Rhodium(III)-Catalyzed Redox-Neutral C-H Activation/Annulation of N-Aryloxyacetamides with Alkynyloxiranes: Synthesis of Highly Functionalized 2,3-Dihydrobenzofurans

Article abstract of DOI:10.1021/acs.joc.8b01166

Alkynyloxiranes have been employed for the first time as effective coupling partners in Cp Rh^III-catalyzed C-H functionalization reactions. Their annulation with N-aryloxyamides then offers a redox-neutral and efficient synthesis of functionali

Full text of DOI:10.1021/acs.joc.8b01166

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Note
Rhodium(III)-Catalyzed Redox-Neutral C-H Activation/
Annulation of N-aryloxyacetamides with Alkynyloxiranes:
Synthesis of Highly Functionalized 2,3-Dihydrobenzofurans
Yang Li, Dandan Shi, Yuhai Tang, Xin He, and Silong Xu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01166 • Publication Date (Web): 22 Jun 2018
Downloaded from http://pubs.acs.org on June 23, 2018
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Rhodium(III)-Catalyzed Redox-Neutral C−H Activation/Annulation
of N-aryloxyacetamides with Alkynyloxiranes: Synthesis of Highly
Functionalized 2,3-Dihydrobenzofurans
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Yang Li*, Dandan Shi, Yuhai Tang, Xin He and Silong Xu*
Department of Chemistry, School of Science, and Xi'an Key Laboratory of Sustainable Energy Materials Chemistry, Xi’an
Jiaotong University, Xi’an, 710049, P. R. China.
Supporting Information Placeholder
ABSTRACT: Alkynyloxiranes have been employed for the first time as effective coupling partners in Cp*RhIII-catalyzed C−H
functionalization reactions. Their annulation with N-aryloxyamides then offers a redox-neutral and efficient synthesis of functionalized 2,3-
dihydrobenzofurans bearing an exocyclic E-allylic alcohol and a tetra-substituted carbon center in good yields with a broad substrate scope.
The products can be easily converted to molecules with more complexity, which provides an opportunity for rapid assembly of structurally
diverse heterocycles.
Transition metal-catalyzed C−H activation has been estab-
lished as a creative and straightforward strategy in organic
synthesis.1 In this regard, redox-neutral C−H activations utiliz-
ing oxidizing directing groups are even more intriguing, which
could not only enrich the reaction patterns of C−H
functionalization but also abstain from the use of a stoichio-
metric amount of external oxidants.2-3 Among various
unsaturated coupling partners applied in C-H activations,1-3
allylic compounds with different leaving groups have been
extensively explored toward C−H allylations4 under various
transition metal catalysis5 (Scheme 1a). Under control condi-
tions, the allylation can be switched to alkenylation via β-H
elimination instead of the departure of leaving groups.5d, 6 Cy-
clic vinyl compounds, e.g. vinyloxiranes, have also been ap-
plied in transition metal-catalyzed C−H allylations to afford
corresponding allylic alcohols via ring-opening reactions
(Scheme 1b). 7 Similar to allylic derivatives, propargylic com-
pounds with appropriate leaving groups also exhibit versatile
reactivity toward transition metal-catalyzed C−H activation,
leading to either allene products8 or various cyclic structures9,
aryloxyacetamides with alkynyloxiranes, which affords 2,3-
dihydrobenzofurans bearing a useful exocyclic (E)-allylic al-
cohol10, and a tetra-substituted carbon center in good yields
with a broad substrate scope (Scheme 1).
Scheme 1. Transition Metal-Catalyzed C−H Functionaliza-
tion with Allylic or Propargylic Coupling Partners
3c
(Scheme 1c). In view of the rich reactivity of propargylic
In connection with our recent work on the C−H activa-
tion/anulation of N-aryloxyacetamides with 1,1-disubstituted
alkenes,11 we commenced our studies on the coupling of N-
phenoxyacetamide (1a) with 2-(phenylethynyl)oxirane (2a)
with 2.5 mol% [Cp*RhCl2]2 and 50 mol% CsOAc in MeOH at
room temperature for 16 h (Table 1, entry 1). To our delight,
the reaction gave an annulative product dihydrobenzofuran
compounds as well as the ring opening potential of oxiranes, it
occurs to us that alkynyloxiranes as coupling partners in tran-
sition metal-catalyzed C−H activation would bring up new
reaction patterns, which, to the best of our knowledge, remains
to be unexplored. Herein, we report an efficient Cp*RhIII-
catalyzed redox-neutral C−H activation/annulation of N-
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3aa bearing an exocyclic allylic alcohol with a tetra-
smoothly, affording product 3ka in 79% yield. Furthermore,
N-(naphthalen-1-yloxy)acetamide was compatible giving
product 3la in a good yield of 57%. Subsequently, a range of
alkynyloxiranes 2 were tested in the annulation with N-
phenoxyacetamide 1a. Under standard reaction conditions, 2-
(arylethynyl)oxiranes with a para- or meta-methyl on the ben-
zene ring worked well giving products 3ab and 3ac in 74%
and 80% yields, respectively; however, ortho-substitution with
a methyl group completely blocked the reaction probably due
to the bulkiness that impeded the binding to the Rh center. The
electronic property of the aryl ring of substrates 2 exerts little
impact on the reaction as shown in products 3ae-ah, which
were obtained in 66-75% yields. Finally, it was found that 1,2-
disubstituted alkynyloxirane 2i-j, with R2 as an aryl or alkyl
group, were also compatible, generating the corresponding
products 3ai and 3aj in 54% and 56% yield, respectively, albe-
it with poor diastereoselectivity. However, alkyl substituted
substituted carbon center in 86% yield with exclusive E-
selectivity. The E-configuration of the double bond was con-
firmed by NOE analysis (see Supporting Information). Com-
pared to CsOAc,12 other additives such as KOAc, NaOAc,
AgOAc, and Cu(OAc)2 all led to lower yields (entries 1−5).
Further screening of solvents revealed that THF, DCE, PhMe,
and dioxane delivered the product 3aa in less than 51% yields,
while CH3CN gave a slightly higher yield of 87% (entries 6−
10). A longer reaction time of 24 h exerted little effect on the
reaction, whereas a shorter time of 10 h resulted in a decreased
66% yield (entries 11 and 12). Reducing the amount of 2a to
1.2 equiv also gave a comparable yield of 84% (entry 13).
Noteworthy is that other transition metal catalysts such as
ruthenium, iridium, and palladium are ineffective for the annu-
lation. Thus, the optimized condition was established by per-
forming the reaction in CH3CN or MeOH in the presence of 50
mol% CsOAc with 2.5 mol% [Cp*RhCl2]2 at room tempera-
ture for 16 hours.
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n
alkynyloxiranes (e.g. R1 = Bu, 3aa'') were ineffective in the
annulation leading to complex mixtures under the standard
conditions.
Table 1. Optimization of Reaction Conditionsa
Table 2. Scope Investigationsa
entry catalyst
solvent
MeOH
MeOH
MeOH
MeOH
MeOH
THF
additive
CsOAc
KOAc
yieldb (%)
86
1
2
3
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[IrCp*Cl2]2
69
75
69
67
38
51
33
29
87
87
66
84
trace
trace
trace
NaOAc
AgOAc
Cu(OAc)2
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
4
5c
6
7
8
9
10
11d
12e
13f
14
15
16
DCE
PhMe
dioxane
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
[RuCl2(p-cymene)]2 CH3CN
Pd(OAc)2 CH3CN
a Unless specified, the reactions were carried out under N2 using
2.5 mol% catalyst, 50 mol% additive, 1.0 equiv of 1a (0.2 mmol)
b
and 1.5 equiv of 2a (0.3 mmol) in 2 mL solvent at rt for 16 h.
Isolated yields. c 25 mol% Cu(OAc)2 was used. d The reaction was
carried out for 24 h. e The reaction was performed for 10 h. f 1.2
equiv of 2a was used.
Under the optimized conditions, the reaction scope was then
investigated (Table 2). With 2-(phenylethynyl)oxirane (2a) as
a partner, a range of N-aryloxyamides 1 were examined. It was
found that switch of the acetamide to a bulky pivalamide also
gave the desired product 3aa' in 61% yield. Substition with
electron-donating or electron-withdrawing groups on the para
position of the benzene ring could be well tolerated, providing
dihydrobenzofuran products 3ba-ga in good yields (57-79%).
meta-Substituted aryloxyacetamides afforded the correspond-
ing products 3ha-ja in 56-76% yields as single regioisomers,
a Isolated yields are given; reaction conditions: under N2, 1 (0.2
mmol, 1.0 equiv), 2 (0.3 mmol, 1.5 equiv), [Cp*RhCl2]2 (2.5
mol%), CsOAc (0.1 mmol, 0.5 equiv) and CH3CN (2 mL) were
sealed in a 25 mL Schlenk tube at rt for 16 h. b Yield of 2 mmol
scale.
As 2,3-dihydrobenzofurans are privileged scaffolds in a va-
riety of natural products, bioactive compounds, and pharma-
ceuticals,13 their synthesis has attracted a long-standing inter-
ests from synthetic community.14 As shown in Table 2, the
Cp*RhIII-catalyzed annulation of N-aryloxyacetamides with
with the C−H activation taken place at less hindered C−H
bonds. Notably, ortho-methylphenoxyacetamide also occurred
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alkynyloxiranes thus offers a mild redox-neutral protocol for
occurs to regenerate the active catalyst Cp*Rh(OAc)2 and
affords an enamide compound E, which delivers the final
product 3aa via an intramolecular SN2' ring opening of
oxirane.3c
the synthesis of highly functionalized 2,3-dihydrobenzofurans.
To demonstrate the practicality, running the reaction in 2
mmol scale could also afford a 76% yield of the product 3aa
(Table 2). Taking advantage of the allylic alcohol moiety,10
cyclization of 3aa was achieved with triethyl orthoformate and
propionic acid to produce a tricyclic heterocycle 4 with two
adjacent quaternary stereogenic centers in 62% yield (Scheme
2a). In addition, a two-step sequence of oxidization and NHC-
catalyzed rearrangement of 3aa was exemplified to furnish a
coumarin product 5 in 61% overall yield (Scheme 2b).
Scheme 4. Proposed Mechanism
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Scheme 2. Derivatization of Product 3aa
In conclusion, we have developed a Cp*RhIII-catalyzed re-
gio- and stereoselectiv C−H activation/annulation of N-
aryloxyamides with alkynyloxiranes, which provides 2,3-
dihydrobenzofurans with an exocyclic E-allylic alcohol and a
tetra-substituted carbon center in good yields with a broad
substrate scope under mild redox-neutral conditions. This
transformation marks the first use of alkynyloxiranes as cou-
pling partners in transition metal-catalyzed C−H functionaliza-
tion. The products can be easily converted to molecules with
more complexity, which provides an opportunity for rapid
assembly of structurally diverse heterocycles. Further studies
to explore synthetic applications of the methodology and de-
veloping new transition metal-catalyzed C−H functionaliza-
tion reactions are undergoing in this lab.
To gain insight into the mechanism, several mechanistic ex-
periments were conducted. Firstly, kinetic isotope effect was
determined using 1a/1a-d5 as substrates for parallel reactions
(Scheme 3a). A value of kH/D = 1.6 was identified, which indi-
cates that the C−H bond cleavage might not be involved in the
rate-limiting step.15 In addition, the reaction of 1a and 2a was
performed in CD3OD solvent under otherwise identical condi-
tions (Scheme 3b). The product 3aa was isolated in 31% yield
with no deuterium incorporation observed, suggesting that the
C−H activation step might be irreversible under the reaction
conditions.
Scheme 3. Mechanistic Studies
EXPERIMENTAL SECTION
General Methods. All reactions and manipulations involv-
ing air-sensitive compounds were performed using standard
Schlenk techniques. Anhydrous THF and dioxane were dis-
tilled from sodium. Anhydrous CH2Cl2, ClCH2CH2Cl were
distilled from CaH2 under an atmosphere of N2. Anhydrous
MeOH was distilled from magnesium under N2 atmosphere.
1H, 13C and 19F NMR spectra were recorded on a 400 MHz
Bruker AV400 spectrometer. Chemical shifts (δ values) were
reported in ppm with internal TMS (1H NMR), CDCl3 (13C
NMR), or external CF3CO2H (19F NMR) references, respec-
tively. HRMS (ESI) were determined on Agilent Technologies
6224 TOF LC/MS or Q-TOF or LTQ Orbitrap XL micro spec-
trometer. The IR spectra were measured on a NICOLET iS10
spectrometer. Column chromatography was performed on
silica gel (200-300 mesh) using a mixture of petroleum ether
(60-90 ºC)/ethyl acetate as the eluent.
Based on the results and literature precedents3c, 5, 11, a plau-
sible mechanism is proposed in Scheme 4. In the presence of
CsOAc, an active catalytic species Cp*Rh(OAc)2 is formed
through anion exchange, which promotes a facile and irre-
versible ortho-C−H activation of 1a to afford a 5-membered
rhodacycle intermediate A. Regioselective alkyne insertion
with 2a forms a 7-membered rhodacycle B with the epoxide
group away from rhodium center, probably due to avoiding
steric clash in the coupling.8, 16 Subsequent reductive elimina-
tion of B occurs to furnish intermediate C bearing rhodium(I)
species, which undergoes oxidative addition to the N−O bond
to generate a rhodium(III) species D. Proto-demetalation then
General procedure for synthesis of N-aryloxyacetamides
1a-l and 1a'. The N-aryloxyacetamides 1a-l and 1a' were syn-
thesized following a procedure reported by Kelly17 and Lu3s.
Compounds 1a-l and 1a' are known compounds and all data
were in agreement with those reported.3h, s,11
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General procedure for synthesis of substrates 2a-i. Pro-
(E)-N-(3-(2-hydroxyethylidene)-2-phenyl-2,3-
pargyl epoxides 2a, 2c-d, 2f, 2h, and 2i-j were synthesized
according to the literature, and all data were in agreement with
those reported18a-c and 2j was obtained as trans/cis isomers
(trans/cis = 5/1).18d The propargyl epoxides 2b, 2e, 2g were
synthesized as a following procedure analogous to that report-
ed by Chang18. In an oven dried flask, to a solution of
ethynylbenzenes (10 mmol, 1 eq.) in Et3N (5 mL) were added
CuI (0.5 mmol, 95.2 mg), Pd(PPh3)4 (0.3 mmol, 210 mg), and
vinyl bromide (15 mmol, 1 M, 15.0 ml) at 0 °C. After being
stirred for 16 h at 25 °C, the mixture was allowed to cool to rt
and then filtered through a pad of Celite with Et2O (100 mL).
The ether solution was washed with water (3 × 100 mL), dried
over Na2SO4, and concentrated in vacuo. The crude residue
was then taken up in CH2Cl2 (50 mL) and cooled to 0 °C, and
m-CPBA (15 mmol, 1.5 eq.) was added. After 30 min, the
reaction mixture was warmed to rt, and stirred for additional
12 h. The reaction mixture was then washed with sat. NaHCO3
(100 mL), brine (20 mL), dried over Na2SO4, filtered and
evaporated under reduced pressure. The crude product was
purified by alkaline Al2O3 column chromatography (petroleum
ether/ethyl acetate = 30/1 to 20/1) to afford the phenylethynyl-
oxiranes 2.
dihydrobenzofuran-2-yl)acetamide, (3aa). White solid, yield
51 mg (86%); 1H NMR (400 MHz, DMSO-d6) δ = 8.92 (s, 1H),
7.42-7.25 (m, 7H), 6.98-6.94 (m, 2H), 5.65 (t, J = 5.6 Hz, 1H),
5.03 (t, J = 5.2 Hz, 1H), 4.41- 4.28 (m, 2H), 1.91 (s, 3H); 13C
NMR (101 MHz, DMSO-d6) δ = 169.5, 160.2, 141.6, 137.7,
129.9, 128.3, 127.8, 126.4, 124.9, 124.6, 123.7,121.0, 109.4,
96.3, 58.2, 23.3; FTIR (neat): υ 3049, 2923, 2151, 1593, 1485,
1439, 1025, 915, 848, 752, 684 cm-1; HRMS calculated for
C18H17NNaO3 (M+Na)+: 318.1101, Found: 318.1098.
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(E)-N-(3-(2-hydroxyethylidene)-2-phenyl-2,3-
dihydrobenzofuran-2-yl)pivalamide, (3aa'). White solid, yield
41 mg (61%); 1H NMR (400 MHz, DMSO-d6) δ = 8.17 (s, 1H),
7.39-7.26 (m, 7H), 6.99-6.93 (m, 2H), 5.63 (t, J = 5.6 Hz, 1H),
5.00 (t, J = 5.3 Hz, 1H), 4.40-4.28 (m, 2H), 1.13 (s, 9H). 13
C
NMR (101 MHz, DMSO-d6) δ = 177.3, 160.3, 142.0, 137.9,
129.9, 128.4, 127.7, 125.9, 124.95, 124.5, 123.96, 120.9,
109.5, 96.5, 58.2, 39.1, 26.9; IR (neat):  3336, 2921, 2852,
1680, 1606, 1460, 1366, 1244, 1173, 1018, 855, 799, 746, 700,
566, 428 cm-1; HRMS calculated for C21H24NO3 (M+H)+:
338.1751, Found: 338.1748.
(E)-N-(3-(2-hydroxyethylidene)-5-methyl-2-phenyl-2,3-
dihydrobenzofuran-2-yl)acetamide, (3ba). White solid, yield
38 mg (62%); 1H NMR (400 MHz, DMSO-d6) δ = 8.88 (s, 1H),
7.40-7.27 (m, 5H), 7.14 (s, 1H), 7.08 (d, J = 8.2 Hz, 1H), 6.86
(d, J = 8.1 Hz, 1H), 5.61 (t, J = 5.6 Hz, 1H), 5.02 (t, J = 5.1 Hz,
1H), 4.41-4.29 (m, 2H), 2.27 (s, 3H), 1.90 (s, 3H); 13C NMR
(101 MHz, DMSO-d6) δ = 169.5, 158.4, 141.8, 137.98, 130.4,
129.8, 128.3, 127.7, 126.1, 125.2, 124.7, 123.7, 109.0, 96.4,
58.2, 23.3, 20.5; IR (neat):  3268, 2924, 2093, 1748, 1731,
1715, 1681, 1541, 1480, 1374, 1244, 1035，920, 809, 704,
674, 590, 533 cm-1; HRMS calculated for C19H23N2O3
(M+NH4)+: 327.1703, Found: 327.1699.
2-p-Tolylethynyl-oxirane, (2b). Colorless liquid, yield 880
1
mg (56%); H NMR (400 MHz, CDCl3) δ = 7.34 (d, J = 8.1
Hz, 2H), 7.11 (d, J = 7.9 Hz, 2H), 3.57 (t, J = 3.3 Hz, 1H),
3.00 (d, J = 3.2 Hz, 2H), 2.34 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ = 139.1, 131.9, 129.2, 119.0, 85.2, 83.7, 49.2, 40.4,
21.6; FTIR (neat): υ 2920, 2235, 1727, 1509, 1376, 1032, 927,
840, 814, 772, 751, 533 cm-1; HRMS calculated for C11H11O
(M+H)+: 159.0804, Found: 159.0804.
2-(4-Fluoro-phenylethynyl)-oxirane, (2e). Colorless liquid,
1
yield 730 mg (45%); H NMR (400 MHz, CDCl3) δ = 7.42-
7.37 (m, 2H), 7.01-6.95 (m, 2H), 3.55-3.53 (m, 1H), 2.99-2.95
(m, 2H); 13C NMR (101 MHz, CDCl3) δ = 162.8 (d, J = 250.2
Hz), 133.9 (d, J = 8.5 Hz), 118.0 (d, J = 3.5 Hz), 115.7 (d, J =
22.1 Hz), 85.6 (d, J = 1.3 Hz), 82.3, 49.0, 40.1; 19F NMR (376
MHz, CDCl3): δ = -109.9; FTIR (neat): υ 2991, 2239, 1653,
1601, 1505, 1377, 1230, 927, 834, 807, 777, 646, 533, 513,
490 cm-1; HRMS calculated for C10H8FO (M+H)+: 163.0554,
Found: 163.0548.
(E)-N-(5-(tert-butyl)-3-(2-hydroxyethylidene)-2-phenyl-
2,3-dihydrobenzofuran-2-yl)acetamide, (3ca). White solid,
1
yield 46 mg (66%); H NMR (400 MHz, DMSO-d6) δ = 8.88
(s, 1H), 7.43-7.18 (m, 7H), 6.90 (d, J = 8.4 Hz, 1H), 5.64 (t, J
= 5.7 Hz, 1H), 5.04 (t, J = 5.1 Hz, 1H), 4.44-4.31 (m, 2H),
1.90 (s, 3H), 1.28 (s, 9H); 13C NMR (101 MHz, DMSO-d6) δ =
169.5, 158.2, 143.3, 141.7, 138.3, 128.3, 127.8, 127.1, 125.7,
124.8, 123.3, 121.4, 108.8, 96.5, 58.2, 34.1, 31.4, 23.4; IR
(neat):  3457, 3306, 2959, 1656, 1482, 1363, 1260, 1243,
1155, 1047, 959, 817, 732, 696, 665, 567, 509, 491 cm-1;
HRMS calculated for C22H29N2O3 (M+NH4)+: 369.2173,
Found: 369.2168.
2-((4-bromophenyl)ethynyl)oxirane, (2g). Colorless liquid,
1
yield 1110 mg (50%); H NMR (400 MHz, CDCl3) δ = 7.47-
7.44 (m, 2H), 7.32-7.29 (m, 2H), 3.58-3.56 (m, 1H), 3.04-2.99
(m, 2H); 13C NMR (101 MHz, CDCl3) δ = 133.5, 131.8, 123.3,
121.0, 87.0, 82.5, 49.2, 40.3; FTIR (neat): υ 2961, 2246, 1583,
1485, 1370, 1285, 1068, 1011, 922, 865, 792, 776, 701, 569,
520, 477 cm-1; HRMS calculated for C10H8BrO (M+H)+:
222.9753, Found: 222.9752.
(E)-N-(5-fluoro-3-(2-hydroxyethylidene)-2-phenyl-2,3-
dihydrobenzofuran-2-yl)acetamide, (3da). White solid, yield
49 mg (79%); 1H NMR (400 MHz, DMSO-d6) δ = 8.98 (s, 1H),
7.45-7.31 (m, 5H), 7.19 (dd, J = 8.9, 2.6 Hz, 1H), 7.12 (td, J =
9.0, 2.7 Hz, 1H), 6.98 (dd, J = 8.8, 4.3 Hz, 1H), 5.73 (t, J = 5.7
Hz, 1H), 5.08 (t, J = 5.2 Hz, 1H), 4.39-4.28 (m, 2H), 1.92 (s,
3H); 13C NMR (101 MHz, DMSO-d6) δ = 169.6, 156.9 (d, J =
234.6 Hz), 156.4, 141.4, 137.6, 128.4, 128.0, 127.6, 124.8,
124.7, 116.1 (d, J = 24.5 Hz), 111.5 (d, J = 25.6 Hz), 109.9 (d,
J = 8.6 Hz), 97.1, 58.0, 23.3; 19F NMR (376 MHz, DMSO-d6)
δ = -123.00; IR (neat,cm-1):  3280, 2924, 2853, 1679, 1471,
1370, 1251, 1196, 1034, 940, 860, 811, 734, 698, 659, 556,
491; HRMS calculated for C18H20FN2O3 (M+NH4)+: 331.1452,
Found: 331.1449.
General procedure for Synthesis of (E)-3. A Schlenk tube
(25 mL) with a stir bar was added aryloxyacetamides 1 (0.20
mmol, 1 eq.), propargyl epoxides 2 (0.30 mmol, 1.5 eq.),
[RhCp*Cl2]2 (0.005 mmol, 2.5 mol%) and CsOAc (0.10 mmol,
0.5 eq.). The tube was purged three times by vacuum and N2,
then the solvent (2 mL, 0.1 M) was added. The mixture was
stirred at room temperature for 16 h, which was then concen-
trated in vacuum. The residue was purified by silica gel col-
umn chromatography (petroleum ether/ethyl acetate = 5/1 to
1/1) to give products (E)-3.
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43 mg (67%); 1H NMR (400 MHz, DMSO-d6) δ = 8.78 (s, 1H),
(E)-N-(5-chloro-3-(2-hydroxyethylidene)-2-phenyl-2,3-
dihydrobenzofuran-2-yl)pivalamide, (3ea). White solid, yield
43 mg (65%); 1H NMR (400 MHz, DMSO-d6) δ = 9.01 (s, 1H),
7.46-7.18 (m, 7H), 6.99 (t, J = 8.5 Hz, 1H), 5.74 (t, J = 5.7 Hz,
1H), 5.08 (t, J = 5.2 Hz, 1H), 4.38-4.25 (m, 2H), 1.91 (s, 3H);
13C NMR (101 MHz, DMSO-d6) δ = 169.7, 158.9, 141.1,
137.1, 129.5, 128.5, 128.1, 127.7, 125.7, 124.7, 124.6, 124.4,
110.8, 97.3, 58.0, 23.3; IR (neat):  3412; 3273, 2923, 2851,
1682, 1461, 1368, 1245, 1159, 1059, 891, 870, 811, 771, 699
cm-1; HRMS calculated for C18H20ClN2O3 (M+NH4)+:
347.1157, Found: 347.1155.
7.40-7.27 (m, 5H), 6.57 (d, J = 15.1 Hz, 2H), 5.48 (t, J = 6.2
Hz, 1H), 4.89 (t, J = 5.1 Hz, 1H), 4.36-4.19 (m, 2H), 2.32 (s,
3H), 2.24 (s, 3H), 1.90 (s, 3H); 13C NMR (101 MHz, DMSO-
d6) δ = 169.2, 160.9, 141.2, 140.3, 137.8, 133.6, 128.1, 127.8,
125.3, 124.8, 124.5, 119.9, 107.9, 97.5, 59.4, 23.5, 21.8, 21.1;
IR (neat):  3268, 2923, 1670, 1620, 1525, 1447, 1373, 1264,
1174, 1031, 836, 804, 737, 699, 574 cm-1; HRMS calculated
for C20H25N2O3 (M+NH4)+: 341.1860, Found: 341.1855.
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(E)-N-(3-(2-hydroxyethylidene)-7-methyl-2-phenyl-2,3-
dihydrobenzofuran-2-yl)acetamide, (3ka). White solid, yield
49 mg (79%); 1H NMR (400 MHz, DMSO-d6) δ = 8.88 (s, 1H),
7.43-7.28 (m, 5H), 7.15-7.10 (m, 2H), 6.86 (t, J = 7.5 Hz, 1H),
5.65 (t, J = 5.6 Hz, 1H), 5.01 (t, J = 5.2 Hz, 1H), 4.39-4.27 (m,
2H), 2.23 (s, 3H), 1.92 (s, 3H); 13C NMR (101 MHz, DMSO-
d6) δ = 169.5, 158.6, 141.7, 138.2, 130.9 128.4, 127.8, 125.8,
124.6, 123.1, 122.4, 120.9, 118.8, 96.0, 58.2, 23.4, 14.9; IR
(neat):  3282, 2925, 1679, 1490, 1371, 1363, 1032, 967, 856,
731, 699, 550, 527 cm-1; HRMS calculated for C19H23N2O3
(M+NH4)+: 327.1703, Found: 327.1696.
(E)-N-(5-bromo-3-(2-hydroxyethylidene)-2-phenyl-2,3-
dihydrobenzofuran-2-yl)acetamide, (3fa). White solid, yield
56 mg (75%); 1H NMR (400 MHz, DMSO-d6) δ = 9.02 (s, 1H),
7.47-7.31 (m, 7H), 6.95 (d, J = 8.5 Hz, 1H), 5.74 (t, J = 5.8 Hz,
1H), 5.08 (t, J = 5.2 Hz, 1H), 4.36-4.26 (m, 2H), 1.91 (s, 3H);
13C NMR (101 MHz, DMSO-d6) δ = 169.7, 159.3, 141.1,
136.97, 132.3, 128.6, 128.2, 127.6, 127.2, 126.3, 124.7, 112.2,
111.4, 97.2, 57.9, 23.3; IR (neat):  3360, 2918, 1679, 1525,
1459, 1245, 1024, 990, 824, 699, 552, cm-1; HRMS calculated
for C18H20BrN2O3 (M+NH4)+: 391.0652, Found: 391.0651.
(E)-N-(3-(2-hydroxyethylidene)-2-phenyl-2,3-
dihydronaphtho[1,2-b]furan-2-yl)acetamide, (3la). White
solid, yield 39 mg (57%); 1H NMR (400 MHz, DMSO-d6) δ =
9.05 (s, 1H), 8.04-8.02 (m, 1H), 7.95-7.93 (m, 1H), 7.59-7.47
(m, 6H), 7.39-7.29 (m, 3H), 5.67 (t, J = 5.9 Hz, 1H), 5.04 (t, J
= 5.3 Hz, 1H), 4.51-4.37 (m, 2H), 1.95 (s, 3H); 13C NMR (101
MHz, DMSO-d6) δ = 169.6, 156.3, 141.5, 138.9 134.1, 128.4,
127.9, 127.1, 125.9, 124.7, 124.1, 122.2, 121.5, 120.8, 119.4,
117.8, 97.5, 57.9, 23.4; IR (neat):  3272, 2922, 2852, 1659,
1517, 1441, 1391, 1265, 1066, 968, 947, 876, 807, 733, 700,
566, 544 cm-1; HRMS calculated for C22H23N2O3 (M+NH4)+:
363.1703, Found: 363.1700.
(E)-N-(3-(2-hydroxyethylidene)-2-phenyl-5-
(trifluoromethyl)-2,3-dihydrobenzofuran-2-yl)acetamide,
1
(3ga). White solid, yield 39 mg (54%); H NMR (400 MHz,
DMSO-d6) δ = 9.12 (s, 1H), 7.65-7.63 (m, 2H), 7.46-7.33 (m,
5H), 7.15 (d, J = 8.2 Hz, 1H), 5.81 (t, J = 5.8 Hz, 1H), 5.13 (t,
J = 5.2 Hz, 1H), 4.42-4.29 (m, 2H), 1.92 (s, 3H); 13C NMR
(101 MHz, DMSO-d6) δ = 169.8, 162.6, 140.7, 136.6, 128.6,
128.4, 128.0, 127.5 (q, J = 4.2 Hz), 124.85, 124.81, 124.6 (q, J
=270.2 Hz), 121.9 (q, J = 3.0 Hz), 121.7 (q, J = 31.0Hz),
110.0, 97.8, 57.9, 23.3; 19F NMR (376 MHz, DMSO-d6) δ = -
59.54; IR (neat):  3417, 3267, 2918, 1683, 1614, 1529, 1489,
1314, 1154, 1116, 1056, 890, 823, 764, 697, 545, 437 cm-1;
HRMS calculated for C19H20F3N2O3 (M+NH4)+: 381.1421,
Found: 381.1417.
(E)-N-(3-(2-hydroxyethylidene)-2-(p-tolyl)-2,3-
dihydrobenzofuran-2-yl)acetamide, (3ab). White solid, yield
46 mg (74%); 1H NMR (400 MHz, DMSO-d6) δ = 8.88 (s, 1H),
7.35-7.25 (m, 4H), 7.17 (d, J = 8.1 Hz, 2H), 6.95 (t, J = 8.4 Hz,
2H), 5.64 (t, J = 5.6 Hz, 1H), 5.04 (t, J = 5.2 Hz, 1H), 4.41-
4.31 (m, 2H), 2.28 (s, 3H), 1.91 (s, 3H); 13C NMR (101 MHz,
DMSO-d6) δ = 169.5, 160.3, 138.8, 137.9, 137.2, 129.9, 128.9,
126.2, 125.0, 124.7, 123.9, 121.0, 109.5, 96.4, 58.3, 23.4, 20.6;
IR (neat):  3283, 2925, 1679, 1525, 1592, 1524, 1489, 1371,
1263, 1032, 967, 856, 786, 731, 693, 657 cm-1; HRMS calcu-
lated for C19H23N2O3 (M+NH4)+: 327.1703, Found: 327.1697.
(E)-N-(3-(2-hydroxyethylidene)-6-methyl-2-phenyl-2,3-
dihydrobenzofuran-2-yl)acetamide, (3ha). White solid, yield
47 mg (76%); 1H NMR (400 MHz, DMSO-d6) δ = 8.88 (s, 1H),
7.40-7.20 (m, 6H), 6.80-6.77 (m, 2H), 5.57 (t, J = 5.6 Hz, 1H),
4.99 (t, J = 5.2 Hz, 1H), 4.38-4.26 (m, 2H), 2.31 (s, 3H), 1.91
(s, 3H); 13C NMR (101 MHz, DMSO-d6) δ = 169.5, 160.5,
141.7, 140.2, 137.9 128.3, 127.7, 125.0, 124.66, 124.61, 121.9,
121.2, 110.0, 96.5, 58.2, 23.3, 21.3; IR (neat):  3275, 3034,
2922, 1673, 1618, 1521, 1492, 1447, 1369, 1336, 1259, 1146,
1033, 948, 809, 734, 699, 569 cm-1; HRMS calculated for
C19H23N2O3 (M+NH4)+: 327.1703, Found: 327.1696.
(E)-N-(3-(2-hydroxyethylidene)-2-(m-tolyl)-2,3-
dihydrobenzofuran-2-yl)acetamide, (3ac). White solid, yield
49 mg (80%); 1H NMR (400 MHz, DMSO-d6) δ = 8.90 (s, 1H),
7.35-7.11 (m, 6H), 6.99-6.94 (m, 2H), 5.65 (t, J = 5.6 Hz, 1H),
5.05 (t, J = 5.2 Hz, 1H), 4.42-4.30 (m, 2H), 2.30 (s, 3H), 1.91
(s, 3H); 13C NMR (101 MHz, DMSO-d6) δ = 169.5, 160.3,
141.6, 137.8, 137.5, 130.0, 128.5, 128.3, 126.3, 125.2, 125.0,
123.9, 121.9, 121.0, 109.5, 96.3, 58.3, 23.4, 21.2; IR (neat): 
3272, 3039, 2923, 1674, 1607, 1520, 1459, 1371, 1238, 1017,
968, 866, 785, 734, 699, 581, 490 cm-1; HRMS calculated for
C19H23N2O3 (M+NH4)+: 327.1703, Found: 327.1697.
(E)-N-(3-(2-hydroxyethylidene)-6-methoxy-2-phenyl-2,3-
dihydrobenzofuran-2-yl)pivalamide, (3ia). White solid, yield
36 mg (56%); 1H NMR (400 MHz, DMSO-d6) δ = 8.88 (s, 1H),
7.41-7.23 (m, 6H), 6.62 (d, J = 2.2 Hz, 1H), 6.53 (dd, J = 8.5,
2.3 Hz, 1H), 5.48 (t, J = 5.7 Hz, 1H), 4.96 (t, J = 5.2 Hz, 1H),
4.34-4.24 (m, 2H), 3.77 (s, 3H), 1.91 (s, 3H); 13C NMR (101
MHz, DMSO-d6) δ = 169.5, 161.9, 161.5, 141.7, 137.7, 128.3,
127.7, 125.5, 124.7, 123.1, 116.5, 107.5, 97.2, 95.5, 58.2, 55.4,
24.3; IR (neat):  3275, 2924, 1679, 1614, 1588, 1521, 1493,
1443, 1369, 1282, 1196,1156, 956, 826, 804, 732, 698, 635,
591 cm-1; HRMS calculated for C19H23N2O4 (M+NH4)+:
343.1652, Found: 343.1649.
(E)-N-(2-(4-fluorophenyl)-3-(2-hydroxyethylidene)-2,3-
dihydrobenzofuran-2-yl)acetamide, (3ae). White solid, yield
42 mg (68%); 1H NMR (400 MHz, DMSO-d6) δ = 8.93 (s, 1H),
7.45-7.41 (m, 2H), 7.35 (d, J = 7.5 Hz, 1H), 7.28 (d, J = 7.7
Hz, 1H), 7.21-7.16 (m, 2H), 6.99-6.95 (m, 2H), 5.65 (t, J = 5.6
Hz, 1H), 5.05 (t, J = 5.2 Hz, 1H), 4.42-4.31 (m, 2H), 1.90 (s,
(E)-N-(3-(2-hydroxyethylidene)-4,6-dimethyl-2-phenyl-2,3-
dihydrobenzofuran-2-yl)acetamide, (3ja). White solid, yield
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3H); 13C NMR (101 MHz, DMSO-d6) δ = 169.6, 161.8 (d, J =
961, 860, 736, 697, 600, 491 cm-1; HRMS calculated for
C24H25N2O3 (M+NH4)+: 389.1860, Found: 389.1857.
244.1 Hz), 160.0, 137.9 (d, J = 2.8 Hz), 137.7, 130.1, 126.9 (d,
J = 8.4 Hz), 126.7, 125.1, 123.6, 121.2, 115.1 (d, J = 21.6 Hz),
109.6, 96.0, 58.2, 23.3; 19F NMR (376 MHz, DMSO-d6) δ = -
115.09; IR (neat):  3259, 3046, 2925, 1672, 1602, 1506, 1460,
1274, 1227, 1159, 1018, 967, 839, 748, 545, 487 cm-1; HRMS
calculated for C18H20FN2O3 (M+NH4)+: 331.1452, Found:
331.1450.
(E)-N-(3-(2-hydroxypropylidene)-2-phenyl-2,3-
dihydrobenzofuran-2-yl)acetamide, (3aj). White solid, yield
35 mg (56%); 1H NMR (400 MHz, DMSO-d6) δ = 8.82 (s, 1H),
7.49-7.24 (m, 7H), 6.97-6.93 (m, 2H), 5.52 (d, J = 7.9 Hz, 1H),
4.93 (d, J = 4.7 Hz, 1H), 4.86-4.77 (m, 1H), 1.91 (s, 3H), 1.21
(d, J = 6.3 Hz, 3H) ppm; 13C NMR (101 MHz, DMSO-d6) δ =
169.4, 160.2, 141.5, 137.3, 130.5, 129.9, 128.3, 127.8, 125.0,
124.9, 123.5, 120.9, 109.6, 96.4, 62.7, 23.4, 23.1; IR (neat): 
3282, 2959, 2924, 1676, 1588, 1525, 1460, 1240, 861, 773,
699, 583, 550, 470 cm-1; HRMS calculated for C19H19NNaO3
(M+Na)+: 332.1257, Found: 332.1254. For the other isomer
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(E)-N-(2-(4-chlorophenyl)-3-(2-hydroxyethylidene)-2,3-
dihydrobenzofuran-2-yl)acetamide, (3af). White solid, yield
49 mg (75%); 1H NMR (400 MHz, DMSO-d6) δ = 8.96 (s, 1H),
7.44-7.28 (m, 6H), 7.02-6.97 (m, 2H), 5.66 (t, J = 5.6 Hz, 1H),
5.06 (t, J = 5.2 Hz, 1H), 4.42-4.31 (m, 2H), 1.92 (s, 3H); 13C
NMR (101 MHz, DMSO-d6) δ = 169.6, 160.1, 140.7, 137.6,
132.4, 130.2, 128.4, 127.1, 126.6, 125.1, 123.4, 121.3, 109.7,
95.8, 58.2, 23.3; IR (neat):  3264, 2923, 1682, 1588, 1525,
1460, 1369, 1270, 1093, 1022, 1006, 822, 747, 732, 545, 501,
464 cm-1; HRMS calculated for C18H20ClN2O3 (M+NH4)+:
347.1157, Found: 347.1154.
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3ajˈ. H NMR (400 MHz, DMSO-d6) δ = 8.83 (s, 1H), 7.45-
7.24 (m, 7H), 6.96-6.93 (m, 2H), 5.59 (d, J = 7.7 Hz, 1H), 4.95
(d, J = 4.5 Hz, 1H), 4.88-4.79 (m, 1H), 1.91 (s, 3H), 1.14 (d, J
= 6.3 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ = 169.3,
160.1, 141.5, 136.7, 130.6, 129.9, 128.3, 127.9, 124.9, 124.8,
123.4, 120.9, 109.6, 96.4, 62.9, 23.4, 23.2; IR (neat):  3725,
3283, 2962, 1679, 1588, 1527, 1460, 1241, 1064, 976, 698,
667, 583, cm-1; HRMS calculated for C19H19NNaO3 (M+Na)+:
332.1257, Found: 332.1256.
(E)-N-(2-(4-bromophenyl)-3-(2-hydroxyethylidene)-2,3-
dihydrobenzofuran-2-yl)acetamide, (3ag). White solid, yield
51 mg (68%); 1H NMR (400 MHz, DMSO-d6) δ = 8.97 (s, 1H),
7.55 (d, J = 7.2 Hz, 2H), 7.36-7.27 (m, 4H), 7.01-6.96 (m, 2H),
5.65 (t, J = 5.6 Hz, 1H), 5.06 (t, J = 5.2 Hz, 1H), 4.41-4.29 (m,
2H), 1.90 (s, 3H); 13C NMR (101 MHz, DMSO-d6) δ = 169.7,
160.1, 141.2, 137.5, 131.3, 130.2, 127.2, 126.9, 125.1, 123.4,
121.4, 121.0, 109.7, 95.9, 58.2, 23.3; IR (neat):  3217, 2916,
2848, 1660, 1589, 1520, 1484, 1457, 1394, 1367, 1314, 1276,
1104, 909, 824, 750, 547 cm-1; HRMS calculated for
C18H16BrKNO3 (M+K) +: 411.9945, Found: 411.9941.
Scaled-up of the Reaction. A Schlenk tube (25 mL) with a
stir bar was added 1a (2.0 mmol, 1 eq.), propargyl epoxides 2a
(3 mmol, 1.5 eq.), [RhCp*Cl2]2 (0.05 mmol, 2.5 mol%) and
CsOAc (1.0 mmol, 0.5 eq.). The tube was purged three times
by vacuum and N2, then the solvent (5 mL, 0.4 M) was added.
The mixture was stirred at room temperature for 16 h, which
was then concentrated in vacuum. The residue was purified by
silica gel column chromatography (petroleum ether/ethyl ace-
tate = 5/1 to 1/1) to give product 450 mg 3aa as white solid in
76% yield.
(E)-N-(2-(4-cyanophenyl)-3-(2-hydroxyethylidene)-2,3-
dihydrobenzofuran-2-yl)acetamide, (3ah). White solid, yield
42 mg (66%); 1H NMR (400 MHz, DMSO-d6) δ = 9.06 (s, 1H),
7.83 (d, J = 8.6 Hz, 2H), 7.55 (d, J = 8.5 Hz, 2H), 7.38-7.30
(m, 2H), 7.06-6.98 (m, 2H), 5.71 (t, J = 5.6 Hz, 1H), 5.08 (t, J
= 5.2 Hz, 1H), 4.41-4.30 (m, 2H), 1.93 (s, 3H); 13C NMR (101
MHz, DMSO-d6) δ = 169.9, 160.1, 147.0, 137.2, 132.5, 130.4,
128.1, 125.5, 125.2, 123.0, 121.6, 118.7, 110.4, 109.8, 95.6,
58.2, 23.2; IR (neat):  3306, 3063, 2230, 1682, 1588, 1502,
1461, 1370, 1264, 1237, 1154, 1017, 696, 842, 731, 556, 483
cm-1; HRMS calculated for C19H20N3O3 (M+NH4)+: 338.1499,
Found: 338.1496.
Synthesis of 4. A Schlenk tube (25 mL) with a stir bar was
added 3aa (0.2 mmol, 1 eq.) and the tube was purged three
times by vacuum and N2. Then triethyl orthoformate (0.6
mmol, 3.0 eq.), EtCOOH (0.01 mmol, 0.05 eq.) and dioxane (2
mL) was added. The mixture was stirred at 100 °C for 6 h,
which then cooled to room temperature. After that the mixture
was concentrated in vacuum. The residue was purified by sili-
ca gel column chromatography (petroleum ether/ethyl acetate
= 10/1 to 5/1) to give product 4 as white solid in 62% yield.
2-Methyl-3a-phenyl-8b-vinyl-3a,8b-dihydrobenzofuro[2,3-
d]oxazole, (4). White solid, yield 34mg (62%); 1H NMR (400
MHz, DMSO-d6) δ = 7.46-7.34 (m, 4H), 7.29-7.22 (m, 3H),
7.13-7.05 (m, 2H), 5.34 (dd, J = 17.2, 10.5 Hz, 1H), 5.20-5.10
(m, 2H), 2.17 (s, 3H); 13C NMR (101 MHz, DMSO-d6) δ =
168.8, 158.6, 137.2, 133.8, 132.0, 128.6, 128.1, 126.6, 126.1,
125.1 121.8, 117.4, 115.8, 110.7, 95.9, 13.90; IR (neat): υ
3304, 2917, 2849, 1657, 1598, 1520, 1462, 1386, 1281, 1064,
983, 752, 698, 665, 491 cm-1; HRMS calculated for
C18H16NO2 (M+H)+: 278.1176, Found: 278.1173.
(E)-N-(3-(2-hydroxy-2-phenylethylidene)-2-phenyl-2,3-
dihydrobenzofuran-2-yl)acetamide, (3ai). White solid, yield
40 mg (54%); 1H NMR (400 MHz, DMSO-d6) δ = 8.95 (s, 1H),
7.58-7.16 (m, 12H), 6.97 (d, J = 8.0, 1H), 6.92 (t, J = 7.5, 1H),
5.79-5.67 (m, 3H), 1.88 (s, 3H); 13C NMR (101 MHz, DMSO-
d6) δ = 169.6, 160.4, 143.9, 141.2, 139.3, 130.3, 128.4, 128.2,
128.1, 128.0, 126.9, 126.2, 125.2, 124.9, 123.7, 120.9, 109.6,
96.6, 67.9, 23.3；IR (neat):  3272, 3053, 2923, 2853, 1659,
1574, 1517, 1441, 1391, 1266, 1066, 1032, 968, 947, 808, 733,
700, 642, 566 cm-1; HRMS calculated for C24H25N2O3
(M+NH4)+: 389.1860, Found: 389.1857. For the other isomer
3aiˈ. 1H NMR (400 MHz, DMSO-d6) δ = 8.95 (s, 1H), 7.51 (t,
J = 6.3 Hz, 1H), 7.39-7.17 (m, 11H), 6.98 (d, J = 8.0 Hz, 1H),
6.92 (t, J = 7.5 Hz, 1H), 5.81-5.69 (m, 3H), 1.96 (s, 3H); 13C
NMR (101 MHz, DMSO-d6) δ = 169.6, 160.5, 143.9, 141.5,
138.3, 130.4, 128.3, 128.2, 128.0, 127.7, 127.1, 126.2, 124.9,
124.8, 123.3, 121.0, 109.7, 96.6, 68.4, 23.4; IR (neat):  3268,
3030, 2922, 1668, 1603, 1520, 1460, 1368, 1316, 1241, 1015,
Synthesis of 5. To a solution of 3aa (0.10 mmol, 1 eq) in
anhydrous dichloromethane (2 ml) at 0 °C was added Dess-
Martin periodinane reagent (DMP) (0.12 mmol, 1.2 eq) and
the reaction mixture was stirred at that temperature for 1 hour.
The reaction was quenched by the addition of 2 ml saturated
aqueous sodium thiosulfate and the aqueous layer was extract-
ed with EtOAc (2 × 10 mL). The combined organic extracts
were washed twice with saturated aqueous sodium bicarbonate
and then dried over anhydrous sodium sulfate, filtered, con-
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Song, G.; Li, X. Substrate Activation Strategies in Rhodium(III)-
centrated and purified by silica gel flash column chromatog-
raphy (petroleum ether/ethyl acetate = 2/1) to give the desired
unsaturated aldehyde as a Z/E mixture in a yield of 76%.A dry
tube charged with a stir bar was added the unsaturated alde-
hyde (0.06 mmol, 1 eq.) and NHC (6, 0.006 mmol, 10 mol%).
The tube was purged three times by vacuum and N2, then THF
(2 mL) and DBU (0.009 mmol, 15 mol%) were added. The
mixture was stirred at room temperature for 12 h, which then
was quenched with sat. NH4Cl. The aqueous layer was ex-
tracted with EtOAc (2 × 10 mL). The combined organic ex-
tracts were washed with brine, then dried over anhydrous so-
dium sulfate, filtered, concentrated and purified by silica gel
flash column chromatography (petroleum ether/ethyl acetate =
5/1) to give the desired product 5 in 80% isolated yield.
Catalyzed Selective Functionalization of Arenes. Acc. Chem. Res.
2015, 48, 1007-1020. (f) Chen, Z.; Wang, B.; Zhang, J.; Yu, W.; Liu,
Z.; Zhang, Y. Transition metal-catalyzed C–H bond functionalizations
by the use of diverse directing groups. Org. Chem. Front. 2015, 2,
1107-1295.
(2) For reviews: (a) Mo, J.; Wang, L.; Liu, Y.; Cui, X. Transition-
Metal-Catalyzed Direct C–H Functionalization under External-
Oxidant-Free Conditions. Synthesis 2015, 47, 439-459. (b) Song, G.;
Wang, F.; Li, X. C–C, C–O and C–N bond formation via
rhodium(III)-catalyzed oxidative C–H activation. Chem. Soc. Rev.
2012, 41, 3651-3678.
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(3) For selected examples: (a) Wu, Y.; Chen, Z.; Yang, Y.; Zhu, W.;
Zhou, B. Rh(III)-Catalyzed Redox-Neutral Unsymmetrical C–H
Alkylation and Amidation Reactions of N-Phenoxyacetamides. J. Am.
Chem. Soc. 2018, 140, 42-45 and references cited therein. (b) Wang,
X.; Lerchen, A.; Gensch, T.; Knecht, T.; Daniliuc, C. G.; Glorius, F.
Combination of Cp*RhIII-Catalyzed C−H Activation and a Wagner–
Meerwein-Type Rearrangement. Angew. Chem., Int. Ed. 2017, 56,
1381-1384. (c) Hu, Z.; Tong, X.; Liu, G. Rhodium(III) Catalyzed
Carboamination of Alkenes Triggered by C–H Activation of N-
Phenoxyacetamides under Redox-Neutral Conditions. Org. Lett. 2016,
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references cited therein. (e) Zhang, X.; Qi, Z.; Li, X. Rhodium(III)-
Catalyzed C−C and C−O Coupling of Quinoline N–Oxides with
Alkynes: Combination of C–H Activation with O-Atom Transfer.
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G.; Li, G.; Huang, H. Rh-Catalyzed Sequential Oxidative C–H and
N–N Bond Activation: Conversion of Azines into Isoquinolines with
Air at Room Temperature. Org. Lett. 2014, 16, 3532-3535. (g) Liu, B.;
Fan, Y.; Gao, Y.; Sun, C.; Xu, C.; Zhu, J. Rhodium(III)-Catalyzed N-
Nitroso-Directed C–H Olefination of Arenes. High-Yield, Versatile
Coupling under Mild Conditions. J. Am. Chem. Soc. 2013, 135, 468-
473 and references cited therein. (h) Shi, Z.; Koester, D. C.;
Boultadakis-Arapinis, M.; Glorius, F. Rh(III)-Catalyzed Synthesis of
Multisubstituted Isoquinoline and Pyridine N-Oxides from Oximes
and Diazo Compounds. J. Am. Chem. Soc. 2013, 135, 12204-12207. (i)
Liu, G.; Shen, Y.; Zhou, Z.; Lu, X. Rhodium(III)-Catalyzed Redox-
Neutral Coupling of N-Phenoxyacetamides and Alkynes with Tunable
Selectivity. Angew. Chem., Int. Ed. 2013, 52, 6033-6037.
N-((2-oxo-2H-chromen-4-yl)(phenyl)methyl)acetamide, (5).
White solid, 18 mg (61%) for two steps; 1H NMR (400 MHz,
DMSO-d6) δ = 8.85 (d, J = 7.9 Hz, 1H), 7.70 (dd, J = 8.0, 1.1
Hz, 1H), 7.63-7.56 (m, 1H), 7.44 (td, J = 5.5, 1.2 Hz, 3H),
7.41-7.25 (m, 4H), 6.48 (d, J = 7.9 Hz, 1H), 6.38 (s, 1H), 1.95
(s, 3H); 13C NMR (101 MHz, DMSO-d6) δ = 168.8, 159.9,
155.5, 153.2, 138.4, 132.1, 128.8, 128.2, 128.1, 125.2, 124.5,
117.5, 116.9, 112.9, 52.2, 22.4; FTIR (neat): υ 3797, 2922,
1719, 1644, 1604, 1526, 1445, 1371, 1291, 1257, 1179, 995,
752, 701, 616, 527 cm-1; HRMS calculated for C18H16NO3
(M+H)+: 294.1125, Found: 294.1121.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
1
Copies of H and 13C NMR spectra of new compounds and
details of deuterium experiments (PDF)
NOE spectra of the compound 3aa (PDF)
AUTHOR INFORMATION
Corresponding Author
* E-mail: yanglee@mail.xjtu.edu.cn
silongxu@mail.xjtu.edu.cn
(4) For a review: Mishra, N. K.; Sharma, S.; Park, J.; Han, S.; Kim, I.
S. Recent Advances in Catalytic C(sp2)–H Allylation Reactions. ACS
Catal. 2017, 7, 2821-2847.
Notes
The authors declare no competing financial interest.
(5) (a) Sk, M. R.; Bera, S. S.; Maji, M. S. Weakly Coordinating,
Ketone-Directed Cp*Co(III)-Catalyzed C–H Allylation on Arenes
and Indoles. Org. Lett. 2018, 20, 134-137 and references cited therein.
(b) Kljajic, M.; Puschnig, J. G.; Weber, H.; Breinbauer R. Additive-
Free Pd-Catalyzed α-Allylation of Imine-Containing Heterocycles.
Org. Lett. 2017, 19, 126-129. (c) Lee, S. Y.; Hartwig, J. F. Palladium-
Catalyzed, Site-Selective Direct Allylation of Aryl C–H Bonds by
Silver-Mediated C–H Activation: A Synthetic and Mechanistic
Investigation. J. Am. Chem. Soc. 2016, 138, 15278-15284. (d) Dai, H.;
Yu, C.; Wang, Z.; Yan, H.; Lu C. Solvent-Controlled, Tunable β-OAc
and β-H Elimination in Rh(III)-Catalyzed Allyl Acetate and Aryl
Amide Coupling via C–H Activation. Org. Lett. 2016, 18, 3410-3413.
(e) Wang, H.; Schröder, N.; Glorius, F. Mild Rhodium(III)-Catalyzed
Direct C–H Allylation of Arenes with Allyl Carbonates. Angew.
Chem., Int. Ed. 2013, 52, 5386-5389.
(6) Kalsi, D.; Laskar, R. A.; Barsu, N.; Premkumar, J. R.;
Sundararaju B. C-8-Selective Allylation of Quinoline: A Case Study
of β-Hydride vs β-Hydroxy Elimination. Org. Lett. 2016, 18, 4198-
4201.
(7) For a review: (a) Wang, F.; Yu, S.; Li, X. Transition metal-
catalysed couplings between arenes and strained or reactive rings:
combination of C–H activation and ring scission. Chem. Soc. Rev.
ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China (Nos.
21602167, 21402149), the Natural Science Basic Research Plan in
Shaanxi Province of China (Nos. 2016JQ2019, 2015JQ2050), the
China Postdoctoral Science Foundation (Nos. 2015M580830,
2014M550484, 2015T81013), and the Fundamental Research
Funds for the Central Universities.
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