Iridium-catalyzed B-H bond insertion reactions using sulfoxonium ylides as carbene precursors toward α-boryl carbonyls

Article abstract of DOI:10.1021/acs.orglett.9b03410

An iridium-catalyzed B-H bond insertion reaction between borane adducts and sulfoxonium ylides to afford α-boryl carbonyls has been developed. The starting materials are safe and readily available. In addition, analogues of sulfoxonium ylides, such as sul

Full text of DOI:10.1021/acs.orglett.9b03410

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Iridium-Catalyzed B−H Bond Insertion Reactions Using Sulfoxonium
Ylides as Carbene Precursors toward α‑Boryl Carbonyls
Jianglian Li,† Hua He,† Mengyi Huang, Yuncan Chen, Yi Luo, Kaichuan Yan, Qiantao Wang,*
and Yong Wu*
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for
Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy,
Sichuan University, Chengdu 610041, P. R. China
S
* Supporting Information
ABSTRACT: An iridium-catalyzed B−H bond insertion
reaction between borane adducts and sulfoxonium ylides to
afford α-boryl carbonyls has been developed. The starting
materials are safe and readily available. In addition, analogues
of sulfoxonium ylides, such as sulfonium salts and sulfonium
ylides could also be amenable to the reaction.
rganoboron compounds have a wide range of
bond insertion using sulfoxonium ylides as carbene precursors
Oapplications in pharmaceuticals, materials chemistry, to constitute a new route to α-boryl carbonyls (Scheme 1d).
organic synthesis, and other fields.1 Several powerful method-
To our best knowledge, no report on the B−H insertion of
sulfoxonium ylides has been reported yet.
ologies for the construction of C−B bonds have been
reported.2 Among them, α-boryl carbonyl species have recently
been regarded as a class of important molecular entities in
organic synthesis due to their exhibited kinetic amphoterism.3
However, reliable methods for the synthesis of stable and
isolable α-boryl carbonyls are scarce and suffer from low
yields,4 harsh conditions, and multistep reaction properties.5
The development of efficient, straightforward synthesis of α-
boryl carbonyls remains to be desirable. Recently, transition-
metal-catalyzed B−H insertion reaction of α-diazo carbonyl
compounds with borane adducts were reported as an effective
alternative for the synthesis of α-boryl carbonyls (Scheme 1a).6
However, diazo compounds are toxic, unstable, and potentially
explosive. Thereafter, Zhou’s group developed an efficient
method that utilized gold-catalyzed oxidative coupling reaction
between the terminal alkynes and borane adducts (Scheme
1b).7 This, however, has a limited practicality because of low
atomic utilization and commercially unavailable catalyst. Most
recently, the group of Curran described a fundamentally new
approach to making α-NHC-boryl ketones from NHC-boranes
and alkenyl triflates. In this procedure, although no catalyst nor
the traditional high energy initiator were needed, its isolated
yields were typically low to moderate (Scheme 1c).8
We initially studied reactions of sulfoxonium ylide 1a with
trimethylamine-borane 2a in 1,2-dichloroethane (DCE) at 60
°C with Rh(OAc)2 as catalyst, unfortunately, no desired
product was detected (Table 1, entry 1). None of CuI,
Cu(OTf)2, and PPh3AuCl as catalysts afforded the desired
product (entries 2−4). To our delight, desired α-boryl ketone
3aa was obtained in 46% yield using [Ir(COD)Cl]2 as catalyst
(entry 5), and the relatively low yield should be due to
decomposition of 1a. In our past research on sulfoxonium
ylides, we found that this catalyst led to the decomposition of
sulfoxonium ylide into ketone 4aa. At the same time, we also
observed that copper salts inhibited the decomposition slightly.
To increase the conversion, we investigated several copper salts
and other additives, CuF2 gave the best result (entries 6−11).
Further exploration of the solvents indicated that using
chlorobenzene (PhCl) could improve the yield to 73% (entries
12−15). Subsequently, increasing the amount of 2a to 4.0
equiv gave a higher yield (entry 16), and low concentrations
could also promote the insertion process by inhibiting
decomposition (entry 17). In addition, we conducted more
detailed investigation of other reaction conditions, such as
temperature, equivalent of catalyst and additive, atmosphere,
concentration, and other borane adducts, but they did not give
better results (see additional details in the Supporting
Information).
Since sulfoxonium ylides were proven to be the alternative
metallocarbene surrogates to diazo compounds,9 many
reactions, such as insertions10 and C−H activations,11 have
been reported by different groups because sulfoxonium ylides
are safe, stable, and easily accessible (obtained from the
corresponding carboxylic acid).12 Inspired by recent reports on
the transition-metal-catalyzed B−H bond insertion of
carbenes6,13 and our previous works of sulfoxonium ylides,11d,e
we envisaged the possibility of transition-metal-catalyzed B−H
With the optimal reaction conditions in hand, we next
evaluated the scope of the insertion reaction using different
sulfoxonium ylides (Scheme 2). The reaction tolerated a
Received: September 26, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03410
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 1. Synthesis of α-Boryl Carbonyl Compounds
Scheme 2. Scope of Sulfoxonium Ylide
a
Table 1. Optimization of the Reaction Conditions
a
Reaction conditions: 1a (0.15 mmol), 2a (0.6 mmol), [Ir(COD)Cl]2
(5 mol %) and CuF2 (20 mol %) in 10 mL of PhCl for 3 h at 60 °C
b
under air. Isolated yield by chromatography on silica gel. 24 h at 60
°C under air. [Ir(COD)Cl]2 (20 mol %) and CuF2 (2.0 equiv).
c
b
b
entry
catalyst
additive
solvent
3aa (%)
4aa (%)
c
c
1
2
3
4
5
6
7
8
Rh(OAc)2
CuI
PPh3AuCl
Cu(OTf)2
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCM
PhCl
H2O
ND
ND
variety of functional groups. Electron-donating and -with-
drawing groups, such as methoxy, methyl, and chloro at the
ortho, meta, and para positions of the phenyl ring proceeded
smoothly, giving the corresponding products in moderate to
excellent yields (3aa−3ia). By comparing the yields of
substrates with the same group at different positions, we
found that ortho-substituted substrates exhibited slightly
reduced efficiency in this transformation, perhaps because of
the steric hindrance. At the same time, possibly due to the
strong inductive effect of electron-withdrawing groups, nitro-
substituted at the para position only afforded moderate yield
(3ja). Notably, nonsubstituted (hetero) aromatic α-boryl
carbonyls were obtained in good to excellent yields (3ka−
3na), but 1-naphthalene was exception, affording a moderate
yield of 3oa. To further evaluate the scope of this process,
several polysubstituted substrates were also studied, substrates
with at least two electron-donating groups on the benzene ring
were fully compatible (3pa−3ua). Unfortunately, if there are
too many electron-withdrawing groups on the benzene ring,
the reaction could not proceed (3va). Next, we turned our
attention to aliphatic sulfoxonium ylides. First, 1w were treated
with 2a under standard conditions, no desired product was
obtained. When we increase the amount of catalyst to 0.2 equiv
ND
ND
ND
46
ND
ND
ND
<10
<10
<10
<5
<10
<10
<10
<5
ND
<10
<10
ND
ND
[Ir(COD)Cl]2
[Ir(COD)Cl]2
[Ir(COD)Cl]2
[Ir(COD)Cl]2
[Ir(COD)Cl]2
[Ir(COD)Cl]2
[Ir(COD)Cl]2
[Ir(COD)Cl]2
[Ir(COD)Cl]2
[Ir(COD)Cl]2
[Ir(COD)Cl]2
[Ir(COD)Cl]2
[Ir(COD)Cl]2
CuCN
Cu(OAc)2
CuF2
ZnCl2
AgOAc
HOAc
CuF2
CuF2
CuF2
CuF2
CuF2
53
34
62
21
9
10
11
12
13
14
15
25
ND
51
73
<5
<10
80
DMSO
PhCl
PhCl
d
16
17
e
CuF2
85
a
Reaction conditions:1a (0.15 mmol), 2a (0.3 mmol), catalyst (5 mol
%), and additive (20 mol %) in 3 mL of solvent for 3 h at 60 °C under
air. COD = 1,5-cyclooctadiene. Isolated yield. ND = not detected.
b
c
d
e
4.0 equiv of 2a was used. 10 mL of solvent was used.
B
DOI: 10.1021/acs.orglett.9b03410
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Organic Letters
Letter
and the equivalent of copper salt to 2.0 equiv, 3wa was
delivered in 97% yield. In addition, substrates with benzyl
group were also compatible (3xa, 3ya). The effect of
substitution at the ylide carbon atom was investigated with
the compound 1z under standard conditions (3za). Because of
the existence of chiral carbon in 1z, theoretically, enantiose-
lectivity can be achieved by using chiral iridium catalysts.
Moreover, this method is also suitable for substrates with
alkenyl group (3-1a).
Scheme 5. Control Experiments
To investigate the efficiency and further practicality of this
transformation, a 10-fold scale-up of the reaction using 1m and
2a in 50 mL of PhCl was then examined. The desired product
3ma was isolated in 76% yield (Scheme 3). The slight decrease
in yield might be attributed to that the decomposition of
sulfoxonium ylide was increased with the increasing concen-
tration.
Scheme 6. Proposed B−H Insertion Mechanism
Scheme 3. 10-Fold Scale-Up Reaction
Afterward, we envisioned that, in analogy with sulfoxonium
ylides, sulfonium salts, and sulfonium ylides could also be
amenable to the reaction. Among them, B−H insertion
reactions of sulfonium salts with B2pin2 has been reported.14
When sulfonium salt 6 was used, 3ka was isolated in 60% yield
(Scheme 4a). Delightedly, when sulfoxonium ylides were
Scheme 4. B−H Bond Insertion of Analogues of
Sulfoxonium Ylides
adduct to affford the product also regenerates the catalyst via a
concerted transition state.
In summary, we have described a protocol for iridium-
catalyzed B−H bond insertion reactions of borane adducts and
sulfoxonium ylides. With this reaction, various α-boryl ketones
were synthesized in good to excellent yields from safe and
readily accessible starting materials. Analogues of sulfoxonium
ylides, sulfonium salts are also applicable to this procedure. We
firmly believe that this successful use of sulfur (sulfonium and
sulfoxonium) ylides as carbene precursors in B−H bond
insertion reactions could open up a new route to organoboron
compounds.
ASSOCIATED CONTENT
* Supporting Information
■
S
replaced by sulfonium ylide 7, corresponding product was also
obtained in 58% yield (Scheme 4b). To our knowledge, to date
there is only one report on X−H (X = C, Si, O, S, N) insertion
reactions of sulfonium ylide derived carbenoids.15
In order to clarify the mechanism of this present process, we
carried out a labeling experiment with 2b-d3 and observed a
kinetic isotope effect (k H/k D = 3.35), the result indicated that
cleavage of the B−H bond is probably involved in the
turnover-limiting step (Scheme 5).
Based on our preliminary studies and previous literature
values,12 we propose the following reaction mechanism
(Scheme 6). Initially, sulfoxonium ylide reacts with Ir species
and extrudes DMSO to generate the iridium carbene complex
III, which was inserted into the B−H bond of the borane
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b03410.
Experimental procedures and spectroscopic data for all
new compounds (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: qiantao_wang@hotmail.com.
*E-mail: wyong@scu.edu.cn.
ORCID
Yong Wu: 0000-0003-0719-4963
C
DOI: 10.1021/acs.orglett.9b03410
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(9) Burtoloso, A. C. B.; Dias, R. M. P.; Leonarczyk, I. A. Eur. J. Org.
Chem. 2013, 2013, 5005−5016.
Author Contributions
†J.L. and H.H. contributed equally.
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D. W.; Vaughan, J. G. J. Chem. Soc., Chem. Commun. 1993, 1434−
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Chem. - Eur. J. 2017, 23, 16980−16984. (d) Jiang, H.; Zhang, H.;
Xiong, W.; Qi, C.; Wu, W.; Wang, L.; Cheng, R. Org. Lett. 2019, 21,
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S. W.; Schomaker, J. M.; Shekhar, S. J. Org. Chem. 2016, 81, 4158−
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for the support from the National Natural
Science Foundation of China (NSFC) (Grant Number
81602954, 81573286, 81373259, and 81773577) and Sichuan
Youth Science and Technology Program (Grant No.
2019YJ0036).
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