl-1-butene
-methyl-2-butene
2
2
styrene
1
R-methylstyrene
cis-4-methyl-2-pentene
2
2
a
The combined yields of the alcohol products were quantitative (g99%) by GC analysis. b The relative yields of the product alcohols were obtained by
GC analysis (Varian-3300) using a Carbowax column with an internal standard.
glycerin-water mixture. The mono-, di-, and some trisub-
stituted olefins were hydroborated rapidly to the correspond-
ing dialkylchloroborane stage within 0.5 h. The more
hindered olefins were rapidly hydroborated to the monoalkyl
stage, with further hydroboration proceeding slowly. The
results are presented in Table 1.
BH
representative olefins were carried out. Hydroborations were
carried out using dioxane-BH Cl (3 mmol) and an olefin
2
Cl, regioselectivity studies in hydroboration of some
2
(6 mmol) in dioxane. The olefin was added at 0 °C and the
reaction mixture further stirred at room temperature. At the
reaction time indicated (Table 1), the reaction mixture was
oxidized using alkaline hydrogen peroxide. The ratio of the
product alcohols was established by GC analysis using a
Carbowax column with an internal standard. Table 2 sum-
marizes the results. Earlier results obtained in a similar study
using monochloroborane-ethyl etherate are included for
In the hydroboration of less hindered olefins using dioxane:
6
BH
2
Cl, only the corresponding dialkylchloroboranes were
11
obtained as observed by the B NMR value (∼+75 ppm).
These product dialkylboranes, being bulkier than BH Cl, do
2
not complex with dioxane. Consequently, they can be used
for further synthetic applications without any problem.
Methanolysis of these products gave B-methoxydialkyl-
boranes cleanly (∼+54 ppm). However, in the hydroboration
of hindered olefins such as 2,3-dimethyl-2-butene and 1,2-
dimethylcyclopentene, considerable amounts of the monoalkyl-
chloroboranes were also formed.
Regioselectivity Studies in the Hydroboration of Rep-
resentative Olefins Using Dioxane-Monochloroborane.
In continuation of the hydroboration studies with dioxane-
1
a
comparison.
The present study clearly demonstrates that the new
dioxane:BH Cl adduct is free of the problems that are
2
associated with the reagents currently used and that clean
hydroborations can be readily achieved with selectivities
similar to those reported for the earlier reagents. Thus this
new reagent should serve as an eco-friendly substitute for
the reagents currently available.
Acknowledgment. Financial support from the Borane
Research Fund is gratefully acknowledged.
(6) The synthesis and applications of such dialkylboranes are under
investigation and will be reported subsequently.
OL990639B
Org. Lett., Vol. 1, No. 2, 1999
317