Palladium-Catalyzed Intermolecular Trans-Selective Carbofunctionalization of Internal Alkynes to Highly Functionalized Alkenes

Article abstract of DOI:10.1021/acscatal.0c02522

A palladium/DPEphos-catalyzed intermolecular trans-selective carbofunctionalization of internal alkynes has been established herein. This method proceeds through a formal anti-carbopalladation, forming trans-alkenyl palladium species, which was trapped by aryl boronic acids to provide all-carbon tetrasubstituted alkenes in 32-92% yields. The trans-selective arylsilylation/remote C-H silylation and hydroarylation/remote C-H borylation of internal alkynes were also achieved using hexamethyldisilane and bis(pinacolato)diboron as trapping reagents, respectively. The reaction features good regio- and stereoselectivity and high functional group tolerance. A preliminary mechanistic study and DFT calculations show that a cis to trans isomerization of cis-alkenyl palladium species was involved in this transformation.

Full text of DOI:10.1021/acscatal.0c02522

Subscriber access provided by University of Rochester | River Campus & Miner Libraries
Article
Palladium-Catalyzed Intermolecular trans-Selective Carbofunctionalization
of Internal Alkynes to Highly Functionalized Alkenes
Weiwei Lv, Shihan Liu, Yanhui Chen, Si Wen, Yu Lan, and Guolin Cheng
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.0c02522 • Publication Date (Web): 24 Aug 2020
Downloaded from pubs.acs.org on August 24, 2020
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 8
ACS Catalysis
1
2
3
4
5
6
Palladium-Catalyzed Intermolecular trans-Selective
Carbofunctionalization of Internal Alkynes to Highly
Functionalized Alkenes
7
8
Weiwei Lv,a Shihan Liu,b Yanhui Chen,a Si Wen,a Yu Lan,*b,c and Guolin Cheng*a
a College of Materials Science & Engineering, Huaqiao University, Xiamen 361021, P. R. China
b School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400030, P. R. China
c College of Chemistry, and Institute of Green Catalysis, Zhengzhou University, Zhengzhou 450001, P. R. China
KEYWORDS: palladium, alkenes, C−H activation, silylation, borylation
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ABSTRACT: A palladium/DPEphos-catalyzed intermolecular trans-selective carbofunctionalization of internal alkynes has been
established herein. This method proceeds through a formal anti-carbopalladation, forming trans-alkenyl palladium species, which
was trapped by aryl boronic acids to provide all-carbon tetrasubstituted alkenes in 32−92% yields. The trans-selective
arylsilylation/remote C–H silylation and hydroarylation/remote C–H borylation of internal alkynes were also achieved by using
hexamethyldisilane and bis(pinacolato)diboron as trapping reagents, respectively. The reaction features good regio- and
stereoselectivity and high functional group tolerance. A preliminary mechanistic study and DFT calculations show that a cis to
trans isomerization of cis-alkenyl palladium species was involved in this transformation.
Introduction
intermolecular formal anti-carbopallation of internal alkynes,
and the subsequent trapping of the trans-alkenyl palladium
species would lead to a variety of trans-tetrasubstituted
Tetrasubstituted alkenes are a highly important motif in many
natural products,1 pharmaceuticals,2 and functional materials.3
Their efficient regio- and stereoselective synthesis has
provided major challenges to synthetic organic chemists due to
the congested nature of the double bond.4 The
carbometalations of internal alkynes are the most
straightforward and widely used methods to form
tetrasubstituted alkenes.5 These methods are understood to
proceed through syn-carbometalation, forming alkenyl metal
complexes, followed by a range of further reactions to provide
cis-tetrasubstituted alkenes. (Scheme 1a). Noteworthy among
them is the Larock’s palladium-catalyzed three-component
reaction of aryl iodides, internal alkynes, and aryl boronic
acids, which could deliver all-carbon tetrasubstituted alkenes
with high efficiency.6,7 Although the initial syn-
carbopalladation across the π bond may be stereospecific, in
some cases cis to trans isomerization of alkenyl palladium
species was observed, which could deliver trans-products as
minor isomers.7f–j,8 Recently, the intramolecular capture of the
trans-alkenyl palladium species, which were formed via cis to
trans isomerization, has been well documented for the
synthesis of trans-tetrasubstituted alkene-containing cyclic
compounds by Werz’s group (Scheme 1b).9 In 2015, Lautens
described a sterically hindered substrate and ligand controlled
intramolecular formal anti-carbopalladation reaction for the
synthesis of chlorocarbamoylation products with high
stereoselectivity (Scheme 1c).10 Undoubtedly, expanding this
alkenes
(Scheme
1d).
Herein,
we
disclose
a
palladium/DPEphos (bis[(2-diphenylphosphino)phenyl]ether)
catalyst system that enables the intermolecular trans-selective
diarylation, arylsilylation/remote C–H silylation, and
hydroarylation/remote C–H borylation of internal alkynes to
deliver highly functionalized trans-acyclic alkenes with
remarkable regio- and stereoselectivity.
Scheme 1. Carbometalation of Internal Alkynes for the
Synthesis of Tetrasubstituted Alkenes
(a) Traditional methods: syn-carbometalation to cis-vinyl metal species
R3
R4
R2
R1
R3
R2
R1
R4
cross-coulping
X
syn-carbometalation
R2
R3
R1
M
+
M
M = Pd, Ni, Cu, Co, Mg, and Zn
Larock (2003): M = Pd, X = B(OH)2
(b) Intramolecular trapping of the trans-vinyl palladium species
Ph
O
OH
Pd
Ln
Ln
I
cis to trans HO
OH
Pd
R
Pd
isomerization
I
Ph
I
+
Ph
Ph
Ph
R
R
Werz (2015)
R =
Ph
3
(c) Intramolecular anti-carbopalladation of alkynes enabled by a bulky substituent
Ln
Cl Pd
Ln
Pd
Cl
TIPS
Cl
TIPS
Pd
TIPS
O
TIPS
cis to trans
isomerization
Cl
O
O
N
N
N
N
O
Bn
Bn
Bn
Lautens (2015)
Bn
chemistry
to
intermolecular
trans-selective
carbofunctionalization of internal alkynes is considerably
appealing yet conceptually challenging. To the best of our
knowledge, there are no reports on the three-component
reactions of aryl iodides, alkynes, and electrophiles, generating
trans-tetrasubstituted alkenes through intermolecular formal
anti-carbopalladation/cross-coupling sequence (Scheme 1c).
Inspired by Lautens’ work, we envisaged that steric hindrance
between the substrate and the ligand could enable the
This work
(d)
: Intermolecular anti-carbopalladation of alkynes enabled by a bulky ligand
cis to trans
Ar2
R
Ar3
Ar2
R
Ar3
X
Pd Ln
isomerization
R
Pd/L
Ar1
I
R
Ar2
+
Ar1
Ar1
Pd
Ln
I
Ar2
Ar1
R = Ar2 or alkyl
L = bulky phosphine ligand
ACS Paragon Plus Environment

ACS Catalysis
Page 2 of 8
Results and Discussion
Scheme 2. Scope of Aryl Iodides, Aryl Boronic Acids, and
Internal Alkynesa
1
2
3
4
5
6
7
8
9
Table 1. Selected Optimization Studiesa
Pd(PPh3)4 (5 mol %)
DPEphos (5 mol %)
Na2CO3 (3 equiv)
Ar3
Ar2
Ar2
Ar3
R
R
Me
MeO
OMe
MeO
Me
Ar3 B(OH)2
Ar2
Ar2
Ar1
I
+
Pd (5 mol %)
Me
+
Ar1
+
Ar1
Ligand (10 mol %)
DMF, 120 °C, 24 h, N2
I
B(OH)2
1
2
3
4
trans- , major
4
cis- , minor
Na2CO3 (3 equiv)
Me
DMF, 120 °C, 24 h, N2
Me
+
1a
3a
+
(a) Scope of aryl iodides
Me
Me
MeO
R
MeO
MeO
OMe
OMe
Me
4aa
, 71%, 16:1
R = Me
R = Et
R = iPr
2a
cis-4aa
trans-4aa
4ab
, 60%, 20:1
OMe
4ac
, 78%, 33:1
Me
Me
(47%, 33:1)b
, 49%, 16:1
, 47%, 8:1
4af
, 45%, 15:1
PCy2
MeO
iPr
PCy2
iPr
PCy2
PPh2
PPh2
4ad
R = CH2OMe
R = F
N
O
O
Fe
iPr
iPr
4ae
O
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
PPh2
PPh2
OMe
OMe
Me
PPh2
PPh2
iPr
Xantphos
Davephos
Dppf
Brettphos
DPEphos
Ruphos
Me
MeO
Me
N
MeO
Me
Me
Me
MeO
Me
MeO
yield (%)b
trans :cisc
Me
MeO2C
entry ligand
catalyst
1
P(1-naphthyl)3 Pd(OAc)2
45
72
70
72
69
72
68
66
74
72
71
66
60
60
1:1
OMe
OMe
Me
Me
OMe
, 92%, 17:1
OMe
F
4ah
4ag,
47%, 10:1
4ai
4aj
, 53%, 12:1
, 66%, 14:1
2
PCy3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
PdCl2
4:1
O
3
Davephos
Ruphos
5:1
MeO
Me
Me
Me
MeO
Me
MeO
Me
MeO
4
8:1
5
Brettphos
Dppfd
5:1
Me
N
6
11:1
14:1
12:1
10:1
9:1
N
Ts
7
DPEphosd
Xantphosd
DPEphosd,e
DPEphosd,f
DPEphosd
DPEphosd
DPEphosd
-
OMe
OMe
OMe
OMe
MeO2C
O
N
OMe
4al
8
4am, 33%, 5:1
4an
, 40%, 6:1
4ak, 74%, 10:1
, 45%, 16:1
Me
9
(b) Scope of aryl boronic acids
R = nBu
R =tBu
4ba
4bb
, 66%, 28:1
10
11
12
13
14
R
MeO
iPr
, 57%, 20:1
R
MeO
16:1
13:1
13:1
6:1
R = CH2OH 4bc, 41%, 20:1
4bd
R = Ph
, 60%, 18:1
, 53%, 38:1
, 82%, 43:1
, 62%, 16:1
4bi
4bj
4bk
R = Me
R = CH2OH
R = Ph
, 67%, 16:1
, 45%, 17:1
, 61%, 14:1
4be
R = OBn
R = SMe
R = Cl
iPr
4bf
Pd(acac)2
Pd(PPh3)4
4bg
4bh
, 59%, 18:1
R =CO2Me
OMe
OMe
R
aReaction conditions: 1a (0.3 mmol), 2a (0.1 mmol), 3a (0.2
mmol), Pd (5 mol%), ligand (10 mol%), and base (0.3 mmol) in
DMF (1 mL) at 120 °C under nitrogen atmosphere for 24 h.
Me
MeO
iPr
F
F
Me
MeO
iPr
MeO
iPr
O
O
MeO
iPr
F
bIsolated combined yields. Isomeric ratios were determined by
c
analysis of 1H NMR spectra of isolated inseparable products.
dLigand (5 mol %) was used. eK2CO3 was used instead of Na2CO3.
OMe
OMe
, 69%, 12:1
OMe
OMe
, 55%, 30:1
4bl
R = Me
R = Cl
, 53%, 18:1
4bm
4bp
4bn
, 63%, 15:1
4bo
, 72%, 22:1
fCS2CO3 was used instead of Na2CO3. DMF
dimethylformamide.
= N,N-
(c) Scope of internal alkynes
Me
Me
OMe
Me
Me
iPr
Me
OMe
At the beginning of study, 2-iodotoluene (1a), 1,2-bis(4-
methoxyphenyl)ethyne (2a), and 4-tolylboronic acid (3a) were
chosen as model substrates to explore the reaction conditions
(Table 1, see the Supporting Information, Table S1 for
details). The reaction was conducted using Pd(OAc)2, P(1-
naphthyl)3, Na2CO3 as catalyst, ligand, and base, respectively,
in a solution of DMF at 120 °C for 24 hours to afford 45%
yield of the desired product (4aa) with poor stereoselectivity
(trans:cis 1:1, Table 1, entry 1). Encouraged by this result, we
then investigated a series of monodentate bulky phosphine
ligands (entries 2−5). Gratifyingly, higher yields of 4aa were
obtained, albeit in moderate isomeric ratios (4:1 to 8:1).
Excitedly, the stereoselectivity was significantly improved
when bidentate ligands were employed, and DPEphos was
found to give the best performance (trans:cis 14:1, entries
6−8). Other bases slightly improved the conversion and were
accompanied by noticeable erosion in stereoselectivity (entries
9 and 10). In our subsequent screenings of catalysts (entries
11−13), we discovered that Pd(PPh3)4 was an effective catalyst
to promote the desired reaction, affording 4aa in 71% yield
with 16:1 isomeric ratio (entry 11). The stereoselectivity was
dramatically decreased in the absence of DPEphos, which
highlighted the importance of steric effect from the ligand in
this current transformation (entry 14). Finally, the optimized
iPr
iPr
iPr
Me
, 39%, 13:1
Me
Me
MeO
4cb
, 47%, 15:1
Me
4cd
4cc
, 61%, 20:1
Me
4ca
, 88%, 10:1
Me
N
nBu
nBu
X
iPr
iPr
iPr
iPr
X
N
OMe
4cf
4cg
X = O,
X = S,
, 41%, 22:1
, 78%, 16:1
ch,
4
49%, 9:1
4ci
, 43%, 10:1
Me
4ce
, 47%, 10:1
Me
Me
Me
O
nBu
EtO
iPr
nPr
iPr
TsHN
iPr
iPr
X
OMe
4cj
X = O,
X = S,
, 32%, 20:1
4ck
4cm
4cl
, 41%, 10:1
, 57%, 16:1
, 33%, 8:1
4cn
, 36%, 3:1
aReaction conditions: 1 (0.3 mmol), 2 (0.1 mmol), 3 (0.2 mmol),
Pd(PPh3)4 (5 mol %), DPEphos (5 mol %), and Na2CO3 (0.3
mmol) in DMF (1 mL) at 120 °C under nitrogen atmosphere for
24 h. b1-Bromo-2-isopropylbenzene was used as substrate.
reaction conditions were identified as follows: 1a (0.3 mmol),
2a (0.1 mmol), 3a (0.2 mmol), Na2CO3·(0.3 mmol), Pd(PPh3)4
ACS Paragon Plus Environment

Page 3 of 8
ACS Catalysis
(5 mol %), and DPEphos (5 mol %) in a solution of DMF (1
Furthermore, internal alkynes containing an electron-donating
aryl substituent (R1 = Me, MeO; 6m, 6n) or an electron-
withdrawing aryl substituent (R1 = F, Cl; 6o, 6p) could also be
1
mL) at 120 °C for 24 hours (entry 11).
2
3
4
5
6
7
8
9
Adopting the optimized three-component sequential
transformation protocol, the generality of this method was first
evaluated via a variety of aryl iodides (Scheme 2a). It was
observed that the steric hindrance on the 2-position of phenyl
iodides improved the stereoselectivity (4aa−ae). The less
sterically hindered 2-fluoro phenyl iodide could give the
corresponding desired product (4ae) in 8:1 isomeric ratio.
Other phenyl iodides bearing ester, fluoro, morpholine, and
Weinreb amide groups also could give the corresponding
products in moderate to good yields with excellent
stereoselectivity (4af−al). Notably, heteroaryl iodides could
give the desired products (4m and 4n) in 33% and 40% yields,
respectively. However, no desired product was observed when
(2-iodophenyl)trimethylsilane (1o) was used. Aryl bromide
was also identified as the suitable substrate for this reaction,
delivering product (4ac) in 47% yield with similar
stereoselectivity. We then turned our attention to examining
the scope of aryl boronic acid substrates (Scheme 2b). Both
the electron-donating and electron-withdrawing groups on aryl
boronic acid were well tolerated to afford 4ba−bp in moderate
to good yields with higher than 12:1 isomeric ratios.
Importantly, benzyl alcohol (4bc, 4bj) was well tolerated in
this reaction system. A variety of 1,2-di(hetero)aryl ethynes
were also tested, and given 4ca−cg with high stereoselectivity
(Scheme 2c). Unsymmetrical internal alkynes have been
successfully employed in this process and the desired products
(4ch−cm) were isolated with decent regio- and
stereoselectivity, albeit in lower yields. It was noteworthy that
ethyl 3-phenylpropiolate was also employed to provide the
corresponding product (4cn) in 36% yield with 3:1 isomeric
ratio. Finally, this reaction was not applied to (3,3-
incorporated
into
the
product
with
satisfactory
stereoselectivity. The configuration of product (6a) was
confirmed by single-crystal X-ray crystallography.
Considering the broad utility of arylboron reagents in
synthesis, we questioned whether borylation reaction is
compatible with this anti-carbopalladation strategy (Scheme
4). We commenced the investigation by using 1a and 2b as
substrates and bis(pinacolato)diboron (8) as the borylation
reagent to verify the hypothesis. Surprisingly, trans-
hydroarylation/remote C–H borylation product trans-9a was
isolated as major isomer.14 We then use a variety of aryl
iodides and internal alkynes to evaluate the substrate scope.
The reactions proceeded smoothly to provide the
corresponding ortho-alkenyl phenylboronic acid pinacol esters
(9a−l) in acceptable yields (47-65%). In all cases, remarkable
stereoselectivity (trans:cis > 10:1) were achieved. Despite our
optimization efforts, only moderate regioselectivities (trans-
9:trans-10; 3:1 to 5:1) were obtained. In contrast with the
recently reported C−H borylation via aryl to alkenyl 1,4-
palladium migration,15c our work represents a rare example on
C–H borylaton involving alkenyl to aryl 1,4-palladium
migration.15,16 The trans-configuration of 9e was determined
by NOE measurement (Supporting Information, Figure S2).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Scope of Aryl Iodides and Internal Alkynesa
R1
Ar1
I
Pd(OAc)2 (5 mol %)
DPEphos (5 mol %)
Na2CO3 (3 equiv)
Ar2
Ar2
1
TMS
TMS
+
R2
Ar2
Ar2
TMS
TMS
+
DMF, 100 °C, 24 h, N2
2
+
Ar2
Ar1
trans-
TMS TMS
7
cis-
6
minor
major
5
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
dimethylbut-1-yn-1-yl)benzene
(2p),
(phenylethynyl)(p-
Me
F
Me
Et
tolyl)sulfane (2q), and dec-5-yne (2r). These results showed
that our work is a good complement to Werz’s intramolecular
anti-carbopalladation,9 in which internal alkynes with tert-
butyl, silyl, and methylthio (rather than aryl) groups directly
attached to the triple bond are suitable substrates. It should be
noted that the connectivity of the obtained product (4aa) was
unambiguously established by single-crystal X-ray
crystallography, and the trans-configuration of 4ck was
determined by NOE measurement (Supporting Information,
Figure S1).
Ph
Ph
Ph
Ph
Me
6a
, 65%, 25:1
6b
6c
, 57%, > 99:1
6d
, 49%, 100:0
TMS
, 48%, 47:1
TMS
TMS
TMS
TMS
TMS
TMS
TMS
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Cl
F
MeO2C
Me
6h
, 53%, > 99:1
6e
6g
, 56%, 13:1
, 52%, 25:1
TMS
6f
, 54%, 17:1
TMS
TMS
TMS
TMS
TMS
TMS
TMS
Me
Me
Me
MeO
N
Ph
Ph
Ph
Ph
Alkenylsilanes are versatile intermediates in organic
synthesis.11 We previously disclosed a three-component bis-
silylation reaction of aryl iodides, norbornadiene, and
hexamethyldisilane for the assembly of (Z)‑β-substituted
alkenylsilanes.12a,12b Based on this work, we envisioned that a
palladacycle, generated upon intramolecular C–H activation of
alkenyl palladium intermediate,13 might be trapped by
hexamethyldisilane to produce the disilylated product.12 In line
with the above hypothesis, we commenced the investigation
by using hexamethyldisilane 5 as the bis-silylation reagent to
evaluate the substrate scope (Scheme 3). To our delight, a
variety of aryl iodides could be smoothly transferred into the
desired products (6a−i) in 48−70% yields with excellent
stereoselectivity (>13:1), while 5:1 and 7:1 isomeric ratios
were obtained in the cases of 6j and 6k, respectively. Various
functional groups were well tolerated, such as halide, ester,
and Weinreb amide. In addition, a pyridine ring (6l) was
compatible to the reaction conditions, demonstrating the
compatibility of this typically coordinating functional group.
MeO
Me
F
MeO2C
N
O
6k, 60%, 7:1
6l
, 33%, 32:1
6i
6j
, 70%, 5:1
, 55%, 13:1
Me
MeO
F
Cl
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
Me
Me
Me
Me
Me
OMe
F
Cl
6p
, 50%, 5:1
6o
, 55%, 17:1
6n
, 33%, 32:1
6m
, 41%, 10:1
aReaction conditions:
1
(0.15 mmol),
2
(0.1 mmol),
hexamethyldisilane (0.15 mmol), Pd(OAc)2 (5 mol %), DPEphos
(5 mol %), and Na2CO3 (0.3 mmol) in DMF (1 mL) at 100 °C
under nitrogen atmosphere for 24 h. Isomeric ratios were
determined by analysis of 1H NMR spectra of the crude products.
The utility of this chemistry was demonstrated by the gram-
scale synthesis of 6a and 9c. The reactions of 1a, 2b, and 5 or
1c, 2b, and 8 completed within 24 h, producing the desired
ACS Paragon Plus Environment

ACS Catalysis
products (6a) and (9c) in 65% and 50% yields, respectively
(Scheme 5a). It is worth mentioning that aryl silanes and aryl
Scheme 4. Scope of Aryl Iodides and Internal Alkynesa
Page 4 of 8
reaction of 6a would lead to tri-aryl substituted alkene (14)
(Scheme 5b, left). The aryl boronic acid pinacol ester (9c) can
be further elaborated through well-established iodination,
cross-coupling, and azidation reactions to generate
synthetically useful tri-aryl substituted alkenes (15−17), which
are difficult to make by other methods (Scheme 5b, right).
1
2
3
4
5
6
7
8
Ar1
1
I
Pd(OAc)2 (5 mol %)
DPEphos (5 mol %)
Na2CO3 (3 equiv)
Ar2
Ar2
R1
Bpin
H
Ar2
Ar2
+
Ar1
Ar2
Ar1
Bpin
+
R2
H
Bpin
Ar2
Ar2
+
+
Ar2
2
+
DMF, 120, °C 24 h, N2
Bpin
Ar2
Ar1
trans-
major
To understand the reaction mechanism, we conducted an
experiment of cis-alkenyl iodide (18) with hexamethyldisilane
under the standard reaction conditions. The desired product
trans-6a was obtained in 67% yield as almost a single isomer
(Eq. 1). Whereas the reaction was performed in the absence of
ligand, the cis-7a was isolated as major product with high
steroselectivity (trans:cis 1:10), which indicated that DPEphos
plays an important role in the cis to trans isomerization of
alkenyl palladium species.
10
minor
cis-11
minor
trans-
10
minor
9
cis-
Bpin Bpin
8
Bpin
H
Bpin
H
Bpin
H
Bpin
H
9
iPr
Me
Et
Me
Ph
Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ph
Ph
Cl
9b
9a
, 57%
, 47%
9c
,64%,
9d
, 43%
9:
10
9:
10
trans- trans- = 4:1
trans:cis = 16:1
trans- trans- = 4:1
trans:cis = 12:1
9:
10
trans- trans- = 4:1
trans:cis > 20:1
9:
10
trans- trans- = 3:1
trans:cis = 17:1
Bpin
H
Bpin
H
Bpin
H
Bpin
H
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
I
Ph
Pd(OAc)2 (5 mol %)
DPEphos (5 mol %)
Na2CO3 (3 equiv)
Pd(OAc)2 (5 mol %)
K2CO3 (1 equiv)
Me4NOAc (1 equiv)
DMF, 100 °C, 24 h, N2
F
TMS
TMS
2-MeC6H4
Ph
Ph
Me
9h
, 45%
F
18
Me
9e
9f
9g
, 67%
9:
, 49%
9:
, 47%
9:
DMF, 100 °C, 24 h, N2
Me
(1)
9:
10
TMS
TMS
10
10
10
trans- trans- = 4:1
trans:cis = 15:1
trans- trans- = 5:1 trans- trans- = 4:1 trans- trans- = 4:1
trans:cis = 17:1
Ph
+
trans:cis > 20:1
trans:cis > 20:1
TMS-TMS
Me
MeO
F
5
7a
cis- , 52%, trans :cis = 1:10
6a
trans- , 67%, trans :cis >99:1
Bpin
H
Bpin
H
Bpin
H
Bpin
H
MeO
Me
On the basis of this result and literature reports, we
proposed that the reaction would proceed as shown in Scheme
6. This reaction is initiated by Ar−I oxidative addition to Pd0,
followed by syn-carbopalladation of internal alkyne to
generate a cis-alkenyl palladium species (II). The steric
hindrance-promoted cis to trans isomerization of (II) could
take place to form the thermodynamically more stable trans-
alkenyl palladium species (III). The subsequent Suzuki-
Miyaura cross-coupling reaction of (III) with aryl boronic
acids could give tetrasubstituted alkenes (4). In another
scenario, (III) could further undergo C−H activation to
Me
Me
Me
Me
OMe
F
MeO
9k
9j
, 74%
, 51%
9l
, 43%
9i
, 63%
9:
10
9:
10
trans- trans- = 4:1
trans:cis = 10:1
trans- trans- = 4:1
trans:cis > 20:1
9:
10
trans- trans- = 4:1
trans:cis > 20:1
9:
10
trans- trans- = 5:1
trans:cis > 20:1
aReaction conditions:
1
(0.15 mmol), 2 (0.1 mmol),
bis(pinacolato)diboron (0.15 mmol), Pd(OAc)2 (5 mol %),
DPEphos (5 mol %), and Na2CO3 (0.3 mmol) in DMF (1 mL) at
100 °C under nitrogen atmosphere for 24 h. Isomeric ratios were
determined by analysis of 1H NMR spectra of the crude products.
generate
a palladacycle (IV), which can react with
Scheme 5. Gram-Scale Reactions and Derivatization
Reactions
hexamethyldisilane leading to the alkenyl silanes (6).
Furthermore, alkenyl palladium species (III) undergoes 1,4-
palladium migration to give aryl palladium intermediate (V),
which could further captured by bis(pinacolato)diboron (8) to
furnish the desired products (9) and regenerate the Pd0
catalyst.
(a) Gram-scale reactions
Pd(OAc)2 (5 mol %)
I
Me
DPEphos (5 mol %)
Na2CO3 (3 equiv)
TMS
TMS
+
Ph
2b
Ph
+
TMS TMS
DMF, 100 °C 24 h, N2
Ph
2-MeC6H4
5
(7.5 mmol)
1a
(7.5 mmol)
I
6a
, 65%, 1.35 g
(5 mmol)
Scheme 6. Plausible Catalytic Cycle
Pd(OAc)2 (5 mol %)
DPEphos (5 mol %)
Na2CO3 (3 equiv)
iPr
Bpin
H
Pd0/L
Ar1
I
+
Ph
2b
Ph
+
Bpin Bpin
1
2-iPrC6H4
9c
Ln
DMF, 120 °C 24 h, N2
Ph
B2pin2
1c
(5 mmol)
Pd
(7.5 mmol)
8
(7.5 mmol)
, 50%, 1.07 g
Bpin
H
H
I
Ar1 Pd
Ar1
(b) Derivatization reactions
Ln
Ph
KI (2 equiv)
Cu2O (5 mol%)
Ar2
I
Ar1
V
9
Ph
1,10-Phen (20 mol%)
MeOH:H2O (4:1)
80 °C, 12 h, O2
I
I
2
NIS (5 equiv)
CH3CN,100°C, 12 h
TMS
TMS
H
TMS
Ph
Ph
Ar3
Ph
Ph
2-iPrC H
Ph
2-MeC6H4
Ar2
4-MeC6H4I (2 equiv)
Pd(OAc)2 (10 mol %)
Dppf (10 mol %)
K2CO3 (3 equiv)
MeCN, 100 °C, 24 h, N2
Ar1
6
4
6
15,
63%
12,
75%
Ar1
Ph
Ph
TMS-TMS
4
Ar1
Br
TMS
4-MeC6H4
H
Pd
I
NBS (1 equiv)
CH3CN, 60°C, 12 h
Ar3(BOH)2
Ln
R
Ln
Pd Ln
Ph
II
6a 9c
Ph
66%
Ph
2-MeC6H4
2-iPrC6H4
16,
Ar1
Pd
I
Ph
71%
13,
IV
Ar1
NaN3 ( 1.5 equiv)
Cu(OAc)2 (0.1 equiv)
MeOH, 60 °C, 24 h
Ph
H
N3
H
III
TBAF•3H2O (3 equiv)
THF, 80°C,12 h, N2
H
Ph
2-iPrC6H4
Ph
2-MeC6H4
14,
17,
92%
90%
Mechanistic Computational Study.
boronic acid pinacol esters are versatile synthetic
intermediates and could be converted into various compounds.
For example, the selective halogenation of aryl TMS group
could be achieved to give compounds (12) and (13), in which
the TMS group at the alkene was not cleaved. The desilylation
In the possible catalytic cycle of trans-selective bis-
functionalization of internal alkynes, the key step would be
considered as the cis to trans isomerization of alkenyl
palladium intermediate. To further understand this process, a
ACS Paragon Plus Environment

Page 5 of 8
ACS Catalysis
density functional theory (DFT) calculation was employed to
study this process by using M06 density functional. As
depicted in Figure 1, when a tetra-coordinated cis-alkenyl
palladium (II) species 19 is formed, the cis to trans
isomerization of alkenyl group would occur via a three-
membered ring type transition state 20-ts. In the geometry of
this transition state, the length of C1-C2 bond is increased to
1.41 Å, which represents a single bond character. The bond
length of Pd-C1 is 1.92 Å, which is shorter than a typical Pd-C
single bond. The distance between palladium and C2 is only
2.22 Å, which reveals a strong interaction between those two
atoms. Therefore, the rotation alkenyl group in transition state
20-ts can be considered as a η2-ligand by using 4e sharing
with palladium. DFT calculation found that in transition state
20-ts, phosphine ligand should be partially dissociated to keep
16e configuration of palladium. Therefore, the calculated
activation free energy for the rotation of alkenyl group in
intermediate 19 is as high as 27.7 kcal/mol due to the
dissociation of phosphine. Following this idea, we proposed
that the dissociation of iodide would be benefit for the cis to
trans isomerization of alkenyl group. DFT calculation found
that the dissociation of iodide is 5.6 kcal/mol endergonic,
1
2
3
4
5
6
7
8
9
P
P
Ph
P
I
P
Ph
Pd
Pd
=
O
P
P
Ph
Ph
23-ts
PPh2
PPh2
20-ts
GM06/DMF
27.7
20-ts
kcal/mol
23.2
23-ts
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
L(Pd-C1) = 1.92
L(Pd-C2) = 2.22
L(C1-C2) = 1.41
20-ts
5.6
22
3.2
24
0.0
19
-0.8
21
I
I
which provides
a
tri-coordinated cationic palladium
P
I
P
P
P
P
P
P
I
P
Pd
Pd
Pd
Ph
Ph
Pd
Ph
Ph
Ph
intermediate 22. The corresponding cis to trans isomerization
of alkenyl group can take place via transition state 23-ts to
afford intermediate 24. The calculated overall activation free
energy for this step is only 23.2 kcal/mol, which could be
achieved under a reaction temperature of 120 °C.
Ph
Ph Ph
L(Pd-C1) = 1.94
L(Pd-C2) = 2.62
L(C1-C2) = 1.38
21
22
24
19
23-ts
Moreover, the frontier molecular orbitals (FMOs) of
transition state 23-ts are given in Figure 2. The energy level of
highest occupied molecular orbital (HOMO) and HOMO-1 of
23-ts are -7.63 and -7.96 eV, respectively, which are about
2.63 eV lower than that of lowest unoccupied molecular
orbital (LUMO) of 23-ts. The profiles of HOMO, HOMO-1
and LUMO clearly reveals that those three molecular orbitals
are contributed by two occupied polarized d orbitals from Pd
and an unoccupied p orbital form C1. Those three molecular
orbitals represent the significant back donation of electrons
from Pd to C1. Therefore, twisted C1-C2 bond in transition
state 23-ts can be stabilized by this back donation interaction
of Pd to achieve the isomerization.
Figure 1. Calculated relative Gibbs energies for the cis to trans
isomerization of [R-Pd(L)I]. Energy values are given in kcal/mol
and represent the relative free energies calculated by using the
M06 method in solvent. Bond lengths are given in Å.
LUMO
-5.00 eV
Conclusion
In summary, we have devised a highly efficient palladium-
catalyzed intermolecular trans-selective carbofunctionalization
reaction that provides access to tri- and tetrasubstituted
alkenes with remarkable regio- and stereoselectivity.
Diarylation, arylsilylation/remote C−H silylation, and
hydroarylation/remote C−H borylation of internal alkynes
have been achieved by using aryl boronic acids,
hexamethyldisilane, and bis(pinacolato)diboron as trapping
reagents, respectively. Detailed mechanistic studies and DFT
calculations have provided support for a cis to trans
isomerization of alkenyl palladium species promoted by steric
bulk of both the substrate and the ligand.
C
Pd
HOMO
-7.63 eV
HOMO-1
-7.96 eV
AUTHOR INFORMATION
Corresponding Author
*E-mail for Y. L. lanyu@cqu.edu.cn
*E-mail for G. C. glcheng@hqu.edu.cn
Notes
The authors declare no competing financial interest.
ASSOCIATED CONTENT
Supporting Information.
Figure 2. FMOs of transition state 23-ts.
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 8
1,3-Cyclohexadienes, and Organoboranes. Tetrahedron 2010, 66,
4265-4277. (b) Zhou, C. X.; Larock, R. C. Regio- and Stereoselective
Route to Tetrasubstituted Olefins by the Palladium-Catalyzed Three-
Component Coupling of Aryl Iodides, Internal Alkynes, and Arylboronic
Acids. J. Org. Chem. 2005, 70, 3765-3777. (c) Zhou, C. X.; Larock, R.
C. Synthesis of tetrasubstituted olefins by Pd-catalyzed addition of
arylboronic acids to internal alkynes. Org. Lett. 2005, 7, 259-262. (d)
Zhou, C. X.; Emrich, D. E.; Larock, R. C. An Efficient, Regio- and
Stereoselective Palladium-Catalyzed Route to Tetrasubstituted Olefins.
Org. Lett. 2003, 5, 1579-1582.
The Supporting Information is available free of charge on the
ACS Publications website.
General experimental procedures, characterization data,
1H and 13C NMR spectra of new compounds, and X-ray data for
4aa (CCDC 1890761) and 6a (CCDC 1893368)
1
2
3
4
5
6
7
8
ACKNOWLEDGMENT
This work was supported by the NSF of China (21672075,
21822303, and 21772020) and the Instrumental Analysis Center
of Huaqiao University.
(7)
Larock type reaction reported by others: (a) Wen, Y.; Huang, L.; Jiang,
H. Access to C(sp3)-C(sp2) and C(sp2)-C(sp2) Bond Formation via
Sequential Intermolecular Carbopalladation of Multiple Carbon-Carbon
Bonds. J. Org. Chem. 2012, 77, 5418-5422. (b) Monks, B. M.; Cook,
S. P. Palladium-Catalyzed Alkyne Insertion/Suzuki Reaction of Alkyl
Iodides. J. Am. Chem. Soc. 2012, 134, 15297-15300. (c) Yamashita,
M.; Hirano, K.; Satoh, T.; Miura, M. Synthesis of 1,4-Diarylbuta-1,3-
dienes through Palladium-Catalyzed Decarboxylative Coupling of
Unsaturated Carboxylic Acids. Adv. Synth. Catal. 2011, 353, 631-636.
(d) Sajna, K. V.; Srinivas, V.; Swamy, K. C. K. Efficient Palladium-
Catalyzed Double Arylation of Phosphonoalkynes and Diarylalkynes in
Water: Use of a Dinuclear Palladium(I) Catalyst. Adv. Synth. Catal.
2010, 352, 3069-3081. (e) Jiang, H.-F.; Xu, Q.-X.; Wang, A. Z.
Stereoselective Synthesis of Tetrasubstituted Olefins via Palladium-
Catalyzed Three-Component Coupling of Aryl Iodides, Internal
Alkynes, and Arylboronic Acids in Supercritical Carbon Dioxide. J.
Supercrit. Fluids. 2009, 49, 377-384. (f) Sakai, N.; Komatsu, R.;
Uchida, N.; Ikeda, R.; Konakahara, T. A Single-Step Synthesis of
Enynes: Pd-Catalyzed Arylalkynylation of Aryl Iodides, Internal
Alkynes, and Alkynylsilanes. Org. Lett. 2010, 12, 1300-1303. (g)
Shibata, K.; Satoh, T.; Miura, M. Palladium-Catalyzed Intermolecular
Three-Component Coupling of Organic Halides with Alkynes and
Alkenes: Efficient Synthesis of Oligoene Compounds. Adv. Synth.
Catal. 2007, 349, 2317-2325. (h) Konno, T.; Taku, K.-i.; Ishihara, T.
Highly Stereoselective One-Pot Synthesis of Tetrasubstituted Alkenes
via Carbopalladation Reaction of Fluorine-Containing Acetylene
Derivatives. J. Fluorine. Chem. 2006, 127, 966-972. (i) Shibata, K.;
Satoh, T.; Miura, M. Palladium-Catalyzed Intermolecular Three-
Component Coupling of Aryl Iodides, Alkynes, and Alkenes to
Produce 1,3-Butadiene Derivatives. Org. Lett. 2005, 7, 1781-1783. (j)
Satoh, T.; Ogino, S.; Miura, M.; Aromitra, M. Synthesis of Highly
Substituted 1,3-Butadienes by Palladium-Catalyzed Arylation of
Internal Alkynes. Angew. Chem. Int. Ed. 2004, 43, 5063-5065.
9
REFERENCES
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(1)
(a) Elliott, M. R.; Dhimane, A. L.; Malacria, M. Biomimetic
Diastereoselective Total Synthesis of Epi-illudol via a Transannular
Radical Cyclizations Strategy. J. Am. Chem. Soc. 1997, 119, 3427-
3428. (b) Takahashi, A.; Kirio, Y.; Sodeoka, M.; Sasai, H.; Shibasaki,
M. Highly Stereoselective Synthesis of Exocyclic Tetrasubstituted Enol
Ethers and Olefins - a Synthesis of Nileprost. J. Am. Chem. Soc. 1989,
111, 643-647.
(2)
Kim, J.; Woo, S. Y.; Im, C. Y.; Yoo, E. K.; Lee, S.; Kim, H.-J.; Hwang,
H.-J.; Cho, J.-h.; Lee, W. S.; Yoon, H.; Kim, S.; Kwon, O.-b.; Hwang,
H.; Kim, K.-H.; Jeon, J.-H.; Singh, T. D.; Kim, S. W.; Hwang, S. Y.;
Choi, H.-S.; Lee, I.-K.; Kim, S. H.; Jeon, Y. H.; Chin, J.; Cho, S. J.
Insights of a Lead Optimization Study and Biological Evaluation of
Novel 4-Hydroxytamoxifen Analogs as Estrogen-Related Receptor
gamma (ERR gamma) Inverse Agonists. J. Med. Chem. 2016, 59,
10209-10227.
(3)
(4)
Kwok, R. T. K.; Leung, C. W. T.; Lam, J. W. Y.; Tang, B. Z. Biosensing
by Luminogens with Aggregation-Induced Emission Characteristics.
Chem. Soc. Rev. 2015, 44, 4228-4238.
(a) Eissen, M.; Lenoir, D. Mass Efficiency of Alkene Syntheses with
Tri- and Tetrasubstituted Double Bonds. ACS Sustainable Chem. Eng.
2017, 5, 10459-10473. (b) Negishi, E.-I.; Huang, Z.; Wang, G.; Mohan,
S.; Wang, C. Recent Advances in Efficient and Selective Synthesis of
Di-, Tri-, and Tetrasubstituted Alkenes via Pd-Catalyzed Alkenylation-
Carbonyl Olefination Synergy. Acc. Chem. Res. 2008, 41, 1474-1485.
(c) Flynn, A. B.; Ogilvie, W. W. Stereocontrolled Synthesis of
Tetrasubstituted Olefins. Chem. Rev. 2007, 107, 4698-4745. (d) Tan,
G.; Zhu, L.; Liao, X.; Lan, Y.; You, J. Rhodium/Copper Cocatalyzed
Highly trans-Selective 1,2-Diheteroarylation of Alkynes with Azoles via
C-H Addition/Oxidative Cross-Coupling: A Combined Experimental
and Theoretical Study. J. Am. Chem. Soc. 2017, 139, 15724-15737.
(e) Milde, B.; Leibeling, M.; Pawliczek, M.; Grunenberg, J.; Jones, P.
G.; Werz, D. B., pi-Helicenes Truncated to a Minimum: Access
Through a Domino Approach Involving Multiple Carbopalladations and
a Stille Coupling. Angew. Chem. Int. Ed. 2015, 54 , 1331-1335.
For a general review on carbometallation reactions, see: (a) Marek, I.;
Minko, Y. In Carbometallation Reactions; de Meijere, A., Brase, S.,
Oestreich, M., Eds.; Wiley-VCH: Weinheim, 2013; Chapter 10, pp 763-
874. (b) Zuo, Z.; Wang, H.; Fan, L.; Liu, J.; Wang, Y.; Luan, X.
Modular Assembly of Spirocarbocyclic Scaffolds through Pd-0-
Catalyzed Intermolecular Dearomatizing 2+2+1 Annulation of
Bromonaphthols with Aryl Iodides and Alkynes. Angew. Chem. Int. Ed.
2017, 56, 2767-2771. (c) Duefert, A.; Werz, D. B. Carbopalladation
Cascades Using Carbon-Carbon Triple Bonds: Recent Advances to
Access Complex Scaffolds. Chem-Eur. J. 2016, 22, 16718-16732. (d)
Blouin, S.; Gandon, V.; Blond, G.; Suffert, J. Synthesis of
Cyclooctatetraenes through a Palladium-Catalyzed Cascade Reaction.
Angew. Chem. Int. Ed. 2016, 55, 7208-7211. (e) Goh, S. S.; Chaubet,
G.; Gockel, B.; Cordonnier, M.-C. A.; Baars, H.; Phillips, A. W.;
Anderson, E. A. Total Synthesis of (+)-Rubriflordilactone A. Angew.
Chem. Int. Ed. 2015, 54, 12618-12621. (f) Wallbaum, J.; Neufeld, R.;
(8)
(a) Schoenhaber, J.; D'Souza, D. M.; Glissmann, T.; Mayer, B.; Janiak,
C.; Rominger, F.; Frank, W.; Mueller, T. J. J. Domino Insertion-
Coupling Synthesis of Solid-State Luminescent Propynylidene
Indolones. Chem-Eur. J. 2018, 24, 14712-14723. (b) Tietze, L. F.;
Hungerland, T.; Eichhorst, C.; Duefert, A.; Maass, C.; Stalke, D.
Efficient Synthesis of Helical Tetrasubstituted Alkenes as Potential
Molecular Switches: A Two-Component Palladium-Catalyzed Triple
Domino Process. Angew. Chem. Int. Ed. 2013, 52, 3668-3671. (c)
Chernyak, N.; Gorelsky, S. I.; Gevorgyan, V. Palladium-Catalyzed
(5)
Carbocyclization of Alkynyl Ketones Proceeding through
a
Carbopalladation Pathway. Angew. Chem. Int. Ed. 2011, 50, 2342-
2345.
(9)
(a) Schitter, T.; Reding, A.; Werz, D. B., Cascades Involving anti-
Carbopalladation Steps: From Our Initial Hypothesis to Natural
Product Synthesis. Synlett 2019, 30, 1275-1288. (b) Schitter, T.;
Stammwitz, S.; Jones, P. G.; Werz, D. B. An anti-
Carbopalladation/Amination Cascade with Alkynes: Access to
Tetrasubstituted Enamines and Pyrroles. Org. Lett. 2019, 21, 9415-
9419. (c) Schitter, T.; Jones, P. G.; Werz, D. B. Intramolecular Pd-
Catalyzed Formal anti-Carboalkoxylation of Alkynes: Access to
Tetrasubstituted Enol Ethers. Chem. Eur. J. 2018, 24, 13446-13449.
(d) Reding, A.; Jones, P. G.; Werz, D. B. trans-Carbocarbonation of
Stalke,
D.;
Werz,
D.
B.
A
Domino
Approach
to
Dibenzopentafulvalenes by Quadruple Carbopalladation. Angew.
Chem. Int. Ed. 2013, 52, 13243-13246.
Internal Alkynes through
a
Formal anti-Carbopalladation/C-H
Activation Cascade. Angew. Chem. Int. Ed. 2018, 57, 10610-10614.
(e) Reding, A.; Jones, P. G.; Werz, D. B. Intramolecular trans-
Carbocarbonation of Internal Alkynes by a Cascade of Formal anti-
(6)
(a) Zhang, X.; Larock, R. C. Synthesis of Highly Substituted 1,3-
Dienes, 1,3,-Trienes, and 3,6-Disubstituted Cyclohexenes by the
Palladium-Catalyzed Coupling of Organic Halides, Internal Alkynes or
ACS Paragon Plus Environment

Page 7 of 8
ACS Catalysis
Carbopalladation/Cyclopropanol Opening. Org. Lett. 2018, 20, 7266-
Arylzinc Reagents to Alkynes to Form Ortho-Alkenylarylzinc Species
through 1,4-Cobalt Migration. Angew. Chem. Int. Ed. 2012, 51, 9610-
9614.
7269. (f) Pawliczek, M.; Schneider, T. F.; Maass, C.; Stalke, D.; Werz,
D. B. Formal anti-Carbopalladation Reactions of Non-Activated
Alkynes: Requirements, Mechanistic Insights, and Applications.
Angew. Chem. Int. Ed. 2015, 54, 4119-4123.
1
2
3
4
5
6
7
8
9
(10) (a) Sperger, T.; Le, C. M.; Lautens, M.; Schoenebeck, F. Mechanistic
Insights on the Pd-Catalyzed Addition of C-X Bonds Across Alkynes -
a Combined Experimental and Computational Study. Chem. Sci. 2017,
8, 2914-2922. (b) Le, C. M.; Menzies, P. J. C.; Petrone, D. A.; Lautens,
M. Synergistic Steric Effects in the Development of a Palladium-
Catalyzed Alkyne Carbohalogenation: Stereodivergent Synthesis of
Vinyl Halides. Angew. Chem. Int. Ed. 2015, 54, 254-257. (c) Le, C. M.;
Hou, X.; Sperger, T.; Schoenebeck, F.; Lautens, M. An Exclusively
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
trans-Selective Chlorocarbamoylation of Alkynes Enabled by
a
Palladium/Phosphaadamantane Catalyst. Angew. Chem. Int. Ed. 2015,
54, 15897-15900.
(11) (a) Komiyama, T.; Minami, Y.; Hiyama, T. Recent Advances in
Transition-Metal-Catalyzed
Synthetic
Transformations
of
Organosilicon Reagents. ACS Catal. 2017, 7, 631-651. (b) Du, X.;
Huang, Z. Advances in Base-Metal-Catalyzed Alkene Hydrosilylation.
ACS Catal. 2017, 7, 1227-1243. (c) Nakao, Y.; Hiyama, T. Silicon-
Based Cross-Coupling Reaction: an Environmentally Benign Version.
Chem. Soc. Rev. 2011, 40, 4893-4901. (d) Denmark, S. E.; Liu, J. H.
C. Silicon-Based Cross-Coupling Reactions in the Total Synthesis of
Natural Products. Angew. Chem. Int. Ed. 2010, 49, 2978-2986.
(12) (a) Lv, W.; Wen, S.; Yu, J.; Cheng, G. Palladium-Catalyzed Ortho-
Silylation of Aryl Iodides with Concomitant Arylsilylation of
Oxanorbornadiene: Accessing Functionalized (Z)-beta-Substituted
Vinylsilanes and Their Analogues. Org. Lett. 2018, 20, 4984-4987. (b)
Lv, W.; Yu, J.; Ge, B.; Wen, S.; Cheng, G. Palladium-Catalyzed
Catellani-Type Bis-silylation and Bis-germanylation of Aryl Iodides and
Norbornenes. J. Org. Chem. 2018, 83, 12683-12693. (c) Xu, Y.; Liu,
X.; Chen, W.; Deng, G.; Liang, Y.; Yang, Y. Palladium/Norbornene
Chemistry: Synthesis of Norbornene-Containing Arylsilanes Involving
Double C-Si Bond Formation. J. Org. Chem. 2018, 83, 13930-13939.
(d) Xiao, G.; Chen, L.; Deng, G.; Liu, J.; Liang, Y. Disilylation of N-(2-
Halopheny1)-2-Phenylacrylamides with Hexamethyldisilane via
Trapping the Spirocyclic Palladacycles. Tetrahedron Lett. 2018, 59,
1836-1840. (e) Lu, A.; Ji, X.; Zhou, B.; Wu, Z.; Zhang, Y. Palladium-
Catalyzed C-H Silylation through Palladacycles Generated from Aryl
Halides. Angew. Chem. Int. Ed. 2018, 57, 3233-3237. (f) Li, W.; Xiao,
G.; Deng, G.; Liang, Y. Pd-Catalyzed Disilylation: an Efficient Route to
2,2'-Bis(trimethylsilyl)biphenyls
via
Trapping
Transient
Dibenzopalladacyclopentadienes with Hexamethyldisilane. Org. Chem.
Front. 2018, 5, 1488-1492. (g) Zhou, B.; Lu, A.; Shao, C.; Liang, X.;
Zhang, Y. Palladium-Catalyzed Sequential Three-Component
Reactions to Access Vinylsilanes. Chem. Commun. 2018, 54, 10598-
10601.
(13) Tian, Q. P.; Larock, R. C. Synthesis of 9-Alkylidene-9H-Fluorenes by a
Novel Palladium-Catalyzed Rearrangement. Org. Lett. 2000, 2, 3329-
3332.
(14) (a) Xu, L.; Wang, G.; Zhang, S.; Wang, H.; Wang, L.; Liu, L.; Jiao, J.;
Li, P. Recent Advances in Catalytic C-H Borylation Reactions.
Tetrahedron 2017, 73, 7123-7157. (b) Dai, H.-X.; Yu, J.-Q. Pd-
Catalyzed Oxidative Ortho-C-H Borylation of Arenes. J. Am. Chem.
Soc. 2012, 134, 134-137.
(15) (a) Wei, D.; Hu, T.-J.; Feng, C.-G.; Lin, G.-Q. Synthesis of Substituted
Naphthalenes by 1,4-Palladium Migration Involved Annulation with
Internal Alkynes. Chin. J. Chem. 2018, 36, 743-748. (b) Hu, T.-J.; Li,
M.-Y.; Zhao, Q.; Feng, C.-G.; Lin, G.-Q. Highly Stereoselective
Synthesis of 1,3-Dienes through an Aryl to Vinyl 1,4-Palladium
Migration/Heck Sequence. Angew. Chem. Int. Ed. 2018, 57, 5871-
5875. (c) Hu, T.-J.; Zhang, G.; Chen, Y.-H.; Feng, C.-G.; Lin, G.-Q.
Borylation of Olefin C-H Bond via Aryl to Vinyl Palladium 1,4-Migration.
J. Am. Chem. Soc. 2016, 138, 2897-2900.
(16) (a) Ming, J.; Shi, Q.; Hayashi, T. Addition of Arylstannanes to Alkynes
Giving Ortho-Alkenylarylstannanes Catalysed Cooperatively by
a
Rhodium Complex and Zinc Chloride. Chem. Sci. 2018, 9, 7700-7704.
(b) Tan, B.-H.; Dong, J.; Yoshikai, N. Cobalt-Catalyzed Addition of
ACS Paragon Plus Environment

ACS Catalysis
Page 8 of 8
Table of Contents
1
Ln
2
3
Ar1
I
Pd
Pd
I
R
E
+
Ar2
anti-carbopalladation
R
Ar2
Ar1
4
5
6
7
R1
R1
Ar3
Ar2
R
Bpin
H
TMS
TMS
Ar2
E = TMS-TMS
Ar1
Ar2
Ar1
Ar1
R = Ar2, alkyl, CO2Et
E = Ar3B(OH)2
E = B2pin2
trans:cis up to 20:1
8
trans:cis up to 100:0
trans:cis up to 43:1
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment