Radical 1,2-Alkylarylation/Acylarylation of Allylic Alcohols with Aldehydes via Neophyl Rearrangement

Article abstract of DOI:10.1021/acs.joc.7b01255

A metal-free 1,2-alkylarylation of allylic alcohols with aliphatic aldehydes through concomitant radical neophyl rearrangement was developed, providing 1,2-diphenyl-3-alkyl propanones in moderate to good yields. Moreover, when cyclopropanecarbaldehyde and aryl carbaldehydes were concerned, acylarylation was involved leading to 1,4-dicarbonyl compounds.

Full text of DOI:10.1021/acs.joc.7b01255

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Note
Radical 1,2-alkylarylation/acylarylation of allylic
alcohols with aldehydes via Neophyl Rearrangement
Changduo Pan, Qingting Ni, Yu Fu, and Jin-Tao Yu
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 18 Jun 2017
Downloaded from http://pubs.acs.org on June 18, 2017
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Radical 1,2-Alkylarylation/Acylarylation of Allylic Alcohols with
Aldehydes via Neophyl Rearrangement
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Changduo Pan,*,† Qingting Ni,† Yu Fu† and Jin-Tao Yu*,‡
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School of Chemical and Environmental Engineering, Jiangsu University of Technology, Changzhou 213001, P. R.
China
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‡
School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology,
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Changzhou University, Changzhou 213164, P. R. China
panchangduo@jsut.edu.cn; yujintao@cczu.edu.cn
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according to the
journal that you are submitting your paper to)
ABSTRACT
A metal-free 1,2-alkylarylation of allylic alcohols with aliphatic aldehydes through concomitant radical neophyl
rearrangement was developed, providing 1,2-diphenyl-3-alkyl propanones in moderate to good yields. Moreover, when
cyclopropanecarbaldehyde and aryl carbaldehydes were concerned, acylarylation was involved leading to
1,4-dicarbonyl compounds.
The difunctionalization of simple alkenes, by means of simultaneous installation of two functional groups
on the hydrocarbons, has become a powerful approach for the assembly of complex structures in organic
synthesis.1 In this field, the radical-mediated difunctionalization of alkenes has made great progress in last
decade, relying on the great advances in the chemo- and regio-selective radical reactions.2,3 Even though, the
vast majority of alkenes utilized are restricted to activated olefins.3 Therefore, radical difunctionalization of
more common, unactivated alkenes still remains as challenging tasks for chemists. The radical migration
which has been demonstrated as a promising tool in organic synthesis,4 provided a feasible approach for the
difunctionalization of unactivated alkenes.5,6,7 For example, Zhu achieved the cyanation, heteroarylation and
alkynylation of unactivated alkenes by means of intramolecular distal functional-group migrations.6 Radical
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1,2-aryl migration classified as radical neophyl rearrangement7 has been utilized for the difunctionalization of
diaryl allylic alcohols using various radical precursors to deliver a variety of α-aryl-β-alkylated ketones.8 In
this area, Ji9 and Han10 reported the alkylarylation of allylic alcohols with ethers and alkanes, respectively.
However, when alkylating reagents with unsymmetric structures were concerned, regioisomers were obtained.
Aldehydes are readily available and cheap chemicals. They can be easily transformed into relevant acyl
radicals in the acylation of organic molecules.11 On the other hand, aliphatic aldehydes were successfully
utilized as ideal linear and branched alkyl radical precursors after decarbonylation under the assistance of
proper oxidants.12 With respect to the universality and importance of aldehydes and alkenes, herein we report
a metal-free 1,2-alkylarylation/acylarylation of allylic alcohols with aldehydes through a concomitant neophyl
rearrangement.
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Table 1. Screening the Reaction Conditions.a
entry
oxidant
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
TBHP
DCP
solvent
PhF
yield (%)
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9
58
PhCF3
PhCl
PhH
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63
84(41)b(82)c(76)d
DCE
DCM
EA
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25
16
12
PhH
PhH
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o
o
a Reaction conditions: 1a (0.2 mmol), 2a (0.6 mmol), oxidant (0.6 mmol) and solvent (2 mL) at 130 C under N2. b At 100 C. c
At 130 oC. d 2a (0.4 mmol) and DTBP (0.4 mmol). DTBP = Di-tert-butyl peroxide, TBHP = tert-Butyl hydroperoxide.
Initially, the reaction of α,α-diphenyl allylic alcohol (1a) with pivalaldehyde (2a) was carried out to
optimize the reaction conditions. Delightedly, the desired product 3aa was isolated in 58% yield when DTBP
was used as the radical initiator in PhF (Table 1, entry 1). Subsequently, other solvents such as PhCF3, PhCl,
PhH, DCE, DCM and EA were investigated (Table 1, entries 2-7). The results indicated that PhH was the best
choice, providing 3aa in 84% yield (Table 1, entry 4). Other common oxidants such as TBHP and DCP were
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all inferior to DTBP (Table 1, entries 8-9). The yield of 3aa dropped obviously at a lower temperature
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(100 °C), whereas no better result was obtained at elevated temperature (130 °C) (Table 1, entry 4).
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Figure 1. Scope of the α,α-Diaryl Allylic Alcohols a
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a Reaction conditions:
1
(0.2 mmol), 2a (0.6 mmol), DTBP (0.6 mmol) in PhH (2 mL) at 120 C under N2 for 16 h. b Total yields
of two isomers, and only major products are shown. c The ratio of isomers was determined by 1H NMR analysis.
With the optimized reaction conditions established, we set out to explore the scope of this protocol as
listed in Figure 1 and 2. Firstly, we studied the substitution pattern on the aryls of α,α-diaryl allylic alcohols.
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As expected, substrates with electron donating or withdrawing group all reacted smoothly to generate the
desired 1,2-diaryl-3-tert-butyl propanones in good to moderate yields. Substrates with methyl, methoxyl,
halogen and trifluoromethyl were all well tolerated. For allylic alcohols with different aryls, two isomers were
detected in most cases, and the electron-deficient groups preferentially migrated, although in low selectivity
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(
3ka-3la, Fig. 1). In addition, pyridyl was good migrating group and provided sole product, albeit in relative
lower yield (3ja). Moreover, the good tolerance of halogen provides potential handles for more functionalized
diaryl ketones (3da-3fa 3ka-3ma). Notably, 2-methyl analogue was also good reaction partner leading to the
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,
corresponding diphenyl ketone in good yield (3na, Fig 1).
Next, the scope of aliphatic aldehydes was also tested. Apart from pivalaldehyde, other common alkyl aldehydes,
such as isobutyraldehyde (2b), 2-methylbutanal (2c), 2-methylpentanal (2d), 2-ethylbutanal (2e), 2-ethylhexanal (2f)
and cyclohexanecarbaldehyde (2g) were all good choice of secondary alkyl radical sources to produce the
corresponding 1,2-diphenyl-3-alkyl propanones in moderate to good yields (3ab-3ag, Fig. 2). Two diastereomers were
observed in the ratios of 1.1:1, if unsymmetrical carbon radicals were involved (3ac, 3ad & 3af, Fig. 2).
Figure 2. Scope of Aliphatic Aldehyde a
a Reaction conditions: 1a (0.2 mmol),
2
(0.6 mmol), DTBP (0.6 mmol) in PhH (2 mL) at 120 C under N2 for 16 h. The ratio of
o
isomers was determined by 1H NMR analysis.
To gain insights into the mechanism of this reaction, control experiments were conducted, as shown in
Scheme
1.
The
transformation
was
completely
inhibited
when
radical
scavenger
2,2,6,6-tetramethylpiperidinooxy (TEMPO) was added to the reaction (eq 1, Scheme 1). The reaction was also
effectively suppressed by BHT (2,6-di-tert-butyl-4-methylphenol) along with the adduct formed by BHT and
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tert-butyl radical detected by GC-MS (eq 2, Scheme 1). These results indicated radical intermediates were
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involved in the transformation.
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Scheme 1. Mechanism Study.
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Based on the above experimental results and former reported works,8 the mechanism of 1,2-alkylarylation
of allylic alcohols with aliphatic aldehydes was proposed in Scheme 2. Firstly, acyl radical
the assistance of DTBP and the following decarbonylation leading to tert-butyl radical . Then,
intermolecular radical addition to diaryl allylic alcohol to give alkyl radical intermediate . The subsequent
intramolecular radical addition provides the spiro[2,5]octadienyl radical intermediate D, which undergoes
A
is produced with
B
B
undergoes
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C
neophyl rearrangement to produce intermediate
cation and further deprotonation.
E. Finally, product 3 is delivered after oxidation by DTBP to a
Scheme 2. Proposed Mechanism.
Surprisingly, when cyclopropanecarbaldehyde (2h) was subjected to the reaction, no decarbonylated diaryl
ketone was detected with the isolation of γ-diketones. Obviously, acylation was involved instead of
decarbonylative alkylation, where cyclopropanecarbaldehyde served as acylating reagent (3ah-3fh, Fig. 3).
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Further studies revealed that aryl carbaldehyde also experienced the same pathway. After neophyl
rearrangement and aroylation, the corresponding triaryl γ-diketones were obtained in good yields (3ai-3am
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,
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Fig. 3). The occurrence of this phenomenon may attribute to the relative stabilities of corresponding radical
intermediates involved in above two cases.
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Figure 3. Scope of Acylation of α,α-Diaryl Allylic Alcohols.a
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a Reaction conditions: 1a (0.2 mmol),
2
(0.6 mmol), DTBP (0.6 mmol) in PhH (2 mL) at 120 C under N2 for 16 h. b 130 oC, 24 h.
In conclusion, we have developed a metal-free decarbonylative alkylarylation of allylic alcohols with
aliphatic aldehydes through concomitant radical neophyl rearrangement, providing 1,2-diaryl-3-alkyl
propanones in moderate to good yields. In addition, acylarylation occurred when cyclopropanecarbaldehyde
and aryl carbaldehydes were used, providing an alternative approach to the synthesis of triaryl γ-diketones.
EXPERIMENTAL SECTION
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General Information: All chemicals were used as received without further purification unless stated otherwise.
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NMR spectra were recorded at ambient temperature on a 400 or 500 MHz NMR spectrometer. Chemical shifts (δ) are
given in ppm relative to TMS, the coupling constants J are given in Hz. HRMS were recorded on a TOF LC/MS
equipped with electrospray ionization (ESI) probe operating in positive or negative ion mode.
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Experimental procedure for the procedure for alkylation/acylation of allylic alcohols with aldehyde: Under N2,
the mixture of aryl allylic alcohols 1 (0.2 mmol), aldehyde 2 (0.6 mmol), DTBP (0.6 mmol, 87.7 mg, 110 μL) and PhH
(2 mL) were added into the sealed tube. The reaction mixture was vigorously stirred at 120 oC for 16 h (130 oC and 24
h for aroylation of allylic alcohols). Then, the solvent was evaporated under reduced pressure and the residue was
purified by flash column chromatography on silica gel to give the products.
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4,4-Dimethyl-1,2-diphenylpentan-1-one (3aa).13 Flash column chromatography on silica gel (petroleum ether/ethyl
acetate 50/1) gave a white solid (44.7 mg, 84%). 1H NMR (CDCl3, 400 MHz): δ 7.99 (d, J = 7.7 Hz, 2H), 7.50-7.47 (m,
1H), 7.42-7.38 (m, 2H), 7.33-7.24 (m, 4H), 7.18-7.14 (m, 1H), 4.72 (d, J = 8.6 Hz, 1H), 2.63 (d, J = 13.9, 8.9 Hz, 1H),
1.58 (d, J = 13.8 Hz, 1H), 0.88 (s, 9H). 13C{1H} NMR (CDCl3, 100 MHz): δ 200.0, 141.1, 137.0, 132.8, 128.9, 128.64,
128.61, 128.2, 126.8, 49.7, 47.6, 31.2, 29.8.
4,4-Dimethyl-1,2-di-p-tolylpentan-1-one (3ba). Flash column chromatography on silica gel (petroleum ether/ethyl
acetate 50/1) gave a coloress liquid (51.1 mg, 87%). 1H NMR (CDCl3, 400 MHz): δ 7.92 (d, J = 7.5 Hz, 2H), 7.21 (d, J
= 7.5 Hz, 4H), 7.07 (d, J = 7.5 Hz, 2H), 4.68 (d, J = 8.6 Hz, 1H), 2.62 (dd, J = 13.8, 8.9 Hz, 1H), 2.36 (s, 3H), 2.27 (s,
3H), 1.55 (d, J = 13.9 Hz, 1H), 0.89 (s, 9H). 13C{1H} NMR (CDCl3, 125 MHz): δ 199.7, 143.5, 138.4, 136.3, 134.5,
129.6, 129.3, 128.8, 127.9, 49.0, 47.5, 31.2, 29.8, 21.6, 21.0. HRMS (ESI) m/z calcd for C21H27O (M+H)+ 295.2056,
found 295.2057.
1,2-Bis(4-methoxyphenyl)-4,4-dimethylpentan-1-one (3ca). Flash column chromatography on silica gel (petroleum
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ether/ethyl acetate 20/1) gave a coloress liquid (51.5 mg, 79%). H NMR (CDCl3, 400 MHz): δ 7.99 (d, J = 8.5 Hz,
2H), 7.23 (d, J = 8.3 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 6.79 (d, J = 8.2 Hz, 2H), 4.63 (dd, J = 8.7, 3.2 Hz, 1H), 3.82 (s,
3H), 3.74 (s, 3H), 2.59 (dd, J = 13.9, 8.7 Hz, 1H), 1.55 (dd, J = 13.9, 3.0 Hz, 1H), 0.87 (s, 9H). 13C{1H} NMR (CDCl3,
100 MHz): δ 198.8, 163.2, 158.3, 133.6, 130.9, 129.9, 129.1, 114.2, 113.8, 55.4, 55.2, 48.2, 47.5, 31.1, 29.9. HRMS
(ESI) m/z calcd for C21H27O3 (M+H)+ 327.1955, found 327.1958.
1,2-Bis(4-fluorophenyl)-4,4-dimethylpentan-1-one (3da). Flash column chromatography on silica gel (petroleum
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ether/ethyl acetate 50/1) gave a white solid (51.3 mg, 85%). m.p. 90-92 C. 1H NMR (CDCl3, 400 MHz): δ 8.03-8.00
(m, 2H), 7.29-7.26 (m, 2H), 7.12-7.08 (m, 2H), 6.99-6.95 (m, 2H), 4.66 (dd, J = 8.3, 2.7 Hz, 1H), 2.57 (dd, J = 13.9,
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8.7 Hz, 1H), 1.56 (dd, J = 13.9, 2.1 Hz, 1H), 0.88 (s, 9H). 13C{1H} NMR (CDCl3, 100 MHz): δ 198.4, 165.6 (d, JC-F
=
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253.4 Hz), 161.8 (d, JC-F= 244.2 Hz), 136.6 (d, JC-F= 3.2 Hz), 133.1 (d, JC-F= 2.9 Hz), 131.1 (d, JC-F= 9.3 Hz), 129.6 (d,
JC-F= 7.9 Hz), 115.9 (d, JC-F= 3.1 Hz), 115.7 (d, JC-F= 3.4 Hz), 48.7, 47.6, 31.2, 29.8. 19F NMR (470 MHz, CDCl3): δ
-105.3, -115.8. HRMS (ESI) m/z calcd for C19H21F2O (M+H)+ 303.1555, found 303.1556.
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1,2-Bis(4-chlorophenyl)-4,4-dimethylpentan-1-one (3ea). Flash column chromatography on silica gel (petroleum
ether/ethyl acetate 50/1) gave a white solid (54.8 mg, 82%). m.p. 97-99 oC. 1H NMR (CDCl3, 400 MHz): δ 7.93 (d, J =
7.8 Hz, 2H), 7.42 (d, J = 7.9 Hz, 2H), 7.28-7.24 (m, 4H), 4.65 (dd, J = 8.5, 3.0 Hz, 1H), 2.59 (dd, J = 14.0, 8.6 Hz, 1H),
1.57 (dd, J = 14.0, 2.9 Hz, 1H), 0.89 (s, 9H). 13C{1H} NMR (CDCl3, 100 MHz): δ 198.5, 139.5, 139.2, 135.0, 132.9,
129.9, 129.4, 129.2, 129.0, 49.0, 47.4, 31.2, 29.8. HRMS (ESI) m/z calcd for C19H21Cl2O (M+H)+ 335.0964, found
335.0966.
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1,2-Bis(4-bromophenyl)-4,4-dimethylpentan-1-one (3fa). Flash column chromatography on silica gel (petroleum
ether/ethyl acetate 50/1) gave a white solid (65.8 mg, 78%). m.p. 99-100 oC. 1H NMR (CDCl3, 400 MHz): δ 7.83 (d, J
= 7.6 Hz, 2H), 7.55 (d, J = 7.7 Hz, 2H), 7.39 (d, J = 7.5 Hz, 2H), 7.16 (d, J = 7.6 Hz, 2H), 4.60 (dd, J = 8.4, 2.7 Hz,
1H), 2.56 (dd, J = 13.9, 8.5 Hz, 1H), 1.54 (dd, J = 13.9, 2.5 Hz, 1H), 0.87 (s, 9H). 13C{1H} NMR (CDCl3, 125 MHz): δ
198.6, 139.7, 135.4, 132.1, 132.0, 130.1, 129.8, 128.3, 120.9, 49.0, 47.4, 31.2, 29.8. HRMS (ESI) m/z calcd for
C19H21Br2O (M+H)+ 422.9954, found 422.9959.
4,4-Dimethyl-1,2-bis(3-(trifluoromethyl)phenyl)pentan-1-one (3ga). Flash column chromatography on silica gel
(petroleum ether/ethyl acetate 50/1) gave a coloress liquid (56.3 mg, 70%). 1H NMR (CDCl3, 400 MHz): δ 8.24 (s, 1H),
8.16 (d, J = 7.8 Hz, 1H), 7.79 (d, J = 7.7 Hz, 1H), 7.61-7.57 (m, 2H), 7.52-7.39 (m, 3H), 4.76 (dd, J = 8.4, 3.3 Hz, 1H),
2.62 (dd, J = 14.0, 8.6 Hz, 1H), 1.61 (dd, J = 14.0, 3.5 Hz, 1H), 0.89 (s, 9H). 13C{1H} NMR (CDCl3, 125 MHz): δ
198.0, 141.3, 137.0, 131.6 (q, JC-F = 26.2 Hz), 131.55, 131.50, 131.3 (q, JC-F = 32.0 Hz), 129.6 (q, JC-F = 3.5 Hz), 129.5,
129.4, 125.3 (q, JC-F = 3.6 Hz), 124.8 (q, JC-F = 3.6 Hz), 124.0 (q, JC-F = 3.5 Hz), 123.9 (q, JC-F = 270.7 Hz), 123.6 (q,
JC-F = 271.0 Hz), 49.6, 47.6, 31.3, 29.8. 19F NMR (470 MHz, CDCl3): δ -62.6, -62.9. HRMS (ESI) m/z calcd for
C21H21F6O (M+H)+ 403.1491, found 403.1494.
4,4-Dimethyl-1-phenyl-2-(4-(trifluoromethyl)phenyl)pentan-1-one (3ha). Flash column chromatography on silica
o
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gel (petroleum ether/ethyl acetate 50/1) gave a white solid (48.1 mg, 72%). m.p. 94-96 C. H NMR (CDCl3, 400
MHz): δ 7.99 (d, J = 7.2 Hz, 2H), 7.55-7.51 (m, 3H), 7.46-7.42 (m, 4H), 4.80 (dd, J = 8.7, 3.4 Hz, 1H), 2.63 (dd, J =
14.0, 8.7 Hz, 1H), 1.58 (dd, J = 14.0, 3.4 Hz, 1H), 0.89 (s, 9H). 13C{1H} NMR (CDCl3, 100 MHz): δ 199.4, 145.1,
136.6, 133.2, 129.1 (q, JC-F = 32.3 Hz), 128.8, 128.6, 128.5, 125.8 (q, JC-F = 3.7 Hz), 124.1 (q, JC-F = 270.3 Hz), 49.4,
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47.6, 31.3, 29.8. 19F NMR (470 MHz, CDCl3): δ -62.5. HRMS (ESI) m/z calcd for C20H22F3O (M+H)+ 335.1617, found
335.1614.
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2-([1,1'-Biphenyl]-4-yl)-4,4-dimethyl-1-phenylpentan-1-one (3ia). Flash column chromatography on silica gel
(petroleum ether/ethyl acetate 30/1) gave a white solid (51.9 mg, 76%). m.p. 178-179 oC. 1H NMR (CDCl3, 400 MHz):
δ 8.06 (d, J = 7.2 Hz, 2H), 7.56-7.51 (m, 5H), 7.46-7.39 (m, 6H), 7.34-7.30 (d, J = 7.6 Hz, 1H), 4.80 (dd, J = 8.8, 3.1
Hz, 1H), 2.72-2.68 (dd, J = 13.9, 8.9 Hz, 1H), 1.54 (dd, J = 13.8, 3.2 Hz, 1H), 0.93 (s, 9H). 13C{1H} NMR (CDCl3, 100
MHz): δ 200.0, 140.7, 140.2, 139.7, 137.0, 132.9, 128.8, 128.7, 128.6, 127.7, 127.3, 127.0, 49.0, 47.7, 31.3, 29.9.
HRMS (ESI) m/z calcd for C25H27O (M+H)+ 343.2056, found 343.2057.
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4,4-Dimethyl-1-phenyl-2-(pyridin-4-yl)pentan-1-one (3ja). Flash column chromatography on silica gel (petroleum
ether/ethyl acetate 10/1) gave a white solid (36.3 mg, 68%). m.p. 87-89 oC. 1H NMR (CDCl3, 400 MHz): δ 8.60 (d, J =
1.9 Hz, 1H), 8.43 (d, J = 4.7 Hz, 1H), 7.99 (d, J = 7.2 Hz, 2H), 7.68-7.65 (m, 1H), 7.55-7.51 (m, 1H), 7.45-7.41 (m,
2H), 7.22-7.18 (m, 1H), 4.77 (dd, J = 8.5, 3.8 Hz, 1H), 2.58 (dd, J = 14.0, 8.5 Hz, 1H), 1.58 (dd, J = 14.0, 3.8 Hz, 1H),
0.88 (s, 9H). 13C{1H} NMR (CDCl3, 100 MHz): δ 199.4, 149.7, 148.2, 136.7, 136.5, 135.4, 133.3, 128.8, 128.5, 123.8,
47.6, 46.7, 31.3, 29.8. HRMS (ESI) m/z calcd for C18H22NO (M+H)+ 268.1696, found 268.1698.
2-(4-Fluorophenyl)-4,4-dimethyl-1-phenylpentan-1-one
(3ka)
and
1-(4-fluorophenyl)-4,4-dimethyl-2-phenylpentan-1-one (3k’a). Flash column chromatography on silica gel
(petroleum ether/ethyl acetate 50/1) gave a white solid (46.0 mg, 81%). 1H NMR (CDCl3, 400 MHz): δ 7.96-7.88 (m,
2H), 7.43-7.39 (m, 0.32H), 7.35-7.31 (m, 0.68H), 7.23-7.16 (m, 3.33H), 7.11-7.06 (m, 0.68H), 6.99-6.95 (m, 1.35H),
6.88-6.84 (m, 0.6H), 4.64 (q, 0.32H), 4.58 (q, 0.69H), 2.56-2.47 (m, 1H), 1.51-1.46 (m, 1H), 0.79 (s, 9H). 13C{1H}
NMR (CDCl3, 100 MHz): δ 199.9, 197.3, 164.2 (d, JC-F = 253.1 Hz), 160.7 (d, JC-F = 244.0 Hz), 139.9, 135.8, 135.7 (d,
JC-F = 3.2 Hz), 132.3 (d, JC-F = 3.0 Hz), 131.9, 130.2 (d, JC-F = 9.2 Hz), 128.6 (d, JC-F = 7.8 Hz), 127.9, 127.6 (d, JC-F
=
10.7 Hz), 127.0, 125.8, 114.7 (d, JC-F = 21.3 Hz), 114.6 (d, JC-F = 21.7 Hz), 48.6, 47.7, 46.6, 46.5, 30.2, 30.1, 28.8, 28.7.
19F NMR (470 MHz, CDCl3): δ -105.6, -116.0. MS (EI): 284, 269, 227.
2-(4-Chlorophenyl)-4,4-dimethyl-1-phenylpentan-1-one
(3la)
and
1-(4-chlorophenyl)-4,4-dimethyl-2-phenylpentan-1-one (3l’a). Flash column chromatography on silica gel
(petroleum ether/ethyl acetate 50/1) gave a white solid (46.2 mg, 77%). 1H NMR (CDCl3, 400 MHz): δ 7.88 (d, J = 8.6
Hz, 1.56H), 7.85 (d, J = 8.6 Hz, 0.49H), 7.44-7.39 (m, 1H), 7.34-7.27 (m, 2H), 7.21-7.07 (m, 4H), 4.62 (q, 0.76H),
4.56 (q, 0.24H), 2.56-2.47 (m, 1H), 1.51-1.45 (m, 1H), 0.79 (s, 9H). 13C{1H} NMR (CDCl3, 100 MHz): δ 198.6,
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197.6, 139.7, 138.5, 138.2, 135.7, 134.2, 131.9, 131.6, 128.9, 128.5, 127.9, 127.8, 127.6, 127.5, 127.0, 125.9, 48.7,
47.8, 46.5, 46.4, 30.2, 30.1, 28.8, 28.7. MS (EI): 300, 285, 243.
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(3ma)
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1-(4-bromophenyl)-4,4-dimethyl-2-phenylpentan-1-one (3m’a). Flash column chromatography on silica gel
(petroleum ether/ethyl acetate 50/1) gave a white solid (50.2 mg, 73%). 1H NMR (CDCl3, 400 MHz): δ 7.89 (d, J = 7.5
Hz, 1.52H), 7.77 (d, J = 8.6 Hz, 0.46H), 7.46-7.41 (m, 1.21H), 7.35-7.29 (m, 2.81H), 7.20-7.17 (m, 1H), 7.11 (d, J =
8.4 Hz, 2H), 4.61 (q, 0.76H), 4.55 (q, 0.23H), 2.56-2.47 (m, 1H), 1.51-1.45 (m, 1H), 0.79 (s, 9H). 13C{1H} NMR
(CDCl3, 100 MHz): δ 199.6, 198.9, 140.8, 140.1, 136.7, 135.7, 133.0, 132.0, 131.9, 130.1, 129.9, 129.0, 128.7, 128.6,
128.1, 127.9, 126.9, 120.8, 49.8, 49.0, 47.5, 47.4, 31.3, 31.2, 29.84, 29.81. MS (EI): 344, 329, 287.
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2,4,4-Trimethyl-1,2-diphenylpentan-1-one (3na). Flash column chromatography on silica gel (petroleum ether/ethyl
acetate 50/1) gave a coloress liquid (44.8 mg, 80%). 1H NMR (CDCl3, 400 MHz): δ 7.40-7.33 (m, 7H), 7.31-7.27 (m,
1H), 7.23-7.19 (m, 2H), 2.39 (d, J = 14.6 Hz, 1H), 2.18 (d, J = 14.6 Hz, 1H), 1.75 (s, 3H), 0.85 (s, 9H). 13C{1H} NMR
(CDCl3, 100 MHz): δ 204.8, 144.9, 137.8, 131.1, 129.4, 128.8, 127.8, 126.8, 126.6, 55.1, 51.3, 32.0, 31.8, 25.7. HRMS
(ESI) m/z calcd for C20H25O (M+H)+ 281.1900, found 281.1899.
4-Methyl-1,2-diphenylpentan-1-one (3ab).14 Flash column chromatography on silica gel (petroleum ether/ethyl
acetate 50/1) gave a coloress liquid (36.8 mg, 73%). 1H NMR (CDCl3, 400 MHz): δ 7.98 (d, J = 7.4 Hz, 2H), 7.51-7.47
(m, 2H), 7.42-7.38 (m, 2H), 7.34-7.27 (m, 4H), 7.21-7.18 (m, 2H), 4.69 (t, J = 7.2 Hz, 1H), 2.12-2.05 (m, 1H),
1.78-1.71 (m, 1H), 1.55-1.45 (m, 1H), 0.95 (d, J = 6.4 Hz, 3H), 0.90 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (CDCl3, 100
MHz): δ 200.1, 139.9, 137.0, 132.8, 128.9, 128.7, 128.6, 128.3, 126.9, 51.3, 43.1, 25.8, 22.9, 22.5.
4-Methyl-1,2-diphenylhexan-1-one (3ac). Flash column chromatography on silica gel (petroleum ether/ethyl acetate
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50/1) gave a coloress liquid (39.9 mg, 75%). H NMR (CDCl3, 400 MHz): δ 7.99 (d, J = 7.4 Hz, 2H), 7.51-7.47 (m,
1H), 7.42-7.38 (m, 2H), 7.34-7.27 (m, 4H), 7.22-7.17 (m, 1H), 4.74-4.67 (m, 1H), 2.34-2.27 (m, 0.52H), 1.94 (t, J =
6.9 Hz, 1H), 1.61-1.54 (m, 0.58H), 1.50-1.40 (m, 0.58H), 1.38-1.29 (m, 1H), 1.27-1.12 (m, 1.57H), 0.93 (d, J = 6.4 Hz,
1.47H), 0.88 (d, J = 7.2 Hz, 3H), 0.81 (t, J = 7.3 Hz, 1.61H). 13C{1H} NMR (CDCl3, 100 MHz): δ 200.2, 200.0, 140.2,
139.7, 137.1, 136.9, 132.8, 132.7, 128.9, 128.8, 128.63, 128.61, 128.54, 128.53, 128.4, 128.2, 126.9, 126.8, 51.2, 51.0,
41.4, 40.6, 32.3, 31.9, 29.7, 29.5, 19.4, 19.1, 11.1. HRMS (ESI) m/z calcd for C19H23O (M+H)+ 267.1743, found
267.1744.
4-Methyl-1,2-diphenylheptan-1-one (3ad).15 Flash column chromatography on silica gel (petroleum ether/ethyl
acetate 50/1) gave a coloress liquid (40.3 mg, 72%). 1H NMR (CDCl3, 400 MHz): δ 8.00 (d, J = 7.7 Hz, 2H), 7.53-7.49
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(m, 1H), 7.44-7.40 (m, 2H), 7.35-7.28 (m, 4H), 7.23-7.19 (m, 1H), 4.76-4.69 (m, 1H), 2.35-2.28 (m, 0.51H), 1.95 (t, J
= 6.8 Hz, 1H), 1.62-1.55 (m, 0.57H), 1.44-1.14 (m, 5H), 0.96-0.94 (m, 1.58H), 0.92-0.88 (m, 3H), 0.83-0.79 (m,
1.48H). 13C{1H} NMR (CDCl3, 100 MHz): δ 200.3, 200.1, 140.2, 139.7, 137.1, 136.9, 132.83, 132.82, 128.9, 128.8,
128.65, 128.63, 128.56, 128.55, 128.4, 128.2, 126.94, 126.91, 51.2, 51.0, 41.8, 40.9, 39.6, 39.3, 30.5, 30.1, 19.9, 19.8,
19.6, 14.4, 14.3.
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4-Ethyl-1,2-diphenylhexan-1-one (3ae).15 Flash column chromatography on silica gel (petroleum ether/ethyl acetate
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50/1) gave a coloress liquid (38.6 mg, 69%). H NMR (CDCl3, 400 MHz): δ 8.00 (d, J = 7.7 Hz, 2H), 7.53-7.49 (m,
1H), 7.44-7.40 (m, 2H), 7.36-7.28 (m, 4H), 7.23-7.19 (m, 1H), 4.71 (t, J = 7.2 Hz, 1H), 2.21-2.13 (m, 1H), 1.82-1.75
(m, 1H), 1.45-1.28 (m, 4H), 1.21-1.15 (m, 1H), 0.89 (d, J = 7.3 Hz, 3H), 0.81 (d, J = 7.4 Hz, 3H). 13C{1H} NMR
(CDCl3, 100 MHz): δ 200.2, 140.0, 137.1, 132.8, 128.9, 128.6, 128.5, 128.3, 126.9, 51.1, 37.8, 37.5, 25.3, 25.2, 10.52,
10.50.
4-Ethyl-1,2-diphenyloctan-1-one (3af). Flash column chromatography on silica gel (petroleum ether/ethyl acetate
50/1) gave a coloress liquid (43.1mg, 70%). 1H NMR (CDCl3, 400 MHz): δ 7.99 (d, J = 7.8 Hz, 2H), 7.53-7.49 (m, 1H),
7.44-7.40 (m, 2H), 7.35-7.28 (m, 4H), 7.23-7.19 (m, 1H), 4.71 (d, J = 7.2 Hz, 1H), 2.21-2.12 (m, 1H), 1.83 (m, 1H),
1.43-1.20 (m, 9H), 0.92-0.90 (m, 1.42H), 0.89-0.87 (m, 1.57H), 0.86-0.85 (m, 1.45H), 0.82-0.79 (m, 1.56H). 13C{1H}
NMR (CDCl3, 125 MHz): δ 200.2, 200.1, 140.1, 139.9, 137.1, 137.0, 132.8, 128.8, 128.6, 128.5, 128.3, 128.2, 126.9,
51.1, 51.0, 38.0, 37.9, 36.4, 36.3, 32.7, 28.5, 28.4, 25.8, 23.1, 23.0, 14.2, 14.1, 10.5, 10.4. HRMS (ESI) m/z calcd for
C22H29O (M+H)+ 309.2213, found 309.2216.
3-Cyclohexyl-1,2-diphenylpropan-1-one (3ag).10 Flash column chromatography on silica gel (petroleum ether/ethyl
acetate 50/1) gave a coloress liquid (46.7mg, 80%). 1H NMR (CDCl3, 400 MHz): δ 7.99 (d, J = 7.2 Hz, 2H), 7.53-7.49
(m, 1H), 7.44-7.40 (m, 2H), 7.35-7.28 (m, 4H), 7.24-7.19 (m, 1H), 4.74 (t, J = 7.3 Hz, 1H), 2.18-2.10 (m, 1H),
1.87-1.83 (m, 1H), 1.76-1.63 (m, 5H), 1.24-1.08 (m, 4H), 1.01-0.89 (m, 2H). 13C{1H} NMR (CDCl3, 100 MHz): δ
200.1, 140.0, 136.9, 132.8, 128.9, 128.7, 128.6, 128.3, 126.9, 50.5, 41.7, 35.3, 33.6, 33.3, 26.5, 26.2, 26.1
4-Cyclopropyl-1,2-diphenylbutane-1,4-dione (3ah). Flash column chromatography on silica gel (petroleum
ether/ethyl acetate 10/1) gave a coloress liquid (47.3mg, 85%). 1H NMR (CDCl3, 400 MHz): δ 7.97 (d, J = 7.8 Hz, 2H),
7.48-7.44 (m, 1H), 7.38-7.35 (m, 2H), 7.29-7.28 (m, 4H), 7.21-7.19 (m, 1H), 5.13 (dd, J = 10.0, 3.6 Hz, 1H), 3.76 (dd,
J = 18.0, 10.1 Hz, 1H), 2.92 (dd, J = 18.0, 3.6 Hz, 1H), 1.99-1.93 (m, 1H), 1.06-0.98 (m, 2H), 0.93-0.82 (m, 2H).
13C{1H} NMR (CDCl3, 100 MHz): δ 208.9, 198.9, 138.6, 136.4, 132.9, 129.1, 128.9, 128.5, 128.2, 127.3, 48.5, 47.8,
20.7, 10.9, 10.8. HRMS (ESI) m/z calcd for C19H19O2 (M+H)+ 279.1380, found 279.1381.
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4-Cyclopropyl-1,2-di-p-tolylbutane-1,4-dione (3bh). Flash column chromatography on silica gel (petroleum
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ether/ethyl acetate 10/1) gave a coloress liquid (52.6 mg, 86%). H NMR (CDCl3, 400 MHz): δ 7.97 (d, J = 8.2 Hz,
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2H), 7.18-7.15 (m, 4H), 7.08 (d, J = 7.9 Hz, 2H), 5.08 (dd, J = 10.0, 4.0 Hz, 1H), 3.72 (dd, J = 17.9, 9.9 Hz, 1H), 2.88
(dd, J = 17.9, 4.0 Hz, 1H), 2.32 (s, 3H), 2.27 (s, 3H), 1.98-1.92 (m, 1H), 1.05-0.98 (m, 2H), 0.92-0.81 (m, 2H). 13C{1H}
NMR (CDCl3, 100 MHz): δ 209.0, 198.6, 143.5, 136.9, 135.8, 133.9, 129.8, 129.2, 129.0, 127.9, 47.9, 47.7, 21.6, 21.0,
20.7, 10.8, 10.7. HRMS (ESI) m/z calcd for C21H23O2 (M+H)+ 307.1693, found 307.1696.
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4-Cyclopropyl-1,2-bis(4-fluorophenyl)butane-1,4-dione (3dh). Flash column chromatography on silica gel
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(petroleum ether/ethyl acetate 10/1) gave a coloress liquid (50.2 mg, 80%). H NMR (CDCl3, 400 MHz): δ 7.99-7.96
(m, 2H), 7.26-7.22 (m, 2H), 7.07-7.02 (m, 2H), 6.99-6.95 (m, 2H), 5.06 (dd, J = 9.9, 4.0 Hz, 1H), 3.72 (dd, J = 18.0,
9.9 Hz, 1H), 2.91 (dd, J = 18.0, 4.0 Hz, 1H), 1.97-1.93 (m, 1H), 1.05-0.97 (m, 2H), 0.94-0.83 (m, 2H). 13C{1H} NMR
(CDCl3, 100 MHz): δ 208.7, 197.3, 165.6 (d, JC-F = 253.3 Hz), 162.0 (d, JC-F = 245.0 Hz), 134.0 (d, JC-F = 3.2 Hz),
132.6 (d, JC-F = 3.0 Hz), 131.4 (d, JC-F = 9.3 Hz), 129.6 (d, JC-F = 8.1 Hz), 134.0 (d, JC-F = 3.2 Hz), 116.1 (d, JC-F = 21.3
Hz), 115.6 (d, JC-F = 21.8 Hz), 47.8, 47.5, 20.6, 10.9, 10.8. 19F NMR (470 MHz, CDCl3): δ -105.2, -114.8. HRMS (ESI)
m/z calcd for C19H17F2O2 (M+H)+ 315.1191, found 315.1194.
1,2-Bis(4-chlorophenyl)-4-cyclopropylbutane-1,4-dione (3eh). Flash column chromatography on silica gel
(petroleum ether/ethyl acetate 10/1) gave a coloress liquid (53.9 mg, 78%). 1H NMR (CDCl3, 400 MHz): δ 7.91 (d, J =
8.6 Hz, 2H), 7.37 (d, J = 8.6 Hz, 2H), 7.28-7.25 (m, 2H), 7.21 (d, J = 8.5 Hz, 2H), 5.05 (dd, J = 10.0, 4.0 Hz, 1H), 3.74
(dd, J = 18.1, 10.0 Hz, 1H), 2.93 (dd, J = 18.0, 4.0 Hz, 1H), 2.00-1.94 (m, 1H), 1.08-0.99 (m, 2H), 0.96-0.86 (m, 2H).
13C{1H} NMR (CDCl3, 100 MHz): δ 208.6, 197.5, 139.5, 136.6, 134.5, 133.4, 130.2, 129.44, 129.41, 128.9, 47.7, 47.6,
20.6, 11.1, 11.0. HRMS (ESI) m/z calcd for C19H17Cl2O2 (M+H)+ 347.0600, found 347.0602.
1,2-Bis(4-bromophenyl)-4-cyclopropylbutane-1,4-dione (3fh). Flash column chromatography on silica gel
(petroleum ether/ethyl acetate 10/1) gave a coloress liquid (70.3 mg, 81%). 1H NMR (CDCl3, 400 MHz): δ 7.89 (d, J =
8.6 Hz, 2H), 7.51 (d, J = 8.6 Hz, 2H), 7.41 (d, J = 8.5 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 5.01 (dd, J = 10.0, 4.0 Hz, 1H),
3.74 (dd, J = 18.0, 10.0 Hz, 1H), 2.93 (dd, J = 18.0, 4.0 Hz, 1H), 1.98-1.92 (m, 1H), 1.03-0.97 (m, 2H), 0.94-0.84 (m,
2H). 13C{1H} NMR (CDCl3, 100 MHz): δ 208.5, 197.7, 137.4, 134.9, 132.4, 131.9, 130.3, 129.8, 128.3, 121.6, 47.8,
47.6, 20.6, 11.1, 11.0. HRMS (ESI) m/z calcd for C19H17Br2O2 (M+H)+ 434.9590, found 434.9597.
1,2,4-Triphenylbutane-1,4-dione (3ai).16 Flash column chromatography on silica gel (petroleum ether/ethyl acetate
10/1) gave a coloress liquid (47.7 mg, 76%). 1H NMR (CDCl3, 400 MHz): δ 8.07 (d, J = 8.0 Hz, 2H), 8.01 (d, J = 8.5
Hz, 2H), 7.59-7.56 (m, 1H), 7.53-7.32 (m, 9H), 7.28-7.24 (m, 1H), 5.36 (dd, J = 10.1, 3.5 Hz, 1H), 4.25 (dd, J = 18.0,
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10.1 Hz, 1H), 3.34 (dd, J = 10.1, 3.7, Hz 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 198.9, 198.1, 138.7, 136.5, 133.3,
132.9, 129.3, 128.9, 128.6, 128.5, 128.3, 128.2, 127.4, 48.7, 43.9.
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1,2-Diphenyl-4-(p-tolyl)butane-1,4-dione (3aj). Flash column chromatography on silica gel (petroleum ether/ethyl
acetate 10/1) gave a coloress liquid (52.5 mg, 80%). 1H NMR (CDCl3, 400 MHz): δ 8.07 (d, J = 8.6 Hz, 2H), 7.90 (d, J
= 8.6 Hz, 2H), 7.53-7.49 (m, 1H), 7.44-7.38 (m, 4H), 7.35-7.31 (m, 2H), 7.28-7.23 (m, 3H), 5.35 (dd, J = 10.1, 3.6 Hz,
1H), 4.22 (dd, J = 17.9, 10.1 Hz, 1H), 3.32 (dd, J = 17.9, 3.6 Hz, 1H), 2.42 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz):
δ 199.0, 197.7, 144.1, 138.7, 136.5, 134.0, 132.9, 129.3, 129.2, 128.9, 128.5, 128.3, 128.2, 127.4, 48.7, 43.8, 21.7.
HRMS (ESI) m/z calcd for C23H21O2 (M+H)+ 329.1536, found 329.1538.
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4-(4-(tert-Butyl)phenyl)-1,2-diphenylbutane-1,4-dione (3ak). Flash column chromatography on silica gel (petroleum
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ether/ethyl acetate 10/1) gave a coloress liquid (57.7 mg, 78%). H NMR (CDCl3, 400 MHz): δ 8.08 (d, J = 8.6 Hz,
2H), 7.97 (d, J = 8.5 Hz, 2H), 7.53-7.49 (m, 3H), 7.45-7.40 (m, 4H), 7.36-7.32 (m, 2H), 7.28-7.24 (m, 1H), 5.39 (dd, J
= 10.0, 3.7 Hz, 1H), 4.25 (dd, J = 17.9, 10.0 Hz, 1H), 3.34 (dd, J = 17.9, 3.7 Hz, 1H), 1.37 (s, 9H). 13C{1H} NMR
(CDCl3, 100 MHz): δ 199.0, 197.8, 157.0, 138.8, 136.5, 133.9, 132.9, 129.2, 128.9, 128.5, 128.3, 128.2, 127.4, 125.6,
48.7, 43.8,35.2, 31.1. HRMS (ESI) m/z calcd for C26H27O2 (M+H)+ 371.2006, found 371.2003.
4-(4-Chlorophenyl)-1,2-diphenylbutane-1,4-dione (3al). Flash column chromatography on silica gel (petroleum
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ether/ethyl acetate 10/1) gave a coloress liquid (50.8 mg, 76%). H NMR (CDCl3, 400 MHz): δ 8.05 (d, J = 8.4 Hz,
2H), 7.94 (d, J = 8.6 Hz, 2H), 7.53-7.49 (m, 1H), 7.45-7.31 (m, 8H), 7.28-7.23 (m, 1H), 5.34 (dd, J = 10.1, 3.6 Hz, 1H),
4.20 (dd, J = 18.0, 10.1 Hz, 1H), 3.28 (dd, J = 18.0, 3.6 Hz, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 198.8, 196.9,
139.7, 138.5, 136.3, 134.8, 133.0, 129.6, 129.3, 128.97, 128.94, 128.6, 128.2, 127.5, 48.8, 43.8. HRMS (ESI) m/z calcd
for C22H18ClO2 (M+H)+ 349.0990, found 349.0991.
4-(4-Bromophenyl)-1,2-diphenylbutane-1,4-dione (3am). Flash column chromatography on silica gel (petroleum
1
ether/ethyl acetate 10/1) gave a coloress liquid (55.7 mg, 71%). H NMR (CDCl3, 400 MHz): δ 8.05 (d, J = 8.6 Hz,
2H), 7.86 (d, J = 8.6 Hz, 2H), 7.60 (d, J = 8.6 Hz, 2H), 7.53-7.49 (m, 1H), 7.44-7.31 (m, 6H), 7.28-7.23 (m, 1H), 5.35
(dd, J = 10.1, 3.6 Hz, 1H), 4.19 (dd, J = 18.0, 10.1 Hz, 1H), 3.27 (dd, J = 10.1, 3.6 Hz, 1H). 13C{1H} NMR (CDCl3,
100 MHz): δ 198.8, 197.1, 138.5, 136.3, 135.2, 133.0, 131.9, 129.7, 129.3, 128.9, 128.6, 128.5, 128.2, 127.5, 48.8,
43.8. HRMS (ESI) m/z calcd for C22H18BrO2 (M+H)+ 393.0485, found 393.0490.
ACKNOWLEDGMENT
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We thank the National Natural Science Foundation of China (21602086 and 21672028), the Natural Science
Foundation for Colleges and Universities of Jiangsu Province (16KJB150002) and Jiangsu Key Laboratory of
Advanced Catalytic Materials & Technology (BM2012110) for financial supports.
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compounds 3da, 3ga, 3ha, 3ka and 3dh. This material is available free of charge via the Internet at http://pubs.acs.org.
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