A regioselectivity switch in Pd-catalyzed hydroallylation of alkynes

Article abstract of DOI:10.1039/c9sc01527b

By exploiting the reactivity of a vinyl-Pd species, we control the regioselectivity in hydroallylation of alkynes under Pd-hydride catalysis. A monophosphine ligand and carboxylic acid combination promotes 1,5-dienes through a pathway involving isomerization of alkynes to allenes. In contrast, a bisphosphine ligand and copper cocatalyst favor 1,4-dienes via a mechanism that involves transmetalation. Our study highlights how to access different isomers by diverting a common organometallic intermediate.

Full text of DOI:10.1039/c9sc01527b

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Regioselectivity Switch in Pd-Catalyzed Hydroallylation of Alkynes
Ding-Wei Ji,a,b Yan-Cheng Hu,a Hao Zheng,a,b Chao-Yang Zhao,a,b Qing-An Chen*a and Vy M. Dongc
Received 00th January 20xx,
Accepted 00th January 20xx
By exploiting the reactivity of a vinyl-Pd species, we control the regioselectivity in hydroallylation of alkynes under Pd-
hydride catalysis. A monophosphine ligand and carboxylic acid combination promotes 1,5-dienes by a pathway involving
isomerization of alkynes to allenes. In contrast, a bisphosphine ligand and copper cocatalyst favor 1,4-dienes via a
mechanism that involves transmetalation. Our study highlights how to access different isomers by diverting a common
organometallic intermediate.
DOI: 10.1039/x0xx00000x
Well-known and divergent reactivity of Pd(II) intermediates
Introduction
R1
R2 "B"
Pd(0)Ln
R1 R2
R1
X
Ln Pd
transmetalation
Inventing novel cross-couplings has relied upon our ability to
divert readily accessible and common organometallic
intermediates.1 For example, Pd(II) intermediates I (generated
from organic halides or their analogues) can transmetallate
with organoborons in a Suzuki-Miyaura cross-coupling2 or
undergo insertion to olefins and subsequent β-hydride
elimination in the Heck reaction (Scheme 1, top).3 Inspired by
the power of this concept, we set out to divert the reactivity of
a vinyl-Pd(II) intermediate II (generated from alkynes, Scheme
1, bottom) to achieve useful skipped dienes.
X
I
Suzuki-Miyaura
R3
reactants
elementary step
transmetalation
organoborons
alkenes
Pd(II)
R3
R1
R3
R1
insertion, -H elim.

-H elimination

Heck
Proposal: Diverting reactivity of a vinyl-Pd(II) intermediate

Me
PdLnX
transmetalation
H-PdLnX

Ar
Me




Ar
Me
Ar
II: Vinyl-Pd
1,4-diene
selective
B(pin)

The hydroallylation of alkynes has attracted attentions due
to occurrence of skipped dienes in bioactive compounds and
natural products.4 While various catalysts have been
developed to generate the 1,4-diene motif,5 access to the 1,5-
diene isomer via hydroallylation of alkynes has been elusive. In
considering this challenge, we were inspired by the work of
Trost,6 Yamamoto,7 and Breit8 who have used alkynes as
redox-neutral allyl precursors.9-12 Early studies established that
Pd−H can add to a alkyne to generate the vinyl-Pd species II.
With this in mind, we set out to manipulate the reactivity of
this Pd(II) species II towards transmetalation or β-H
elimination to enable selective access to the 1,4 or 1,5-dienes,
respectively (Scheme 1, bottom). Herein, we report the use of
ligands and promoters to enable a regiodivergent synthesis of
skipped dienes. Our study contributes to the art of diverging
catalytic intermediates to access different constitutional
isomers.13
promoter & L
Cu(II) & "P–P"
Acid & "P"
elementary step
transmetalation
-H elimination


Ar
-H elimination


1,5-diene

selective

Scheme 1. Divergent reactivity of Pd(II) species
Results and discussion
We began our study with 1-phenyl-1-propyne 1a and allyl-
B(pin) 2a as the model substrates. After examining various
combinations of ligands and additives, we obtained compelling
results (Chart 1). In the presence of Pd2(dba)3 (2.5 mol%) and a
proton source nBuOH (2.0 equiv.), we found that
monophosphine ligands such as PPhCy2 and PCy3 could give
1,5-diene (Chart 1A) as major product. With the aid of PCy3,
1,5-diene 3a could be obtained in 18% yield accompanied by
trace amounts of 1,4-dienes 4a and 4a' mixture. To improve
the yield of 1,5-diene 3a, we chose Brønsted acid to facilitate
the formation of active Pd(II)−H catalyst.7 By adding 10 mol%
1-adamantanecarboxylic acid, we observed 3a in 83% yield
with excellent selectivity (Chart 1B). Bisphosphine ligands gave
only trace amount of 1,5-diene 3a because these ligands
occupy the otherwise vacant sites needed for β-hydride
elimination.1,14
a. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023
P. R. China, E-mail: qachen@dicp.ac.cn
b. University of Chinese Academy of Sciences, Beijing 100049, P. R. China
c. Department of Chemistry, University of California, Irvine, California, 92697-2025,
USA.
Electronic
Supplementary
Information
(ESI)
available:
See
DOI: 10.1039/x0xx00000x
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ARTICLE
Journal Name
Chart 1. Ligand and promoter effects on hydroallylation[a]
Next, we aimed to selectively prepare the 1,4-diene 4a,
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which is the minor isomer that results frDoOmI: d10ir.1e0c3t9/cCo9uSpCl0in15g27oBf
alkyne 1a and allylboron 2a. To alter regioselectivity, we
pursued a co-catalyst that would accelerate transmetalation
between the allyl species and the vinyl-Pd intermediate,
therefore enable the synthesis of 1,4-dienes. An evaluation of
co-catalysts revealed that Cu(OAc)2 promoted the formation of
4a/4a' (Chart 1C). Moreover, in contrast to the monphophine
ligands that promotes the formation of 3a, bisphosphine
ligands such as dppe and dpp-benz gave higher yield of 4a/4a'.
When dppe was used as ligand, 4a/4a' was delivered in 58%
combined yield as a 10:1 mixture of regioisomers. Using
methanol instead of butanol as the proton source improved
the yield of 4a to 79%. In the absence of palladium, no
products were detected, which indicates this transformation is
not catalyzed by copper alone.
As shown in Table 1A, we obtained various 1,5-dienes in
moderate to good yields and high selectivities (>20:1, 3 vs 4).
Substrates with electron-donating groups proceed smoothly to
deliver 1,5-dienes 3b-3d. Fluoro and chloro groups are also
well tolerated, yielding products 3e and 3f in 74% and 78%.
Aryl alkynes bearing electron-withdrawing substituents (CF3,
Ph, Ac, and CO2Me) show slightly higher reactivities, providing
the linear products (3g-3j) in high yields (81-90%). High
selectivities are still obtained for meta-substituted 1-arylalkyne
1k-1m. The steric hindrance of alkyne influences the reactivity
and offers 3n with 52% yield. On replacing the phenyl group
Me
1a
2a
Ph
Me
Pd2(dba)3 (2.5 mol%)
ligand (5 -10 mol%)
Ph
Ph
3a
4a
+
+
additive (10 mol%)
nBuOH (2.0 equiv.)
dioxane, 90 °C, 6 h
Me
B(pin)
Ph
3a' (n.d.)
Ph
4a'
1,5-dienes
1,4-dienes
PtBu3
n.d.
A
Mono P:
PCy3
18%
PPh3
PPhCy2
Xphos
[b] 3a
[b] 4a/4a'
Yield
:
:
n.d.
n.d.
9%
trace
n.d.
n.d.
trace/2%
n.d.
Yield
No Promoter
Bis P-P:
[b] 3a
dppm
dppe
dpp-benz
dCype
dppp
Yield
:
n.d.
trace
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
[b] 4a/4a'
Yield
Yield
Yield
Yield
Yield
:
PtBu3
B
Mono P:
[b] 3a
PCy3
PPh3
PPhCy2
Xphos
Yield
:
34%.
2%/2%
80%
trace
21%
n.d.
83%
trace
12%
n.d.
[b] 4a/4a'
:
AdCO2H
(10 mol%)
Bis P-P:
[b] 3a
dppm
dppe
dpp-benz
dCype
dppp
Yield
:
2%.
3%/2%
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
[b] 4a/4a'
:
PtBu3
Mono P:
[b] 3a
PPh3
PPhCy2
Xphos
PCy3
C
Yield
:
3%.
trace
9%.
trace
10%.
n.d.
trace
n.d.
9%.
n.d.
[b] 4a/4a'
:
Cu(OAc)2
(10 mol%)
Bis P-P:
[b] 3a
dppe
dppm
dpp-benz
dCype
dppp
Yield
:
n.d.
trace
12%
34%/4%
n.d.
n.d.
n.d.
[b] 4a/4a'
5%/trace
17%/1%
:
53%/5%
79%/7%[c]
1a
2a
(2.0 equiv), Pd2(dba)3 (2.5 mol%), monophosphine (10 mol%) or bis-
[a]
(0.20 mmol),
phosphine (5 mol%), promoter (10 mol%), nBuOH (2.0 equiv), dioxane (1.0 mL), 90 °C, 6 h.
[b] Determined by 1H NMR or GC-FID with 1,3,5-trimethoxybenzene as the internal standard.
[c] MeOH (3.0 equiv) instead of nBuOH, dioxane (0.5 mL), 70 °C, 24 h.
Table 1. Regioselective hydroallylation of alkynes[a]
Pd2(dba)3 (2.5 mol%)
PCy3 (10 mol%)
Pd2(dba)3 (2.5 mol%)
dppe (5 mol%)
Me
Ar
Me
Ar
B(pin)
or
or
Ar
R
+
AdCO2H (10 mol%)
nBuOH (2.0 equiv.)
dioxane, 80-90 oC, 6-10 h
Cu(OAc)2 (10 mol%)
MeOH (3.0 equiv.)
dioxane, 70 oC, 24 h
Ar
R
Ar
R
3
3'
1
2a
4
4'
(2 equiv.)
B) 1,4-Dienes Synthesis Promoted By Transmetalation
A) 1,5-Dienes Synthesis Promoted By -H Elimination

Me
Me
Me
Me
Me
Cl
Et
MeO
Me
4b/4b'
Et
4c/4c'
MeO
4d/4d'
b
b
3a
3e
3b
3c
4a/4a'
: 82%
: 74%
: 78%
: 71%
: 71% (11.9:1)
Me
: 62% (7.9:1)
Me
: 70% (8.7:1)
Me
3d
: 75%
: 70% (5.6:1)
Me
F
F3C
Ph
F
Cl
F3C
Ph
3f
3g
3h
4e/4e'
4f/4f'
4g/4g'
4h/4h':
88% (17.9:1)
: 78%
: 84%
: 84%
: 71% (12.0:1)
Me
: 75% (18.5:1)
Me
: 86%
Me
Me
Ac
MeO2C
Ac
MeO2C
Me
CO2Me
3l
Me
4k/4k':
CO2Me
b
3i
3j
3k
4i:
4j:
4l/4l':
: 81%
: 90%
: 72%
: 78%
78%
99%
Me
87% (9.6:1)
Me
93% (20.0:1)
Me
Me
Et
Me
Me
Me
Me
Me
3m:
Me
b
c
3o 3o'
/
3p:
4m/4m':
4n/4n':
4o/4o':
80% (18.4:1)
84%
: 78% (1:1.7)
n.d.
65% (11.8:1)
trace
3n:
4p/4p':
52%
49% (13.3:1)
Me
nBu
Me
Me
H
H
H
H
nPr
H
H
N
N
N
N
Me
Me
4t/4t':
25% (13.6:1)
O
3q:
3r:
3s 3s'
3t:
4q/4q':
4r:
1
4s:
O
n.d.
56%
/
: 57% (11.5:1)
38%
60% (12.8:1)
23%
65%
aIsolated Yield of the all isomers. Unless otherwise noted, selectivity > 20:1; bAccompanied by small amount of inseparable alkyne , the yield of product has been adjusted accordingly.
cIsolated product together with 1-phenyl-1,3-butadiene in a 4.0:1 ratio, the yield of product has been adjusted accordingly.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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DOI: 10.1039/C9SC01527B
ARTICLE
Table 2. The scope of allylborons
with 2-naphthalenyl groups, the substrate transforms into a
mixture of linear product 3o and branched product 3o' in a
1:1.7 ratio. The branched product 3o' probably originates from
the formation η3-π-benzyl-palladium intermediate.15 No
desired 1,5-diene product is obtained when alkyl-substituted
alkyne 1p or 1q is subjected to standard conditions. Instead,
isomerization product 1-phenyl-1,3-butadiene is observed for
the conversion of 1p. Notably, substrates bearing pyridine
rings, which were incompatible in previously reported
palladium catalysis,16 also lead to 3r and 3s in moderate yields.
Finally, the late-stage modification of the estrone derivative 1t
affords 3t in 38% yield. This 1,5-diene synthesis complements
known allyl-allyl couplings that require pre-functionalized allyl
precursors such as allyl chlorides or carbonates.16-17
Pd2(dba)3 (2.5 mol%)
PCy3 (10 mol%)
R
B(pin)
Ph
Me
+
Ph
AdCO2H (10 mol%)
nBuOH (2.0 equiv.)
dioxane, 90 oC, 18 h
R
R
1
2
(2 equiv.)
3
yield (%)
2
product
w/o Cu(OAc)2
Cu(OAc)2
6
34a
Ph
Ph
2b
3x
3y
Ph
B(pin)
B(pin)
Ph
Me
Me
n.d.
13
< 5a
2c
2d
Me
Me Me
B(pin)
Me
38a
Then, we examined the substrate scope for the synthesis of
1,4-dienes (Table 1B). Various alkynes transform to 1,4-dienes
using the Pd/Cu catalyst combo. Although substrates bearing
electron-donating groups lead to skipped dienes in moderate
to good regioselectivities (4b-4d, 4k, 4m), electron-
withdrawing substrates perform well in terms of yields and
selectivities (4e-4j, 4l). Ortho-Substituted alkyne 1n exhibits no
reactivity due to steric hindrance. It is noteworthy that 4p and
4p' are successfully acquired in 49% yield, while accompanied
by a small amount of isomerization side product (1-phenyl-1,3-
butadiene). Comparatively, the cross-coupling between 1-
phenyl-1-hexyne 1q and 2a provides 1,4-diene products 4q/4q'
without any 1,3-diene side product. Heterocyclic substituted
alkynes (1r and 1s) and estrone derivative all successfully
deliver the 1,4-diene products.
aCu(OAc)2 (10 mol%)
reported by Morken's group that substituted allylborons were
comparatively reluctant in Pd-catalyzed allyl-allyl coupling
reactions.17g To improve the reactivity, Cu(OAc)2 was
employed as additional promoter to facilitate transmetalation.
The yields of 3x and 3y were successfully increased to 34% and
38%, respectively. It should be noted that these reactions all
give interesting linear-branched coupling products, this
selectivity is rare in Suzuki-type allyl-allyl coupling reactions.17
While further studies are warranted, we propose the
following mechanisms on the basis of literature7 and our own
observations (Figure 1A, right). First, the oxidative addition of
the carboxylic acid with a Pd(0) precursor generates Pd(II)-
hydride species A. Syn-migratory insertion of alkyne 1 into the
Pd(II)−H A affords vinyl-Pd intermediate B. For 1,5-dienes
pathway, a vacant coordination site of complex B is spared for
β-hydride elimination in the presence of monophosphine
ligand. Allene 5 is subsequently produced and undergoes
reinsertion to Pd(II)−H forming the π-allyl-Pd intermediate C.
Then, electrophilic intermediate C reacts with allylB(pin) 2 to
deliver bis(allyl)Pd species D.19 Reductive elimination yields the
allyl-allyl coupling product 3a and turns over Pd(0) catalyst
(allyl-allyl coupling cycle).
Besides internal alkynes, terminal alkyne 1u couples with
allylB(pin) 2a to yield 1,5-diene 3a (Scheme 2). The bis-
allylations of di(prop-1-yn-1-yl)benzene 1v and 1w proceed
smoothly with high selectivities and moderate yields. These
olefin products are potential monomers for polymerization.18
We also tested the scope of allylborons under our Pd-acid
condition (Table 2). Generally, substrates 2b-2d were less
reactive in allyl-allyl couplings. This agrees with previous work
Me
Me
In the presence of a Cu(II) co-catalyst, we propose that
transmetalation of allylboron 2a to generate allylcopper
species 2' is favored.5i,17k Under this protocol, vinyl-Pd species
B is also generated by a syn-migratory of alkyne 1 into the
Pd(II)−H A (Figure 1A, left). However, when coordinated with a
Me
Me
1u
1v
1w
bidentate ligand, vinyl-Pd intermediate
B prefers direct
transmetalation with allylcopper species 2' to form D' rather
than undergoing β-hydride elimination to produce allene 5.
Reductive elimination from D' yields product 1,4-diene 4a
(allyl-vinyl coupling cycle).
3a
3v
3w
: 8 h, 64%
: 6 h, 66%
: 10 h, 57%
Pd-Acid Catalysis
Scheme 2. Hydroallylation of terminal and bis-alkynes
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DOI: 10.1039/C9SC01527B
ARTICLE
A
B
C
) Proposed Mechanism for Selectivity Manipulation
) Allene intermediate study
Me
Ph
•
H3C
Ph
Pd/Acid cat.
Ph
Pd/Cu cat.
5
H
X
HX
HX
Pd0Ln
Ln Pd
Pd0Ln
B(pin)
Ph
Ph
4a 4a'
4a
3a
A
2a
3a
: 46% yield
(
): n.d
) Deuterium-labeling study
X = AdCO2 or OnBu
X = OAc or OMe
15% D
D
> 99% D
D3C
61% D
D
D
Ph
Ph
CD3
PdLn
Pd/Acid cat.
Alkyne
1
Pd/Cu cat.
Allyl-Vinyl Coupling
Allyl-Allyl Coupling
1a-d3
B(pin)
2a
Ph
Ph
D
Ph
4a-d
11% D
D
2a
Ph
•
n: 55% yield
3a-d
n: 81% yield
5
2a
CuX
CuX2
24% D
D
PdIILnX
CH3
PdIILnX
2'

44% D
D
P
P
Me
Ph
D
Me
PdII
Pd/Cu cat.
Pd/Acid cat.
A
1a
B(pin)
2a
Ph
II
Path
I
Path
Ph
Ph
C

D
CD3OD
CD3OD
B
Ph
CH3
D'
18% D
D
94% D
4a-d '
n : 62% yield
(3.0 equiv.)
(2.0 equiv.)
Bis P-P/Cu facilitate transmetalation
Mono P/Acid facilitate -H elimination
3a-d '
n : 73% yield
Figure 1. Divergent reactivity of Pd(II) species
To probe the feasibility of an allene intermediate,
phenylallene 5 was subjected to couple with allyl-B(pin) 2a
under two standard conditions (Figure 1B, see the SI for
details). The allene was transformed into the 1,5-diene 3a in
46% yield. No formation of 4a or 4a' under the Pd-Cu
conditions supports that the 1,4-diene products does not arise
from the addition of allylB(pin) 2a to allene 5. The
hydroallylation was also performed with deuterated alkyne 1a-
d3 or methanol (Figure 1C). Under Pd/acid catalysis, we found
the deuterium label was scrambled into the α-, β-, and γ-
positions of 1,5-diene 3a-dn using 1a-d3. Similar deuterium
scrambling was observed when conducting reaction with
deuterated methanol as proton source. This observation
supports a reversible hydrometallation of the internal π-
system of the allene in the synthesis of 1,5-dienes. When
experiments were carried out under Pd-Cu catalysis, the
deuterium label remained intact in 1,4-diene 4a-dn with
deuterated alkyne 1a-d3. Only α-deuterated product was
achieved using deuterated methanol (Figure 1C). This indicates
β-hydride elimination is not involved under Pd/Cu catalysis.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We thank Prof. Yong-Gui Zhou (DICP) and Dr. Kevin G. M. Kou
(UCR) for helpful discussion and paper revisions. Q.A.C thanks
Dalian Institute of Chemical Physics and the National Natural
Science Foundation of China (21702204), LiaoNing
Revitalization Talents Program (XLYC1807181) and the
"Thousand Youth Talents Plan" for financial support. V.M.D
thanks the National Institutes of Health (R35GM127071) for
financial support.
Notes and references
1
For a book, see: J. F. Hartwig, Organotransition Metal
Chemistry: From Bonding to Catalysis, University Science
Books, Sausalito, 2010.
For selected reviews on Suzuki-Miyaura cross-coupling, see:
(a) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457; (b)
A. F. Littke and G. C. Fu, Angew. Chem. Int. Ed., 2002, 41,
4176; (c) R. Jana, T. P. Pathak and M. S. Sigman, Chem. Rev.,
2011, 111, 1417; (d) A. Suzuki, Angew. Chem. Int. Ed., 2011,
50, 6722.
2
Conclusions
Our work complements other alkyne hydroallylation methods
for the synthesis of 1,4-dienes including those developed by
Hilt, Hartwig, Lalic and Zhang.5 Key to the success of this
method is the switchable reactivity of vinyl-Pd intermediates.
Acid additive promotes the β-hydride elimination pathway for
allyl-allyl coupling with the aid of a monophosphine ligand.
Whereas Cu co-catalyst facilitates the direct transmetalation
for vinyl-allyl coupling in the presence of a bisphosphine ligand.
Transmetalation and β-hydride elimination are two elementary
steps featured in many well-known organometallic
mechanisms, including the Suzuki-Miyaura and Heck cross-
coupling. Insights from this study will guide the future
development of related regiodivergent methods in catalysis.
3
4
For selected reviews on Heck reaction, see: (a) I. P.
Beletskaya and A. V. Cheprakov, Chem. Rev., 2000, 100,
3009; (b) R. F. Heck, Acc. Chem. Res., 1979, 12, 146.
(a) M. Jie, M. K. Pasha and M. S. K. SyedRahmatullah, Nat.
Prod. Rep., 1997, 14, 163; (b) E. Breitmaier, Terpenes:
Flavors, Fragrances, Pharmaca, Pheromones, Wiley-VCH,
Weinheim, Germany, 2006.
For selected examples for hydroallylation of alkynes, see: (a)
K. Oshima, T. Nishikawa and H. Yorimitsu, Synlett, 2004,
1573; (b) H. Yasui, T. Nishikawa, H. Yorimitsu and K. Oshima,
Bull. Chem. Soc. Jpn., 2006, 79, 1271; (c) G. Hilt and J.
Treutwein, Angew. Chem. Int. Ed., 2007, 46, 8500; (d) G. Hilt,
F. Erver and K. Harms, Org. Lett., 2011, 13, 304; (e) L. Ilies, T.
5
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Page 5 of 6
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Journal Name
ARTICLE
Yoshida and E. Nakamura, J. Am. Chem. Soc., 2012, 134,
16951; (f) Y. Yamamoto, S. Yamada and H. Nishiyama, Chem.
Eur. J., 2012, 18, 3153; (g) W. Kong, C. Che, L. Kong and G.
Zhu, Tetrahedron Lett., 2015, 56, 2780; (h) D. P. Todd, B. B.
Thompson, A. J. Nett and J. Montgomery, J. Am. Chem. Soc.,
2015, 137, 12788; (i) Y. Yamamoto, E. Ohkubo and M.
Shibuya, Green Chem., 2016, 18, 4628; (j) M. Mailig, A. Hazra,
M. K. Armstrong and G. Lalic, J. Am. Chem. Soc., 2017, 139,
6969; (k) K. Troshin and J. F. Hartwig, Science, 2017, 357,
175; (l) G. Xu, H. Zhao, B. Fu, A. Cang, G. Zhang, Q. Zhang, T.
Xiong and Q. Zhang, Angew. Chem. Int. Ed., 2017, 56, 13130.
B. M. Trost, W. Brieden and K. H. Baringhaus, Angew. Chem.
Int. Ed., 1992, 31, 1335.
(c) K. B. Smith and M. K. Brown, J. Am. Chem. Soc., 2017, 139,
View Article Online
7721; (d) J. W. Park, B. Kang and V. MD. ODIo: n10g.,10A3n9g/Ce9wS.CC01h5e2m7B.
Int. Ed., 2018, 57, 13598; (e) A. M. Bergmann, S. K. Dorn, K.
B. Smith, K. M. Logan and M. K. Brown, Angew. Chem. Int.
Ed., 2019, 58, 1719; (f) X. H. Yang, R. T. Davison, S. Z. Nie, F.
A. Cruz, T. M. McGinnis and V. M. Dong, J. Am. Chem. Soc.,
2019, 141, 3006; (g) Y. Ye, S. T. Kim, J. Jeong, M. H. Baik and
S. L. Buchwald, J. Am. Chem. Soc., 2019, 141, 3901. h) Y. C.
Hu, D. W. Ji, C. Y. Zhao, H. Zheng, Q. A. Chen, Angew. Chem.
Int. Ed. 2019, 58, 5438.
14 (a) J. H. Kirchhoff, M. R. Netherton, I. D. Hills and G. C. Fu, J.
Am. Chem. Soc., 2002, 124, 13662; (b) A. V. Vorogushin, X. H.
Huang and S. L. Buchwald, J. Am. Chem. Soc., 2005, 127,
8146.
6
7
(a) I. Kadota, A. Shibuya, Y. S. Gyoung and Y. Yamamoto, J.
Am. Chem. Soc., 1998, 120, 10262; (b) I. Kadota, A. Shibuya, 15 (a) S. Lu, Z. Xu, M. Bao and Y. Yamamoto, Angew. Chem. Int.
L. M. Lutete and Y. Yamamoto, J. Org. Chem., 1999, 64, 4570;
(c) L. M. Lutete, I. Kadota and Y. Yamamoto, J. Am. Chem.
Soc., 2004, 126, 1622.
For reviews, see: (a) P. Koschker and B. Breit, Acc. Chem.
Res., 2016, 49, 1524; (b) A. M. Haydl, B. Breit, T. Liang and M.
J. Krische, Angew. Chem. Int. Ed., 2017, 56, 11312.
For selected Pd-catalyzed allylation with alkynes, see: (a) S.
Ed., 2008, 47, 4366; (b) B. Peng, X. Feng, X. Zhang, S. Zhang
and M. Bao, J. Org. Chem., 2010, 75, 2619; (c) S. Zhang, A.
Ullah, Y. Yamamoto and M. Bao, Adv. Synth. Catal., 2017,
359, 2723; (d) M. Komatsuda, K. Muto and J. Yamaguchi,
Org. Lett., 2018, 20, 4354.
8
9
16 E. Ferrer Flegeau, U. Schneider and S. Kobayashi, Chem. Eur.
J., 2009, 15, 12247.
Gao, Z. Wu, X. Fang, A. Lin and H. Yao, Org. Lett., 2016, 18, 17 (a) P. Zhang, L. A. Brozek and J. P. Morken, J. Am. Chem. Soc.,
3906; (b) C. J. Lu, H. Chen, D. K. Chen, H. Wang, Z. P. Yang, J.
Gao and H. Jin, Org. Biomol. Chem., 2016, 14, 10833; (c) S.
Gao, H. Liu, Z. Wu, H. Yao and A. Lin, Green Chem., 2017, 19,
1861; (d) S. Gao, H. Liu, C. Yang, Z. Fu, H. Yao and A. Lin, Org.
Lett., 2017, 19, 4710; (e) G. Cera, M. Lanzi, D. Balestri, N.
Della Ca, R. Maggi, F. Bigi, M. Malacria and G. Maestri, Org.
Lett., 2018, 20, 3220; (f) X. Fang, Q. Li, R. Shi, H. Yao and A.
Lin, Org. Lett., 2018, 20, 6084; (g) J. T. D. Lee and Y. Zhao,
Chem. Eur. J., 2018, 24, 9520; (h) Y. Minami, Y. Furuya and T.
Hiyamera, Asian J. Org. Chem., 2018, 7, 1343; (i) Y. L. Su, L. L.
Li, X. L. Zhou, Z. Y. Dai, P. S. Wang and L. Z. Gong, Org. Lett.,
2018, 20, 2403; (j) Z. Wu, X. Fang, Y. Leng, H. Yao and A. Lin,
Adv. Synth. Catal., 2018, 360, 1289; (k) J. Zheng and B. Breit,
Org. Lett., 2018, 20, 1866.
2010, 132, 10686; (b) L. A. Brozek, M. J. Ardolino and J. P.
Morken, J. Am. Chem. Soc., 2011, 133, 16778; (c) A. Jimenez-
Aquino, E. F. Flegeau, U. Schneider and S. Kobayashi, Chem.
Commun., 2011, 47, 9456; (d) P. Zhang, H. Le, R. E. Kyne and
J. P. Morken, J. Am. Chem. Soc., 2011, 133, 9716; (e) M. B. Li,
Y. Wang and S. K. Tian, Angew. Chem. Int. Ed., 2012, 51,
2968; (f) V. Hornillos, M. Perez, M. Fananas-Mastral and B. L.
Feringa, J. Am. Chem. Soc., 2013, 135, 2140; (g) M. J.
Ardolino and J. P. Morken, J. Am. Chem. Soc., 2014, 136,
7092; (h) J. Y. Hamilton, N. Hauser, D. Sarlah and E. M.
Carreira, Angew. Chem. Int. Ed., 2014, 53, 10759; (i) J. Y.
Hamilton, D. Sarlah and E. M. Carreira, J. Am. Chem. Soc.,
2014, 136, 3006; (j) K. Semba, N. Bessho, T. Fujihara, J. Terao
and Y. Tsuji, Angew. Chem. Int. Ed., 2014, 53, 9007; (k) Y.
Yasuda, H. Ohmiya and M. Sawamura, Angew. Chem. Int. Ed.,
2016, 55, 10816; (l) X. Wang, X. Wang, Z. Han, Z. Wang and K.
Ding, Angew. Chem. Int. Ed., 2017, 56, 1116.
10 For selected Rh-catalyzed allylation with alkynes, see: (a) A.
Lumbroso, P. Koschker, N. R. Vautravers and B. Breit, J. Am.
Chem. Soc., 2011, 133, 2386; (b) U. Gellrich, A. Meissner, A.
Steffani, M. Kahny, H. J. Drexler, D. Heller, D. A. Plattner and 18 (a) J. A. Smith, K. R. Brzezinska, D. J. Valenti and K. B.
B. Breit, J. Am. Chem. Soc., 2014, 136, 1097; (c) K. Xu, V.
Khakyzadeh, T. Bury and B. Breit, J. Am. Chem. Soc., 2014,
136, 16124; (d) Q.-A. Chen, Z. Chen and V. M. Dong, J. Am.
Chem. Soc., 2015, 137, 8392; (e) P. Koschker, M. Kahny and
Wagener, Macromolecules, 2000, 33, 3781; (b) J. Pecher and
S. Mecking, Macromolecules, 2007, 40, 7733; (c) B. Inci, I.
Lieberwirth, W. Steffen, M. Mezger, R. Graf, K. Landfester
and K. B. Wagener, Macromolecules, 2012, 45, 3367.
B. Breit, J. Am. Chem. Soc., 2015, 137, 3131; (f) Z. Liu and B. 19 For a review, see: K. J. Szabo, Chem. Eur. J., 2004, 10, 5268.
Breit, Angew. Chem. Int. Ed., 2016, 55, 8440; (g) F. A. Cruz, Y.
Zhu, Q. D. Tercenio, Z. Shen and V. M. Dong, J. Am. Chem.
Soc., 2017, 139, 10641; (h) J. Kuang, S. Parveen and B. Breit,
Angew. Chem. Int. Ed., 2017, 56, 8422; (i) W.-F. Zheng, Q.-J.
Xu and Q. Kang, Organometallics, 2017, 36, 2323; (j) J. Zheng
and B. Breit, Angew. Chem. Int. Ed., 2019, 58, 3392.
11 For Ir-catalyzed allylation with alkynes, see: (a) Y. Obora, S.
Hatanaka and Y. Ishii, Org. Lett., 2009, 11, 3510; (b) Y. Obora,
T. Sawaguchi, K. Tsubakimoto, H. Yoshida, S. Ogawa and S.
Hatanaka, Synthesis, 2013, 45, 2115; (c) T. Liang, W. Zhang
and M. J. Krische, J. Am. Chem. Soc., 2015, 137, 16024.
12 For Ru-catalyzed allylation with alkynes, see: (a) B. Y. Park, K.
D. Nguyen, M. R. Chaulagain, V. Komanduri and M. J. Krische,
J. Am. Chem. Soc., 2014, 136, 11902; (b) Q. A. Chen, F. A.
Cruz and V. M. Dong, J. Am. Chem. Soc., 2015, 137, 3157; (c)
T. Liang, K. D. Nguyen, W. Zhang and M. J. Krische, J. Am.
Chem. Soc., 2015, 137, 3161; (d) T. Liang, W. Zhang, T. Y.
Chen, K. D. Nguyen and M. J. Krische, J. Am. Chem. Soc.,
2015, 137, 13066.
13 For selected examples, see: (a) R. Y. Liu, Y. Yang and S. L.
Buchwald, Angew. Chem. Int. Ed., 2016, 55, 14077; (b) S. R.
Sardini and M. K. Brown, J. Am. Chem. Soc., 2017, 139, 9823;
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ARTICLE
Graphical Abstracts (Table of Contents Entry)
Journal Name
View Article Online
DOI: 10.1039/C9SC01527B
controlling the reactivity of vinyl-Pd(II) species
H
Pd
CuOAc)2
dppe
AdCO2H
PCy3

Me

Ar
Me


Ar

Ar

in
p
Allyl-
B
B
p
in
Allyl-
1,4-Dienes
1,5-Dienes
Pd
H
+
Ar
Me
transmetalation path
-H elimination path

Through rational evaluation of ligands and promoters, the
reactivity of a key Pd(II) species towards transmetalation or
β-H elimination is manipulated.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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