Lithium tert-Butoxide-catalyzed Hydroboration of Carbonyl Compounds

Article abstract of DOI:10.1002/bkcs.11855

We report the successful hydroboration of aldehydes and ketones with pinacolborane using 1 mol % lithium tert-butoxide under ambient conditions. The present protocol was applicable to various aldehydes and ketones, and the corresponding boronate esters and subsequent alcohols were obtained in good to excellent yields. In addition, this high-yielding practical method could be extended to the reduction of ester groups. Under optimized conditions, LiO^tBu facilitate the hydroboration of ester groups quantitatively.

Full text of DOI:10.1002/bkcs.11855

Article
DOI: 10.1002/bkcs.11855
BULLETIN OF THE
J. H. Kim et al.
KOREAN CHEMICAL SOCIETY
Lithium tert-Butoxide-catalyzed Hydroboration of Carbonyl
Compounds
*
Jea Ho Kim, Ashok Kumar Jaladi, Hyun Tae Kim, and Duk Keun An
Department of Chemistry, Kangwon National University, and Institute for Molecular Science and Fusion
Technology, Chunchon 24341, Republic of Korea. *E-mail: dkan@kangwon.ac.kr
Received July 7, 2019, Accepted July 26, 2019, Published online August 28, 2019
We report the successful hydroboration of aldehydes and ketones with pinacolborane using 1 mol % lith-
ium tert-butoxide under ambient conditions. The present protocol was applicable to various aldehydes and
ketones, and the corresponding boronate esters and subsequent alcohols were obtained in good to excel-
lent yields. In addition, this high-yielding practical method could be extended to the reduction of ester
groups. Under optimized conditions, LiOtBu facilitate the hydroboration of ester groups quantitatively.
Keywords: Hydroboration, Lithium tert-butoxide, Aldehydes, Ketones, Esters, Pinacolborane (HBpin)
Introduction
(LiAlH4, LiBH4)13 require stoichiometric amount of
reagents, while metal-mediated hydrogenation requires high
pressure and temperatures.14 Therefore, metal-catalyzed
In recent years, hydroboration reactions have gained much
attention because of their simplicity and mildness as well
as the practical application of resulting boron derivatives.1
Moreover, a diverse range of catalytic systems toward
hydroboration of carbonyl compounds, including transition
metals,2 main group metals,3 lanthanide complexes,4 and
acid–base pairs have been investigated.5 More recently,
mild reagents such as commercial metal alkyls, alkoxides,
and hydride reducing agents have been identified as cata-
lysts for the efficient hydroboration of aldehydes and
ketones.
hydro-functionalization
(hydrosilylations/hydroboration)
under ambient conditions would be most useful, and several
metal-mediated hydrosilylations have been reported for
ester reduction.15 However, there are very few examples of
catalyzed hydroborations for esters.16
Given the synthetic utility of the abovementioned
transformation (hydroboration of aldehydes, ketones,
and esters) and successful recent findings in this regard,
we attempted to understand the effect of counter metal
cation (Li+) on catalytic hydroboration. Herein, we wish
to report the lithium tert-butoxide (LiOtBu) mediated
hydroboration of aldehydes, ketones, and esters
(Scheme 1).
Clark et al. reported the alkoxide (NaOtBu)-mediated
hydroboration of ketones with pinacolborane and
achieved complete reduction with 5 mol % catalyst load-
ing.6 More recently, Wu et al.7 reported that hydro-
boration of aldehydes and ketones with powdered NaOH
as catalyst and HBpin. Wu and coworkers reported the
use of a cobalt(II) coordination polymer and KOtBu as
the activator to catalyze the hydroboration of aldehydes
and ketones.8 We previously developed an effective
method for the selective hydroboration of aldehyde over
ketones with sodium hydride (NaH).9 Stachowiak
et al.10 reported the solvent- and catalyst-free hydro-
boration of aldehydes, but this method was not feasible
to other carbonyl compounds. Zhu et al.11 described the
selective hydroboration of aldehydes and ketones using
n-butyllithium as catalyst, thus confirming the impor-
tance of the present transformation. Each of these cata-
lytic systems has its specific advantages in terms of
yields and selectivities.
Results and Discussion
First, we optimized various reaction parameters such as cat-
alyst load, number of equivalents of the reagent (HBpin),
and reaction time for aldehyde hydroboration. The results
are summarized in Table 1. Accordingly, benzaldehyde was
treated with 1 mol % LiOtBu and 1.3 equiv. HBpin in THF
(entry 1), and complete conversion of the aldehyde
occurred in 30 min (>99%). Further, 96% conversion was
achieved when the reaction was carried out with 0.5 mol %
LiOtBu (entry 2). A similar conversion (96%) was afforded
with 1 mol % catalyst loading within 5 min reaction (entry
3). Up on decreasing the amount of pinacolborane
(1.1 equiv), no deviation in stochiometric conversion of
aldehyde was found, observed 83% of boronate ester in GC
(entry 4). We mainly focused on the stochiometric conver-
sion of benzaldehyde to the corresponding boronate ester,
hence we chose the conditions corresponding to entry 1 as
the optimal conditions. Further, we optimized the
On the other hand, the preparation of alcohols from ester
has been encountered during the chemical transformation of
many complex natural molecule syntheses.12 Traditional
reduction systems using highly reactive metal hydrides
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increased (entry 2). Prior to achieving the maximum
conversion, the catalyst load was slightly increased. A
high yield of 99% was obtained when 0.4 equiv of the
catalyst used (entry 4). Reducing the mole ratio of
pinacolborane from 3.0 to 2.5 equiv reduced the yield
of the alcohol to 85% (entry 5). Under reflux condi-
tions, stoichiometric conversion was achieved with
0.3 equiv (30 mol %) of LiOtBu (entry 6). Nevertheless,
a reasonable yield of the product was obtained when
reaction was carried out under reflux condition with
0.2 equiv of the catalyst (89% entry 7). From the above
data, we concluded that 0.4 equiv (40 mol %) of LiOtBu
and 3.0 equiv of pinacolborane are required for stoi-
chiometric hydroboration of the ester group at room
temperature.
Given the successful hydroboration of ethyl benzoate,
we explored the optimized conditions for expanding the
substrate scope with various ester groups. The results are
shown in Table 4. Most of the esters we considered were
amenable to the present system and underwent quantita-
tive conversion to the corresponding alcohols. Isopropyl
benzoate reduced quantitatively under reflux condition
(entry 2). While tert-butyl benzoate did not undergo the
hydroboration due to its bulky nature (entry 3). Aromatic
esters with electron-donating/electron-withdrawing substit-
uents showed similar reactivity in this system. Poly-
aromatic and heteroaromatic esters reacted with
pinacolborane to afford the corresponding alcohols in
excellent yields (entries 11 and 12). Further, an aliphatic
ester (ethyl hexanoate) smoothly underwent the catalytic
hydroboration and afforded corresponding alcohol in good
yield (entry 13).
Scheme 1. LiOtBu catalyzed hydroboration of aldehydes, ketones,
and esters
conditions for the reaction of ketone (acetophenone), which
was perfectly reduced to corresponding boronate ester with
1.3 equiv HBpin and 1 mol % LiOtBu (entry 5).
With the optimized conditions in hand, we next
focused on the reduction of various aldehyde and
ketones to the corresponding boronate esters, followed
by conversion to the subsequent alcohols (Table 2). All
the tested substrates underwent the hydroboration
smoothly to allow for complete conversion of the
aldehydes/ketones. Electron-withdrawing substrates
were furnished stoichiometric yields, compare to elec-
tron donating ones. Heteroaryl (furan-2-carbaldehyde),
conjugated
(cinnamaldehyde),
and
aliphatic
(hexanaldehyde) aldehydes also successfully underwent
hydroboration with 1 mol % LiOtBu (entries 8–10). Var-
ious ketones (benzophenone, acetophenone, 4-nitro
acetophenone, and cyclohexanone) were also converted
smoothly, and the hydroboration proceeded stoichiomet-
rically under similar conditions (entries 11–14).
Given the rapid hydroboration of aldehyde and
ketones, we next turned our interest to the reduction of
an ester group. Accordingly, the reaction conditions
were optimized to achieve the maximum yield and con-
version. As seen in Table 3, ethyl benzoate was treated
with pinacolborane in the presence of 30 mol % LiOtBu
to obtain the corresponding alcohol in 74% yield (entry
1). A similar yield was obtained when reaction time was
Finally, chemoselective reduction was conducted for
aldehyde in the presence of an ester. Accordingly, benzal-
dehyde was treated with pinacolborane over ethyl benzoate
with excellent chemoselectivity (Scheme 2).
Table 1. Optimization of reaction conditions for hydroboration of aldehyde and ketones
Reaction condition
Entry
R
HBpin
LiOtBu
Time
Conversion(%)a (alcohol)
Yield(%)b
1
2
3
4
5c
H
H
H
H
CH3
1.3
1.3
1.3
1.1
1.3
1.0 mol %
0.5 mol %
1.0 mol %
1.0 mol %
1.0 mol %
30 min
30 min
5 min
30 min
30 min
99 (0)
96 (0)
96 (0)
99 (16)
99 (0)
99
95
94
99
99
a Conversions were determined on the basis of the consumption of the aldehyde or ketone.
b Yields were determined by GC.
c Yields were determined by 1H NMR.
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Catalytic Hydroboration of Carbonyl Compounds with Lithium t-butoxide
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Table 2. Scope of the hydroboration of aldehydes and ketones
Table 3. Optimization of parameters for hydroboration of ester
group
mediated by 1 mol % LiOtBu
Reaction condition
Entry HBpin LiOtBu (mol %) Time Temp. Yield(%)a
Entry
1
Aldehydes
Conversiona
99
Product
Yield(%)b
99
1
2
3
4
5
6
7
3.0
3.0
3.0
3.0
2.5
3.0
3.0
30
30
40
40
40
30
20
6 h
12 h
3 h
6 h
6 h
RT
RT
RT
RT
RT
74
73
97
99
85
99
89
2
94
94
3
4
99
99
90
90
3 h
24 h
reflux
reflux
a Yields were determined by GC.
5
99
89
various aldehydes and ketones with stoichiometric conver-
sion. In addition, suitable reaction conditions for the hydro-
boration of esters were established. This method is a
practical alternative to existing complex metal systems and
is the best addition to the existing literature on catalyzed
hydroboration.
6
7
88(35)
88
79
79 (17)
8c
9
99
99
97
99
Experimental
General. All glassware used was dried thoroughly in an
oven, assembled hot, and cooled under a stream of dry
nitrogen prior to use. All reactions and manipulations of
air- and moisture-sensitive materials were carried out using
standard techniques for the handling of such materials. All
chemicals were commercial products of the highest purity
which were further purified before use by using standard
methods. HBpin, aldehydes, and ketones were purchased
from Aldrich Chemical Company (Seoul, Korea), Alfa
Aesar (Lancashire, UK), and Tokyo Chemical Industry
Company (TCI, Tokyo, Japan). 1H NMR spectra were mea-
sured at 400 MHz with CDCl3 as a solvent at ambient tem-
perature unless otherwise indicated and the chemical shifts
were recorded in parts per million downfield from tetra-
methylsilane (δ = 0 ppm) or based on residual CDCl3
(δ = 7.26 ppm) as the internal standard. 13C NMR spectra
were recorded at 100 MHz with CDCl3 as a solvent and
referenced to the central line of the solvent (δ = 77.0 ppm).
The coupling constants (J) are reported in hertz. Analytical
thin-layer chromatography (TLC) was performed on glass
precoated with silica gel (60 F254; Merck, Darmstadt, Ger-
many). Column chromatography was carried out using
70–230 mesh silica gel (Merck) at normal pressure. GC
analyses were performed on a Younglin Acme 6100 M and
6500 GC FID chromatography (Seoul, Korea), using an
10
99
99
99
99
11c
12c
13c
99
99
99
99
14c
99
99
a Conversions were determined on the basis of the consumption of the
aldehyde or ketone.
b Yields were determined by GC.
c Yields were determined by 1H NMR.
Conclusion
In conclusion, we have identified an efficient catalytic sys-
tem for the hydroboration of aldehydes and ketones under
ambient condition. Experimental results showed that 1 mol
% LiOtBu successfully enabled the hydroboration of
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Catalytic Hydroboration of Carbonyl Compounds with Lithium t-butoxide
KOREAN CHEMICAL SOCIETY
Table 4. Scope of hydroboration of esters mediated by LiOtBu
Yield
Entry
1
Esters
Conversiona
99
Product
(%)b
99
Scheme 2. LiOtBu catalyzed hydroboration of aldehyde over an
ester
2c
3d
4e
96
0
96
0
(0.05 mL, 0.5 mmol), pinacolborane (0.09 mL, 0.65 mmol),
t
ꢀ
and 5 mL of THF at 0 C. To this, LiO Bu (0.1 mL 0.05 M
in THF, 1 mol %) was added dropwise and stirred for
30 min at room temperature. After completion of the reac-
tion (GC), it was stopped by H2O (two drops). GC analysis
99
99
showed
99%
of
2-(benzyloxy)-4,4,5,5-tetramethyl-
5e
99
99
1,3,2-dioxaborolane. To the reaction mixture was added
1 N NaOH (2 mL) and stirred for 1 h at room temperature.
The crude mixture was extracted with diethyl ether (2 × 10
mL) and combined organic layers were dried over MgSO4.
GC analysis showed a 99% yield of benzyl alcohol. All
products in Table 2 were confirmed through comparison
with 1H NMR and GC data of the authentic sample.
6e
7
99
99
99
99
General Procedure for the Catalyzed Hydroboration of
Esters. The following experimental procedure for the syn-
thesis of benzyl alcohol from ethyl benzoate is representa-
tive (Table 4). A dry and argon-flushed flask, equipped
with a magnetic stirring bar was charged with ethyl benzo-
ate (0.07 mL, 0.5 mmol), pinacolborane (0.22 mL,
8e
99
99
9e
99
99
99
99
99
99
t
ꢀ
10e
11f
1.5 mmol), and 5 mL of THF at 0 C. To this, LiO Bu
(0.4 mL 0.5 M in THF, 1 mol %) was added dropwise and
stirred for 30 min at room temperature. After completion
of the reaction (GC), it was stopped by H2O (two drops).
GC analysis showed 99% of 2-(benzyloxy)-4,-
4,5,5-tetramethyl-1,3,2-dioxaborolane. To the reaction
mixture was added 1 N NaOH (2 mL) and stirred for 1 h
at room temperature. The crude mixture was extracted
with diethyl ether (2 × 10 mL) and combined organic
layers were dried over MgSO4. GC analysis showed a
99% yield of benzyl alcohol. All products in Table 4 were
12e
13
99
99
96
90
a Conversions were determined on the basis of the consumption of the
ester.
1
confirmed through comparison with H NMR and GC data
b Yields were determined by GC.
c Reflux 3 h.
of the authentic sample.
d Reflux 24 h.
Procedure for the Chemoselective Catalytic Hydro-
boration of Benzaldehyde over Ethyl 4-Methylbenzoate.
A dry and argon-flushed flask, equipped with a magnetic
stirring bar was charged with benzaldehyde (0.05 mL,
0.5 mmol), ethyl 4-methylbenzoate (0.08 mL, 0.5 mmol),
pinacolborane (0.09 mL, 0.65 mmol), and 5 mL of THF
at room temperature. To this, LiOtBu (0.1 mL 0.05 M in
THF, 1 mol %) was added dropwise and stirred for
30 min at the same temperature (Scheme 1). After com-
pletion of the reaction, it was stopped by H2O (two
drops). GC analysis showed 95% of 2-(benzyloxy)-4,-
4,5,5-tetramethyl-1,3,2-dioxaborolane and 99% of ethyl
4-methylbenzoate.
e Yields were determined by 1H NMR.
f Reaction time was 12 h.
HP-5 capillary column (30 m). All GC yields were deter-
mined with the use of naphthalene as the internal standard
and the authentic sample.
General Procedure for the Catalyzed Hydroboration of
Aldehydes and Ketones. The following experimental pro-
cedure for the synthesis of benzyl alcohol is representative
(Table 2). A dry and argon-flushed flask, equipped with a
magnetic stirring bar was charged with benzaldehyde
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M. Xue, Y. Hong, Y. Yao, Q. Shen, Org. Lett. 2017,
19, 3382.
Acknowledgments. This study was supported by the
National Research Foundation of Korea Grant funded by
the Korean Government (2017R1D1A1B03035412).
5. (a) J. Schneider, C. P. Sindlinger, S. M. Freitag, H. Schubert,
L. Wesemann, Angew. Chem. Int. Ed. 2017, 56, 333.
(b) P. Eisenberger, A. M. Bailey, C. M. Crudden, J. Am.
Chem. Soc. 2012, 134, 17384. (c) M. Fleige, J. Möbus,
T. vom Stein, F. Glorius, D. W. Stephan, Chem. Commun.
2016, 52, 10830. (d) J. R. Lawson, L. C. Wilkins,
R. L. Melen, Chem. Eur. J. 2017, 23, 10997.
(e) J. R. Lawson, R. L. Melen, Inorg. Chem. 2017, 56, 8627.
6. I. P. Query, P. A. Squier, E. M. Larson, N. A. Isley,
T. B. Clark, J. Org. Chem. 2011, 76, 6452.
7. Y. Wu, C. Shan, J. Ying, J. Su, J. Zhu, L. Leo, Y. Zhao,
Green Chem. 2017, 19, 4169.
8. J. Wu, H. Zeng, J. Cheng, S. Zheng, J. A. Golen,
D. R. Manke, G. Zhang, J. Org. Chem. 2018, 83, 9442.
9. W. K. Shin, H. Kim, A. K. Jaladi, D. K. An, Tetrahedron
2018, 74, 6310.
References
1. (a) C. C. Chong, R. Kinjo, ACS Catal. 2015, 5, 3238.
(b) J. V. Obligacion, P. J. Chirik, Nat. Rev. Chem. 2018,
2, 15.
2. (a) S. Bagherzadeh, N. P. Mankad, Chem. Commun. 2016,
52, 3844. (b) J. Guo, J. Chen, Z. Lu, Chem. Commun. 2015,
51, 5725. (c) G. Zhang, H. Zeng, J. Wu, Z. Yin, S. Zheng,
J. C. Fettinger, Angew. Chem. Int. Ed. 2016, 55, 14369.
(d) N. Eedugurala, Z. Wang, U. Chaudhary, N. Nelson,
K. Kandel, T. Kobayashi, I. I. Slowing, M. Pruski,
A. D. Sadow, ACS Catal. 2015, 5, 7399. (e) M. W. Drover,
L. L. Schafer, J. A. Love, Angew. Chem. Int. Ed. 2016, 55,
3181. (f) S. R. Tamang, M. Findlater, J. Org. Chem. 2017,
82, 12857. (g) R. Arévalo, C. M. Vogels, G. A. MacNeil,
L. Riera, J. Pérez, S. A. Westcott, Dalton Trans. 2017, 46, 7750.
(h) A. A. Oluyadi, S. Ma, C. N. Muhoro, Organometallics 2013,
32, 70. (i) A. Harinath, J. Bhattcharjee, K. R. Gorantla,
B. S. Mallik, T. K. Panda, Eur. J. Org. Chem. 2018, 24, 3180.
(j) W. Wang, X. Shen, F. Zhao, H. Jiang, W. Yao,
S. A. Pullarkat, L. Xu, M. Ma, J. Org. Chem. 2018, 83, 69.
3. (a) L. Fohlmeister, A. Stasch, Chem. Eur. J. 2016, 22, 10235.
(b) C. C. Chong, H. Hirao, R. Kinjo, Angew. Chem. Int. Ed.
2015, 54, 190. (c) M. Arrowsmith, T. J. Hadlington,
M. S. Hill, G. Kociok-Koehn, Chem. Commun. 2012, 48,
4567. (d) T. J. Hadlington, M. Hermann, G. Frenking, C. Jones,
J. Am. Chem. Soc. 2014, 136, 3028. (e) Z. Yang, M. Zhong,
X. Ma, S. De, C. Anusha, P. Parameswaran, H. W. Roesky,
Angew. Chem. Int. Ed. 2015, 54, 10225. (f) V. K. Jakhar,
M. K. Barman, S. Nembenna, Org. Lett. 2016, 18, 4710.
(g) Y. Wu, C. Shan, Y. Sun, P. Chen, J. Ying, J. Zhu, L. Liu,
Y. Zhao, Chem. Commun. 2016, 52, 13799. (h) D. Mukherjee,
S. Shirase, T. P. Spaniol, K. Mashima, J. Okuda, Chem.
Commun. 2016, 52, 13155. (i) K. Manna, P. Ji, F. X. Greene,
W. Lin, J. Am. Chem. Soc. 2016, 138, 7488. (j) V. A. Pollard,
S. A. Orr, R. McLellan, A. R. Kennedy, E. Hevia,
R. E. Mulvey, Chem. Commun. 2018, 54, 1233.
10. H. Stachowiak, J. Kaźmierczak, K. Kucinski, G. Hreczycho,
Green Chem. 2018, 20, 1738.
11. Z. Zhu, X. Wu, X. Xu, Z. Wu, M. Xue, Y. Yao, Q. Shen,
X. Bao, J. Org. Chem. 2018, 83, 10677.
12. P. Wipf, J. T. Reeves, R. Balachandran, B. W. Day, J. Med.
Chem. 2002, 45, 1901.
13. (a) J. Seyden-Penne, Reductions by the Alumino- and Borohy-
drides, Wiley-VCH, New York, 1991. (b) H. C. Brown,
S. Narasimhan, Y. M. Choi, J. Org. Chem. 1982, 47, 4702.
(c) L. Pasumansky, D. Haddenham, J. W. Clary, G. B. Fisher,
C. T. Goralski, B. Singaram, J. Org. Chem. 2008, 73, 1898.
14. Y. Pouilloux, F. Autin, J. Barrault, Catal. Today 2000,
63, 87.
15. (a) L. Pehlivan, E. Metay, S. Laval, W. Dayoub,
D. Delbrayelle, G. Mignani, M. Lemaire, Eur. J. Org. Chem.
2011, 2011, 7400. (b) D. Addis, S. Das, K. Junge, M. Beller,
Angew. Chem. Int. Ed. 2011, 50, 6004. (c) X. Verdaguer,
M. C. Hansen, S. C. Berk, S. L. Buchwald, J. Org. Chem.
1997, 62, 8522. (d) M. T. Reding, S. L. Buchwald, J. Org.
Chem. 1995, 60, 7884. (e) S. C. Berk, K. A. Kreutzer,
S. L. Buchwald, J. Am. Chem. Soc. 1991, 113, 5093.
16. (a) D. Mukherjee, A. Ellern, A. D. Sadow, Chem. Sci. 2014,
5, 959. (b) D. Mukherjee, S. Shirase, T. P. Spaniol,
K. Mashima, J. Okuda, Chem. Commun. 2016, 52, 13155.
(c) M. K. Barman, A. Baishya, S. Nembenna, Dalton Trans.
2017, 46, 4152.
4. (a) V. L. Weidener, C. J. Barger, M. Delferro, T. L. Lohr,
T. J. Marks, ACS Catal. 2017, 7, 1244. (b) S. Chen, D. Yan,
Bull. Korean Chem. Soc. 2019, Vol. 40, 971–975
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