Palladium-Catalyzed Sequential Heteroarylation/Acylation Reactions of Iodobenzenes: Synthesis of Functionalized Benzo [d] oxazoles

Article abstract of DOI:10.1021/acs.joc.7b03055

We report an efficient palladium-catalyzed approach to the synthesis of benzoxazole derivatives via sequential heteroarylation/acylation reaction of iodobenzenes. Three readily available starting materials, iodobenzenes, anhydrides, and benzoxazoles, were

Full text of DOI:10.1021/acs.joc.7b03055

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Note
Palladium-Catalyzed Sequential Heteroarylation/Acylation Reactions
of Iodobenzenes: Synthesis of Functionalized Benzo[d]oxazoles
Pingshun Zhang, Shanfei Pan, Wanzhi Chen, Miaochang Liu, and Huayue Wu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b03055 • Publication Date (Web): 20 Feb 2018
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PalladiumꢀCatalyzed Sequential
Heteroarylation/Acylation Reactions of
Iodobenzenes: Synthesis of Functionalized
Benzo[d]oxazoles
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Pingshun Zhang† Shanfei Pan† Wanzhi Chen,†* Miaochang Liu‡ and Huayue Wu‡*
†Department of Chemistry, Zhejiang University, Yuquan Campus, Hangzhou 310027, China.
‡College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, 325027,
China.
ABSTRACT: We report an efficient palladiumꢀcatalyzed approach to the synthesis of
benzoxazoles derivatives via sequential heteroarylation / acylation reaction of iodobenzenes.
Three readily available starting materials iodobenzenes, anhydrides, and benzoxazoles were
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smoothly coupled forming new CꢀC bonds at the ortho and ipso positions of the iodobenzenes to
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afford 2ꢀheteroarylꢀ3ꢀacylbenzene derivatives in good yields.
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KEYWORDS: CꢀH activation, Catellani reaction, acylation, heteroarylation, palladium catalysis
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Benzoxazole derivatives are an important class of heterocyclic compounds found in many
natural and functional products such as UKꢀ1, MUKꢀ1, DMUKꢀ1, AJI9561,1 estrogen receptor
ligand,2 A33853, and Tetraacetyl A33853,3 which show antimicrobial, antiꢀbacterial, and antiꢀ
tumor activities (Figure 1). 2ꢀArylbenzoxazoles are important structural units for the construction
of functional materials, agrochemicals, and pharmaceutically active compounds.4 Benzoxazoles
are typically prepared from the condensation of 2ꢀaminophenols and carboxylates.5 Recently, the
C−H arylation of benzoxazoles with an aryl electrophiles has been reported, and the reaction
offers an efficient protocol for the derivatization of readily available benzoxazoles. In the
presence of oxidants, compounds such as aryl halides,6 acyl chlorides,7 and
aryltrimethylammonium triflates,8 or arylboronates,9 arylsilanes,10 and polyfluorinated arenes11
were able to couple with benzoxazoles to generate 2ꢀarylated benzoxazoles in good yields by
using an appropriate palladium catalyst. These approaches are quite practical but limited to
readily available electrophiles.
O
O
OR1
R2O
OH
O
N
O
N
HO
N
O
N
O
UK-1 (R1 = Me, R2 = H)
MUK-1 (R1 = Me, R2 = Me)
DMUK-1 (R1 = H, R2 = H)
AJI9561
OR
N
RN
RO
O
OR
O
HO
N
N
O
OH
O
OMe
A33853
(I) R = H
estrogen receptor ligand
Tetraacetyl A33853 (II) R = CH3CO
Figure 1. Important molecules featuring benzoxazole core structure
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The palladiumꢀcatalyzed Catellani reaction allows dual functionalization of aryl halides at both
the ortho and ipso sites in one pot.12 Through this protocol, ortho CꢀH arylation, alkylation,
acylation, and amination and ipso CꢀI alkenylation, alkynylation, cyanation, borylation have
been realized in recent years.12,13 The reaction proceeds via a Pdꢀcatalyzed norborneneꢀmediated
activation of the ortho CꢀH position and subsequent crossꢀcoupling at the ipso position.12,14
Direct CꢀH activation and functionalization of benzoxazoles have been recently reported.15
Palladiumꢀcatalyzed tandem ortho alkylation/CꢀH functionalization reactions between aryl
iodides and Nꢀbromoalkylindoles,16 3ꢀ(bromoalkyl)thiophenes or furans17 have also been
reported to give polycyclic heterocycles. We envisioned that this strategy could be applied to the
2ꢀarylation of benzoxazoles in which benzoxazoles act as the nucleophilic partner, and an
additional functional group could be simultaneously introduced at the ipso site. Herein, we report
palladiumꢀcatalyzed threeꢀcomponent reactions of iodoarenes, aromatic anhydrides, and
benzoxazoles. A number of 2ꢀarylated benzoxazoles were obtained in good yields.
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Initially, we chose 2ꢀiodotoluene (1a), benzoic anhydride (2a), and benzoxazole (3a) as the
starting materials and used the typical conditions previously reported for acylation/cyanation of
iodobenzene.14,18 The results are summarized in Table 1. Reaction did not occur in the presence
of palladium chloride (10 mol%), TFP (20 mol%), norbornene (NBE, 2 equiv.), and Cs2CO3 (3
equiv.) at 100 °C in 1,4ꢀdioxane (Table 1, entry 1). To our delight, the same reaction did proceed
smoothly when one equivalent of CuBr was added, and target product 4a was isolated in 58%
yield (entry 2). When Cs2CO3 was replaced by K2CO3, the yield of 4a sharply increased to 83%
(entry 3). Other bases such as Na2CO3 did not work well, and only a trace amount of 4a was
obtained (entry 4). After further screening several common solvents, we identified CH3CN as the
most effective solvent, and the yield could be further increased to 93% (entries 5ꢀ7). The reaction
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resulted in a lower yield when other solvents such as toluene and DME were chosen. Further
experiments showed that without PdCl2 the reaction did not proceed, and other palladium
catalysts such as Pd2(dba)3·CHCl3, Pd(OAc)2,and [Pd(C3H5)Cl]2 were not effective for this threeꢀ
component reaction (entries 8ꢀ11).
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Table 1. Optimization of the catalysts and the reaction conditions a
Entry
[Pd]
Ligand
TFPb
TFP
TFP
TFP
TFP
TFP
TFP
TFP
Base
Solvent
Additive Yield (%)
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PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
ꢀꢀ
Cs2CO3
Cs2CO3
K2CO3
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
toluene
ꢀꢀ
0
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
58
83
trace
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35
93
0
DME
CH3CN
CH3CN
Pd2(dba)3·CH
Cl3
9
TFP
TFP
TFP
K2CO3
K2CO3
CH3CN
CH3CN
CH3CN
CuBr
CuBr
CuBr
trace
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11
Pd(OAc)2
trace
[Pd(C3H5)Cl]
2
K2CO3
Trace
a Reaction conditions: 1a (0.3 mmol), 2a (0.9 mmol), 3a (0.6 mmol), catalyst (0.03 mmol), TFP (0.06
mmol), NBE (0.6 mmol), base (0.9 mmol), CuBr (0.3 mmol), solvent (3.0 mL), 100 °С, 16 h in a sealed
tube under N2. b TFP is tri(2ꢀfuryl)phosphine.
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Under the optimized reaction conditions described above, we next examined the scope of the
acid anhydride substrates. Various acid anhydrides bearing either electronꢀwithdrawing or
electronꢀdonating functional groups such as methyl, methoxyl, and fluoride reacted smoothly
with iodobenzene and benzoxazoles and afforded the corresponding products 4a–4m in good
yields (Table 2). Generally, electronꢀrich aromatic acid anhydrides were good reaction partners,
and target products 4a and 4d could be obtained in greater than 90% yields. The reactions of acid
anhydrides containing strong electronꢀwithdrawing groups gave somewhat lower yields. When
2ꢀnaphthoic anhydride was used, 4g was obtained in 58% yield, illustrating that steric hindrance
has little influence on the reaction. Unfortunately, we found that aliphatic acid anhydrides were
not active in the threeꢀcomponent reaction.
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The substrate scope of the reaction was further extended to a range of iodobenzenes and
heterocyclic compounds, and the results are shown in Tables 3 and 4, respectively. In general, all
the reactions occurred smoothly and gave the desired products in moderate yields. The reactions
of iodobenzenes bearing alkyl and alkoxyl groups afforded the corresponding products in good
yields. However, iodobenzenes bearing fluoro and chloro substituents were much less active.
When 1ꢀiodonaphthalene was used, 5a was obtained in 85% yield. These results illustrated that
strong electronꢀdonating groups have a significant influence on the reaction. 2,4ꢀ
Difluoroiodobenzene was also tolerated and afforded corresponding product 5e in moderate
yield.
To examine the compatibility of benzo[d]oxazoles, a few substituted benzo[d]oxazoles were
subjected to the optimized reaction conditions. The results are given in Table 3.
Benzo[d]oxazoles with electronꢀdonating and electronꢀwithdrawing groups were all compatible
with the reaction conditions. The desired products were obtained in moderate yields. Under the
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same conditions, thiazoles could also participate in the reaction and gave 2ꢀarylated thiazole
derivatives. When benzo[d]thiazole and 4ꢀmethylthiazole were used, 6h and 6i were obtained in
58% and 24% yields, respectively. However, when 5ꢀ(tertꢀbutyl)benzo[d]oxazole was used, 6g
was only obtained in 45% yield, illustrating that steric hindrance has a significant influence on
the reaction. Other heterocyclic compounds such as benzofuran, benzothiophene, and
benzoimidazole were also tested. Unfortunately, no desired coupling products were obtained.
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Table 2. Scope of acid anhydrides
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Reaction conditions: 1 (0.3 mmol), 2 (0.9 mmol), 3a (0.6 mmol), PdCl2 (0.03 mmol), TFP
(0.06 mmol), NBE (0.6 mmol), K2CO3 (0.9 mmol), CuBr (0.3 mmol), acetonitrile (3.0 mL), 100
°С, 16 h in a sealed tube under N2.
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Table 3. Scope of iodobenzenes and heterocycles
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Reaction conditions: 1a (0.3 mmol), 2a (0.9 mmol), 3a (0.6 mmol), PdCl2 (0.03 mmol), TFP
(0.06 mmol), NBE (0.6 mmol), K2CO3 (0.9 mmol), CuBr (0.3 mmol), acetonitrile (3.0 mL), 100
°С, 16 h in a sealed tube under N2.
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In the case of 6ꢀnitrobenzo[d]oxazole, the reaction with 2ꢀiodotoluene and benzoic anhydride
under the standard conditions afforded two products, 7a and 7a’, in 45% and 30% yields,
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respectively (Table 4). H NMR and mass spectral analyses showed that 7a is the normal threeꢀ
component coupling product, and 7a’ contains a bicyclo[2.2.1]heptane moiety. Similarly, the
reactions of 2,4ꢀdimethyliodobenzene, 2,4ꢀfluoroiodobenzene, 2ꢀisopropyliodobenzene, and 1ꢀ
iodonaphthalene with 6ꢀnitrobenzo[d]oxazole under the optimized reaction conditions also gave
mixtures of two products. It seemed that in the case of electronꢀdeficient benzoxazoles the
elimination of norbornene is more difficult. The ratios of the two products depends on the
reactants. Single crystals of compound 7c’ were grown by slow diffusion of its hexane solution,
and its structure determined by Xꢀray diffraction analysis and is shown in the Supporting
Information. However, when 4ꢀnitrobenzoic anhydride and 2ꢀiodophenol were used, the normal
threeꢀcomponent coupling product was not obtained, but 7g and 7f were obtained in 46% and
65% yields, respectively. Acylation at the ortho position did not occur. Obviously, anhydrides
with strong electronꢀwithdrawing groups disfavored the acylation process.
Table 4. Reactions of 6ꢀnitrobenzo[d]oxazole
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Reaction conditions: 1a (0.3 mmol), 2a (0.9 mmol), 3a (0.6 mmol), PdCl2 (0.03 mmol),
TFP (0.06 mmol), NBE (0.6 mmol), K2CO3 (0.9 mmol), CuBr (0.3 mmol), acetonitrile
(3.0 mL), 100 °С, 16 h in sealed tube under N2.
A plausible mechanism of the threeꢀcomponent reaction was proposed based on the literature
reports and is depicted in Figure 2.12ꢀ14 The first step involves oxidative addition of the
iodobenzene on to Pd(0) to produce intermediate I. Insertion of a molecule of norbornene into
the CꢀPd bond of I would form intermediate II. Subsequent CꢀH activation and elimination of HI
leads to palladacycle III. Further oxidative addition of acid anhydride to III was proposed to
form Pd(IV) species IV. Reductive elimination of intermediate IV leads to orthoꢀacylated
intermediate V. Decarbopalladation with expulsion of norbornene would give intermediate VI.
Reductive elimination would release the final product. Because nitroꢀcontaining benzoxazole is
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more acidic, the oxidative addition of the CꢀH bond would form Pd(IV) species IV'. In this case,
products 7’ were obtained.
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Figure 2. A plausible mechanism
CONCLUSION
In summary, we have described a palladiumꢀcatalyzed sequential ortho acylation/ipso
heteroarylation of iodobenzenes using readily available anhydrides and benzoxazoles as the
coupling reagents. The reaction proceeds via a palladiumꢀcatalyzed/norborneneꢀmediated
regioselective ortho CꢀH activation/acylation and subsequent oxidative coupling at the CꢀI
position. A number of 2ꢀheteroarylꢀ3ꢀacylbenzene derivatives were obtained in good yields in a
oneꢀpot manner.
EXPERIMENTAL SECTION
All chemicals were of reagent grade quality obtained from commercial sources and used as
received. Benzoic anhydrides 219 and benzoxazoles 320 were prepared according to the
literatures.
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General Procedure for Synthesis of 4, 5, 6 and 7. To a 15 mL of Schlenk tube equipped with
a Teflonꢀcoated magnetic stir bar was charged with aryl iodide 1a (65.4 mg, 0.3 mmol, 1.0
equiv), benzoxazole 3a (71.4 mg, 0.6 mmol, 2.0 equiv), anhydride 2a (203.5 mg, 0.9 mmol, 3.0
equiv), PdCl2 (5.4 mg, 0.03 mmol, 10 mol%), TFP (13.9 mg, 0.06 mmol, 20 mol%), K2CO3
(124.4 mg, 0.9 mmol, 3.0 equiv), CuBr (43.0 mg, 0.3 mmol, 1.0 equiv), norbornene (56.5 mg,
0.6 mmol, 2.0 equiv), and acetonitrile (3.0 mL). The resulting suspension was stirred at room
temperature for 5 min under N2, and then heated to 100 °C for 16 h. Upon completion of the
reaction as monitored by TLC, the reaction was allowed to cool to room temperature, diluted
with ethyl acetate (10 mL) and water (15 mL), and extracted with ethyl acetate (15 mL x 3). The
organic phase was collected and washed with brine, dried over Na2SO4, then filtered and
concentrated. The crude residue was purified by flash column chromatography on silica gel using
petroleum ether/ethyl acetate (10/1) as eluent to give the corresponding products 4ꢀ7.
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(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)(phenyl)methanone (4a)
1
Light yellow oil. Yield: 87.4 mg, 93%. H NMR (400 MHz, CDCl3): δ 7.66ꢀ7.70 (m, 2H),
7.59ꢀ7.64 (m, 1H), 7.53 (d, J = 4.8 Hz, 2H), 7.46ꢀ7.49 (m, 1H), 7.31ꢀ7.40 (m, 2H), 7.21ꢀ7.28 (m,
4H), 2.59 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 197.0, 161.2, 150.3, 141.4, 141.1, 139.3,
137.1, 133.2, 132.7, 130.2, 129.4, 128.1, 127.0, 126.5, 125.1, 124.3, 121.5, 120.1, 111.5, 110.5,
20.7. HRMS (EIꢀTOF) m/z calcd. for C21H15NO2: 313.1103; found: 313.1108.
(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)(o-tolyl)methanone (4b)
1
Light yellow oil. Yield: 82.4 mg, 84%. H NMR (400 MHz, CDCl3): δ 7.59ꢀ7.64 (m, 1H),
7.49ꢀ7.54 (m, 3H), 7.36ꢀ7.41 (m, 1H) , 7.23ꢀ7.29 (m, 2H), 7.19 (dd, J = 1.2, 7.6 Hz, 1H), 7.08
(dt, J = 1.6, 7.6 Hz, 1H), 6.98 (t, J = 7.6 Hz, 1H), 6.92 (d, J = 7.6 Hz, 1H), 2.49 (s, 3H), 2.45 (s,
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3H). 13C NMR (100 MHz, CDCl3): δ 198.6, 161.4, 150.4, 142.1, 141.3, 139.2, 138.5, 137.2,
133.5, 130.9, 130.3, 130.1, 127.7, 127.0, 125.0, 124.9, 124.3, 120.1, 110.5, 20.7, 20.3. HRMS
(EIꢀTOF) m/z calcd. for C22H17NO2: 327.1259; found: 327.1262.
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(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)(m-tolyl)methanone (4c)
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Light yellow oil. Yield: 70.7 mg, 72%. H NMR (400 MHz, CDCl3): δ 7.60ꢀ7.66 (m, 1H),
7.50ꢀ7.54 (m, 3H), 7.43ꢀ7.49 (m, 2H), 7.36ꢀ7.41 (m, 1H), 7.22ꢀ7.28 (m, 2H), 7.10ꢀ7.17 (m, 2H),
2.58 (s, 3H), 2.25 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 197.2, 161.3, 150.4, 141.4, 141.2,
139.3, 137.9, 137.1, 133.4, 133.1, 130.1, 129.9, 127.9, 127.1, 126.9, 126.7, 125.1, 124.3, 120.1,
110.5, 21.2, 20.6. HRMS (EIꢀTOF) m/z calcd. for C22H17NO2: 327.1259; found: 327.1258.
(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)(3,5-dimethylphenyl)methanone (4d)
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Light yellow oil. Yield: 96.2 mg, 94%. H NMR (400 MHz, CDCl3): δ 7.60ꢀ7.66 (m, 1H),
7.49ꢀ7.53 (m, 2H), 7.45ꢀ7.48 (m, 1H), 7.36ꢀ7.41 (m, 1H), 7.29 (s, 2H), 7.22ꢀ7.27 (m, 2H), 6.97
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(s, 1H), 2.56 (s, 3H), 2.21 (s, 6H). C NMR (100 MHz, CDCl3): δ 197.3, 161.4, 150.4, 141.5,
141.3, 139.3, 137.7, 137.1, 134.3, 133.0, 130.0, 127.4, 127.1, 126.8, 125.0, 124.2, 120.1, 110.5,
21.1, 20.6. HRMS (EIꢀTOF) m/z calcd. for C23H19NO2: 341.1416; found: 341.1417.
(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)(p-tolyl)methanone (4e)
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Light yellow solid, mp: 83ꢀ85 °C. Yield: 78.5 mg, 80%. H NMR (400 MHz, CDCl3): δ 7.58ꢀ
7.66 (m, 3H), 7.48ꢀ7.51 (m, 2H), 7.42ꢀ7.46 (m, 1H), 7.35ꢀ7.41 (m, 1H), 7.21ꢀ7.27 (m, 2H), 7.07
(d, J = 8.0 Hz, 2H), 2.58 (s, 3H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 196.6, 161.4,
150.4, 143.6, 139.4, 134.5, 132.9, 130.1, 129.7, 128.8, 127.6, 126.9, 126.5, 125.8, 125.1, 124.3,
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121.5, 120.2, 111.5, 110.5, 21.6, 20.7. HRMS (EIꢀTOF) m/z calcd. for C22H17NO2: 327.1259;
found: 327.1257.
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(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)(mesityl)methanone (4f)
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White solid, mp: 189ꢀ191 °C. Yield: 67.1 mg, 63%. H NMR (400 MHz, CDCl3): δ 7.71ꢀ7.76
(m, 1H), 7.49ꢀ7.54 (m, 2H), 7.44ꢀ7.48 (m, 2H), 7.29ꢀ7.34 (m, 2H), 6.70 (s, 2H), 2.35 (s, 3H),
2.18 (s, 3H), 2.13 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 199.8, 162.0, 150.8, 141.6, 140.0,
139.1, 136.1, 135.3, 134.4, 130.5, 128.5, 128.3, 127.6, 124.9, 124.2, 120.1, 110.6, 29.7, 21.1,
20.0, 19.7. HRMS (EIꢀTOF) m/z calcd. for C24H21NO2: 355.1572; found: 355.1574.
(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)(naphthalen-2-yl)methanone (4g)
Light yellow oil. Yield: 63.2 mg, 58%. 1H NMR (400 MHz, CDCl3): δ 8.13 (s, 1H), 7.89 (dd, J
= 1.6, 8.8 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.42ꢀ7.58 (m, 6H), 7.28ꢀ
7.34 (m, 1H), 7.14ꢀ7.19 (m, 2H), 2.61 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 196.9, 161.4,
150.4, 141.4, 141.3, 139.6, 135.3, 134.5, 133.2, 132.1, 131.9, 130.1, 129.5, 128.4, 128.2, 127.7,
127.0, 126.8, 126.6, 125.1, 124.8, 124.3, 120.1, 110.5, 20.8. HRMS (EIꢀTOF) m/z calcd. for
C25H17NO2: 363.1259; found: 363.1263.
(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)(2-methoxyphenyl)methanone (4h)
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Light yellow solid, mp: 110ꢀ111 °C. Yield: 57.6 mg, 56%. H NMR (400 MHz, CDCl3): δ
7.52ꢀ7.58 (m, 1H) , 7.39ꢀ7.48 (m, 3H), 7.31ꢀ7.36 (m, 1H) , 7.26 (dd, J = 1.6, 7.6 Hz, 1H), 7.17ꢀ
7.21 (m, 2H) , 7.06ꢀ7.13 (m, 1H), 6.65 (dt, J = 0.4, 7.2 Hz, 1H) , 6.60 (d, J = 8.4 Hz, 1H), 3.57
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(s, 3H), 2.39 (s, 3H). C NMR (100 MHz, CDCl3): δ 195.9, 161.6, 158.1, 150.5, 142.3, 141.5,
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138.8, 133.1, 132.9, 131.1, 130.1, 127.5, 127.3, 126.6, 124.8, 124.1, 120.0, 119.9, 111.3, 110.6,
55.7, 20.1. HRMS (EIꢀTOF) m/z calcd. for C22H17NO3: 343.1208; found: 343.1207.
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(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)(3-fluorophenyl)methanone (4i)
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Light yellow oil. Yield: 51.7 mg, 52%. H NMR (400 MHz, CDCl3): δ 7.61ꢀ7.65 (m, 1H),
7.53ꢀ7.57 (m, 2H), 7.46ꢀ7.50 (m, 1H), 7.37ꢀ7.44 (m, 3H), 7.25ꢀ7.28 (m, 2H), 7.18ꢀ7.23 (m, 1H),
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7.00ꢀ7.06 (m, 1H), 2.61 (s, 3H). C NMR (100 MHz, CDCl3): δ 195.6 (d, JCꢀF = 2.3Hz), 162.4
(d, JCꢀF = 246.5 Hz), 161.0, 150.3, 141.3, 140.5, 139.5, 139.2 (d, JCꢀF = 6.3), 133.5, 130.3, 129.8
(d, JCꢀF = 7.4 Hz), 127.0, 126.5, 125.3, 125.2 (d, JCꢀF =2.8), 124.4, 120.2, 119.6 (d, JCꢀF = 21.5
Hz), 115.8 (d, JCꢀF = 22,2 Hz), 110.5, 20.7. HRMS (EIꢀTOF) m/z calcd. for C21H14FNO2:
331.1009; found: 331.1011.
(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)(4-fluorophenyl)methanone (4j)
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Light yellow oil. Yield: 47.8 mg, 48%. H NMR (400 MHz, CDCl3): δ 7.61ꢀ7.68 (m, 2H),
7.53ꢀ7.59 (m, 1H), 7.47 (d, J = 4.8 Hz, 2H), 7.39 (t, J = 4.4 Hz, 1H), 7.29ꢀ7.34 (m, 1H), 7.19ꢀ
7.24 (m, 2H), 6.86 (t, J = 8.8 Hz, 2H), 2.53 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 195.5, 165.4
(d, JCꢀF = 253.4 Hz), 161.1, 150.3, 141.1 (d, JCꢀF = 44.4 Hz), 139.4, 133.5 (d, JCꢀF =3.0 Hz),
133.2, 132.0 (d, JCꢀF = 9.6 Hz), 130.3, 126.8, 126.4, 125.3, 124.5, 120.2, 115.3 (d, JCꢀF = 21.8
Hz), 110.5, 29.7, 20.7. HRMS (EIꢀTOF) m/z calcd. for C21H14FNO2: 331.1009; found: 331.1012.
(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)(2-fluorophenyl)methanone (4k)
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Light yellow oil. Yield: 44.7 mg, 45%. H NMR (400 MHz, CDCl3): δ 7.60ꢀ7.66 (m, 1H),
7.51ꢀ7.58 (m, 3H), 7.40ꢀ7.47 (m, 2H), 7.19ꢀ7.29 (m, 3H), 6.95 (td, J = 0.8, 7.6 Hz, 1H), 6.82ꢀ
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6.89 (m, 1H), 2.53 (s, 3H). C NMR (100 MHz, CDCl3): δ 193.6, 161.1, 160.6 (d, JCꢀF = 254.7
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Hz), 150.4, 141.6, 141.4, 139.3, 133.8, 133.6 (d, JCꢀF = 8.9 Hz), 131.0 (d, JCꢀF = 1.4 Hz), 130.4,
127.0, 126.4, 126.3 (d, JCꢀF = 11.3 Hz), 125.1, 124.3, 123.7 (d, JCꢀF = 3.6 Hz), 120.1, 116.1 (d, JCꢀ
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= 21.7 Hz), 110.6, 20.3. HRMS (EIꢀTOF) m/z calcd. for C21H14FNO2: 331.1009; found:
F
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(3-methyl-2-(5-methylbenzo[d]oxazol-2-yl)phenyl)(p-tolyl)methanone (4l)
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Light yellow solid, mp: 94ꢀ95 °C. Yield: 51.2 mg, 50%. H NMR (400 MHz, CDCl3): δ 7.61
(d, J = 8.4 Hz, 2H), 7.46ꢀ7.51 (m, 2H), 7.40ꢀ7.44 (m, 2H), 7.23ꢀ7.26 (m, 1H), 7.03ꢀ7.10 (m, 3H),
2.57 (s, 3H), 2.40 (s, 3H), 2.27 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 196.6, 161.4, 148.6,
143.6, 141.7, 141.3, 139.3, 134.5, 134.0, 132.9, 130.0, 129.8, 128.9, 126.8, 126.6, 126.2, 120.0,
109.9, 21.6, 21.4, 20.7. HRMS (EIꢀTOF) m/z calcd. for C23H19NO2: 341.1416; found: 341.1420.
1-(2-(benzo[d]oxazol-2-yl)-3-methylphenyl)ethan-1-one (4m)
Orange yellow solid, mp: 59ꢀ61 °C. Yield: 37.6 mg, 56%.1H NMR (400 MHz, CDCl3): δ 7.79ꢀ
7.81 (m, 1H), 7.66 (dd, J = 1.6, 6.8 Hz, 1H), 7.58ꢀ7.60 (m, 1H), 7.49ꢀ7.55 (m, 2H), 7.38ꢀ7.40 (m,
2H), 2.42 (s, 3H), 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 200.1, 162.2, 150.7, 141.6,
140.4, 140.0, 133.8, 130.5, 126.4, 126.3, 125.2, 124.5, 120.3, 110.8, 28.5, 20.0. HRMS (EIꢀTOF)
m/z calcd. for C16H13NO2: 251.0946; found: 251.0943.
(1-(benzo[d]oxazol-2-yl)naphthalen-2-yl)(phenyl)methanone (5a)
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Light yellow solid, mp: 134ꢀ136 °C. Yield: 89.0 mg, 85%. H NMR (400 MHz, CDCl3): δ
8.46ꢀ8.65 (m, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.83ꢀ7.89 (m, 1H), 7.48ꢀ7.64 (m, 6H), 7.23ꢀ7.29 (m,
1H), 7.12ꢀ7.20 (m, 3H), 7.05ꢀ7.12 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 197.3, 160.5, 150.4,
141.5, 139.3, 137.0, 134.3, 132.7, 131.4, 130.9, 129.3, 128.5, 128.5, 128.1, 127.9, 126.5, 125.4,
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125.3, 124.6, 124.3, 121.5, 120.3, 111.5, 110.6. HRMS (EIꢀTOF) m/z calcd. for C24H15NO2:
349.1103; found: 349.1101.
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White solid, mp: 87ꢀ89 °C. Yield: 81.4 mg, 83%. 1H NMR (400 MHz, CDCl3): δ 7.61ꢀ7.66 (m,
3H), 7.39ꢀ7.42 (m, 3H), 7.32ꢀ7.34 (m, 1H), 7.22ꢀ7.26 (m, 4H), 2.44 (s, 3H), 2.39 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ 196.8, 161.9, 150.4, 141.4, 141.1, 138.6, 137.9, 137.2, 132.4, 131.4,
129.5, 128.0, 127.4, 127.2, 125.0, 124.2, 120.1, 110.6, 20.8, 16.9. HRMS (EIꢀTOF) m/z calcd.
for C22H17NO2: 327.1259; found: 327.1257.
(3-methoxy-2-(5-methylbenzo[d]oxazol-2-yl)phenyl)(phenyl)methanone (5c)
Brown oil. Yield: 84.4 mg, 82%. 1H NMR (400 MHz, CDCl3): δ 7.67ꢀ7.69 (m, 2H), 7.60 (t, J =
8.0 Hz, 1H), 7.39 (s, 1H), 7.34 (t, J = 7.3Hz, 1H), 7.24 (t, J = 8.0 Hz, 5H), 7.04 (d, J = 8.4 Hz,
1H), 3.94 (s, 3H), 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 196.2, 159.2, 158.4, 148.7,
142.2, 141.6, 136.9, 133.9, 132.7, 131.9, 129.4, 128.1, 126.1, 121.4, 120.0, 116.5, 113.7, 109.8,
56.4, 21.4. HRMS (EIꢀTOF) m/z calcd. for C22H17NO3: 343.1208; found: 343.1205.
(2-(benzo[d]oxazol-2-yl)-3,5-dimethylphenyl)(phenyl)methanone (5d)
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Light yellow solid, mp: 80ꢀ82 °C. Yield: 75.6 mg, 77%. H NMR (400 MHz, CDCl3): δ 7.65ꢀ
7.70 (m, 2H), 7.57ꢀ7.62 (m, 1H), 7.30ꢀ7.36 (m, 3H), 7.29 (s, 1H), 7.25ꢀ7.27 (m, 1H), 7.21ꢀ7.25
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(m, 3H), 2.58 (s, 3H), 2.45 (s, 3H),. C NMR (100 MHz, CDCl3): δ 197.3, 161.4, 150.2, 141.4,
141.2, 140.7, 139.1, 137.2, 133.9, 132.5, 129.3, 128.0, 127.6, 124.9, 124.2, 123.6, 120.0, 110.4,
21.4, 20.7. HRMS (EIꢀTOF) m/z calcd. for C22H17NO2: 327.1259; found: 327.1259.
(2-(benzo[d]oxazol-2-yl)-3,5-difluorophenyl)(phenyl)methanone (5e)
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Light yellow solid, mp = 105ꢀ106 °C, (53%yeild). mp: 105ꢀ106 °C. Yield: 53.3 mg, 53%. H
NMR (400 MHz, CDCl3): δ 7.61ꢀ7.68 (m, 2H), 7.52ꢀ7.58 (m, 1H), 7.28ꢀ7.37 (m, 2H), 7.21ꢀ7.28
(m, 2H), 7.16ꢀ7.20 (m, 2H), 7.06ꢀ7.14 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 193.9, 163.9 (dd,
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CꢀF = 12.3, 256.3 Hz), 161.4 (dd, JCꢀF = 11.8, 260 Hz), 156.1, 150.4, 143.9 (dd, JCꢀF = 1.2, 8 Hz),
141.2, 136.1, 133.5, 129.3, 128.5, 125.6, 124.6, 120.4, 112.7 (dd, JCꢀF = 3.6, 22.8 Hz), 111.8 (dd,
JCꢀF = 4.1, 13.5 Hz), 110.6, 106.8 (t, JCꢀF = 25.3 Hz). HRMS (EIꢀTOF) m/z calcd. for
C20H11F2NO2: 335.0758; found: 335.0757.
(2-(benzo[d]oxazol-2-yl)-3-fluorophenyl)(phenyl)methanone (5f)
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Light yellow solid, mp: 90ꢀ92 °C. Yield: 50.4 mg, 53%. H NMR (400 MHz, CDCl3): δ 7.71ꢀ
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7.76 (m, 2H), 7.60ꢀ7.67 (m, 2H), 7.36ꢀ7.49 (m, 4H), 7.28ꢀ7.33 (m, 2H), 7.24ꢀ7.27 (m, 2H). C
NMR (100 MHz, CDCl3): δ 195.2 (d, JCꢀF = 2.5 Hz), 160.7 (d, JCꢀF = 256.8 Hz), 156.9 (d, JCꢀF
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3.4 Hz), 150.5, 142.4, 141.3, 136.7, 133.1, 132.5 (d, JCꢀF = 8.9 Hz), 129.4, 128.4, 125.6, 124.9 (d,
JCꢀF = 3.5 Hz), 124.5, 120.5, 118.6 (d, JCꢀF = 21.8 Hz), 115.2 (d, JCꢀF = 13.5 Hz), 110.6. HRMS
(EIꢀTOF) m/z calcd. for C20H12FNO2: 317.0852; found: 317.0851.
(2-(5-methylbenzo[d]oxazol-2-yl)-1,3-phenylene)bis(phenylmethanone) (5g)
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Light brown solid, mp: 165ꢀ167 °C. Yield: 52.6 mg, 42%. H NMR (400 MHz, CDCl3): δ
7.71ꢀ7.77 (m, 7H), 7.34ꢀ7.38 (m, 2H), 7.25ꢀ7.28 (m, 4H), 7.17 (s, 1H), 7.00 (d, J = 8.4 Hz, 1H),
6.90 (dd, J = 1.2, 8.4 Hz, 1H), 2.28 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 196.2, 159.1, 148.6,
141.3, 140.8, 136.7, 134.1, 133.1, 130.6, 130.6, 130.2, 129.4, 128.5, 128.3, 126.5, 125.2, 120.1,
109.6, 21.3. HRMS (EIꢀTOF) m/z calcd. for C28H19NO3: 417.1365; found: 417.1363.
(2-(benzo[d]oxazol-2-yl)-3-isopropylphenyl)(phenyl)methanone (5h)
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White solid, mp: 100ꢀ101 °C. Yield: 40.9 mg, 40%. H NMR (400 MHz, CDCl3): δ 7.65ꢀ7.71
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7.24ꢀ7.30 (m, 4H), 3.33 (m, 1H), 1.28 (d, J = 6.8 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 197.0,
161.3, 150.5, 150.1, 141.4, 140.8, 137.0, 132.6, 130.4, 129.7, 128.5, 128.0, 127.1, 126.2, 125.8,
125.0, 124.3, 121.5, 120.2, 111.5, 110.6, 30.3, 24.0. HRMS (EIꢀTOF) m/z calcd. for C23H19NO2:
341.1416; found: 341.1420.
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(3-chloro-2-(5-methylbenzo[d]oxazol-2-yl)phenyl)(phenyl)methanone (5i)
Light yellow oil. Yield: 36.4 mg, 35%. 1H NMR (400 MHz, CDCl3): δ 7.72ꢀ7.74 (m, 1H),
7.67 (d, J = 8.4 Hz, 2H), 7.57ꢀ7.59 (m, 2H), 7.37ꢀ7.42 (m, 2H), 7.28ꢀ7.32 (m, 3H), 7.10 (d, J =
8Hz, 1H), 2.42 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 195.5, 158.8, 148.8, 142.6, 141.3, 136.4,
135.2, 134.3, 133.1, 132.4, 131.3, 129.6, 128.2, 127.7, 126.9, 126.7, 120.2, 110.0, 21.4. HRMS
(EIꢀTOF) m/z calcd. for C21H14ClNO2: 347.0713; found: 347.0711.
(3,4-dimethyl-2-(5-methylbenzo[d]oxazol-2-yl)phenyl)(phenyl)methanone (6a)
Light yellow oil. Yield: 74.7 mg, 73%. 1H NMR (400 MHz, CDCl3): δ 7.64ꢀ7.67 (m, 3H),
7.39ꢀ7.40 (m, 3H), 7.31ꢀ7.33 (m, 1H), 7.22ꢀ7.27 (m, 3H), 7.05 (d, J = 8.4 Hz, 1H), 2.42 (s, 3H),
2.40 (s, 3H), 2.38 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 196.8, 162.0, 148.7, 141.6, 141.0,
138.6, 137.9, 137.3, 134.0, 132.5, 131.3, 129.6, 128.0, 127.6, 127.1, 126.1, 120.0, 109.9, 21.4,
20.8, 16.9. HRMS (EIꢀTOF) m/z calcd. for C23H19NO2: 341.1416; found: 341.1415.
(3,5-dimethyl-2-(5-methylbenzo[d]oxazol-2-yl)phenyl)(phenyl)methanone (6b)
Light yellow solid, mp: 99ꢀ101 °C. Yield: 71.6 mg, 70%. 1H NMR (400 MHz, CDCl3): δ 7.65ꢀ
7.70 (m, 2H), 7.38 (s, 1H), 7.31ꢀ7.36 (m, 2H), 7.19ꢀ7.28 (m, 4H), 7.03 (dd, J = 1.2, 8.4 Hz, 1H),
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2.57 (s, 3H), 2.44 (s, 3H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 197.3, 161.5, 148.5,
141.6, 141.2, 140.5, 139.1, 137.2, 134.0, 133.8, 132.6, 129.4, 128.0, 127.5, 126.0, 123.7, 119.9,
109.7, 31.0, 21.4, 21.4, 20.7. HRMS (EIꢀTOF) m/z calcd. for C23H19NO2: 341.1416; found:
341.1420.
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(2-(5-chlorobenzo[d]oxazol-2-yl)-3-methylphenyl)(phenyl)methanone (6c)
Light brown oil. Yield: 43.7 mg, 42%. 1H NMR (400 MHz, CDCl3): δ 7.66ꢀ7.71 (m, 2H), 7.61
(d, J = 2.0 Hz, 1H), 7.51ꢀ7.55 (m, 2H), 7.46ꢀ7.50 (m, 1H), 7.36ꢀ7.42 (m, 1H), 7.25ꢀ7.32 (m, 3H),
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7.22 (dd, J = 2, 8.8 Hz, 1H), 2.57 (s, 3H). C NMR (100 MHz, CDCl3): δ 196.8, 162.7, 148.9,
142.5, 141.0, 139.4, 137.0, 133.3, 132.9, 130.4, 129.8, 129.5, 128.2, 127.2, 126.1, 125.4, 120.1,
111.3, 20.7. HRMS (EIꢀTOF) m/z calcd. for C21H14ClNO2: 347.0713; found: 347.0712.
(3-methyl-2-(6-methylbenzo[d]oxazol-2-yl)phenyl)(phenyl)methanone (6d)
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Light yellow solid, mp: 78ꢀ79 °C. Yield: 53.0 mg, 54%. H NMR (400 MHz, CDCl3): δ 7.67ꢀ
7.71 (m, 2H), 7.50ꢀ7.54 (m, 2H), 7.44ꢀ7.50 (m, 2H), 7.33ꢀ7.39 (m, 1H), 7.24ꢀ7.30 (m, 2H), 7.18
(s, 1H), 7.06 (dd, J = 0.8, 8.0 Hz, 1H), 2.59 (s, 3H), 2.42 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
197.0, 160.6, 150.6, 141.1, 139.3, 139.2, 137.1, 135.5, 133.1, 132.6, 130.0, 129.5, 128.1, 126.9,
126.6, 125.6, 119.5, 110.6, 21.7, 20.7. HRMS (EIꢀTOF) m/z calcd. for C22H17NO2: 327.1259;
found: 327.1260.
(3-methyl-2-(5-methylbenzo[d]oxazol-2-yl)phenyl)(phenyl)methanone (6e)
Light yellow oil. Yield: 51.0 mg, 52%. 1H NMR (400 MHz, CDCl3): δ 7.66ꢀ7.70 (m, 2H),
7.50ꢀ7.54 (m, 2H), 7.44ꢀ7.49 (m, 1H), 7.40 (s, 1H), 7.33ꢀ7.38 (m, 1H), 7.22ꢀ7.29 (m, 3H), 7.06
(dd, J = 1.2, 8.4 Hz, 1H), 2.59 (s, 3H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 197.0,
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161.3, 148.5, 141.6, 141.1, 139.3, 137.1, 134.1, 133.1, 132.7, 130.1, 129.5, 128.1, 126.9, 126.7,
126.2, 120.0, 109.8, 21.4, 20.7. HRMS (EIꢀTOF) m/z calcd. for C22H17NO2: 327.1259; found:
327.1259.
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(2-(5-chlorobenzo[d]oxazol-2-yl)-3,5-dimethylphenyl)(phenyl)methanone (6f)
Light yellow oil. Yield: 53.1 mg, 49%. 1H NMR (400 MHz, CDCl3): δ 7.65ꢀ7.70 (m, 2H),
7.58 (d, J = 2.0 Hz, 1H), 7.33ꢀ7.40 (m, 2H), 7.23ꢀ7.30 (m, 4H), 7.20 (dd, J = 2.0, 8.4 Hz, 1H),
2.56 (s, 3H), 2.45 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 197.1, 162.9, 148.8, 142.5, 141.2,
141.0, 139.2, 137.1, 134.0, 132.8, 129.7, 129.4, 128.1, 127.7, 126.1, 125.3, 123.1, 120.0, 111.2,
21.4, 20.7. HRMS (EIꢀTOF) m/z calcd. for C22H16ClNO2: 361.0870; found: 361.0869.
(2-(5-(tert-butyl)benzo[d]oxazol-2-yl)-3-methylphenyl)(phenyl)methanone (6g)
White solid, mp: 84ꢀ86 °C. Yield: 49.8 mg, 45%. 1H NMR (400 MHz, CDCl3): δ 7.68ꢀ7.74 (m,
2H), 7.65 (d, J = 1.2 Hz, 1H), 7.49ꢀ7.54 (m, 2H), 7.43ꢀ7.47 (m, 1H), 7.35ꢀ7.41 (m, 1H), 7.24ꢀ
7.32 (m, 4H), 2.59 (s, 3H), 1.34 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 207.0, 197.0, 161.3,
148.4, 147.8, 141.3, 141.0, 139.4, 137.1, 133.1, 132.6, 129.9, 129.6, 128.1, 126.9, 126.8, 122.9,
116.6, 109.6, 34.9, 31.7, 30.9, 20.7. HRMS (EIꢀTOF) m/z calcd. for C25H23NO2: 369.1729;
found: 369.1728.
(2-(benzo[d]thiazol-2-yl)-3-methylphenyl)(phenyl)methanone (6h)
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Light yellow solid, mp: 82ꢀ84 °C. Yield: 57.3 mg, 58%. H NMR (400 MHz, CDCl3): δ 7.93
(d, J = 8.0 Hz, 1H), 7.78 (dd, J = 0.8, 8.0 Hz, 1H), 7.66ꢀ7.72 (m, 2H), 7.46ꢀ7.50 (m, 2H), 7.36ꢀ
7.43 (m, 3H), 7.24ꢀ7.35 (m, 3H), 2.43 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 197.3, 165.2,
152.9, 140.7, 138.2, 137.4, 136.2, 132.8, 132.8, 129.9, 129.3, 128.0, 126.6, 126.0, 125.2, 123.4,
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121.3, 31.6, 22.7, 20.5, 14.1. HRMS (EIꢀTOF) m/z calcd. for C21H15NOS: 329.0874; found:
329.0874.
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Light brown solid, mp: 59ꢀ60 °C. Yield: 21.1 mg, 24%. H NMR (400 MHz, CDCl3): δ 7.61ꢀ
7.67 (m, 2H), 7.40ꢀ7.47 (m, 3H), 7.35ꢀ7.40 (m, 1H), 7.27ꢀ7.34 (m, 2H), 6.77 (d, J = 0.8 Hz, 1H),
2.41 (s, 3H), 2.28 (d, J = 1.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 197.8, 163.4, 152.7,
140.9, 137.8, 137.5, 132.6, 132.5, 132.3, 129.7, 129.0, 128.0, 126.4, 115.2, 20.6, 16.8. HRMS
(EIꢀTOF) m/z calcd. for C18H15NOS: 293.0874; found: 293.0878.
(3-methyl-2-(6-nitrobenzo[d]oxazol-2-yl)phenyl)(phenyl)methanone (7a)
Light yellow oil. Yield: 32.2 mg, 30%. 1H NMR (400 MHz, CDCl3): δ 8.31ꢀ8.35 (m, 1H), 8.24
(dd, J = 2.0, 8.8 Hz, 1H), 7.72ꢀ7.76 (m, 3H), 7.58ꢀ7.59 (m, 2H), 7.50ꢀ7.52 (m, 1H), 7.42ꢀ7.46
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(m, 1H), 7.32ꢀ7.36 (m, 2H), 2.60 (s, 3H). C NMR (100 MHz, CDCl3): δ 196.5, 166.2, 156.6,
149.5, 146.5, 145.2, 141.1, 139.8, 136.8, 133.5, 133.1, 130.9, 130.2, 129.7, 128.3, 127.5, 125.6,
120.5, 120.1, 107.2, 20.7. HRMS (EIꢀTOF) m/z calculated for C21H14N2O4: 358.0954, found:
358.0954.
6-nitro-2-(3-(o-tolyl)bicyclo[2.2.1]heptan-2-yl)benzo[d]oxazole (7a’)
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Light yellow solid, mp: 91ꢀ93 °C. Yield: 47.0 mg, 45%. H NMR (400 MHz, CDCl3): δ 8.07
(dd, J = 2.0, 8.8 Hz, 1H), 8.05 (d, J = 5.0 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H), 7.20 (d, J = 7.6 Hz,
1H), 6.87 (t, J = 7.6 Hz, 1H), 6.82 (d, J = 7.2 Hz, 1H), 6.74 (t, J = 7.6 Hz, 1H), 3.69 (dd, J = 1.2,
9.6 Hz, 1H), 3.48 (d, J = 9.6 Hz, 1H), 2.71ꢀ2.81 (m, 3H), 2.37 (s, 3H), 1.80ꢀ1.84 (m, 2H), 1.67ꢀ
1.70 (m, 1H), 1.53 (dd, J = 2.0, 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 172.4, 149.2, 146.0,
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144.5, 139.2, 136.2, 129.7, 126.1, 125.9, 125.5, 120.0, 119.0, 106.3, 49.6, 49.1, 41.6, 41.2, 37.8,
31.2, 29.1, 20.3. HRMS (EIꢀTOF) m/z calculated for C21H20N2O3: 348.1474, found: 348.1477.
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Light yellow oil. Yield: 49.1 mg, 44%. H NMR (400 MHz, CDCl3): δ 8.28 (d, J = 2.0 Hz,
1H), 8.22 (dd, J = 1.6, 8.8 Hz, 1H), 7.72 (d, J = 8.0 Hz, 3H), 7.40ꢀ7.44 (m, 1H), 7.38 (s, 1H),
7.30ꢀ7.34 (m, 3 H), 2.59 (s, 3H), 2.47 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 196.8, 166.4,
156.6, 149.4, 146.6, 145.1, 141.7, 141.3, 139.6, 136.9, 134.2, 133.0, 129.5, 128.3, 128.0, 122.5,
120.5, 120.0, 107.1, 21.5, 20.7. HRMS (EIꢀTOF) m/z calculated for C22H16N2O4: 372.1110,
found: 372.1108.
2-(3-(2,4-dimethylphenyl)bicyclo[2.2.1]heptan-2-yl)-6-nitrobenzo[d]oxazole (7b’)
Light yellow oil. Yield: 53.2 mg, 49%. 1H NMR (400 MHz, CDCl3): δ 8.05ꢀ8.12 (m, 2H), 7.54
(d, J = 8.8 Hz,1H), 7.08 (d, J =8.0 Hz, 1H), 6.67 (d, J = 8.0 Hz, 1H), 6.64 (s, 1H), 3.67 (d, J =
9.6 Hz, 1H), 3.44 (d, J = 9.6 Hz, 1H), 2.64ꢀ2.83 (m, 3H), 2.32 (s, 3H), 2.00 (s, 3H), 1.75ꢀ1.86
(m, 2H), 1.67 (d, J = 10.0 Hz, 1H), 1.52 (dd, J = 2.0, 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3):
δ 172.6, 149.2, 146.1, 144.4, 136.1, 136.0, 135.4, 130.5, 126.1, 125.8, 119.9, 119.1, 106.3, 49.4,
49.2, 41.7, 41.1, 37.8, 31.2, 29.1, 20.6, 20.2. HRMS (EIꢀTOF) m/z calculated for C22H22N2O3:
362.1630, found: 362.1630.
(3,5-difluoro-2-(6-nitrobenzo[d]oxazol-2-yl)phenyl)(phenyl)methanone (7c)
Light yellow solid, mp: 152ꢀ154 °C. Yield: 61.6 mg, 54%. 1H NMR (400 MHz, CDCl3): δ 8.34
(d, J = 2.0 Hz, 1H), 8.24 (dd, J = 2.4, 8.8 Hz, 1H), 7.72ꢀ7.78 (m, 3H), 7.49ꢀ7.52 (m, 1H), 7.39 (t,
J = 7.6 Hz, 2H), 7.18ꢀ7.25 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ 193.3, 164.5 (dd, J = 12.7,
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258.4 Hz), 161.7 (dd, J = 11.9, 261.4 Hz), 160.9 (d, J = 29.0 Hz), 149.6, 146.1, 145.5, 144.3 (d, J
= 7.6 Hz), 135.8, 133.9, 129.5, 128.7, 120.8, 120.5, 113.1 (dd, J = 3.6, 23.1 Hz), 107.4, 107.0 (t,
J = 25.2 Hz), 29.7. HRMS (EIꢀTOF) m/z calculated for C20H10F2N2O4: 380.0609, found:
380.0611.
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2-(3-(2,4-difluorophenyl)bicyclo[2.2.1]heptan-2-yl)-6-nitrobenzo[d]oxazole (7c’)
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Colorless solid, mp: 148ꢀ149 °C. Yield: 44.4 mg, 40%. H NMR (400 MHz, CDCl3): δ 8.12ꢀ
8.18 (m, 2H), 7.58 (dd, J = 1.2, 8.4 Hz, 1H), 7.11ꢀ7.21 (m, 1H), 6.45ꢀ6.59 (m, 2H), 3.68 (d, J =
9.6 Hz, 1H), 3.61 (d, J = 9.6 Hz, 1H), 2.86 (s, 1H), 2.64 (s, 1H), 2.60 (d, J = 10.4 Hz, 1H), 1.83
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(dd, J = 2.8, 10.8 Hz, 2H), 1.68 (d, J = 10.4 Hz, 1H), 1.52ꢀ1.58 (m, 2H). C NMR (100 MHz,
CDCl3): δ 172.1, 161.3 (dd, J = 12.0, 246.0 Hz,), 160.4 (dd, J = 11.7, 246.5 Hz), 149.2, 146.0,
144.7, 128.3 (d, J = 5.6 Hz ), 128.2 (d, J = 5.6 Hz ), 124.2 (dd, J = 3.8, 14.8 Hz), 120.2, 119.3,
110.6 (dd, J = 3.5, 20.7 Hz), 106.4, 102.9 (t, J = 25.8 Hz), 49.0, 44.9, 41.6, 40.6, 37.5, 30.7, 28.8.
HRMS (EIꢀTOF) m/z calculated for C20H16F2N2O3: 370.1129, found: 370.1130.
(3-isopropyl-2-(6-nitrobenzo[d]oxazol-2-yl)phenyl)(phenyl)methanone (7d)
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Light yellow oil. Yield: 34.8 mg, 30%. H NMR (400 MHz, CDCl3): δ 8.37 (d, J = 2.0 Hz,
1H), 8.26 (dd, J = 2.4, 8.8 Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.69ꢀ7.74 (m, 3H), 7.66 (t, J = 7.6
Hz, 1H), 7.52 (dd, J = 1.2, 8.8Hz, 1H), 7.43ꢀ7.49 (m, 1H), 7.33ꢀ7.37 (m, 2H), 3.18ꢀ3.28 (m, 2H),
1.31 (d, J = 6.8 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 196.5, 166.5, 150.4, 149.7, 146.6,
145.2, 140.6, 136.8, 133.1, 131.1, 129.8, 129.0, 128.3, 127.7, 125.3, 120.5, 120.2, 107.4, 30.6,
24.0. HRMS (EIꢀTOF) m/z calcd. for C23H18N2O4: 386.1267; found: 386.1271.
2-(3-(2-isopropylphenyl)bicyclo[2.2.1]heptan-2-yl)-6-nitrobenzo[d]oxazole (7d’)
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Orange yellow oil. Yield: 73.3 mg, 65%. 1H NMR (400 MHz, CDCl3): δ 8.09 (dd, J = 2.4, 8.8
Hz, 1H), 8.02 (d, J = 2.0 Hz, 1H), 7.53 (d, J = 8.8 Hz, 1H), 7.21ꢀ7.23 (m, 1H), 6.92ꢀ6.95 (m,
1H), 6.84ꢀ6.87 (m, 2H), 3.71 (d, J = 9.2 Hz, 1H), 3.55 (d, J = 9.6 Hz, 1H), 3.28ꢀ3.25 (m, 1H),
2.77ꢀ2.82 (m, 2H), 2.71 (s, 1H), 1.81ꢀ1.84 (m, 2H), 1.70 (d, J = 10.4 Hz, 1H), 1.53ꢀ1.55 (m, 2H),
1.27 (d, J = 6.8 Hz, 3H), 1.16 (d, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 172.3, 149.2,
146.5, 146.1, 144.5, 137.4, 126.5, 126.1, 125.2, 124.4, 120.0, 119.0, 106.2, 49.8, 48.5, 41.6, 41.4,
37.9, 31.2, 29.3, 29.1, 25.3, 22.2. HRMS (EIꢀTOF) m/z calculated for C23H24N2O3: 376.1787,
found: 376.1792.
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(1-(6-nitrobenzo[d]oxazol-2-yl)naphthalen-2-yl)(phenyl)methanone (7e)
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Light yellow solid, mp: 173ꢀ174 °C. Yield: 68.6 mg, 58%. H NMR (400 MHz, CDCl3): δ
8.51ꢀ8.54 (m, 1H), 8.32 (d, J = 2.4 Hz, 1H), 8.27 (dd, J = 2.0, 8.8 Hz, 1H), 8.20 (d, J = 8.4 Hz,
1H), 8.03ꢀ8.06 (m, 1H), 7.82 (d, J = 8.8 Hz, 1H), 7.70ꢀ7.76 (m, 5H), 7.41 (t, J = 7.6 Hz, 1H),
7.30 (t, J = 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 196.7, 165.4, 149.5, 146.5, 145.4,
139.8, 136.8, 134.3, 133.2, 132.3, 130.8, 129.5, 128.9, 128.7, 128.4, 128.2, 126.0, 125.3, 123.2,
120.7, 120.3, 107.3. HRMS (EIꢀTOF) m/z calcd. for C24H14N2O4: 394.0954; found: 394.0956.
2-(3-(naphthalen-1-yl)bicyclo[2.2.1]heptan-2-yl)-6-nitrobenzo[d]oxazole (7e’)
Colorless solid, mp: 147ꢀ148 °C. Yield: 34.6 mg, 30%. 1H NMR (400 MHz, CDCl3): δ 8.16 (d,
J = 8.4 Hz, 1H), 7.95 (dd, J = 2.4, 8.8 Hz, 1H), 7.72 (d, J = 2.0 Hz, 1H), 7.43ꢀ7.57 (m, 3H), 7.39
(d, J = 8.4 Hz, 1H), 7.30ꢀ7.36 (m, 2H), 7.20 (t, J = 7.6 Hz, 1H), 4.11 (d, J = 9.6 Hz, 1H), 3.90
(dd, J = 0.8, 9.6 Hz, 1H), 2.93 (s, 1H), 2.78ꢀ2.87 (m, 2H), 1.83ꢀ1.96 (m, 2H), 1.75 (d, J = 10.0
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Hz, 1H), 1.66 (d, J = 7.2 Hz, 2H). C NMR (100 MHz, CDCl3): δ 172.3, 148.7, 145.8, 144.3,
136.9, 133.2, 131.5, 128.4, 126.8, 125.4, 125.3, 124.9, 124.0, 123.6, 119.8, 118.8, 106.0, 50.0,
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48.9, 42.4, 41.1, 37.6, 30.9, 29.4. HRMS (EIꢀTOF) m/z calculated for C24H20N2O3: 384.1474,
found: 384.1473.
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Light yellow oil. Yield: 79.8 mg, 65%. H NMR (400 MHz, CDCl3): δ 8.42 (d, J = 7.2 Hz,
2H), 7.67ꢀ7.72 (m, 1H), 7.61 (t, J = 7.6 Hz, 2H), 7.50ꢀ7.53 (m, 1H), 7.37 (dd, J = 2.0, 7.6 Hz,
1H), 7.20ꢀ7.24 (m, 1H), 7.10ꢀ7.15 (m, 2H), 6.93ꢀ7.02 (m, 2H), 6.88 (dd, J = 1.6, 7.6 Hz, 1H),
3.60 (d, J = 9.6 Hz, 1H), 3.43 (d, J = 9.2 Hz, 1H), 2.76 (br. s, 1H), 2.72 (br. s, 1H), 2.68 (d, J =
10.4 Hz, 1H), 1.75 (d, J = 8.0 Hz, 2H), 1.61 (d, J = 10.0 Hz, 1H), 1.43 (dd, J = 2.0, 8.0 Hz, 2H).
13C NMR (100 MHz, CDCl3): δ 167.3, 164.8, 150.2, 148.7, 140.9, 133.7, 133.4, 130.4, 129.9,
128.8, 127.4, 127.0, 125.4, 124.1, 123.6, 121.6, 119.3, 109.9, 49.2, 46.7, 42.1, 40.5, 37.2, 30.6,
29.2. HRMS (EIꢀTOF) m/z calculated for C27H23NO3: 409.1678, found: 409.1688.
2-(3-(o-tolyl)bicyclo[2.2.1]heptan-2-yl)benzo[d]oxazole (7g)
1
Colorless solid, mp: 67ꢀ69 °C. Yield: 41.8 mg, 46%. H NMR (400 MHz, CDCl3): δ 7.44ꢀ7.50
(m, 1H), 7.24 (d, J = 8.0 Hz, 1H), 7.05ꢀ7.16 (m, 3H), 6.88 (t, J = 7.2 Hz, 1H), 6.81 (d, J = 7.2
Hz, 1H), 6.75 (t, J = 7.6 Hz, 1H), 3.66 (d, J = 8.8 Hz, 1H), 3.43 (d, J = 9.6 Hz, 1H), 2.75ꢀ2.82
(m, 2H), 2.69 (s, 1H), 2.37 (s, 3H), 1.75ꢀ1.85 (m, 2H), 1.65 (d, J = 10.4 Hz, 1H), 1.52 (dd, J =
1.6, 7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 167.3, 150.2, 140.6, 139.8, 136.3, 129.5, 126.0,
125.8, 125.3, 123.9, 123.5, 119.2, 109.6, 49.4, 49.0, 41.8, 41.2, 37.7, 31.2, 29.2, 20.4. HRMS
(EIꢀTOF) m/z calculated for C21H21NO: 303.1623, found: 303.1626.
Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website at
DOI: Crystallographic data for 7c’ (CIF) and 1H NMR and 13C NMR spectra for new products
(PDF).
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AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: chenwzz@zju.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The National Natural Science Foundation of China (21572203 and 21472140) and Zhejiang
Provincial Natural Science Foundation (LZ16B020001) are acknowledged for the financial
support.
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