5162 J . Org. Chem., Vol. 63, No. 15, 1998
Brown et al.
ratio of an amine-borane signal and the signals due to the
Red u ction of Or ga n ic F u n ction a l Gr ou p s w ith 2 At
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 2 (5.00 M,
8.3 mmol) in freshly distilled THF (20 mL). To this solution
was slowly added the compound to be reduced in THF (5.00
mL, 6.25 mmol) for 5 min. The final solution is 0.25 M in
reducible compound and 1 M in hydride. At appropriate time
intervals, samples were withdrawn and hydrolyzed using
glycerol-2 N HCl-THF (1:3:1) and the hydrogen evolved was
measured using the Brown 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 at-
tached 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 2 (1 equ iv)
in THF a t Room Tem p er a tu r e. An oven-dried two-necked
RB flask, provided with a condenser, septum inlet, and stirring
bar, was cooled to 0 °C under nitrogen. Into the flask was
placed freshly distilled THF (21.80 mL) and 2 (1.66 mL, 5.00
M, 8.3 mmol). Benzaldehyde (1.68 mL, 16.6 mmol) was added
slowly for 5 min, and the contents were further stirred at room
temperature for 2 h. The reaction was quenched with water
(2 mL), 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 anhydrous
magnesium sulfate. The solvent was removed on a rotary
evaporator, and the crude product was subjected to column
chromatography on silica gel. Amine, eluted using 2% ethyl
acetate in hexane and alcohol, eluted with 10% ethyl acetate
in hexane, were compared with authentic samples. The yield
of benzyl alcohol was 1.47 g (82%), and that of the amine was
1.23 g (91%)
Red u ction of Acetop h en on e (2 equ iv) w ith 2 (1 equ iv)
in THF a t Room Tem p er a tu r e. An oven-dried two-necked
RB flask, provided with a condenser, septum inlet, and stirring
bar, was cooled to 0 °C under nitrogen. Into the flask was
placed freshly distilled THF (21.3 mL) and 2 (1.66 mL, 5.00
M, 8.3 mmol). Acetophenone (1.99 g, 16.6 mmol) was added
slowly for 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 N HCl, and dried over anhydrous MgSO4.
Evaporation of the solvent gave essentially pure 1-phenyl-
ethanol 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 1 in a purity of 97%. The yield of recovered amine
was 1.21 g (90%).
hydroboration product.
Regioselectivity Stu d ies. Regioselectivity studies in hy-
droborations of 1-hexene, styrene, and allyl chloride using 2
were carried out. To study the solvent effect, reactions were
carried out in tetrahydrofuran, dioxane, monoglyme, diglyme,
toluene, diethyl ether, tert-butyl methyl ether, and n-pentane.
The procedure followed for tetrahydrofuran is representative
for water miscible solvents. For water immiscible solvents, 5
mL of ethanol or THF was added to facilitate hydrogen
peroxide oxidation.
Hyd r obor a tion of 1-Hexen 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 (1.00
mL, 5.00 M, 5 mmol) in freshly distilled THF (7.5 mL) and
undecane (7.5 mmol, GC standard). 1-Hexene (15 mmol, 1.26
g) was added slowly for 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 mL of 3.00 N NaOH was added,
followed by the slow addition of 2 mL of 30% hydrogen peroxide
for 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 OV-17 column). The ratio of 1-hex-
anol-2-hexanol is 96:4.
Hyd r obor a tion of Allyl Ch lor id e w ith 2 in Tetr a h y-
d r ofu r a n . An oven-dried hydroboration flask was cooled
under a stream of nitrogen. In the flask was placed 2 (4.0
mL, 5.00 M, 20 mmol) in dry THF (14.5 mL) at 0 °C, and allyl
chloride (20 mmol, 1.53 g) was added slowly for 5 min. The
contents were further stirred for 4 h at 25 °C. After excess
hydride was destroyed with water, 3 M NaOH (12 mL) was
added at 10 °C and the reaction mixture was refluxed for 3 h
at 64 °C to remove gaseous products, which were collected in
a cold trap attached. The reaction mixture was cooled to 10
°C, and 2 mL of 30% hydrogen peroxide was added slowly. The
contents were stirred for 2 h at room temperature and 1 h at
50 °C to ensure complete oxidation. After separation of the
layers, the aqueous phase was saturated with potassium
carbonate and extracted with ether. The combined organic
extract was dried over anhydrous magnesium sulfate and
analyzed by GC using the Carbowax column. The combined
yield of 1- and 2-propanols was 28%, with a ratio of 1-pro-
panol-2-propanol of 92:8.
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 . Into an oven- dried hydroboration flask
was placed 2 (1.00 mL, 5.00 M, 5 mmol) in freshly distilled
THF (7.5 mL). Cyclohexene (10 mmol, 0.82 g) was added
slowly for 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 mL of 3 N NaOH was added followed by the slow
addition of 1 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 potassium
carbonate and extracted with ether. The combined organic
layer was washed with 3 N HCl, then with brine, and dried
over anhydrous magnesium sulfate. Evaporation of the sol-
vent gave essentially pure cyclohexanol, which was further
purified by passing through a small silica gel pad, providing
a yield of 1.06 g (89%).
Red u ction of Rep r esen ta tive Ester s w ith 2 in THF
a n d Dioxa n e a t Reflu x. Amine-borane adduct 2 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, RB flask (50 mL), provided with a condenser,
septum inlet, and a stirring bar, was cooled under a flow of
nitrogen. Into the flask was placed freshly distilled THF (21.6
mL) and 2 (1.80 mL, 5 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
The aqueous layer was neutralized with 3 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 product 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 85% (0.75 g) yield.