Palladium-Catalyzed Intermolecular Heck-Type Reaction of Epoxides

Article abstract of DOI:10.1021/acscatal.8b02029

The palladium-catalyzed intermolecular Heck-type reaction of both cyclic and acyclic epoxides is reported with tolerance of typical polar groups and acidic protons. Suitable alkenes include styrenes, conjugate dienes, and some electron-deficient olefins. In reactions of aliphatic terminal epoxides, ring opening occurs selectively at terminal positions, and stereocenters of epoxides are fully retained. Mechanistic studies provide evidence for in situ conversion of epoxides to β-halohydrins, generation of alkyl radicals, and radical addition to alkenes as key steps. Cyclovoltammetric determination of reduction potentials suggests that during activation of alkyl iodides by palladium(0) complexes, inner-sphere halogen abstraction is more likely than outer-sphere single electron transfer.

Full text of DOI:10.1021/acscatal.8b02029

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Article
Palladium-Catalyzed Intermolecular Heck-Type Reaction of Epoxides
Shenghan Teng, Malcolm Eugene Tessensohn, Richard D. Webster, and Jianrong Steve Zhou
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b02029 • Publication Date (Web): 02 Jul 2018
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Palladium-Catalyzed Intermolecular Heck-Type Reaction of
Epoxides
*
Shenghan Teng, Malcolm E. Tessensohn, Richard D. Webster and Jianrong Steve Zhou
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang
Link, Singapore 637371
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Supporting Information Placeholder
ABSTRACT: Palladium-catalyzed intermolecular Heck-type reaction of both cyclic and acyclic epoxides is reported with tolerance of typical
polar groups and acidic protons. Suitable alkenes include styrenes, conjugate dienes and some electron-deficient olefins. In reactions of ali-
phatic terminal epoxides, ring opening occurs selectively at terminal positions and stereocenters of epoxides are fully retained. Mechanistic
studies provide evidence for in situ conversion of epoxides to β-halohydrins, generation of alkyl radicals and addition to alkenes as key steps.
Cyclic voltammetric determination of reduction potentials suggests that during activation of alkyl iodides by palladium(0) complexes, inner-
sphere halogen abstraction is more likely than outer-sphere single electron transfer.
KEYWORDS: Heck reaction, palladium catalysis, alkylation, epoxides, alkyl radicals
Epoxides are versatile in cross-coupling reactions due to ready avail-
ability and high tendency towards ring opening with various nucleo-
philes.1 In recent years, there has been significant advance in unconven-
tional Heck reaction of unactivated alkyl halides and other alkyl precur-
sors,2 but the success of Heck-type alkylation with another common
family of alkyl electrophiles, epoxides remains very limited.3-4 The
products from these reactions, homoallylic alcohols are commonly
used in organic synthesis.
membered rings.3b Unfortunately, strong base NaOt-Bu was used in
methanolic solvent.
Herein, we report a palladium-catalyzed Heck-type reaction of both
cyclic and acyclic epoxides (Scheme 1b). In comparison, direct cou-
pling of a β-iodohydrin and styrene led to low yield of the desired
product (30%), under the conditions that we prescribed for Heck-type
alkylation with alkyl halides (Scheme 1c).5 Other byproducts included
cyclohexanone (45%), cyclohexanol (5%) and a small amount of bicy-
clic ethers (14%). Furthermore, our efforts in trying other Pd catalysts
and conditions did not lead to satisfactory results. For example, a cata-
lyst of Pd(PPh3)4 and Xantphos together with Et3N base furnished 55%
yield of two isomers in a trans/cis ratio of 3:1.
(a) Cobalt-catalyzed reaction of epoxides with styrene
OH
OH
O
cat. CoBr2(dpph)
Ph +
Ph
Ph
R
TMSCH2MgBr 2.5 equiv
(Oshima et al. 2004)
R
R
R = n-butyl
58%, ratio 1.3 :1
Strongly basic Grignard reagents are incompatible with polar groups
HO
I
O
(b) Palladium-catalyzed Heck-type reaction of epoxides
a)
b)
c)
Et3N•HI
Et3N•HI
PhCF3
80 oC, 2 h
Ph
O
100%
Pd catalyst
HO
OH
Ph
O
cat. Et3N•HI
PhO
I
PhO
Ph
dioxane
(this work)
80 oC, 2 h
100%
OH
77% yield , trans/cis 10:1
I
(c) Attempts at Pd-catalyzed Heck-type reaction using β-iodohydrins
O
I
OH
Et3N•HI
Ph
CHO
Ph
Ph
dioxane
Ph
80 oC, 5 h
60%
17%
13%
O
OH
HO
Pd(PPh3)4 5 mol%
dppf 7 mol%
HO
I
(90% conversion)
Ph
Cy2NMe 1.5 equiv
Scheme 2. Stoichiometric ring opening of epoxides with Et3N·HI
PhCF3, 110 oC, 36 h
30%
(trans/cis 4:1)
45%
5%
2 equiv
In our reaction design, a catalytic amount of an alkylamine salt of HI
is used to open epoxides in situ under palladium-catalyzed reaction
conditions.6 The resulting β-iodohydrins then participate in palladium
radical catalysis7 with alkenes such as styrenes, while the resulting free
alkylamine can function as the base in the later partof the Heck-type
catalytic cycle. Thus, a mild, nearly neutral condition can be main-
tained during catalysis and the use of strong bases avoided. After many
trials, we identified that 0.2 equiv of Et3N·HI was sufficient for rapid
H
H
Ph
Ph
O
O
H
H
2%
12%
(endo/exo 1:1)
(endo/exo 1:1)
Scheme 1. Examples of Heck-type reaction of epoxides and β-iodohydrins
For example, in 2004, Oshima et al. reported Heck-type reaction of
o
ring opening of cyclohexene oxide at 80 C after 2 hours in dioxane or
epoxides and styrene using
a cobalt catalyst ligated with
trifluorotoluene, while a terminal aliphatic epoxide underwent exclu-
sive ring opening at the terminal carbon (Scheme 2a-b). In contrast,
the reaction of styrene oxide was less regioselective with a ratio of 3.5:1,
along with an aldehyde as side product (Scheme 2c).
bis(diphenylphosphino)hexane (dpph) as depicted in Scheme 1a.3a
Unfortunately, the use of strongly basic Grignard reagents severely
limited the compatibility of polar groups in this reaction. In 2016, Mo-
randi et al. also reported cobalt-catalyzed intramolecular cyclization
between epoxides and alkenes that quickly cyclized to form 5- and 6-
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Ph
Ph
In a model reaction between cyclopentene oxide 1a and styrene, we
Pd(PPh3)4 5 mol%
Xantphos 7 mol%
HO
O
HO
established that the use of Pd(PPh3)4 (5 mol%) and Xantphos (7
mol%) resulted in 80% yield of 3a with a 10:1 trans/cis ratio (Table 1,
entry 3). Other palladium sources Pd(OAc)2 and Pd(dba)2 led to
worse results than Pd(PPh3)4 (entries 1-2). To our surprise, the per-
formance of the palladium catalysts was highly dependent on natural
bite angles of chelating bisphosphines (entries 7-10). For example, the
Pd catalysts of dppp or BINAP furnished <10% yield of 3a, while the
catalyst of DPEphos or dppf led to only 40% yield. When the solvent
was switched to dioxane, toluene and veratrole (1,2-
dimethoxybenzene), the yield of 3a was 73%, 55% and 70%, respective-
ly. Furthermore, the model reaction did not need additional bases. We
found that inorganic bases K3PO4 and Cs2CO3 inhibited the productive
pathway, while addition of 1.5 equiv of Et3N and i-Pr2NEt led to lower
yields of 3a (60% and 57%, respectively). Cy2NMe (1.5 equiv) did not
have any deleterious effect (entry 4). Reducing the stoichiometry of 1a
to 1.5 equiv resulted in 75% yield of 3a.
Ph
Et3N•HI 20 mol%
PhCF3, 110 oC, 48 h
1a (2 equiv) 2a
3a 77% yield, trans/cis 10:1
Other examples
MeO
OAc
OMe
OMe
OMe
Me
HO
HO
HO
HO
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3b 82% (7:1)
3c 73% (8:1)
3d 65% (9:1)
3e 51% (7:1)
Me
CO2Me
COMe
O
O
Me
HO
HO
HO
HO
3g 70% (9:1)
with Cy2NMe
1.5 equiv
3f 68% (8:1)
3h 62% (6:1)
3i 61% (10:1)
(X-ray structure)
CF3
CN
Cl
Under the optimized conditions with 5 mol% Pd catalyst and
Xantphos, many substituted styrenes coupled with satisfactory yields
and good trans selectivity on the cyclic ring and the products contained
exclusively (E)-geometry (Scheme 3). We established that both elec-
tron-donating and electron-withdrawing groups were tolerated on the
styrenes. In particular, alcohols, esters (3d and 3h), a nitrile (3k), an
acetal (3g), a methyl ketone (3i) and an indole (3n) were compatible
with the reaction conditions. Moreover, an ortho-methyl group can be
present in a styrene derivative (3f). In the example of 3g, addition of
Cy2NMe improved the yield from 42% to 70%. The configuration of
the major isomer of 3i was determined to be trans by X-ray diffraction.8
Moreover, 1,1-diphenylethylene also coupled with epoxide 1a to pro-
duce 3o in high yield, while in reaction of α-methylstyrene, Pd/dppf
was a better catalyst delivering terminal alkene 3p as major isomer.
HO
HO
HO
HO
3j 78% (7:1)
Bn
3k 69% (6:1)
3l 56% (5:1)
3m 58% (6:1)
N
Ph
Ph
HO
HO
Ph
HO
3p 52% (term/int 9:1)
3o 90% (10:1)
3n 42% (5:1)
with dppf in dioxane
Scheme 3. Examples of Heck-type reaction of cyclopentene oxide
Ph
Ph
O
Pd(PPh3)4 5 mol%
Xantphos 7 mol%
HO
HO
(a)
Ph
Et3N•HI 20 mol%
Table 1. Optimization of conditions for Heck-type reaction of a model
epoxide
PhCF3, 110 oC, 48 h
1b 1.5 equiv 2a
4a
4a'
85% yield, trans/cis 3:1
O
Other examples (with only major isomers shown)
OMe
Ph
Me
Pd source (5 mol%)
phosphine (7 mol%)
HO
O
Me
Ph
Ph
Ph
HO
Et3N•HI 20 mol%
HO
HO
HO
PhCF3, 110 oC, 48 h
3a
1a (2 equiv) 2a
4b 70% (2.7:1)
4c 80% (3.2:1)
4d 63% (2.7:1)
4e 81% (2.7:1)
b
Entry
Pd source
Pd(OAc)2
Pd(dba)2
Phosphine
Xantphos
Xantphos
Xantphos
Xantphos
none
Conv (%)
Yield (%) (trans/cis)
Ph
Ph
Ph
HO
HO
1
2
3
50
48
87
87
96
57
55
70
90
78
36 (8:1)
41 (8:1)
80 (10:1)
80 (10:1)
30 (8:1)
2
HO
O
CO2Me
MeO2C
4f 80% (4.5:1)
4g 74% (11:1)
4h 79% (15:1)
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
styrene
Ph
Pd(PPh3)4 5 mol%
Xantphos 7 mol%
H4
H2
H
H
a
4
(b)
Me
Me
Me
OH
Et3N•HI 20 mol%
O
PhCF3, 110 oC, 48 h
Ph
OH
4i'
4i
5
6
7
8
9
1c (+)-limonene oxide
60%, cis/trans 3:1
PCy3
styrene
Ph
Me
Me
Me
Me
COMe
H
Me
Pd(PPh3)4 5 mol%
Xantphos 7 mol%
COMe
Me
COMe
H
(c)
AcO
O
H
dppp
0
HO
HO
AcO
Et3N•HI 20 mol%
PhCF3, 110 oC, 48 h
AcO
1d
4j
4j'
Ph
rac-BINAP
DPEphos
6
53%, α/β 2.3:1
36 (7:1)
42 (8:1)
Scheme 4. Examples of Heck-type reaction of cyclohexene oxide and other
10
dppf
cyclic epoxides
a
b
1.5 equiv of Cy2NMe was added. Trans/cis ratio was determined by GC.
We next studied other cyclic epoxides in the Heck-type reaction
(Scheme 4). Cyclohexene oxide also reacted with good efficiency with
both electron-rich and deficient styrenes, but the trans/cis selectivity
was only around 3:1. Notably, very little cyclized byproducts of the
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fused tetrahydrofurans were detected in the reaction of 1b and 2a (2%
tion.9 Notably, 5n was obtained in only 60% ee. Close examination of
the reaction mixture revealed that starting material 1i underwent par-
tial racemization under the catalytic conditions, for example, its ee
value decreased to 88% and 66% after 10 min and 30 min, respectively.
yield; see Scheme 1c). We also found that cycloheptene oxide was
reactive and delivered products 4f and 4f' in high yields, in a ratio of
4.5:1. Interestingly, other five-membered cyclic epoxides such as 2,5-
dihydrofuran oxide and 3,3-disubstituted cyclopentene oxides afforded
desired products 4g and 4h in a good trans selectivity (>10:1). How-
ever, cyclooctene oxide led to low conversion.
R
Ph
cyclopentene oxide 1a
Pd(PPh3)4 5 mol%
Xantphos 7 mol%
HO
R
Ph
(a)
Et3N•HI 20 mol%
PhCF3, 110 oC, 48 h
We also tested some elaborate cyclic epoxides that have preexisting
stereocenters on the ring framework. Remarkably, treatment of (+)-
trans-limonene oxide 1c with styrene resulted in two diastereomers 4i
and 4i´ with a ratio of 3:1 (Scheme 4b). The configuration of the major
isomer 4i was assigned by a strong NOE signal between hydrogen
atoms H2 and H4. Notably, the new C-C bond in both isomers was
formed selectively at the less-substituted carbon of the epoxide. Simi-
larly, β-epoxide 1d derived from pregnenolone acetate also ring-
opened at the less-substituted carbon of the strained ring and the new
C-C bond in the major product 4j was formed at the equatorial posi-
tion, too (Scheme 4c).
R = H 6a 53%, trans/cis 10:1
R = Me 6b 60%, trans/cis 10:1
R = H 2b
R = Me 2c
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Other products
Ph
cyclopentene oxide 1a
Ph
Pd(PPh3)4 5 mol%
Xantphos 7 mol%
HO
Ph
HO
Y
CO2Et
(b)
O
CO2Et
Et3N•HI 20 mol%
PhCF3, 110 oC, 48 h
2d
Y = NEt2 6d 53% (3:1) with Cy2NMe
Y = morpholine 6e 49% (1.9:1)
6c 46%
trans/cis 2.6:1
Other product
Me
cyclopentene oxide 1a
O
R
N
Pd(PPh3)4 5 mol%
Xantphos 7 mol%
O
O
O
R
HO
HO
(c)
O
Et3N•HI 20 mol%
Cy2NMe 1.5 equiv
PhCF3, 110 oC, 48 h
styrene
Ph
2e
Pd(PPh3)4 5 mol%
dppf 7 mol%
6h 52% (2.5:1)
R = H 6f 68% trans/cis 3.5:1
R = Me 6g 80% (2.8:1)
OH
O
(a)
Ph
OH
Ph
Ph
Ph
Et3N•HI 20 mol%
dioxane, 110 οC, 48 h
1e 2 equiv
5a'
5a
Scheme 6. Examples of Heck-type reaction using 1,3-dienes and electron-
deficient alkenes
64%, ratio 11:1
OH
Other examples
OH
OH
OH
Me
Ph
Me
Ph
Ph
OH
Me
Ph
Me
Me
OH
7%
O
Pd(PPh3)4 0.5 equiv
Xantphos 0.7 equiv
OH
I
3
5
(a)
(b)
(c)
5b 76% (9:1)
in veratrole
5e 52% (12:1)
with Cy2NMe
PhCF3, 110 oC, 12 h
5c 70% (12:1)
5d 62% (8:1)
76%
1j
(Xantphos)PdI2
OH
OH
OH
OH
OH
Me
Ph
Ph
Ph
Ph
Ph
Me
Me
OH
O
O
Pd(PPh3)4 0.5 equiv
Xantphos 0.7 equiv
n
O
Ph
Ph
Ph
O
5f 60% (20:1)
5g 75% (20:1)
n = 1 5i 70% (16:1)
n = 5 5j 66% (15:1)
Et3N•HI 1 equiv
PhCF3, 110 oC, 12 h
5h 64% (12:1)
in veratrole
71%
6%
N
1b
(Xantphos)PdI2
OH
(b)
styrene
Me
Me
O
PhO
PhO
Ph
Ph
O
OH
4%
Pd(PPh3)4 10 mol%
Xantphos 14 mol%
same as (a)
O
Me
Me
HO
5k 62% (9:1); 99.7% ee
1f 99.6% ee
O
HO
Ph
Et3N•HI 0.5 equiv
PhCF3, 110 οC, 12 h
TEMPO 1 equiv
39%
1a 2 equiv
OH
2a
3a 0% yield
7a 23% yield
(c)
O
styrene
RO
R = H
Ph
RO
same as (a)
5l 48% (8:1); 98.5% ee
O
OH
R = H 1g 99.6% ee
R = TBS 1h
R = TBS 5m 68% (18:1); 99.6% ee
Pd(PPh3)4 5 mol%
Xantphos 7 mol%
Ph
HO
O
(d)
HO
Ph
Ph
Et3N•HI 20 mol%
OH
PhCF3, 110 οC, 48 h
styrene
same as (a)
O
44%
4%
7b 37%
(trans/cis 8:1)
(d)
Ph
Ph
1a 2 equiv
2f
80% conversion
OH
Ph
Ph
Ph
CHO
1i 99.5% ee
5n'' 52% (E/Z 7:1)
5n 28%, 60% ee
5n' 14%
Pd(PPh3)4 5 mol%
dppf 7 mol%
O
HO
(e)
Scheme 5. Examples of Heck-type reaction of acyclic epoxides
Ph
Ph
Et3N•HI 20 mol%
dioxane, 110 οC, 48 h
2a
1k 2 equiv
7c 47% (1.6:1)
This Heck-type reaction is not confined to cyclic epoxides. Various
terminal epoxides in Scheme 5 delivered the desired products in the
presence of a combination of catalytic Pd(PPh3)4 and dppf. In compar-
ison, the Pd catalyst of Xantphos gave 5c in only 21% yield. The termi-
nal epoxides opened selectively at the less hindered terminal carbon,
with a ratio of >10:1 in most cases. Previously, NH4I was reported to
regioselectively open aliphatic epoxides at the less hindered carbon.6
The catalytic alkylation was carried out successfully with monoalkyl,
1,1-dialkyl and benzyl substituted epoxides, which resulted in predom-
inant C-C bond formation at the less substituted carbon center of
epoxides. Interestingly, nearly enantiopure glycidyl ethers 1f-1h (R =
Ph, H and TBS) reacted smoothly under the reaction conditions and
delivered the desired products with almost no loss of enantiomeric
excess. Unfortunately, we found that enantiopure styrene oxide 1i
afforded both products 5n and 5n´ in 42% yields, along with a signifi-
cant amount of byproduct 5n", which was derived from epoxide isom-
erization to phenylacetaldehyde and subsequent self-aldol condensa-
Scheme 7. Mechanistic studies
Other types of olefins also reacted well (Scheme 6). We found that
conjugate dienes such as 2b and 2c furnished the corresponding prod-
ucts 6a and 6b in good yields. The alkylation proceeded selectively at
the terminal position of the dienes. We found that in reactions of elec-
tron-deficient α-phenylacrylate 2d and α-phenylacrylamides, the alkyla-
tion occurred at the terminal carbon of the alkenes to provide (Z)-
isomers selectively, although the trans/cis ratio on the cyclopentane
ring was in the range of 2:1 to 3:1. Moreover, coumarins 2e-f and N-
methyl-2-quinolinone also reacted smoothly under the catalytic condi-
tions and notably, the alkylation took place selectively at C3 positions,
as confirmed by X-ray crystallography (6f-h).8 Similar regioselectivity
was also reported by Zhang et al. in Pd-catalyzed difluoroacetylation of
coumarins and quinolinones, which is known to be sensitive to a com-
bination of both electronic and steric effects.2f Unfortunately, methyl
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acrylate and acrylonitrile did not give Heck-type products due to phos-
Next, radical A adds to styrene to produce benzylic radical B, which
is a fast process.16 Radical B then combines with (L-L)PdI to form
alkylpalladium(II) species C, followed by β-H elimination17 to deliver
the olefinic product. An alternative pathway involving electron transfer
from radical B to complexes of Pd(I) (Scheme 8b) or Pd(II) to form
benzyl cation D is unlikely, owing to high endergonics of the reaction.
The half-wave oxidation potential of a secondary benzylic radical is
around 0.0 V vs Fc+/Fc,18 while half-wave reduction potentials of
(Xantphos)PdI and (Xantphos)PdI2 were -1.5 V and -1.0 V vs Fc+/Fc,
respectively. We also discounted a third possibility of a radical chain
reaction between benzylic radical B and β-iodohydrin, since the result-
ing radical is much less stable than B. Previously, we ruled out a path-
way involving based elimination of benzylic halides as key intermedi-
ates to produce olefins in Heck-type alkylation.5
phine-promoted polymerization.10
To understand the reaction mechanism, we initially examined stoi-
chiometric reactions of in situ formed palladium(0) complex of
Xantphos with iodohydrin 1j. It formed cyclohexanone and cyclohexa-
nol (83% yield) in a ratio of 11:1 (Scheme 7a). A similar conversion of
β-bromohydrins to ketones under photolysis was reported previously.11
Another stoichiometric reaction of the palladium(0) complex with
cyclohexene oxide 1b gave similar results in the presence of 1 equiv of
Et3N·HI (77% yield of cyclohexanone and cyclohexanol), while no
such a reaction was detected in the absence of Et3N·HI (Scheme 7b).
Additionally, when 1 equiv of TEMPO was added to the model catalyt-
ic reaction of cyclopentene oxide 1a and styrene, no desired C-C bond
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formation was detected. Instead,
a TEMPO adduct 7a of β-
In summary, we reported Pd-catalyzed intermolecular Heck-type
reaction of epoxides and olefins, which was compatible with many
sensitive polar groups and acidic hydrogens. In reactions of unsymmet-
rical epoxides, new C-C bonds were formed regioselectively at the less-
substituted positions of epoxides. Moreover, configurations of stereo-
centers in aliphatic terminal epoxides were well preserved. In compari-
son, Heck-type alkylations using β-hydroxyalkyl iodides resulted in low
yields of alkenes, due to formation of ketones as a major side reaction.
There is an advantage of in situ generating β-hydroxyalkyl iodides from
epoxides, by maintaining transient alkyl radicals in low concentrations
under catalytic conditions.
hydroxycyclopentyl radical was isolated in 23% yield; its configuration
was determined to be cis (Scheme 7c).12 The main byproduct in this
reaction was found to be cyclopentanone. If the Pd catalyst was omit-
ted in the reaction above, none of the products were detected.
Next, we used a styrene derivative 2f with α-cyclopropyl group in al-
kylation with epoxide 1a. It afforded byproduct 7b in 37% yield, via
opening of the cyclopropyl unit (with the ring opening rate of 6 x 104 s-
1
13
)
and subsequent radical cyclization on the arene ring (Scheme 7d).
Furthermore, we tested an epoxide 1k carrying a pendant homoallyl
group. Only ring-closure isomers 7c with styrene were isolated
(Scheme 7e).
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website. Experimental procedures, characterization of
compounds and mechanistic studies.
Herein, we propose a catalytic cycle, taking into account of reduc-
tion potentials of (Xantphos)PdI (Scheme 8a). The β-iodohydrin,
which is in situ produced from the epoxide and Et3N·HI, reacts with
(Xantphos)palladium(0) species to give out β-hydroxyalkyl radical A
and a (L-L)PdI complex.14 The latter complex behaves like a persistent
radical.15 In cyclic voltammetry in CH2Cl2, the reduction potential of β-
iodohydrin (-2.2 V vs Fc+/Fc) was determined to be much more nega-
tive than half-wave reduction potential of (Xantphos)PdI (-1.5 V vs
Fc+/Fc). Thus, we deduce that an outer-sphere single electron transfer
between (phosphine)Pd(0) and alkyl iodides is unfavorable with an
endergonics of +16 kcal·mol-1. An alternative mechanism of inner-
sphere halogen abstraction is more likely.
Supporting information experimental procedures.pdf
Supporting information NMR charts.pdf
AUTHOR INFORMATION
Corresponding Author
E-Mail: jrzhou@ntu.edu.sg
(a) A proposed pathway
Ph
HO
I
HO
ORCID
base
(E1/2 = -2.2 V)
Jianrong Steve Zhou: 0000-0002-1806-7436
(L-L)Pd0
[(L-L)PdH]
4a
(L-L)PdII
Notes
(E1/2 = -1.5 V)
The authors declare no competing financial interest.
Ph
PdIII(L-L)
HO
HO
ACKNOWLEDGMENTS
A
C
We thank Singapore Ministry of Education Academic Research
Fund (Tier 1 grants MOE2015-T1-001-166 and 2016-T1-002-093)
and Nanyang Technological University for financial support.
Ph
HO
Ph
(L-L)PdII
B
REFERENCES
(b) Involvement of a benzyl cation is discounted
Ph
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Scheme 8. A proposed reaction pathway and discount of involvement of a
benzylic cation
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R
R
HO
1
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OH
O
Pd catalyst
R1
R1
R1
R
R1
O
or
R
or
R
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cat. Et3N•HI
X
major isomers
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