Radical trans-Hydroboration of Alkynes with N-Heterocyclic Carbene Boranes

Article abstract of DOI:10.1002/anie.201804515

Hydroboration of internal alkynes with N-heterocyclic carbene boranes (NHC-boranes) occurs to provide stable NHC (E)-alkenylboranes upon thermolysis in the presence of di-tert-butyl peroxide. The E isomer results from an unusual trans-hydroboration, and the E/Z selectivity is typically high (90:10 or greater). Evidence suggests that this hydroboration occurs by a radical-chain reaction involving addition of an NHC-boryl radical to an alkyne to give a β-NHC-borylalkenyl radical. Ensuing hydrogen abstraction from the starting NHC-borane provides the product and returns the starting NHC-boryl radical. Experiments suggest that the observed trans-selectivity results from kinetic control in the hydrogen-transfer reaction.

Full text of DOI:10.1002/anie.201804515

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Radical trans-Hydroboration of Alkynes with N-Heterocyclic
Carbene Boranes
Authors: Masaki Shimoi, Takashi Watanabe, Katsuhiro Maeda, Dennis
P. Curran, and Tsuyoshi Taniguchi
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201804515
Angew. Chem. 10.1002/ange.201804515
Link to VoR: http://dx.doi.org/10.1002/anie.201804515
http://dx.doi.org/10.1002/ange.201804515

10.1002/anie.201804515
Angewandte Chemie International Edition
COMMUNICATION
Radical trans-Hydroboration of Alkynes with N-Heterocyclic
Carbene Boranes
Masaki Shimoi,[a] Takashi Watanabe,[b] Katsuhiro Maeda,[a,c] Dennis P. Curran,*,[d] and Tsuyoshi
Taniguchi*,[a,b]
Abstract: Hydroboration of internal alkynes with N-heterocyclic
carbene boranes (NHC-boranes) occurs to provide stable NHC-(E)-
alkenylboranes upon thermolysis in the presence of di-tert-butyl
peroxide. The (E)-isomer results from an unusual trans-hydroboration,
and the E/Z selectivity is typically high (90:10 or greater). Evidence
suggests that this hydroboration occurs by a radical chain reaction
involving addition of an NHC-boryl radical to an alkyne to give a -
NHC-borylalkenyl radical. Ensuing hydrogen abstraction from the
starting NHC-borane provides the product and returns the starting
NHC-boryl radical. Experiments suggest that the observed trans-
selectivity results from kinetic control in the hydrogen transfer reaction.
and their derivatives.[4b] Similarly, the selectivity is directed by
coordination of substrates to a boron atom.
Also in 2016, Ingleson reported that reactions of N-
heterocyclic carbene (NHC) complexes of 9-BBN with terminal
alkynes and B(C6F5)3 provided trans-hydroboration products
(Figure 1c).[5] These reactions are thought to occur by hydride
abstraction by B(C6F5)3 to give an NHC-9-BBN borenium ion. This
adds electrophilically to the alkyne followed by back hydride
transfer. The 9-BBN borenium ion lacks B–H bonds so the usual
syn-hydroboration path is unavailable. Borenium ions formed
from simpler N-heterocyclic carbene boranes (NHC-BH3) also
hydroborate alkynes, but by the syn-addition pathway.[6]
Hydroboration of multiple bonds is a fundamental method for
synthesis of organoboron compounds.[1] Hydroborations of
alkynes with trivalent boranes provide synthetically useful alkenyl
boron compounds, but only cis-adducts are readily accessible.
This is because typical trivalent boranes induce concerted
hydroboration in a syn-selective manner.[2] Direct hydroboration
of alkynes in an anti-selective fashion is usually called trans-
hydroboration. This is an attractive complement classical cis-
selective hydroboration, but examples are sparse.
Radical-mediated hydroboration processes are conceptually
appealing because they may offer different regio- or
stereoselectivities. But such processes are not practical for most
kinds of boranes both because ionic hydroborations are already
fast and because most kinds of B–H bonds are too strong to
undergo radical hydrogen transfer reactions. In contrast, NHC-
boranes do not thermally hydroborate unstrained alkynes. And
they are good precursors of boryl radicals because their BH
bond dissociation energies are lower than either free boranes or
typical borane complexes with ethers, amines and sulfides.[7]
Several examples of transition-metal-catalyzed trans-
hydroborations of alkynes have been reported since Miyaura and
co-workers first reported rhodium- and iridium-catalyzed trans-
hydroborations of terminal alkynes in 2000 (Figure 1a).[3] In 2016,
Wang reported that a combination of 2-alkynylpyridines and 9-
borabicyclo[3.3.1]nonane (9-BBN) caused trans-hydroboration
without a catalyst (Figure 1b).[4a] This is an example of a directed
trans-hydroboration. Quite recently, Ohmiya and Sawamura
reported phosphine-catalyzed trans-hydroboration of alkynoates
[a]
[b]
M. Shimoi, Prof. K. Maeda, Dr. T. Taniguchi
Graduate School of Natural Science and Technology
Kanazawa University
Kakuma-machi, Kanazawa 920-1192 (Japan)
E-mail: tsuyoshi@p.kanazawa-u.ac.jp
T. Watanabe, Dr. T. Taniguchi
School of Pharmaceutical Sciences, Institute of Medical,
Pharmaceutical and Health Sciences
Kanazawa University
Kakuma-machi, Kanazawa 920-1192 (Japan)
Prof. K. Maeda
Nano Life Science Institute (WPI-NanoLSI)
Kanazawa University
Kakuma-machi, Kanazawa 920-1192 (Japan)
Prof. D. P. Curran
[c]
[d]
Figure 1. Methods for trans-hydroboration of alkynes.
Department of Chemistry
University of Pittsburgh
Pittsburgh, PA 15260 (USA)
E-mail: curran@pitt.edu
Recently, we disclosed radical borylation-cyclization
reactions of strained cyclic diynes with NHC-boranes.[8] Likewise,
Wang and co-workers reported radical borylation-cyclization
reactions of enynes with NHC-boranes and thiols as polarity
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.

10.1002/anie.201804515
Angewandte Chemie International Edition
COMMUNICATION
reversal reagents.[9] These reactions can be viewed as
The use of an increased amount of DTBP (1.5 equiv)
accelerated the reaction, and the use of an increased amount of
DTBP NHC-borane 2 improved the yield of 3 (Entries 2‒4). The
pure trans-hydroboration product (E)-3 was isolated in 66% yield
in the reaction using 4 equiv of 2 and 1.5 equiv of DTBP (Entry 4).
Similar results were obtained in larger scale experiments (see the
Supporting Information). Further increase in the amount of NHC-
borane 2 did not improve the results (Entry 5). In all cases, the
high E-selectivity was observed.
hydroboration reactions that are interrupted by
a radical
cyclization. In these cases, stereoselectivity of resultant cyclic
alkenes is not of interest because only a geometry is possible in
such five- or six-membered ring compounds. We set out to learn
whether direct radical 1,2-hydroboration reactions of alkynes
were possible, and if so, whether these reactions were
stereoselective.
Here we report that radical hydroboration of alkynes with
NHC-boranes is achieved by heating with di-tert-butyl peroxide
(Figure 1d). This reaction is a new approach to trans-selective
hydroborations of alkynes without the need for a catalyst or a
directing group.
When di-tert-butyl hyponitrite (tBuON=NOtBu, TBHN) was
used as an initiator in place of DTBP, the reaction was complete
with lower loading of the initiator (0.5 equiv) and at lower
temperature (80 °C) (Entry 6). However, DTBP is an inexpensive
commercial reagent so we used it in the preparative experiments
going forward unless otherwise noted.
We initially studied the reaction of 1-phenyl-1-propyne (1) and
1,3-dimethylimidazol-2-ylidene borane (2) as a model. Di-tert-
butyl peroxide (DTBP) was chosen as a radical initiator because
the tert-butoxyl radical rapidly abstracts hydrogen atoms from
NHC-boranes to form boryl radicals.[7c,8] A benzene solution of
alkyne 1 (0.2 mmol), NHC-borane 2 (2 equiv), DTBP (1 equiv) was
heated at 120 °C. Alkyne 1 was mostly consumed after 16 h, and
1H and 11B NMR analyses of the crude product indicated
production of two hydroborated isomers in 44% total yield and in
high selectivity (94:6) (Table 1, Entry 1). The products were
separated by silica gel chromatography, and they turned out to be
stereoisomers (rather than regioisomers). Both products 3 are -
NHC-boryl styrenes and NOE experiments showed that the (E)-3
predominates. This results from anti-addition of the NHC-boryl
group and a hydrogen atom. In other words, trans-selective
hydroboration occurs.
The hydroboration reaction of 1 affords surprisingly high
trans-selectivity given the high reaction temperature (120 °C). We
conducted three experiments to shed light on the origin of this
selectivity. First, a reaction similar to that in entry 4 was assessed
by 11B NMR after 30 min and showed an E/Z selectivity of 95:5
(see the Supporting Information). Thus, there is little selectivity
change between 30 min (95:5) and 5 h (94:6). Second, a similar
reaction was continued for about 19 h after the starting alkyne 1
was consumed (24 h total time, Entry 7). This resulted in a
decreased total yield of 3 (from 70% to 53%) and a decreased E/Z
ratio (from 94:6 to 48:52). The decreased yield must result from
slow decomposition, but the change in E/Z ratio cannot be
accounted for by selective decomposition of the E-isomer. This
means that some isomerization has occurred upon extended
reaction and accordingly that initial 95:5 ratio is not the
thermodynamic product ratio. Finally, third, no isomerization was
observed when a benzene solution of isolated (E)-3 and NHC-
borane 2 was heated for 24 h at 120 °C in the absence of DTBP.
This indicates that (E)-3 is thermally stable, and therefore that
radicals are involved in the isomerization process (see the
Supporting Information for a proposed mechanism).
Table 1. Reactions of 1-phenyl-1-propyne (b) and diMe-Imd-BH3 (2).[a]
Taken together, these results suggest that the predominate
formation of the E-isomer is a kinetically controlled result. Radical
isomerization to the Z-isomer can occur at long reaction times but
is inefficient.
Entr
y
2 [equiv]
DTBP
[equiv]
Time [h]
Yield
[%][b]
Ratio
[E/Z][b]
1
2
3
4
5
6
7
2
2
4
4
5
4
4
1
1.5
1
16
7
44
47
94:6
95:5
91:9
94:6
93:7
94:6
48:52
Scheme 1 shows a radical chain mechanism that is consistent
with these results. To initiate the chain, DTBP thermolyzes to tert-
butoxyl radical (tBuO•), which in turn abstracts a hydrogen atom
from NHC-borane 2 to form NHC-boryl radical 4 [step (i)].[7d] In
the first propagation step, the boryl radical 4 adds to alkyne 1 to
form an alkenyl radical 5 stabilized by the phenyl ring [step (ii)].
This step dictates the regioselectivity. In the second propagation
step, a hydrogen transfer reaction between alkenyl radical 5 and
NHC-borane 2 gives (E)-and (Z)-3 and the starting NHC-boryl
radical 4.[8] This step is kinetically controlled and dictates the
stereoselectivity.[10] The fact that stoichiometric amounts of the
initiator are helpful suggests that chain lengths in these reactions
are rather short.
16
5
60
1.5
1.5
0.5[d]
1.5
70 [66][c]
73
5
1
52
24
53
[a]Conditions: 1 (0.2 mmol), 2 (0.41.0 mmol), DTBP (0.20.3 mmol) in
benzene (0.4 mL) at 120 ˚C in a sealed tube. [b]Total yield and ratio of (E)-
and (Z)-3 estimated by 1H and 11B NMR analysis of the crude product
(internal standard for 1H NMR: dimethyl sulfone). [c]Yield of (E)-3 isolated by
silica gel chromatography (0.2 and 1.0 mmol scales). [d]Di-tert-butyl
hyponitrite (TBHN) was used instead of DTBP at 80 ˚C.
When the reaction of alkyne 1 with NHC-BD3 2-d (90% D) was
conducted under the standard conditions, a deuterium atom was
incorporated on the alkene of both isomers of hydroboration
This article is protected by copyright. All rights reserved.

10.1002/anie.201804515
Angewandte Chemie International Edition
COMMUNICATION
product 3 (Scheme 2). This supports the step (ii) shown in
Scheme 1. The 75% D incorporation of (E)-3-d can be rationalized
by a kinetic isotope effect due to 90% D purity of the deuterated
NHC-borane. On the other hand, 45% D incorporation on the
olefin of (Z)-3-d was observed, and a hydrogen atom of an NHC-
methyl group was partially replaced with a deuterium atom (30%
D). This suggests that the (Z)-isomer is partially formed via 1,6-
hydrogen atom transfer (HAT) of radical 5 onto an NHC-methyl
group.[11] Overall, these results are consistent with the radical
mechanism shown in Scheme 1.
Preparative experiments with other representative NHC-
borane reagents were conducted under the standard conditions
(Table 1, Entry 4), and Figure 2 shows the products and isolated
yields. All products were separable and stable, and the isolated
yields are for the pure E-isomers. Small amounts of Z-isomers
were formed, and the E/Z ratios taken from the 1H and 11B NMR
spectra of the crude products are also reported.
The reactions of alkyne 1 with 1,4-dimethyl-1,2,4-triazolium-
5-ylidene borane and 1,3,4,5-tetramethylimidazol-2-ylidene
borane were faster than those of 2 and gave the corresponding
hydroboration products 6 and 7 in similar yields (63% and 67%)
and E/Z ratios (90:10 and 96:4). When 4,5-dichloro-1,3-
dimethylimidazol-2-ylidene borane was used, alkyne 1 was
gradually consumed over 9 h, but a complex mixture resulted. 1H
and 11B NMR analyses of the crude product suggested
decomposition of the starting borane or products, and
hydroboration product 8 was hardly detected. The reaction with
1,3-diisopropylimidazol-2-ylidene borane was extremely sluggish
and afforded only
a trace amount of the corresponding
hydroboration product 9. Accordingly, the hydroboration reaction
might be sensitive to sterics and small N-substituents are
preferred on the NHC ring. On the other hand, we cannot rule out
promotion of 1,6-hydrogen atom transfer on an N-isopropyl
(Scheme 2), which breaks the radical chain reaction by formation
of
a
stable
tertiary
radical.
Tetra-n-butylammonium
cyanoborohydride (nBu4NBH3CN) can mediate radical reactions
such as reductive dehalogenation,[14] but little hydroboration
product 10 was detected in a reaction between nBu4NBH3CN and
1.
Scheme 1. Proposed reaction mechanism.
Scheme 2. Reaction of 1 with NHC-BD3.
Figure 2. Results of reactions of 1-phenyl-1-propyne (1) and several boranes.
Reaction conditions: 1 (0.2 mmol), borane (0.8 mmol), DTBP (0.3 mmol) in
benzene (0.4 mL) at 120 ˚C in a sealed tube. Yields of the isolated (E)-isomer
are shown unless otherwise noted. Ratios of E/Z estimated by 1H and 11B NMR
analysis of the crude product are shown in parentheses. [a]Results from 1H and
11B NMR analysis of the crude product.
Compare the reaction of 1 and NHC-borane 2 with standard
hydroborations of 1. For example, hydroboration of 1 with 9-BBN
(at room temperature in THF) provides the α-boryl styrene isomer
as the major product, though the α/ regioselectivity is modest
(65/35).[12] Of course both products are Z-isomers resulting from
cis-hydroboration. Borane itself gives more α-isomer than 9-BBN,
whereas some bulky boranes give more -isomer. Such boranes
are air-sensitive and must be converted in situ to other products.
In contrast, radical hydroboration of 1 with NHC-borane 2 needs
high temperature but gives almost only the -NHC-boryl styrene
regioisomer with good E-selectivity.[13] This trans-hydroboration
product is not air- or moisture sensitive.
Figure 3 shows additional examples of radical hydroboration
products from reactions of various alkynylarene derivatives with
NHC-borane 2. The standard conditions were used, and reaction
times typically ranged from 5–11 h. The E/Z ratios are of the
crude products, whereas the percentage yields are of the E-
isomers only. Few α-isomers were detected in most cases.[13] All
the products are bench-stable compounds. NHC-borane 2 is
This article is protected by copyright. All rights reserved.

10.1002/anie.201804515
Angewandte Chemie International Edition
COMMUNICATION
readily available, but it can be easily recovered during flash
chromatography if desired.
The reactions of representative 1-aryl-1-propyne derivatives
provided the corresponding trans-hydroboration products 11–18
in yields ranging from 50 to 75% with selectivities typically ranging
from 90:10 to 98:2.
Figure 3. Reactions of various alkynes and diMe-Imd-BH3 (2). Reaction conditions: Alkyne (0.2 mmol), 2 (0.8 mmol), DTBP (0.3 mmol) in benzene (0.4 mL) for 2‒
24 h at 120 ˚C in a sealed tube. Yields of the isolated (E)-isomer are shown unless otherwise noted. Ratios of E/Z estimated by 1H and 11B NMR analysis of the
crude product are shown in parentheses. [a]Shown (E)-isomers were inseparable from small amounts of (Z)-isomers by silica gel chromatography, so yields of the
(E)-isomers estimated from 1H and 11B NMR spectra of the isolated mixture are shown (combined yields of inseparable isomeric mixtures: 11: 72%; 15: 80%; 16:
78%; 21: 59%, 32: 71%). [b]TBHN (0.2 equiv) was used instead of DTBP at 80 ˚C. [c]The reaction was carried out in a flask on a 2.0 mmol scale. [d]tert-Dodecanethiol
(20 mol%) was used as an additive. [e]8 equiv of 2 (1.6 mmol) was used. [f]Regioisomers were produced in 15% yield. [g]Yield was estimated by 1H NMR analysis of
the crude product (internal standard: dimethyl sulfone). [h]2,4-diphenylbuta-1,3-dien-1-ylborane derivatives were detected in 1H NMR spectra of the crude product.
[i]TBHN (0.5 equiv) was used instead of DTBP at 80 ˚C. TBS = tert-butyldimethylsilyl.
The reaction of an alkynylarene with a cyano group was
complicated at high temperature, but the reaction at 80 ˚C in the
presence of TBHN (0.2 equiv) gave radical hydroboration product
14 in high trans-selectivity on 0.2 and 2.0 mmol scales.[15] The
analogue having a bulky mesityl group gave slightly lower
selectivity (87:13), but the starting alkyne was fully consumed in
5 h to give hydroboration product (E)-19 in 67% yield.
The reaction of phenylacetylene was complete in 2 h and
afforded a rather complex mixture from which alkenylborane 30
was obtained in 15% yield. Alkene 30 again results from trans-
hydroboration but is a Z-isomer due to a CIP priority change. Side
products were tentatively identified as stereoisomers of 2,4-
1
diphenylbuta-1,3-dien-1-ylborane [NHC-BH2(CH=CPh)2H] by H
NMR analysis of the crude product. These are double adducts to
phenylacetylene, which in turn suggests that radical
oligomerization competes with this terminal alkyne.[16]
Substrates having a thiophene ring worked well and afforded
alkenylboranes 20 and 21. The reactions of representative 2-
substituted phenylacetylenes gave the corresponding trans-
hydroboration products 22–28 in high selectivity (90:10‒97:3).
These results indicate that trans-selectivity is independent of 2-
substituted groups of alkynes. The cyclopropyl ring in product 25
remains intact. The yield of alkenyl borane 27 having a cyclohexyl
group was moderate (31%), but an increase of NHC-borane 2 to
8 equiv improved the yield to 54%.
When ethyl 3-phenylpropiolate was subjected to the standard
conditions, the ionic hydroboration induced 1,4-hydride addition
to the alkyne competes with radical hydroboration (see the
Supporting Information).[17] Since the ionic path could be
suppressed by lowering the temperature (80 ˚C), using TBHN as
an initiator at lower temperature (80 ˚C) again gave mainly 31
1
(90:10) in moderate yield (Figure 3). Yield was estimated by H
NMR analysis of the crude product because small amounts of
regioisomers were detected (<5% yield) and because products
and unreacted 2 were inseparable.
The high regioselectivity finally broke down with 2-tert-butyl-
1-phenylacetylene. This reaction was sluggish (24 h) and gave
the usual -NHC-boryl styrene 29 in 16% yield along with its α-
NHC-boryl regioisomer (not shown) in 15% yield. The trans-
selectivity, however, was still good (88:12). We also observed
moderate regioselectivity in the reactions non-symmetric diaryl
and dialkyl alkynes (see the Supporting Information).
TBS-protected but-2-yne-1,4-diol was less reactive and was
not consumed in 24 h. The trans-hydroboration product 32 was
formed in low yield (<10%). However, we found that addition of 20
mol% of tert-dodecanethiol (TDT) as a polarity reversal catalyst
This article is protected by copyright. All rights reserved.

10.1002/anie.201804515
Angewandte Chemie International Edition
COMMUNICATION
improved yield (67%) with good trans-electivity (95:5) in 5 h
(Figure 3).[7e] Turning back to conjugated alkynes, the reactions
of substrates that gave 24 and 27 in moderate yields (45% and
31%) under the standard conditions gave improved yields of 24
and 27 (61% and 68%) in the presence of 20 mol% of TDT
(Figure 3). However, E/Z ratios estimated from NMR spectra of
crude products were somewhat lower (75:25 and 82:18) probably
because an isomerization process was also promoted by TDT in
these reactions. The total yields of E- and Z-isomers were more
than 80%. Promotion of reactions by a polarity reversal catalyst
suggests that the hydrogen transfer step (to 3 from 5 in Scheme
1) is slow in this reaction like radical dehalogenation with NHC-
boranes.[7d]
In summary, we have discovered that radical hydroboration of
internal alkynes with NHC-boranes is trans-selective.
Experimental results suggest that this selectivity is due to kinetic
control in the hydrogen atom transfer step. The reaction works
best with conjugated internal alkynes, which provide good yields
of stable (E)-NHC-boryl alkenes.
From a standpoint of
organoboron chemistry, this reaction is a method for synthesis of
new boron-containing π-systems. From a standpoint of radical
chemistry, this reaction suggests expanded potential for
preparative reactions with boron-centered radicals.
Acknowledgements
Examples of preparation of (E)-phenylalkenyl boron
compounds such as (E)-3 are limited,[18] and such compounds
can be useful for synthesis of 1,2-bisaryl alkenes having a Z
configuration. To illustrate, we targeted two retinoid mimics
having a Z configuration. Mimics bearing a 1,1,4,4-tetramethyl-
1,2,3,4-tetrahydronaphthalene ring act on retinoic acid receptors
(RARs) and retinoid X receptors (RXRs) and are potential anti-
cancer agents.[19]
This work was supported by JSPS KAKENHI Grant-in-Aid for
Scientific Research (C) (Grant No. 16K08159). D.P.C thanks the
US National Science Foundation for support.
Keywords: Alkynes • Boranes • Hydroboration • Radical
reactions • Synthetic methods
[1] a) H. C. Brown, Organic Syntheses via Boranes; Wiley: New York, 1975.
(b) Pelter, A.; Smith, K.; Brown, H. C. Borane Reagents; Academic Press:
New York, 1988.
[2] M. Vaulter, G. Alcaraz, Science of Synthesis, Vinylboranes, Georg
Thieme Verlag KG, 2014.
[3] a) T. Ohmura, Y. Yamamoto, N. Miyaura, J. Am. Chem. Soc. 2000, 122,
4990-4991; b) C. Gunanathan, M. Hꢀlscher, F. Pan, W. Leitner, J. Am.
Chem. Soc. 2012, 134, 14349−14352; c) B. Sundararaju, A. Fꢁrstner,
Angew. Chem. Int. Ed. 2013, 52, 14050−14054; Angew. Chem. 2013, 125,
14300−14304; d) Q. Wang, S. E. Motika, N. G. Akhmedov, J. L. Petersen,
X. Shi, Angew. Chem. Int. Ed. 2014, 53, 5418−5422; Angew. Chem. 2014,
126, 5522−5526; e) J. V. Obligacion, J. M. Neely, A. N. Yazdani, I. Pappas,
P. J. Chirik, J. Am. Chem. Soc. 2015, 137, 5855−5858; f) W. J. Jang, W.
L. Lee, J. H. Moon, J. Y. Lee, J. Yun, Org. Lett. 2016, 18, 1390−1393; g)
S. Xu, Y. Zhang, B. Li, S.-Y. Liu, J. Am. Chem. Soc. 2016, 138,
14566−14569; h) N. Gorgas, L. G. Alves, B. Stöger, A. M. Martins, L. F.
Veiros, K. Kirchner, J. Am. Chem. Soc. 2017, 139, 8130−8133.
[4] a) K. Yuan, N. Suzuki, S. K. Mellerup, X. Wang, S. Yamaguchi, S. Wang,
Org. Lett. 2016, 18, 720−723; b) K. Nagao, A. Yamazaki, H. Ohmiya, M.
Sawamura, Org. Lett. 2018, 20, 1861−1865.
[5] a) J. S. McGough, S. M. Butler, I. A. Cade, M. J. Ingleson, Chem. Sci.
2016, 7, 3384−3389; a related reaction: b) T. Wang, X. Jentgens, C. G.
Daniliuc, G. Kehr, G. Erker, ChemCatChem 2017, 9, 651−658.
[6] A. Boussonniꢂre, X. Pan, S. J. Geib, D. P. Curran, Organometallics 2013,
32, 7445−7450.
[7] a) S.-H. Ueng, A. Solovyev, X. Yuan, S. J. Geib, L. Fensterbank, E. Lacꢃte,
M. Malacria, M. Newcomb, J. C. Walton, D. P. Curran, J. Am. Chem. Soc.
2009, 131, 11256−11262; b) A. Solovyev, S.-H. Ueng, J. Monot, L.
Fensterbank, M. Malacria, E. Lacôte, D. P. Curran. Org. Lett. 2010, 12,
2998–3001; c) J. C. Walton, M. Makhlouf Brahmi, L. Fensterbank, E.
Lacôte, M. Malacria, Q. Chu, S.-H. Ueng, A. Solovyev, D. P. Curran, J.
Am. Chem. Soc. 2010, 132, 2350–2358; d) X. Pan, E. Lacôte, J. Lalevée,
D. P. Curran, J. Am. Chem. Soc. 2012, 134, 5669–5674; e) T. Kawamoto,
S. J. Geib, D. P. Curran, J. Am. Chem. Soc. 2015, 137, 8617–8622.
[8] T. Watanabe, D. Hirose, D. P. Curran, T. Taniguchi, Chem. Eur. J. 2017,
23, 5404–5409.
Scheme 3. Representative examples of synthesis of trisubstituted alkenes
using Suzuki-Miyaura reaction. Conditions (0.1 mmol scale): NCS (2 equiv), 1,4-
dioxane (1 mL) for 15 min at room temperature, then H2O (0.2 mL), aryl bromide
(1.3 equiv), PdCl2(dppf) (5 mol %), Na2CO3 (5 equiv) for 3 h at reflux. NCS = N-
chlorosuccinimide.
(Z)-Retinoid derivative 33[18] was synthesized by a one-pot
procedure involving treatment of NHC-alkenylborane (E)-3 with
N-chlorosuccinimide (NCS) in 1,4-dioxane (Scheme 3). Water
was then added (to form a boronic acid) along with 6-bromo-
1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene, PdCl2(dppf)
and Na2CO3. A Suzuki-Miyaura reaction ensued,[20,21] and 33 was
isolated in 50% yield. The strategy was reversed in the synthesis
of cyano analog 34.[19] Here the 1,1,4,4-tetramethyl-1,2,3,4-
tetrahydro-naphthalene is present in the starting alkenylborane
(E)-18. Reaction of this with NCS followed by direct Suzuki-
Miyaura coupling with 4-bromobenzonitrile provided 34 is 50%
yield. Since NMR spectra of (Z)-1,2-bisaryl alkenes 33 and 34
accorded with those of literature, trans-hydroboration of alkyne 1
was synthetically confirmed.
[9] S.-C. Ren, F.-L. Zhang, J. Qi, Y.-S. Huang, A.-Q. Xu, H.-Y. Yan, Y.-F.
Wang, J. Am. Chem. Soc. 2017, 139, 6050–6053.
[10] Radical hydrostannation and hydrosilylation of 1,2-disubstituted
phenylacetylenes (PhCCR) give moderate trans-selectivity at relatively
low temperature: (a) K. Nozaki, K. Oshima, K. Utimoto, J. Am. Chem. Soc.
1987, 109, 2547−2549; b) B. Kopping, C. Chatgilialoglu, M. Zehnder, B.
Giese, J. Org. Chem. 1992, 57, 3994−4000.
[11] M. Nechab, S. Mondal, M. P. Bertrand, Chem. Eur. J. 2014, 20,
16034−16059.
[12] H. C. Brown, C. G. Scouten, R. Liotta, J. Am. Chem. Soc. 1979, 101,
96−99.
[13] In addition to two -isomers, trace signals (<1%) were sometimes
detected in 11B NMR analysis of the reactions of 1-aryl-1-propyne
derivatives. Although those might be based on α-isomers, isolation and
assignment of those compounds were difficult due to very small amounts.
[14] T. Kawamoto, I. Ryu, Org. Biomol. Chem. 2014, 12, 9733–9742.
This article is protected by copyright. All rights reserved.

10.1002/anie.201804515
Angewandte Chemie International Edition
COMMUNICATION
[15] An alkynylarene having a nitro group was also tested, but a complex
mixture was obtained even at low temperature.
phenylethynylboronate: L. Deloux, M. Srebnik, M. Sabat, J. Org. Chem.
1995, 60, 3276−3277.
[16] S. Amdur, A. T. Y. Cheng, C. J. Wong, P. Ehrlich, R. D. Allendoerfer, J.
Polym. Sci. Polym. Chem. Ed. 1978, 16, 407−414.
[17] T. R. McFadden, C. Fang, S. J. Geib, E. Merling, P. Liu, D. P. Curran, J.
Am. Chem. Soc. 2017, 139, 1726−1729.
[18] For instance, there is only one example of the selective synthesis of the
pinacolborane derivative corresponding to (E)-3 via hydrozirconation of a
[19] G. Garipova, A. Gautier, S. R. Piettre, Tetrahedron 2005, 61, 4755−4759.
[20] S. Nerkar, D. P. Curran, Org. Lett. 2015, 17, 3394−3397.
[21] a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457−2483; b) A. Suzuki,
Angew. Chem. Int. Ed. 2011, 50, 6722−6737; Angew. Chem. 2011, 123,
6854−6869.
This article is protected by copyright. All rights reserved.

10.1002/anie.201804515
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
Masaki Shimoi, Takashi Watanabe,
Katsuhiro Maeda, Dennis P. Curran,*
Tsuyoshi Taniguchi*
Page No. – Page No.
Radical trans-Hydroboration of
Alkynes with N-Heterocyclic Carbene
Boranes
Radical hydroboration of alkynes with N-heterocyclic carbene boranes (NHC-
boranes) has been developed. The reaction occurs in a highly trans-selective
manner to provide bench-stable NHC-(E)-alkenylboranes from internal alkynes.
This article is protected by copyright. All rights reserved.