Molecular addition compounds. 13. N,N-diisopropyl-n-isobutylamine-borane: The first highly reactive trialkylamine-borane reagent for hydroborations

Article abstract of DOI:10.1021/om980629z

N,N-Diisopropyl-N-isobutylamine (1) forms a stable liquid borane adduct (4.7 M in BH₃), when diborane is bubbled into the neat amine. The adduct thus formed is stable indefinitely at room temperature under an inert atmosphere. Hydroboration studies with this new, highly reactive amine-borane adduct, H₃B:NPrⁱ₂Buⁱ (2) and representative olefins, such as 1-hexene, styrene, β-pinene, cyclopentene, norbornene, cyclohexene, 2-methyl-2-butene, α-pinene, and 2,3-dimethyl-2-butene, were carried out at room temperature (22 ± 3°C) in selected solvents, tetrahydrofuran, dioxane, tert-butyl methyl ether, n-pentane, and dichloromethane. The reactions are faster in dioxane and n-pentane, requiring ～2 h for the hydroboration of simple, unhindered olefins to the trialkylborane stage.

Full text of DOI:10.1021/om980629z

1
310
Organometallics 1999, 18, 1310-1317
Molecu la r Ad d ition Com p ou n d s. 13.
N,N-Diisop r op yl-N-isobu tyla m in e-Bor a n e: Th e F ir st
High ly Rea ctive Tr ia lk yla m in e-Bor a n e Rea gen t for
Hyd r obor a tion s
,
†
†,‡,1
and Marek Zaidlewicz*,‡
Herbert C. Brown,* J . V. Bhaskar Kanth,
H. C. Brown and R. B. Wetherill Laboratories of Chemistry, Purdue University,
West Lafayette, Indiana 47907, and Faculty of Chemistry, Nicolaus Copernicus University,
Torun 87-100, Poland
Received J uly 23, 1998
3
N,N-Diisopropyl-N-isobutylamine (1) forms a stable liquid borane adduct (4.7 M in BH ),
when diborane is bubbled into the neat amine. The adduct thus formed is stable indefinitely
at room temperature under an inert atmosphere. Hydroboration studies with this new, highly
i
i
reactive amine-borane adduct, H
styrene, â-pinene, cyclopentene, norbornene, cyclohexene, 2-methyl-2-butene, R-pinene, and
,3-dimethyl-2-butene, were carried out at room temperature (22 ( 3 °C) in selected solvents,
3 2
B:NPr Bu (2) and representative olefins, such as 1-hexene,
2
tetrahydrofuran, dioxane, tert-butyl methyl ether, n-pentane, and dichloromethane. The
reactions are faster in dioxane and n-pentane, requiring ∼2 h for the hydroboration of simple,
unhindered olefins to the trialkylborane stage. Moderately hindered olefins, such as
cyclohexene and 2-methyl-2-butene, give the corresponding dialkylboranes rapidly, with
further hydroboration to the trialkylborane stage slower. However, the hindered R-pinene
and 2,3-dimethyl-2-butene structures give stable monoalkylboranes very rapidly, with further
hydroboration proceeding relatively slowly. The hydroborations also proceed readily in other
solvents, such as THF and tert-butyl methyl ether. However, a dramatic rate retardation in
dichloromethane is observed. The hydroboration of less hindered olefins is not complete even
after 48 h at room temperature, and starting amine-borane still persisted as observed by
1
1
B NMR analysis of the reaction mixture. Surprisingly, more hindered olefins, such as
R-pinene and 2,3-dimethyl-2-butene, underwent hydroboration relatively rapidly with no
1
1
detectable starting amine-borane in B NMR analysis of the reaction mixture. The
alkylboranes obtained after hydroboration were oxidized with hydrogen peroxide/sodium
hydroxide, and the product alcohols were obtained in quantitative yields, as established by
GC analysis. The carrier amine was recovered by simple acid-base manipulations in good
yield and can be readily recycled to make the borane adduct. This new amine-borane adduct
was also very efficient for the synthesis of important dialkylborane reagents. Various
d
d
2 2 2
dialkylboranes, such as disiamylborane, Ipc BH, 2- Icr BH, 9-BBN, and Chx BH, were
conveniently prepared in dioxane and THF. In the case of solid dialkylborane products, the
amine can usually be separated by simple filtration. When the product is a liquid
dialkylborane, such as disiamylborane, the presence of amine in the reaction medium usually
does not interfere with further reactions.
Diborane is a versatile reagent with a multitude of
applications in organic and inorganic syntheses.
Since it is a pyrophoric gas, it is preferably handled in
the form of liquid borane complexes with suitable Lewis
base carriers. Among the various borane-Lewis base
complexes that have been explored, borane-tetra-
hydrofuran (BH3:THF) and borane-dimethyl sulfide
2
-7
*
Corresponding author. Phone: (765)494-5316. Fax: 765-494-0239.
(
BMS) are the reagents of choice for most hydrobora-
E-mail: hcbrown@chem.purdue.edu.
†
2,3
Purdue University.
Nicolaus Copernicus University.
tions and reductions. However, these important re-
agents are not free from certain disadvantages. For
example, the low concentration of borane in commercial
BH3:THF limits its applications to only one solvent,
THF. Unfortunately, the complex is not stable over long
periods. Although BMS does not possess these dis-
advantages, the volatility, flammability, and unpleasant
odor of the dimethyl sulfide create problems from the
environmental viewpoint. Amines as borane carriers are
‡
(
1) Postdoctoral associate with support from Aldrich Chemical Co.
(2) Brown, H. C. Organic Syntheses via Boranes; Wiley: New York,
1
975; p 18. A reprinted edition is currently available: Organic
Syntheses via Boranes, vol. 1; Aldrich Chemical Co., Inc.: Milwaukee,
997.
3) Pelter, A.; Smith, K.; Brown, H. C. Borane Reagents; Academic
Press: London, 1988.
1
(
(
4) Lane, C. F. Aldrichem. Acta 1973, 6, 51.
(5) Yardley, J . P.; Fletcher, H., III; Russell, P. B. Eperientia 1978,
3
4, 1124.
(
(
6) Follet, M. Chem. Ind, 1986, 123.
7) Ren, O.; Meatres, C. F. Bioconjugate Chem, 1992, 3, 563.
4
free of these problems. However, the amine-borane
1
0.1021/om980629z CCC: $18.00 © 1999 American Chemical Society
Publication on Web 03/11/1999

Molecular Addition Compounds. 13
Organometallics, Vol. 18, No. 7, 1999 1311
adducts previously described are much less reactive
than BH3:THF and BMS.8-10
niently followed by taking out aliquots at intervals,
hydrolyzing with 3 M HCl-glycerol-THF (2:1:0.2), and
measuring the hydrogen evolved. The reactions were
also followed by B NMR, monitoring a decreasing
amine-borane signal and an increasing alkylborane
signal.
In the hope of developing new, highly reactive amine-
boranes for hydroborations and reductions, we recently
initiated an extensive study in this area. We synthesized
many new amines and amine-boranes with varying
1
1
1
1,12
electronic and steric factors around nitrogen.
Al-
Under the conditions indicated, the hydroboration of
though N,N-diisopropyl-N-ethylamine has been com-
mercially available for some time, the corresponding
borane adduct is unreactive and the hydroboration of
1
-hexene by N,N-diiisopropyl-N-isobutylamine-borane
(
2) in THF is complete in 4 h, forming the trihexyl-
borane. Hydrolysis of the reaction mixture does not
evolve any hydrogen, indicating complete utilization of
borane. Disubstituted olefins, such as â-pinene and
cyclopentene, are also hydroborated to the trialkyl-
borane stage in 4 h. The moderately hindered 2-methyl-
1
-octene is incomplete, even after 24 h at room temper-
ature. Accordingly, we synthesized several N,N-diiso-
propyl-N-alkylamines and their borane adducts.1 Among
the various amine-borane adducts prepared, the most
promising, N,N-diisopropyl-N-isobutylamine-borane,
was selected for a detailed study, and the results are
herein described.
3
11
2
-butene gave disiamylborane after 2 h ( B NMR, δ
ppm, +30.8), with further hydroboration proceeding
more slowly. Cyclohexene forms dicyclohexylborane
1
1
rapidly in 30 min ( B NMR, δ ppm, +51.2 after
Resu lts a n d Discu ssion
methanolysis), and 2.88 hydride equivalents are utilized
1
1
in 24 h ( B NMR, δ ppm, +81.3 after methanolysis,
corresponding to the formation of tricyclohexylborane).
However, the more hindered R-pinene consumes one
hydride rapidly in 40 min, and then the reaction
continues slowly, with the hydride utilization increasing
to 1.76 in 24 h at room temperature, indicating incom-
P r ep a r a tion a n d Sta bility. The borane adduct of
N,N-diisopropyl-N-isobutylamine (1) was prepared by
passing a slight excess of diborane gas into the neat
amine at 0-5 °C (eq 1). The concentration of the
adsorbed borane was established to be 4.7 M by hy-
drolysis of an aliquot, using a 2 M HCl-glycerol-water
mixture, measuring the hydrogen evolved.
plete formation of Ipc2BH. This is also confirmed by 11
NMR, which reveals two peaks after methanolysis, at
31.5 (minor, due to IpcB(OMe)2) and +52.6 (major, due
B
+
to Ipc2BOMe). Further substitution on the olefin, i.e.,
the tetrasubstituted 2,3-dimethyl-2-butene, results in
a further lowering of the hydride uptake. Here also, the
addition of the first hydride is very fast, giving thexyl-
1
1
borane ( B NMR, δ ppm +24.6) with the olefin/BH3
The adduct thus obtained, maintained under nitrogen,
11
ratio then rising to 1.45 after 24 h ( B NMR, δ ppm
1
1
is stable at room temperature indefinitely. B NMR
reveals a peak at -13.2 (q, CCl4). The stability of this
adduct in THF was also studied. Thus a solution of the
adduct in THF (2.0 M in BH3) was sealed in an NMR
+23.9 and +80.8, after methanolysis +31.1 and +52.9).
H yd r ob or a t ion of Olefin s in Ot h er Solven t s.
Hydroborations with 2 were also conducted in solvents
such as dioxane, tert-butyl methyl ether, n-pentane, and
dichloromethane. In dioxane, 2 shows an enhanced
reactivity when compared to solutions of 2 in tetrahy-
drofuran. Thus, in dioxane 2 hydroborates unhindered
mono- and disubstituted olefins to the corresponding
trialkylborane stage within 2 h. Enhanced reactivity is
also observed for hindered olefins. For example, R-pinene
is cleanly hydroborated to the Ipc2BH stage. This is also
1
1
tube and monitored over several months using B NMR
1
1
at appropriate intervals. No new peaks in the B NMR
spectra other than that given by the adduct appeared
during the first three months of observation. However,
after four months there appeared a small additional
peak at 18.3 (3-5%), probably arising from a slow
cleavage of THF by borane.
Hyd r obor a tion of Olefin s in Tetr a h yd r ofu r a n .
Hydroboration of representative mono-, di-, tri-, and
tetrasubstituted olefins with 2 was conducted in THF
at room temperature. To establish the rate and stoichi-
ometry, the reactions were carried out in solutions that
were 0.5 M in BH3 and 1.5 M in olefin. The procedure
followed was to add the THF solution of the olefin (3
equiv) to the amine-borane (1 equiv) in THF at 0 °C,
stirring the mixture further at room temperature (22
11
confirmed by B NMR observation, which reveals the
exclusive presence of Ipc2BOMe after methanolysis (δ
ppm +53). Figure 1 illustrates the plots of hydroboration
of hindered olefins with time in dioxane at room
temperature.
In n-pentane also, the hydroborations are faster than
in THF, requiring only 2 h to reach the trialkylborane
stage with simple unhindered olefins. However, the
hydroboration of moderately hindered olefins, such as
cyclohexene and 2-methyl-2-butene, does not give tri-
alkylboranes cleanly, even after 24 h. In the case of
cyclohexene, 2.88 equiv of hydride was consumed after
(
3 °C). The progress of the hydroboration was conve-
(8) Long, L. H.; Mellor, W. J . In A Comprehensive Treatise on
Inorganic and Theoretical Chemistry; Longman: London, 1981, Suppl.
Vol. 5, Part B1, p 1.
2
4 h, whereas it is 2.95 for 2-methyl-2-butene. More
(9) Mueller, A. In Gmelin Handbook of Inorganic and Organome-
tallic Chemistry; Springer: Berlin, 1992; 4th Suppl., Vol. 3, p 1.
hindered R-pinene and 2,3-dimethyl-2-butene were rap-
idly hydroborated to the monoalkyl stage within 40 min,
with further hydroboration proceeding slowly, consum-
ing only 1.91 and 1.76 hydride equivalents, respectively,
after 24 h (see Table 1)
(
(
10) Brown, H. C.; Murray, L. T. Inorg. Chem. 1984, 23, 2746.
11) Brown, H. C.; Zaidlewicz, M.; Dalvi, P. V. Organometallics 1998,
1
7, 4202.
(12) Brown, H. C.; Kanth, J . V. B.; Zaidlewicz, M. J . Org. Chem.
1
998, 63, 5154.
(13) Brown, H. C.; Zaidlewicz, M.; Dalvi, P. V.; Narasimhan, S.;
Mukhopadyay, A. Organometallics 1999, 18, 1305.
In tert-butyl methyl ether the reactivity of the bo-

1
312 Organometallics, Vol. 18, No. 7, 1999
Ta ble 1. Hyd r obor a tion of Rep r esen ta tive Olefin s Usin g 2 in Va r iou s Solven ts a t Room Tem p er a tu r ea
dioxane THF tert-butyl methyl ether n-pentane dichloromethane
hydrides hydrides
Brown et al.
time
(h)
time
(h)
time
(h)
hydrides
utilized
time
hydrides
utilized
time
(h)
hydrides
utilized
olefin
utilized
utilized
(h)
1
-hexene
2
1
2
1
2
1
2
1
2
3.00
2.78
3.00
2.80
3.00
2.78
3.00
2.80
3.00
2.80
2.95
2.00
2.95
2.00
2.00
1.00
1.71
1.00
4
1
4
1
4
1
4
1
4
3.00
2.45
3.00
2.14
3.00
2.40
2.93
2.52
2.95
2.36
2.88
2.00
2.94
2.00
1.76
1.00
1.45
1.00
4
1
4
1
4
1
4
1
4
3.00
2.57
3.00
2.52
3.00
2.52
3.00
2.40
3.00
2.37
2.95
2.00
2.90
2.00
1.81
1.00
1.69
1.00
2
1
2
1
2
1
2.5
1
2.5
1
24
0.66
24
2.66
24
0.66
24
0.50
3.00
2.29
3.00
2.29
3.00
2.31
3.00
2.36
3.00
2.40
2.88
2.00
2.95
2.00
1.91
1.00
1.76
1.00
48
48
48
48
48
48
48
48
48
1.76
1.92
2.03
2.11
2.14
2.79
2.75
1.54
1.64
styrene
â-pinene
cyclopentene
norbornene
cyclohexene
1
24
1
1
24
1
24
1.16
24
0.66
24
0.91
24
0.83
24
2.16
24
0.66
24
0.91
0
24
1
24
0
.83
.83
.33
.66
2
-methyl-2-butene
R-pinene
2
,3-dimethyl-2-butene
24
0
a
Reactions were carried out using amine-borane 2 (5.0 mmol) and an olefin (15.0 mmol) in a total volume of 10.0 mL of solution.
R-pinene and 2,3-dimethyl-2-butene. This unusual re-
activity may be due to the following.
It is well established from our earlier studies2 that
the rate-determining step in the hydroboration of olefins
with BH3:LB is the formation of free “BH3”. However,
such dissociation is not observed when borane adduct
,3
1
1
2
was taken in dichloromethane. The B NMR exami-
nation of the amine-borane in dichloromethane over a
period of time showed only signals due to amine-
borane, and no gas evolution was noted in gasimeter
studies (diborane, after dimerization of dissociated
“
BH3”), whereas in coordinating solvents, such as THF,
1
1
small amounts (2%) of BH3-THF ( B NMR, 0.9 ppm,
q) were noted. Also, the amine-borane may be stabi-
lized by the hydrogen in dichloromethane carrying a
positive charge. This could be the reason for initial
slower reactivity of olefins toward the borane adduct 2
in dichloromethane.
F igu r e 1. Hydroboration of hindered olefins using 2 in
dioxane at room temperature.
rane-amine adduct 2 is very similar to that observed
in THF. However, in dichloromethane an unusual rate
retardation in hydroboration was observed. Thus, the
hydroboration of simple unhindered olefins, such as
In the case of less bulkier olefins, the RBH2 formed
after first hydroboration may coordinate with the carrier
amine 1 to form RBH2:NR3, leading to slower further
1
-hexene, is incomplete even after 48 h at room tem-
hydroboration. This is confirmed with 1-hexene by 11
B
perature, consuming only 1.76 equiv of hydride out of
the 3.00 available. 11B NMR analysis of the reaction
mixture showed the presence of unreacted amine-
borane (2) (∼40%). The hydride uptake is higher for
moderately hindered cyclohexene and 2-methyl-2-
butene, 2.79 and 2.75, respectively. Also, B NMR
analysis of the reaction mixture after 48 h did not show
the presence of any starting amine-borane. A similar
reactivity was also observed for the more hindered
NMR analysis, which showed the formation of major
amounts of RB(OCH3)2 after methanolysis of the reac-
tion mixture at 24 h. However, such coordination is
minimal or absent in the case of hindered olefins, due
to the more bulky alkyl groups, leading to relatively
faster hydroborations with second and third equivalents
of olefin. Figure 2 illustrates plots of hydroboration of
hindered olefins with time in dichloromethane at room
temperature.
1
1

Molecular Addition Compounds. 13
Organometallics, Vol. 18, No. 7, 1999 1313
oxidation was instantaneous; however the yield of
cyclohexanol was slightly lower (∼91% by GC). In the
case of 1-hexene, the yield of 1- and 2-hexanols was even
less (80% by GC) and the isomeric ratio was 89:11.
Apparently, the oxidation is not complete. The complete
oxidation can be achieved by the addition of 20 mol %
of carrier amine to the reaction mixture before oxidation.
Also, these preparative scale experiments can be carried
out in other solvents such as dioxane, tert-butyl methyl
ether, and n-pentane. When the hydroboraions are
carried out in water-immiscible solvents, such as tert-
butyl methyl ether and n-pentane, addition of small
amounts of methanol or ethanol is essential to ensure
complete oxidation using NaOH/H2O2.
Con ven ien t P r ep a r a tion s of Rep r esen ta tive Di-
a lk ylbor a n e Rea gen ts Usin g 2. The hydroboration
of certain moderately hindered olefins with 2 proceeds
relatively rapidly to the mono- or dialkylborane stage,
with further reaction being slow. Consequently, we
undertook a study of the preparation of several well-
F igu r e 2. Hydroboration of hindered olefins using 2 in
dichloromethane at room temperature.
1
4
Summarizing the data for all the solvents, the fol-
lowing order of reactivity with solvent in the hydrobo-
ration of representative olefins with 2 was noted:
dioxane > n-pentane > tetrahydrofuran > tert-butyl
methyl ether . dichloromethane. Table 1 summarizes
the results in various solvents.
established dialkylboranes, such as diisopinocampheyl-
borane, (1S)-2-diisocaranylborane, 9-borabicyclo[3,3,1]-
nonane, disiamylborane, and dicyclohexylborane, using
the new environmentally benign amine-borane reagent
(2).
d
P r ep a r a tion of Diisop in oca m p h eylbor a n e, Ip c -
2
Hyd r obor a tion -Oxid a tion of Olefin s. To further
establish the synthetic applicability of this new highly
reactive amine-borane adduct, the hydroboration-
oxidation of representative olefins was also studied.
Hydroboration-oxidation of 1-hexene in THF gave
mixture of 1-, 2-hexanols in quantitative yield, as
observed by GC analysis with an internal standard. The
ratio of the boron addition to internal vs terminal
positions in 1-hexene was established as 4:96 from the
relative ratios of the corresponding alcohols after oxida-
tion. These selectivities are similar to that reported for
THF:BH3 or BMS.2
BH. The reaction of borane with R-pinene, not optically
pure, was originally studied in diglyme and THF.15
Asymmetric hydroboration of cis-2-butene with Ipc BH
2
thus formed and not isolated yielded 2-butanol in 87%
and 78% ee, respectively. The lower ee in THF compared
to that in diglyme was attributed to greater solubility
of tetraisopinocampheyldiborane in THF and hence to
more dissociation of the reagent to triisopinocampheyl-
diborane and R-pinene (eq 5).
In recent years, it has been demonstrated that Ipc2-
BH approaching almost 100% ee can be prepared by
hydroboration of R-pinene with borane-tetrahydrofuran
1
6,17
or BMS. Several procedures
the most convenient one starting with (+)-R-pinene of
1% ee gives Ipc2BH of >99% ee in 91% yield.18 The
have been developed;
9
Hydroboration-oxidation of cyclohexene with 2 in
THF gave cyclohexanol in quantitative yields (∼99% by
GC, 91% isolated, eq 4). The recovered amine using
acid-base manipulations can be used again for the
preparation of borane adducts.
Since the basic amine 1 was present in the reaction
mixture after hydroboration, oxidation of the organo-
borane with hydrogen peroxide was also examined
without the usual addition of sodium hydroxide. The
(
14) All these partially substituted boranes exist mainly as diborane
dimers, but the monomeric forms are shown for the sake of conven-
ience.
(15) Brown, H. C.; Moerikoffer, A. W. J . Am. Chem. Soc. 1962, 84,
1
478.
16) (a) Braun, L. M.; Braun, R. A.; Crissman, H. R.; Opperman,
M.; Adams, R. M.; J . Org. Chem. 1971, 36, 2388. (b) Lane, C. F. Ibid.
(
1
1
974, 39, 1437. (c) Brown, H. C.; Mandal, A. K.; Kulkarni, S. U. Ibid.
977, 42, 1392.
(
17) Brown, H. C.; Yoon, N. M. Isr. J . Chem. 1977, 15, 12.
(18) Brown, H. C.; J oshi, N. N. J . Org. Chem. 1988, 53, 4059.

1
314 Organometallics, Vol. 18, No. 7, 1999
Brown et al.
Sch em e 1
temperature. The reaction was complete in 3 h, as
revealed by estimation of residual hydride. Oxidation
of an aliquot with alkaline hydrogen peroxide gave 1,4-
and 1,5-cyclooctanediol (29% and 71%), corresponding
to borabicyclo[4.2.1]nonane and -[3,3,1]nonane, respec-
tively (eq 7). Thermal isomerization of the mixture of
organoboranes in refluxing solvents was complete in 2
h. After cooling, 9-BBN was obtained as a crystalline
solid, free from amine, in 70% yield, with the mother
liquor containing about 20% 9-BBN in dissolved form.
Alternatively, after the thermal isomerization, the
amine and the solvent dioxane or THF can be pumped
off, and recrystallization of the residue from monoglyme
or diglyme provides crystalline 9-BBN in 89% yield.
reagent hydroborates cis-2-butene to afford after oxida-
tion 2-butanol in 97.2% ee. Hence, it was interesting to
use the new amine-borane for the preparation of this
remarkable reagent.
A considerable increase in the yield of Ipc2BH was
observed when the hydroboration of (+)-R-pinene with
d
2
was carried out in dioxane. Thus, when (+)-R-pinene
(87.3% ee) in 25% excess was added to 2 in dioxane (1.25
M in borane) at 0 °C and the reaction mixture was left
d
at room temperature for 15 h, a white crystalline Ipc2-
BH was obtained in almost quantitative yields (98-
9
9%). The supernatant solution did not show the
presence of active hydride. The (+)-R-pinene was liber-
ated from the product by the addition of benzaldehyde
in the presence of catalytic amounts of boron trifluoride-
1
8
etherate. It was obtained in 86% yield and 99.5% ee,
indicating effective upgradation during the crystalliza-
d
tion of Ipc2BH (eq 4). Further confirmation was ob-
tained by recovering (+)-R-pinene of 78% ee from the
d
supernatant dioxane solution. Ipc2BH thus obtained
was free from amine. See Scheme 1.
In tetrahydrofuran, the adduct 2 also gave Ipc2BH
d
of >99% ee. However, the yield was lower (89-90%),
similar to that reported for borane-tetrahydrofuran and
BMS.
P r ep a r a tion of Disia m ylbor a n e, Sia 2BH. The
reaction of 2-methyl-2-butene with 2 in dioxane and
tetrahydrofuran was complete within 2.5 h at room
temperature (eq 8). The formation of disiamylborane
d
P r epar ation of (1S)-2-Diisocar an ylbor an e, 2- Icr 2-
d
BH . Recently, it was reported that 2- Icr2BH hydro-
borates prochiral cis-disubstituted olefins, giving the
1
9
corresponding alcohols in high enantiomeric excess.
11
was confirmed by B NMR, from the disappearance of
Its B-allyl derivative proved to be a highly enantio-
selective allylborating reagent for aldehydes.20 Accord-
ingly, the synthesis of this important chiral auxiliary
using the new amine-borane 2 was examined.
a peak at δ -13.2 corresponding to 2 and the appear-
ance of absorption at δ +31.1. The reagent thus pre-
pared can be utilized for hydroborations or can be
converted by methanolysis to methyl disiamylborinate,
which is valuable for the synthesis of unsymmetrical
It was prepared by the addition of (+)-2-carene, 98%
ee (10% excess), to a dioxane solution of 2 at 0 °C and
keeping the mixture undisturbed at room temperature
2
1
diynes. Oxidation of the reaction mixture gave 3-meth-
yl-2-butanol in quantitative yields.
d
for 15 h. The 2- Icr2BH started crystallizing out from
the dioxane solution in the form of needles, 20 min after
mixing the reagents. The crystals can be conveniently
washed with pentane, and the carrier amine can be
d
removed by decantation. Thus, amine-free 2- Icr2BH
was obtained in excellent yields (99%). Enantiomeric
purity of the product was checked by oxidation, which
gave (-)-2-isocaranol of >99% ee (eq 6). In tetrahydro-
Ap p lica tion of Disia m ylbor a n e for Regiosp ecific
Hyd r obor a tion of Styr en e. The reagent prepared as
described above was reacted with styrene at room
temperature. The reaction was complete in 1 h both in
dioxane and in THF (eq 9). Oxidation of the product with
alkaline hydrogen peroxide gave 2-phenylethanol (99%)
and 1-phenylethanol (1%).
d
furan, 2- Icr2BH was obtained in lower yields (85-86%).
P r ep a r a t ion of 9-Bor a b icyclo[3,3,1]n on a n e,
9
-BBN. The hydroboration of 1,5-cyclooctadiene with 2
in dioxane and tetrahydrofuran was carried out at room
Clearly, the amine present in the reagents does not
interfere in the subsequent hydroborations. The amines
(
19) Brown, H. C.; Vara Prasad, J . V. N.; Zaidlewicz, M. J . Org.
Chem. 1988, 53, 2911.
20) Brown, H. C.; Randad, R. S.; Bhat, K. S.; Zaidlewicz, M.;
Racherla, U. S. J . Am. Chem. Soc. 1990, 112, 2381.
(
(21) Sinclair, J . A.; Brown, H. C. J . Org. Chem. 1976, 41, 1078.

Molecular Addition Compounds. 13
Organometallics, Vol. 18, No. 7, 1999 1315
column chromatography and can be easily recycled for
the preparation of the borane adduct.
The present study also demonstrates the usefulness
of this new amine-borane adduct for the preparation
of well-established dialkylborane reagents. In certain
cases the adduct showed advantages over borane-
d
tetrahydrofuran and BMS; for example, Ipc2BH and
d
2
- Icr2BH were prepared in higher yields and excellent
optical purity. Other partially substituted boranes, such
as disiamylborane, dicyclohexylborane, and 9-BBN, can
also be prepared conveniently. Crystalline dialkylborane
products are readily isolated free of amines by simple
filtration. The liquid dialkylborane products can be used
for further applications, such as selective hydrobora-
tions, in the presence of carrier amine. However, ad-
ditional studies are needed to establish the scope of such
applications. It should be pointed out that we now have
for the first time a highly reactive trialkylamine-borane
adduct, 2, for hydroborations, which can serve as an eco-
friendly substitute for the currently popular hydro-
borating agents, such as borane-dimethyl sulfide and
borane-tetrahydrofuran.
can be readily separated from the product alcohol by
simple acid-base manipulations.
P r ep a r a tion of Dicycloh exylbor a n e. The hydro-
borations of cyclohexene with 2 in 2:1 ratio were
complete within 1 h at room temperature in both
dioxane and tetrahydrofuran (eq 10). Dicyclohexyl-
borane precipitated from the solution and was isolated
in 89% yield.
Exp er im en ta l Section
Meth od s. All manipulations and reactions with air-sensi-
tive compounds were carried out in an atmosphere of dry
nitrogen. The special techniques employed in handling air-
2
sensitive materials are described elsewhere. The glassware
was oven-dried for several hours, assembled while hot, and
1
13
11
cooled in a stream of dry nitrogen gas. H, C, and B NMR
spectra were recorded on a 200 MHz multinuclear instrument.
The 11B NMR chemical shifts δ are in ppm relative to BF
:
3
2
OEt . GC analyses were carried out either on a chromatograph
equipped with a SPB-5 (0.25 µm × 30 m) capillary column or
with a chromatograph provided with a FID and a CI-100A
integrator. The following columns were used: 6 ft × 0.125 in.,
Oxidation of the methanolized solution in THF using
alkaline hydrogen peroxide afforded cyclohexanol in
quantitative yields (99% by GC), which was also iso-
lated, free of amine by simple acid-base manipulations,
in 84% yield.
1
5% Carbowax 20M on Chromosorb W, 9 ft × 0.125 in., 3%
OV-17 on Chromosorb-G, and 3 ft × 0.125 in., 10% SE 30 on
Chromosorb W. Optical rotations were measured on a pola-
rimeter. The hydride analysis studies were carried out using
the gasimeter.2
Ma ter ia ls. N,N-Diisopropyl-N-isobutylamine and its borane
adduct were prepared following the procedure reported in
preceding paper.13 All solvents were purified according to
literature procedures and stored under nitrogen. Tetrahydro-
furan and dioxane were freshly distilled from benzophenone
ketyl before use. All olefins were distilled from a small amount
Con clu sion s
The present study demonstrates the synthetic poten-
tial of the new, highly reactive amine-borane adduct
N,N-diisopropyl-N-isobutylamine-borane (2). Simple
unhindered olefins can be hydroborated to the trialkyl-
borane stage, whereas hindered olefins can be partially
hydroborated to the mono- or dialkylborane stage. The
hydroborations can be carried out conveniently in a
variety of solvents. The amine-borane adduct shows
enhanced reactivity in dioxane but low reactivity in
dichloromethane. This unusual reactivity in dichlo-
romethane may be used for selective hydroborations.
The hydroboration products were oxidized using hydro-
gen peroxide/sodium hydroxide to give the correspond-
ing alcohols in quantitative yields, without any inter-
ference by the amine. As carrier amine is basic, oxidation
in the absence of sodium hydroxide can also be carried
out. However, under these conditions, the oxidation is
incomplete. It can be made complete by the addition of
of lithium aluminum hydride and stored under nitrogen. (+)-
R-Pinene, [R]22
+45.2° (87.3% ee), and (+)-2-carene, [R]
22
D
D
+
92.0°(Camphor and Allied Products, Bombay), were used.
Hyd r obor a tion of Rep r esen ta tive Olefin s w ith 2, Gen -
er a l P r oced u r e. An oven-dried, 50 mL hydroboration flask,
provided with a septum inlet to introduce and remove com-
pounds, a stirring bar, and a stopper, was cooled to 0 °C under
nitrogen. The flask was charged with an amine-borane adduct
(5.0 mmol) and a solvent. A solution of an olefin (15.0 mmol,
6.0 M, 2.5 mL) was added at 0 °C, and the contents were
further stirred at room temperature (19-25 °C). The contents
of the reactions were always maintained in the temperature
range. Aliquots (1.0 mL) were taken out at intervals and
hydrolyzed using 3.0 M HCl-glycerol-THF (2:1:0.2) as the
hydrolysis solvent. The hydrogen evolved was measured using
a gasimeter to establish the presence of active hydride. The
11
reactions were simultaneously followed by B NMR, observing
2
0 mol % of the carrier amine to the reaction mixture
the relative ratio of an amine-borane signal and the signals
due to the hydroboration product.
Hyd r obor a tion -Oxid a tion of 1-Hexen e w ith 2 in Tet-
r a h yd r ofu r a n . An oven-dried hydroboration flask was cooled
before the oxidation. The borane carrier amine 1 can
be readily recovered from the hydroboration products
by simple acid-base manipulations, distillation, or

1
316 Organometallics, Vol. 18, No. 7, 1999
Brown et al.
d
to 0 °C under a stream of nitrogen gas. In the flask was placed
(1.1 mL, 4.5 M, 5.0 mmol) in freshly distilled THF (7.4 mL)
and undecane (7.5 mmol, GC standard). 1-Hexene (15.0 mmol,
.26 g) was added slowly during 5 min at 0 °C. The contents
were further stirred for 2 h at room temperature. The reaction
was quenched with careful addition of water. The reaction
mixture was cooled to 10 °C, and 3.0 mL of 3.0 N NaOH was
added, followed by the slow addition of 2.0 mL of 30% hydrogen
peroxide during 10 min. The contents were further stirred at
reaction) to Ipc
2
BH (6.91 g, 24 mmol) keeping the reaction
2
temperature about 50 °C. Once the initial reaction subsided,
the mixture was slowly heated to 100 °C (bath temperature),
boron trifluoride-etherate (0.06 mL, 0.5 mmol) was added, and
the mixture was stirred for 1 h at 100 °C. The liberated
R-pinene was distilled off at reduced pressure. Redistillation
from lithium aluminum hydride gave (+)-R-pinene: 5.40 g,
1
2
2
83% yield, bp 50-51 °C/17 mmHg, [R]
D
+51.34° (neat), 99.5%
ee, lit.22 [R]
22
+51.4° (neat).
D
5
0 °C for 2 h to ensure completion of oxidation. The reaction
P r ep a r a tion of [1S]-Diisoca r a n ylbor a n e, 2- Icr BH. A
d
2
mixture was cooled to room temperature, and the organic layer
was separated. The aqueous layer was saturated with potas-
sium carbonate and extracted with ether, and the combined
organic extract was washed with brine and dried over anhy-
drous magnesium sulfate. The combined yield of 1- and
50 mL round-bottomed flask provided with a septum inlet and
magnetic stirring bar was charged with 2 (3.3 mL, 15.0 mmol)
in dioxane (6.5 mL). To this was added (+)-2-carene (5.2 mL,
33.0 mmol) during 5 min. The ice bath was removed, and the
reaction mixture was kept at room temperature undisturbed
2
-hexanols was 98% (by GC using an OV-17 column). The ratio
for 15 h. Crystalline needles of Icr BH started separating out
2
of 1-hexanol:2-hexanol is 96:4.
after 20 min. The supernatant solution was decanted using a
double-ended needle. The crystalline mass was broken, washed
with n-pentane, and kept under reduced pressure to remove
Hyd r obor a tion -Oxid a tion of Cycloh exen e w ith 2 in
Tetr a h yd r ofu r a n . An oven-dried hydroboration flask was
cooled to 0 °C under a stream of nitrogen gas. In the flask
was placed 2 (1.1 mL, 4.5 M, 5.0 mmol) in freshly distilled
THF (7.4 mL). Cyclohexene (10.0 mmol, 0.82 g) was added
slowly during 5 min at 0 °C. The contents were further stirred
for 1 h at room temperature. The reaction was quenched with
careful addition of water. The reaction mixture was cooled to
d
solvent, yielding pure 2- Icr BH, 4.23 g, 98.6% yield. The solid
2
thus obtained was suspended in 15 mL of THF, and 0.8 mL
(20.0 mmol) of methanol was added slowly at 0 °C. After the
evolution of hydrogen ceased the liberated hydrogen was
vented out, and the mixture was oxidized by using 5.0 mL of
3.0 M NaOH solution and 3.0 mL of 30% hydrogen peroxide
at 30 °C for 3 h and at 50 °C for 1 h. The mixture was cooled
to room temperature, saturated with potassium carbonate, and
extracted with ether. The combined organic extract was
washed with brine and dried over anhydrous magnesium
sulfate. (-)-2-Isocaranol was isolated by distillation: bp 60-
1
0 °C, and 3.0 mL of 3.0 N NaOH was added followed by the
slow addition of 1.0 mL of 30% hydrogen peroxide. The
contents were further stirred at 50 °C for 2 h. The reaction
mixture was cooled to room temperature, and the organic layer
was separated. The aqueous layer was saturated with potas-
sium carbonate and extracted with ether. The combined
organic layer was washed with 3.0 N HCl, then with brine,
and dried over anhydrous magnesium sulfate. Evaporation of
the solvent gave essentially pure cyclohexanol, which was
further purified by passing through a small silica gel pad,
providing a yield of 1.07 g (90.3%).
2
2
19
62 °C/2 mmHg, 3.87 g (85.5%), [R]
D
-31.2° (neat) [lit. bp
50-52 °C/0.05 mm, [R]22 -31.5° (neat)].
D
P r ep a r a tion of 9-BBN. An oven-dried hydroboration flask
was cooled to 0 °C under a stream of nitrogen gas. The flask
was charged with 2 (2.2 mL, 10.0 mmol) in 1.6 mL of dioxane
at room temperature, and 1,5-cyclooctadiene (1.08 g, 10.0
mmol) was added dropwise to a well-stirred solution. The
mixture was further stirred for 3 h. The reaction was complete
within that period, as indicated by active hydride estimation.
An aliquot was taken out and oxidized with aqueous
alkaline hydrogen peroxide in THF. A few drops (0.3 mL) of
this THF solution was taken in a vial and dried with
magnesium sulfate. The 0.3 mL of dry pyridine and 0.3 mL of
N,O-bis(trimethylsilyl)acetamide (BSA) were added. The mix-
ture was heated for 10-15 min while shaking. The product
was analyzed on GC using an SE 30 column. The isomeric
distribution of 1,4- and 1,5-cyclooctanediols (29:71) was de-
termined from the integration of peaks, assuming the same
response factor for both diols.
The aqueous layer was neutralized with 3.0 N KOH solution
and extracted with ether. The combined organic extract was
washed with brine and dried over anhydrous magnesium
sulfate. GC analysis of the crude showed the presence of
cyclohexanol (2%) in addition to 1 (98%). Amine was recovered
in pure form by column chromatography using hexane:ethyl
acetate (95:5) as eluent in 86% (0.68 g) yield.
P r ep a r a t ion of Diisop in oca m p h eylb or a n e, d Ip c
BH .
2
An oven-dried hydroboration flask was cooled to 0 °C under a
stream of nitrogen gas. (+)-R-Pinene (8.52 g, 62.5 mmol, 87.3%
ee) was added with stirring to a solution of 2 (5.55 mL, 25
mmol) in dioxane (4.45 mL) over 5 min at 0 °C. The ice bath
was removed, and the solution was left undisturbed. After 30
min crystals started separating out. The mixture was left for
The dioxane solution was refluxed and the progress of
isomerization was controlled by GC analysis of the oxidized
product as described above. After 2 h, the isomerization was
complete, as indicated by the exclusive presence of 1,5-
cyclooctanediol in the oxidation product.
1
5 h at room temperature, and the supernatant solution was
decanted using a double-ended needle. The crystalline mass
was broken, washed with pentane, and kept under reduced
pressure to remove the remaining solvent, and solid Ipc
.91 g, 98% yield, was obtained.
Methanol (1.0 mL) was slowly added to a mixture of Ipc
2
BH,
6
Isola tion of 9-BBN. In a preweighted 50 mL flask equipped
with a reflux condenser and a magnetic stirring bar was placed
d
2
-
BH (5.72 g, 20.0 mmol) in tetrahydrofuran. The hydrogen
evolved was vented out, and 3.0 M sodium hydroxide (6.8 mL,
2
(2.2 mL, 10.0 mmol) in 1.6 mL of dioxane under nitrogen.
The flask was placed in a water bath (20 °C), and 1,5-
cyclooctadiene (1.08 g, 10.0 mmol) was added slowly with
stirring. The stirring continued for another 3 h at room
temperature and 2 h under reflux. After cooling the reaction
mixture to room temperature, the 9-BBN crystallized out. The
supernatant liquid was decanted using a double-ended needle;
the crystals were washed with ice cold n-pentane and left
under reduced pressure: yield 0.92 g (70%), recrystallized from
THF, mp 152 °C [lit.23 mp 153 °C].
2
0.0 mmol) was added followed slowly by hydrogen peroxide
(4.0 mL, 30%, 40.0 mmol) at 10-20 °C. The mixture was
stirred at room temperature for 1 h at 45 °C. It was cooled to
room temperature, saturated with potassium carbonate, and
extracted with ether. The combined organic extracts were dried
over anhydrous magnesium sulfate. GC analysis did not show
the presence of 1. Evaporation of the solvent afforded (-)-
isopinocampheol, which was further purified by column chro-
matography on silica gel using hexane/ethyl acetate (8:2) as
2
2
an eluant, 5.29 g, 86% yield, [R]
D
-34° (c 20, EtOH), >99%
1
6c
22
(22) Based on the maximum rotation reported for (+)-R-pinene,
ee (lit. [R]
D
-34° (c 20, EtOH)).
Liber a tion of (+)-R-P in en e fr om Ip c
7.6 mL, 75.0 mmol) was cautiously added (caution! exothermic
2
[
1
R]2
D
+51.6°: J ohnson, W. S.; Frei, B.; Gopalan, A. S. J . Org. Chem.
d
2
BH. Benzaldehyde
981, 46, 1512.
(23) Brown, H. C.; Mandal, A. K. J . Org. Chem. 1992, 57, 4970.
(

Molecular Addition Compounds. 13
Organometallics, Vol. 18, No. 7, 1999 1317
P r ep a r a tion of Disia m ylbor a n e. An oven-dried hydro-
boration flask was cooled to 0 °C under a stream of nitrogen
gas. The flask was charged with 2 (2.2 mL, 10.0 mmol) in
dioxane (5.7 mL) at 0 °C, and 2-methyl-2-butene (2.1 mL, 20.0
mmol) was slowly added to this solution. The reaction mixture
was further stirred at room temperature. The reaction was
complete within 1 h as indicated by active hydride analysis
and the presence of one peak at δ +31.1 in the 11B NMR
spectrum. The reaction mixture was oxidized using 3.0 M
NaOH (4.0 mL) and 30% hydrogen peroxide (4.0 mL). The GC
analysis of the oxidation product using an OV-17 column
revealed the quantitative formation of 3-methyl-2-butanol.
Ap p lica tion of Disia m ylbor a n e in Regioselective Hy-
d r obor a tion of Styr en e. To a solution of disiamylborane
mmol) in dioxane (5.0 mL) and n-nonane (1.78 mL, GC
standard). Cyclohexene (0.82 g, 20.0 mmol) was added slowly
at 0 °C during 5 min, and the mixture was stirred at room
temperature. The reaction was complete within 1 h, as
indicated by active hydride estimation. The reaction mixture
was oxidized using alkaline hydrogen peroxide. The aqueous
layer was saturated with potassium carbonate, and GC
analysis of the organic layer using a Carbowax 20M column
revealed a 99% yield of cyclohexanol.
Isola tion of Dicycloh exylbor a n e. Hydroboration of cy-
clohexene was carried out with 2 in 10 mmol scale in dioxane
as described above in a preweighted centrifuge flask. After the
hydroboration was complete, the reaction mixture was cen-
trifuged and the supernatant liquid was decanted using a
double-ended needle. The precipitate was washed with cold
n-pentane and kept under reduced pressure to yield 1.52 g of
dicyclohexylborane: 85% yield, free from amine, mp 102-3
°C (lit.23 mp 103-4 °C, after sublimation).
(10.0 mmol) in dioxane prepared as described above was added
styrene (1.04 g, 10.0 mmol) at room temperature, and stirring
was continued at room temperature for 1 h, by which time
the hydroboration was complete. The mixture was oxidized by
alkaline hydrogen peroxide, and GC analysis of the oxidized
product revealed the formation of 2-phenylethanol (99%) and
Ack n ow led gm en t. J .V.B.K. thanks Aldrich Chemi-
cal Co. for the financial support and Nicolaus Coperni-
cus University, Poland, for the laboratory facilities.
1
-phenylethanol (1%).
P r ep a r a tion of Dicycloh exylbor a n e. An oven-dried 50
mL hydroboration flask was cooled to 0 °C under a stream of
nitrogen gas. The flask was charged with 2 (2.2 mL, 10.0
OM980629Z