Insertion of Alkylidene Carbenes into B-H Bonds

Article abstract of DOI:10.1021/jacs.0c09596

We have developed a protocol for insertion of alkylidene carbenes into the B-H bonds of amine-borane adducts, enabling, for the first time, the construction of C(sp2)-B bonds by means of carbene-insertion reactions. Various acyclic and cyclic alkenyl borane-amine adducts were prepared from readily accessible starting materials in good to high yields and were subsequently subjected to a diverse array of functional group transformations. The unprecedented spiro B-N heterocycles prepared in this study have potential utility as building blocks for the synthesis of pharmaceuticals. Preliminary mechanistic studies suggest that insertion of the alkylidene carbenes into the B-H bonds of the amine-borane adducts proceeds via a concerted process involving a three-membered-ring transition state.

Full text of DOI:10.1021/jacs.0c09596

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Insertion of Alkylidene Carbenes into B−H Bonds
Ji-Min Yang,‡ Feng-Kai Guo,‡ Yu-Tao Zhao, Qiao Zhang, Ming-Yao Huang, Mao-Lin Li, Shou-Fei Zhu,*
and Qi-Lin Zhou*
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ABSTRACT: We have developed a protocol for insertion of alkylidene carbenes into the B−H bonds of amine−borane adducts,
enabling, for the first time, the construction of C(sp2)−B bonds by means of carbene-insertion reactions. Various acyclic and cyclic
alkenyl borane−amine adducts were prepared from readily accessible starting materials in good to high yields and were subsequently
subjected to a diverse array of functional group transformations. The unprecedented spiro B−N heterocycles prepared in this study
have potential utility as building blocks for the synthesis of pharmaceuticals. Preliminary mechanistic studies suggest that insertion of
the alkylidene carbenes into the B−H bonds of the amine−borane adducts proceeds via a concerted process involving a three-
membered-ring transition state.
rganoboron compounds are widely used in organic
synthesis, the pharmaceutical and agrochemical indus-
in the presence of tBuOK, alkylidene carbenes generated in situ
from readily available alkenyl triflates smoothly inserted into
the B−H bonds of borane adducts to produce alkenyl boranes
in good to high yields. An intramolecular version of this
reaction allowed us to synthesize various BN heterocycles,
which have not previously been reported and hard to prepare
through the well-established C−B-bond-forming reactions.1,6
The alkenyl borane adducts produced by this method could
undergo many types of C−C- and C−X- (X = heteroatom)
bond-forming reactions to afford trisubstituted olefins.
O
tries, materials science, and many other fields.1 Therefore, the
development of new C−B-bond-forming reactions that permit
efficient synthesis of organoboron compounds has long been of
interest to synthetic chemists. Recently, the insertion of
carbenes into the B−H bonds of stable borane adductssuch
as amine boranes, phosphine boranes, and N-heterocyclic
carbene boraneshas emerged as a promising method for
constructing C−B bonds (Scheme 1a).2 This method has
Inspired by the work of Stang et al.,7 who reported that
alkylidene carbenes can be generated by base-induced α-
elimination reactions of alkenyl triflates, we began our study
with the reaction of alkenyl triflate 1a and trimethylamine−
Scheme 1. B−H Bond Insertion Reactions
t
borane (2a, 2 equiv) in the presence of BuOK in 1,2-
dimethoxyethane at 0 °C (Table 1). To our delight, these
conditions afforded desired alkenyl borane 3aa in 47% yield
(entry 1). The O−H bond insertion product (4-(tert-
butoxymethylene)cyclohexyl)benzene was the main byproduct.
Tetrahydrofuran, tert-butyl methyl ether, dichloromethane,
PhCl, toluene, and hexane were also suitable solvents (entries
2−7), with dichloromethane giving the highest yield (entry 4).
The strength of the base was critical to the reaction outcome:
the use of the weaker base tBuONa markedly reduced the yield
t
(entry 8), and no reaction occurred when BuOLi or MeONa
many advantages for the synthesis of functionalized organo-
boranes because boron adducts are readily accessible and
highly stable3 and carbenes can be generated from a variety of
precursors.4 However, to date, only saturated carbenes (that is,
disubstituted carbenes) have been successfully used in B−H
bond insertion reactions, which form alkyl boranes.2
was used (entries 9 and 10). This reaction is temperature
dependent and the one performed at 0 °C exhibiting best
outcomes (Table S1). Higher yields were achieved by
increasing the amount of adduct 2a (entries 11 and 12). The
electronic and steric nature of the donor in the borane adduct
We envisioned that alkenyl boron compounds could be
accessed by B−H bond insertion reactions if borane adducts
could trap alkylidene carbenes, which are typical unsaturated
carbenes and which have been utilized in the synthesis of
functionalized and unfunctionalized olefins5 (Scheme 1b).
Herein, we report a protocol for B−H bond insertion reactions
involving alkylidene carbenes and borane adducts. Specifically,
Received: September 7, 2020
https://dx.doi.org/10.1021/jacs.0c09596
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© XXXX American Chemical Society
A

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Communication
a
Table 1. B−H Bond Insertion of Alkylidene Carbene: Optimization of the Reaction Conditions
b
entry
adducts
base
equiv of 2
solvents
products
yield (%)
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuONa
tBuOLi
MeONa
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
2
2
2
2
2
2
2
2
2
2
3
4
4
4
4
4
4
DME
THF
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3ab
3ac
3ad
3ae
3af
47
50
60
70
50
39
39
MTBE
DCM
PhCl
toluene
hexane
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
c
30
d
e
9
N.D.
d
10
11
12
N.D.
72
77
f
13
70
14
15
75
<5
d
16
N.D.
17
N.D.
a
Reaction conditions: 1a (0.3 mmol), 2 (0.6−1.2 mmol), tBuOK (0.36 mmol), 3 mL of CH2Cl2, 0 °C. Full conversion of 1a was observed unless
b
c
d
e
f
1
otherwise noted. Isolated yield. Reaction time: 12 h. <10% conversion of 1a. N.D. = not detected. Determined by H NMR using 1,3,5-
trimethoxybenzene as an internal standard.
also affected the reaction outcome. Specifically, tributylphos-
phine−borane adduct 2b and N-heterocyclic carbene−borane
adduct 2c gave yields similar to that obtained with 2a, whereas
tributylamine−borane adduct 2d afforded a poorer yield
(entries 13−15). Dimethylamine−borane adduct 2e and
pyridine−borane adduct 2f did not undergo the desired
reaction under the tested conditions (entries 16 and 17 and
Table S2).
Using the optimized conditions (Table 1, entry 12), we
evaluated various alkenyl triflates 1 in B−H bond insertion
reactions with amine−borane adduct 2a (Table 2). Cyclic and
acyclic 2,2-dialkylsubstiuted alkenyl triflates were suitable
carbene precursors and gave satisfactory yields of the
corresponding products (3ba−3ha, entries 2−8). The reaction
of acyclic alkenyl triflates with long alkyl chain (1g)
accompanied by the intramolecular C−H bond insertion,
which generated a cyclopentene derivative as a major
byproduct. The reaction of a mixture of (Z)- and (E)-2,2-
dialkylsubstituted alkenyl triflates 1h, which have two different
alkyl groups, gave a mixture of E- and Z-3ha (entry 8). Under
the standard conditions, a phenyl-substituted alkenyl triflate
did not undergo the bond-insertion reaction, instead affording
1-phenylpropyne (entry 9).
BN-cyclopentene 5a in 61% yield (Scheme 2). Then we
systematically explored the substrate scope of the reaction.
First, the effect of the amine moiety of the amine−borane
adduct was evaluated. Borane adducts derived from aliphatic
tertiary amines generally afforded the desired insertion
products (5a−5h) in moderate to good yields. The reaction
could be scaled up with no reduction in the yield (a 76% yield
of 5c was obtained from a gram-scale reaction). Substrates
derived from secondary amines also gave the desired products
(5i and 5j), albeit in lower yields. To our delight, borane
adducts derived from cyclic amines produced the correspond-
ing BN spirocycles (5d−5h) in good yields under the standard
conditions; to the best of our knowledge, BN spirocycles have
not previously been reported. We also demonstrated that our
protocol could be used for modification of drug molecules. As
examples, borane derivatives of the drugs paroxetine, nortripty-
line, and fluoxetine were prepared (5k−5m). In the intra-
molecular B−H bond insertion reactions, controlling the
stereochemistry of the trisubstituted alkene products was not a
problem, because the insertion reaction could take place only
on the same face of the double bond as the amino group. For
instance, both (E)- and (Z)-4e gave the cyclic product 5e in
essentially the same yield.
Next, we turned our attention to the synthesis of boron-
containing heterocycles, which are attracting increasing
attention because of their great promise for a variety of
applications.8 We expected that intramolecular B−H bond
insertion reactions of alkylidene carbenes would allow us to
prepare BN heterocycles. We began by attempting an
intramolecular B−H bond insertion reaction of adduct 4a (R
= Bn, R1 = R2 = Me) with tBuOK as a base, which afforded 1,2-
The electronic properties of the substituent on the benzyl
group of the alkenyl triflate slightly affected the yields of
products 5n−5q. In addition to a benzyl group, R could be a
linear or branched alkyl group; desired products 5r−5u were
obtained in acceptable yields. Some alkylidene carbene
intermediates behaved differently in inter- and intramolecular
reactions. For instance, intermolecular reactions of 2-phenyl-
substituted alkenyl triflates yielded not the expected B−H
B
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Communication
Table 2. Intermolecular B−H Bond Insertion of Alkylidene
Scheme 2. Intramolecular B−H Bond Insertion of
a
a
Carbenes
Alkylidene Carbenes
a
Reaction conditions: 4a/tBuOK = 0.3:0.36 (mmol), in 3 mL CH2Cl2
a
Reaction conditions: 1a/2/tBuOK = 0.3:1.2:0.36 (mmol), in 3 mL
b
at 0 °C. Reaction was conducted with 5.5 mmol 4c, and 1.1 g of 5c
was obtained. Reaction was conducted with 0.5 mmol 4i.
b
CH2Cl2 at 0 °C. Isolated yield.
c
Scheme 3. Transformations of B−H Bond Insertion
Products
bond insertion products but rather phenyl migration by-
products. However, an intramolecular reaction of 2-phenyl-
substituted alkenyl triflate 4v afforded phenyl-substituted 1,2-
BN-cyclopentene 5v in 40% yield. To our knowledge, this is
the first example of the trapping of a phenyl-substituted
alkylidene carbene generated from an alkenyl triflate.5a,c,7b
Further experiments revealed that a substrate with a strongly
electron-withdrawing CF3 group on the phenyl ring (4y) gave
a higher yield than one with an electron-donating OMe group
(4w). The structure of 5q was confirmed by X-ray diffraction
analysis of a single crystal.9
The alkenyl borane compounds prepared in this study were
stable to common purification procedures (e.g., chromatog-
raphy and recrystallization) and were stable during long-term
storage. More importantly, they could undergo a diverse array
of transformations (Scheme 3a). For example, 3aa underwent
Pd-catalyzed Suzuki coupling with both an aryl bromide and an
alkenyl bromide to form C−C bonds (6 and 7), as well as Cu-
catalyzed Ullman coupling with imidazole to form a C−N
bond (8), and the yields were good in all cases. Reaction of 3aa
with CuX2 (X = Cl or Br) afforded halide 9a or 9b in high
yield. In addition, 3aa could be converted to alkenyl borate 10
or 11 by means of a condensation reaction with pinacol or N-
methylimidodiacetic acid, respectively.
Intramolecular insertion product 5c could also undergo
Suzuki coupling reactions, affording Z-allyl amines 12 and 13
in good yields (Scheme 3b). Allylamines are commonly found
in natural products and pharmaceuticals10 and can serve as
multipurpose intermediates in organic synthesis.11 Moreover,
the BN heterocycles obtained by means of this reaction are
isosteres of cyclopentene, which is a ubiquitous moiety in
natural products and pharmaceuticals.12 Therefore, our
protocol has high potential utility for applications in drug
discovery.
To elucidate the reaction mechanism, we carried out a
labeling experiment using BH3 and BD3 adducts, which
showed no kinetic isotope effect (kH/kD = 1.01, Scheme 4a),
indicating that B−H bond insertion was not involved in the
rate-limiting step. However, the result of a labeling experiment
using alkenyl triflate 1a and alkenyl triflate 1a-d with one
C
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Communication
2), yielding the desired product 3ca. This B−H bond insertion
step has an activated energy of 2.4 kcal/mol, which is much
lower than 13.7 kcal/mol for α-elimination step. This
calculation indicates that α-elimination rather than B−H
bond insertion is the rate-limiting step, a conclusion that is
supported by the results of the kinetic isotope effect
experiment (Scheme 4). Even both the B−H bond insertion
of alkylidene carbenes and hydroboration of alkynes can afford
alkenyl boron compounds, the mechanisms of these two
reactions are quite different according to calculations.14
Scheme 4. Kinetic Isotopic Effect Experiments
In summary, we have developed what is, to our knowledge,
the first protocol for B−H bond insertion reactions of
unsaturated carbenes. This protocol serves as an efficient
method for the construction of C(sp2)−B bonds, and when
used for intramolecular B−H bond insertion reactions of
alkylidene carbenes, it constitutes a new strategy for the
preparation of BN heterocycles. The acyclic and cyclic alkenyl
borane adducts prepared by this method can undergo efficient
C−C- and C−X-bond-forming reactions, making these adducts
promising synthetic building blocks. Mechanistic studies
showed that the B−H bond insertion reaction occurs via a
concerted insertion process. Our findings provide a bridge
between unsaturated carbene chemistry and organoboron
chemistry and can be expected to advance both fields.
terminal D (kD/kH = 2.57, Scheme 4b) indicated that
deprotonation may be involved in the rate-limiting step.
Then, we performed the calculations of the B−H bond
insertion reaction between alkenyl triflate 1c and amine−
borane adduct 2a by means of the M06-2X-D3/6-311+
+G(2df, 2p)//B3LYP/6-31+G(d) method in dichloromethane
solution (using the SMD model) with the Gaussian 09
program package (Scheme 5; see the Supporting Information
Scheme 5. Density Functional Theory Calculations: (A)
Free Energy Profile for B−H Bond Insertion of 1c and 2a;
(B) Optimized Structures of Key Transition States and
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.0c09596.
a
Intermediate with Key Bond Length (Å)
Experimental procedures and characterization data,
computational study results, Cartesian coordinates, and
spectral data (PDF)
Crystal data for 5q (CIF)
AUTHOR INFORMATION
■
Corresponding Authors
Shou-Fei Zhu − State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China; orcid.org/0000-
0002-6055-3139; Email: sfzhu@nankai.edu.cn
Qi-Lin Zhou − State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China; orcid.org/0000-
0002-4700-3765; Email: qlzhou@nankai.edu.cn
Authors
Ji-Min Yang − State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China
Feng-Kai Guo − State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China
a
Trivial H atoms have been omitted for clarity.
t
for details). The calculations suggested that the BuOK
tetramer13 in DCM facilitates α-elimination of 1c to generate
INT2 via TS1. The activated energy for this step is 13.7 kcal/
mol. Once formed, the INT2 (ΔG = 8.8 kcal/mol) can release
the electrophilic alkylidene carbene intermediates CB (ΔG =
1.3 kcal/mol), which is a thermodynamically favorable process.
This carbene can be captured quickly by trimethylamine−
borane 2a via a concerted process in which cleavage of the B−
H bond and formation of the C−H and C−B bonds occur
synchronously via a three-membered-ring transition state (TS-
Yu-Tao Zhao − State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China
Qiao Zhang − State Key Laboratory and Institute of Elemento-
Organic Chemistry, College of Chemistry, Nankai University,
Tianjin 300071, China
Ming-Yao Huang − State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China
D
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Communication
Insertion into Heteroatom−Hydrogen Bonds with Trifluorodiazoal-
kanes. Angew. Chem., Int. Ed. 2016, 55, 3785−3789. (j) Allen, T. H.;
Kawamoto, T.; Gardner, S.; Geib, S. J.; Curran, D. P. N-Heterocyclic
Carbene Boryl Iodides Catalyze Insertion Reactions of N-Hetero-
cyclic Carbene Boranes and Diazoesters. Org. Lett. 2017, 19, 3680−
3683. (k) Kan, S. B. J.; Huang, X.-Y.; Gumulya, Y.; Chen, K.; Arnold,
F. H. Genetically Programmed Chiral Organoborane Synthesis.
Nature 2017, 552, 132−136. (l) Yang, J.-M.; Li, Z.-Q.; Li, M.-L.;
He, Q.; Zhu, S.-F.; Zhou, Q.-L. Catalytic B−H Bond Insertion
Reactions Using Alkynes as Carbene Precursors. J. Am. Chem. Soc.
2017, 139, 3784−3789. (m) Yang, J.-M.; Zhao, Y.-T.; Li, Z.-Q.; Gu,
X.-S.; Zhu, S.-F.; Zhou, Q.-L. Gold-Catalyzed Oxidative Coupling of
Terminal Alkynes and Borane Adducts: Efficient Synthesis of α-Boryl
Ketones. ACS Catal. 2018, 8, 7351−7355. (n) Pang, Y.; He, Q.; Li,
Z.-Q.; Yang, J.-M.; Yu, J.-H.; Zhu, S.-F.; Zhou, Q.-L. Rhodium-
Catalyzed B−H Bond Insertion Reactions of Unstabilized Diazo
Compounds Generated in Situ from Tosylhydrazones. J. Am. Chem.
Soc. 2018, 140, 10663−10668. (o) Ye, J.-H.; Quach, L.; Paulisch, T.;
Glorius, F. Visible-Light-Induced, Metal-Free Carbene Insertion into
B−H Bonds between Acylsilanes and Pinacolborane. J. Am. Chem. Soc.
2019, 141, 16227−16231. (p) Li, J.-L.; He, H.; Huang, M.-Y.; Chen,
Y.-C.; Luo, Y.; Yan, K.-C.; Wang, Q.-T.; Wu, Y. Iridium-Catalyzed B−
H Bond Insertion Reactions Using Sulfoxonium Ylides as Carbene
Precursors toward α-Boryl Carbonyls. Org. Lett. 2019, 21, 9005−
9008. (q) Zhang, S.-S.; Xie, H.; Shu, B.; Che, T.; Wang, X.-T.; Peng,
D.-M.; Yang, F.; Zhang, L.-Y. Iridium-Catalyzed B−H Insertion of
Sulfoxonium Ylides and Borane Adducts: A Versatile Platform to α-
Boryl Carbonyls. Chem. Commun. 2020, 56, 423−426.
Mao-Lin Li − State Key Laboratory and Institute of Elemento-
Organic Chemistry, College of Chemistry, Nankai University,
Tianjin 300071, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.0c09596
Author Contributions
‡J.-M.Y., and F.-K.G. contributed equally to this work.
Notes
The authors declare no competing financial interest.
Metrical parameters for the structures 5q are available free of
charge from the Cambridge Crystallographic Data Centre
under reference numbers CCDC-1908176.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(21625204, 21790332, 21532003, 21971119), the “111”
project (B06005) of the Ministry of Education of China, and
Key-Area Research and Development Program of Guangdong
Province (2020B010188001) for financial support. Dedicated
to the 100th Anniversary of Chemistry at Nankai University.
REFERENCES
■
(1) (a) For selected reviews, see: Hall, D. G. Boronic Acids:
Preparation and Applications in Organic Synthesis, Medicine and
Materials, 2nd ed.; Wiley-VCH: Weinheim, 2012. (b) Miyaura, N.;
Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organo-
boron Compounds. Chem. Rev. 1995, 95, 2457−2483. (c) Braunsch-
weig, H.; Dewhurst, R. D.; Schneider, A. Electron-Precise
Coordination Modes of Boron-Centered Ligands. Chem. Rev. 2010,
110, 3924−3957. (d) Dembitsky, V. M.; Quntar, A. A. A. A.; Srebnik,
M. Natural and Synthetic Small Boron-Containing Molecules as
Potential Inhibitors of Bacterial and Fungal Quorum Sensing. Chem.
Rev. 2011, 111, 209−237. (e) Leonori, D.; Aggarwal, V. K.
Stereospecific Couplings of Secondary and Tertiary Boronic Esters.
Angew. Chem., Int. Ed. 2015, 54, 1082−1096. (f) Brooks, W. L. A.;
Sumerlin, B. S. Synthesis and Applications of Boronic Acid-
Containing Polymers: From Materials to Medicine. Chem. Rev.
2016, 116, 1375−1397.
(3) For reviews, see: (a) Carboni, B.; Monnier, L. Recent
Developments in The Chemistry of Amine- and Phosphine-Boranes.
Tetrahedron 1999, 55, 1197−1248. (b) Staubitz, A.; Robertson, A. P.
M.; Sloan, M. E.; Manners, I. Amine- and Phosphine-Borane Adducts:
New Interest in Old Molecules. Chem. Rev. 2010, 110, 4023−4078.
(c) Curran, D. P.; Solovyev, A.; Brahmi, M. M.; Fensterbank, L.;
̂
Malacria, M.; Lacote, E. Synthesis and Reactions of N-Heterocyclic
Carbene Boranes. Angew. Chem., Int. Ed. 2011, 50, 10294−10317.
(4) (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds: From Cyclo-
propanes to Ylides; Wiley: New York, 1998. (b) Ford, A.; Miel, H.;
Ring, A.; Slattery, C. N.; Maguire, A. R.; McKervey, M. A. Modern
Organic Synthesis with α-Diazocarbonyl Compounds. Chem. Rev.
2015, 115, 9981−10080. (c) Jia, M.-Q.; Ma, S.-M. New Approaches
to the Synthesis of Metal Carbenes. Angew. Chem., Int. Ed. 2016, 55,
9134−9166.
(2) For a review, see: (a) Yang, J.-M.; Li, Z.-Q.; Zhu, S.-F. Progresses
on the Application of Stable Borane Adducts in the Synthesis of
Organoborons. Chin. J. Org. Chem. 2017, 37, 2481−2497. (b) Bedel,
C.; Foucaud, A. Reaction of Dichlorocarbene with 1,2-Dihydro 1,2 λ3-
Azaphosphinine-Boranes: Dichlorocyclopropanation and Insertion
into Boron-Hydrogen Bond. Tetrahedron Lett. 1993, 34, 311−314.
For selected examples: (c) Imamoto, T.; Yamanoi, Y. Methylene
Insertion Reactions of Samarium Carbenoids into Boron-Hydrogen
and Phosphorus-Hydrogen Bonds. Chem. Lett. 1996, 25, 705−706.
(d) Monnier, L.; Delcros, J.-G.; Carboni, B. Creation of New Boron−
Carbon Bonds by Dichlorocarbene Insertion into the Boron−
Hydrogen Bond of Amine− and Phosphine−Boranes. Tetrahedron
2000, 56, 6039−6046. (e) Li, X.; Curran, D. P. Insertion of Reactive
Rhodium Carbenes into Boron-Hydrogen Bonds of Stable N-
Heterocyclic Carbene Boranes. J. Am. Chem. Soc. 2013, 135,
12076−12081. (f) Cheng, Q.-Q.; Zhu, S.-F.; Zhang, Y.-Z.; Xie, X.-
L.; Zhou, Q.-L. Copper-Catalyzed B−H Bond Insertion Reaction: A
Highly Efficient and Enantioselective C−B Bond-Forming Reaction
with Amine-Borane and Phosphine-Borane Adducts. J. Am. Chem. Soc.
2013, 135, 14094−14097. (g) Chen, D.; Zhang, X.; Qi, W.-Y.; Xu, B.;
Xu, M.-H. Rhodium(I)-Catalyzed Asymmetric Carbene Insertion into
B−H Bonds: Highly Enantioselective Access to Functionalized
Organoboranes. J. Am. Chem. Soc. 2015, 137, 5268−5271.
(h) Cheng, Q.-Q.; Xu, H.; Zhu, S.-F.; Zhou, Q.-L. Enantioselective
Copper-Catalyzed B-H Bond Insertion Reaction of α-Diazoketones.
(5) (a) Stang, P. J. Unsaturated Carbenes. Chem. Rev. 1978, 78,
383−405. (b) Kirmse, W. Alkenylidenes in Organic Synthesis. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1164−1170. (c) Knorr, R.
Alkylidenecarbenes, Alkylidenecarbenoids, and Competing Species:
Which Is Responsible for Vinylic Nucleophilic Substitution, [1 + 2]
Cycloadditions, 1,5-CH Insertions, and the Fritsch-Buttenberg-
Wiechell Rearrangement? Chem. Rev. 2004, 104, 3795−3849.
(d) Grainger, R. S.; Munro, K. R. Recent Advances in Alkylidene
Carbene Chemistry. Tetrahedron 2015, 71, 7795−7835.
(6) (a) Organoboranes for Syntheses: Ramachandran, P. V., Brown,
H. C., Eds. ACS Symposium Series 783; American Chemical Society:
Washington, DC, 2001. (b) Huang, M.-Y.; Zhu, S.-F. Recent
Advances of Catalytic Asymmetric C-B Bond Forming Reactions.
Chem. J. Chin. Univ. 2020, 41, 1426−1448.
(7) (a) Stang, P. J. Vinyl Triflate Chemistry: Unsaturated Cations
and Carbenes. Acc. Chem. Res. 1978, 11, 107−114. (b) Stang, P. J.;
Mangum, M. G.; Fox, D. P.; Haak, P. Unsaturated Carbenes from
Primary Vinyl Triflates. I. Method and Scope. J. Am. Chem. Soc. 1974,
96, 4562−4569. (c) Stang, P. J. From Solvolysis to Self-Assembly. J.
Org. Chem. 2009, 74, 2−20.
(8) (a) Giustra, Z. X.; Liu, S.-Y. The State of the Art in Azaborine
Chemistry: New Synthetic Methods and Applications. J. Am. Chem.
Soc. 2018, 140, 1184−1194. (b) Frath, D.; Massue, J.; Ulrich, G.;
Ziessel, R. Luminescent Materials: Locking π-Conjugated and
́
Acta Chim. Sinica 2015, 73, 326−329. (i) Hyde, S.; Veliks, J.; Liegault,
B.; Grassi, D.; Taillefer, M.; Gouverneur, V. Copper-Catalyzed
E
https://dx.doi.org/10.1021/jacs.0c09596
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
Heterocyclic Ligands with Boron (III). Angew. Chem., Int. Ed. 2014,
53, 2290−2310.
(9) CCDC 1908176 contains the supplementary crystallographic
data for compound 5q. See the Supporting Information for details.
(10) (a) Trost, B. M.; Crawley, M. L. Asymmetric Transition-Metal-
Catalyzed Allylic Alkylations: Applications in Total Synthesis. Chem.
Rev. 2003, 103, 2921−2943. (b) Monk, J. P.; Brogden, R. N.
Naftifine. A Review of its Antimicrobial Activity and Therapeutic Use
in Superficial Dermatomycoses. Drugs 1991, 42, 659−672.
(11) (a) Greenberg, A.; Breneman, C. M.; Liebman, J. F. The Amide
Linkage: Structural Significance in Chemistry, Biochemistry, and
Materials Science; Wiley: New York, 2000. (b) Johannsen, M.;
Jørgensen, K. A. Allylic Amination. Chem. Rev. 1998, 98, 1689−1708.
(c) Huang, L.-B.; Arndt, M.; Gooßen, K.; Heydt, H.; Gooßen, L. J.
Late Transition Metal-Catalyzed Hydroamination and Hydroamida-
tion. Chem. Rev. 2015, 115, 2596−2697.
(12) (a) Roach, B.; Eisner, T.; Meinwald, J. Defense Mechanisms of
Arthropods. α- and β-Necrodol, Novel Terpenes from A Carrion
Beetle (Necrodes surinamensis, Silphidae, Coleoptera). J. Org. Chem.
1990, 55, 4047−4051. (b) Jacobs, R. T.; Feutrill, G. I.; Meinward, J.
Defense Mechanisms of Arthropods. Synthesis of (−)-α-Necrodol
and (−)-β-Necrodol: Novel Cyclopentanoid Terpenes from a Carrion
Beetle. J. Org. Chem. 1990, 55, 4051−4062. (c) Huff, J. R. New
Drugs-Reports of New Drugs Recently Approved by FDA. Bioorg.
Med. Chem. 1999, 7, 2667−2669. (d) Babu, Y. S.; Chand, P.; Bantia,
S.; Kotian, P.; Dehghani, A.; El-Kattan, Y.; Lin, T.-H.; Hutchison, T.
L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. L.; Laver, G.
W.; Montgomery, J. A. BCX-1812 (RWJ-270201): Discovery of a
Novel, Highly Potent, Orally Active, and Selective Influenza
Neuraminidase Inhibitor through Structure-Based Drug Design. J.
Med. Chem. 2000, 43, 3482−3486. (e) Velasco, J.; Ariza, X.; Badía, L.;
̀
Bartra, M.; Berenguer, R.; Farras, J.; Gallardo, J.; Garcia, J.; Gasanz, Y.
Total Synthesis of Entecavir. J. Org. Chem. 2013, 78, 5482−5491.
(f) Zhang, H.-W.; Schinazi, R. F.; Chu, C. K. Synthesis of Neplanocin
F Analogues as Potential Antiviral Agents. Bioorg. Med. Chem. 2006,
14, 8314−8322.
(13) (a) Chisholm, M. H.; Drake, S. R.; Naiini, A. A.; Streib, W. E.
Synthesis and X-ray Crystal Structures of the One-dimensional
Ribbon Chains [MOtBu·tBuOH] and the Cubane Species [MOtBu]4
(M = K and Rb). Polyhedron 1991, 10, 337−345. (b) Liu, W.-B.;
Schuman, D. P.; Yang, Y.-F.; Toutov, A. A.; Liang, Y.; Klare, H. F. T.;
Nesnas, N.; Oestreich, M.; Blackmond, D. G.; Virgil, S.; Banerjee, C.
S.; Zare, R. N.; Grubbs, R. H.; Houk, K. N.; Stoltz, B. M. Potassium
tert-Butoxide-Catalyzed Dehydrogenative C-H Silylation of Hetero-
aromatics: A Combined Experimental and Computational Mecha-
nistic Study. J. Am. Chem. Soc. 2017, 139, 6867−6879.
(14) Feng, Q.; Wu, H.; Li, X.; Song, L.; Chung, L. W.; Wu, Y. D.;
Sun, J. Ru-Catalyzed Geminal Hydroboration of Silyl Alkynes via a
New gem-Addition Mechanism. J. Am. Chem. Soc. 2020, 142, 13867−
13877.
F
https://dx.doi.org/10.1021/jacs.0c09596
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX