Palladium-Catalyzed Carbonylative Coupling of Aryl Iodides with Alkyl Bromides: Efficient Synthesis of Alkyl Aryl Ketones

Article abstract of DOI:10.1002/adsc.201800879

Alkyl aryl ketones are important structures with applications in many areas of chemistry. Hence, efficient procedures for their production are particularly attractive. In this communication, a general and efficient carbonylative cross-coupling of aryl iodides and unactivated alkyl bromides is presented. By using a simple palladium catalyst, a series of alkyl aryl ketones were synthesized in moderate to excellent yields from readily available alkyl and aryl halides in an In-Ex tube with formic acid as the CO source. In this study both primary and secondary alkyl bromides/iodides were suitable coupling partners. Additionally, this method can also be employed for the late-stage functionalization of complex natural products and polyfunctionalized molecules. (Figure presented.).

Full text of DOI:10.1002/adsc.201800879

Title: Palladium-Catalyzed Carbonylative Coupling of Aryl Iodides with
Alkyl Bromides: Efficient Synthesis of Alkyl Aryl Ketones
Authors: Xiao-Feng Wu, bo chen, jin-bao peng, xinxin qi, and jun Ying
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10.1002/adsc.201800879
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.2018
Palladium-Catalyzed Carbonylative Coupling of Aryl Iodides
with Alkyl Bromides: Efficient Synthesis of Alkyl Aryl Ketones
Jin-Bao Peng,#[a] Bo Chen,#[a] Xinxin Qi,[a] Jun Ying,[a] and Xiao-Feng Wu*[a,b]
a
Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People’s Republic of
China
E-mail: xiao-feng.wu@catalysis.de
Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Straße 29a, 18059 Rostock, Germany
b
[#] J.-B. Peng and B. Chen contributed equally to this work.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.2018
Abstract. Alkyl aryl ketones are important structures with In this study both primary and secondary alkyl
applications in many areas of chemistry. Hence, efficient bromides/iodides were suitable coupling partners.
procedures for their production are particularly attractive. In Additionally, this method can also be employed for the late-
this communication, a general and efficient carbonylative stage functionalization of complex natural products and
cross-coupling of aryl iodides and unactivated alkyl polyfunctionalized molecules.
bromides is presented. By using a simple palladium catalyst,
a series of alkyl aryl ketones were synthesized in moderate to
excellent yields from readily available alkyl and aryl halides
in an In-Ex tube with formic acid as the CO source.
Keywords: Palladium catalysis • Carbonylation • Ketone •
Aryl iodide • Alkyl bromide
established as well, for example, Ryu and co-workers
reported a general Pd/light induced carbonylative
coupling of alkyl iodides and arylboronic acids.
However, irradiation with a Xe lamp and high
pressure of CO was required.[6a] Comparably, base
metals have shown better activity in carbonylation of
alkyl halides.[7] For example, Mankad’s group has
recently developed a Cu/Mn bimetallic system that
enables the carbonylative Suzuki-Miyaura coupling
of alkyl halides.[8] Despite having many advantages,
the main drawback of these methods is that the
organometallic compounds need to be pre-prepared,
which sometimes limits their application. Recently,
Pd-catalyzed Barbier-Negishi coupling of aryl and
alkyl halides have been developed by the groups of
Lipshutz,[9] Buchwald[10] and Baudoin.[11] Alkyl zinc
reagents were generated in situ and cross-coupled
with aryl halides under the catalysis of palladium.
From the point of view of step-economy and
substrate diversity, the direct carbonylative coupling
of aryl and alkyl halides via the in situ generated
alkyl-metallic intermediates provides an attractive
choice for the synthesis of alkyl aryl ketones (Scheme
1, iii). Our group has reported a palladium-catalyzed
carbonylative Negishi coupling of aryl iodides with
benzyl chlorides.[12] Weix and co-workers have also
developed a nickel-catalyzed reductive carbonylative
coupling for the synthesis of alkyl aryl ketones with
zinc as the reducing reagent (six examples, 60%
average yield) but with limited substrate scope.[13]
Thus, the development a general carbonylative
coupling of alkyl and aryl halides is highly desirable
Introduction
Unsymmetrical ketones, especially alkyl aryl ketones,
represent a large family of valuable structure units
that have been widely applied in pharmaceutical,
agrochemical, and material industries.[1] Additionally,
a vast array of organic transformations use ketones as
substrates leading to the production of a range of
functional groups. As a result, various procedures
have been established for their construction.
Traditionally, alkyl aryl ketones are prepared by the
Friedel-Crafts acylation of arenes with acyl chlorides
or anhydrides.[2] However, not only electron-rich
arenes, but also stoichiometric amounts of Lewis acid
catalyst are required. Thus, alternative routes have
been developed for their synthesis.[3] Among these,
transition metal-catalyzed carbonylative coupling of
organic halides with carbon nucleophiles represents a
direct and convenient methodology.[4] In general,
cross-coupling of aryl halides with pre-formed
alkylmetal nucleophiles such as RZnX, RB(OR’)2
and RSnX in the presence of CO are the most
frequently investigated methods (Scheme 1, a).
Beside the carbonylation of alkyl halides, reactions
with arylmetal compounds have also been reported.[6]
Owing to the difficulty of many reaction steps
including oxidative addition of Pd[0] to C(sp3)-X
bond, metal-hydride β-hydride elimination and
related reactions of the known reactions in this area
are mainly studied with alkyl halides without β-
hydrogen.[5] Some exceptional procedures have been
1
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10.1002/adsc.201800879
Advanced Synthesis & Catalysis
and of great interest. Herein, we report a palladium-
catalyzed carbonylative coupling of aryl iodides with
unactivated alkyl bromides in In-Ex tube[17] with
formic acid as the CO source.[6b]
alkylmetallic reagents would react directly with the
ketone product. In addition to Pd2(dba)3, other
palladium precursors such as PdCl2 and Pd(OAc)2
were also able catalyze this reaction, albeit in lower
yields (Table 1, entries 7 and 8, see details in SI).
A series of phosphine ligands were also
examined to determine the ligand effect on this
transformation (Table 1, entries 9-11, see details in
SI).[16] Bidentate phosphine ligands showed lower
activity, the yields decreased to 42% and 2% for dppf
and xantphos respectively. Monodentate phosphine
ligands such as trianisylphosphine were effective to
catalyze this reaction and provided the product 3gb in
comparable yield. The reaction temperature played a
significant role in this transformation. The best result
was obtained when the reaction was performed at
55°Cwhere the desired product 3gb was isolated in
75% yield (Table 1, entry 12). Further screening of
the solvents revealed that THF was the optimal
reaction media. Notably, when Zn/MgCl2 were used
instead of Mg/ZnCl2 in this reaction, no desired
product was observed (Table 1, entry 15). This
observation excluded the reductive carbonylative
coupling pathway (direct reaction between acyl-
palladium and alkyl bromide, then reduce Pd(II) to
Pd(0) by metallic zinc). Notably, our model system
was performed under 1 bar of CO gas (balloon) as
well, and 25% of the desired product was formed.
Additionally, only trace amount of the target product
could be detected in the case of using Mo(CO)6 as the
CO source.
Scheme 1. Carbonylative Coupling in the Synthesis of
Alkyl Aryl Ketones.
Table 1. Optimization of the Reaction Conditions.[a]
Results and Discussion
We began our study with 4-methoxy-iodobenzene
(1g) and 1-bromopropane (2b) as the model
substrates and carried this reaction out in the presence
of 2 mmol of [CO]. However, the initial attempt by
stirring 4-methoxy-iodobenzene 1g and 1-
bromopropane 2b under the catalysis of
Pd2(dba)3/PPh3 in the presence of zinc powder failed
to give the desired 1-(4-methoxyphenyl)butan-1-one
3gb (Table 1, entry 1). This is thought to be due to
the difficulty in the insertion of zinc into the
unactivated carbon-bromide bond.[14] Knochel and
colleagues demonstrated that the alkylzinc bromides
can be conveniently generated by trapping the in situ
formed alkylmagnesium reagents with ZnCl2.[15] This
strategy was recently been applied in the Barbier-
Negishi coupling by Baudoin and co-workers.[11] To
our delight, when Mg/ZnCl2 were used instead of
zinc powder, the carbonylative cross-coupling
proceeded successfully and produced 3gb in 23%
yield (Table 1, entry 2). The ratio of the two coupling
partners was then explored where increasing the
amount of alkyl bromide resulted in higher yields of
3gb (Table 1, entries 2-6). The ketone 3gb was
obtained in 60% yield when 2.5 equivalent of 2b was
used. Unfortunately, when more than 3 equivalent of
2b was used, the yield dropped significantly. This
observation is explainable since the excess
Eq.
(2b)
Yield
(%)
Entry [Pd]
Ligand
Temp.
1[b]
2
Pd2(dba)3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
dppf
1
60
60
60
60
60
60
60
60
60
60
0
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
PdCl2
1
23
35
56
60
27
22
36
42
2
3
1.5
2
4
5
2.5
3
6
7
2.5
2.5
2.5
2.5
8
Pd(OAc)2
Pd2(dba)3
Pd2(dba)3
9
10
xantphos
P(p-
anisyl)3
11
Pd2(dba)3
2.5
60
57
84
12
Pd2(dba)3 PPh3
2.5
55
(75)[c]
13
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
PPh3
PPh3
PPh3
2.5
2.5
2.5
50
65
55
53
28
0
14
15[d]
2
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10.1002/adsc.201800879
Advanced Synthesis & Catalysis
[a] Reaction conditions: 4-methoxy-iodobenzene 1g (0.5
mmol), 1-bromopropane 2b, (2b : Mg : ZnCl2 = 1 : 1 : 1.2),
Pd2(dba)3 (3 mol%), Ligand (6 mol%), solvent (2 mL), CO
(2 mmol), 12 h, yields were determined by GC analysis
using dodecane as an internal standard. [b] Zn (1.0 mmol)
was instead of Mg/ZnCl2. [c] Isolated yield. [d] Zn/MgCl2
were used instead of Mg/ZnCl2.
With the optimized reaction conditions in hand
(Table 1, entry 12), we examined the substrate scope
of this reaction with a variety of aryl iodides. As
shown in Scheme 2, the carbonylative Barbier-
Negishi coupling reaction showed good substrate
scope. A range of mono- and di-substituted
iodobenzenes were successfully applied to this
reaction and produced the corresponding alkyl aryl
ketones in moderate to good yields. The sterics of
substituents on benzene ring affected the reaction
yields; ortho-substituted iodobenzenes gave lower
yields than substrates with para-substituent (3bb vs
3db, 3eb vs 3gb). Aryl iodides containing electron-
donating groups (Scheme 2, 3ab-3mb) and electron-
withdrawing groups (Scheme 2, 3nb-3pb) on the
phenyl rings were carbonylated smoothly to produce
the desired products in moderate to good yields.
Notably, aryl iodides containing fluoro-, chloro- and
bromo- substituent were compatible in this reaction
and provided the corresponding products in 54%,
60% and 63% yields, respectively (3nb, 3ob and
3pb). Unfortunately, electrophilic substituents such
as acetyl, cyano and nitro groups were not well
tolerated in this transformation most likely because of
the incompatibility with the in-situ generated
organomagnesium reagent. In the case of using 4-
iodobenzotrifluoride as the substrate, only 21% of the
desired product could be detected; this could be
attributed to the low stability of the corresponding
acyl–palladium complex. In addition to substituted
iodobenzenes, heteroaryl iodides such as 3-
iodothiophene were suitable coupling partners.
Unfortunately, in the case of nitrogen-containing
compounds including 3-iodopyridine, 2-iodopyridine,
8-iodoquinoline and 2-iodo-1-methyl-1H-indole, no
desired product could be detected. Moreover, both α-
and β-iodonaphthalene were successfully converted
into the corresponding products in 65% and 41%
yields, respectively (3rb and 3sb). Finally,
bromobenzene, 1-bromo-4-(trifluoromethyl)benzene,
Reaction conditions: aryl iodide (0.5 mmol), 1-
bromopropane (1.25 mmol), Mg (1.25 mmol), ZnCl2 (1.5
mmol), Pd2(dba)3 (3 mol%), PPh3 (6 mol%), THF (2 mL),
CO (2 mmol), 12 h, isolated yields.
Scheme 3. Substrate Scope of Alkyl Halides.
chlorobenzene
and
1-chloro-4-
(trifluoromethyl)benzene were tested with 1-
bromopropane under our standard conditions as well.
No desired ketones could be detected and the aryl
halides stay unreacted.
Scheme 2. Substrate Scope of Aryl Iodides.
Reaction conditions: aryl iodide (0.5 mmol), alkyl halides
(1.25 mmol), Mg (1.25 mmol), ZnCl2 (1.5 mmol),
3
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10.1002/adsc.201800879
Advanced Synthesis & Catalysis
Pd2(dba)3 (3 mol%), PPh3 (6 mol%), THF (2 mL), CO (2
mmol), 12 h, isolated yields.
of TEMPO; two equivalents of TEMPO were added
to the model system and the reaction was not
influenced.
Subsequently, we investigated the generality of
alkyl bromides as coupling partners. As highlighted
in Scheme 3, a range of primary (3ia-3ig) and
secondary alkyl bromides (3ih-3il) readily
participated in this carbonylative cross-coupling
reaction and delivered the corresponding ketones in
good to excellent yields. It should be noted that when
secondary alkyl bromides were used in the Negishi
coupling, the alkylpalladium intermediate was
reported to be able to undergo migration via β-
hydride elimination and alkene insertion, thus leading
to a mixture of isomeric products.[4] However, when
2-bromopantane,
2-bromobutane
and
3-
bromopentane were employed in our catalytic system,
the corresponding products 3ih, 3ii and 3ij were
isolated in 94%, 67% and 82% yields, respectively.
Fortunately, no migration and isomerization were
observed. Notably, alkyl bromides could be easily
obtained from other various functional groups, such
as hydroxyl and amino, which invariably allows a
great number of alkyl coupling partners for this late-
stage carbonylation via this Barbier-Negishi cross-
coupling reaction. In addition, we anticipated that this
method might be applicable to the carbonylation of
secondary metabolites with high complexity because
of its mild conditions. The synthetic potential of this
method was elucidated via late-stage carbonylation of
two natural product derivatives. As shown in Scheme
3, alkyl bromides derived from lithocolic acid and
cholesterol were successfully carbonylative coupled
with aryl iodide and produced the corresponding
ketones in 25% and 38% yield, respectively (3im and
3in). However, no desired product could be detected
when tert-butyl iodide was applied as the reaction
partner. Additionally, alkyl iodides were tested under
our standard conditions as well and comparable
yields were achieved resulting in compounds 3io, 3ip,
3iq. In the case of alkyl chloride, no corresponding
product could be formed. however a reaction with
alkyl tosylate resulted in the desired product (3ir)
being formed in 33% yield
Based on these results alongside previous literature
studies a plausible mechanism is proposed (Scheme
4). Initially, the oxidative addition of aryl iodide to
the in-situ generated Pd(0) forms an aryl palladium
complex 4. Complex 4 can be converted into acyl
palladium intermediate 5, after coordination and
insertion of CO. Meanwhile, oxidative insertion of
magnesium to carbon-bromide bond of 2 forms an
alkylmagnesium reagent 6, which then could be
trapped by ZnCl2 to give an alkylzinc species 7. Then,
transmetalation of acyl palladium 5 and alkylzinc
species 7 generates the intermediate 8. Finally, the
desired product 3 can be released after reductive
elimination and concomitant regeneration of the
active catalyst. The possibility that this reaction
involves radical intermediates can be excluded by the
successful preparation of product 3ie in the presence
Scheme 4. Plausible mechanism.
Conclusion
In summary, we have developed a palladium-
catalyzed carbonylative Barbier-Negishi coupling of
aryl iodides with unactivated alkyl bromides. The
reaction proceeded via the in-situ generation of
alkylzinc species under mild conditions. A series of
alkyl aryl ketones were synthesized in moderate to
excellent yields from readily available alkyl and aryl
halides. Both primary and secondary alkyl bromides
were suitable coupling partners for this reaction. The
present method also provides a mild procedure for the
late-stage carbonylation of complex natural products.
Experimental Section
General procedure: Under nitrogen atmosphere, Pd2dba3
(14 mg, 3 mol%), PPh3 (7.8 mg, 6 mol%), aryl iodide (0.5
mmol), alkyl bromide (1.25 mmol), Mg (1.25 mmol) and
ZnCl2 (1.5 mmol) were transferred into an oven-dried In-
Ex tube[17] (25 mL). THF (2 mL) was then injected
followed by 2 mmol of Ac2O and 2 mmol of formic acid
were added to the small inner tube,. Subsequently, the tube
was sealed and the mixture was stirred at 55 °C for 12 h.
After the reaction finished, the crude product was filtered
and concentrated under vacuum and was purified by
column chromatography (silica gel) EtOAc/petroleum
ether (1:50, v/v) to give the desired product.
Analytic data:
1-Phenylbutan-1-one (3ab), 61% yield. Following the
general procedure, using iodobenzene (56 μL, 0.5 mmol),
compound 3ab (44.9 mg, 61% yield) was a colorless oil.
1H NMR (400 MHz, Chloroform-d) δ 8.01 (dd, J = 8.0, 3.4
Hz, 2H), 7.59 (dd, J = 6.9, 3.4 Hz, 1H), 7.50 (td, J = 7.9,
3.2 Hz, 2H), 3.00 (td, J = 7.4, 3.5 Hz, 2H), 1.83 (dt, J = 7.2,
3.6 Hz, 2H), 1.06 (td, J = 7.6, 3.4 Hz, 3H). 13C NMR (101
MHz, CDCl3) δ 200.39, 137.16, 132.86, 128.55, 128.05,
4
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10.1002/adsc.201800879
Advanced Synthesis & Catalysis
40.53, 17.80, 13.90.
Hz, 2H), 2.97 (t, J = 7.3 Hz, 2H), 2.75 (q, J = 7.6 Hz, 2H),
1.85 – 1.77 (m, 2H), 1.30 (t, J = 7.6 Hz, 3H), 1.05 (t, J =
7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 200.11,
149.76, 134.90, 128.28, 128.03, 40.44, 28.92, 17.91, 15.21,
13.92.
1-(4-(tert-Butyl)phenyl)butan-1-one (3ib), 82% yield.
Following the general procedure, using 1-(tert-butyl)-4-
iodobenzene (89 μL, 0.5 mmol), compound 3ib (83.7 mg,
82% yield) was a colorless oil. 1H NMR (400 MHz,
Chloroform-d) δ 7.95 (d, J = 8.5 Hz, 2H), 7.51 (d, J = 8.5
Hz, 2H), 2.97 (t, J = 7.3 Hz, 2H), 1.81 (h, J = 7.4 Hz, 2H),
1.38 (s, 9H), 1.04 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 200.07, 156.52, 134.60, 128.02, 125.47, 40.43,
35.07, 31.10, 17.90, 13.93.
1-([1,1'-Biphenyl]-4-yl)butan-1-one (3jb), 72% yield.
Following the general procedure, using 4-iodo-1,1'-
biphenyl (140 mg, 0.5 mmol), compound 3jb (80.8 mg,
72% yield) was a white power. 1H NMR (400 MHz,
Chloroform-d) δ 8.11 – 8.05 (m, 2H), 7.75 – 7.71 (m, 2H),
7.70 – 7.65 (m, 2H), 7.55 – 7.49 (m, 2H), 7.47 – 7.42 (m,
1H), 3.03 (t, J = 7.3 Hz, 2H), 1.86 (h, J = 7.4 Hz, 2H), 1.08
(t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 200.00,
145.55, 139.96, 135.86, 128.96, 128.66, 128.19, 127.27,
127.21, 40.59, 17.89, 13.95.
1-(o-Tolyl)butan-1-one (3bb), 60% yield. Following the
general procedure, using 1-iodo-2-methylbenzene (64 μL,
0.5 mmol), compound 3bb (48.1 mg, 60% yield) was a
1
colorless oil. H NMR (400 MHz, Chloroform-d) δ 7.65
(dd, J = 7.5, 1.7 Hz, 1H), 7.43 – 7.37 (m, 1H), 7.32 – 7.27
(m, 2H), 2.91 (t, J = 7.3 Hz, 2H), 2.53 (s, 3H), 1.78 (h, J =
7.4 Hz, 2H), 1.03 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 204.84, 138.46, 137.72, 131.84, 130.95, 128.21,
125.59, 43.61, 21.10, 17.86, 13.83.
1-(m-Tolyl)butan-1-one (3cb), 58% yield. Following the
general procedure, using 1-iodo-3-methylbenzene (65 μL,
0.5 mmol), compound 3cb (47.1 mg, 58% yield) was a
1
colorless oil. H NMR (400 MHz, Chloroform-d) δ 7.82 –
7.76 (m, 2H), 7.41 – 7.37 (m, 2H), 2.98 (t, J = 7.3 Hz, 2H),
2.46 (s, 3H), 1.80 (h, J = 7.4 Hz, 2H), 1.05 (t, J = 7.4 Hz,
3H). 13C NMR (101 MHz, CDCl3) δ 200.69, 138.32,
137.20, 133.61, 128.57, 128.41, 125.28, 40.59, 21.37,
17.85, 13.90.
1-(p-Tolyl)butan-1-one (3db), 83% yield. Following the
general procedure, using 1-iodo-4-methylbenzene (109 mg,
0.5 mmol), compound 3db (67.1 mg, 83% yield) was a
colorless oil. 1H NMR (400 MHz, Chloroform-d) δ 7.90 (d,
J = 8.2 Hz, 2H), 7.31 – 7.27 (m, 2H), 2.96 (t, J = 7.3 Hz,
2H), 2.45 (s, 3H), 1.81 (h, J = 7.4 Hz, 2H), 1.04 (t, J = 7.4
Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 200.11, 143.57,
134.68, 129.22, 128.18, 40.43, 21.60, 17.91, 13.92.
1-(2-Methoxyphenyl)butan-1-one (3eb), 56% yield.
Following the general procedure, using 1-iodo-2-
methoxybenzene (65 μL, 0.5 mmol), compound 3eb (50.1
1-(3,4-Dimethylphenyl)butan-1-one (3kb), 82% yield.
Following the general procedure, using 4-iodo-1,2-
dimethylbenzene (72 μL, 0.5 mmol), compound 3kb (72.5
1
mg, 82% yield) was a colorless oil. H NMR (400 MHz,
Chloroform-d) δ 7.78 (d, J = 1.9 Hz, 1H), 7.73 (dd, J = 7.8,
1.9 Hz, 1H), 7.24 (d, J = 7.8 Hz, 1H), 2.95 (t, J = 7.3 Hz,
2H), 2.36 (d, J = 1.3 Hz, 6H), 1.80 (q, J = 7.4 Hz, 2H),
1.04 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
200.37, 142.27, 136.83, 135.10, 129.75, 129.18, 125.81,
40.43, 19.96, 19.76, 17.97, 13.92.
1
mg, 56% yield) was a colorless oil. H NMR (400 MHz,
Chloroform-d) δ 7.69 (dd, J = 7.7, 1.8 Hz, 1H), 7.48 (ddd,
J = 8.3, 7.3, 1.8 Hz, 1H), 7.07 – 6.98 (m, 2H), 3.94 (s, 3H),
2.99 (t, J = 7.3 Hz, 2H), 1.76 (h, J = 7.4 Hz, 2H), 1.01 (t, J
= 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 203.17,
158.34, 133.02, 130.09, 120.63, 111.51, 55.49, 45.71,
17.84, 13.92.
1-(2,4-Dimethylphenyl)butan-1-one (3lb), 91% yield.
Following the general procedure, using 1-iodo-2,4-
dimethylbenzene (71 μL, 0.5 mmol), compound 3lb (79.7
1
mg, 91% yield) was a colorless oil. H NMR (400 MHz,
1-(3-Methoxyphenyl)butan-1-one (3fb), 43% yield.
Following the general procedure, using 1-iodo-3-
methoxybenzene (60 μL, 0.5 mmol), compound 3fb (37.6
Chloroform-d) δ 7.62 (d, J = 8.4 Hz, 1H), 7.13 – 7.08 (m,
2H), 2.90 (t, J = 7.3 Hz, 2H), 2.54 (s, 3H), 2.39 (s, 3H),
1.78 (h, J = 7.4 Hz, 2H), 1.03 (t, J = 7.4 Hz, 3H). 13C NMR
(101 MHz, CDCl3) δ 204.02, 141.55, 138.39, 135.31,
132.80, 128.90, 126.24, 43.25, 21.42, 21.31, 18.02, 13.87.
1-(Benzo[d][1,3]dioxol-5-yl)butan-1-one (3mb), 84%
yield. Following the general procedure, using 5-
iodobenzo[d][1,3]dioxole (65 μL, 0.5 mmol), compound
1
mg, 43% yield) was a colorless oil. H NMR (400 MHz,
Chloroform-d) δ 7.60 (dt, J = 7.7, 1.2 Hz, 1H), 7.55 (dd, J
= 2.7, 1.5 Hz, 1H), 7.42 (t, J = 7.9 Hz, 1H), 7.15 (ddd, J =
8.2, 2.7, 1.0 Hz, 1H), 3.91 (s, 3H), 2.99 (t, J = 7.3 Hz, 2H),
1.83 (h, J = 7.4 Hz, 2H), 1.06 (t, J = 7.4 Hz, 3H). 13C NMR
(101 MHz, CDCl3) δ 200.25, 159.86, 138.56, 129.53,
120.72, 119.32, 112.36, 55.45, 40.66, 17.87, 13.90.
1
3mb (80.7 mg, 84% yield) was a colorless oil. H NMR
(400 MHz, Chloroform-d) δ 7.64 – 7.57 (m, 1H), 7.47 (t, J
= 1.2 Hz, 1H), 6.87 (dd, J = 8.2, 0.9 Hz, 1H), 6.07 (d, J =
1.0 Hz, 2H), 2.97 – 2.83 (m, 2H), 1.79 (p, J = 7.4 Hz, 2H),
1.02 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
198.45, 151.54, 148.14, 132.05, 124.17, 107.80, 101.76,
40.30, 18.04, 13.89.
1-(4-Fluorophenyl)butan-1-one (3nb), 55% yield.
Following the general procedure, using 1-fluoro-4-
iodobenzene (58 μL, 0.5 mmol), compound 3nb (45.1 mg,
55% yield) was a colorless oil. 1H NMR (400 MHz,
Chloroform-d) δ 8.06 – 7.99 (m, 2H), 7.17 (dd, J = 9.6, 7.6
Hz, 2H), 2.96 (t, J = 7.3 Hz, 2H), 1.81 (h, J = 7.4 Hz, 2H),
1.05 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
198.76, 166.90, 164.37, 130.68, 130.59, 115.71, 115.49,
40.44, 17.76, 13.86.
1-(4-Methoxyphenyl)butan-1-one (3gb), 75% yield.
Following the general procedure, using 1-iodo-4-
methoxybenzene (116 mg, 0.5 mmol), compound 3gb
1
(66.8 mg, 75% yield) was a colorless oil. H NMR (400
MHz, Chloroform-d) δ 7.98 (d, J = 8.9 Hz, 2H), 6.96 (d, J
= 8.9 Hz, 2H), 3.90 (s, 3H), 2.93 (t, J = 7.3 Hz, 2H), 1.80
(h, J = 7.4 Hz, 2H), 1.03 (t, J = 7.4 Hz, 3H). 13C NMR
(101 MHz, CDCl3) δ 199.03, 163.31, 130.28, 113.66,
55.43, 40.20, 18.02, 13.94.
1-(4-Ethylphenyl)butan-1-one
(3hb),
83% yield.
Following the general procedure, using 1-ethyl-4-
iodobenzene (73 μL, 0.5 mmol), compound 3hb (73.3 mg,
83% yield) was a colorless oil. 1H NMR (400 MHz,
Chloroform-d) δ 7.93 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.1
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800879
Advanced Synthesis & Catalysis
1-(4-Chlorophenyl)butan-1-one (3ob), 60% yield.
Following the general procedure, using 1-chloro-4-
iodobenzene (120 mg, 0.5 mmol), compound 3ob (54.8
2H), 1.40 (s, 9H), 1.01 (t, J = 7.4 Hz, 3H). 13C NMR (101
MHz, CDCl3) δ 200.18, 156.50, 137.09, 128.06, 125.48,
38.25, 35.08, 31.13, 26.65, 22.55, 13.97.
1
mg, 60% yield) was a colorless oil. H NMR (400 MHz,
1-(4-(tert-Butyl)phenyl)hexan-1-one (3id), 74% yield.
Following the general procedure, using 1-bromopentane
(155 μL, 1.25 mmol), compound 3id (85.8 mg, 74% yield)
Chloroform-d) δ 7.94 (d, J = 8.6 Hz, 2H), 7.47 (d, J = 8.6
Hz, 2H), 2.96 (t, J = 7.3 Hz, 2H), 1.81 (h, J = 7.4 Hz, 2H),
1.05 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
199.12, 139.29, 131.31, 129.46, 128.86, 40.49, 17.70,
13.83.
1
was a colorless oil. H NMR (400 MHz, Chloroform-d) δ
7.95 (d, J = 8.5 Hz, 2H), 7.51 (d, J = 8.5 Hz, 2H), 2.98 (t, J
= 7.4 Hz, 2H), 1.84 – 1.74 (m, 2H), 1.44 – 1.37 (m, 13H),
0.98 – 0.93 (m, 3H). 13C NMR (101 MHz, CDCl3) δ
200.22, 156.50, 134.60, 128.04, 125.46, 38.49, 35.06,
31.61, 31.10, 24.21, 22.54, 13.95.
1-(4-Bromophenyl)butan-1-one (3pb), 63% yield.
Following the general procedure, using 1-bromo-4-
iodobenzene (142 mg, 0.5 mmol), compound 3pb (71.4
1
mg, 63% yield) was a colorless oil. H NMR (400 MHz,
1-(4-(tert-Butyl)phenyl)hex-5-en-1-one (3ie), 63% yield.
Following the general procedure, using 5-bromopent-1-ene
(150 μL, 1.25 mmol), compound 3ie (72.4 mg, 63% yield)
Chloroform-d) δ 7.86 (d, J = 8.6 Hz, 2H), 7.63 (d, J = 8.6
Hz, 2H), 2.95 (t, J = 7.3 Hz, 2H), 1.80 (q, J = 7.3 Hz, 2H),
1.04 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
199.27, 135.85, 131.85, 129.58, 127.97, 40.46, 17.69,
13.82.
1
was a colorless oil. H NMR (400 MHz, Chloroform-d) δ
7.95 (d, J = 8.5 Hz, 2H), 7.52 (d, J = 8.5 Hz, 2H), 5.87 (ddt,
J = 17.0, 10.2, 6.7 Hz, 1H), 5.13 – 5.03 (m, 2H), 3.00 (t, J
= 7.4 Hz, 2H), 2.25 – 2.15 (m, 2H), 1.90 (p, J = 7.4 Hz,
2H), 1.39 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 199.87,
156.59, 138.11, 134.56, 128.02, 125.49, 115.22, 37.63,
35.08, 33.25, 31.10, 23.46.
1-(Thiophen-3-yl)butan-1-one
(3qb),
55% yield.
Following the general procedure, using 3-iodothiophene
(51 μL, 0.5 mmol), compound 3qb (42.6 mg, 55% yield)
1
was a colorless oil. H NMR (400 MHz, Chloroform-d) δ
8.08 (dd, J = 2.9, 1.2 Hz, 1H), 7.59 (dd, J = 5.1, 1.3 Hz,
1-(4-(tert-Butyl)phenyl)-3-phenylpropan-1-one
(3if),
1H), 7.35 (dd, J = 5.1, 2.9 Hz, 1H), 2.90 (t, J = 7.3 Hz, 2H), 79% yield. Following the general procedure, using (2-
1.80 (h, J = 7.4 Hz, 2H), 1.04 (t, J = 7.4 Hz, 3H). 13C NMR
(101 MHz, CDCl3) δ 194.79, 142.54, 131.62, 127.00,
126.22, 41.84, 17.84, 13.88.
bromoethyl)benzene (171 μL, 1.25 mmol), compound 3if
(104.8 mg, 79% yield) was a colorless oil. H NMR (400
1
MHz, Chloroform-d) δ 8.00 (d, J = 8.6 Hz, 2H), 7.55 (d, J
= 8.5 Hz, 2H), 7.41 – 7.33 (m, 4H), 7.31 – 7.27 (m, 1H),
3.40 – 3.33 (m, 2H), 3.16 (dd, J = 8.6, 6.8 Hz, 2H), 1.43 (s,
9H). 13C NMR (101 MHz, CDCl3) δ 198.84, 156.79,
141.49, 134.42, 128.56, 128.49, 128.09, 126.14, 125.58,
1-(Naphthalen-1-yl)butan-1-one (3rb), 65% yield.
Following the general procedure, using 1-iodonaphthalene
(73 μL, 0.5 mmol), compound 3rb (64.6 mg, 65% yield)
1
was a colorless oil. H NMR (400 MHz, Chloroform-d) δ
8.63 (dt, J = 8.5, 0.7 Hz, 1H), 8.02 (dt, J = 8.3, 1.1 Hz, 1H), 40.38, 35.14, 31.15, 30.28.
7.90 (ddd, J = 14.2, 7.7, 1.5 Hz, 2H), 7.66 – 7.51 (m, 3H),
3.08 (t, J = 7.3 Hz, 2H), 1.88 (h, J = 7.4 Hz, 2H), 1.09 (t, J
= 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 204.99,
136.49, 134.01, 132.28, 130.17, 128.42, 127.78, 127.17,
126.41, 125.81, 124.40, 44.20, 18.23, 13.92.
1-(4-(tert-Butyl)phenyl)-5-phenylpentan-1-one (3ig), 75%
yield. Following the general procedure, using (4-
bromobutyl)benzene (220 μL, 1.25 mmol), compound 3ig
1
(110.2 mg, 75% yield) was a colorless oil. H NMR (400
MHz, Chloroform-d) δ 7.95 (d, J = 8.5 Hz, 2H), 7.52 (d, J
= 8.5 Hz, 2H), 7.34 – 7.30 (m, 2H), 7.27 – 7.22 (m, 3H),
3.02 (t, J = 7.1 Hz, 2H), 2.73 (t, J = 7.4 Hz, 2H), 1.88 –
1.73 (m, 4H), 1.40 (s, 9H). 13C NMR (101 MHz, CDCl3) δ
199.94, 156.61, 142.31, 134.56, 128.42, 128.31, 128.04,
125.74, 125.50, 38.33, 35.84, 35.10, 31.15, 31.12, 24.16.
1-(Naphthalen-2-yl)butan-1-one (3sb), 41% yield.
Following the general procedure, using 2-iodonaphthalene
(127 mg, 0.5 mmol), compound 3sb (40.5 mg, 41% yield)
1
was a colorless oil. H NMR (400 MHz, Chloroform-d) δ
8.56 – 8.50 (m, 1H), 8.08 (dd, J = 8.6, 1.8 Hz, 1H), 8.03 –
7.99 (m, 1H), 7.96 – 7.90 (m, 2H), 7.62 (dddd, J = 18.4,
8.2, 6.9, 1.4 Hz, 2H), 3.13 (t, J = 7.3 Hz, 2H), 1.88 (h, J =
7.4 Hz, 2H), 1.10 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 200.38, 135.53, 134.50, 132.59, 129.59, 129.53,
128.38, 128.31, 127.76, 126.70, 123.97, 40.62, 17.98,
13.95.
1-(4-(tert-Butyl)phenyl)propan-1-one (3ia), 80% yield.
Following the general procedure, using bromoethane (94
μL, 0.5 mmol), compound 3ia (75.8 mg, 80% yield) was a
colorless oil. 1H NMR (400 MHz, Chloroform-d) δ 7.96 (d,
J = 8.6 Hz, 2H), 7.52 (d, J = 8.6 Hz, 2H), 3.03 (q, J = 7.3
Hz, 2H), 1.39 (s, 9H), 1.27 (t, J = 7.3 Hz, 3H). 13C NMR
(101 MHz, CDCl3) δ 200.48, 156.52, 134.42, 127.95,
125.47, 35.06, 31.67, 31.10, 8.35.
1-(4-(tert-Butyl)phenyl)-2-methylpropan-1-one
(3ih),
94.1% yield. Following the general procedure, using 2-
bromopropane (118 μL, 1.25 mmol), compound 3ih (95.9
1
mg, 94% yield) was a colorless oil. H NMR (400 MHz,
Chloroform-d) δ 7.96 (d, J = 8.5 Hz, 2H), 7.53 (d, J = 8.5
Hz, 2H), 3.60 (hept, J = 6.9 Hz, 1H), 1.39 (s, 9H), 1.27 (d,
J = 6.9 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 204.05,
156.44, 133.64, 128.30, 125.53, 35.22, 35.06, 31.11, 19.23.
1-(4-(tert-Butyl)phenyl)-2-methylbutan-1-one (3ii), 67%
yield. Following the general procedure, using 2-
bromobutane (137 μL, 1.25 mmol), compound 3ii (72.8
1
mg, 67% yield) was a colorless oil. H NMR (400 MHz,
Chloroform-d) δ 7.96 (d, J = 8.5 Hz, 2H), 7.53 (d, J = 8.6
Hz, 2H), 3.44 (h, J = 6.8 Hz, 1H), 1.97 – 1.78 (m, 1H),
1.62 – 1.47 (m, 1H), 1.39 (s, 9H), 1.23 (d, J = 6.8 Hz, 3H),
0.96 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
204.01, 156.44, 134.25, 128.22, 125.53, 42.02, 35.06,
31.11, 26.75, 16.88, 11.83.
1-(4-(tert-Butyl)phenyl)pentan-1-one (3ic), 84% yield.
Following the general procedure, using 1-bromobutane
(135 μL, 1.25 mmol), compound 3ic (91.9 mg, 84% yield)
1
was a colorless oil. H NMR (400 MHz, Chloroform-d) δ
7.97 (d, J = 8.5 Hz, 2H), 7.53 (d, J = 8.6 Hz, 2H), 3.00 (t, J
= 7.4 Hz, 2H), 1.78 (p, J = 7.5 Hz, 2H), 1.51 – 1.44 (m,
1-(4-(tert-Butyl)phenyl)-2-ethylbutan-1-one (3ij), 82%
yield. Following the general procedure, using 3-
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800879
Advanced Synthesis & Catalysis
bromopentane (137 μL, 1.25 mmol), compound 3ij (94.7
mg, 82% yield) was a colorless oil. H NMR (400 MHz,
24.26, 23.41, 21.27, 20.84, 18.61, 18.33, 12.02, -4.57.
HRMS (ESI) Calcd for C41H68O2Si+ [M+H]+: 621.5067,
found: 621.5062.
(4-(tert-Butyl)phenyl)((3R,8S,9S,10R,13R,14S,17R)-
10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-
1
Chloroform-d) δ 7.96 (d, J = 8.5 Hz, 2H), 7.52 (d, J = 8.5
Hz, 2H), 3.34 (tt, J = 7.6, 5.5 Hz, 1H), 1.93 – 1.77 (m, 2H),
1.67 – 1.54 (m, 2H), 1.39 (s, 9H), 0.92 (t, J = 7.4 Hz, 6H).
13C NMR (101 MHz, CDCl3) δ 203.99, 156.39, 135.26,
128.14, 125.51, 49.05, 35.04, 31.11, 24.94, 11.93.
2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-
cyclopenta[a]phenanthren-3-yl)methanone (3in), 38%
yield. Following the general procedure, using 2n (2n was
synthesized according to the literature procedure.[19]),
compound 3in (99.4 mg, 38% yield) was a white power. 1H
NMR (400 MHz, Chloroform-d) δ 7.94 (d, J = 8.5 Hz, 2H),
7.51 (d, J = 8.5 Hz, 2H), 5.44 – 5.40 (m, 1H), 3.31 (dddd, J
= 12.7, 9.9, 7.0, 3.8 Hz, 1H), 2.58 (td, J = 13.2, 12.2, 2.7
Hz, 1H), 2.21 (dd, J = 14.2, 3.6 Hz, 1H), 2.04 (ddt, J =
22.6, 12.9, 3.3 Hz, 5H), 1.85 (ddt, J = 22.5, 8.8, 4.3 Hz,
5H), 1.60 – 1.53 (m, 5H), 1.39 (s, 9H), 1.30 (s, 3H), 1.17
(d, J = 3.8 Hz, 3H), 1.09 (s, 3H), 0.97 (dd, J = 6.6, 4.4 Hz,
5H), 0.92 – 0.90 (m, 9H), 0.74 (s, 3H). 13C NMR (101
MHz, CDCl3) δ 202.86, 156.54, 141.91, 133.69, 128.24,
125.54, 120.81, 56.89, 56.24, 50.53, 47.03, 42.35, 39.86,
39.55, 39.15, 37.22, 36.23, 35.79, 35.56, 35.07, 32.01,
31.88, 31.10, 29.69, 28.24, 28.02, 25.81, 24.30, 23.85,
22.81, 22.56, 20.95, 19.48, 18.75, 11.88. HRMS (ESI)
Calcd for C38H59O+ [M+H]+: 532.4566, found: 532.4557.
(4-(tert-Butyl)phenyl)(cyclopentyl)methanone
(3ik),
76% yield. Following the general procedure, using
bromocyclopentane (134 μL, 1.25 mmol), compound 3ik
1
(87.6 mg, 76% yield) was a colorless oil. H NMR (400
MHz, Chloroform-d) δ 7.98 (d, J = 8.6 Hz, 2H), 7.52 (d, J
= 8.5 Hz, 2H), 3.76 (p, J = 7.9 Hz, 1H), 2.01 – 1.94 (m,
4H), 1.80 – 1.69 (m, 4H), 1.39 (s, 9H). 13C NMR (101
MHz, CDCl3) δ 202.37, 156.32, 134.40, 128.43, 125.43,
46.29, 35.05, 31.12, 30.05, 26.34.
(4-(tert-Butyl)phenyl)(cyclohexyl)methanone (3il), 85%
yield. Following the general procedure, using
bromocyclohexane (154 μL, 1.25 mmol), compound 3il
1
(103.8 mg, 85% yield) was a colorless oil. H NMR (400
MHz, Chloroform-d) δ 7.94 (d, J = 8.5 Hz, 2H), 7.51 (d, J
= 8.5 Hz, 2H), 3.30 (tt, J = 11.5, 3.2 Hz, 1H), 1.95 – 1.75
(m, 6H), 1.60 – 1.44 (m, 4H), 1.38 (s, 9H). 13C NMR (101
MHz, CDCl3) δ 203.40, 156.34, 133.78, 128.23, 125.49,
45.56, 35.04, 31.11, 29.49, 26.02, 25.91.
Synthesis of 2m: To a solution of A (A was synthesized
according to the literature procedure.[18] ) (400 mg, 0.94
mmol) in anhydrous CH2Cl2 (20 mL) at 0 ℃ was added
TBDMSCl (170 mg, 1.13 mmol), followed by the addition
of imidazole (128 mg, 1.88 mmol). The reaction was
maintained at 0 ℃ for 30 min, warmed to ambient
temperature (22 ℃), and stirred overnight. When 4m was
completely consumed as evidenced by TLC (eluent:
petroleum ether), the reaction was diluted with CH2Cl2 (40
mL). The organic phase was washed with saturated
Acknowledgements
The authors thank the NSFC (21472174, 21772177) and Zhejiang
Natural Science Fund for Distinguished Young Scholars
(LR16B020002) for financial support. We also appreciated the
English improvement from Professor Scott G. Stewart at The
University of Western Australia.
aqueous NaHCO3 solution (50 mL), dried (anhydrous References
Na2SO4), and concentrated in vacuo. Column
chromatography (eluent: petroleum ether) afforded 2m
(440 mg, 87%) as a white solid. H NMR (400 MHz,
[1] a) H. G. Franck, J. W. Stadelhofer, Industrial Aromatic
1
Chemistry; Springer-Verlag: Berlin, 1988; b) H.
Surburg, J. Panten, Common Fragrance and Flavor
Materials, 5th ed.; Wiley-VCH: Weinheim, 2006.
Chloroform-d) δ 4.16 (q, J = 7.1 Hz, 1H), 3.62 (tt, J = 10.9,
4.6 Hz, 2H), 3.42 (qt, J = 9.6, 6.9 Hz, 4H), 1.95 – 1.83 (m,
6H), 1.62 (s, 3H), 1.45 – 1.41 (m, 6H), 1.20 – 1.08 (m, 9H),
0.93 (s, 12H), 0.68 (s, 6H), 0.10 (s, 6H). 13C NMR (101
MHz, CDCl3) δ 72.85, 56.44, 56.11, 42.74, 42.33, 40.26,
40.17, 36.96, 35.90, 35.61, 35.24, 34.61, 34.52, 31.05,
29.68, 28.29, 27.32, 26.43, 25.98, 24.22, 23.40, 20.83,
18.65, 18.32, 12.02, -4.58.
[2] G. A. Olah, Friedel-Crafts Chemistry; Wiley: New
York, 1973.
[3] a) M. Liu, Z. Hyder, Y. Sun, W. Tang, L. Xu, J. Xiao,
Org. Biomol. Chem. 2010, 8, 2012–2015; b) Y. Liu, B.
Yao, C.-L. Deng, R.-Y. Tang, X.-G. Zhang, J.-H. Li,
Org. Lett. 2011, 13, 2184–2187; c) X. Wang, M. Liu, L.
Xu, Q. Wang, J. Chen, J. Ding, H. Wu, J. Org. Chem.
2013, 78, 5273–5281; d) M. Yousuf, T. Das, S.
Adhikari, New J. Chem. 2015, 39, 8763–8770; e) X.
Liu, C.-C. Hsiao, L. Guo, M. Rueping, Org. Lett. 2018,
20, 2976–2979.
(5R)-1-(4-(tert-Butyl)phenyl)-5-
((3R,8R,9S,10S,13R,14S,17R)-3-((tert-
butyldimethylsilyl)oxy)-10,13-dimethylhexadecahydro-
1H-cyclopenta[a]phenanthren-17-yl)hexan-1-one (3im),
25% yield. Following the general procedure, using 2m,
compound 3im (77.6 mg, 25% yield) was a white power.
1H NMR (400 MHz, Chloroform-d) δ 7.94 (d, J = 8.5 Hz,
2H), 7.52 (d, J = 8.4 Hz, 2H), 3.63 (dd, J = 10.4, 5.5 Hz,
1H), 3.03 – 2.86 (m, 2H), 2.03 – 1.94 (m, 2H), 1.93 – 1.79
(m, 7H), 1.64 – 1.62 (m, 3H), 1.41 (s, 3H), 1.39 (s, 9H),
1.30 (s, 3H), 1.18 – 1.08 (m, 7H), 0.94 (s, 18H), 0.68 (s,
3H), 0.10 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 200.34,
156.49, 130.02, 128.03, 125.45, 72.87, 56.44, 56.20, 42.73,
42.36, 40.28, 40.18, 39.02, 36.98, 35.92, 35.78, 35.62,
35.07, 34.62, 31.11, 29.69, 28.31, 27.35, 26.44, 25.99,
[4] For selected recent reviews, see: a) M. Beller, Applied
Homogeneous
Catalysis
with
Organometallic
Compounds, Vol. 1, 2nd ed., Wiley-VCH, Weinheim,
2002, pp. 145–156; b) A. Brennführer, H. Neumann, M.
Beller, Angew. Chem. Int. Ed. 2009, 48, 4114–4133; c)
X.-F. Wu, H. Neumann, M. Beller, Chem. Soc. Rev.
2011, 40, 4986–5009; d) Q. Liu, H. Zhang, A. Lei,
Angew. Chem. Int. Ed. 2011, 50, 10788–10799; e) B.
Gabriele, R. Mancuso, G. Salerno, Eur. J. Org. Chem.
7
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10.1002/adsc.201800879
Advanced Synthesis & Catalysis
2012, 6825–6839; f) J.-B. Peng, X. Qi, X.-F. Wu,
[12] X.-F. Wu, J. Schranck, H. Neumann, M. Beller,
Synlett 2017, 28, 175–194; g) X.-F. Wu, RSC Adv.
2016, 6, 83831–83837; h) J.-B. Peng, X. Qi, X.-F. Wu,
ChemSusChem 2016, 9, 2279–2283.
Chem. Asian J. 2012, 7, 40–44.
[13] A. C. Wotal, R. D. Ribson, D. J. Weix,
Organometallics 2014, 33, 5874−5881.
[5] a) M. Medio-Simón, C. Mollar, N. Rodríguez, G.
Asensio, Org. Lett. 2005, 7, 4669–4672; b) J.
Sävmarker, J. Lindh, P. Nilsson, Tetrahedron Lett.
2010, 51, 6886–6889; c) X.-F. Wu, H. Neumann, M.
Beller, Tetrahedron Lett. 2010, 51, 6146–6149.
[14] a) R. D. Rieke, Science 1989, 246, 1260–1264; b) A.
Guijarro, D. M. Rosenberg, R. D. Rieke, J. Am. Chem.
Soc. 1999, 121, 4155–4167; c) H. Fíllon, C. Gosmini, J.
Périchon, J. Am. Chem. Soc. 2003, 125, 3867–3870.
[15] a) A. Krasovskiy, V. Malakhov, A. Gavryushin, P.
Knochel, Angew. Chem. Int. Ed. 2006, 45, 6040–6044;
b) F. M. Piller, P. Appukkuttan, A. Gavryushin, M.
Helm, P. Knochel, Angew. Chem. Int. Ed. 2008, 47,
6802–6806; c) T. D. Blgmke, F. M. Piller, P. Knochel,
Chem. Commun. 2010, 46, 4082–4084.
[6] a) S. Sumino, T. Ui, I. Ryu, Org. Lett. 2013, 15, 3142–
3145; b) C. Brancour, T. Fukuyama, Y. Mukai, T.
Skrydstrup, I. Ryu, Org. Lett. 2013, 15, 2794-2797.
[7] J.-B. Peng, F.-P. Wu, X.-F. Wu, Chem. Rev. DOI:
10.1021/acs.chemrev.8b00068.
[8]D. R. Pye, L.-J. Cheng, N. P. Mankad, Chem. Sci. 2017,
8, 4750–4755.
[16] J.-B. Peng, X.-F. Wu, Angew. Chem. Int. Ed. 2018,
57, 1152–1160.
[9] a) A. Krasovskiy, C. Duplais, B. H. Lipshutz, J. Am.
Chem. Soc. 2009, 131, 15592–15593; b) C. Duplais, A.
Krasovskiy, A. Wattenberg, B. H. Lipshutz, Chem.
Commun. 2010, 46, 562–564; c) A. Krasovskiy, C.
Duplais, B. H. Lipshutz, Org. Lett. 2010, 12, 4742–
4744; d) V. Krasovskaya, A. Krasovskiy, B. H.
Lipshutz, Chem. Asian J. 2011, 6, 1974–1976.
[17] a) Z. Yin, X.-F. Wu, Org. Process Res. Dev., 2017,
21, 1869-1871; b) In-Ex Tube is commercially
available from FengTecEx GmbH (Order number:
29T1020).
[18] X.-B. Yan, C.-L. Li, W.-J. Jin, P. Guo, X.-Z. Shu,
Chem. Sci. 2018, 9, 4529-4534.
[10] V. R. Bhonde, B. T. O’Neill, S. L. Buchwald, Angew.
Chem. Int. Ed. 2016, 55, 1849–1853.
[19] G.-Z. Wang, R. Shang, W.-M. Cheng, Y. Fu, J. Am.
Chem. Soc. 2017, 139, 18307-18312.
[11] a) S. Dupuy, K.-F. Zhang, A.-S. Goutierre, O.
Baudoin, Angew. Chem. Int. Ed. 2016, 55, 14793–
14797; b) K.-F. Zhang, F. Christoffel, O. Baudoin,
Angew. Chem. Int. Ed. 2018, 57, 1982–1986.
8
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Advanced Synthesis & Catalysis
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