Molecular addition compounds. 15. Synthesis, hydroboration, and reduction studies of new, highly reactive tert-butyldialkylamine-borane adducts

Article abstract of DOI:10.1021/jo990379b

Two series of tert-butyldialkylamines have been prepared and examined for borane complexation. The complexing ability of each amine in the two series examined decreases in the order shown. First series: t- BuN(CH₂CH₂)₂O 1a > t-BuNEt₂ 1b > t-BuNPr(n)₂1c > t-BuN(CH₂CH₂OMe)₂ 1d >> t-BuNBu(i)₂ 1e. Second series: t-BuNBu(i)Me 2a > t-BuNPr(i)Me 2b > t- BuNBu(i)Et 2c > t-BuNBu(i)Pr(n) 2d >>t-BuNPr(i)Et 2e. The reactivity of the corresponding borane adducts toward 1-octene increases in the reverse order. The following amines form highly reactive liquid borane adducts hydroborating 1-octene in tetrahydrofuran at room temperature in less than 1 h: t- BuN(CH₂CH₂OMe)₂, t-BuNBu(i)Et, and t-BuNPr(i)Me. The limit of borane complexation among the amines examined is reached for t-BuNBu(i)2 exchanging borane neither with BMS nor with BH₃-THF. Among the various borane adducts prepared, the more promising borane adducts, t-Bu(CH₃OCH₂CH₂)₂N-BH₃ (7), t-BuMePr(i)N-BH₃ (8), and t-BuEtBu(i)N-BH₃ (9), were selected for complete hydroboration and reduction studies. Hydroboration studies with the new, highly reactive trialkylamine-borane adducts 7-9 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, in tetrahydrofuran, dioxane, tert-butyl methyl ether, n-pentane, and dichloromethane, at room temperature (22 ± 3°C) were carried out. The reactions are faster in dioxane, requiring 1-2 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 slow hydroboration. However, the more hindered olefins, α-pinene and 2,3-dimethyl-2-butene, give stable monoalkylboranes very rapidly, with further hydroboration proceeding relatively slowly. The hydroborations can also be carried out conveniently in other solvents, such as THF, tert-butyl methyl ether, and n-pentane. A significant rate retardation is observed in dichloromethane. Regioselectivity studies of 1-hexene and styrene using these amine-borane adducts show selectivities similar to that of BH₃-THF. The rates and stoichiometry of the reaction of t-BuMePr(i)N-BH₃ in tetrahydrofuran with selected organic compounds containing representative functional groups were also examined at room temperature. The reductions of esters, amides, and nitriles, which exhibit a sluggish reaction at room temperature, proceed readily under reflux conditions in tetrahydrofuran and dioxane and without solvent (at 85-90°C). The carrier amines can be recovered by simple acid-base manipulations in good yield and readily recycled to make the borane adducts.

Full text of DOI:10.1021/jo990379b

J . Org. Chem. 1999, 64, 6263-6274
6263
Molecu la r Ad d ition Com p ou n d s. 15. Syn th esis, Hyd r obor a tion , a n d
Red u ction Stu d ies of New , High ly Rea ctive
ter t-Bu tyld ia lk yla m in e-Bor a n e Ad d u cts
Herbert C. Brown,*,† J osyula V. B. Kanth,†,‡,1 Pramod V. Dalvi,†,2 and Marek Zaidlewicz*,‡,3
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 March 2, 1999
Two series of tert-butyldialkylamines have been prepared and examined for borane complexation.
The complexing ability of each amine in the two series examined decreases in the order shown.
First series: t-BuN(CH2CH2)2O 1a > t-BuNEt2 1b > t-BuNPrn21c > t-BuN(CH2CH2OMe)2 1d .
t-BuNBui 1e. Second series: t-BuNBuiMe 2a > t-BuNPriMe 2b > t-BuNBuiEt 2c > t-BuNBuiPrn
2
2d .t-BuNPriEt 2e. The reactivity of the corresponding borane adducts toward 1-octene increases
in the reverse order. The following amines form highly reactive liquid borane adducts hydroborating
1-octene in tetrahydrofuran at room temperature in less than 1 h: t-BuN(CH2CH2OMe)2,
t-BuNBuiEt, and t-BuNPriMe. The limit of borane complexation among the amines examined is
reached for t-BuNBui2 exchanging borane neither with BMS nor with BH3-THF. Among the various
borane adducts prepared, the more promising borane adducts, t-Bu(CH3OCH2CH2)2N-BH3 (7),
t-BuMePriN-BH3 (8), and t-BuEtBuiN-BH3 (9), were selected for complete hydroboration and
reduction studies. Hydroboration studies with the new, highly reactive trialkylamine-borane
adducts 7-9 and representative olefins, such as 1-hexene, styrene, â-pinene, cyclopentene,
norbornene, cyclohexene, 2-methyl-2-butene, R-pinene, and 2,3-dimethyl-2-butene, in tetrahydro-
furan, dioxane, tert-butyl methyl ether, n-pentane, and dichloromethane, at room temperature (22
( 3 °C) were carried out. The reactions are faster in dioxane, requiring 1-2 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
slow hydroboration. However, the more hindered olefins, R-pinene and 2,3-dimethyl-2-butene, give
stable monoalkylboranes very rapidly, with further hydroboration proceeding relatively slowly. The
hydroborations can also be carried out conveniently in other solvents, such as THF, tert-butyl methyl
ether, and n-pentane. A significant rate retardation is observed in dichloromethane. Regioselectivity
studies of 1-hexene and styrene using these amine-borane adducts show selectivities similar to
that of BH3-THF. The rates and stoichiometry of the reaction of t-BuMePriN-BH3 in tetrahydro-
furan with selected organic compounds containing representative functional groups were also
examined at room temperature. The reductions of esters, amides, and nitriles, which exhibit a
sluggish reaction at room temperature, proceed readily under reflux conditions in tetrahydrofuran
and dioxane and without solvent (at 85-90 °C). The carrier amines can be recovered by simple
acid-base manipulations in good yield and readily recycled to make the borane adducts.
Borane-amine adducts are important reducing agents
with a multitude of applications in organic synthesis and
industrial processes.4 They have a wide range of reac-
tivities, are soluble in various solvents including hydro-
carbons, and often show low sensitivity to moisture and
air. In contrast, their use as hydroborating agents is of
limited scope due to the formation of strong borane
complexes, rendering the reactivity toward olefins lower
than that of the adducts with ethers and sulfides.5
Recently, we6 and others7 developed a number of new,
highly reactive borane adducts with N,N-dialkylanilines,
alkyldiisopropylamines, and N-silylamines as demon-
strated by their success in hydroborating 1-octene in
tetrahydrofuran at room temperature in less than 1 h.
For the first time, aliphatic amines have been shown to
be useful borane carriers for hydroboration. Their poten-
(5) (a) Lane, C. F. Aldrichim. Acta 1973, 6, 21. (b) Kollonitsch, J . J .
Am. Chem. Soc. 1961, 83, 1515. (c) Burg, A. B.; Schlesinger, H. I. J .
Am. Chem. Soc. 1937, 59, 780. (d) Long, L. H.; Mellor, W. J . A
Comprehensive Treatise on Inorganic and Theoretical Chemistry;
Longman: London, 1981; Supplement Vol. 5, Part B1, p 1. (e) Mueller,
A. Gmelin Handbook of Inorganic and Organometallic Chemistry;
Springer: Berlin, 1992, 4th Supplement, Vol. 3, p 1. (f) Brown, H. C.;
Murray, L. T. Inorg. Chem. 1984, 23, 2746.
(6) (a) Brown, H. C.; Zaidlewicz, M.; Dalvi, P. V. Organometallics
1998, 17, 4202. (b) Brown, H. C.; Kanth, J . V. B.; Zaidlewicz, M. J .
Org. Chem. 1998, 63, 5154. (c) Brown, H. C.; Zaidlewicz, M.; Dalvi, P.
V.; Narasimhan, S.; Mukhopadyay, A. Organometallics 1999, 18, 1305.
(d) Brown, H. C.; Kanth, J . V. B.; Zaidlewicz, M. Organometallics 1999,
18, 1310.
† Purdue University.
‡ Nicolaus Copernicus University.
(1) Postdoctoral Associate with support from the Aldrich Chemical
Co.
(2) Postdoctoral Associate with support from the Borane Research
Fund.
(3) Visiting Professor from Nicolaus Copernicus University, Torun,
Poland, supported by the Borane Research Fund.
(4) (a) Lane, C. F. Aldrichim. Acta 1973, 6, 51. (b) Pelter, A.; Smith,
K.; Brown, H. C. Borane Reagents; Academic Press: London, 1988. (c)
Follet, M. Chem. Ind. 1986, 123. (d) Ren, O.; Meatres, C. F. Biocon-
jugate Chem. 1992, 3, 563.
(7) (a) Soderquist, J . A.; Medina, J . R.; Huertas, R. Tetrahedron Lett.
1998, 39, 6119. (b) Soderquist, J . A.; Huertas, R.; Medina, J . R.
Tetrahedron Lett. 1998, 39, 6123.
10.1021/jo990379b CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/30/1999

6264 J . Org. Chem., Vol. 64, No. 17, 1999
Ta ble 1. Bor a n e Ad d u cts w ith t-Bu NR2
Brown et al.
amine-BH3
exchange,a
%
hydroboration of 1-octenee
amine
BH3-SMe2
BH3-THF
stateb (mp, °C)
[BH3]c M
11B NMRd (δ)
in THFf
neat
t-BuN(CH2CH2)2O (1a )
t-BuNEt2 (1b)
100
85
70
50
0
100
100
100
95
-16.88
-14.89
-14.13
-14.26
6 h
6 h
3 h
t-BuNPrn2 (1c)
t-BuN(CH2CH2OMe)2 (1d )
liquid
4.5
30 min
1 h
t-BuNBui2 (1e)
0
a
Amine mixed with BH3-SMe2 or 1 M BH3-THF in 1:1 molar ratio at room temperature and analyzed by 11B NMR at equilibrium.
At 0 °C. c Estimated by hydrolysis in 2.00 M HCl-glycerol-water (2:1:1) and measuring the hydrogen evolved. From the exchange
b
d
with BH3-SMe2. e 5% excess of 1-octene, room temperature. f 3.00 M solution of 1-octene and 1.00 M in BH3.
Ta ble 2. Bor a n e Ad d u cts w ith t-Bu NRR′
amine-BH3
exchange,a
%
hydroboration of 1-octenee
amine
BH3/SMe2
BH3/THF
stateb (mp, °C)
[BH3],c M
11B NMRd (δ)
in THFf
neat
t-BuNBuiMe (2a )
t-BuNPriMe (2b)
t-BuNBuiEt (2c)
t-BuNBuiPrn (2d )
1,2,2,6,6-penta-
methylpiperidine
t-BuNPriEt (2e)
73
50
33
24
8
100
90
73
71
51
-14.15
-16.23
-14.71
-14.10
-16.04
20 h
liquid
liquid
5.3
4.4
30 min
20 min
20 min
20 min
3 h
2 h
(78-80)
0
32
liquid
5f3
-14.14g
15 min
1 h
a
Amine mixed with BH3-SMe2 or 1.00 M BH3-THF in 1:1 molar ratio at room temperature and analyzed by 11B NMR at equilibrium.
At 0 °C. c Estimated by hydrolysis in 2.00 M HCl-glycerol-water (2:1:1) and measuring the hydrogen evolved. From the exchange
b
d
with BH3-SMe2. e 5% excess of 1-octene, room temperature. f 3.00 M solution of 1-octene and 1.00 M in BH3. From the exchange with
g
BH3-THF, since no exchange occurred with BMS.
tial advantages over traditional carriers, such as tet-
rahydrofuran or dimethyl sulfide, for large-scale appli-
cations have been pointed out. We also demonstrated that
borane complexation depends strongly on the steric
requirements of the amine. The results obtained with
alkylisopropylamines prompted us to examine tert-bu-
tyldialkylamines, with the objective of developing borane
adducts meeting the following requirements: (1) hy-
droboration of 1-octene in tetrahydrofuran at room tem-
perature in less than 1 h and (2) liquid adduct of high
borane concentration, stable at room temperature, and
soluble in representative solvents.
Alkyl-tert-butylisobutylamines 1e and 2a ,c,d were
prepared from a common intermediate, t-BuNHBui, 4,
as shown in eq 3. The alkylation of tert-butylamine with
isobutyl bromide is very slow. Only 3% of 4 was formed
after 24 h at reflux. Fortunately, a small amount of
tetraalkylammonium iodide dissolved in adiponitrile
markedly accelerates the reaction, and 4 is obtained in
good yield in a reasonable time (eq 3).
Resu lts a n d Discu ssion
Two series of amines, 1a -e and 2a -e, with increasing
steric bulk of the alkyl groups within each series were
selected for the study. 1,2,2,6,6-Pentamethylpiperidine
was also included for comparison.
t-BuNR2
1a R ) -CH2CH2OCH2CH2-
1bR ) Et
t-BuNRR1
2a R ) Me, R1 ) Bui
2bR ) Me, R1 ) Pri
2cR ) Et, R1 ) Bui
2d R ) Prn, R1 ) Bui
2eR ) Et, R1 ) Pri
1cR ) Prn
Introduction of the second isobutyl group on 4 by direct
alkylation is difficult. No product was obtained after
refluxing 4 with isobutyl iodide for 24 h. Consequently,
1e was prepared by acylation-reduction (eq 3). Similarly,
alkyl-tert-butylisopropylamines 2b,e were prepared from
a common intermediate, t-BuNHPri, 5, according to eq
4.
1d R ) -CH2CH2OMe
1eR ) Bui
Syn th esis of Am in es. The amines 1a -d having two
primary unbranched alkyl groups were prepared by the
alkylation of tert-butylamine, following routine proce-
dures (eq 1).
The amino ether 1d was obtained by methylation of
tert-butyldiethanolamine with dimethyl sulfate in the
presence of a phase transfer catalyst (eq 2).
Although 5 is commercially available, it is costly. The
synthesis shown in eq 4 is simple, employing low-cost
starting materials. Alternatively, 5 can be prepared by

Molecular Addition Compounds
J . Org. Chem., Vol. 64, No. 17, 1999 6265
the alkylation of tert-butylamine with isopropyl bromide
in the presence of tetraalkylammonium iodide and by
other methods.8,9
of a solution in diethyl ether shows only one signal
(quartet) at δ -15.8. In deuterated chloroform, a mixture
of free amine and the adduct (40:60) was observed by 1H
NMR.
Bor a n e-Am in e Ad d u cts. The complexing ability of
amines toward borane was tested by the exchange with
BMS (borane-methyl sulfide) and BH3-THF (borane-
tetrahydrofuran) mixed in a 1:1 molar ratio. The amount
of borane taken by an amine in the equilibrium was
determined by 11B NMR and is shown in Tables 1 and 2.
Values for the exchange with BH3-THF, a 1 M solution,
should be considered qualitative since THF is in consid-
erable excess. As revealed by the exchange experiments,
dialkyl-tert-butylamines 1a -c having two primary un-
branched alkyl groups, take more than 50% of borane
from BMS and 100% from BH3-THF (Table 1). The lower
complexing ability of t-BuNEt2, as compared to N-tert-
butylmorpholine suggested that substituting 2-methoxy-
ethyl groups for ethyl groups might result in weaker
borane complexation. Previously, it was also observed
that diisopropyl(2-methoxyethyl)amine forms a weaker
adduct with borane than did diisopropylethylamine.7
Indeed, the amino ether 1d takes only 50% of borane
from BMS. The adduct hydroborates 1-octene in THF at
room temperature in 30 min and under neat conditions
in 1 h. It is a liquid, 4.5 M in borane, meeting well our
requirements. The reactivity of borane adducts with
1a -d toward 1-octene increases in the following order:
Deta iled Hyd r obor a tion Stu d ies. The above initial
studies clearly demonstrated that borane adducts of
amines 1d , 2b, and 2c are more reactive toward hy-
droboration of 1-octene. Encouraged by these observa-
tions and in order to establish the complete potential of
these new borane adducts, detailed hydroboration studies
of the borane adducts of tert-butylbis(2-methoxyethyl)-
amine (1d ), tert-butyl-N-methyl-N-isopropylamine (2b),
and tert-butyl-N-ethyl-N-isobutylamine (2c) were under-
taken. The borane adducts were prepared by passing a
slight excess of diborane gas into the neat amine at 0-5
°C (eq 5). The concentration of the adsorbed borane was
established by hydrolysis of an aliquot, using 2.00 M
HCl-glycerol-water mixture, measuring the hydrogen
evolved.
The adducts thus obtained, maintained under nitrogen,
are stable at room temperature indefinitely. The stability
of solutions of these adducts in THF, tert-butyl methyl
ether, and dioxane were also studied. Solutions of the
adduct in solvents (2.00 M in BH3) were sealed in NMR
tubes and monitored using 11B NMR at intervals. The
adducts 8 and 9 did not show any new peaks in the 11B
NMR spectra other than that given by the adducts during
6 months of observation. In THF, the adduct 8 developed
small amounts (2-4%) of solvent-cleaved products after
two months, but no further increase in this solvent-
cleaved product was noted in the next 4 months.
H yd r ob or a t ion of Olefin s in Tet r a h yd r ofu r a n .
Hydroboration of representative mono-, di-, tri-, and
tetrasubstituted olefins with the adducts 7, 8, and 9 was
conducted in THF at room temperature. To establish the
rate and stoichiometry, the reactions were carried out
in solutions that were 0.50 M in BH3 and 1.50 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 ( 3 °C). The progress of the hydroboration was
conveniently followed by taking out aliquots at intervals,
hydrolyzing with 3.00 M HCl-glycerol-THF (2:1:0.2),
and measuring the hydrogen evolved. The reactions were
also followed by 11B NMR, monitoring a decreasing
amine-borane signal and an increasing alkylborane
signal.
1a -BH3 ≈ 1b-BH3 < 1c-BH3 , 1d -BH3
Higher reactivity of the borane adduct with t-BuNPrn
,
2
as compared to t-BuNEt2, indicates the sensitivity of the
systems to even minor differences in the steric require-
ments of the amines.
In the series of alkyl-tert-butylisobutylamines, the
methyl derivative 2a takes 73% of borane from BMS,
giving a relatively strong adduct, which hydroborates
1-octene only very slowly (Table 2). The ethyl and
n-propyl derivatives 2c,d give highly reactive adducts,
meeting our requirements. The limit of borane complex-
ation is reached with t-BuNBui , 1e. This amine does not
2
only fail to take borane from BMS but also fails to take
it from BH3-THF! This is the most hindered amine for
borane complexation among the amines examined in the
present study.
Similarly, as observed for the dialkylisopropylamines,
the substitution of the isopropyl group for the isobutyl
group in the series decreases the complexing ability of
amines. Thus, the methyl derivative 2b takes 50% of
borane from BMS as compared to 73% for 2a . The adduct
of 2b is a liquid, 5.3 M, in borane, hydroborating 1-octene
in THF at room temperature in less than 1 h. The ethyl
derivative 2e forms a weaker adduct, losing borane upon
storage.
Hydroborations are relatively faster with the adduct
7, which hydroborated simple unhindered olefins, such
as 1-hexene, styrene, and â-pinene to the trialkylborane
stage within 1 h. The other adducts (8 and 9) required
∼2 h for hydroboration to the trialkylborane stage.
Hydrolysis of aliquots of the reaction mixture does not
evolve any hydrogen, confirming complete utilization of
borane. The moderately hindered 2-methyl-2-butene gave
disiamylborane after 1 h (11B NMR, δ ppm, +31.1), with
further hydroboration slower. Cyclohexene forms dicy-
clohexylborane rapidly in ∼1 h (11B NMR, δ, ppm, +51.5
after methanolysis), and 2.84 hydride equivalents are
It was interesting to examine 1,2,2,6,6-pentamethylpi-
peridine, 6, in comparison with the N-methyl derivatives
2a and 2b. The exchange with BMS and BH3-THF
reveals the complexing order 2a > 2b > 6, as might be
expected considering the increasing steric bulk of the
alkyl groups attached to the nitrogen atom. Despite its
high steric hindrance, 6 takes as much as 51% of borane
from BH3-THF. Regrettably, for the purpose of this
study its borane adduct is a solid. The 11B NMR spectrum
(8) Stowell, J . C.; Padegimas, S. J . Synthesis 1974, 127.
(9) Schwartz, M. A.; Hu, X. Tetrahedron Lett. 1992, 1689.

6266 J . Org. Chem., Vol. 64, No. 17, 1999
Brown et al.
Ta ble 3. Hyd r obor a tion of Rep r esen ta tive Olefin s w ith t-Bu (CH3OCH2CH2)2N-BH3 in Selected Solven ts a t Room
Tem p er a tu r ea
dioxane
hydrides
time (h) utilized
THF
hydrides
time (h) utilized
tert-butyl methyl ether
n-pentane
hydrides
time (h) utilized
dichloromethane
hydrides
hydrides
time (h) utilized
olefin
1-hexene
time (h)
utilized
1.00
1.00
1.00
1.00
1.00
3.00
3.00
3.00
3.00
3.00
1.00
1.00
1.00
1.50
2.00
3.00
3.00
3.00
3.00
3.00
1.50
1.00
1.50
1.00
2.00
1.00
2.50
1.00
2.50
1.00
24
1.00
24
0.91
24
0.40
24
0.75
3.00
2.78
3.00
2.90
3.00
2.74
3.00
2.71
3.00
2.62
2.85
2.00
2.93
2.00
1.88
1.00
1.69
1.00
1.00
1.00
1.00
3.00
3.00
3.00
18
1.00
18
1.00
18
15
15
18
24
3.00
0.53
3.00
0.46
3.00
styrene
â-pinene
cyclopentene
norbornene
1.50
1.00
2.00
1.00
24
0.83
24
2.00
24
0.41
24
0.83
3.00
2.85
3.00
2.75
2.95
2.00
2.93
2.00
1.57
1.00
1.70
1.00
3.00
3.00
2.95
2.93
cyclohexene
2-methyl-2-butene
R-pinene
24
0.66
24
0.58
24
0.33
24
0.33
2.95
2.00
2.95
2.00
2.00
1.00
1.80
1.00
24
1.16
24
0.83
24
0.40
24
0.66
2.84
2.00
2.93
2.00
1.89
1.00
1.73
1.00
48
24
24
1.78
1.18
1.70
2,3-dimethyl-2-butene
a
Reactions were carried out using amine-borane 7 (5 mmol) and an olefin (15 mmol) in a total volume of 10 mL solution.
Ta ble 4. Hyd r obor a tion of Rep r esen ta tive Olefin s t-Bu MeP r iN-BH3 in Selected Solven ts a t Room Tem p er a tu r ea
dioxane
hydrides
time (h) utilized
THF
hydrides
time (h) utilized
tert-butyl methyl ether
n-pentane
hydrides
time (h) utilized
dichloromethane
hydrides
hydrides
time (h) utilized
olefin
1-hexene
time (h)
utilized
1.50
1.00
2.00
1.00
2.00
1.00
2.00
1.00
2.00
1.00
3.00
2.93
3.00
2.88
3.00
2.85
3.00
2.88
3.00
2.85
2.95
2.00
2.95
2.00
2.00
1.00
1.64
1.00
2.00
1.00
2.00
1.00
3.00
1.00
3.00
1.00
3.00
1.00
3.00
2.86
3.00
2.86
3.00
2.85
3.00
2.78
3.00
2.76
2.88
2.00
2.85
2.00
1.78
1.00
1.38
1.00
2.00
1.00
2.00
1.00
2.50
1.00
3.00
1.00
3.00
1.00
24
1.25
24
1.16
24
0.40
24
0.91
3.00
2.88
3.00
2.90
3.00
2.78
3.00
2.76
3.00
2.73
2.90
2.00
2.88
2.00
1.59
1.00
1.47
1.00
2.00
1.00
2.00
1.00
2.00
1.00
2.00
1.00
2.50
1.00
3.00
2.37
3.00
2.03
3.00
2.40
3.00
2.40
3.00
2.28
2.95
2.00
2.95
2.00
1.65
1.00
1.57
1.00
1.00
48
2.70
1.85
1.88
styrene
48
48
48
48
48
48
48
48
â-pinene
2.00
2.39
2.47
2.38
2.50
1.55
1.65
cyclopentene
norbornene
cyclohexene
2-methyl-2-butene
R-pinene
24
0.91
24
0.91
24
0.58
24
0.50
24
0.91
24
1.00
24
0.50
24
0.58
24
1.16
24
3.66
24
0.66
24
0.91
2,3-dimethyl-2-butene
a
Reactions were carried out using amine-borane 8 (5 mmol) and an olefin (15 mmol) in a total volume of 10 mL solution.
utilized in 24 h (11B NMR, δ, ppm, +81.0 after metha-
nolysis corresponding to the formation of tricyclohexyl-
borane). However, the more hindered R-pinene consumes
one hydride rapidly in 30 min, but then the reaction
continues only slowly, with the hydride utilization in-
creasing to 1.89, 1.78, and 1.71 in 24 h for the adducts 7,
8, & 9, respectively, at room temperature, indicating
incomplete formation of Ipc2BH. This is also confirmed
by 11B NMR, which gave two peaks after methanolysis
at +32 (minor, due to IpcB(OMe)2) and +53 (major, due
to Ipc2BOMe). Further substitution on the olefin, i.e., the
tetrasubstituted 2,3-dimethyl-2-butene, results in further
lowering of the hydride uptake. Here also, addition of the
first hydride is very fast, giving thexylborane (11B NMR,
δ ppm, +24). The olefin/BH3 ratio then rises to 1.73, 1.38,
and 1.69 after 24 h for the adducts 7, 8, and 9, respec-
tively, at room temperature (11B NMR δ ppm +24 and
+81, after methanolysis +31 and +53). The order of
reactivity of these adducts toward representative olefins
in THF is 7 > 9 > 8 (Tables 3-5).
in solvents, such as dioxane, tert-butyl methyl ether,
n-pentane, and dichloromethane. In dioxane, the adducts
showed an enhanced reactivity when compared to their
solutions in tetrahydrofuran. Thus, in dioxane 7 and 9
hydroborate unhindered mono- and disubstituted olefins
to the corresponding trialkylborane stage within 1 h.
Enhanced reactivity is also observed for hindered olefins.
For example, R-pinene is cleanly hydroborated to the Ipc2-
BH stage. This is also confirmed by 11B NMR observation,
which reveals the exclusive presence of Ipc2BOMe after
methanolysis (δ ppm +53). The reactivity of the adduct
8 toward representative olefins was slightly lower. Thus
the adduct 8 required 2 h to hydroborate simple unhin-
dered olefins, such as 1-hexene, styrene, and cyclopen-
tene, to the trialkylborane stage. However, in the case
of hindered R-pinene, the adduct cleanly hydroborated
to the Ipc2BH stage. In tert-butyl methyl ether and
n-pentane the reactivity of the borane-amine adducts
7-9 is similar to that observed in THF. In dichlo-
romethane, a remarkable retardation of the rates of
hydroboration is observed. Only with the adduct 7 was
the hydroboration of simple unhindered olefins is com-
Hyd r obor a tion of Olefin s in Oth er Solven ts. Hy-
droborations with the adducts 7-9 were also conducted

Molecular Addition Compounds
J . Org. Chem., Vol. 64, No. 17, 1999 6267
Ta ble 5. Hyd r obor a tion of Rep r esen ta tive Olefin s w ith t-Bu EtBu iN-BH3 in Selected Solven ts a t Room Tem p er a tu r ea
dioxane
hydrides
time (h) utilized
THF
hydrides
time (h) utilized
tert-butyl methyl ether
n-pentane
hydrides
time (h) utilized
dichloromethane
hydrides
hydrides
time (h) utilized
olefin
1-hexene
time (h)
1.00
utilized
1.00
1.00
1.00
1.00
1.00
3.00
3.00
3.00
3.00
3.00
2.00
1.00
2.00
1.00
3.00
1.00
3.00
1.00
3.00
1.00
3.00
2.95
3.00
2.86
3.00
2.83
3.00
2.85
3.00
2.74
2.84
2.00
2.88
2.00
1.71
1.00
1.69
1.00
3.00
1.00
1.00
3.00
3.00
48
48
48
48
48
48
48
48
48
1.91
1.85
1.97
2.69
2.74
2.80
2.87
1.66
1.71
styrene
1.00
3.00
â-pinene
1.50
1.00
2.00
1.00
2.00
1.00
24
0.91
24
0.91
24
3.00
2.93
3.00
2.83
3.00
2.83
2.95
2.00
2.88
2.00
1.59
1.00
1.47
1.00
1.50
1.00
2.00
1.00
2.50
1.00
24
0.91
24
2.83
24
0.33
24
0.50
3.00
2.76
3.00
2.52
3.00
2.40
2.92
2.00
2.93
2.00
1.65
1.00
1.57
1.00
cyclopentene
norbornene
cyclohexene
2-methyl-2-butene
R-pinene
24
0.58
24
0.58
24
0.33
24
0.33
2.93
2.00
2.95
2.00
2.00
1.00
1.74
1.00
24
1.16
24
1.16
24
0.33
24
0.33
0.33
24
0.66
2,3-dimethyl-2-butene
a
Reactions were carried out using amine-borane 9 (5 mmol) and an olefin (15 mmol) in a total volume of 10 mL solution.
plete in 18 h, whereas, with the adducts 8 and 9, the
hydroborations were not complete even after 48 h at room
temperature and the 11B NMR studies showed the
presence of starting amine-borane. This unusual rate
retardation may be due to interaction of the solvent,
dichloromethane, with the amine-borane, as reported
earlier.7d
nipulations in 82% yield and can be used again for the
preparation of borane adducts.
Summarizing all the solvents, the following order of
reactivity with change of solvent in the hydroboration of
representative olefins with 7-9 was noted: dioxane >
tetrahydrofuran ≈ tert-butyl methyl ether ≈ n-pentane
. dichloromethane. Tables 3-5 summarize the results
of these hydroboration studies with the adducts 7-9 in
various solvents.
Regioselectivity of Hyd r obor a tion . Regioselectivity
studies for 1-hexene and styrene with 7-9 were carried
out in THF. 1-Hexene and styrene were hydroborated
using 1 equiv of amine-borane for 3 equiv of an olefin.
All the reactions were followed by 11B NMR. The inter-
mediate organoboranes were oxidized with H2O2/NaOH,
and the product alcohols were analyzed by GC. The
regioselectivities of hydroboration of 1-hexene and sty-
rene with 7-9 are similar to those reported for BH3-
THF.10 Thus, the hydroboration of 1-hexene formed the
1- and 2-hexanols in a ratio of 96:4. Similarly, with
styrene, 1- and 2-phenylethanols were formed in a ratio
of 85:15.
Similar hydroborations were also carried out with
borane adducts 7 and 9, and the product cyclohexanol
was isolated in 92% and 90.5% yields, respectively. Since
the basic carrier amine was present in the reaction
mixture after hydroboration, oxidation of the organobo-
rane with hydrogen peroxide was also examined without
the usual addition of sodium hydroxide. The oxidation
was instantaneous; however, the yield of cyclohexanol
was slightly lower (91% by GC). In the case of styrene,
the yield of 1- and 2-phenylethanols was even less (85%
by GC) and the isomeric ratio was 79:21. Apparently, the
oxidation is not complete under these conditions. It was
made complete by the addition of 20 mol % excess carrier
amine after hydroboration was complete. The hydrobo-
ration can be conveniently carried out in a variety of
solvents. However, for water immiscible solvents, such
as n-pentane, ethyl ether, and tert-butyl methyl ether,
either ethanol or THF should be added to facilitate
oxidation with hydrogen peroxide.
Selective Red u ction s
Most of the literature reported studies on reducing
properties of known amine-borane adducts are limited
to high-temperature reductions and reductions under
acidic conditions.4a,5f The amine-boranes reported in the
literature so far fail to reduce ketones at room temper-
ature. However, the presence of Lewis acids such as BF3‚
OEt2 or oxazaborolidines facilitates the reduction of
ketones with amine-boranes, such as N,N-diethyl-
aniline-borane at room temperature.4a,11-14 On the other
Hyd r obor a tion -Oxid a tion of Olefin s. To further
establish the synthetic applicability of these new highly
reactive amine-borane adducts, hydroboration-oxida-
tion of olefins was also studied. Hydroboration-oxidation
of cyclohexene with 8 in THF gave cyclohexanol in
quantitative yields (96% by GC, 91% isolated, eq 7). The
carrier amine (2b) was recovered using acid-base ma-
(11) Brown, H. C.; Keblys, K. A. J . Am. Chem. Soc. 1963, 86, 1971.
(12) Periasamy, M.; Kanth, J . V. B.; Reddy, C. K. J . Chem. Soc.,
Perkin Trans. 1 1995, 427.
(13) Salunkhe, A. M.; Burkhardt, E. R. Tetrahedron Lett. 1997, 38,
1523.
(10) Brown, H. C. Hydroboration; Benjamin: New York, 1962.

6268 J . Org. Chem., Vol. 64, No. 17, 1999
Brown et al.
Ta ble 7. Rea ction of t-Bu MeP r iN-BH3 w ith
Rep r esen ta tive Ald eh yd es a n d Keton es a t a Mola r Ra tio
of 1.33:1 in THF a t Room Tem p er a tu r e
Ta ble 6. Rea ction of t-Bu MeP r iN-BH3 w ith
Rep r esen ta tive Alcoh ols a t a Mola r Ra tio of 1.33:1 in
THF a t Room Tem p er a tu r e
t-BuMePriN-BH3
t-BuMePriN-BH3
hydrogen
equiv
evolved
hydride
equiv
used
hydride equiv
used for
reduction
compounda
time (h)
hydride equiv for reduction
time
(min)
caproaldehyde
benzaldehyde
2-hexanone
1.00
0.50
1.00
0.50
1.00
2.50
0.50
3.00
6.00
18
1.00
1.00
1.00
0.51
0.77
1.00
0.03
0.17
0.36
0.93
1.00
compounda
benzyl alcohol
1-butanol
2-pentanol
2-methyl-
2-butanol
phenol
5
5
10
15
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
0.00
0.00
0.00
0.00
acetophenone
benzophenone
30
1.00
1.00
0.00
a
6.25 mmol of compound was added to 8.3 mmol of amine-
borane (25 mmol of hydride) in 25 mL of solution (0.25 M in
compound and 1.00 M in hydride).
24
a
6.25 mmol of compound was added to 8.3 mmol of amine-
borane (25 mmol of hydride) in 25 mL of solution 0.25 M in
compound and 1.00 M in hydride.
hand, borane reagents have been proven to be reagents
of choice for many organic functional group reductions.
To establish further the synthetic potential of the new,
highly reactive amine-boranes, reduction studies of the
representative organic functional groups at room tem-
perature was undertaken. For these detailed studies,
from the three adducts, tert-butyl-N-methyl-N-isopropyl-
amineborane (8), which contains the higher percentage
of borane, was selected.
Hindered tertiary alcohols gave only dialkoxyborane (11B
NMR, +26, doublet).
Ald eh yd es a n d Keton es. The aldehydes and ketones
examined all consumed one hydride, indicating reduction
to the alcohol stage. Caproaldehyde, benzaldehyde, and
2-hexanone were reduced rapidly within 1 h. In the case
of acetophenone and benzophenone the reactions were
slower, which may be due to the combined steric and
electronic effects exerted by the phenyl group. The results
are summarized in Table 7.
For better synthetic utility, reductions were also tried
using 2 equiv of compound for 1 equiv of amine-borane.
However, under these molarity conditions the reactions
require more time to go to completion than observed
above. For example, using adduct 8, benzaldehyde took
2 h for complete reaction and acetophenone 18 h. The
reduction of benzaldehyde with 8 under these conditions
was carried out on a preparative scale and the benzyl
alcohol was isolated in 80% yield, while the amine was
recovered in 89% yield. Similarly, the reduction of
acetophenone gave 1-phenylethanol in 91% yield, and
tert-butyl-N-methyl-N-isopropylamine was recovered in
86% yield.
Ca r boxylic Acid s, An h yd r id es, a n d Acid Ch lo-
r id es. The reaction with caproic acid is very fast, whereas
the reaction with benzoic acid is somewhat slower. Both
reactions consume ∼3 hydride equiv, one for hydrogen
evolution and two for the reduction to the alcohol stage.
11B NMR studies for the reduction of caproic acid with 8
shows a peak at +18.5 and traces of unreacted amine-
borane are also indicated. Among the other acyl deriva-
tives, only acetic anhydride was reduced to the alcohol
stage, taking 3.8 hydride equiv from 8 out of the expected
4 for complete reduction.16 The 11B NMR analysis shows
trialkoxyborane (+18.1, singlet) as a major peak. The
other anhydrides such as succinic anhydride and phthalic
anhydride formed a precipitate, which did not dissolve
even after 48 h. Hydride analysis revealed very little
hydride uptake. The 11B NMR of the THF solution
showed only the presence of amine-borane in solution.
Hydrolysis with water and the usual workup of the
reaction mixture gives unreacted anhydride in major
amounts. Under the standard conditions, both the ali-
phatic and aromatic acid chlorides, caproyl chloride and
Ra te a n d Stoich iom etr ic Stu d ies. The procedure
adopted was to add 6.25 mmol of the organic compound
to 8.3 mmol of amine-borane in sufficient THF to give
25 mL of solution. This makes the reaction mixture 0.33
M in “BH3” (1.00 M hydride) and 0.25 M in compound.
The compound was added at 0 °C and stirred further at
room temperature (contents maintained at room tem-
perature, ∼20 °C). Aliquots are removed at appropriate
intervals and analyzed for residual hydride by hydrolysis
using glycerol-3.00 N HCl-THF (1:1:0.2) and measuring
the hydrogen evolved. This establishes both the rate and
the stoichiometry of the reaction. The reactions are also
cross-checked either by 11B NMR analysis or GC analysis.
Alcoh ols. Alcohols reacted with 8 rapidly and liber-
ated hydrogen quantitatively. No further reaction was
observed. Table 6 shows the reactivity of various alcohols
with amine-boranes. The rate of hydrogen evolution for
the alcohols decreases in the order primary > secondary
> tertiary. This is in agreement with the usual inter-
pretation that the acidity of the hydroxylic hydrogen in
these alcohols decreases in this order.15 However, the
slow reactivity of phenol may be attributed to the weaker
basic character of the oxygen atom which may oppose the
formation of a prior addition complex (eq 8).
To further understand the reactivity of these alcohols
toward amine-boranes, another set of experiments was
carried out by using 3 equiv of alcohol for 1 equiv of
amine-borane. Reaction of 8 with 3 equiv of simple
unhindered hydroxy compounds, such as 1-butanol and
benzyl alcohol, was very fast and gave trialkoxyborane
(11B NMR, +18.2, singlet). Moderately hindered 2-pen-
tanol took a relatively long time to react completely.
(14) Periasamy, M.; Kanth, J . V. B.; Prasad, A. S. B. Tetrahedron
1994, 50, 6411.
(15) House, H. O. Modern Synthetic Methods; Benjamin Inc.: New
York, 1965; Chapter 7.
(16) Brown, H. C.; Heim, P.; Yoon, N. M. J . Am. Chem. Soc. 1970,
92, 1637.

Molecular Addition Compounds
J . Org. Chem., Vol. 64, No. 17, 1999 6269
Ta ble 8. Rea ction of t-Bu MeP r iN-BH3 w ith
Rep r esen ta tive Ca r boxylic Acid a n d Acyl Der iva tives a t
a Mola r Ra tio of 1.33:1 in THF a t Room Tem p er a tu r e
Ta ble 10. Rea ction of t-Bu MeP r iN-BH3 w ith
Rep r esen ta tive Am in es, Im in es, a n d Am id es a t a Mola r
Ra tio of 1.33:1 in THF a t Room Tem p er a tu r e
t-BuMePriN-BH3
t-BuMePriN-BH3
hydrogen hydride hydride
hydrogen hydride hydride
equiv
evolved
equiv
used
equiv for
reduction
time
(h)
equiv
evolved
equiv
used
equiv for
reduction
compounda
caproic acid
time (h)
1.50
0.25
6.00
0.25
2.00
6.00
24
compounda
n-hexylamine
1.00
1.00
1.00
0.00
0.00
0.00
0.00
3.00
1.02
3.00
0.55
2.21
3.34
3.80
2.00
0.02
2.00
0.55
2.21
3.34
3.80
0.50
1.00
24
0.03
0.08
0.11
0.00
0.00
0.00
0.00
0.00
0.00
1.32
1.35
1.35
1.35
1.35
1.14
1.19
1.31
1.31
1.31
1.31
0.61
0.68
0.85
0.85
0.85
0.85
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.03
0.08
0.11
0.89
1.00
0.41
0.79
0.92
1.00
1.45
1.65
2.22
2.25
2.25
1.15
1.21
1.56
2.04
2.32
2.40
0.64
0.74
1.54
1.99
2.22
2.45
0.26
1.01
2.00
0.15
0.21
0.85
1.40
2.00
0.00
0.08
0.11
0.89
1.00
0.41
0.79
0.92
1.00
0.13
0.30
0.87
0.90
0.90
0.01
0.02
0.25
0.73
1.01
1.09
0.04
0.06
0.69
1.14
1.37
1.60
0.26
1.01
2.00
0.15
0.21
0.85
1.40
2.00
benzoic acid
acetic anhydride
N-butylbenzylimine
N-phenylbenzylimine
0.50
1.00
0.50
2.00
4.00
8.00
0.50
1.00
18
24
48
0.50
1.00
4.00
18
succinic anhydride precipitate
formed
phthalic anhydride precipitate
formed
caproyl chloride
benzoyl chloride
caproamide
benzamide
24
24
0.00
0.00
0.26
0.22
0.26
0.22
a
6.25 mmol of compound was added to 8.3 mmol of amine-
borane (25 mmol of hydride) in 25 mL of solution 0.25 M in
compound and 1.00 M in hydride.
Ta ble 9. Rea ction of t-Bu MeP r iN-BH3 w ith
Rep r esen ta tive Ester s a t a Mola r Ra tio of 1.33:1 in THF
a t Room Tem p er a tu r e
36
72
N-methylbenzamide
0.50
1.00
4.00
8.00
24
t-BuMePriN-BH3
hydride equiv
for reduction
compounda
time (h)
48
ethyl butyrate
0.50
2.00
4.00
24
0.03
0.13
0.21
0.33
0.53
0.00
0.11
0.23
0.42
0.61
0.64
0.03
0.03
0.03
0.06
0.12
N,N-dimethylcaproamide 0.50
1.00
3.00
0.50
1.00
4.00
8.00
N,N-dimethylbenzamide
72
methyl caproate
methyl benzoate
0.50
2.00
8.00
24
24
48
96
a
6.25 mmol of compound was added to 8.3 mmol of amine-
borane (25 mmol of hydride) in 25 mL of solution 0.25 M in
compound and 1.00 M in hydride.
0.50
1.00
2.00
24
Primary amides are reduced very slowly, exhibiting
only about 50% reduction even after long hours. The
reactions evolve hydrogen (1.3 equiv) rapidly, with
further reduction slow, though the presence of unreacted
48
a
6.25 mmol of compound was added to 8.3 mmol of amine-
borane (25 mmol of hydride) in 25 mL of solution 0.25 M in
compound and 1.00 M in hydride.
amine-borane in the reaction medium is observed by 11
B
NMR. In the case of the secondary amide, N-methylbenz-
amide, rapid hydrogen (0.85 equiv) evolution is also
observed, with the formation of a white precipitate and
only slow further reaction. On the other hand, the rates
of reaction of tertiary amides is considerably faster,
exhibiting hydride uptake of two required for reduction
to the amine stage.16 Table 10 summarizes the results.
Nitr iles a n d Nitr o Com p ou n d s. Nitriles react very
slowly with 8, and the reaction fails to proceed to
completion. Only 1.68 equiv of hydride was consumed
even after 96 h, whereas 2 hydride equiv is required for
reduction to the amine stage.16,17
A detailed account of more rapid reductions at higher
temperatures, with isolation of the products, is discussed
in the following text.
Nitro compounds such as nitromethane and nitroben-
zene failed to react under the present conditions. This
inertness of borane toward the nitro group is presumably
due to the very weakly basic properties of this group. The
benzoyl chloride, fail to react even after prolonged periods
of time (Table 8).
Ester s. Both aliphatic and aromatic esters fail to react
with 8 under the present conditions. Very little hydride
uptake was noted even after 72 h. The 11B NMR analysis
showed exclusively unreacted amine-borane. Table 9
summarizes the results.
Am in es, Im in es, a n d Am id es. n-Hexylamine liber-
ates only 0.11 equiv of hydrogen upon the reaction with
8 over 24 h. The resulting solution, after 24 h, was found
to contain n-hexylamine-borane (60%), reagent amine-
borane (29%), and borane-THF (10%) complexes as
revealed by 11B NMR (δ -19.9, -14.1, and -1.1 respec-
tively), indicating the presence of an equilibrium mixture.
Imines are reduced to the corresponding amines rapidly
with the uptake of one hydride, and the resulting amine-
boranes were in equilibrium with the reagent amine-
borane. N-Phenylbenzylimine takes a relatively longer
time for the reduction (∼8 h), which may be attributed
to the presence of phenyl groups on both sides of the
imine functionality.
(17) Emeleus, H. J .; Wade, K. J . Chem. Soc. 1960, 2614.

6270 J . Org. Chem., Vol. 64, No. 17, 1999
Brown et al.
Ta ble 11. Rea ction of t-Bu MeP r iN-BH3 w ith
Rep r esen ta tive Nitr iles a n d Nitr o Com p ou n d s a t a Mola r
Ra tio of 1.33:1 in THF a t Room Tem p er a tu r e
Ta ble 12. Red u ction of Rep r esen ta tive Ester s, Nitr iles,
a n d Am id es w ith t-Bu MeP r iN-BH3 in Tetr a h yd r ofu r a n
a n d Dioxa n e a t Reflu x a n d w ith ou t Solven t
t-BuMePriN-BH3
t-BuMePriN-BH3 time (h)
compounda
time (h)
hydride equiv for reduction
compound
THF
dioxane
neata,b
heptanenitrile
2.00
12
24
48
96
2.00
12
24
48
72
0.00
0.19
1.16
1.33
1.56
0.00
0.19
0.59
1.11
1.52
1.68
0.00
0.00
0.00
ethyl undecanoatec
methyl caproatec
methyl benzoatec
n-heptanenitriled
benzonitriled
0.50
0.50
2.50
2.00
6.00
10
12
10
0.25
0.50
0.25
0.25
0.50
0.50
0.50
2.00
2.00
1.00
0.25
0.25
0.25
0.25
10
benzonitrile
caproamidee
benzamidee
N-methylbenzamidef
N,N-dimethylcaproamideg
N,N-dimethylbenzamideg
96
1.00
24
a
Amine-borane in 30% excess was taken to compensate the loss
nitromethane
of diborane in heating. At 85-90 °C. c 12.5 mmol of compound
b
was added to 9.1 mmol of amine-borane (10% excess of hydride)
nitrobenzene
24
d
in 25 mL solution (0.5 M in compound). 6.25 mmol of compound
a
6.25 mmol of compound was added to 8.3 mmol of amine-
borane (25 mmol of hydride) in 25 mL of solution 0.25 M in
compound and 1.00 M in hydride.
was added to 8.3 mmol of amine-borane (25 mmol of hydride) in
25 mL of solution 0.25 M in compound and 1.00 M in hydride.
e 6.25 mmol of compound was added to 9 mmol of amine-borane
(10% excess) in 25 mL of solution in THF or dioxane. f 6.25 mmol
of compound was added to 13.7 mmol of amine-borane (10%
excess) in 25 mL solution of THF or dioxane. 6.25 mmol of
compound was added to 11.6 mmol of amine-borane (10% excess)
in 25 mL solution of THF or dioxane.
reduction studies with the nitriles and the nitro com-
pounds are presented in Table 11.
g
Ep oxid es. The reaction of epoxides is slow. With
simple 1,2-propylene oxide, the hydride uptake is almost
one after 24 h, but the usual workup and GC analysis
reveals only 30% of propanols. Similar results are also
realized with styrene oxide. It consumes 2 hydride equiv
after 24 h, though only one hydride is required for
reduction, and the usual workup gave only small amounts
of 1- or 2-phenylethanols. These observations were
similar to those reported for BH3-THF, and it was also
known that presence of sodium borohydride or boron
trifluoride markedly changes the reaction of epoxides
with diborane.18 However, in the present study, no
further efforts were made to improve the reactivity of
epoxides with 8.
Rea ction of 8 w ith Ester s, Am id es, a n d Nitr iles
a t Reflu x Tem p er a tu r es. The reduction of some func-
tional groups, such as esters, amides, nitriles, etc., are
sluggish at room temperature. However, BH3-THF19 and
BMS20 have proven to be the reagents of choice for these
reductions over any complex metal hydride.21-24 To
further establish the potential of this new, reactive
amine-borane adduct and in a bid to find an alternative
for BH3-THF and BMS, it was decided to examine
whether a modest increase in the temperature would
facilitate the reduction. Thus, reductions with 8 toward
esters, amides, and nitriles were also examined in
tetrahydrofuran and dioxane at reflux temperature and
also without solvent at 85-90 °C.
to the alcohol stage. Accordingly, reductions were carried
out in 1:1.5 amine-borane/ester molar ratio using 10%
excess hydride to ensure complete reaction. The proce-
dure adopted was to add 12.5 mmol of ester to a solution
of 9 mmol of amine-borane in 21.6 mL of the solvent,
reacting the mixture under reflux. Aliquots were taken
out at intervals, worked up, and checked for the presence
of the starting ester by GC analysis. The reactions were
also cross-checked by 11B NMR analysis. The results are
presented in Table 12.
In dioxane, the reductions are very fast. Aliphatic
esters are reduced in 15 min, and methyl benzoate is
reduced in 30 min. In THF, the reductions are relatively
slower, perhaps because of the somewhat lower refluxing
temperature. Thus, 8 reduced ethyl undecanoate to
1-undecanol in 0.5 h. The difference is more pronounced
for aromatic esters, requiring 2.5 h for the reduction of
methyl benzoate to the corresponding alcohol.
Reductions without solvent were carried out by mixing
the amine-borane adduct 8 with esters and heating to
85-90 °C. Under these conditions, aliphatic esters reduce
rapidly within 15 min. However, methyl benzoate reacts
much slower, and some loss of diborane was observed
leading to incomplete reduction. This was also confirmed
by 11B NMR, which showed the presence of only tri-
alkoxyborane, with absence of amine-borane, confirmed
by GC analysis which showed the presence of unreacted
ester. The reactions could be forced to completion by
taking an excess of 8.
Nitr iles. Reductions of n-heptanenitrile and benzoni-
trile were carried out with 8. From studies at room
temperature, it was established that nitriles consume 2
hydride equiv to give the corresponding borazine deriva-
tive, which can be hydrolyzed to the product amine (eq
9).17
Ester s. The reductions of ethyl undecanoate, methyl
caproate, and methyl benzoate with 8 in THF and
dioxane at reflux temperatures were studied. It was
established from previous experiments at room temper-
ature that esters require 2 hydride equiv for the reduction
(18) Brown, H. C.; Yoon, N. M. J . Chem. Soc., Chem. Commun. 1968,
1549.
(19) Brown, H. C.; Heim, P. J . Org. Chem. 1973, 38, 912.
(20) Lane, C. F. Aldrichim. Acta 1975, 8, 20.
(21) Gaylord, N. G. Reductions with Complex Metal Hydrides;
Interscience: New York, 1956; p 544.
(22) Zabicky, J . The Chemistry of Amides; Interscience: New York,
1970; p 795.
(23) Brown, H. C.; Weissman, P. M.; Yoon, N. M. J . Am. Chem. Soc.
1966, 88, 1458.
Accordingly, reactions were carried out by adding 9
mmol amine-borane (10% excess) and 8.3 mmol nitrile
to THF or dioxane and refluxing the mixture. The
reactions were followed by taking aliquots at intervals
and GC analysis for the remaining nitrile after workup.
The results are presented in Table 12. As follows from
(24) Lane, C. F. Aldrichim. Acta 1977, 10, 49.

Molecular Addition Compounds
J . Org. Chem., Vol. 64, No. 17, 1999 6271
liberated from its borane adduct by the addition of boron
trifluoride-etherate.
Con clu sion
This study has demonstrated that several tert-butyl-
dialkylamines are convenient borane carriers for hy-
droboration. The complexing ability of amines can be
varied in a predictable manner by a proper choice of alkyl
groups. Stable, highly reactive liquid adducts of 1d , 2b,
and 2c have been prepared. Simple procedures for the
synthesis of the majority of amines examined have been
worked out. As the result of this and our previous
studies,6 a group of new, highly reactive borane-amine
adducts has become available for the first time. The
present study also clearly demonstrates the synthetic
potential of the new, highly reactive amine-borane
adducts tert-butyl-bis(2-methoxyethyl)amine-borane (7),
tert-butyl-N-methyl-N-isopropylamine-borane (8), and
tert-butyl-N-ethyl-N-isobutylamine-borane (9). Simple
unhindered olefins can be hydroborated to the trialkyl-
borane stage rapidly, 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. The present study also indicates that
the reactivity of these borane adducts toward representa-
tive olefins is similar to that of BMS, so the accumulated
data on the rates and stoichiometry of hydroboration with
these reagents can be used to predict the hydroboration
results with 7-9. In the great majority of cases, the
hydroboration products were oxidized using hydrogen
peroxide/sodium hydroxide to give the corresponding
alcohols in quantitative yields, without any interference
by the amine. This study also demonstrates that 8 can
substitute for borane-dimethyl sulfide (BMS) in the
reduction of various functional groups. Aldehydes, ke-
tones, acids, imines, and tertiary amides are reduced
conveniently at room temperature. Functional groups
that show sluggish reactivity at room temperature, such
as esters, primary and secondary amides, and nitriles,
can be readily reduced in tetrahydrofuran or dioxane
under reflux conditions.
the results, in THF the aliphatic nitrile is reduced faster
than the aromatic one. In dioxane, the reductions are
faster, being complete in 30 min for both nitriles. Reduc-
tions of nitrile in neat condition were not studied because
loss of diborane during the reaction was observed leading
to incomplete reduction.
Am id es. Reductions of primary, secondary, and ter-
tiary amides using 8 in THF and dioxane at reflux
temperature were followed by 11B NMR, hydrolysis of
aliquots at intervals, and GC examination for unreacted
amide. The product of the reduction is an amine that
forms a relatively stable borane-amine, so that 1 mol of
borane reagent is required per mole of amine product.
Accordingly, tertiary amides require five hydrides, sec-
ondary six, and primary four hydrides.25 The reductions
gave quantitative yields of amine products (by GC). The
results are presented in Table 12.
In refluxing THF, reactions with primary amides
evolve hydrogen (2 equiv) rapidly and further reduction
is slow. N-Methylbenzamide, a secondary amide, evolves
hydrogen (1 equiv) rapidly; here also, further reaction is
slow. In both cases, reduction to the amine stage requires
10 h of refluxing in THF. Tertiary amides are reduced
rapidly in 0.5 h, giving the corresponding borane adducts
as products. In dioxane, the reductions are faster, being
complete in 2 h for the slowest reacting primary amides
and in only 15 min for the tertiary amides.
Isola t ion of t h e P r od u ct s. In case of reduction of
aldehydes, ketones, acids, esters, etc., the product alco-
hols are readily separated by simple acid-base manipu-
lations. When the product is a water-soluble alcohol, it
can be easily isolated by either distillation or column
chromatography.
In refluxing dioxane, the reductions of esters, amides,
and nitriles are complete in 15 min to 2 h. The reductions
are faster than with BMS in refluxing THF, even when
dimethyl sulfide is removed from the reaction mixture.25
The borane carrier amines 1d , 2b, and 2c can be readily
recovered from the hydroboration or reduction products
by simple acid-base manipulations, distillation, or col-
umn chromatography and can be easily recycled for the
preparation of the borane adduct. Consequently, the
borane adducts 7, 8, and 9 described in the present study
can serve as eco-friendly substitutes for the currently
popular hydroborating-reducing agents borane-di-
methyl sulfide and borane-tetrahydrofuran.
Two procedures for the isolation of product amines
obtained from imines, nitriles, and amides can be used.
The first procedure is used when the product amine and
the carrier amine differ in boiling points or polarities.
The reduction product, the amine-borane, is hydrolyzed
with 6.00 M hydrochloric acid, and the mixture of both
amines obtained by treatment of the acidic phase with
sodium hydroxide is separated by distillation or column
chromatography. The second procedure is applied when
the product amine is strongly complexed with borane (as
in the case with less hindered amines, e.g., N-methyl-
benzylamine and N,N-dimethylbenzylamine), the reac-
tion product is treated with dilute hydrochloric acid.
Under these conditions, the product borane-amine com-
plex is stable. The more hindered carrier amine is
extracted into the acidic aqueous phase, separated, and
recovered by alkalization. The product amine can be
Exp er im en ta l Section
Manipulations and reactions with air-sensitive compounds
were carried out under nitrogen atmosphere. Glassware was
oven-dried for several hours, assembled while hot, and cooled
in a stream of dry nitrogen gas. Techniques for handling air-
sensitive compounds described elsewhere were followed.26 1H,
13C, and 11B NMR spectra were recorded on either a 200 or
300 MHz multinuclear NMR spectrometer. The 11B NMR
(25) Brown, H. C.; Choi, Y. M.; Narasimhan, S. J . Org. Chem. 1982,
47, 3153.

6272 J . Org. Chem., Vol. 64, No. 17, 1999
Brown et al.
chemical shifts are in δ relative to BF3‚Et2O. GC analyses were
performed on a chromatograph (catharometer) equipped with
the following columns: a 12 ft × 0.125 in. packed with 10%
SE 30 on Chromosorb W 100-120 mesh; 6 ft × 0.125 in, 15%
Carbowax 20M on Chromosorb W; 9 ft × 0.125 in, 3% OV-17
on Chromosorb-G; SPB-5 (0.25 µm × 30 m) capillary column.
Optical rotations were measured on a polarimeter. Hydride
analysis studies were carried out using the gasimeter. Micro-
analyses were performed at the Microanalytical Laboratory,
Purdue University.
tetrabutylammonium iodide (1.85 g, 5 mmol) was refluxed with
stirring for 30 h. The temperature of the mixture increased
from 53 to 78 °C. Aqueous 5.00 M potassium hydroxide (30
mL, 0.15 mmol) was added, and the mixture was extracted
with n-pentane. Three layers were formed. Adiponitrile (middle
layer) was recovered. The pentane solution was dried over
anhydrous magnesium sulfate, and tert-butylisopropylamine
was isolated by distillation: 8.18 g, (71%), bp 97-99 °C/760
mmHg.
ter t-Bu tyld ieth yla m in e 1b. Diethyl sulfate (33.9 g, 0.22
mol) was slowly added to tert-butylamine (14.62 g, 0.2 mol),
keeping the reaction mixture at reflux, and it was then stirred
for 15 min. Aqueous 8.00 M potassium hydroxide (40 mL, 0.32
mol) was added to the warm mixture. The organic layer was
separated, dried over anhydrous magnesium sulfate, and
treated with diethyl sulfate (33.9 g, 0.22 mol), followed by
heating at 120 °C for 0.5 h. The organic layer, separated after
treatment with potassium hydroxide, was heated at 120 °C
for 0.5 h. Two layers were formed. The upper layer was
separated and dried over anhydrous magnesium sulfate, and
the product was isolated by distillation: 23.0 g, (88%), bp 126-
128 °C (lit.35 chloroplatinate mp 223-225 °C, dec).
Ma ter ia ls. N-tert-Butylmorpholine,27 1a , and diisopropyl
sulfate28 were prepared according to the literature. N-tert-
Butyldiethanolamine (Fluka) and other starting amines (Al-
drich) were commercial products. All solvents were purified
according to literature procedures and stored under nitrogen.
Tetrahydrofuran and dioxane were freshly distilled from
benzophenone ketyl before use. All olefins were distilled from
a small amount of lithium aluminum hydride and stored under
nitrogen. All compounds except amides were commercial
samples and were used as obtained. Amides used in this study
were prepared following literature procedures29 and were fully
analyzed before use.
Bor a n e-Am in e Ad d u cts. Gen er a l P r oced u r e. Diborane
generated as described elsewhere30,31 was passed into a neat
amine (50 mmol) at 0 °C and placed in a bubbler provided with
a sintered glass tip and a magnetic stirring bar. Excess of
diborane not absorbed by the amine was absorbed in a
following bubbler containing tetrahydrofuran (10 mL) over
mercury and cooled in ice-water. A mercury bubbler was
connected to the exit. Diborane was passed into the amine until
the concentration of borane in the THF in the following bubbler
was ∼1.0 M. The borane-amine adduct was stirred overnight
at room temperature prior to disconnecting the bubblers and
then analyzed for active hydride by a standard procedure32
using a 2.00 M hydrochloric acid-glycerol-water (2:1:1)
hydrolysis solution.
ter t-Bu tylisobu tyla m in e 4. A mixture of tert-butylamine
(11.0 g, 0.15 mol), isobutyl bromide (13.7 g, 0.1 mol), adiponi-
trile (10.8 g, 0.1 mol), and tetrabutylammonium iodide (1.85
g, 5 mmol) was refluxed with stirring for 12 h. Aqueous 5.00
M potassium hydroxide (30 mL, 0.15 mmol) was added, and
the mixture was extracted with n-pentane. Three layers were
formed. Adiponitrile (middle layer) was recovered. The pentane
solution was dried over anhydrous magnesium sulfate, and
the product isolated by distillation: 9.56 g, (74%), bp 45-47
°C/40 mmHg.33,34
ter t-Bu tylisop r op yla m in e 5. By Alk yla tion of ter t-
Bu tyla m in e w ith Diisop r op yl Su lfa te. The mixture of tert-
butylamine (14.6 g, 0.2 mol) and diisopropyl sulfate (18.2 g,
0.1 mol) was refluxed for 1 h with stirring. The temperature
increased from 58 to 83 °C. Two phases formed. Aqueous 5.00
M potassium hydroxide (50 mL, 0.25 mol) was added. The
organic layer was separated, and the aqueous layer was
extracted with diethyl ether. The organic solutions were
combined and dried over anhydrous magnesium sulfate, and
the product was isolated by distillation: 9.55 g (83%), bp 98-
100 °C/760 mmHg (lit.8 bp 99-99.5 °C).
ter t-Bu tyld i-n -p r op yla m in e 1c. A mixture of tert-butyl-
amine (29.3 g, 0.4 mol), 1-iodopropane (51.0 g, 0.3 mol), and
glycerol (13.8 g, 0.15 mol) was refluxed for 4 h. Aqueous 8.00
M potassium hydroxide (62.5 mL, 0.5 mol) was added, and the
organic layer was separated and dried over anhydrous mag-
nesium sulfate. tert-Butylamine was removed, and crude tert-
butyl-n-propylamine, 25.1 g, 72% was obtained. It was treated
with 1-iodopropane (25.5 g, 0.15 mol) and glycerol (6.9 g, 75
mmol), and the mixture was refluxed for 6 h. The workup, as
described above, followed by distillation gave 1c: 14.4 g, (61%),
bp 62-63 °C/20 mmHg.
ter t-Bu tylbis(2-m eth oxyeth yl)a m in e 1d . Dimethyl sul-
fate (50.5 g, 0.4 mol) was added dropwise to a vigorously stirred
mixture of N-tert-butyldiethanolamine (16.1 g, 0.1 mol), dichlo-
romethane (100 mL), tetrabutylammonium bromide (3.22 g,
10 mmol), and 50% aqueous sodium hydroxide (80 g, 1 mol),
at 30-40 °C. The stirring was continued for 1 h after the
addition was completed. The organic solution was separated,
and the aqueous layer was extracted with dichloromethane.
The organic solutions were combined. GC analysis showed a
mixture of mono- and diethylated product. The methylation
was repeated using the same amounts of reagents as described
above. The dichloromethane solution after the second workup
was stirred with concentrated aqueous ammonia (50 mL) for
1 h at room temperature, separated, and dried over anhydrous
magnesium sulfate, and the product was isolated by distilla-
tion: 17.0 g, (90%), bp 42-44 °C/0.1 mmHg.
ter t-Bu tyld iisobu tyla m in e 1e. Isobutyryl chloride (10.9
g, 0.1 mol) was added to a solution of tert-butylisobutylamine
(25.9 g, 0.2 mol) in tetrahydrofuran (150 mL) at room tem-
perature and stirred for 1 h. Solids were filtered off and
washed with tetrahydrofuran. N,N-tert-Butylisobutyl-2-meth-
ylpropionamide was isolated by distillation: 18.5 g, 90%, bp
59-60 °C/1.3 mmHg.
A 1.00 M BH3-THF (150 mL, 0.15 mol) was added dropwise
to a solution of the amide (18.0 g, 90 mmol) in tetrahydrofuran
(50 mL) at room temperature, and the mixture was refluxed
for 1 h. Water was added after cooling, followed by slow
addition of 6.00 M hydrochloric acid (60 mL). Tetrahydrofuran
was distilled off, and solid sodium hydroxide (20.0 g, 0.5 mol)
was added. The organic layer was separated, and the aqueous
solution was extracted with n-pentane. The organic solutions
were combined and dried over anhydrous magnesium sulfate,
and the product was isolated by distillation: 14.2 g, (85%), bp
34-35 °C/1.5 mmHg.
By Alk yla tion of ter t-Bu tyla m in e w ith Isop r op yl Br o-
m id e. A mixture of tert-butylamine (11.0 g, 0.15 mol), isopropyl
bromide (12.3 g, 0.1 mol), adiponitrile (10.8 g, 0.1 mol), and
(26) Brown, H. C. Organic Syntheses via Boranes; Wiley-Inter-
science: New York, 1975, p 191. A reprinted edition is currently
available: Organic Syntheses via Boranes; Aldrich Chemical Co.,
Inc.: Milwaukee, WI, 1997; Vol. 1.
(27) Cook, M. J .; Katritzky, A. R.; Moreno Manas, M. J . Chem. Soc.
B 1971, 1330.
(28) Kranzfelder, A. L.; Sowa, F. J . J . Am. Chem. Soc. 1937, 59,
1491.
(29) Vogel, A. I. Practical Organic Chemistry, 5th ed.; Longman:
Essex, 1989.
(30) Reference 8, p 18.
(31) For small-scale generation of diborane, see ref 5a.
(32) Reference 26, p 241.
(33) DeKimpe, N.; Verhe, R.; DeBuyck, L.; Schamp, N. Rec. Trav.
Chim Pays-Bas 1977, 96, 242.
ter t-Bu tylisobu tylm eth yla m in e 2a . A 37% solution of
formaldehyde (6.89 g, 85 mmol) was added dropwise to a
mixture of tert-butylisobutylamine (10.0 g, 77 mmol) and 88%
formic acid (7.85 g, 0.15 mol) at room temperature. The
mixture was heated at 50-55 °C for 5 h. Aqueous 8.00 M
(34) Bu¨ttner, G.; Hu¨nig, S. Ber. 1971, 104, 1088.
(35) Reiber, H. G.; Stewart, T. D. J . Am. Chem. Soc. 1940, 62, 3026.

Molecular Addition Compounds
J . Org. Chem., Vol. 64, No. 17, 1999 6273
potassium hydroxide (12.5 mL, 0.1 mol) was added, the organic
layer was separated, and the aqueous layer was extracted with
n-pentane. The extract was combined with the organic layer
and dried over anhydrous magnesium sulfate. The product was
isolated by distillation: 9.25 g, (84%), bp 44-45 °C/18 mmHg.
ter t-Bu tylisop r op ylm eth yla m in e 2b. A 37% solution of
formaldehyde (5.32 g, 73 mmol) was added to a mixture of tert-
butylisopropylamine (7.60 g, 66 mmol) and 88% formic acid
(5.52 g, 0.12 mol) at 0 °C. The reaction mixture was kept at
50-55 °C for 2 h. Aqueous 8.00 M potassium hydroxide (12
mL, 96 mmol) was added, the organic layer was separated,
and the aqueous layer was extracted with n-pentane. The
organic solutions were combined and dried over anhydrous
magnesium sulfate, and the product was isolated by distilla-
tion: 6.50 g, (80%), bp 126-128 °C/760 mmHg (lit.36 bp 130
°C).
ter t-Bu t ylisobu t ylet h yla m in e 2c. A mixture of tert-
butylisobutylamine (25.8 g, 0.2 mol) and diethyl sulfate (46.3
g, 0.3 mol) was warmed to 70 °C with stirring. An exothermic
reaction started, and the temperature increased in a few
minutes to 150 °C with vigorous boiling of the mixture. When
it cooled to ∼50 °C, 5.00 M aqueous potassium hydroxide (100
mL, 0.5 mol) was added. The organic layer was separated and
dried over anhydrous magnesium sulfate. GC analysis indi-
cated 10% of diethyl sulfate and 17% of unreacted starting
amine. Diethyl sulfate (10 mL) was added, and the mixture
was stirred at 100 °C for 1 h. Aqueous 5.00 M potassium
hydroxide (100 mL) was added, and the mixture was stirred
at 80 °C for 1 h. The organic layer was separated and the
aqueous layer extracted with diethyl ether. The organic
solutions were combined and dried over anhydrous magnesium
sulfate, and the product was isolated by distillation. A small
amount (1-2%) of tert-butylisobutylamine was removed by the
addition of 2.5 M n-butyllithium in hexanes (5 mL, 10 mmol)
and distillation: 22.56 g, (72%), bp 68-70 °C/40 mmHg.
ter t-Bu tylisobu tyl-n -p r op yla m in e 2d . A mixture of tert-
butylisobutylamine (19.4 g, 0.15 mol), 1-iodopropane (20.4 g,
0.12 mol), and glycerol (5.53 g, 60 mmol) was refluxed for 40
h. Aqueous 8.00 M potassium hydroxide (30 mL, 0.24 mol) was
added, the organic layer was separated, and the aqueous layer
was extracted with n-pentane. The organic solutions were
combined and dried over anhydrous magnesium sulfate, and
the product was isolated by distillation: 12.5 g, (61%), bp 72-
73 °C/18 mmHg.
ter t-Bu tylisop r op yleth yla m in e 2e. A mixture of tert-
butylisopropylamine (11.5 g, 0.1 mol) and diethyl sulfate (15.4
g, 0.1 mol) was refluxed for 2 h. Aqueous 8 M potassium
hydroxide (20 mL, 0.16 mol) was added and the organic layer
separated. The aqueous layer was extracted with pentane. The
organic solutions were combined and dried over magnesium
sulfate, and the product was isolated by distillation: 7.16 g,
(50%), bp 140-142 °C.
Hyd r obor a tion of Rep r esen ta tive Olefin s w ith th e
Ad d u cts 7-9. 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 compounds, a stirring bar, and a stopper, was
cooled to 0 °C under nitrogen. The flask was charged with an
amine-borane adduct (5 mmol) and a solvent. A solution of
an olefin (15 mmol, 6.00 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 3.00 M HCl-glycerol-THF
(2:1:0.2) hydrolysis solvent. The hydrogen evolved was mea-
sured using a gasimeter to establish the presence of active
hydride. The reactions were simultaneously followed by 11B
NMR, observing the relative ratio of an amine-borane signal
and the signals due to the hydroboration product.
Hyd r obor a tion of 1-Hexen e w ith 8 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 8 (0.94
mL, 5.30 M, 5 mmol) in freshly distilled THF (7.6 mL) and
undecane (7.5 mmol, GC standard). 1-Hexene (15 mmol, 1.26
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 3.00 N NaOH was added,
followed by the slow addition of 2.0 mL 30% hydrogen peroxide
during 10 min. The contents were further stirred at 50 °C for
2 h to ensure completion of oxidation. The reaction mixture
was cooled to room temperature, and the organic layer was
separated. The aqueous layer was saturated with potassium
carbonate and extracted with ether, and the combined organic
extract was washed with brine and dried over anhydrous
magnesium sulfate. The combined yield of 1- and 2-hexanols
was 98% (by GC using the OV-17 column). The ratio of
1-hexanol-2-hexanol is 96:4.
Hyd r obor a tion -Oxid a tion Stu d ies. Hydroboration and
oxidation studies using the adducts 7-9 toward olefins, such
as 1-hexene, styrene, and cyclohexene, were carried out in THF
on a preparative scale. The procedure followed for cyclohexene
with 9 in tetrahydrofuran is representative.
Into an oven-dried hydroboration flask was placed 9 (1.11
mL, 4.50 M, 5 mmol) in freshly distilled THF (7.4 mL).
Cyclohexene (10 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 10 °C, and 3.0
mL of 3.00 N NaOH was added followed by the slow addition
of 1.0 mL 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 potassium carbonate and
extracted with ether. The combined organic layer was washed
with 3.00 N HCl and 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 1.06 g (89%).
The aqueous layer was neutralized with 3.00 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 (3%) in addition to 2c (97%). Amine
was recovered in pure form by distillation in 82% (0.65 g) yield.
Red u ction of Or ga n ic F u n ction a l Gr ou p s w ith 8 a t
Room Tem p er a tu r e in THF . Gen er a l P r oced u r e. All
reductions were carried out under a dry nitrogen atmosphere.
In a 50 mL flask, fitted with a sidearm capped by a rubber
septum (to permit introduction and removal of material with
a hypodermic syringe), was placed amine-borane 8 (5.30 M,
8.3 mmol) in freshly distilled THF (20 mL). To this solution
was added the compound to be reduced in THF (5.00 mL, 6.25
mmol) slowly during 5 min. The final solution is 0.25 M in
reducible compound and 1.00 M in hydride. At appropriate
time intervals, samples were withdrawn and hydrolyzed using
glycerol-2.00 N HCl-THF (1:3:1), and hydrogen evolved was
measured using the gasimeter to determine the amount of
residual hydride. Progress of the reaction was also checked
by 11B NMR and GC analysis. In a separate run using the same
quantities and conditions, the reaction flask was attached to
a gasimeter to measure the hydrogen evolved.
In a number of cases, the reduction was carried out as
described above to establish yield and stoichiometry. However,
the reaction mixtures were then worked up to isolate and
characterize the reduction products. A few representative
examples are described below for isolation of the reduced
product and recovery of borane carrier amine.
Red u ction of Ben za ld eh yd e (2 Equ iv) w ith 8 (1 Equ iv)
in THF a t Room Tem p er a tu r e. An oven-dried two-necked
round bottom flask provided with a condenser, septum inlet,
and stirring bar was cooled to 0 °C under nitrogen. Into the
flask were placed freshly distilled THF (21.90 mL) and 8 (1.56
mL, 5.30 M, 8.3 mmol). Benzaldehyde (1.68 mL, 16.6 mmol)
Regioselectivity Stu d ies. Regioselectivity studies in hy-
droborations of 1-hexene and styrene using 7-9 in THF were
carried out. The procedure followed for 1-hexene using 4 in
tetrahydrofuran is representative.
(36) Brit. Pat. 876,465, 1961; Chem. Abstr. 1963, 58, 10077a.

6274 J . Org. Chem., Vol. 64, No. 17, 1999
Brown et al.
was added slowly during 5 min, and the contents were further
stirred at room temperature for 2 h. The reaction was
quenched with water, and the organic layer was separated.
The aqueous layer was extracted with ether, and the combined
organic extract was washed with brine and dried over anhy-
drous magnesium sulfate. The solvent was removed on a rotary
evaporator, and the crude product was subjected to distillation
under reduced pressure: the yield of benzyl alcohol was 1.47
g (82%) and amine was 0.93 g (87%).
Red u ction of Acetop h en on e (2 Equ iv) w ith 8 (1 Equ iv)
in THF a t Room Tem p er a tu r e. An oven-dried two-necked
round bottom flask, provided with a condenser, septum inlet,
and stirring bar, was cooled to 0 °C under nitrogen. Into the
flask were placed freshly distilled THF (21.4 mL) and 8 (1.56
mL, 5.30 M, 8.3 mmol). Acetophenone (1.99 g, 16.6 mmol) was
added slowly during 5 min, and the contents were further
stirred at room temperature for 18 h. The reaction was
quenched with water, and diethyl ether was added. The
organic layer was separated, washed with 3.00 N HCl, and
dried over anhydrous MgSO4. Evaporation of the solvent gave
essentially pure 1-phenylethanol, which was further purified
by passing through a small silica gel pad. The yield of
1-phenylethanol was 1.72 g (86%).
The combined aqueous layer was neutralized using aqueous
KOH and extracted with ether. The combined organic extract
was washed with brine and dried over anhydrous MgSO4. The
solvent was removed on a rotary evaporator, and the GC
analysis of crude product on the OV-17 column revealed the
presence of 2b in a purity of 97%. The yield of recovered amine
after distillation was 0.91 g (85%).
Red u ction of Rep r esen ta tive Ester s w ith 8 in THF
a n d Dioxa n e a t Reflu x. Amine-borane adduct 8 in THF or
dioxane was treated with representative esters such as ethyl
undecanoate, methyl caproate, and methyl benzoate. The
procedure followed for methyl benzoate in THF is representa-
tive.
An oven-dried, round bottom flask (50 mL), provided with
a condenser, septum inlet, and a stirring bar, was cooled under
a flow of nitrogen. Into the flask were placed freshly distilled
THF (21.7 mL) and 8 (1.69 mL, 5.30 M, 9 mmol) at room
temperature. Methyl benzoate (1.55 mL, 12.5 mmol) was
added, and the reaction mixture was stirred under reflux.
Aliquots of the reaction mixture were removed at appropriate
intervals, hydrolyzed, and tested for the remaining unreacted
ester on GC using the OV-17 column. Thus, the progress of
reaction was monitored. After 12 h no residual ester was
detected and the exclusive formation of benzyl alcohol noted
in addition to 2b.
In a separate run, the contents were refluxed for 12 h and
cooled, the reaction was then quenched with water, and
aqueous NaOH was added (3.00 N). The organic layer was
separated, and the aqueous layer was saturated with K2CO3
and extracted with ether. The combined organic extract was
dried over anhydrous magnesium sulfate, the solvent was
evaporated, and benzyl alcohol and carrier amine were sepa-
rated by distillation.
In the case of water-insoluble alcohol products, such as
1-undecanol (reduction of ethyl undecanoate), the workup
procedure can be simplified as follows. After completion of the
reduction, the reaction mixture was quenched with water,
ether was added, and amine was extracted in to the aqueous
layer using HCl (3.00 N). The organic layer was dried over
anhydrous MgSO4, and evaporation of the solvent provided
essentially pure 1-undecanol (99% by GC). The aqueous layer
was neutralized with NaOH to liberate amine (97% pure by
GC).
Red u ction of Rep r esen ta tive Nitr iles w ith 8 in THF
a n d Dioxa n e a t Reflu x. Reduction studies of heptanenitrile
and benzonitrile using amine-borane adduct 8 in THF and
dioxane under reflux conditions were carried out. The proce-
dure followed for benzonitrile in THF is representative.
An oven-dried round bottom flask (50 mL), provided with a
reflux condenser, a septum inlet, and a stirring bar, was cooled
under a flow of nitrogen. Into the flask were placed freshly
distilled THF (22.4 mL) and 8 (1.69 mL, 5.30 M, 9 mmol).
Benzonitrile (0.85 mL, 8.3 mmol) was added, and the reaction
mixture was stirred under reflux. Aliquots were removed at
appropriate intervals and after hydrolysis tested for the
presence of residual benzonitrile using GC analysis on the OV-
17 column. After refluxing for 6 h, no residual nitrile was
found. In a separate experiment, after refluxing for 6 h, the
reaction mixture was cooled and quenched with water, and
HCl (6.00 N) was added. The contents were refluxed further
for 1 h, cooled, and neutralized by the addition of solid NaOH.
The organic layer was separated, and the aqueous layer was
extracted with ether. The combined organic extract was dried
over anhydrous MgSO4. Analysis (by GC) of the reaction
mixture revealed a quantitative yield of benzylamine.
Red u ction of Rep r esen ta tive Am id es w ith 8 in THF
a n d Dioxa n e u n d er Reflu x. Reduction studies of capro-
amide, benzamide, N-methylbenzamide, N,N-dimethylcapro-
amide, and N,N-dimethylbenzamide using 8 in dioxane and
THF were carried out under reflux conditions. The course of
the reaction was followed by GC analysis of the reaction
mixture after hydrolysis. The reactions were quenched as soon
as the starting amide is fully consumed. The reduction of N,N-
dimethylbenzamide with 8 in dioxane is representative.
Red u ction of N,N-Dim eth ylben za m id e w ith 8. An oven-
dried 50 mL round bottom flask, provided with reflux con-
denser, septum inlet, and a stirring bar, was cooled under a
flow of nitrogen. The outlet of the condenser was connected to
a mercury bubbler. Into the flask was placed N,N-dimethyl-
benzamide (1.76 g, 12.5 mmol) in dry dioxane (21.0 mL), and
8 (4.15 mL, 22 mmol) was added. The contents were heated
under reflux for 15 min, by which time no starting amide was
present (by GC analysis). The reaction was quenched with
water, 6.00 N HCl (18 mL) was added, and the contents were
heated to reflux for 1 h. The reaction mixture was cooled to 0
°C, and solid NaOH was added until the mixture became basic.
The organic compounds were extracted with ether, and the
combined organic extracts were dried over MgSO4. GC analysis
of the mixture revealed the quantitative conversion. Distilla-
tion under reduced pressure gave 2b (2.32 g, 82% yield
(isolated), 95% (pure by GC) and N,N-dimethylbenzylamine
(1.31 g, 78%, 98% pure by GC).
An alternate procedure can also be used to isolate the
amines. In a similar experiment as outlined above, after the
reduction was complete the excess active hydride was de-
stroyed by the addition of water. The reaction mixture was
taken in ether and washed with dilute HCl (3.00 N), and the
organic layer was dried over anhydrous MgSO4. Evaporation
of the solvent provided essentially pure N,N-dimethylbenzyl-
amine-borane (11B NMR δ -8.3, quartet, in THF) adduct from
which the amine was liberated by the addition of BF3‚OEt2.
The combined aqueous layer was neutralized with base to
obtain tert-butyl-N-methyl-N-isopropylamine in 90% pure form
(by GC).
Ack n ow led gm en t. Financial support of this study
by the Borane Research Fund is acknowledged. J .V.B.K.
thanks Aldrich Chemical Co. for financial support and
Nicolaus Copernicus University, Poland, for laboratory
facilities.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR, 13C NMR,
mass spectral, elemental analysis data for the amines reported.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O990379B