Nickel-catalyzed Suzuki Coupling of Cycloalkyl Silyl Peroxides with Boronic Acids

Article abstract of DOI:10.1021/acs.joc.0c00250

A nickel-catalyzed Suzuki alkyl-aryl coupling of cycloalkyl silyl peroxides with boronic acids is reported. The primary and secondary ketoalkyl electrophiles generated through C-C bond cleavage were amenable, providing rapid access to a variety of distal arylated alkyl ketones. A radical pathway is proposed for this reaction.

Full text of DOI:10.1021/acs.joc.0c00250

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Note
Nickel-Catalyzed Suzuki Coupling of
Cycloalkyl Silyl Peroxides with Boronic Acids
Lei Chen, Juncheng Yang, Pengfei Xu, Jun-Jie Zhang, Xin-Hua Duan, and Lina Guo
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00250 • Publication Date (Web): 29 Apr 2020
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Nickel-Catalyzed Suzuki Coupling of Cycloalkyl Silyl Peroxides with Boronic
5
6
Acids
Lei Chena, Jun-Cheng Yanga, Pengfei Xua, Jun-Jie Zhanga, Xin-Hua Duana,b and Li-Na Guoa*
7
8
9
aDepartment of Chemistry, School of Science, Xi'an Key Laboratory of Sustainable Energy Material Chemistry,
and MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi’an Jiaotong
University, Xi’an 710049, China.
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bState Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China.
Email: guoln81@ xjtu.edu.cn
R
OOTMS
R'
NiBr2diglyme (5 mol %)
dtbpy (5 mol %)
O
R'
( )n
42 examples
Ar B(OH)2
+
R
Ar
Et3N (2.0 equiv)
CH3CN, 90 oC,12 h
( )n
n = 1, 2, 3, 4, 8
R = aryl, alkyl
up to 98% yield
ABSTRACT
A nickel-catalyzed Suzuki alkyl-aryl coupling of cycloalkyl silyl peroxides with boronic acids is
reported. The primary and secondary ketoalkyl electrophiles generated through C-C bond cleavage
were amenable, providing rapid access to a variety of distal arylated alkyl ketones. A radical
pathway is proposed for this reaction.
Over past decades, the Suzuki-Miyaura cross-coupling has become a powerful and
frequently utilized tool for the C-C bond formations.1 The reasons for its popularity include
the mild conditions, excellent functional group tolerance as well as the ready availability of
the boronic acids. Additionally, not only aryl electrophiles but also alkyl electrophiles were
viable for this transformation.2, 3 Since the pioneering work of Suzuki, significant progress
has been made in the alkyl-aryl cross couplings. For instance, Fu et al. demonstrated a
series of Ni-catalyzed Suzuki couplings of the activated and unactivated alkyl halides with
organoboranes.4 Recently, the group of Baran disclosed the Ni-catalyzed cross-coupling of
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redox-active esters (RAEs) with boronic acids.5 Later on, they also presented the
Ni-catalyzed decarboxylative cross-coupling to construct the alkyl-aryl bonds. In those
reactions, new catalytic systems (including catalysts and ligands) and catalytic cycles
(single electron-transfer) have been explored to overcome the β-hydride elimination side
reaction. Especially, merging transition-metal catalysis with radical chemistry has become
a booming and attractive trend in current organic synthesis, which shows great potential in
Csp3-C bond formations.6
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In recent years, the oxygen-centered radical triggered C-C bond cleavage has attracted
much attention of chemists and has emerged as an efficient strategy to construct the Csp3-C
and Csp3-X bonds.7 To access the oxygen-centered radicals, different methods including
single electron oxidation,8 single electron reduction,9 PCET (proton-coupled electron
transfer)10 and LMCT (ligand-to-metal charge transfer)11 have been developed. In these
transformations, the ketoalkyl radical intermediates generated via C-C bond cleavage could
be captured with structurally diverse radical acceptors such as double bonds, aromatic
rings and other radicals, delivering the structurally diverse functionalized alkyl ketones. In
this field, our group recently disclosed catalytic borylation and decarboxylative olefination
of cycloalkyl silyl peroxides relying on alkoxyl radical induced carbon-carbon bond
cleavage.12d, 12e To fully exploit the potential of the ketoalkyl radicals, we expected to trap
them with transition metal species, enabling novel chemical transformations. Herein, we
report the Ni-catalyzed Suzuki alkyl-aryl coupling of cycloalkyl silyl peroxides with
boronic acids via C-C bond cleavage. A range of primary and secondary ketoalkyl
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electrophiles reacted well to afford the distal arylated alkyl ketones, which are difficult to
obtain via the direct Friedel-Crafts alkylation reactions.13
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We began our studies with the reaction of cyclopentyl silyl peroxide 1a and phenylboronic acid
2a under Ni catalysis (Table 1). Treatment of 1a with 2a in the presence of 5 mol % of NiBr2, 5
mol % of 4,4'-di-tert-butyl bipyridine (dtbpy) and 2.0 equiv of Et3N in DMAc at 90 °C led to the
desired 1,5-diphenyl-1-pentanone 3a in 80% yield (entry 1). Screening of ligands including
bipyridines, phenanthrolines and others showed that dtbpy afforded the best yield (entry 2). The
choice of base turned out to be a crucial factor in determining the outcome of this reaction. The
organic base Et3N proved to be most efficient, while K2CO3 and tBuOK were not suitable for this
reaction (entries 3 and 4). Other nickel catalysts such as NiCl2·6H2O, Ni(OAc)2 and
NiBr2·diglyme, all displayed catalytic activity, and NiBr2·diglyme gave a slight higher yield than
NiBr2 (entries 5 and 6). The palladium catalyst such as PdCl2 was also efficient, while FeCl2 and
CoCl2 failed to give any product (entries 7 and 8). With regard to solvents, CH3CN is superior to
DMAc, resulting in 93% yield of 3a (entry 9). 1,4-Dioxane afforded a comparable yield with
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o
DMAc, but toluene was totally ineffective (entry 10). Lowering temperature to 60 C or room
temperature led to a reduced yield of 3a (entry 11). Control experiments revealed that the Ni
catalyst was essential for this reaction. In the absence of ligand or base, poor yield of 3a was
obtained (entry 12). Finally, changing the leaving group to triethylsilyl group (1a’) resulted in a
slight lower yield of 3a (entry 9).
With the optimal conditions in hand, the generality and limitations of boronic acids 2 were
evaluated with 1a. It was found that a variety of arylboronic acids worked well in this reaction
(Scheme 1). While using phenylboronic acid pinacol ester and potassium phenyltrifluoroborate
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Table 1. Optimization of the Reaction Conditionsa
Ph
OOLG
O
7
8
9
NiBr2 (5 mol %), dtbpy (5 mol %)
Et3N (2.0 equiv), DMAc, 90 oC, 12 h
PhB(OH)2
+
Ph
Ph
1a
1a'
LG = TMS,
LG = TES,
2a
3a
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entry
variations from the standard conditions
none
yield (%)b
80
1
2
bpy or phenanthroline as the ligand
DIPEA as the base
34, 36
61
3
4
K2CO3 or tBuOK as the base
NiCl2·6H2O or Ni(OAc)2 as the catalyst
NiBr2·diglyme as the catalyst
FeCl2, CoCl2 as the catalyst
PdCl2 as the catalyst
trace
47, 24
84
5
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7
trace
26
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9
CH3CN as the solvent
93b (81)c
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1,4-dioxane or toluene as the solvent
At 60 oC or room temperature
no Ni, no ligand or no base
82b, traceb
85b, 39b
0, 20, 30
aReaction conditions: catalyst (5 mol %), 4,4'-di-tert-butyl bipyridine (dtbpy) (5 mol %), 1a (0.2 mmol, 1.0 equiv),
2a (0.3 mmol, 1.5 equiv), base (0.4 mmol, 2.0 equiv) in solvent (2.0 mL) at 90 oC for 12 h under N2. Isolated yield.
bNiBr2·diglyme was used as the catalyst. c1a’ was used.
instead of phenylboronic acid 2a led to no formation of 3a. The reactions of electron-deficient
arylboronic acids performed better than the electron-rich substrates. For example, a set of
para-substituted arylboronic acids with electron-withdrawing groups gave the corresponding
products 3c-h in 80%-98% yields. While the arylboronic acid 2b with electron-donating group
only afforded 61% yield. The ortho-substituted boronic acids 2i and 2j furnished poor yields and
2-phenyl substrate didn’t give any anticipated product. These results indicated that the reaction is
significantly hampered by the steric hindrance, which is different with Maruoka's Cu catalytic
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system. The meta-substituted arylboronic acids with electron-donating or -withdrawing groups all
provided moderate to good yields (3k-3m). The 3,4-disubstituted substrate 2n also gave the
desired product 3n in 89% yield.
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Scheme 1 Scope of Boronic Acids
.
Ph
NiBr2 diglyme (5 mol %)
OOTMS
+
O
O
dtbpy (5 mol %)
ArB(OH)2
Ph
Ph
Ar
Et3N (2.0 equiv)
CH3CN, 90 oC,12 h
1a
2
3
O
O
Cl
F
R
Ph
Ph
R
3n
, 89%
3b
, R = OCH3, 61%
, R = Cl, 85%
, R = Br, 80%
, R = F, 95%
3i
3j
, R = 2-OCH3, 35%
, R = 2-CN, 31%
3c
3d
3e
O
O
S
S
3k
, R = 3-OCH3, 56%
( )3
Ph
3l
3m
, R = 3-F, 89%
3f
3g
3h
, R = CF3, 98%
, R = CN, 81%
, R = SO2CH3, 92%
, R = 3-COCH3, 70%
O
3o
, 64%
O
Ph
Ph
Ph
Ar
Ph
N
Boc
O
3p
3q
, Ar = 1-naphthyl, 32%
, Ar = 2-naphthyl, 81%
3r
, 40%
3s
, 56%
O
O
O
Ph
Ph
Ph
3t
,
65%
N
N
N
R
3v
3w
, R = F, 77%
, R = CF3, 66%
3u
, 72%
Ph
O
Cl
O
O
H
( )3
3y
Ph
H
H
N
Ph
( )3
, 44%
3x
, 39%
3z
, 52%
O
Unsuccessful exmples
B(OH)2
N
Ph
B(OH)2
B(OH)2
N
B(OH)2
S
B(OH)2
N
N
aReaction conditions: catalyst (5 mol %), dtbpy (5 mol %), 1a (0.2 mmol, 1.0 equiv), 2 (0.3 mmol, 1.5 equiv),
Et3N (0.4 mmol, 2.0 equiv) in MeCN (2.0 mL) at 90 oC for 12 h under N2. b1,4-dioxane was used as the solvent.
However, the 3,5-bis(trifluoromethyl)phenylboronic acid failed to participate in this
transformation (not shown). A wide variety of functional groups such as halogens (3c-e, 3l), nitrile
(3g, 3j), sulfone (3h), and ketone (3m) were tolerated well under the standard conditions. As
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expected, 2-naphthylboronic acid delivered much better yield than the 1-naphthylboronic acid (3p
vs. 3q). Satisfactorily, a series of heteroarylboronic acids 2r-2x could deliver the corresponding
products in good yields. The existence of electron-withdrawing substituent is beneficial for the
reaction (3u-3w). Vinylic boronic acid 2y also underwent coupling smoothly to afford the product
3y in moderate yield. Notably, the estrone-derived arylboronic acid reacted successfully to provide
the desired product 3z in 52% yield, which highlights its potential application for late-stage
functionalization of complex molecules. However, when quinolyl or pyrimidinyl and others
boronic acid using as substrate, no corresponding products were obtained, neither
protodeboronation nor homocoupling of the boronic acids were detected in these cases (Scheme 1).
Unfortunately, the alkyl boronic acids such as cyclopentyl boronic acid didn’t give the desired
product, along with the ring-opened/hydrogenation byproduct observed (not shown).
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Subsequently, the scope of cycloalkyl silyl peroxides 1 was investigated using 2e as the
coupling partner (Scheme 2). The 1-aryl cyclopentylsilyl peroxides underwent the C-C bond
cleavage/coupling efficiently to afford the desired products 4a-d in moderate to good yields. The
thienyl-substituted peroxide survived well and gave the product 4e in 93% yield. The 1-alkyl
cyclopentylsilyl peroxide also reacted smoothly to form the desired product 4f in 93% yield.
Satisfactorily, peroxides with larger-ring systems including six-, seven-, eight- and even
twelve-membered rings were also amenable, delivering the desired coupling products 4g-j in
57-88% yields. The size of the ring systems didn’t largely affect the reaction. A vareity of
secondary alkyl electrophiles were also applicable to the Suzuki cross-couplings. By changing the
solvent to 1,4-dioxane, the reactions proceeded efficiently to give the corresponding products
4k-4o in good yields. In Maruoka's work, only one example was investigated. Peroxide 1p was
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also suitable, generating the desired product 4p in 81% yield with excellent regioselectivity.
Unfortunately, the ter-tiary alkyl electrophiles were unavailable at present.
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To gain insight into the reaction, some control experiments were conducted. Firstly, using the
alkyl hydroperoxide 1a’’ instead of 1a led to only trace amount of 3a, and the 1a’’ was
decomposed to the corresponding alcohol (eq 1). In addition, TEMPO and BHT, well known
Scheme 2 Scope of Cycloalkyl Silyl Peroxides
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OOTMS
R'
NiBr2.diglyme (5 mol %)
R
B(OH)2
O
R'
( )n
dtbpy (5 mol %)
+
R
Et3N (2.0 equiv)
CH3CN, 90 oC,12 h
F
( )n
F
1
2e
4
Primary alkyl electrophiles
O
O
O
S
F
F
R
F
a
4a
4b
4c
, R = F, 89%
a
a
4e
4d
, 93%
, 47%
a
, R = CH3, 71%
a
, R = CF3, 72%
O
O
a
a
4g
4h
, n = 2, 57%
, n = 3, 88%
( )n
a
a
4i
4j
, n = 4, 72%
, n = 8, 62%
F
4f
, 93%
F
Secondary alkyl electrophiles
Me
CO2Et
F
O
R'
O
O
Me
F
b
4k
, R' = Me, 84%
b
b
F
4n
, 58%
4m
, 76%
b
4l
, R' = n-hepyl, 61%
F
O
O
F
OOTMS
Ph
1p
S
Me
b
a
4o
4p
, 81% (d.r. = 1:1)
, 51%
aReaction conditions: catalyst (5 mol %), dtbpy (5 mol %), 1 (0.2 mmol, 1.0 equiv), 2e (0.3 mmol, 1.5 equiv), Et3N
(0.4 mmol, 2.0 equiv) in MeCN (2.0 mL) at 90 oC for 12 h under N2. b1,4-dioxane was used as the solvent.
radical scavengers, were subjected into the reaction, respectively (eqs 2 and 3). In the
presence of 2.0 equiv of TEMPO, the TEMPO-adduct 5a was obtained in 80% yield and
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no product 3a was detected. The addition of BHT could also inhibit the reaction. These
results implied that the reaction probably proceed through a radical pathway. A proposed
mechanism has been described in the Supporting Information (for details, see SI).14
Satisfactorily, the reaction of 1a with 2a could also be scaled up to 2.0 mmol, and the
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product 3a was obtained in 83% yield (eq 4)
Ph
NiBr2 (5 mol%)
dtbpy (5 mol%)
OOH
+
O
PhB(OH)2
(1)
(2)
(3)
Ph
Ph
, trace
Et3N (2.0 equiv)
DMAc, 90 oC, 12 h
1a''
2a
3a
Ph
OOTMS
O
standard conditions
TEMPO (2.0 equiv)
N
3a
+
PhB(OH)2
2a
+
Ph
O
1a
5a
no detected
, 80%
Ph
OOTMS
O
standard conditions
PhB(OH)2
+
Ph
Ph
1a
2a
3a
, 87%
3a
, 16%
BHT (2.0 equiv)
BHT (4.0 equiv)
Ph
OOTMS
+
NiBr2 (5 mol%)
dtbpy (5 mol%)
O
(4)
PhB(OH)2
2a
Ph
Ph
Et3N (2.0 equiv)
DMAc, 90 oC, 12 h
1a
3a
83%, 0.40g
2.0 mmol
3.0 mmol
In conclusion, a Ni-catalyzed Suzuki alkyl-aryl coupling via alkoxyl radical induced C-C bond
cleavage has been developed. A wide range of cycloalkyl silyl peroxides and boronic acids reacted
efficiently to afford the distal arylated alkyl ketones in moderate to good yields. The electronic
and steric effects of arylboronic acids displayed obvious influence on the reaction efficiency.
Mechanistic studies suggest that the reaction proceeds via a radical pathway.
EXPERIMENTAL SECTION
General Methods. 1H NMR and 13C NMR spectra were recorded on Bruker Advance III-400 and
Bruker Advance III-600 in solvents as indicated. Chemical shift are reported in ppm from TMS
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with the solvent resonance as internal standard (CDCl3: H NMR: δ = 7.26; 13C NMR: δ = 77.0).
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7
8
9
Coupling constants are reported in Hz with multiplicities denoted as s (singlet), d (doublet), t
(triplet), q (quartet) and m (multiplet). IR spectra were recorded on a Bruker Tensor 27
spectrometer and only major peaks are reported in cm-1. HRMS were obtained on WATERS
I-Class VION IMS QTof. TGA was obtained on METTLER TOLEDO TGA2. All catalytic
reactions were conducted in oven-dried Schlenk-tube under an atmosphere of nitrogen. Oil bath is
used for reactions that require heating. Reactions were monitored by thin layer chromatography
(aluminum backed plates pre-coated (0.25 mm) with Merck Silica Gel 60F-254.) and visualized
using UV light. Column chromatography purifications were carried out using 200-300 mesh silica
gel. Unless otherwise stated, all reagents were purchased from commercial sources and used
without further purification.
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Starting Materials
All of cycloalkylsilyl peroxides were prepared from the corresponding cycloalkyl alcohols
according to the literature.12 All of the NMR spectra of known compounds were in full accordance
with the data in the literatures. Note: The alkyl trimethylsilyl peroxides should be stored at -20oC.
The primary studies indicated that thermal degradation of 1a occurred at 105.1 °C (measured by
TGA, for details, see the SI). The hydrolytic stability of 1a is nice, even stirring it in CH3CN/H2O
(v/v=10/1) for 12h at room temperature.
Triethyl((1-phenylcyclopentyl)peroxy)silane (1a’): The compound was synthesized from
(1-hydroperoxycyclopentyl)benzene on a 2 mmol scale, colorless oil, 0.22 g, 38% yield; 1H NMR
(400 MHz, CDCl3) δ = 7.48 (d, J = 7.6 Hz, 2H), 7.34 (t, J = 7.6 Hz, 2H), 7.28 (s, 1H), 2.40– 2.30
(m, 2H), 1.97 – 1.85 (m, 4H), 1.83 – 1.74 (m, 2H), 0.96 – 0.92 (m, 9H), 0.62 (q, J = 8.0 Hz, 6H).
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13C{1H} NMR (100 MHz, CDCl3) δ = 144.3, 127.6, 126.7, 126.6, 94.9, 36.6, 24.3, 6.7, 3.7. ppm.
IR (neat): υmax 3031, 2956, 2880, 1456, 1329, 1249, 1090, 1015, 972, 850, 805, 736, 548, cm-1;
HRMS (ESI) calcd for C17H28NaO2Si [M+Na]+ 315.1751, found 315.1751.
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Representative Procedure for the Ni-Catalyzed Suzuki Coupling of Cycloalkyl Silyl
Peroxides 1 with Boronic Acids 2
An oven-dried 10 mL Schlenk-tube equipped with a magnetic stir bar was charged with boron
acid 2 (0.3 mmol, 1.5 equiv), NiBr2·diglyme (5 mol %) and dtbpy (5 mol %). Then, the tube was
evacuated and backfilled with nitrogen (three times). Subsequently, a solution of cycloalkyl silyl
peroxide 1 (0.2 mmol, 1.0 equiv) in CH3CN (1 mL) followed by a solution of Et3N (0.4 mmol, 2.0
equiv) in CH3CN (1 mL) were injected into the tube by syringe under nitrogen atmosphere. The
mixture was stirred at the specified temperature for the indicated reaction time. After the reaction
completed, the mixture was directly concentrated in vacuo. Purification of the crude product by
flash chromatography on silica gel (petroleum ether/ethyl acetate: 100:1) affords the product 3 or
4 in yields listed in Scheme 1 and 2.
Note: For 2-substituted cycloalkyl silyl peroxides, 1,4-dioxane was used as the solvent.
Larger Scale for the Ni-Catalyzed Suzuki Coupling of 1a with 2a
An oven-dried 50 mL Schlenk-tube equipped with a magnetic stir bar was charged with boron
acid 2a (3 mmol, 1.5 equiv), NiBr2·diglyme (5 mol %) and dtbpy (5 mol %). Then, the tube was
evacuated and backfilled with nitrogen (three times). Subsequently, a solution of cycloalkyl silyl
peroxide 1a (2 mmol, 1.0 equiv) in CH3CN (10 mL) followed by a solution of Et3N (4 mmol, 2.0
equiv) in CH3CN (10 mL) were injected into the tube by syringe under nitrogen atmosphere. The
o
mixture was stirred at the 90 C for the 12 h. After the reaction completed, the mixture was
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directly concentrated in vacuo. Purification of the crude product by flash chromatography on silica
gel (petroleum ether/ethyl acetate: 100:1) affords the product 3a (396.5mg, 83%).
Characterization of Products 3 and 4
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1,5-Diphenylpentan-1-one (3a) (known compound) Colorless oil (93%, 44.3 mg); Rf 0.40
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.97 (d, J = 7.3 Hz, 2H), 7.57 (t,
J = 7.3 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 7.35 – 7.29 (m, 2H)., 7.23 – 7.19 (m, 3H)., 3.01 (t, J =
7.1 Hz, 2H), 2.70 (t, J = 7.4 Hz, 2H), 1.86 – 1.71 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ =
200.0, 142.0, 136.7, 132.7, 128.3, 128.2, 128.1, 127.8, 125.5, 38.1, 35.6, 30.9, 23.7 ppm. Spectral
data match those previously reported.15a
5-(4-Methoxyphenyl)-1-phenylpentan-1-one (3b): (known compound) Colorless oil (61%, 32.6
1
mg); Rf 0.35 (EtOAc/petroleum ether = 1:15). H NMR (400 MHz, CDCl3) δ = 7.99 – 7.96 (m,
2H), 7.60 – 7.56 (m, 1H), 7.50 – 7.46 (m, 2H), 7.15 – 7.11 (m, 2H), 6.87 – 6.83 (m, 2H), 3.81 (s,
3H), 3.01 (t, J = 7.2 Hz, 2H), 2.64 (t, J = 7.5 Hz, 2H), 1.85 – 1.67 (m, 4H). 13C{1H} NMR (100
MHz, CDCl3) δ = 200.3, 157.7, 137.0, 134.3, 132.9, 129.2, 128.5, 128.0, 113.7, 55.2, 38.4, 34.8,
31.3, 23.9 ppm. IR (neat): υmax 2935, 2856, 1683, 1608, 1511, 1453, 1362, 1291, 1245, 1181, 1035,
821, 747 cm-1. Spectral data match those previously reported.15b
5-(4-Chlorophenyl)-1-phenylpentan-1-one (3c): Colorless oil (85%, 43.1 mg); Rf 0.31
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.85 (d, J = 7.8 Hz, 2H), 7.47 (t,
J = 7.2 Hz, 1H), 7.37 (t, J = 7.4 Hz, 2H), 7.15 (d, J = 7.3 Hz, 2H), 7.02 (d, J = 7.5 Hz, 2H), 2.90 (t,
J = 7.0 Hz, 2H), 2.55 (t, J = 7.4 Hz, 2H), 1.73 – 1.66 (m, 2H), 1.64 – 1.56(m, 2H). 13C{1H} NMR
(100 MHz, CDCl3) δ = 200.0, 140.6, 137.0, 132.9, 131.4, 129.7, 128.5, 128.3, 128.0, 38.2, 35.1,
30.9, 23.8 ppm. IR (neat): υmax 3050, 2932, 2859, 2306, 1964, 1904, 1674, 1587, 1492, 1454, 1405,
1372, 1308, 1249, 1197, 1089, 1017, 940, 900, 809, 741 cm-1; HRMS (ESI) calcd for C17H18ClO
[M+H]+ 273.1041, found 273.1039.
5-(4-Bromophenyl)-1-phenylpentan-1-one (3d): Colorless oil (80%, 50.7 mg); Rf 0.31
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.94 (d, J = 7.4 Hz, 2H), 7.56 (t,
J = 7.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.39 (d, J = 8.3 Hz, 2H), 7.06 (d, J = 8.3 Hz, 2H), 2.98 (t,
J = 7.1 Hz, 2H), 2.62 (t, J = 7.5 Hz, 2H), 1.82 – 1.75 (m, 2H), 1.72 – 1.65 (m, 2H). 13C{1H} NMR
(100 MHz, CDCl3) δ = 200.0, 141.1, 136.9, 132.9, 131.3, 130.1, 128.5, 128.0, 119.4, 38.2, 35.2,
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30.8, 23.8 ppm. IR (neat): υmax 3057, 2935, 2861, 2312, 1683, 1591, 1487, 1450, 1405, 1362, 1218,
1072, 1008, 969, 805, 746cm-1; HRMS (ESI) calcd for C17H18BrO [M+H]+ 317.0536, found
317.0529.
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5-(4-Fluorophenyl)-1-phenylpentan-1-one (3e): (Known compound) Colorless oil (95%, 48.6
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mg); Rf 0.44 (EtOAc/petroleum ether = 1:15). H NMR (400 MHz, CDCl3) δ = 7.96 – 7.94 (m,
2H), 7.56 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.15 – 7.12 (m, 2H), 6.96 (t, J = 8.7 Hz, 2H),
2.99 (t, J = 7.1 Hz, 2H), 2.64 (t, J = 7.5 Hz, 2H), 1.82 – 1.75 (m, 2H), 1.73 – 1.65 (m, 2H). 13C{1H}
NMR (100 MHz, CDCl3) δ = 200.1, 161.2 (d, J = 243.1 Hz), 137.8 (d, J = 3.2 Hz), 136.9, 132.9,
129.6 (d, J = 7.7 Hz), 128.5, 128.0, 115.0 (d, J = 21.0 Hz), 38.3, 34.9, 31.2, 23.8 ppm. IR (neat):
υmax 3055, 2934, 2861, 1684, 1596, 1508, 1450, 1409, 1363, 1221, 1165, 1093, 1007, 827, 750
cm-1. Spectral data match those previously reported.15c
1-Phenyl-5-(4-(trifluoromethyl)phenyl)pentan-1-one (3f): Colorless oil (98%, 50.0 mg); Rf 0.40
1
(EtOAc/petroleum ether = 1:15). H NMR (400 MHz, CDCl3) δ = 7.95 (d, J = 7.7 Hz, 2H),
7.58-7.51 (m, 3H), 7.46 (t, J = 7.6 Hz, 2H), 7.30 (d, J = 7.9 Hz, 2H), 3.00 (t, J = 6.9 Hz, 2H), 2.73
(t, J = 7.3 Hz, 2H), 1.84 – 1.70 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ = 200.0, 146.3,
136.9, 133.0, 128.7, 128.6, 128.0, 125.2 (q, J = 3.8 Hz), 124.4 (q, J = 270.6 Hz), 38.2, 35.6, 30.7,
23.8 ppm. IR (neat): υmax 3059, 2939, 2863, 1917, 1684, 1611, 1451, 1415, 1325, 1258, 1221,
1164, 1118, 1068, 1017, 810, 745 cm-1; HRMS (ESI) calcd for C18H17F3NaO [M+Na]+ 329.1124,
found 329.1121.
4-(5-Oxo-5-phenylpentyl)benzonitrile (3g): Colorless oil (81%, 42.7 mg); Rf 0.22
(EtOAc/petroleum ether = 1:8). 1H NMR (400 MHz, CDCl3) δ = 7.94 (d, J = 7.5 Hz, 2H), 7.57 –
7.55 (m, 3H), 7.46 (t, J = 7.7 Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H), 3.00 (t, J = 6.9 Hz, 2H), 2.73 (t, J
= 7.4 Hz, 2H), 1.83 – 1.68 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ = 199.9, 147.9, 136.9,
133.0, 132.2, 129.2, 128.6, 128.0, 119.1, 109.6, 38.1, 36.0, 30.5, 23.7 ppm. IR (neat): υmax 3055,
2932, 2858, 2310, 2220, 1739, 1675, 1603, 1505, 1452, 1406, 1311, 1250, 1194, 1087, 1019, 973,
809, 742 cm-1; HRMS (ESI) calcd for C18H18NO [M+H]+ 264.1383, found 264.1382.
5-(4-(Methylsulfonyl)phenyl)-1-phenylpentan-1-one (3h): Colorless oil (92%, 58.1 mg); Rf 0.35
(EtOAc/petroleum ether = 1:3). 1H NMR (400 MHz, CDCl3) δ = 7.95 – 7.93 (m, 2H), 7.84 (d, J =
8.3 Hz, 2H), 7.58 – 7.54 (m, 1H), 7.47 – 7.44 (m, 2H), 7.38 (d, J = 8.3 Hz, 2H), 3.03 (s, 3H), 3.00
(t, J = 6.9 Hz, 2H), 2.76 (t, J = 7.3 Hz, 2H), 1.83 – 1.69 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3)
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δ = 199.9, 148.8, 137.9, 136.8, 133.0, 129.3, 128.6, 127.9, 127.4, 44.6, 38.1, 35.7, 30.6, 23.6 ppm.
IR (neat): υmax 3019, 2933, 2863, 2312, 1682, 1593, 1451, 1408, 1364, 1306, 1220, 1148, 1091,
1018, 961, 802, 759 cm-1; HRMS (ESI) calcd for C18H21O3S [M+H]+ 317.1206, found 317.1201.
5-(2-Methoxyphenyl)-1-phenylpentan-1-one (3i): Colorless oil (35%, 18.8 mg); Rf 0.36
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.64 (dd, J = 7.7, 1.8 Hz, 1H),
7.46 – 7.42 (m, 1H), 7.28 (d, J = 1.6 Hz, 1H), 7.25 (s, 1H), 7.19 – 7.15 (m, 3H), 7.01 – 6.94 (m,
2H), 3.87 (s, 3H), 2.99 (t, J = 7.1 Hz, 2H), 2.64 (t, J = 7.3 Hz, 2H), 1.78 – 1.64 (m, 4H). 13C{1H}
NMR (100 MHz, CDCl3) δ = 203.0, 158.3, 142.5, 133.1, 130.1, 128.7, 128.4, 128.2, 125.6, 120.6,
111.4, 55.4, 43.6, 35.8, 31.2, 24.1 ppm. IR (neat): υmax 2944, 2870, 2384, 2307, 1675, 1596, 1483,
1250, 1094, 1015, 802, 755, 706 cm-1; HRMS (ESI) calcd for C18H20NaO2 [M+Na]+ 291.1356,
found 291.1351.
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2-(5-Oxo-5-phenylpentyl)benzonitrile (3j): Colorless oil (31%, 16.3 mg); Rf 0.34
(EtOAc/petroleum ether = 1:10). 1H NMR (600 MHz, CDCl3) δ = 7.96 – 7.94 (m, 2H), 7.62 – 7.60
(m, 1H), 7.57 – 7.54 (m, 1H), 7.52 – 7.49 (m, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.34 (d, J = 7.8 Hz,
1H), 7.30 – 7.27 (m, 1H), 3.04 (t, J = 7.0 Hz, 2H), 2.91 (t, J = 7.5 Hz, 2H), 1.86 – 1.76 (m, 4H).
13C{1H} NMR (150 MHz, CDCl3) δ = 199.9, 146.2, 136.9, 133.0, 132.8, 132.8, 129.6, 128.6,
128.0, 126.5, 118.2, 112.3, 38.1, 34.4, 30.4, 23.6 ppm. IR (neat): υmax 3061, 2927, 2859. 2386,
2302, 2220, 1680, 1590, 1449, 1362, 1258, 1215, 1092, 1009, 802, 757 cm-1; HRMS (ESI) calcd
for C18H17NNaO [M+Na]+ 286.1202, found 286.1209.
5-(3-Methoxyphenyl)-1-phenylpentan-1-one (3k): Colorless oil (56%, 29.8 mg); Rf 0.36
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.95 – 7.93 (m, 2H), 7.58 – 7.53
(m, 1H), 7.47 – 7.44 (m, 2H), 7.21 – 7.18 (m, 1H), 6.79 (d, J = 7.6 Hz, 1H), 6.74 – 6.72 (m, 2H),
3.80 (s, 3H), 2.99 (t, J = 7.1 Hz, 2H), 2.65 (t, J = 7.5 Hz, 2H), 1.84 – 1.68 (m, 4H). 13C{1H} NMR
(100 MHz, CDCl3) δ = 200.2, 159.6, 143.9, 137.0, 132.9, 129.2, 128.5, 128.0, 120.8, 114.1, 111.0,
55.1, 38.4, 35.8, 31.0, 24.0 ppm. IR (neat): υmax 2936, 2862, 2311, 1683, 1594, 1484, 1451, 1362,
1259, 1158, 1045, 969, 867, 744 cm-1; HRMS (ESI) calcd for C18H21O2 [M+H]+ 269.1536, found
269.1531.
5-(3-Fluorophenyl)-1-phenylpentan-1-one (3l): Colorless oil (89%, 45.4 mg); Rf 0.42
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.96 – 7.94 (m, 2H), 7.58 – 7.54
(m, 1H), 7.48 – 7.44 (m, 2H), 7.25 – 7.20 (m, 1H), 6.96 (d, J = 7.6 Hz, 1H), 6.91 – 6.84 (m, 2H),
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2.99 (t, J = 7.1 Hz, 2H), 2.67 (t, J = 7.5 Hz, 2H), 1.84 – 1.67 (m, 4H). 13C{1H} NMR (100 MHz,
CDCl3) δ = 200.1, 162.9 (d, J = 245.2 Hz), 144.8 (d, J = 7.0 Hz), 137.0, 133.0, 129.7 (d, J = 8.3
Hz), 128.6, 128.0, 124.0 (d, J = 2.7 Hz), 115.1 (d, J = 20.7 Hz), 112.6 (d, J = 21.0 Hz), 38.3, 35.5,
30.8, 23.8 ppm. IR (neat): υmax 3062, 2935, 2862, 2312, 1684, 1588, 1486, 1449, 1363, 1253, 1139,
1081, 1016, 930, 872, 790, 745 cm-1; HRMS (ESI) calcd for C17H18FO [M+H]+ 257.1336, found
257.1332.
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5-(3-Acetylphenyl)-1-phenylpentan-1-one (3m): Colorless oil (70%, 39.5 mg); Rf 0.32
(EtOAc/petroleum ether = 1:3). 1H NMR (400 MHz, CDCl3) δ = 7.96 – 7.93 (m, 2H), 7.79 – 7.76
(m, 2H), 7.58 – 7.53 (m, 1H), 7.47 – 7.44 (m, 2H), 7.41 – 7.35 (m, 2H), 3.00 (t, J = 7.0 Hz, 2H),
2.73 (t, J = 7.4 Hz, 2H), 2.60 (s, 3H), 1.84 – 1.70 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ =
200.1, 198.4, 142.7, 137.2, 136.9, 133.3, 133.0, 128.6, 128.5, 128.1, 128.0, 126.0, 38.3, 35.6, 30.9,
26.7, 23.8 ppm. IR (neat): υmax 2940, 2383, 2312, 1721, 1682, 1519, 1447, 1361, 1276, 967, 744,
695, 592, 514, 427 cm-1; HRMS (ESI) calcd for C19H20NaO2 [M+Na]+ 303.1356, found 303.1350.
5-(3-Chloro-4-fluorophenyl)-1-phenylpentan-1-one (3n): Colorless oil (89%, 51.1 mg); Rf 0.29
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.94 (d, J = 8.0 Hz, 2H), 7.56 (t,
J = 7.0 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 7.20 (d, J = 7.0 Hz, 1H), 7.02 (d, J = 6.8 Hz, 2H), 2.99 (t,
J = 7.0 Hz, 2H), 2.62 (t, J = 7.5 Hz, 2H), 1.81 – 1.74 (m, 2H), 1.72 – 1.65 (m, 2H). 13C{1H} NMR
(100 MHz, CDCl3) δ = 200.0, 156.4 (d, J = 246.2 Hz), 139.14 (d, J = 3.9 Hz), 136.9, 133.0, 130.2,
128.6, 128.0, 127.9, 120.4 (d, J = 17.6 Hz), 116.2 (d, J = 20.7 Hz), 38.2, 34.8, 30.9, 23.7 ppm. IR
(neat): υmax 3059, 2937, 2863, 1684, 1592, 1499, 1451, 1406, 1363, 1251, 1061, 1009, 885, 816,
742cm-1; HRMS (ESI) calcd for C17H17ClFO [M+H]+ 291.0946, found 291.0947.
5-(5a, 9a-Dihydrothianthren-2-yl)-1-phenylpentan-1-one (3o): Colorless oil (64%, 47.8 mg); Rf
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0.41 (EtOAc/petroleum ether = 1:15). H NMR (600 MHz, CDCl3) δ = 7.96 (d, J = 7.3 Hz, 2H),
7.56 (t, J = 7.4 Hz, 1H), 7.50 – 7.45 (m, 4H), 7.38 – 7.35 (m, 1H), 7.25 – 7.22 (m, 2H), 7.15 –
7.14 (m, 2H), 3.04 (t, J = 7.3 Hz, 2H), 2.93 (t, J = 7.7 Hz, 2H), 1.90 – 1.85 (m, 2H), 1.77 – 1.72
(m, 2H). 13C{1H} NMR (150 MHz, CDCl3) δ = 200.2, 141.8, 137.0, 136.5, 135.6, 135.5, 135.1,
132.9, 129.0, 128.6, 128.5, 128.4, 128.0, 127.8, 127.6, 127.3, 126.9, 38.3, 34.6, 30.3, 24.0 ppm. IR
(neat): υmax 3055, 2932, 2860, 2382, 2313, 1682, 1565, 1446, 1409, 1362, 1259, 1185, 1105, 1018,
908, 791, 744 cm-1; HRMS (ESI) calcd for C23H22KOS2 [M+H]+ 417.0744, found 417.0730.
5-(Naphthalen-1-yl)-1-phenylpentan-1-one (3p): Colorless oil (32%, 18.3 mg); Rf 0.45
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(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 8.04 (d, J = 8.2 Hz, 1H), 7.97 –
7.94 (m, 2H), 7.87 – 7.84 (m, 1H), 7.71 (d, J = 8.3 Hz, 1H), 7.58 – 7.44 (m, 5H), 7.39 (d, J = 8.0
Hz, 1H), 7.34 (d, J = 6.4 Hz, 1H), 3.14 (t, J = 7.3 Hz, 2H), 3.02 (t, J = 7.0 Hz, 2H), 1.95 – 1.81 (m,
4H). 13C{1H} NMR (100 MHz, CDCl3) δ = 200.3, 138.3, 137.0, 133.8, 132.9, 131.8, 128.7, 128.6,
128.0, 126.6, 125.9, 125.7, 125.5, 125.4, 123.8, 38.4, 33.0, 30.4, 24.4 ppm. IR (neat): υmax 3054,
2936, 2864, 2384, 2312, 1725, 1682, 1592, 1515, 1451, 1403, 1364, 1263, 1095, 1013, 788, 736
cm-1; HRMS (ESI) calcd for C21H20NaO [M+Na]+ 311.1406, found 311.1402.
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5-(Naphthalen-2-yl)-1-phenylpentan-1-one (3q): Colorless oil (81%, 46.9 mg); Rf 0.31
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.84 (d, J = 7.3 Hz, 2H), 7.71 –
7.66 (m, 3H), 7.53 (s, 1H), 7.44 (t, J = 7.4 Hz, 1H), 7.37 – 7.30 (m, 4H), 7.26 – 7.23 (m, 1H), 2.90
(t, J = 6.8 Hz, 2H), 2.74 (t, J = 7.0 Hz, 2H), 1.79 – 1.67 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3)
δ = 200.2, 139.7, 137.0, 133.6, 132.9, 132.0, 128.5, 128.0, 127.8, 127.6, 127.4, 127.3, 126.3, 125.8,
125.0, 38.4, 35.9, 30.9, 24.0 ppm. IR (neat): υmax 3051, 2936, 2862, 2383, 2311, 1680, 1592, 1508,
1450, 1363, 1227, 1009, 966, 894, 855, 815, 745 cm-1; HRMS (ESI) calcd for C21H20NaO
[M+Na]+ 311.1406, found 311.1401.
5-(Furan-3-yl)-1-phenylpentan-1-one (3r): Colorless oil (40%, 18.3 mg); Rf 0.30
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.95 (d, J = 7.3 Hz, 2H), 7.56 (t,
J = 7.3 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 7.34 (s, 1H), 7.22 (s, 1H), 6.27 (s, 1H), 3.00 (t, J = 7.2
Hz, 2H), 2.48 (t, J = 7.5 Hz, 2H), 1.83 – 1.76 (m, 2H), 1.69 – 1.61 (m, 2H). 13C{1H} NMR (100
MHz, CDCl3) δ = 200.2, 142.7, 138.8, 137.0, 133.0, 128.6, 128.0, 124.8, 110.9, 38.3, 29.6, 24.6,
23.9 ppm. IR (neat): υmax 2962, 2384, 2312, 1685, 1518, 1450, 1404, 1260, 1088, 1023, 869, 801
cm-1; HRMS (ESI) calcd for C15H16NaO2 [M+Na]+ 251.1043, found 251.1048.
Tert-butyl 3-(5-oxo-5-phenylpentyl)-1H-indole-1-carboxylate (3s): Colorless oil (56%, 42.1
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mg); Rf 0.28 (EtOAc/petroleum ether = 1:15). H NMR (400 MHz, CDCl3) δ = 8.12 – 8.11 (m,
1H), 7.96 – 7.94 (m, 2H), 7.58 – 7.52 (m, 2H), 7.48 – 7.44 (m, 2H), 7.40 – 7.35 (m, 1H), 7.33 –
7.29 (m, 1H), 7.25 – 7.21 (m, 1H), 3.03 (t, J = 7.0 Hz, 2H), 2.75 (t, J = 6.9 Hz, 2H), 1.91 – 1.77
(m, 4H), 1.67 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ = 200.2, 136.9, 132.9, 128.5, 128.0,
124.2, 122.3, 122.2, 120.8, 118.9, 115.2, 38.3, 28.8, 28.2, 24.8, 24.1 ppm. IR (neat): υmax 2934,
2312, 1729, 1684, 1597, 1452, 1375, 1311, 1258, 1161, 1089, 1019, 854, 804, 753 cm-1; HRMS
(ESI) calcd for C24H27NNaO3 [M+Na]+ 400.1883, found 400.1894.
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1-Phenyl-5-(9-phenyl-9H-carbazol-3-yl)pentan-1-one (3t): Colorless oil (65%, 41.6 mg); Rf
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0.34 (EtOAc/petroleum ether = 1:15). H NMR (400 MHz, CDCl3) δ = 8.13 (d, J = 7.9 Hz, 1H),
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7.97 – 7.95 (m, 3H), 7.62 – 7.53 (m, 6H), 7.45 (t, J = 7.6 Hz, 3H), 7.41 – 7.37 (m, 2H), 7.34 (d, J
= 8.4 Hz, 1H), 7.29 – 7.27 (m, 1H), 3.03 (t, J = 6.8 Hz, 2H), 2.88 (t, J = 7.0 Hz, 2H), 1.91 – 1.79
(m, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ = 200.4, 141.0, 139.4, 137.8, 137.0, 133.9, 132.9,
129.8, 128.5, 128.0, 127.2, 127.0, 126.6, 125.7, 123.4, 123.2, 120.2, 119.7, 119.6, 109.7, 109.5,
38.5, 35.8, 31.9, 24.0 ppm. IR (neat): υmax 3055, 2932, 2858, 2383, 2313, 1724, 1682, 1595, 1495,
1452, 1361, 1327, 1230, 1081, 1016, 910, 805, 744 cm-1; HRMS (ESI) calcd for C29H25NNaO
[M+Na]+ 426.1828, found 426.1837.
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5-(2-Chloropyridin-4-yl)-1-phenylpentan-1-one (3u): Colorless oil (72%, 54.6 mg); Rf 0.12
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 8.26 (d, J = 5.1 Hz, 1H), 7.94 (d,
J = 7.6 Hz, 2H), 7.56 (t, J = 7.3 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.16 (s, 1H), 7.05 (d, J = 5.0 Hz,
1H), 3.01 (t, J = 6.9 Hz, 2H), 2.66 (t, J = 7.5 Hz, 2H), 1.83 – 1.69 (m, 2H). 13C{1H} NMR (100
MHz, CDCl3) δ = 199.7, 154.5, 151.6, 149.5, 136.9, 133.1, 128.6, 128.0, 124.1, 122.6, 38.0, 34.9,
29.6, 23.6 ppm. IR (neat): υmax 3058, 2930, 2860, 1732, 1683, 1591, 1545, 1456, 1382, 1220, 1125,
1084, 997, 882, 834, 743 cm-1; HRMS (ESI) calcd for C16H17ClNO [M+H]+ 274.0993, found
274.0993.
5-(6-Fluoropyridin-3-yl)-1-phenylpentan-1-one (3v): Colorless oil (77%,39.5 mg); Rf 0.15
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 8.02 (s, 1H), 7.94 (d, J = 7.9 Hz,
2H), 7.62 – 7.54 (m, 2H), 7.46 (t, J = 7.6 Hz, 2H), 6.84 (dd, J = 8.3, 2.8 Hz, 1H), 3.00 (t, J = 7.0
Hz, 2H), 2.66 (t, J = 7.5 Hz, 2H), 1.83 – 1.76 (m, 2H), 1.73 – 1.66 (m, 2H). 13C{1H} NMR (100
MHz, CDCl3) δ = 199.85, 162.3 (d, J = 236.9 Hz), 146.92 (d, J = 14.2 Hz), 140.9 (d, J = 7.7 Hz),
136.9, 134.9 (d, J = 4.5 Hz), 133.0, 128.6, 128.0, 109.0 (d, J = 37.4 Hz), 38.1, 31.9, 30.8, 23.6
ppm. IR (neat): υmax 2927, 2859, 2312, 1681, 1591, 1479, 1391, 1244, 967, 831, 745 cm-1; HRMS
(ESI) calcd for C16H17FNO [M+H]+ 258.1289, found 258.1288.
1-Phenyl-5-(6-(trifluoromethyl)pyridin-3-yl)pentan-1-one (3w): Colorless oil (66%, 40.4 mg);
Rf 0.18 (EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 8.56 (s, 1H), 7.94 (d, J
= 7.7 Hz, 2H), 7.68 (d, J = 7.8 Hz, 1H), 7.61 – 7.54 (m, 2H), 7.46 (t, J = 7.4 Hz, 2H), 3.02 (t, J =
6.7 Hz, 2H), 2.76 (t, J = 7.3 Hz, 2H), 1.86 – 1.71 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ =
198.7, 149.1,145.0 (q, J = 34.7 Hz), 139.8, 135.9, 135.9, 132.1, 127.6, 127.0, 120.7 (q, J = 272.0
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Hz), 119.1 (q, J = 2.7 Hz), 37.0, 31.8, 29.4, 22.6 ppm. IR (neat): υmax 2940, 2866, 1684, 1590,
1451, 1403, 1339, 1256, 1176, 1135, 1087, 1025, 802, 748 cm-1; HRMS (ESI) calcd for
C17H17F3NO [M+H]+ 308.1257, found 308.1257.
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1-Phenyl-5-(quinolin-3-yl)pentan-1-one (3x): Colorless oil (39%, 22.5 mg); Rf 0.23
(EtOAc/petroleum ether = 1:10). 1H NMR (400 MHz, CDCl3) δ = 8.79 (s, 1H), 8.08 (t, J = 8.6 Hz,
1H), 7.95 (d, J = 8.1 Hz, 3H), 7.77 (d, J = 8.1 Hz, 1H), 7.66 (t, J = 7.6 Hz, 1H), 7.57 – 7.50 (m,
2H), 7.45 (t, J = 7.5 Hz, 2H), 3.03 (t, J = 6.5 Hz, 2H), 2.87 (t, J = 6.9 Hz, 2H), 1.92 – 1.78 (m, 4H).
13C{1H} NMR (100 MHz, CDCl3) δ = 200.0, 152.0, 146.8, 136.9, 134.7, 134.2, 133.0, 129.1,
128.6, 128.1, 128.0, 127.3, 126.6, 38.2, 33.1, 30.7, 23.8 ppm. IR (neat): υmax 2943, 2383, 2311,
1684, 1629, 1519, 1451, 1404, 1239, 1052, 1008, 794, 750 cm-1; HRMS (ESI) calcd for C20H20NO
[M+H]+ 290.1539, found 290.1537.
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(E)-1,7-Diphenylhept-6-en-1-one (3y): Known Compound Colorless oil (44%, 23.0 mg); Rf 0.40
(EtOAc/petroleum ether = 1:15). 1H NMR (600 MHz, CDCl3) δ = 7.98 – 7.96 (m, 2H), 7.57 – 7.54
(m, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.34 (d, J = 7.3 Hz, 2H), 7.29 (t, J = 7.7 Hz, 2H), 7.20 (t, J = 7.3
Hz, 1H), 6.41 (d, J = 15.8 Hz, 1H), 6.26 – 6.21 (m, 1H), 3.01 (t, J = 7.4 Hz, 2H), 2.30 – 2.26 (m,
2H), 1.85 – 1.80 (m, 2H), 1.61 – 1.57 (m, 2H). 13C{1H} NMR (150 MHz, CDCl3) δ = 200.3, 137.7,
137.0, 132.9, 130.4, 130.1, 128.5, 128.4, 128.0, 126.8, 125.9, 38.4, 32.8, 29.0, 23.9 ppm. IR (neat):
υmax 3025, 2932, 2312, 1684, 1592, 1493, 1448, 1362, 1278, 1222, 1073, 968, 744 cm-1. Spectral
data match those previously reported.12e
(8R,9S,13S,14S)-13-Methyl-3-(5-oxo-5-phenylpentyl)-6,7,8,9,11,12,13,14,15,16-decahydro-17
H-cyclopenta[a]phenanthren-17-one (3z): Colorless oil (52%, 43.0 mg); Rf 0.34
(EtOAc/petroleum ether = 1:8). 1H NMR (400 MHz, CDCl3) δ = 7.95 (d, J = 7.3 Hz, 2H), 7.56 (t,
J = 7.4 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.21 (d, J = 8.0 Hz, 1H), 6.99 (d, J = 7.9 Hz, 1H), 6.93 (s,
1H), 2.99 (t, J = 7.2 Hz, 2H), 2.90 – 2.87 (m, 2H), 2.61 (t, J = 7.5 Hz, 2H), 2.54 – 2.47 (m, 1H),
2.44 – 2.39 (m, 1H), 2.31 – 2.25 (m, 1H), 2.19 – 2.12 (m, 1H), 2.10 – 2.05 (m, 1H), 2.04 – 1.92 (m,
2H), 1.84 – 1.77 (m, 2H), 1.74 – 1.68 (m, 2H), 1.63 – 1.44 (m, 6H), 0.90 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 221.0, 200.3, 139.7, 137.1, 137.0, 136.3, 132.9, 129.0, 128.5, 128.0, 125.8,
125.3, 50.5, 48.0, 44.3, 38.4, 38.2, 35.9, 35.2, 31.6, 31.1, 29.4, 26.6, 25.7, 24.0, 21.6, 13.8 ppm. IR
(neat): υmax 2929, 2863, 2383, 2313, 2250, 1736, 1684, 1594, 1501, 1451, 1407, 1367, 1261, 1221,
1086, 1016, 910, 805, 737cm-1; HRMS (ESI) calcd for C29H34NaO2 [M+Na]+ 437.2451, found
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1,5-Bis(4-fluorophenyl)pentan-1-one (4a): Known Compound Colorless oil (89%, 48.2 mg); Rf
0.40 (EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.98 – 7.93 (m, 2H), 7.15 –
7.09 (m, 4H), 6.97 – 6.93 (m, 2H), 2.95 (t, J = 7.1 Hz, 2H), 2.64 (t, J = 7.4 Hz, 2H), 1.81 – 1.74
(m, 2H), 1.72 – 1.64 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ = 198.4, 165.6 (d, J = 254.5
Hz), 161.1 (d, J = 243.2 Hz), 137.7 (d, J = 3.1 Hz), 133.4 (d, J = 3.0 Hz), 130.6 (d, J = 9.2 Hz),
129.6 (d, J = 7.7 Hz), 115.6 (d, J = 21.8 Hz), 115.0 (d, J = 21.0 Hz), 38.2, 34.9, 31.1, 23.7 ppm.
IR (neat): υmax 3068, 2936, 2862, 1892, 1685, 1598, 1508, 1453, 1410, 1362, 1226, 1156, 1097,
1009, 833, 757, 702 cm-1. Spectral data match those previously reported.15d
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5-(4-Fluorophenyl)-1-(p-tolyl)pentan-1-one (4b): Colorless oil (71%, 38.6 mg); Rf 0.40
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.87 (d, J = 8.1 Hz, 2H), 7.27 (d,
J = 8.4 Hz, 2H), 7.17 – 7.14 (m, 2H), 7.00 – 6.96 (m, 2H), 2.98 (t, J = 7.1 Hz, 2H), 2.66 (t, J = 7.4
Hz, 2H), 2.43 (s, 3H), 1.83 – 1.76 (m, 2H), 1.74 – 1.67 (m, 2H). 13C{1H} NMR (100MHz, CDCl3)
δ = 199.8, 161.2 (d, J = 243.1 Hz), 143.7, 137.8 (d, J = 3.1 Hz), 134.5, 129.7 (d, J = 7.7 Hz),
129.2, 128.1, 115.0 (d, J = 21.0 Hz), 38.2, 35.0, 31.2, 23.9, 21.6 ppm. IR (neat): υmax 2925, 2859,
2384, 2312, 1725, 1682, 1608, 1556, 1453, 1406, 1366, 1262, 1180, 1098, 814, 733 cm-1; HRMS
(ESI) calcd for C18H20FO [M+H]+ 271.1493, found 271.1489.
5-(4-Fluorophenyl)-1-(4-(trifluoromethyl)phenyl)pentan-1-one (4c): Colorless oil (72%, 46.5
mg); Rf 0.39 (EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 8.04 (d, J = 7.7 Hz,
2H), 7.72 (d, J = 7.7 Hz, 2H), 7.13 (t, J = 5.7 Hz, 2H), 6.96 (t, J = 8.1 Hz, 2H), 3.01 (t, J = 6.7 Hz,
2H), 2.65 (t, J = 7.0 Hz, 2H), 1.81 – 1.77 (m, 2H), 1.71 – 1.68 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3) δ = 199.0, 161.2 (d, J = 243.3 Hz), 139.6, 137.6 (d, J = 3.2 Hz), 134.3 (q, J = 32.7 Hz),
129.6 (d, J = 7.7 Hz), 128.3, 125.6 (q, J = 3.7 Hz), 124.4 (q, J = 270.0 Hz),115.0 (d, J = 21.1 Hz),
38.6, 34.9, 31.0, 23.5 ppm. IR (neat): υmax 2935, 2863, 2312, 1692, 1599, 1510, 1454, 1409, 1324,
1223, 1169, 1129, 1067, 1010, 833, 756 cm-1; HRMS (ESI) calcd for C18H17F4O [M+H]+
325.1210, found 325.1207.
5-(4-Fluorophenyl)-1-(naphthalen-2-yl)pentan-1-one (4d): Colorless oil (47%, 29.0 mg); Rf
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0.37 (EtOAc/petroleum ether = 1:15). H NMR (400 MHz, CDCl3) δ = 8.45 (s, 1H), 8.04 – 8.01
(m, 1H), 7.97 – 7.95 (m, 1H), 7.91 – 7.87 (m, 2H), 7.62 – 7.58 (m, 1H), 7.58 – 7.54 (m, 1H), 7.17
– 7.12 (m, 2H), 6.99 – 6.93 (m, 2H), 3.12 (t, J = 7.2 Hz, 2H), 2.67 (t, J = 7.5 Hz, 2H), 1.88 – 1.81
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(m, 2H), 1.77 – 1.69 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ = 200.1, 161.2 (d, J = 243.1
Hz), 137.8 (d, J = 3.2 Hz), 135.5, 134.3, 132.5, 129.7 (d, J = 7.2 Hz), 129.6, 129.5, 128.4, 127.8,
126.7, 123.9, 115.0 (d, J = 21.0 Hz), 38.4, 35.0, 31.2, 24.0 ppm. IR (neat): υmax 3056, 2933, 2860,
2312, 1680, 1598, 1508, 1462, 1364, 1265, 1222, 1170, 1092, 1022, 816, 751 cm-1; HRMS (ESI)
calcd for C21H20FO [M+H]+ 307.1493, found 307.1489.
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5-(4-Fluorophenyl)-1-(thiophen-2-yl)pentan-1-one (4e): Colorless oil (93%, 48.7 mg); Rf 0.20
(EtOAc/petroleum ether = 1:15). 1H NMR (600 MHz, CDCl3) δ = 7.69 – 7.68 (m, 1H), 7.62 – 7.61
(m, 1H), 7.14 – 7.11 (m, 3H), 6.97 – 6.94 (m, 2H), 2.91 (t, J = 7.3 Hz, 2H), 2.63 (t, J = 7.6 Hz,
2H), 1.81 – 1.76 (m, 2H), 1.71 – 1.66 (m, 2H). 13C{1H} NMR (150 MHz, CDCl3) δ = 193.1, 161.2
(d, J = 243.1 Hz), 144.4, 137.7 (d, J = 3.0 Hz), 133.4, 131.7, 129.6 (d, J = 7.7 Hz), 128.0, 115.0 (d,
J = 21.1 Hz), 39.1, 34.9, 31.1, 24.2 ppm. IR (neat): υmax 2937, 2864, 2383, 2312, 1662, 1603, 1511,
1451, 1414, 1361, 1224, 1160, 1052, 923, 827, 726 cm-1; HRMS (ESI) calcd for C15H16FOS
[M+H]+ 263.0900, found 263.0896.
1-(4-Fluorophenyl)decan-5-one (4f): Colorless oil (93%, 46.5 mg); Rf 0.39 (EtOAc/petroleum
ether = 1:15). 1H NMR (600 MHz, CDCl3) δ = 7.12 – 7.10 (m, 2H), 6.95 (t, J = 8.7 Hz, 2H), 2.58
(t, J = 7.0 Hz, 2H), 2.41 (t, J = 6.7 Hz, 2H), 2.36 (t, J = 7.5 Hz, 2H), 1.59 – 1.53 (m, 6H), 1.33 –
1.29 (m, 2H), 1.27 – 1.22 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ =
211.3, 161.2 (d, J = 243.2 Hz), 137.8 (d, J = 3.2 Hz), 129.6 (d, J = 7.7 Hz), 115.0 (d, J = 21.1 Hz).
42.8, 42.5, 34.9, 31.4, 31.1, 23.5, 23.3, 22.4, 13.9 ppm. IR (neat): υmax 2941, 2866, 2384, 2312,
1712, 1602, 1510, 1458, 1408, 1369, 1261, 1222, 1089, 1023, 807, 756 cm-1; HRMS (ESI) calcd
for C18H19FNaO [M+Na]+ 293.1312, found 293.1307.
6-(4-Fluorophenyl)-1-phenylhexan-1-one (4g): Colorless oil (57%, 33.0 mg); Rf 0.42
(EtOAc/petroleum ether = 1:15). 1H NMR (600 MHz, CDCl3) δ = 7.96 – 7.94 (m, 2H), 7.57 – 7.54
(m, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.13 – 7.10 (m, 2H), 6.97 – 6.93 (m, 2H), 2.96 (t, J = 7.4 Hz,
2H), 2.60 (t, J = 7.7 Hz, 2H), 1.80 – 1.75 (m, 2H), 1.68 – 1.62 (m, 2H), 1.44 – 1.39 (m, 2H).
13C{1H} NMR (150 MHz, CDCl3) δ = 200.4, 161.2 (d, J = 243.2 Hz), 138.1 (d, J = 2.8 Hz), 137.0,
132.9, 129.6 (d, J = 7.7 Hz), 128.6, 128.0, 114.9 (d, J = 21.0 Hz), 38.5, 34.9, 31.4, 28.8, 24.1 ppm.
IR (neat): υmax 3055, 2928, 2870, 2383, 2312, 1682, 1518, 1455, 1408, 1262, 1084, 842, 808, 734
cm-1; HRMS (ESI) calcd for C18H19FNaO [M+Na]+ 293.1312, found 293.1309.
7-(4-Fluorophenyl)-1-phenylheptan-1-one (4h): Colorless oil (88%, 50.1 mg); Rf 0.44
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(EtOAc/petroleum ether = 1:15). 1H NMR (600 MHz, CDCl3) δ = 7.96 (d, J = 7.3 Hz, 2H), 7.55 (t,
J = 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.11 (dd, J = 8.4, 5.6 Hz, 2H), 6.95 (t, J = 8.7 Hz, 2H),
2.96 (t, J = 7.4 Hz, 2H), 2.58 (t, J = 7.6 Hz, 2H),, 1.77 – 1.72 (m, 2H), 1.63 – 1.58 (m, 2H), 1.44 –
1.35 (m, 4H). 13C{1H} NMR (150 MHz, CDCl3) δ = 200.4, 161.1 (d, J = 243.2 Hz), 138.2 (d, J =
3.2 Hz), 137.0, 132.9, 129.6 (d, J = 7.7 Hz), 128.5, 128.0, 114.9 (d, J = 21.0 Hz), 38.5, 35.0, 31.4,
29.1, 28.9, 24.2 ppm. IR (neat): υmax 2932, 2860, 2384, 2312, 1685, 1597, 1539, 1510, 1451, 1365,
1220, 1072, 970, 830, 751 cm-1; HRMS (ESI) calcd for C19H22FO [M+H]+ 285.1649, found
285.1648.
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8-(4-Fluorophenyl)-1-phenyloctan-1-one (4i): Colorless oil (72%, 42.9 mg); Rf 0.29
(EtOAc/petroleum ether = 1:15). 1H NMR (600 MHz, CDCl3) δ = 7.96 – 7.95 (m, 2H), 7.57 – 7.54
(m, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.12 – 7.10 (m, 2H), 6.96 – 6.93 (m, 2H), 2.96 (t, J = 7.4 Hz,
2H), 2.57 (t, J = 7.8 Hz, 2H), 1.76 – 1.71 (m, 2H), 1.61 – 1.56 (m, 2H), 1.41 – 1.32 (m, 6H).
13C{1H} NMR (150 MHz, CDCl3) δ = 200.5, 161.1 (d, J = 242.9 Hz), 138.3 (d, J = 3.2 Hz), 137.0,
132.9, 129.6 (d, J = 7.7 Hz), 128.5, 128.0, 114.9 (d, J = 20.9 Hz), 38.6, 35.1, 31.5, 29.3, 29.2, 29.0,
24.3 ppm. IR (neat): υmax 3054, 2923, 2856, 2383, 2312, 1682, 1516, 1455, 1408, 1223, 1085,
1009, 900, 805, 736 cm-1; HRMS (ESI) calcd for C20H24FO [M+H]+ 299.1806, found 299.1801.
12-(4-Fluorophenyl)-1-phenyldodecan-1-one (4j): Colorless oil (62%, 44.1 mg); Rf 0.52
(EtOAc/petroleum ether = 1:15). 1H NMR (600 MHz, CDCl3) δ = 7.96 (d, J = 8.0 Hz, 2H), 7.55 (t,
J = 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.13 – 7.10 (m, 2H), 6.95 (t, J = 8.7 Hz, 2H), 2.96 (t, J =
7.4 Hz, 2H), 2.56 (t, J = 7.6 Hz, 2H), 1.76 – 1.71 (m, 2H), 1.40 – 1.26 (m, 16H). 13C{1H} NMR
(150 MHz, CDCl3) δ = 200.6, 161.1 (d, J = 243.0 Hz), 138.5 (d, J = 3.2 Hz), 137.1, 132.8, 129.6
(d, J = 7.7 Hz), 128.5, 128.0, 114.9 (d, J = 21.0 Hz), 38.6, 35.1, 31.6, 29.6, 29.5, 29.5, 29.4, 29.3,
29.2, 24.4 ppm. IR (neat): υmax 2983, 2918, 2853, 2384, 2312, 1683, 1518, 1461, 1405, 1283, 1239,
1083, 933, 821, 733 cm-1; HRMS (ESI) calcd for C24H32FO [M+H]+ 355.2432, found 355.2425.
5-(4-Fluorophenyl)-1-phenylhexan-1-one (4k): Colorless oil (84%, 48.4 mg); Rf 0.42
(EtOAc/petroleum ether = 1:15). 1H NMR (600 MHz, CDCl3) δ = 7.92 – 7.90 (m, 2H), 7.55 (t, J =
7.4 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.16 – 7.13 (m, 2H), 6.99 – 6.95 (m, 2H), 2.97 – 2.88 (m,
2H), 2.76 – 2.70 (m, 1H), 1.74 – 1.64 (m, 2H), 1.63 – 1.56 (m, 2H), 1.25 (d, J = 6.9 Hz, 3H).
13C{1H} NMR (150 MHz, CDCl3) δ = 200.2, 161.2 (d, J = 243.2 Hz), 142.8 (d, J = 3.0 Hz), 136.9,
132.9, 128.2 (d, J = 7.7 Hz), 128.2, 128.0, 115.0 (d, J = 20.9 Hz), 39.2, 38.4, 38.0, 22.5, 22.4 ppm.
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IR (neat): υmax 2961, 2383, 2312, 1685, 1598, 1514, 1450, 1405, 1283, 1222, 1053, 833, 748 cm-1;
HRMS (ESI) calcd for C18H19FNaO [M+Na]+ 293.1312, found 293.1307.
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5-(4-Fluorophenyl)-1-phenyldodecan-1-one (4l): Colorless oil (61%, 43.1 mg); Rf 0.39
(EtOAc/petroleum ether = 1:15). 1H NMR (600 MHz, CDCl3) δ = 7.91 – 7.89 (m, 2H), 7.54 (t, J =
7.4 Hz, 1H), 7.43 (t, J = 7.7 Hz, 2H), 7.11 – 7.08 (m, 2H), 6.98 – 6.95 (m, 2H), 2.98 – 2.83 (m,
2H), 2.55 – 2.50 (m, 1H), 1.74 – 1.68 (m, 1H), 1.59 – 1.47 (m, 3H), 1.26 – 1.08 (m, 12H), 0.86 (t,
J = 7.2 Hz, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ = 200.2, 161.2 (d, J = 243.2 Hz), 141.3 (d, J
= 3.0 Hz), 136.9, 132.9, 128.8 (d, J = 7.7 Hz), 128.5, 128.0, 115.0 (d, J = 20.9 Hz). 45.3, 38.5,
37.0, 36.5, 31.8, 29.6, 29.2, 27.5, 22.6, 22.4, 14.1 ppm. IR (neat): υmax 2983, 2891, 2384, 2312,
1696, 1519, 1403, 1283, 1238, 1052, 889 cm-1; HRMS (ESI) calcd for C24H31FNaO [M+Na]+
377.2251, found 377.2252.
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Ethyl 2-(4-(1-(4-fluorophenyl)-5-oxo-5-phenylpentyl)phenyl)propanoate (4m): Colorless oil
(76%, 65.7 mg); Rf 0.22 (EtOAc/petroleum ether = 1:15). 1H NMR (600 MHz, CDCl3) δ = 7.88 –
7.87 (m, 2H), 7.54 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.7 Hz, 2H), 7.14 – 7.12 (m, 2H), 7.06 – 7.04
(m, 2H), 6.95 – 6.91 (m, 4H), 4.15 – 4.06 (m, 2H), 3.64 (q, J = 7.1 Hz, 1H), 2.93 – 2.78 (m, 5H),
1.79 – 1.74 (m, 1H), 1.70 – 1.66 (m, 1H), 1.61 – 1.56 (m, 2H), 1.46 (d, J = 7.2 Hz, 3H), 1.19 (td, J
= 7.1, 2.0 Hz, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ = 200.1, 174.6 , 161.3 (d, J = 243.6 Hz) ,
140.1 (d, J = 2.8 Hz), 139.0, 138.1, 136.9, 132.9, 129.2, 129.0 (d, J = 7.7 Hz), 128.5, 127.9, 127.1,
115.0 (d, J = 21.0 Hz), 60.6, 47.2, 47.2, 45.1, 45.1, 43.5, 38.4, 35.1, 22.2, 18.5, 18.4, 14.1 ppm. IR
(neat): υmax 2978, 2932, 2312, 1730, 1685, 1598, 1509, 1452, 1369, 1325, 1218, 1168, 1087, 1020,
833, 746 cm-1; HRMS (ESI) calcd for C29H31FNaO3 [M+Na]+ 469.2149, found 469.2152.
6-(4-Fluorophenyl)-1-phenylheptan-1-one (4n): Colorless oil (58%, 33.1 mg); Rf 0.45
(EtOAc/petroleum ether = 1:15). 1H NMR (600 MHz, CDCl3) δ = 7.93 (d, J = 7.3 Hz, 2H), 7.55 (t,
J = 7.4 Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 7.13 – 7.11 (m, 2H), 6.96 (t, J = 8.7 Hz, 2H), 2.91 (t, J =
7.4 Hz, 2H), 2.72 – 2.66 (m, 1H), 1.77 – 1.66 (m, 2H), 1.61 – 1.57 (m, 2H), 1.26 – 1.19 (m, 5H).
13C{1H} NMR (150 MHz, CDCl3) δ = 199.4, 160.1 (d, J = 243.1 Hz), 142.1 (d, J = 2.9 Hz), 136.0,
131.9, 127.5, 127.2 (d, J = 7.7 Hz), 127.0, 114.0 (d, J = 21.0 Hz), 38.1, 37.5, 37.3, 26.4, 23.2, 21.5
ppm. IR (neat): υmax 3055, 2957, 2862, 2312, 1727, 1684, 1597, 1508, 1453, 1409, 1367, 1262,
1223, 1154, 1093, 1020, 803, 745 cm-1; HRMS (ESI) calcd for C19H22FO [M+H]+ 285.1649,
found 285.1645.
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6-(4-Fluorophenyl)-1-(thiophen-2-yl)heptan-1-one (4o): Colorless oil (51%, 29.4 mg); Rf 0.36
(EtOAc/petroleum ether = 1:15). 1H NMR (400 MHz, CDCl3) δ = 7.67 (d, J = 3.7 Hz, 1H), 7.61 (d,
J = 4.9 Hz, 1H), 7.13 – 7.10 (m, 3H), 6.96 (t, J = 8.6 Hz, 2H), 2.84 (t, J = 7.4 Hz, 2H), 2.72 – 2.63
(m, 1H), 1.79 – 1.64 (m, 2H), 1.61 – 1.55 (m, 2H), 1.31 – 1.20 (m, 5H). 13C{1H} NMR (100 MHz,
CDCl3) δ = 193.3, 161.1 (d, J = 243.6 Hz), 144.4, 143.1 (d, J = 3.2 Hz), 133.4, 131.6, 128.2 (d, J
= 7.7 Hz), 128.0, 115.0 (d, J = 20.9 Hz), 39.3, 39.1, 38.2, 27.3, 24.6, 22.5 ppm. IR (neat): υmax
3094, 2957, 2863, 2312, 1663, 1602, 1510, 1454, 1414, 1364, 1260, 1226, 1156, 1191, 1024, 803,
726 cm-1; HRMS (ESI) calcd for C17H19FNaOS [M+Na]+ 313.1033, found 313.1043.
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2-(3-(4-Fluorophenyl)cyclopentyl)-1-phenylethan-1-one (4p): Colorless oil (81%, 45.5 mg); Rf
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0.42 (EtOAc/petroleum ether = 1:15). H NMR (400 MHz, CDCl3) δ = 7.98 (d, J = 7.6 Hz, 2H),
7.57 (t, J = 7.3 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 7.20 – 7.17 (m, 2H), 6.96 (t, J = 8.7 Hz, 2H),
3.20 – 3.03 (m, 3H), 2.80 – 2.69 (m, 0.5H), 2.66 – 2.56 (m, 0.5H), 2.36 – 2.30 (m, 0.5H), 2.17 –
2.04 (m, 2H), 2.00 – 1.93 (m, 0.5H), 1.83 – 1.76 (m, 0.5H), 1.73 – 1.58 (m, 1H), 1.54 – 1.44 (m,
0.5H), 1.42 – 1.25 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ = 199.9, 161.10 (d, J = 244.2 Hz),
141.9 (d, J = 3.2 Hz), 141.4, 137.1, 132.9, 128.6, 128.3, 128.0, 114.9 (d, J = 21.0 Hz), 45.3, 45.0,
44.8, 43.6, 42.2, 40.4, 35.8, 35.1, 34.9, 33.3, 33.2, 31.8 ppm. IR (neat): υmax 3055, 2948, 2868,
2312, 1683, 1596, 1509, 1451, 1406, 1369, 1332, 1272, 1220, 1164, 1090, 1011, 828, 753 cm-1;
HRMS (ESI) calcd for C19H20FO [M+H]+ 283.1493, found 283.1490.
Investigation of the Reaction Mechanism
When 2.0 equiv of TEMPO was added to the reaction of 1a with 2a under the standard conditions,
no product 3a was detected. Meanwhile, the TEMPO-adduct 5a was isolated in 80% yield. These
results indicate that radical intermediate was probably involved in this transformation.
1-phenyl-5-((2,2,6,6-tetramethylpiperidin-1-yl)oxy)pentan-1-one (5a) Known Compound12.
1
Colorless oil (80%, 51.0 mg); Rf 0.39 (EtOAc/petroleum ether = 1:15). H NMR (600 MHz,
CDCl3) δ = 7.97 (d, J = 7.5 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 3.78 (t, J =
6.4 Hz, 2H), 3.02 (t, J = 7.4 Hz, 2H), 1.87 – 1.82 (m, 2H), 1.65 – 1.60 (m, 3H), 1.47 – 1.43 (m,
4H), 1.32 – 1.30 (m, 1H), 1.15 (s, 2H), 1.08 (s, 2H). 13C NMR (150 MHz, CDCl3) δ = 200.4,
137.0, 132.9, 128.5, 128.0, 59.6, 39.6, 38.6, 33.1, 28.4, 21.5, 20.1, 17.1 ppm.
When 2.0 equiv of BHT was added to the reaction of 1a with 2a under the standard conditions, the
yield of 3a just reduced a little bit. Increasing it to 4.0 equiv led to a largely reduced yield. These
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results indicate that the reaction probably proceed via a radical pathway.
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ASSOCIATED CONTENT
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Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website at DOI:
10.1021/acs.joc. XXXXX
1H and 13C spectra of all new compounds; the primary mechanistic studies of the reactions.
AUTHOR INFORMATION
Corresponding Author
Li-Na Guo - Department of Chemistry, School of Science, Xi'an Key Laboratory of Sustainable Energy Material
Chemistry, and MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi’an
Jiaotong University, Xi’an 710049, China. orcid.org/0000-0002-9789-6952; Email: guoln81@xjtu.edu.cn
Authors
Lei Chen, Department of Chemistry, School of Science, Xi'an Key Laboratory of Sustainable Energy Material
Chemistry, and MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi’an
Jiaotong University, Xi’an 710049, China.
Jun-Cheng Yang, Department of Chemistry, School of Science, Xi'an Key Laboratory of Sustainable Energy
Material Chemistry, and MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed
Matter, Xi’an Jiaotong University, Xi’an 710049, China.
Pengfei Xu, Department of Chemistry, School of Science, Xi'an Key Laboratory of Sustainable Energy Material
Chemistry, and MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi’an
Jiaotong University, Xi’an 710049, China.
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Jun-Jie Zhang, Department of Chemistry, School of Science, Xi'an Key Laboratory of Sustainable Energy Material
Chemistry, and MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi’an
Jiaotong University, Xi’an 710049, China.
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Xin-Hua Duan, Department of Chemistry, School of Science, Xi'an Key Laboratory of Sustainable Energy
Material Chemistry, and MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed
Matter, Xi’an Jiaotong University, Xi’an 710049, China; State Key Laboratory of Applied Organic Chemistry,
Lanzhou University, Lanzhou 730000, P. R. China; orcid.org/0000-0002-9789-6952
ACKNOWLEDGMENTS
Financial support from the National Natural Science Foundation of China (21971201), Natural
Science Basic Research Plan in Shaanxi Province of China (No. 2019JM-299), Key Laboratory
Construction Program of Xi'an Municipal Bureau of Science and Technology (No.
201805056ZD7CG40) is greatly appreciated. We also thank Mr. Chang and Miss Lu at Instrument
Analysis Center of Xi’an Jiaotong University for their assistance with NMR and HRMS analysis.
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Bulger, P. G.; Sarlah, D. Palladium-Catalyzed Cross-Coupling Reactions in Total Synthesis.
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with Non-activated Alkyl Halides. Angew. Chem., Int. Ed. 2005, 44, 674-688. (e) Rudolph, A.;
Lautens, M. Secondary Alkyl Halides in Transition-Metal-Catalyzed Cross-Coupling Reactions.
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Cross-Coupling Reactions of Alkyl Halides. Chem. Soc. Rev. 2011, 40, 4937-4947. (g) Jana, R.;
Pathak, T. P.; Sigman, M. S. Advances in Transition Metal (Pd, Ni, Fe)-Catalyzed Cross-Coupling
Reactions Using Alkyl-organometallics as Reaction Partners. Chem. Rev. 2011, 111, 1417-1492.
(h) Hu, X. Nickel-Catalyzed Cross Coupling of Non-activated Alkyl Halides: a Mechanistic
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(3) For selected examples, see: (a) Sun, Y.-Y.; Yi, J.; Lu, X.; Zhang, Z.-Q.; Xiao, B.; Fu, Y. Cu
Catalyzed Suzuki-Miyaura Reactions of Primary and Secondary Benzyl Halides with
Arylboronates. Chem. Commun. 2014, 50, 11060-11062. (b) Jiang, X.; Sakthivel, S.; Kulbitski,
K.; Nisnevich, G.; Gandelman, M. Efficient Synthesis of Secondary Alkyl Fluorides via Suzuki
Cross-Coupling Reaction of 1-Halo-1-fluoroalkanes. J. Am. Chem. Soc. 2014, 136, 9548-9551. (c)
Su, Y.; Feng, G.; Wang, Z.; Lan, Q.; Wang, X. Nickel-Catalyzed Monofluoromethylation of Aryl
Boronic Acids. Angew. Chem., Int. Ed. 2015, 54, 6003-6007. (d) Jiang, X.; Gandelman, M.
Enantioselective Suzuki Cross-Couplings of Unactivated 1-Fluoro-1-haloalkanes: Synthesis of
Chiral β-, γ-, δ-, and ε-Fluoroalkanes. J. Am. Chem. Soc. 2015, 137, 2542-2547. (e) Xiao, Y.-L.;
Min, Q.-Q.; Xu, C.; Wang, R.-W.; Zhang, X. Nickel-Catalyzed Difluoroalkylation of
(Hetero)arylborons with Unactivated 1-Bromo-1,1-difluoroalkanes. Angew. Chem., Int. Ed. 2016,
55, 5837-5841. (f) Brambilla, M.; Tredwell, M. Palladium-Catalyzed Suzuki-Miyaura
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Cross-Coupling of Secondary α-(Trifluoromethyl)benzyl Tosylates. Angew. Chem., Int. Ed. 2017,
56, 11981-11985. (g) Bao, X.; Wang, Q.; Zhu, J. Remote C(sp3)-H Arylation and Vinylation of
N-Alkoxypyridinium Salts to δ-Aryl and δ-Vinyl Alcohols. Chem. Eur. J . 2019, 25,
11630-11634.
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(4) For selected examples, see: (a) Zhou, J.; Fu, G. C. Suzuki Cross-Couplings of Unactivated
Secondary Alkyl Bromides and Iodides. J. Am. Chem. Soc. 2004, 126, 1340-1341. (b)
González-Bobes, F.; Fu, G. C. Amino Alcohols as Ligands for Nickel-Catalyzed Suzuki Reactions
of Unactivated Alkyl Halides, Including Secondary Alkyl Chlorides, with Arylboronic Acids. J.
Am. Chem. Soc. 2006, 128, 5360-5361. (c) Zultanski, S. L.; Fu, G. C. Catalytic Asymmetric
γ-Alkylation of Carbonyl Compounds via Stereoconvergent Suzuki Cross-Couplings. J. Am.
Chem. Soc. 2011, 133, 15362-15364. (d) Wilsily, A.; Tramutola, F.; Owston, N. A.; Fu, G. C.
New Directing Groups for Metal-Catalyzed Asymmetric Carbon-Carbon Bond-Forming
Processes: Stereoconvergent Alkyl-Alkyl Suzuki Cross-Couplings of Unactivated Electrophiles. J.
Am. Chem. Soc. 2012, 134, 5794-5797. (e) Dudnik, A. S.; Fu, G. C. Nickel-Catalyzed Coupling
Reactions of Alkyl Electrophiles, Including Unactivated Tertiary Halides, To Generate
Carbon-Boron Bonds. J. Am. Chem. Soc. 2012, 134, 10693-10697. (f) Zultanski, S. L.; Fu, G. C.
Nickel-Catalyzed Carbon-Carbon Bond-Forming Reactions of Unactivated Tertiary Alkyl
Halides: Suzuki Arylations. J. Am. Chem. Soc. 2013, 135, 624-627.
(5) For selected examples, see: (a) Wang, J.; Qin, T.; Chen, T. G.; Wimmer, L.; Edwards, J. T.;
Cornella, J.; Vokits, B.; Shaw, S. A.; Baran, P. S. Nickel-Catalyzed Cross-Coupling of
Redox-Active Esters with Boronic Acids. Angew. Chem., Int. Ed. 2016, 55, 9676-9679. (b)
Sandfort, F.; O’Neill, M. J.; Cornella, J.; Wimmer, L.; Baran, P. S. Alkyl-(Hetero)Aryl Bond
Formation via Decarboxylative Cross-Coupling: A Systematic Analysis. Angew. Chem., Int. Ed.
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Formation of Remote Double Bonds by Ferrous Sulfate-Cupric Acetate Promoted Decomposition
of Alkyl Hydroperoxides. J. Am. Chem. Soc. 1974, 96, 3000-3002. (b) Kundu, R.; Ball, Z. T.
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(10) For selected examples of PCET, see: (a) Yayla, H. G.; Wang, H.; Tarantino, K.T.; Orbe, H.
S.; Knowles, R. R.; Catalytic Ring-Opening of Cyclic Alcohols Enabled by PCET Activation of
Strong O-H Bonds. J. Am. Chem. Soc. 2016, 138, 10794-10797. (b) Wang, D.; Mao, J.; Zhu, C.
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Xia, W. Visible-Light-Mediated Ring-Opening Strategy for the Regiospecific
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(11) For selected examples of LMCT, see: (a) Guo, J.-J.; Hu, A.; Chen, Y.; Sun, J.; Tang, H.;
Zuo, Z. Photocatalytic C-C Bond Cleavage and Amination of Cycloalkanols by Cerium(III)
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Transfer. J. Am. Chem. Soc. 2018, 140, 1612-1616. (d) Hu, A.; Chen, Y.; Guo, J. J.; Yu, N.; An,
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Amides and Arylamines. Chem.-Eur. J. 2017, 23, 9030-9033. (b) Sakamoto, R.; Kato, T.; Sakurai,
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Peroxides via a Radical Mechanism. Org. Lett. 2018, 20, 1400-1403. (c) Seihara, T.; Sakurai, S.;
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Reagents. Org. Lett. 2019, 21, 2477-2481. (d) Yang, J.-C.; Chen, L.; Yang, F.; Li, P.; Guo, L.-N.
Copper-Catalyzed Borylation of Cycloalkylsilyl Peroxides via Radical C-C Bond Cleavage. Org.
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