Synthesis of Polyaryl-Substituted Olefins via a Rh(III)-Catalyzed One-Pot Reaction Using N-Phenoxyacetamides, Ketones, and Hydrazines

Article abstract of DOI:10.1021/acs.joc.8b00108

A Rh(III)-catalyzed one-pot reaction of N-phenoxyacetamides, ketones, and hydrazines for a facile access to disubstituted and trisubstituted ethylenes is reported. In this method, various ketones are transformed into donor-donor diazo compounds, which engage in insertion with N-phenoxyacetamides, following β-H elimination under Rh(III) catalysis to generate (E)-polyaryl-substituted olefins. This chemistry features simple starting materials, mild reaction conditions, and good functional group tolerance.

Full text of DOI:10.1021/acs.joc.8b00108

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Article
Synthesis of Polyaryl Substituted Olefins via Rh(III)-Catalyzed One-
Pot Reaction Using N-phenoxyacetamides, Ketones, and Hydrazines
Yan Zhang, Yu He, Lisha Li, Mingming Ji, Xiao-Zong Li, and Gangguo Zhu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00108 • Publication Date (Web): 07 Feb 2018
Downloaded from http://pubs.acs.org on February 12, 2018
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Synthesis of Polyaryl Substituted Olefins via Rh(III)-Catalyzed One-Pot Reaction Using
N-phenoxyacetamides, Ketones, and Hydrazines
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Yan Zhang,* Yu He, Lisha Li, Mingming Ji, Xiao-Zong Li and Gangguo Zhu
Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of
Chemistry, Zhejiang Normal University, Jinhua 321004, China
zhangyan001@zjnu.edu.cn
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A Rh(III)-catalyzed one-pot reaction of N-phenoxyacetamides, ketones, and hydrazines for facile
access to di- and trisubstituted ethylenes is reported. In this method, various ketones are transformed
into donor-donor diazo compounds, which engage in insertion with N-phenoxyacetamides, following
β-H elimination under Rh(III) catalysis to generate (E)-polyaryl substituted olefins. This chemistry
features simple starting materials, mild reaction conditions and good functional group tolerance.
INTRODUCTION
Di- and triarylsubstituted ethylenes are privilege scaffolds, which frequently exist in biologically
active compounds and aggregation-induced emission (AIE) molecules.1 Representative examples are
depicted in Figure 1. Tamoxifen, a selective estrogen receptor modulator, is used for the treatment of
breast cancer;2 Clomifene has been used for the induction of ovulation in anovulatory women and for
the treatment of oligospermia in men;3 Bexarotene is another anticancer agent which is used as a
treatment for cutaneous T cell lymphoma;4 Acrivastine and Lumefantrine are antiallergic agent and
antimalarial drug, respectively;5 Triphenylethylene derivative (TrPECl2) has been reported as a new
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type AIE molecule.6 Therefore, the reaction to access these types of polyaryl substituted ethylenes
from simple materials in mild conditions is highly desired.
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Figure 1. Selected examples of drugs and AIE molecules containing di- or triarylsubstituted
olefins.
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The well established synthetic approaches to form polyarylsubstituted olefins include Horner-Wittig
7 and Suzuki-Miyaura reactions (Scheme 1a),8 as well as various metal-catalyzed C-H hydroarylations
of alkynes.9 Obviously, direct C-H functionalization protocol is more attractive than others, as
prefunctionalized substrates are not necessary (Scheme 1b). However, the stereoselectivity issue
constantly exists when using the unsymmetrical diaryl acetylenes for the synthesis of triarylsubstituted
ethylenes.
Scheme 1. Methods for the synthesis of polyarylsubstituted ethylenes.
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Rh(III)-catalyzed chelation-assisted (especially by oxidizing directing groups10) have been well
developed by Miura, Fagnou, Glorius, Li, Wang, Rovis, etc. over the past seven years.11, 12 Among
these, [4+n] cyclization was usually observed when a protic X-H (X = N or O) bond is present, and
this anionic X atom acts as a sufficient directing group. However, there is seldom report on selective
formation of olefins by β-H elimination when facing reductive elimination as the other possible route
to form cyclocompounds.13 Meanwhile, the group of Wang has developed an efficient
Rh(III)-catalyzed synthesis of ortho-alkenyl phenols from N-Tosylhydrazones or diazoesters. This
transformation needs relatively harsh conditions or must be limited to the stable donor/acceptor diazo
compounds.14 Herein we report a facile synthesis of polyarylsubstituted olefins via a Rh(III)-catalyzed
one-pot reaction of N-phenoxyacetamides and ketones using MnO2 as oxidant.15 This process
demonstrates many advantages: reaction proceeds under mild conditions, starting from simpler
materials and products featuring broader substrate scope (Scheme 1c).
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RESULTS AND DISCUSSION
Table 1. Optimization of the reaction conditions.a
Entry
Additive
Solvent
Yield (%) b
1
2
CsOAc (1 eq)
CsOAc (1 eq)
CsOAc (1 eq)
CsOAc (1 eq)
KOAc (1 eq)
NaOAc (1 eq)
Na2CO3 (1 eq)
CsOAc (1 eq)
CsOAc (0.5 eq)
CsOAc (1 eq)
1,4-dioxane
MeOH
DCM
THF
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25
49
69
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60
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70
72
3
4
5
THF
6
THF
7
THF
8 c
THF
9
10d
THF
THF
a Reaction Conditions: 1a (0.2 mmol), 2a (0.24 mmol), solvent (2.0 mL), 3 (0.26 mmol), [Cp*RhCl2]2 (2
b
c
d
mol%) and additive, RT, 8 h. Yields of isolated products. 8.0 eq MnO2. Replacing 2a and 3 with
acetophenone(2-phenyl)hydrazone.
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Phenol derivatives are of great importance, thus, we selected a phenol derivatives containing an
N-O bond as oxidizing directing group. We commenced our study by investigating the one-pot
reaction of N-phenoxyacetamide 1a, 2-phenylacetophenone 2a, and hydrazone 3 with catalytic
amount of [Cp*RhCl2]2 and AcOH (accelerate the formation of the hydrazine intermediate) in
1,4-dioxane at room temprature. To our delight, we found the formation of triarylsubstituted ethylene
4a in 34% yield (Table 1, entry 1). The next survey of solvents (entries 2-4) showed that THF was
optimal to furnish the product in 69% yield (entry 4). Replacement of CsOAc to other additives
resulted in a lower yield (entries 5-7). An attempt to lower MnO2 loading failed as a decreased yield
(entry 8), while lower CsOAc loading to 0.5 equiv without loss of the yield (entry 9). Direct use of
(1,2-diphenylethylidene)hydrazine would deliver the product in a slightly higher yield (entry 10).
Table 2. Substrate scope of N-phenoxyacetamidesa
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a Isolated yields are given. Reaction conditions: 3 (0.26 mmol), 2 (0.24 mmol), HOAc (0.04 mmol), THF (2
mL), 2-3 h, 60 oC; then 1 (0.2 mmol), MnO2 (12 eq), CsOAc (0.1 mmol), [Cp*RhCl2]2 (2 mol%), RT, 5-10
h. Isolated yields.
With the optimized conditions in hand, we evaluated the generality of this reaction. The scope of
the N-phenoxyacetamides was first examined. As depicted in Table 2, various N-phenoxyacetamides
with ortho, meta or para substituents on the aromatic ring were reacted smoothly with
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2-phenylacetophenone 2a, affording the desired triarylsubstituted ethylenes in good yields (4a-4d and
4i). Additionally, good regioselectivity favouring activation of the less hindered C-H bond was
observed in product 4b. Electron-deficient functional groups like fluoro, chloro, bromo and ester were
also tolerated in this one-pot transformation in relatively lower yields (4e-4h).
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Table 3. Substrate Scope of aromatic ketones.a
a
Isolated yields are given. Reaction conditions: 3 (0.26 mmol), 2 (0.24 mmol), HOAc (0.04 mmol), THF (2 mL),
2-3 h, 60 oC; then 1 (0.2 mmol), MnO2 (12 eq), CsOAc (0.1 mmol), [Cp*RhCl2]2 (2 mol%), RT, 5-10 h. Isolated yields
b The value in parenthese refers to 2 mmol scale. c PMP = para-methoxyphenyl.
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Next, a variety of aryl ketones were utilized to construct diverse polysubstituted olefins (Table 3).
Many important functional groups like alcohols, ester (on the alkyl), ether, trifluoromethyl, terminal
alkenes and internal alkenes could react smoothly with 1 to afford the corresponding olefins in
moderate to good yields (5l-5r). In addition, ketones bearing naphthalene and heterocyclic groups (5d,
5e, and 5j) also reacted well. Notably, in the case of all the meta-substituted substrates, 5o-5q, and 5j
were isolated as the sole products, which suggesting that good regioselectivity favouring activation of
the less hindered C-H bonds. Moreover, using 1,6-diphenyl-1,6-hexanedinone (2t) as substrate, the
expected symmetrical product 5s was isolated after reaction with 2 equiv N-phenoxyacetamide 1b.
However, we could not get 5g when 2h was used as the starting material. For one thing, it’s hard to
form of the hydrazine intermediate for the ketones substituted with two alkyls at the α-position of
carbonyl in this recation condition; What’s more, β-H elimination may also become hard due to the
additional alkyl, as we failed by using hydrazine 2h’ as starting material which is prepared from other
reaction conditions.
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We also have tried to use other oxidizing directing group 1’ to react with this type of hydrazine 2h’
(Scheme 2).16 Luckily, the expected β-H elimination product 7 was observed, showing that the
reaction pathway would be changed by choice of different directing groups.
Scheme
2
Rh(III)-catalyzed C-H activation of N-pivaloyloxy benzamides with
(2-methyl-1-phenylpropylidene)hydrazine 2h’.
Derivation of the products was also performed (Scheme 3). Since the olefin and the phenol units in
these products offer additional synthetic opportunities. For example, either diarylsubstituted olefin 5k
or triarylsubstituted ethylene 4f could convert to 2, 3-disubstituted benzofurans 8 and 9 at high
temperature using Ag2O as oxidant.17 Saturated biphenyl molecule 10 could be prepared by reduction
in the presence of Pd/C (10%) with excellent yield.
Scheme 3 Derivatization of compound 4f and 5k.
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Considering that this conversion process includes a C-H activation step, a kinetic isotope effect
(KIE) study was conducted to probe the mechanism. The KIE was determined to be 2.8 under the
standand reaction conditions, thus, indicating that C-H bond cleavage occurs during the
rate-determining step (Scheme 4).
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Scheme 4 The study of the kinetic isotope effects.
Scheme 5 Proposed Catalytic Cycle.
A plausible mechanism for this C-H activation/β-H elimination process is proposed in Scheme 5,
which is similar to those reported in the literature.12i, 14 First, the active catalyst [Cp*Rh(OAc)2] is
generated from [Cp*RhCl2]2 and CsOAc through anion exchange, and a carboxylate-assisted C-H
activation of N-phenoxyacetamide 1a occurs via a concerted metalation/deprotonation (CMD)
pathway to form rhodacycle A. Then a dediazoniation occurs between A and B, which is generated in
situ from the ketones, hydrazine, and MnO2 to form intermediate C. The subsequent 1,1-migratory
insertion of C generates D.18 β-H elimination and oxidative addition of N-O bond to Rh(I) gives
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intermediate E. Finally, protonation of E to furnish the polysubstituted olefin product 4 or 5 with the
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regeneration of Rh(III) catalyst.
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CONCLUSION
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In summary, we have developed a unique Rh(III)-catalyed one-pot reaction of N-phenoxyacetamide,
ketones, and hydrazines for efficient synthesis of stereodefined di- and triarylsubstituted olefins. This
transformation tolerates a wide variety of ketones and generates the desired polyarylsubstituted olefins
in moderate to good yields. A kinetic isotope effect study was conducted and a plausible mechanism is
proposed.
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EXPERIMENTAL SECTION
General Information
1H, 13C and 19F NMR spectra were recorded on 600 or 400 spectrometer using CDCl3 as the solvent.
Chemical shifts were referenced relative to residual solvent signal (CDCl3: 1H NMR: δ 7.26 ppm, 13
C
NMR: δ 77.16 ppm). The following abbreviations are used to describe peak patterns where
appropriate: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet. Coupling
constants (J) are reported in Hertz (Hz). HRMS were performed on AB Sciex LC 30A-Triple TOF
4600 apparatus (ESI). Melting points were measured with micro melting point apparatus.
General Experimental Procedure for the Synthesis of 4 and 5
Typical procedure for synthesis of di- or triarylsubstituted ethylenes: Ketone 2 (0.24 mmol),
hydrazine hydrate 3 (21
μ
μL, 0.04 mmol) were added to
a 5 mL round-bottomed flask and stirred for 2-3 h at 60 oC (monitored by TLC). Then
N-phenoxyacetamides 1 (0.2 mmol), [Cp*RhCl2]2 (2 mol%, 2.4 mg), CsOAc (20 mg, 0.5 equiv) were
added to this vial and the solution was cooled to 0-5 oC. Afterwards, activated MnO2 (210 mg, 12
equiv.) was added in one portion and the solution was kept at RT. After completion (8h - 10 h), it was
diluted with CH2Cl2 and transferred to a round bottom flask. Silica was added to the flask and
volatiles were evaporated under vacuum. The purification was performed by flash column
chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1:10) as eluent to give the
product 4 or 5.
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1
3-methyl-3-phenylisoindolin-1-one (4a): 40 mg, 70% yield; Oil; H NMR (CDCl3, 600 MHz), δ:
7.40-7.31 (m, 5H), 7.22-7.14 (m, 6H), 7.11 (dd, J1 = 10.2 Hz, J2 = 1.8 Hz, 1H), 6.91 (s, 1H), 6.86 (d, J
= 8.4 Hz 1H), 4.98 (s, 1H), 2.27 (s, 3H); 13C NMR (CDCl3, 150 MHz), δ: 150.6, 142.1, 136.7, 136.4,
131.2, 130.5, 130.41, 130.38, 129.1, 128.7, 128.5, 128.2, 128.0, 127.2, 125.8, 115.9, 20.7; HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C21H19O 287.1431; found 287.1426.
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1
(E)-2-(1,2-diphenylvinyl)-5-methylphenol (4b): 38.3 mg, 67% yield; Oil; H NMR (CDCl3, 600
MHz), δ: 7.40-7.32 (m, 5H), 7.21-7.16 (m, 6H), 6.98 (d, J = 8.4 Hz, 1H), 6.80-6.79 (m, 2H), 5.06 (s,
1H), 2.38 (s, 3H); 13C NMR (CDCl3, 150 MHz), δ: 152.8, 142.1, 140.1, 136.7, 136.5, 130.9, 130.4,
129.1, 128.7, 128.5, 128.2, 127.9, 127.3, 123.1, 122.2, 116.7, 21.5; HRMS (ESI-TOF) m/z: [M+H]+
calcd for C21H19O 287.1431; found 287.1430.
1
(E)-2-(1,2-diphenylvinyl)-6-methylphenol (4c): 31.4 mg, 55% yield; Oil; H NMR (CDCl3, 600
MHz), δ: 7.39-7.31 (m, 5H), 7.20-7.11 (m, 7H), 6.94 (dd, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 6.87 (t, J = 7.2
Hz, 1H), 5.14 (s, 1H), 2.25 (s, 3H); 13C NMR (CDCl3, 150 MHz), δ: 151.1, 141.9, 136.8, 136.4, 131.0,
130.7, 129.1, 128.7, 128.52, 128.49, 128.3, 127.9, 127.2, 125.6, 125.1, 120.8, 16.3; HRMS (ESI-TOF)
m/z: [M+H]+ calcd for C21H19O 287.1431; found 287.1430.
1
(E)-2-(1,2-diphenylvinyl)phenol (4d): 34.2 mg, 63% yield; Oil; H NMR (CDCl3, 600 MHz), δ:
7.39-7.30 (m, 6H), 7.21-7.18 (m, 4H), 7.13 - 7.09 (m, 3H), 6.96 (t, J = 7.2 Hz, 2H), 5.09 (s, 1H); 13
C
NMR (CDCl3, 150 MHz), δ: 153.0, 141.8, 136.5, 136.3, 131.2, 130.7, 129.8, 129.1, 128.8, 128.5,
128.3, 128.0, 127.2, 126.1, 121.3, 116.1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C20H17O 273.1274;
found 273.1273.
1
(E)-2-(1,2-diphenylvinyl)-4-fluorophenol (4e): 26.1 mg, 45% yield; Oil; H NMR (CDCl3, 600
MHz), δ: 7.38-7.35 (m, 5H), 7.24-7.22 (m, 4H), 7.15(q, J = 3.0 Hz, 2H), 7.03-7.00(m, 1H), 6.91 (q, J
= 4.8 Hz, 1H), 6.85 (dd, J1 = 6.0 Hz, J2 = 3.0 Hz, 1H), 5.03 (s, 1H); 13C NMR (CDCl3, 150 MHz), δ:
157.3 (d, J = 239 Hz), 149.10, 149.09, 141.2, 135.9, 135.6, 131.1, 129.1, 128.8, 128.6, 128.5, 128.3,
127.1, 117.2 (d, J = 12 Hz), 117.1 (d, J = 3 Hz), 116.4 (d, J = 22.5 Hz); HRMS (ESI-TOF) m/z:
[M-H]- calcd for C20H14FO 289.1034; found 289.1023.
1
(E)-4-chloro-2-(1,2-diphenylvinyl)phenol (4f): 37.3 mg, 61% yield; Oil; H NMR (CDCl3, 600
MHz), δ: 7.38-7.35 (m, 5H), 7.27-7.23 (m, 5H), 7.16-7.12 (m, 3H), 6.90 (dd, J1 = 8.4 Hz, J2 = 1.2 Hz,
1H), 5.18 (s, 1H); 13C NMR (CDCl3, 150 MHz), δ: 151.6, 141.2, 135.9, 135.3, 131.2, 130.6, 129.7,
129.1, 128.8, 128.7, 128.5, 128.3, 127.7, 127.2, 125.9, 117.5; HRMS (ESI-TOF) m/z: [M-H]- calcd for
C20H14ClO 305.0739; found 305.0729.
1
(E)-4-bromo-2-(1,2-diphenylvinyl)phenol (4g): 36.4 mg, 70% yield; Oil; H NMR (CDCl3, 600
MHz), δ: 7.40-7.35 (m, 6H), 7.24-7.21 (m, 5H), 7.15-7.12 (m, 2H), 6.84 (d, J = 9.0 Hz, 1H), 5.15 (s,
1H); 13C NMR (CDCl3, 150 MHz), δ: 152.2, 141.3, 135.8, 135.2, 133.4, 132.7, 131.3, 129.1, 128.9,
128.7, 128.6, 128.4, 128.3, 127.2, 118.0, 113; HRMS (ESI-TOF) m/z: [M-H]- calcd for C20H14BrO
349.0234; found 349.0228.
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Methyl (E)-3-(1,2-diphenylvinyl)-4-hydroxybenzoate (4h): 33 mg, 50% yield; Oil; 1H NMR
(CDCl3, 600 MHz), δ: 8.01 (dd, J1 = 10.8 Hz, J2 = 2.4 Hz, 1H), 7.87 (d, J = 2.4 Hz, 1H), 7.37-7.33 (m,
6H), 7.19 (t, J = 3.0 Hz, 3H), 7.12-7.10 (m, 2H), 6.98 (d, J = 9.0 Hz, 1H), 5.90 (s, 1H), 3.84 (s, 3H);
13C NMR (CDCl3, 150 MHz), δ: 166.9, 157.1, 141.4, 136.0, 135.4, 133.3, 131.7, 131.2, 129.0, 128.8,
128.6, 128.4, 128.2, 127.1, 126.3, 123.2, 116.1, 52.0; HRMS (ESI-TOF) m/z: [M+H]+ calcd for
C22H19O3 331.1329; found 331.1325.
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(E)-2-(1,2-diphenylvinyl)-3,5-dimethylphenol (4i): 39 mg, 65% yield; Oil; H NMR (CDCl3, 600
MHz), δ: 7.40-7.39 (m, 2H), 7.35-7.30 (m, 4H), 7.21-7.18 (m, 3H), 7.12 (dd, J1 = 7.2 Hz, J2 = 2.4 Hz,
2H), 6.71 (s, 1H), 6.67 (s, 1H), 5.07 (s, 1H), 2.36 (s, 3H), 1.99 (s, 3H); 13C NMR (CDCl3, 150 MHz),
δ: 152.4, 141.0, 139.3, 137.6, 136.4, 135.2, 131.5, 128.84, 128.76, 128.6, 128.1, 128.0, 126.4, 123.7,
122.7, 113.7, 21.5, 19.9; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C22H21O 301.1587; found
301.1572.
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(E)-4-methyl-2-(1-phenyl-2-(p-tolyl)vinyl)phenol (5a): 44.4 mg, 74% yield; Oil; H NMR (CDCl3,
600 MHz), δ: 7.40-7.31 (m, 5H), 7.17 (s, 1H), 7.11 (d, J = 8.4 Hz, 1H), 7.04 (q, J = 8.4 Hz, 4H), 6.92
(s, 1H), 6.88 (d, J = 8.4 Hz, 1H), 5.04 (s, 1H), 2.30 (s, 3H), 2.28 (s, 3H); 13C NMR (CDCl3, 150 MHz),
δ: 150.6, 142.2, 138.0, 135.6, 133.5, 131.2, 130.4, 130.3, 129.3, 129.0, 128.6, 128.0, 127.2, 126.0,
115.8, 21.4, 20.7; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C22H21O 301.1587; found 301.1560.
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(E)-2-(1-(4-chlorophenyl)-2-phenylvinyl)-4-methylphenol (5b): 44.8 mg, 70% yield; Oil; H NMR
(CDCl3, 600 MHz), δ: 7.31 (s, 4H), 7.21 (dd, J1 = 4.8 Hz, J2 = 2.4 Hz, 3H), 7.16-7.14 (m, 3H), 7.12
(dd, J1 = 8.4 Hz, J2 = 1.8 Hz, 1H), 6.88 (d, J = 1.8 Hz, 1H), 6.86 (d, J = 8.4 Hz, 1H), 4.98 (s, 1H), 2.27
(s, 3H); 13C NMR (CDCl3, 150 MHz), δ: 150.6, 140.6, 136.1, 135.6, 134.0, 131.1, 130.60, 130.59,
130.5, 129.1, 128.8, 128.6, 128.5, 128.2, 125.4, 116.0, 20.7; HRMS (ESI-TOF) m/z: [M+Na]+ calcd
for C21H17ClO 343.0860; found 343.0838.
2-(1-phenylvinyl)phenol (5c): 22.3 mg, 57% yield; Oil; 1H NMR (CDCl3, 600 MHz), δ: 7.39-7.34 (m,
5H), 7.28-7.25 (m, 1H), 7.15 (dd, J1 = 7.8 Hz, J2 = 1.8 Hz, 1H), 7.00-6.92 (m, 2H), 5.88 (d, J = 1.2 Hz
1H), 5.43 (d, J = 1.2 Hz 1H), 5.17 (s, 1H); 13C NMR (CDCl3, 150 MHz), δ: 153.2, 145.4, 139.5, 130.6,
129.6, 128.9, 128.8, 127.7, 127.2, 120.6, 116.9, 116.0; HRMS (ESI-TOF) m/z: [M+H]+ calcd for
C14H13O 197.0961; found 197.0960.
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2-(1-(naphthalen-1-yl)vinyl)phenol (5d): 24.6 mg, 50% yield; Oil; H NMR (CDCl3, 600 MHz), δ:
7.92 (q, J = 8.4 Hz, 3H), 7.54-7.53 (m, 3H), 7.42 (dt, J1 = 6.6 Hz, J2 = 1.2 Hz, 1H), 7.21 (dt, J1 = 8.4
Hz, J2 = 1.8 Hz, 1H), 7.15 (dd, J1 = 7.8 Hz, J2 = 1.8 Hz, 1H), 6.94 (dd, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H),
6.86 (dt, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 5.90 (d, J = 1.2 Hz, 1H), 5.73 (d, J = 1.8 Hz, 1H), 5.63 (s, 1H);
13C NMR (CDCl3, 150 MHz), δ: 153.0, 145.6, 139.5, 134.1, 131.3, 129.7, 129.5, 129.0, 128.6, 128.5,
127.3, 126.6, 126.2, 125.6, 125.5, 120.8, 120.2, 116.4; HRMS (ESI-TOF) m/z: [M+H]+ calcd for
C18H14O 247.1118; found 247.1116.
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2-(1-(thiophen-2-yl)vinyl)phenol (5e): 21 mg, 52% yield; Oil; H NMR (CDCl3, 600 MHz), δ:
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7.29-7.26 (m, 2H), 7.21 (dd, J1 = 7.8 Hz, J2 = 1.8 Hz, 1H), 6.98-6.94 (m, 3H), 6.83 (dd, J1 = 9.6 Hz, J2
= 0.6 Hz, 1H), 5.87 (s, 1H), 5.27 (s, 1H), 5.25 (s, 1H); 13C NMR (CDCl3, 150 MHz), δ: 153.0, 143.7,
138.7, 130.2, 129.9, 127.9, 127.1, 126.9, 126.3, 120.5, 116.0, 115.4; HRMS (ESI-TOF) m/z: [M+H]+
calcd for C12H10OS 203.0525; found 203.0525.
(E)-2-(1-phenylprop-1-en-1-yl)phenol (5f): 31.5 mg, 75% yield; Oil; 1H NMR (CDCl3, 600 MHz), δ:
7.34-7.27 (m, 6H), 7.08-7.04 (m, 2H), 6.99 (dt, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 6.51 (q, J =7.2 Hz, 1H),
5.13 (s, 1H), 1.77 (d, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 150 MHz), δ: 153.0, 140.6, 136.8, 130.7,
129.3, 128.6, 127.66, 127.61, 126.6, 125.4, 120.7, 115.4, 15.8; HRMS (ESI-TOF) m/z: [M+H]+ calcd
for C15H14O 211.1118; found 211.1117.
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2-(1H-inden-3-yl)phenol (5h): 22.9 mg, 55% yield; Oil; H NMR (CDCl3, 600 MHz), δ: 7.58 (d, J
=7.2 Hz, 1H), 7.38-7.29 (m, 5H), 7.06-7.01 (m, 2H), 6.68 (t, J = 7.8 Hz, 1H), 5.40 (s, 1H), 3.61 (d, J =
1.8 Hz, 2H); 13C NMR (CDCl3, 150 MHz), δ: 153.3, 144.5, 144.0, 140.7, 133.0, 129.7, 129.5, 126.6,
125.7, 124.3, 121.8, 120.8, 120.6, 115.8, 38.9; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C15H12O
209.0961; found 209.0960.
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2-(3,4-dihydronaphthalen-1-yl)-4-methylphenol (5i): 27.4 mg, 58% yield; Oil; H NMR (CDCl3,
600 MHz), δ: 7.26-7.21 (m, 2H), 7.16 (dt, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 7.12 (dd, J1 = 8.4 Hz, J2 = 1.8
Hz, 1H), 7.02 (d, J = 2.4 Hz, 1H), 6.93-6.91 (m, 2H), 6.20 (t, J = 4.2 Hz, 1H), 4.93 (s, 1H), 2.95 (t, J =
7.8 Hz, 2H), 2.52 (s, 2H), 2.34 (s, 3H); 13C NMR (CDCl3, 150 MHz), δ: 151.0, 136.3, 134.9, 133.8,
131.0, 130.6, 129.8, 128.0, 127.9, 126.9, 126.1, 125.1, 115.4, 28.0, 23.5, 20.6; HRMS (ESI-TOF) m/z:
[M+H]+ calcd for C17H17O 237.1274; found 237.1275.
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2-(2H-chromen-4-yl)-5-methylphenol (5j): 24.3 mg, 51% yield; White solid; m.p. 84-86 C; H
NMR (CDCl3, 600 MHz), δ: 7.18-7.15 (m, 1H), 7.06 (d, J = 7.2 Hz, 1H), 6.89-6.80 (m, 5H), 5.86 (d, J
= 9.6 Hz, 1H), 5.13 (s, 1H), 4.91 (d, J = 3.6 Hz, 2H), 2.37 (s, 3H); 13C NMR (CDCl3, 150 MHz), δ:
154.5, 153.0, 140.1, 132.5, 130.3, 130.0, 125.7, 122.8, 122.6, 121.7, 121.6, 121.0, 116.5, 116.4, 65.4,
21.4; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C16H14O2 239.1067; found 239.1048.
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(E)-4-methyl-2-(1-phenylpent-1-en-1-yl)phenol (5k): 30.2 mg, 60% yield; Oil; H NMR (CDCl3,
600 MHz), δ: 7.29-7.24 (m, 5H), 7.07 (dd, J1 = 8.4 Hz, J2 = 1.8 Hz, 1H), 6.89 (d, J = 8.4 Hz, 1H), 6.83
(d, J = 1.8 Hz, 1H), 6.39 (t, J = 7.8 Hz, 1H), 4.92 (s, 1H), 2.28 (s, 3H), 2.05 (q, J = 7.2 Hz, 2H), 1.49
(q, J = 7.2 Hz, 2H), 0.92 (t, J = 7.8 Hz, 3H); 13C NMR (CDCl3, 150 MHz), δ: 150.8, 140.8, 135.9,
133.4, 130.9, 129.8, 129.78, 129.75, 127.6, 126.7, 125.5, 115.1, 32.0, 22.8, 20.7, 14.0; HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C18H20O 253.1587; found 253.1574.
(E)-2-(3-(4-methoxyphenyl)-1-phenylprop-1-en-1-yl)phenol (5l): 41.7 mg, 66% yield; Oil; 1H
NMR (CDCl3, 400 MHz), δ: 7.33 - 7.25 (m, 6H), 7.13 - 7.09 (m, 3H), 7.04 - 6.97 (m, 2H), 6.85 (dd, J1
= 10.2 Hz, J2 = 3.0 Hz, 2H), 6.54 (d, J = 11.4 Hz, 1H), 5.06 (s, 1H), 3.79 (s, 3H), 3.34 (d, J = 10.8 Hz,
2H); 13C NMR (CDCl3, 150 MHz), δ: 158.2, 153.2, 140.1, 135.9, 132.1, 131.9, 130.9, 129.5, 128.7,
127.9, 126.7, 125.4, 120.9, 115.7, 114.2, 55.4, 35.4; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for
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C22H20O2 339.1356; found 339.1336.
(E)-2-(1-(4-methoxyphenyl)-4-(pyridin-2-ylthio)but-1-en-1-yl)phenol (5m): 44.3 mg, 61% yield;
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7.16-7.14 (m, 1H), 7.07 (d, J = 8.4 Hz, 2H), 7.01-6.97 (m, 2H), 6.93-6.89 (m, 2H), 6.75 (d, J = 9.0 Hz,
2H), 6.45 (s, 1H), 6.33 (t, J = 7.8 Hz, 1H), 3.77 (s, 3H), 3.28 (t, J = 7.2 Hz, 2H), 2.45 (q, J = 7.2 Hz,
2H); 13C NMR (CDCl3, 150 MHz), δ: 159.3, 158.9, 153.6, 149.3, 137.2, 136.2, 132.9, 130.7, 130.4,
128.5, 127.7, 126.0, 122.6, 120.5, 119.4, 116.1, 113.9, 129.2, 55.4, 30.3, 29.5; HRMS (ESI-TOF) m/z:
[M+H]+ calcd for C22H21NO2S 364.1366; found 364.1368.
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(E)-4-(2-hydroxy-5-methylphenyl)-4-phenylbut-3-en-1-yl acetate (5n): 38.5 mg, 65% yield; Oil;
1H NMR (CDCl3, 400 MHz), δ: 7.28 (s, 5H), 7.07 (d, J = 8.4 Hz, 1H), 6.90 (d, J = 6.6 Hz, 1H), 6.82 (s,
1H), 6.32 (t, J = 10.8 Hz, 1H), 5.12 (s, 1H), 4.17 (d, J = 9.6 Hz, 2H), 2.42 (q, J = 3,6 Hz, 2H), 2.27 (s,
3H), 2.06 (s, 3H); 13C NMR (CDCl3, 150 MHz), δ: 171.2, 150.6, 140.4, 138.8, 130.9, 130.0, 129.9,
128.7, 127.9, 127.0, 126.7, 125.1, 115.6, 63.7, 29.7, 21.1, 20.6; HRMS (ESI-TOF) m/z: [M+H]+ calcd
for C19H20O3 297.1485; found 297.1479.
(E)-5-methyl-2-(7,7,7-trifluoro-1-(4-fluorophenyl)hept-1-en-1-yl)phenol (5o): 50.7 mg, 72% yield;
Oil; 1H NMR (CDCl3, 400 MHz), δ: 7.28-7.25 (m, 2H), 6.99 (t, J = 8.4 Hz, 2H), 6.90 (d, J = 7.6 Hz,
1H), 6.82 (d, J = 7.6 Hz, 2H), 6.29 (t, J = 7.6 Hz, 1H), 4.97 (s, 1H), 2.39 (s, 3H), 2.01 (m, 4H),
1.57-1.55 (m, 4H); 13C NMR (CDCl3, 150 MHz), δ: 162.5 (d, J = 246 Hz), 152.7, 139.8, 136.7, 135.7,
131.7, 130.3, 128.2 (d, J = 7.5 Hz), 127.3 (q, J = 274.5 Hz), 122.3, 121.8, 116.1, 115.4(d, J = 21 Hz),
33.5 (q, J = 28.5 Hz), 29.4, 28.6, 21.5(q, J = 3 Hz), 21.4; HRMS (ESI-TOF) m/z: [M+H]+ calcd for
C20H20OF4 353.1523; found 353.1532.
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(E)-2-(1-(3-methoxyphenyl)hexa-1,5-dien-1-yl)-5-methylphenol (5p): 30.6 mg, 52% yield; Oil; H
NMR (CDCl3, 400 MHz), δ: 7.20 (t, J = 8.0 Hz, 1H), 6.92-6.75 (m, 6H), 6.36 (t, J = 6.8 Hz, 1H),
5.81-5.72 (m, 1H), 5.05-4.95 (m, 3H), 3.77 (s, 3H), 2.35 (s, 3H), 2.35-2.16 (m, 4H); 13C NMR (CDCl3,
150 MHz), δ: 159.8, 152.8, 142.3, 139.5, 137.9, 136.1, 132.8, 130.4, 129.6, 122.6, 121.6, 119.3,
116.1, 115.5, 112.7, 55.3, 29.4, 33.6, 29.3, 21.5; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C20H22O2
295.1693; found 295.1692.
2-((1E,5E)-7-hydroxy-1-(3-methoxyphenyl)-7-methylocta-1,5-dien-1-yl)-5-methylphenol
(5q):
53.5 mg, 76% yield; Oil; 1H NMR (CDCl3, 400 MHz), δ: 7.21 (t, J = 8.0 Hz, 1H), 6.93 (d, J = 7.6 Hz,
1H), 6.87 (d, J = 8.4 Hz, 1H), 6.87-6.77 (m, 4H), 6.33 (s, 1H), 5.65-5.58 (m, 2H), 5.30 (s, 1H), 3.77 (s,
3H), 2.36 (s, 3H), 2.18 (d, J = 6.0 Hz, 4H), 1.30 (s, 6H), 1.19 (s, 1H); 13C NMR (CDCl3, 150 MHz), δ:
159.7, 152.7, 142.3, 139.3, 138.9, 136.4, 132.5, 130.5, 129.5, 126.2, 122.8, 121.5, 119.2, 116.2, 112.6,
70.7, 55.3, 31.9, 29.8, 21.4; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for C23H28O3 375.1931; found
375.1927.
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2-((1E,5E)-6-phenyl-1-(p-tolyl)hexa-1,5-dien-1-yl)phenol (5r): 46.2 mg, 68% yield; Oil; H NMR
(CDCl3, 600 MHz), δ: 7.34-7.33 (m, 2H), 7.29 (t, J = 7.8 Hz, 3H), 7.17 (d, J = 8.4 Hz, 2H), 7.09 (d, J
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= 7.8 Hz, 2H), 7.03 (dd, J1 = 7.2 Hz, J2 = 1.8 Hz, 1H), 7.00 (dd, J1 = 7.8 Hz, J2 = 0.6 Hz, 1H), 6.95 (dt,
J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 6.38 (t, J = 3.0 Hz, 2H), 6.19-6.15 (m, 1H), 5.04 (s, 1H), 2.37-2.33 (m,
6H), 2.23 (d, J = 7.2 Hz, 2H); 13C NMR (CDCl3, 150 MHz), δ: 153.0, 137.7, 137.6, 137.5, 136.2,
131.5, 130.8, 130.7, 129.7, 129.4, 129.3, 128.6, 127.1, 126.6, 126.1, 125.8, 120.7, 115.5, 33.0, 29.7,
21.2; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C25H24O 341.1900; found 341.1914.
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6,6'-((1E,5E)-1,6-diphenylhexa-1,5-diene-1,6-diyl)bis(3-methylphenol) (5s): 44.6 mg, 50% yield;
Oil; 1H NMR (CDCl3, 400 MHz), δ: 7.28 (s, 12H), 6.90-6.78 (m, 6H), 6.33 (s, 2H), 5.03 (s, 2H), 2.40
(s, 6H), 2.24 (s, 2H); 13C NMR (CDCl3, 100 MHz), δ: 152.8, 140.5, 139.5, 136.7, 131.8, 130.5, 128.6,
127.7, 126.6, 122.6, 121.6, 116.1, 29.8, 21.5; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for C32H30O2
469.2138; found 469.2122.
3-isopropyl-5-methyl-3-phenylisoindolin-1-one (6): 34 mg, 65% yield; White solid; m.p. 203-205
oC; 1H NMR (CDCl3, 600 MHz), δ: 7.69 (d, J = 7.8 Hz, 2H), 7.61 (d, J = 7.8 Hz, 2H), 7.37 (t, J = 7.8
Hz, 2H), 7.28 (d, J = 6.0 Hz, 1H), 7.20 (t, J = 7.8 Hz, 2H), 2.95 (m, J = 7.2 Hz, 1H), 2.41 (s, 3H), 2.33
(d, J = 6.6 Hz, 3H), 0.69 (d, J = 6.6 Hz, 3H); 13C NMR (CDCl3, 150 MHz), δ: 171.8, 151.8, 143.1,
142.3, 129.1, 129.0, 128.1, 127.5, 125.3, 123.8, 122.6, 70.9, 35.2, 22.2, 18.4, 16.5; HRMS (ESI-TOF)
m/z: [M+H]+ calcd for C18H19NO 266.1540; found 266.1542.
4-methyl-2-(2-methyl-1-phenylprop-1-en-1-yl)benzamide (7): 8 mg, 15% yield; White solid; m.p.
120-122 oC; 1H NMR (CDCl3, 600 MHz), δ: 7.93 (d, J = 7.8 Hz, 1H), 7.35 (t, J = 7.8 Hz, 2H), 7.28 (t,
J = 8.4 Hz, 3H), 7.23 (d, J = 7.8 Hz, 1H), 7.07 (s, 1H), 6.65 (s, 1H), 6.15 (s, 1H), 2.45 (s, 3H), 2.03 (s,
3H), 1.82 (s, 3H); 13C NMR (CDCl3, 150 MHz), δ: 170.6, 141.5, 140.8, 136.1, 133.9, 131.9, 130.4,
130.1, 129.8, 128.1, 128.0, 126.7, 23.1, 22.3, 21.5; HRMS (ESI-TOF) m/z: [M+H]+ calcd for
C18H19NO 266.1539; found 266.1540.
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2-(4-methoxybenzyl)-3-phenylbenzofuran (8): 37.7 mg, 60% yield; Oil; H NMR (CDCl3, 400
MHz), δ: 7.62 (d, J = 1.8 Hz, 1H), 7.56-7.51 (m, 2H), 7.51-7.47 (m, 2H), 7.41 (t, J = 0.8 Hz, 1H),
7.30-7.25 (m, 2H), 7.20 (d, J = 1.2 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 4.18 (s, 2H), 3.81 (s, 3H), 1.59
(s, 3H); 13C NMR (CDCl3, 150 MHz), δ: 158.4, 154.4, 153.1, 132.7, 130.1, 129.6, 129.2, 129.0, 128.8,
127.4, 124.0, 122.8, 119.8, 118.1, 114.2, 111.3, 55.4, 32.1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for
C22H18O2 315.1380; found 315.1371.
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5-chloro-2,3-diphenylbenzofuran (9): 41.3 mg, 68% yield; Yelllow solid; m.p. 83-85 C; H NMR
(CDCl3, 400 MHz), δ: 7.67-7.64 (m, 2H), 7.48-7.46 (m, 7H), 7.33-7.27 (m, 4H); 13C NMR (CDCl3,
100 MHz), δ: 152.5, 152.0, 132.3, 131.8, 130.3, 129.8, 129.3, 128.9, 128.7, 128.6, 128.1, 127.2, 125.0,
119.8, 117.2, 112.3.
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2-(3-(4-methoxyphenyl)-1-phenylpropyl)phenol (10): 60.4 mg, 95% yield; Oil; H NMR (CDCl3,
600 MHz), δ: 7.33-7.29 (m, 5H), 7.23-7.21 (m, 1H), 7.13-7.09 (m, 3H), 6.96 (dt, J1 = 7.2 Hz, J2 = 0.6
Hz, 1H), 6.84 (d, J = 2.4 Hz, 2H), 6.74 (dt, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 4.76 (s, 1H), 4.25 (d, J = 7.8
Hz, 1H), 3.80 (s, 3H), 2.58 (t, J = 7.8 Hz, 2H), 2.36 (m, 2H); 13C NMR (CDCl3, 150 MHz), δ: 157.8,
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153.5, 144.1, 134.3, 130.9, 129.4, 128.7, 128.2, 128.1, 127.5, 126.5, 121.1, 116.1, 113.9, 55.4, 43.7,
36.8, 33.2; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for C22H22O2 341.1521; found 341.1504.
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ACKNOWLEDGMENTS
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We are grateful for financial supports from NSFC of China (21702188, 21672191) and the Natural
Science foundation of Zhejiang Province (LQ17B020001).
Supporting Information. Spectroscopic data of products 4 and 5. This material is available free of
charge via the Internet at http://pubs.acs.org.
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