Fast Enantio- and Chemoselective Arylation of Ketones with Organoboronic Esters Enabled by Nickel/N-Heterocyclic Carbene Catalysis

Article abstract of DOI:10.1002/anie.202015021

A general, efficient, highly enantio- and chemoselective N-heterocyclic carbene (NHC)/Ni-catalyzed addition of readily available and stable arylboronic esters to ketones is reported. This protocol provides unexpectedly fast access (usually 10 min) to various chiral tertiary alcohols with exceptionally broad substrate scope and excellent functional group tolerance (76 examples, up to 98 % ee). This process is orthogonal to other known Ni-mediated Suzuki–Miyaura couplings, as it tolerates aryl chlorides, fluorides, ethers, esters, amides, nitriles, and alkyl chlorides. The reaction is applied to late-stage modifications of various densely functionalized medicinally relevant molecules. Preliminary mechanistic studies suggest that a rare enantioselective η²-coordinating activation of ketone carbonyls is involved. This cross-coupling-like mechanism is expected to enable other challenging transformations of ketones.

Full text of DOI:10.1002/anie.202015021

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Accepted Article
Title: Fast Enantio- and Chemoselective Arylation of Ketones with
Organoboronic Esters Enabled by Nickel/NHC Catalysis
Authors: Yuan Cai, Lin-Xin Ruan, Abdul Rahman, and Shi-Liang Shi
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Fast Enantio- and Chemoselective Arylation of Ketones with
Organoboronic Esters Enabled by Nickel/NHC Catalysis
Yuan Cai,[a] Lin-Xin Ruan,[a] Abdul Rahman,[a] Shi-Liang Shi*[a][b]
Dedication to the 70th anniversary of Shanghai Institute of Organic Chemistry (SIOC)
[a] Dr. Y. Cai, Mr. L.-X. Ruan, Dr. A. Rahman, and Prof. Dr. S.-L. Shi
State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of
Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China. E-mail: shiliangshi@sioc.ac.cn
[b] Prof. Dr. S.-L. Shi
School of Pharmacy, Fudan University, Shanghai 201203, China.
Supporting information for this article is given via a link at the end of the document.
Abstract: A general, efficient, highly enantio- and chemoselective
NHC/Ni-catalysed addition of readily available and stable arylboronic
esters to ketones is reported. This protocol provides unexpectedly
fast access (usually 10 min) to various chiral tertiary alcohols with
exceptionally broad substrate scope and excellent functional group
tolerance (76 examples, up to 98% ee). This process is orthogonal
to other known Ni-mediated Suzuki-Miyaura couplings, as it tolerates
aryl chlorides, fluorides, ethers, esters, amides, nitriles, and alkyl
chlorides. We successfully applied the reaction to late-stage
modifications of various densely functionalized medicinally relevant
molecules. Preliminary mechanistic studies suggest that a rare
enantioselective η2-coordinating activation of ketone carbonyls is
involved. This cross-coupling-like mechanism is expected to enable
other challenging transformations of ketones.
Optically active tertiary alcohols constitute an important
class of structural units that are commonly found in
pharmaceuticals, agrochemicals, and bioactive natural products
(Fig. 1A)1. Moreover, they served as versatile building blocks for
Figure 1. Construction of chiral tertiary alcohols via ketone additions
the synthesis of challenging targets, including all-carbon
quaternary stereocenters2. Consequently, general methods to
construct chiral tertiary alcohols have long been sought after in
the chemical community3-4. Since the discovery of the Grignard
reaction, the nucleophilic addition of organometallic reagents to
ketones has been recognized as the most convenient method to
addition generally suffers from low reactivities due to the
increased steric hindrance and attenuated electrophilicity of the
carbonyl group. Furthermore, the enantiofacial differentiation of
ketones is more challenging3-5. Indeed, although there are
various reports on asymmetric arylboration of aldehyde8,
examples of analogous ketone addition are scarce and largely
limited to electronically activated substrates9 and intramolecular
reactions10, or resulted in low enantioselectivity11. The single
example of highly enantioselective catalytic arylboration of
simple ketones has recently been reported by Deng, Tang, and
co-workers, although the use of a noble metal (rhodium) catalyst,
aryl ketones, and arylboroxines substrates is required12.
Therefore, a general, practical, and enantioselective addition to
simple ketones of arylboronic esters for the synthesis of chiral
tertiary alcohols remains to be established.
We sought a chiral ligand for an earth-abundant metal
catalyst to address the abovementioned longstanding unmet
problems. We have recently developed a series of bulky C2-
symmetric chiral N-heterocyclic carbenes (NHCs)13, namely
ANIPE- and SIPE-type ligands, and successfully applied them to
asymmetric transition-metal catalysis14. We anticipate the
presence of multiple C2-symmetric chiral axes, as well as bulky
and tunable N-substituents on the NHCs, would allow for high
levels of enantiocontrol. Herein, we describe a general and
highly enantioselective addition of arylboronic esters to simple
ketones enabled by a Ni/NHC catalysis, providing exceptionally
synthesize achiral or chiral tertiary alcohols5-6
. Although
tremendous efforts have been devoted to carbonyl addition
chemistry in the past century, several longstanding challenges
remain (Fig. 1B). First, the use of highly basic and nucleophilic
organometallic reagents, such as organomagnesium,
organozinc, or organoaluminium, makes the reactions less
tolerant to functional groups. Moreover, the moisture- and air-
sensitive nature of these organometallics further complicates
their preparation. As a result, these methods are usually not
suitable for the direct transformation of highly functionalized
compounds or late-stage functionalization of bioactive molecules.
In contrast, the wide availability and stability of organoboron
nucleophiles have imparted exceptional functional group
tolerance and great operational simplicity to the Suzuki-Miyaura
couplings, making it one of the most frequently used reactions in
organic chemistry7. In this context, we envisioned that an
enantioselective addition method to ketones using arylboron
nucleophiles instead of difficult-to-handle organometallics would
greatly facilitate the preparation of chiral tertiary alcohols.
However, in sharp contrast to aldehyde additions, the ketone
1
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efficient and expedient access to a wide variety of chiral tertiary
alcohols (Fig. 1C). Importantly, this protocol was found
Table 1. Reaction Optimization
applicable to
a series of highly functionalized drugs or
intermediates derived from biologically relevant molecules.
We started the studies by treating the model substrate 2-
acetonaphthone (1a) with phenylboronic acid neopentylglycol
ester (PhBneo, 2a) in the presence of nickel catalyst and CsF.
At first, a series of commonly used chiral phosphine and NHC
ligands were tested and found to be ineffective for this arylation
reaction (see Supporting Information (SI)). However, the use of
our ANIPE ligand (L1/HCl, Table 1, entry 1) gave promising
results; the tertiary alcohol product 3a was obtained in
quantitative yield with 80% ee. The use of a bulkier ligand L2
successfully delivered 3a in improved enantioselectivity of 86%
ee (entry 2). Saturated SIPE-type and unsaturated IPE-type
ligands all decreased the enantioselectivity (entries 3-5).
Compared to the arene solvent, ether and hydrocarbon solvent
both afford slightly higher enantioselectivity (entries 6-7), and
cyclohexane was chosen as the optimal solvent to give 3a in 90%
ee. Decreasing the reaction temperature to 50 oC could maintain
the reactivity and increase the enantioselectivity to 94% ee
(entry 8). The use of bulkier phenylboronic acid pinacol ester
(PhBpin) could give similar reaction outcomes (94 % ee, entry 9).
Importantly, we found that 2 mol% catalyst loading was enough
to promote this reaction (entry 10). Further screening using
MeONa as the base gave 3a in quantitative yield with 95% ee
(entry 11). To our surprise, this reaction was extremely fast and
finished in 10 min at 50 ℃ to afford the product in 98% isolated
yield with 95% ee (entry 12). Interestingly, we found the use of a
less bulky ligand (L6, with 2,6-diisopropylaniline fragments) and
Entry
Ligand
Solvent
Temp.
(oC)
80
80
80
80
80
80
80
50
50
50
50
50
50
50
Yield
(%)[a]
99
99
99
82
98
99
99
99
95
99
99
99(98)
54
5
ee
(%)[b]
80
86
67
69
67
88
90
94
94
94
95
95
-
1
2
3
4
5
6
7
8
9[c]
10[d]
11[d,e]
12[d,e,f]
13[d,e,f]
14[d,e,f]
L1/HCl
L2/HCl
L3/HCl
L4/HCl
L5/HCl
L2/HCl
L2/HCl
L2/HCl
L2/HCl
L2/HCl
L2/HCl
L2/HCl
L6/HCl
L7/HCl
toluene
toluene
toluene
toluene
toluene
THF
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
-
[a] Determined by GC using crude samples, isolated yield shown in
parentheses. [b] Determined by HPLC analysis with a chiral stationary phase.
[c] PhBPin was used. [d] 2 mol% catalyst loading. [e] Using MeONa instead of
CsF. [f] 10 min.
discriminate and can readily undergo enolization, also furnishes
products with synthetically useful outcomes (4p-4s). It bears
mentioning that most reactions were conducted in 10 min, with
several exceptions due to the low solubility or large steric
hindrance of substrates. Notably, many functional groups,
a
more hindered ligand (L7, with 2,6-dibenzhydrylaniline
fragments) both decreased the reactivity significantly (entries 13-
14). As such, we concluded that the proper steric hindrance of
ligands was critical for the arylation reaction to proceed fast.
With the optimized reaction conditions in hand, we next
investigated the generality of ketone partners for this arylation
reaction. As shown in Figure 2, a wide variety of commercially
available ketones were applicable, furnishing chiral tertiary
alcohols (3a-4s) in good to excellent yield and enantioselectivity
(70-98% ee). The use of aryl methyl ketones delivered the
corresponding products in outstanding enantioselectivity (3a-3q,
91-97% ee). Both electron-rich and electron-deficient aromatic
ketones with para-, meta-, or ortho-substitutions serve as
suitable substrates. Moreover, substrates bearing medicinally
important heterocycles, such as a morpholine (3e), a benzofuran
(3r), a benzothiophene (3s), furans (3u, 3v), a thiophene (3x), a
pyridine (3w), an indole (3t), a thiazole (3z), a carbazole (3y),
and a quinoline (4a), were all compatible. Chiral heterocyclic
tertiary alcohols (3r-4a) were obtained in good to high yield with
remarkable enantiocontrol (93-97% ee). In addition to acyclic
substrates, the use of cyclic ketones with different ring sizes (4b-
4d) and heteroaromatic cyclic ketones (4e-4h) all afforded
products in exceptional enantioselectivity (94-98% ee). For alkyl
aryl ketones with small differences of two substituents on the
prochiral carbon center, good to excellent enantioselectivity
could still be obtained (4i-4o). In the case of benzoylpropionate,
lactonization product (4o) was obtained from the corresponding
tertiary alcohol in a single operation. Interestingly, the use of
dialkyl ketones, whose enantiofaces are challenging to
including ethers (3b, 3e, 3k),
a
trifluoromethoxyl (3f),
trifluoromethyl groups (3g, 3l), an ester (3h), a nitrile (3i), a
sulfuryl (3j), a ferrocenyl (3p), an unprotected alcohol (3q), an
alkyl chloride (4n), an aryl chloride(3m) and fluoride (3n), can be
well tolerated. The absolute stereochemistry of 3w was
determined by X-ray crystallography. Finally, we successfully
performed a gram-scale reaction (5-mmol scale, 3a) while
simultaneously lowering the catalyst loading to 1 mol%. The
alcohol product was obtained in undiminished yield and
enantioselectivity, highlighting the practicality of this method.
Subsequently, we explored the scope of organoboron
coupling partners. As shown in Figure 2, we found that both
electron-rich and electron-poor arylboronic esters (5a-h), as well
as heteroaryl boronic esters (5i-p), smoothly undergo arylation
to give products in high yield and enantioselectivity (91-96% ee,
5a-p). Organoboron and ketone substrates that possess many
sensitive functional groups to nickel catalysts were all well-
tolerated. For example, the competitive Ni-catalysed Suzuki
reactions of various well-developed electrophiles15, including aryl
chlorides, fluorides, ethers, esters, nitriles, amides, alkyl
chlorides, as well as the undesired reactivity of benzylic alcohol
derivatives, were smoothly avoided under the current reaction
conditions, providing excellent opportunities for further
elaborations.
The excellent functional group compatibility of this protocol
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Figure 2. Substrate scope. Isolated yields are shown; ee values were determined by chiral HPLC analysis. 2-Np = 2-naphthyl. a1 h; b24 h; c80 oC; dusing 5 mol%
catalyst; etoluene as the solvent; fL1/HCl was used; gusing ent-L2/HCl; husing 3.0 equiv of PhBneo.
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and the wide occurrence of ketone groups encouraged us to
expand the scope of this arylation method. The applicability of
new methodologies to the late-stage modification of complex
natural products or highly functionalized synthetic
intermediates is a highly desirable feature, as analogs of
bioactive molecules can be prepared without laborious de
novo synthesis. Accordingly, substrates derived from
diflufenican (6, an herbicide), dyclonine (7, a local anesthetic),
and celestolide (8, a spice) were subjected to our arylation
conditions and were all successfully arylated to give products
with high yield and enantioselectivity (80-93% ee). Complex
carbohydrate and amino acid derivatives were also applied to
this arylation protocol, providing products (9-10) in high yields
with excellent, catalyst-controlled diastereoselectivity (97:3-
98:2 dr). Moreover, asymmetric arylation reactions using
arylboronates derived from pharmaceuticals, such as
fenofibrate (11) and ezetimibe (12), two widely prescribed
drugs for the treatment of hyperlipidemia, loratadine (13, an
antiallergic medication), estrone (14, a hormone), and δ-
vitamin E (15, an antioxidant), were successfully performed.
Highly functionalized chiral tertiary alcohols were generated in
excellent enantioselectivity (93-95% ee) or catalyst-controlled
diastereoselectivity (92:8-98:2 dr). Interestingly, aryl methyl
ketones could be selectively arylated in the presence of diaryl
ketone (12) and bulky dialkyl ketone (14), probably due to
steric reasons.
Next, we conducted preliminary mechanistic studies to
probe the plausible mechanism. We prepared complex 16 by
simply mixing NHC/Ni(0) complex and ketones (Fig. 3A).
Complex 16 with a 14e configuration was unstable. The
addition of secondary ligands like PCy3 or a pyridine-
containing ketone could stabilize oxanickelacycle to give 17
or 18 bearing a 16e configuration. The 13C NMR chemical
shifts for 16-18 (78.2, 77.9, 73.2 ppm) are shifted dramatically
upfield compared with that of corresponding ketone
substrates. The structure of 18, a dimer, was unambiguously
confirmed by X-ray crystal diffraction. These observations
would suggest the η2-coordinating activation of ketone and
the subsequent oxidative cyclization step16. We then treated
16 with PhBneo in the absence of base at 50 oC for two hours;
alcohol product was obtained in 78% yield. Remarkably, we
found the addition of MeONa accelerates the catalytic
reaction, which might promote the transmetalation step (Fig.
3B). While almost no conversions were observed in the
absence of excess base (2 mol% of base used for the in-situ
generations of the Ni/NHC catalyst), the use of 0.5 equiv or
more MeONa finished the reaction in 10 min. Based on our
observations and previous reports from the groups of Ogoshi,
Itami, and others16-17, we proposed a catalytic cycle shown in
Fig. 3C. An electron-donating NHC chelated Ni(0) species
facilitates the η2-activation of ketone carbonyls and oxidative
cyclization to afford an oxanickelacycle. A subsequent base-
promoted transmetalation forms an aryl-alkyl nickel complex,
which undergoes reductive elimination to give alcohol product
and Ni(0) catalyst for the next catalytic cycle.
Figure 3. Proposed mechanism
In conclusion, we have developed a general, efficient,
highly enantio- and chemoselective NHC/Ni-catalysed
arylboration of ketones. The key to the fast reaction and
excellent enantiocontrol is the employment of a bulky C2-
symmetric chiral NHC ligand for Ni catalyst. This process
tolerates an exceptionally broad scope of functional groups
and heterocycles, providing various chiral tertiary alcohols
from readily available and stable reactants. Beyond the
immediate synthetic utility, we anticipate that this rare
enantioselective η2-coordinating activation of ketone would
inspire further development of other challenging yet important
asymmetric transformations of ketones.
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Acknowledgments
see: (h) C. Bolm, J. Rudolph, J. Am. Chem. Soc. 2002, 124, 14850–
14851.
[9]
For additions to -keto esters, see: (a) H.-F. Duan, J.-H. Xie, X.-C.
Qiao, L.-X. Wang, Q.-L. Zhou, Angew. Chem. Int. Ed. 2008, 47,
4351–4353. (b) F. Cai, X. Pu, X. Qi, V. Lynch, A. Radha, J. M.
Ready, J. Am. Chem. Soc. 2011,133, 18066–18069. (c) Y.
Yamamoto, T. Shirai, M. Watanabe, K. Kurihara, N. Miyaura,
Molecules 2011, 16, 5020–5034. (d) T.-S. Zhu, S.-S. Jin, M.-H. Xu,
Angew. Chem. Int. Ed. 2012, 51, 780–783. For additions to
trifluoromethyl ketones, see: (e) S. L. X. Martina, R. B. C. Jagt, J. G.
de Vries, B. L. Feringa, A. J. Minnaard, Chem. Commun. 2006,
4093–4095. (f) R. Li, K. Luo, Y. Hu, W. Tang, Adv. Synth. Catal.
2013, 355, 1297–1302. For additions to isatins, see: (g) R. Shintani,
M. Inoue, T. Hayashi, Angew. Chem. Int. Ed. 2006, 45, 3353–3356.
(h) Z. Liu, P. Gu, M. Shi, P. McDowell, G. Li, Org. Lett. 2011, 13,
2314–2317.
This work is supported by the National Natural Science
Foundation of China (Grant No. 91856111, 21871288,
21690074, 21821002) and the Chinese Academy of Sciences
(Grant No. XDB 20000000).
Keywords: chiral tertiary alcohol • arylation • chiral NHC
ligand • nickel catalysis • arylboronic ester
[1]
For books, see: (a) Quaternary stereocenters, challenges and
solutions for organic synthesis; Eds.: J. Christoffers, A. Baro, Wiley-
VCH: Weinheim, Germany, 2005. (b) Comprehensive Asymmetric
Catalysis; Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto, Springer,
Berlin, 1999.
[10] Intramolecular additions: (a) G. Liu, X. Lu, J. Am. Chem. Soc. 2006,
128, 16504–16505. (b) G. Liu, X. Lu, Tetrahedron 2008, 64, 7324–
7330. (c) D. Tomita, K. Yamatsugu, M. Kanai, M. Shibasaki, J. Am.
Chem. Soc., 2009, 131, 6946–6948. (d) R. Sarpong, G. L. Gallego,
Chem. Sci., 2012, 3, 1338–1342. (e) D. W. Low, G. Pattison, M. D.
Wieczysty, G. H. Churchill, H. W. Lam, Org. Lett. 2012, 14, 2548–
2551. (f) D.-X. Zhu, W.-W. Chen, M.-H. Xu, Tetrahedron, 2016, 72,
2637–2642. (g) C. Ni, J. Gao, X. Fang, Chem. Commun. 2020, 54,
2654–2657.
[2]
[3]
(a) L. Chen, X.-P. Yin, C.-H. Wang, J. Zhou, Org. Biomol. Chem.
2014, 12, 6033–6048. (b) Q. Zhou, K. M. Cobb, T. Tan, M. P.
Watson, J. Am. Chem. Soc. 2016, 138, 12057–12060.
For selected reviews, see: (a) M. Shibasaki, M. Kanai, Chem. Rev.
2008, 108, 2853–2873. (b) O. Riant, J. Hannedouche, Org. Biomol.
Chem. 2007, 5, 873–888. (c) D. Leonori, V. K. Aggarwal, Acc. Chem.
Res., 2014, 47, 3174–3183. (d) Y.-L. Liu, X.-T. Lin, Adv. Synth.
Catal. 2019, 361, 876–918.
[4]
For selected examples, see: (a) J. L. Stymiest, V. Bagutski, R. M.
French, V. K. Aggarwal, Nature 2008, 456, 778–782. (b) K. C.
Harper, M. S. Sigman, Science 2011, 333, 1875–1878. (c) Y. Yang,
I. B. Perry, G. Lu, P. Liu, S. L. Buchwald, Science 2016, 353, 144–
150. (d) S.-L. Shi, L.-W. Xu, K. Oisaki, M. Kanai, M. Shibasaki, J.
Am. Chem. Soc. 2010, 132, 6638–6639.
[11] (a) J. Bouffard, K. Itami, Org. Lett. 2009, 11, 4410–4413. (b) Y.-X.
Liao, C.-H. Xing, Q.-S. Hu, Org. Lett. 2012, 14, 1544–1547. (c) T.
Korenaga, A. Ko, K. Uotani, Y. Tanaka, T. Sakai, Angew. Chem. Int.
Ed. 2011, 50, 10703–10707.
[12] L. Huang, J. Zhu, G. Jiao, Z. Wang, X. Yu, W.-P. Deng, W. Tang,
Angew. Chem., Int. Ed. 2016, 55, 4527–4531.
[5]
[6]
(a) R. Noyori, M. Kitamura, Angew. Chem., Int. Ed. 1991, 30, 49–69.
(b) L. Pu, H.-B. Yu, Chem. Rev. 2001, 101, 757–824. (c) M. Hatano,
K. Ishihara, Synthesis 2008, 1647–1675. (d) J. F. Collados, R. Solꢀ,
S. R. Harutyunyan, B. Maciꢁ, ACS Catal. 2016, 6, 1952–1970.
For selected enantioselective examples of organometallic addition to
ketones, see: Zn: (a) P. I. Dosa, G. C. Fu, J. Am. Chem. Soc. 1998,
120, 445–446. (b) D. J. Ramon, M. Yus, Angew. Chem. Int. Ed.
2004, 43, 284–287. (c) H. Li, C. Garcia, P. J. Walsh, Proc. Natl.
Acad. Sci. 2004, 101, 5425–5427. Al: (d) C.-A. Chen, K.-H. Wu, H.-
M. Gau, Angew. Chem. Int. Ed. 2007, 46, 5373–5376.Ti: (e) K.-H.
Wu, Y.-Y. Kuo, C.-A. Chen, Y.-L. Huang, H.-M. Gau, Adv. Synth.
Catal. 2013, 355, 1001–1008. Mg: (f) E. Fernández-Mateos, B.
Maciá, M. Yus, Eur. J. Org. Chem. 2014, 2014, 6519–6526.
A. Suzuki, Angew. Chem. Int. Ed. 2011, 50, 6722–6737.
[13] (a) D. Janssen-Müller, C. Schlepphorst, F. Glorius, Chem. Soc. Rev.
2017, 46, 4845–4854. (b) F. Wang, L.-J. Liu, W. Wang, S. Li, M. Shi,
Coord. Chem. Rev. 2012, 256, 804–853.
[14] (a) Y. Cai, X.-T. Yang, S.-Q. Zhang, F. Li, Y.-Q. Li, L.-X. Ruan, X.
Hong, S.-L. Shi, Angew. Chem., Int. Ed. 2018, 57, 1376–1380. (b) Y.
Cai, J.-W. Zhang, F. Li, J.-M. Liu, S.-L. Shi, ACS Catal. 2019, 9, 1–6.
(c) W.-B. Zhang, X.-T. Yang, J.-B. Ma, Z.-M. Su, S.-L. Shi, J. Am.
Chem. Soc. 2019, 141, 5628–5634. (d) D. Shen, Y. Xu, S.-L. Shi, J.
Am. Chem. Soc. 2019, 141, 14938–14945. (e) Y. Cai, X. Ye, S. Liu,
S.-L. Shi, Angew. Chem., Int. Ed. 2019, 58, 13433–13437. (f) D.
Shen, W.-B. Zhang, Z. Li, S.-L. Shi, Y. Xu, Adv. Synth. Catal. 2020,
362, 1125–1130. For a concomitant development of ligands, see: (g)
J. Diesel, A. M. Finogenova, N. Cramer, J. Am. Chem. Soc. 2018,
140, 4489–4493. (h) J. Diesel, D. Grosheva, S. Kodama, N. Cramer,
Angew. Chem., Int. Ed. 2019, 58, 11044–11048.
[7]
[8]
For selected examples on metal-catalyzed asymmetric arylboration
of aldehyde, see: Rh: (a) M. Sakai, M. Ueda, N. Miyaura, Angew.
Chem. Int. Ed. 1998, 37, 3279–3281. (b) H.-F. Duan, J.-H. Xie, W.-J.
Shi, Q. Zhang, Q.-L. Zhou, Org. Lett. 2006, 8, 1479–1481. (c) T.
Nishimura, H. Kumamoto, M. Nagaosa, T. Hayashi, Chem. Commun.
2009, 5713–5715. Ru: (d) Y. Yamamoto, K. Kurihara, N. Miyaura,
Angew. Chem. Int. Ed. 2009, 48, 4414–4416. Cu: (e) D. Tomita, M.
Kanai, M. Shibasaki, Chem. Asian J. 2006, 1, 161–166. Ni: (f) T.
Arao, K. Kondo, T. Aoyama, Tetrahedron Lett. 2007, 48, 4115–4117.
Co: (g) J. Karthikeyan, M. Jeganmohan, C.-H. Cheng, Chem. Eur. J.
2010, 16, 8989–8992. For amino- or iminoalcohol-catalyzed
asymmetric aldehyde arylation via boron-to-zinc transmetalation,
[15] F.-S. Han, Chem. Soc. Rev. 2013, 42, 5270–5298.
[16] (a) Y. Hoshimoto, M. Ohashi, S. Ogoshi, Acc. Chem. Res. 2015, 48,
1746–1755. (b) J. Montgomery, Angew. Chem., Int. Ed. 2004, 43,
3890–3908. (c) E. A. Standley, S. Z. Tasker, K. L. Jensen, T. F.
Jamison, Acc. Chem. Res. 2015, 48, 1503–1514.
[17] (a) R. Kumar, Y. Hoshimoto, H. Yabuki, M. Ohashi, S. Ogoshi, J.
Am. Chem. Soc. 2015, 137, 11838–11845. (b) K. Hirano, H.
Yorimitsu, K. Oshima, Org. Lett. 2005,7, 4689–4691. (c) C. Lei, Y. J.
Yip, J. S. Zhou, J. Am. Chem. Soc. 2017, 139, 6086–6089. (d) D. K.
Nielsen, A. G. Doyle, Angew. Chem., Int. Ed. 2011, 50, 6056–6059.
Also, see 11a, 8f.
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10.1002/anie.202015021
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
Yuan Cai, Lin-Xin Ruan, Abdul Rahman,
Shi-Liang Shi*
Page No. – Page No.
Fast Enantio- and Chemoselective
Arylation of Ketones with Organo-
boronic Esters Enabled by
Nickel/NHC Catalysis
Text for Table of Contents
Reported is the first general asymmetric addition of arylborons to simple ketones enabled by a nickel/NHC catalysis, furnishing chiral
tertiary alcohols in high efficiency with broad substrate scope and excellent levels of enantio- and chemocontrol.
This article is protected by copyright. All rights reserved.