Cobalt-catalyzed asymmetric hydroboration of aryl ketones with pinacolborane

Article abstract of DOI:10.1039/c5cc01084e

The highly enantioselective cobalt-catalyzed hydroboration reaction of aryl ketones with HBpin was developed using iminopyridine oxazoline ligands. Halides, amines, ethers, sulfides, esters and amides are well tolerated under the mild reaction conditions, demonstrating its synthetic advantage. Substituted diaryl ketones could also be hydroborated with high enantioselectivity.

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Cobalt-Catalyzed Asymmetric Hydroboration of Aryl
Ketones with Pinacolborane
Cite this: DOI: 10.1039/x0xx00000x
Jun Guo,† Jianhui Chen † and Zhan Lu *
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
Highly enantioselective cobalt-catalyzed hydroboration of aryl
ketones with HBpin was developed using iminopyridine
oxazoline ligands. Halides, amines, ethers, sulfides, esters and
amides are well tolerated under the mild reaction conditions,
demonstrating its synthetic advantage. Substituted diaryl
ketones could also be hydroborated with high enantioselectivity.
Optically active sencondary alcohols are extremely useful precursors
for bioactive molecules1 (Fig. 1), as well as valuable synthetic
intermediates. One of the most fundamental methods for synthesis of
these compounds is enantioselective reduction of prochiral ketones,
for example, asymmetric hydrogenation2 and hydrosilylation.3
Asymmetric hydroboration of ketones is also an efficient strategy to
achieve optically active alcohols.4 Since Itsuno5 and Corey6
disclosed the first oxazoboroline-catalyzed asymmetric reduction of
ketones with borane reagents, enormous progress has been made in
borane reduction. Pinacolborane (HBpin) is a synthetic useful borane
reagent,7 and could potentially tolerate a variety of different
functional groups. To the best of our knowledge, it has not been
sucessfully applied in asymmetric hydroboration of ketones.8
Due to the lower costs and toxicity, as well as the excellent
tolerance to various functional groups, cobalt catalysts have received
growing attention during the last two decades.9 Enantioselective
cobalt catalysis has also contributed to the development of various
asymmetric transformations.10 Cobalt-catalyzed asymmetric
hydroboration of ketones was firstly reported by Mukaiyama in
199511 and developed by Yamada12. The modified borohydride
solution has to be prepared by mixing of over stoichiometric amount
of NaBH4, CHCl3, ethanol and tetrahydrofurfuryl alcohol at 0 oC
under nitrogen or argon atmosphere and stirred for 3 h, additionally,
the reactions were usually carried out at low temperature (-40-0 oC).
Although aryl ketones and steric bulky aliphatic ketones were
successfully reduced to afford the corresponding alcohols in 61-99%
ee, the chiral ligands are still limited in semicorrin structure.
Recently, the Huang group13 and our group14 independently
developed cobalt-catalyzed asymmetric hydroboration of styrenes
Fig. 1 Bioactive compounds derivatized from chiral sencondary alcohols.
with pinacolborane (HBpin)15 using iminopyridine oxazoline ligands.
We also disclosed that a chiral iron catalyst could pomote the highly
enantioselective hydroboration of 1,1-disubstituted styrenes.16
Herein, we demonstrate iminopyridine oxazoline metal complex–
catalyzed highly enantioselective hydroboration of aryl ketones with
HBpin under the mild conditions.
We chose acetophenone 2a as the model substrate to conduct the
hydroboration reaction with HBpin in the presence of earth abundant
transition metal complexes (2.5 mol%) and NaHBEt3 under a
nitrogen atmosphere using diethyl ether as the solvent at room
temperature (Table 1). Using 1a as a catalyst and NaHBEt3 as a
redutive reagent, which is the best catalytic system for asymmetric
hydroboration of alkenes, the hydroboration of 2a is quite efficient
to afford the (R)-1-phenylethan-1-ol in an excellent yield with 83%
ee. After screening a variety of metal catalysts, we found that cobalt
catalyst 1g gave a high yield and best enantioselectivity , and the
reaction could be easily reproduced (entry 7). Using iron complex
(1h) instead of 1g, the enantioselectiveity was decreased (entry 8).17
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Table 1 Optimization studies for asymmetric hydroboration of ketones with
HBpina
Scheme 1 Gram-Scale Reaction.
equiv of HBpin gave a similar result (entry 12). Although a
additional water still gave a high yield, it did diminish the
enantioselectivity (entry 13).
With the best complex 1g in hands, studies exploring the scope of
Entry
Cat. (mol%)
Yield (%)b
ee (%)c
this process are summarized in Table 2. 1)
A variety of
acetophenones with both electron-rich and electron-deficient groups
at the para-, meta- or ortho- positions on the phenyl ring are capable
of being reduced to afford chiral 1-arylethan-1-ols in good yields
with excellent enantioselectivities; 2) Halides, amines, ethers,
sulfides, esters and amides are well tolerated, demonstrating the
synthetic advantage; 3) Long alkyl chains or functionalized alkyl
chains have been shown to be suitable partners for aryl ketones,
leading to the desired products with high enantioselectivities; 4)
Five-, six- and seven-membered cyclic aryl ketones also reacted to
afford cyclic alcohols in excellent yields with ≥99% ee; 5) 2-
Acetonaphthone and acetylferrocene provide chiral alcohols with
1
2
3
4
5
6
7
8
1a (2.5)
1b (2.5)
1c (2.5)
1d (2.5)
1e (2.5)
1f (2.5)
1g (2.5)
1h (2.5)
1g (1.0)
1g (0.5)
1g (2.5)
1g (2.5)
1g (2.5)
99
99
96
97
99
89
98
98
98
83
99
97
92
83
89
45
81
78
66
98
67
95
92
97
97
84
9
10
11d
12e
13f
≥95% ee, but 2-acetylbenzylfuran gives
a
slightly lower
enantioselectivity; 6) Dialiphatic ketones also participate in this
reaction to afford the alcohols in 67-94% yield with 17-64% ee; 7)
Gratifyingly, diaryl ketones (2an and 2ano) with ortho-substitution
could be hydroborated in 90% ee and 87% ee, respectively.
Gram-scale reaction took place smoothly to give the
corresponding chiral alcohol 3ao in 98% yield. (Scheme 1).
a The reactions were conducted using 2a (1.0 mmol), HBpin (1.2 mmol) in a
solution of ether (1 mL) at room temperature under the atmosphere of N2 for
2 h. b Yields were determined by 1H NMR using trimethylsilylbenzene as an
internal standard. Ee values were determined by HPLC. d At 0 C. e Using
c
0
1.0 mmol of HBpin. f 0.1 mmol of water was added.
In summary, we have developed a cobalt-catalyzed highly
enantioselective hydroboration of aryl ketones with pinacolborane.
Halides, amines, ethers, sulfides, esters and amides are well tolerated
under the mild conditions, demonstrating its synthetic advantage.
Substituted diaryl ketones could also be reduced with high
Even with 0.5 mol% of catalyst loading, high ee value (92%) could
still be achieved (entry 10). Decreasing the temperature to 0 C, no
further improvement was observed (entry 11). The reaction with 1
o
a
Table 2 Products of the Cobalt-Catalyzed Asymmetric Hydroboration of Aryl Ketones with HBpin
a Standard conditions: Unless otherwise noted, ketone (1 mmol), HBpin (1.2 mmol), 1g (0.025 mmol), NaBHEt3 (0.025 mmol) in 1 mL of Et2O at rt under
nitrogen for 2 h. b THF instead of Et2O
2 | J. Name., 2012, 00, 1-3
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our laboratory are underway to understand the mechanistic
intricacies of this process and develop new asymmetric reactions
based on non-noble transition metals.
We thank the National Science Foundation of China (21472162)
and the “Thousand Youth Talents Plan” for finacial support. We
thank Mr. Tuo Xi, Mr. Bo Yang and Mr. Xiang Ren for synthesis of
ligands and racemic alcohols.
J. Guo and J.-H. Chen are contributed equally to this work.
Notes and references
Department of chemistry, Zhejiang University, Hangzhou 310027, China
8
luzhan@zju.edu.cn
† Electronic Supplementary Information (ESI) available: Experimental
procedures,
NMR
spectra
and
HPLC
spectra.
See
DOI: 10.1039/c000000x/
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