Chemoselective reduction of ketones using decaborane
The reduction of ketones to secondary alcohols is a fundamental and significant process in
organic synthesis, widely employed for the production of alcohols. The transition has been
facilitated by the use of reducing agents, such as NaBH4 and Bu3SnH, in both aqueous and
organic solvent environments.
Decaborane is an intriguing and versatile organic molecule that is classified within the boranes
group. The unique geometry and electrical structure of decaborane contribute to its remarkable
reactivity and utility across multiple disciplines. It can serve as a powerful reducing agent for
the reduction of ketones to secondary alcohols.
In recent years, there has been a growing interest in the field of organic chemistry for the
development of new methods for the reduction of ketones, despite the availability of numerous
reagents for this purpose. The focus lies on developing a novel approach for the reduction of
ketones that exhibits minimal impact on other functional groups and operates in an aqueous
environment, as opposed to predominantly using organic media. This preference for aqueous
media stems from the environmental advantages connected with this transition.
For the chemoselective reduction of ketones, previously decaborane was used in the presence
of pyrrolidine and cerium(III) chloride heptahydrate in methanol. However, they reported that
without cerium chloride heptahydrate, the reaction did not proceed at all.
In this paper, we present the utilisation of decaborane in aqueous solutions at room temperature
for the purpose of selectively reducing ketones by chemoselective methods (Scheme 1).
Additionally, we conducted the reduction in an organic medium to compare the reaction time
and yield. Additionally, we have employed microwave-assisted reduction of ketones to achieve
faster reaction times and enhanced yields.
Scheme 1. R= Aliphatic or aromatic
During the preliminary phase of the investigation, an attempt was made to reduce ketones in an aqueous
environment, which led to a significantly reduced reaction rate. Following this, the reduction was
carried out in tetrahydrofuran (THF), resulting in an output that exhibited partial reduction. After doing
additional analysis, it was noticed that the use of a mixture consisting of water and THF in a proportion
of 1:9 yielded the most advantageous circumstances, leading to a comprehensive reduction with the
utmost efficiency. Within the context of this particular solvent system, water was employed as the
principal solvent, whereas tetrahydrofuran (THF) fulfilled the role of a co-solvent. The methodology
we present provides a straightforward implementation approach while ensuring environmentally
friendly reaction conditions.
Similarly, a study was undertaken to investigate the ideal molar ratio of decaborane necessary to attain
the most advantageous result. The findings of the experiment indicated that the utilisation of decaborane
and the ketone in a 1:1 molar ratio resulted in the most advantageous outcomes. Conversely, a lower
amount of decaborane resulted in partial reduction.
Finally, after different study, the reduction of ketone was conducted within a solvent system comprised
of tetrahydrofuran (THF) and water, utilizing a molar ratio of 1:9, while employing a single equivalent
of decaborane. The implemented procedure resulted in a satisfactory yield. Interestingly, the reduction
did not have any impact on the presence of other functional groups such as bromo, iodo, nitro, and
hydroxy groups. Moreover, the findings of the study revealed that ketones with electron-donating
groups exhibited comparatively lower yields and required extended reaction times in contrast to their
counterparts bearing electron-withdrawing groups.
Table 1. Reduction of ketones using decaborane
Sl
No.
Substrate
Product
1
2
3
4
5
6
7
Solvent
Time
(in
hours)
Temper
ature
(in oC)
Yield
(in %)
THF
17
60
75
THF:H₂O
(1:9)
12
R.T.
83
THF
-
-
-
THF:H₂O
(1:9)
2
R.T.
80
THF
18
60
62
THF:H₂O
(1:9)
1
R.T.
84
THF
12
60
70
THF:H₂O
(1:9)
2
R.T.
82
THF
-
-
-
THF:H₂O
(1:9)
3
R.T.
82
THF
12
60
72
THF:H₂O
(1:9)
1
R.T.
81
THF
-
-
-
THF:H₂O
(1:9)
1
R.T.
84
Microwave
Time(in
minutes)
Yield
(in %)
25
90
5
91
5
96
5
94
5
93
5
93
5
96
EXPERIMENTAL SECTION
General procedure for the reduction of different ketones. A ketone (1
equivalent) and decaborane (1 equivalent) was taken in a flask. THF and water was added to it
in the ratio 1:9 at room temperature under nitrogen and stirred for 1 hour and the completion
of the reaction was monitored by TLC. After completion, the reaction mixture was quenched
with excess water and then extracted with ethanol. The combined organic layer was dried with
Na2SO4. The crude reaction mixture was purified by silica gel column chromatography.
1. Decaborane (91.085mg, 0.745mmol), ketone 1 (200mg, 0.745mmol) in THF:H2O(1:9) gave
pure product 1 as a colourless solid, yield:- 112mg(83%), melting point:-88oC.1H NMR (400
MHz, CDCl3): δ 7.07(d,2H, J = 8.0Hz), 6.70(d,2H, J = 8.8Hz), 3.81(s,1H,-CH), 2.90(s,3H,CH3). 13C NMR (100MHz): δ 149.05, 13.56, 129.52, 113.23, 41.11, 39.97. IR (KBr): 3467(OH stretching).
2. Decaborane (134.14mg, 1.09mmol), ketone 2 (200mg, 1.09mmol) in THF:H2O(1:9) gave
pure product 2 as a colourless solid, yield:- 161mg(80%), melting point:- 68oC.1H NMR (400
MHz, CDCl3): δ 7.38–7.24(m,10H), 5.82(s,1H,-CH). 13C NMR (100MHz): δ 143.89, 128.60,
127.67, 126.64, 76.35. IR (KBr): 3375(-OH stretching).
3. Decaborane (148mg, 1.21mmol), ketone 3 (200mg, 1.21mmol) in THF:H2O(1:9) gave pure
product 3 as an oily liquid, yield:- 169mg(84%).1H NMR (400 MHz, CDCl3): δ 8.14(d, 2H, J
= 9.2Hz), 7.50(d,2H, J = 8.8Hz), 4.98(q,1H,-CH, J = 6.4Hz), 1.48(d,3H,-CH3, J = 6.4Hz).
13
C NMR (100MHz): δ 153.30, 147.14, 126.21, 123.80, 69.51, 25.51. IR (KBr): 3412(-OH
stretching).
4. Decaborane (99.34mg, 0.812mmol), ketone 4 (200mg, 0.812mmol) in THF:H2O(1:9) gave
pure product 4 as an oily liquid, yield:- 166mg(82%).1H NMR (400 MHz, CDCl3): δ
7.65(d,2H , J = 8.4Hz), 7.10(d,2H , J = 8.4Hz), 4.82(q,1H, -CH , J = 6.4Hz), 1.44(d,3H,-CH3
, J = 6.4Hz). 13C NMR (100MHz): δ 145.40, 137.44, 127.36, 92.65, 69.76, 25.17. IR (KBr):
3377(-OH stretching).
5. Decaborane (122.5mg, 1.004mmol), ketone 5 (200mg, 1.004mmol) in THF:H2O(1:9) gave
pure product 5 as an oily liquid, yield:- 166mg(82%).1H NMR (400 MHz, CDCl3): δ
7.41(d,2H , J = 8.0Hz), 7.16(d,2H , J = 8.8Hz), 4.74(q,1H,-CH , J = 6.4Hz), 1.39(d,3H,-CH3 ,
J = 6.4Hz). 13C NMR (100MHz): δ 144.85, 131.57, 127.28, 121.14, 69.67, 25.25. IR (KBr):
3367(-OH stretching).
6. Decaborane (202.88mg, 1.66mmol), ketone 6 (0.2ml, 1.66mmol) in THF:H2O(1:9) gave
pure product 6 as an oily liquid, yield:- 163mg(81%).1H NMR (400 MHz, CDCl3): δ 7.357.27(m,5H), 4.81(q,1H,-CH , J = 6.4Hz), 1.45(d,3H,-CH3 , J = 6.4Hz). 13C NMR (100MHz):
δ 146.07, 128.54, 127.43, 70.24, 25.27. IR (KBr): 3382(-OH stretching).
7. Decaborane (179.53mg, 1.46mmol), ketone 7 (200mg, 1.46mmol) in THF:H2O(1:9) gave
pure product 7 as an oily liquid, yield:- 171mg(84%).1H NMR (400 MHz, CDCl3): δ
7.10(d,2H, J = 8.0Hz), 6.83(d,2H, J = 8.0Hz), 2.63(q,1H,-CH, J = 7.6Hz), 1.26(d,3H,-CH3, J
= 7.6Hz). 13C NMR (100MHz): δ 153.12, 136.47, 128.85, 115.17, 27.88, 15.79. IR (KBr):
3367(-OH stretching).