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Synthesis 2010(4): 579-586  
DOI: 10.1055/s-0029-1218589
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Benzoxazoles by an Efficient Ullmann-Type Intramolecular C(aryl)-O Bond-Forming Coupling Cyclization with a BINAM-Copper(II) Catalyst

Ajay B. Naidu, Govindasamy Sekar*
Department of Chemistry, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India
Fax: +91(44)22574202; e-Mail: gsekar@iitm.ac.in;

Further Information

Publication History

Received 2 October 2009
Publication Date:
07 December 2009 (online)

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Abstract

A wide range of 2-substituted benzoxazoles were synthesized from the corresponding N-(2-iodophenyl)benzamides through intramolecular C(aryl)-O bond formation via Ullmann-type coupling cyclization in the presence of a catalytic amount of an easily available BINAM-copper(II) complex under very mild reaction conditions (82 ˚C). Less reactive bromo and chloro analogues of the N-(2-halophenyl)benzamides were also successfully cyclized to produce benzoxazoles, without increasing the catalyst loading.

Key words

copper catalyst - nitrogen ligands - C-O bond formation - Ullmann coupling - benzoxazole synthesis

Benzoxazole motifs are found in several important natural products [¹] and have many applications in the field of medicinal chemistry, such as their use as HIV-1 reverse transcriptase inhibitors, [²] antitumor agents, [³] Rho kinase inhibitors, [4] estrogen receptor agonists, [5] and melatonin receptor agonists. [6] Also, benzoxazoles are recognized as an important scaffold in fluorescent probes as anion and metal cation sensors. [7] Although there are several methods available for the synthesis of benzoxazoles, [8] generally o-aminophenols are condensed with carboxylic acid derivatives in the presence of strong acids at high reaction temperatures [9] or under microwave-assisted reaction conditions. [¹0] Alternatively, the o-aminophenols are treated with an aldehyde in the presence of an oxidant. [¹¹] Recently, Batey and co-workers developed an efficient route for the synthesis of benzoxazoles starting from N-(2-halo­aryl)benzamides using a 1,10-phenanthroline-copper(I) complex catalyzed cyclization. [¹²] Domínguez and co-workers used a superexcess amount of the ligand TMEDA with copper(I) iodide to carry out the intramolecular cyclization of N-(2-bromo- or N-(2-chloroaryl)benzamides in water at 120 ˚C. [¹³] Very recently, Bonnamour and Bolm demonstrated that an easily available diketone-iron complex can be used as an efficient catalyst for the synthesis of benzoxazoles from N-(2-iodoaryl)benzamides. [¹4] Though significant progress has been reported for the synthesis of benzoxazoles from N-(2-haloaryl)benzamides through intramolecular C(aryl)-O bond formation, there is still a need to develop a new catalytic system as most of the literature procedures require high reaction temperatures (>100 ˚C) or excess ligand, or catalysis of the cyclization fails when the halo amide has aliphatic substitution.

As part of our ongoing research on copper-catalyzed oxidation chemistry, [¹5] very recently we reported a copper complex catalyzed arylation of alcohols, phenols, indoles, thiols, and terminal alkynes through C(aryl)-O, C(aryl)-N (N-arylation of indoles), C(aryl)-S, and C(aryl)-C bond formation, with applications in heterocycle synthesis. [¹6] Herein, we report for the first time the synthesis of benz­oxazoles from the corresponding N-(2-halophenyl)benz­amides through intramolecular C(aryl)-O bond-forming cyclization catalyzed by an easily available BINAM-copper(II) complex (Scheme  [¹] ).

Scheme 1

In preliminary studies, we used 20 mol% of N,N′-dibenzyl-1,1′-binaphthyl-2,2′-diamine (dibenzyl-BINAM, L1) (Figure  [¹] ) as ligand with 20 mol% of copper(I) iodide for the intramolecular coupling cyclization of N-(2-iodophenyl)benzamide in N,N-dimethylformamide at 110 ˚C. After 32 hours, the coupling reaction provided 52% isolated yield of the corresponding benzoxazole (Table  [¹] , entry 1). Surprisingly, when the ligand L1 was replaced by the unsubstituted BINAM ligand (L2), the reaction provided 80% yield of the benzoxazole in just 10 hours (Table  [¹] , entry 2). Replacing ligand L2 by L3 or L4, however, reduced the yield of the coupling product to 41% and 62%, respectively, and the cyclization reaction took a much longer time for completion (Table  [¹] , entries 3 and 4). When the reaction was carried out only with copper(I) iodide without ligand, only 12% yield of the coupling product was obtained (Table  [¹] , entry 11) which shows that the ligand is mandatory for good conversion in the coupling cyclization reaction. Carrying out the coupling reaction without copper catalyst did not provide even a trace amount of the coupling product which shows that the presence of a copper catalyst is necessary for this reaction (Table  [¹] , entry 12).

Figure 1 BINAM-based ligands for Ullmann-type intramolecular C(aryl)-O bond-forming cyclization

Table 1 Screening of Ligands and Copper Salts for the Synthesis of 2-Phenylbenzoxazole

Entry Ligand Copper salt Time (h) Yielda (%)
 1 L1 CuI 32 52
 2 L2 CuI 10 80
 3 L3 CuI 20 41
 4 L4 CuI 30 62
 5 L2 CuBr 11 66
 6 L2 CuCl 13 58
 7 L2 Cu(OTf) 2 10 87
 8 L2 Cu(OAc)2 11 54
 9 L2 CuCl2 12 61
10 L2 CuSO4 12 76
11 - CuI 24 12
12 - - 32  0
a Isolated yield.

Then, the reaction was further screened with several copper salts, solvents, and bases, and with different catalyst loadings to increase the efficiency of the intramolecular coupling reaction. Although several copper salts catalyzed the coupling cyclization reaction, copper(II) trifluoromethanesulfonate [Cu(OTf)2] turned out to be the copper salt of choice in terms of isolated yield (Table  [¹] , entry 7). Similarly, acetonitrile was the best solvent among those examined, with catalysis of the reaction at 82 ˚C to produce 86% yield of the benzoxazole in 14 hours (Table  [²] , entry 5). Cesium carbonate as the base gave the best yield of product in comparison with bases such as sodium carbonate and potassium carbonate (Table  [²] , entries 8-11). Importantly, reducing the catalyst loading from 20 mol% each of Cu(OTf)2 and BINAM to 5 mol% of Cu(OTf)2 and 10 mol% of BINAM (1:2 complex) [¹7] provided the same 86% yield for the coupling reaction with the same reaction time (Table  [²] , cf. entries 5 and 8).

Table 2 Effect of Solvent, Base, and Catalyst Loading

Entry BINAM (mol%) Cu(OTf)2 (mol%) Solvent Temp (˚C) Time
(h) 		Yielda (%)
 1 20 20 DMF 110 10 87
 2 20 20 toluene 110 30 74
 3 20 20 DMSO 110 11 70
 4 20 20 dioxane 110  9 70
 5 20 20 MeCN  82 14 86
 6 20 20 THF  70 24 50
 7 10 10 MeCN  82 14 84
 8 10  5 MeCN  82 14 86
 9 10  5 MeCN  82 40 20b
10 10  5 MeCN  82 32 40c
11 10  5 MeCN  82 28 60d
a Isolated yield.
b Na2CO3 used as base.
c K2CO3 used as base.
d K3PO4 used as base.

Using the optimized conditions, we initiated our investigations into the scope of the BINAM-Cu(OTf)2 complex catalyzed Ullmann-type intramolecular coupling cyclization; the results are summarized in Table  [³] . Various N-(2-halophenyl)benzamides reacted with the BINAM-Cu(OTf)2 catalyst in acetonitrile to give the corresponding benzoxazoles under very mild reaction conditions (82 ˚C). For N-(2-iodophenyl)benzamides, we found that the amide phenyl moiety could contain either an electron-releasing or an electron-withdrawing group with reaction giving the corresponding substituted 2-arylbenzoxazoles; however, in both cases the yields were reduced to some extent. In particular, the presence of a very strong electron-donating group such as methoxy at the ortho position reduced the yield to 49% (Table  [³] , entry 3). A 2-alkylbenzoxazole was also successfully synthesized in good isolated yield from the corresponding alkylamide precursor (Table  [³] , entry 13). A heterocycle-containing halo amide also provided the corresponding benzoxazole with a good conversion (Table  [³] , entry 12).

It is important to mention that less reactive bromo precursors also provided moderate to good yields of the Ullmann-type intramolecular coupling cyclization products, without the catalytic loading and reaction temperature being increased (Table  [³] , entries 14-20). For N-(2-bromophenyl)benzamide, substitution on the aryl moiety of both the aryl halide as well as the amide is well tolerated. In particular, the presence of a methyl group in the bromophenyl moiety and a methoxy group at the para position of the amide phenyl moiety resulted in an increase in the yield by 12% and the reaction took comparatively less time than with other bromides (Table  [³] , cf. entries 19 and 14).

Table 3 BINAM-Cu(OTf)2 Complex Catalyzed Synthesis of Benzoxazoles from N-(2-Iodo- or N-(2-Bromophenyl)benzamides by Ullmann-Type Intramolecular Coupling (continued)

Entry N-(2-Halophenyl)benzamide Benzoxazole Time (h) Yielda (%)
 1

14 86
 2

18 79
 3

36 49b
 4

14 76
 5

19 71
 6

14 70
 7

36 60
 8

17 66
 9

17 62
10

36 65
11

17 70
12

30 65
13

16 77
14

36 72
15

36 54
16

36 49
17

42 61
18

36 71
19

28 84
20

36 69
a Isolated yield.
b Unreacted starting material (30%) was recovered.

We are pleased to note that the synthesis of benzoxazoles from the corresponding very less reactive chlorides can be achieved in moderate yields by increasing the reaction temperature to 135 ˚C in N,N-dimethylformamide as solvent, without increasing the catalytic loading (Table  [4] ). Electron-releasing or electron-withdrawing groups on the amide phenyl moiety are tolerated, to produce the benzoxazoles from the corresponding N-(2-chlorophenyl)benz­amides.

Table 4 BINAM-Cu(OTf)2 Complex Catalyzed Synthesis of Benzoxazoles from N-(2-Chlorophenyl)benzamides by Ullmann-Type Intramolecular Coupling

Entry N-(2-Chlorophenyl)benzamide Benzoxazole Time (h) Yielda (%)
1

28 55
2

32 52
3

36 44
4

48 52
5

48 50
6

40 45
a Isolated yield.

In summary, we have developed an efficient, experimentally simple, and economically attractive copper-catalyzed Ullmann-type intramolecular C(aryl)-O bond-forming coupling cyclization for the synthesis of a variety of benzoxazoles from the corresponding N-(2-iodophenyl)benzamides. Less reactive bromo precursors were also used for the synthesis of benzoxazoles under the same reaction conditions, without increasing the reaction temperature and catalyst loading. For the very less reactive N-(2-chlorophenyl)benzamides, the intramolecular coupling cyclization was achieved by increasing the reaction temperature in N,N-dimethylformamide as solvent, without increasing the catalyst loading.

All reactions were carried out in a reaction tube under nitrogen atmosphere and reaction temperatures were controlled with a temperature modulator. 1,1′-Binaphthyl-2,2′-diamine [¹8] (BINAM, L2) was purchased from Gerchem Labs, Hyderabad, India. Thin-layer chromatography (TLC) was performed using precoated silica gel 60 F254 plates (0.25 mm) which were visualized using a UV fluorescent lamp. ¹H and ¹³C NMR spectra were recorded on a Bruker 400 MHz instrument. ¹H NMR spectra are reported relative to TMS (δ 0.0) or residual CDCl3 (δ 7.26). ¹³C NMR spectra are reported relative to CHCl3 (δ 77.16). FTIR spectra were recorded on a Nicolet 6700 spectrophotometer and are reported in frequency of absorption (cm-¹). High-resolution mass spectra (HRMS) were recorded on a Micromass Q-Tof mass spectrometer.

2-Phenylbenzoxazole [¹²a] (Table 3, Entry 1); Typical Procedure for the Intramolecular C (aryl) -O Bond-Formation Reaction

N-(2-Iodophenyl)benzamide (161.5 mg, 0.50 mmol), BINAM (L2; 14.2 mg, 0.05 mmol), Cu(OTf)2 (9 mg, 0.025 mmol), and Cs2CO3 (325 mg, 1.0 mmol) were taken into a 10-mL reaction tube equipped with a septum. The reaction tube was evacuated and backfilled with nitrogen. MeCN (2.5 mL) was added to the mixture at r.t. and the mixture was heated at 82 ˚C for 14 h. After complete disappearance of N-(2-iodophenyl)benzamide (progress of the reaction was followed by TLC), the mixture was allowed to cool to r.t. and the solvent was removed by evaporation. The crude residue was directly purified by column chromatography on silica gel (EtOAc-hexanes) to afford 2-phenylbenzoxazole [¹²a] as a white solid; yield: 84 mg (86%).

Mp 100-101 ˚C (Lit. [¹²a] 101-102 ˚C); R f  = 0.70 (hexanes-EtOAc, 9:1).

FTIR (neat): 760, 1242, 1552, 2922, 3100 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 7.32-7.38 (m, 2 H), 7.49-7.55 (m, 2 H), 7.56-7.60 (m, 2 H), 7.76-7.82 (m, 1 H), 8.23-8.30 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 110.7, 120.1, 124.7, 125.2, 127.3, 127.7, 129.0, 131.6, 142.2, 150.8, 163.1.

HRMS: m/z [M + H+] calcd for C13H10NO: 196.0762; found: 196.0763.

2- o -Tolylbenzoxazole [¹¹a] (Table 3, Entry 2)

White solid; mp 69-70 ˚C (Lit. [¹¹a] 68-69 ˚C); R f  = 0.67 (hexanes-EtOAc, 9:1).

FTIR (neat): 744, 1241, 1548, 2921, 3100 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 2.83 (s, 3 H), 7.32-7.45 (m, 5 H), 7.57-7.63 (m, 1 H), 7.80-7.85 (m, 1 H), 8.17-8.23 (m, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 22.3, 110.6, 120.2, 124.5, 125.1, 126.1, 126.3, 130.0, 130.9, 131.9, 138.9, 142.2, 150.4, 163.5.

HRMS: m/z [M + H+] calcd for C14H12NO: 210.0919; found: 210.0920.

2-(2-Methoxyphenyl)benzoxazole [¹²a] (Table 3, Entry 3)

White solid; mp 50-52 ˚C (Lit. [¹²a] 53-55 ˚C); R f  = 0.25 (hexanes-EtOAc, 9:1).

IR (neat): 748, 1248, 1548, 2922, 3050 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 4.00 (s, 3 H), 7.05-7.13 (m, 2 H), 7.30-7.37 (m, 2 H), 7.46-7.52 (m, 1 H), 7.58 (dd, J = 3.2, 6.0 Hz, 1 H), 7.82 (dd, J = 3.2, 6.0 Hz, 1 H), 8.14 (dd, J = 2.0, 8.0 Hz, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 56.4, 110.6, 112.3, 116.4, 120.4, 120.6, 120.9, 124.4, 125.1, 131.5, 132.9, 142.3, 150.5, 158.6.

HRMS: m/z [M + H+] calcd for C14H12NO2: 226.0868; found: 226.0874.

2-(3-Methoxyphenyl)benzoxazole (Table 3, Entry 4)

White solid; mp 52-55 ˚C; R f  = 0.45 (hexanes-EtOAc, 9:1).

IR (neat): 741, 1234, 1551, 2923, 3100 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 3.90 (s, 3 H), 7.07 (dd, J = 2.4, 8 Hz, 1 H), 7.31-7.37 (m, 2 H), 7.41 (t, J = 8 Hz, 1 H), 7.54-7.59 (m, 1 H), 7.75-7.80 (m, 2 H), 7.82-7.86 (m, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 55.6, 110.7, 112.0, 118.4, 120.1, 120.2, 124.7, 125.2, 128.4, 130.1, 142.1, 150.8, 160.0, 163.0.

HRMS: m/z [M + H+] calcd for C14H12NO2: 226.0868; found: 226.0874.

2-(4-Methoxyphenyl)benzoxazole [¹²a] (Table 3, Entry 5)

White solid; mp 97 ˚C (Lit. [¹²a] 97-98 ˚C); R f  = 0.38 (hexanes-EtOAc, 9:1).

FTIR (neat): 786, 1282, 1583, 2923, 3050 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 3.83 (s, 3 H), 6.98 (d, J = 8.8 Hz, 2 H), 7.25-7.34 (m, 2 H), 7.49-7.54 (m, 1 H), 7.69-7.76 (m, 1 H), 8.16 (d, J = 8.4 Hz, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 55.6, 110.5, 114.5, 119.7, 119.8, 124.5, 124.7, 129.5, 142.4, 150.8, 162.5, 163.3.

HRMS: m/z [M + H+] calcd for C14H12NO2: 226.0868; found: 226.0864.

2-(4-Bromophenyl)benzoxazole [¹²a] (Table 3, Entry 6)

White solid; mp 155-158 ˚C (Lit. [¹²a] 157-158 ˚C); R f  = 0.57 (hexanes-EtOAc, 9:1).

IR (neat): 829, 1069, 1244, 1591, 3057 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 7.34-7.41 (m, 2 H), 7.54-7.61 (m, 1 H), 7.65-7.70 (m, 2 H), 7.75-7.80 (m, 1 H), 8.09-8.15 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 110.7, 120.2, 124.8, 125.4, 126.1, 126.3, 129.0, 132.3, 142.1, 150.8, 162.2.

HRMS: m/z [M + H+] calcd for C13H9NOBr: 273.9868; found: 273.9860.

2-(3-Bromophenyl)benzoxazole [¹9] (Table 3, Entry 7)

White solid; mp 127-128 ˚C (Lit. [¹9] 128-130 ˚C); R f  = 0.63 (hexanes-EtOAc, 9:1).

FTIR (neat): 737, 1070, 1241, 1570, 3057 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 7.32-7.39 (m, 3 H), 7.53-7.59 (m, 1 H), 7.60-7.65 (m, 1 H), 7.73-7.79 (m, 1 H), 8.12-8.17 (m, 1 H), 8.38 (t, J = 1.6 Hz, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 110.8, 120.3, 123.1, 124.9, 125.6, 126.1, 129.1, 130.5, 130.6, 134.4, 142.0, 150.8, 161.5.

HRMS: m/z [M + H+] calcd for C13H9NOBr: 273.9868; found: 273.9860.

2-(4-Fluorophenyl)benzoxazole [²0] (Table 3, Entry 8)

White solid; mp 95-96 ˚C (Lit. [²0] 94-95 ˚C); R f  = 0.62 (hexanes-EtOAc, 9:1).

FTIR (neat): 741, 1054, 1245, 1600, 3061 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 7.16-7.23 (m, 2 H), 7.31-7.38 (m, 2 H), 7.52-7.59 (m, 1 H), 7.71-7.79 (m, 1 H), 8.20-8.28 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 110.7, 116.2, 116.4, 120.1, 124.8, 125.3, 129.9, 130.0, 142.2, 150.9, 166.2.

HRMS: m/z [M + H+] calcd for C13H9NOF: 214.0668; found: 214.0665.

2-(4-Chlorophenyl)benzoxazole [¹¹a] (Table 3, Entry 9)

White solid; mp 140-142 ˚C (Lit. [¹¹a] 144-145 ˚C); R f  = 0.66 (hexanes-EtOAc, 9:1).

FTIR (neat): 832, 1091, 1244, 1596, 3100 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 7.31-7.37 (m, 2 H), 7.43-7.49 (m, 2 H), 7.51-7.57 (m, 1 H), 7.72-7.78 (m, 1 H), 8.12-8.17 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 110.7, 120.2, 124.8, 125.4, 125.7, 128.9, 129.3, 137.8, 142.0, 150.8, 162.0.

HRMS: m/z [M + H+] calcd for C13H9NOCl: 230.0373; found: 230.0369.

2-(3-Chlorophenyl)benzoxazole [¹9] (Table 3, Entry 10)

White solid; mp 122 ˚C (Lit. [¹9] 124-125 ˚C); R f  = 0.61 (hexanes-EtOAc, 9:1).

IR (neat): 745, 1080, 1244, 1590, 3100 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 7.30-7.50 (m, 4 H), 7.51-7.59 (m, 1 H), 7.72-7.80 (m, 1 H), 8.06-8.13 (m, 1 H), 8.19-8.25 (m, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 110.8, 120.3, 124.9, 125.6, 125.7, 127.7, 128.9, 130.3, 131.5, 135.1, 142.0, 150.8, 161.7.

HRMS: m/z [M + H+] calcd for C13H9NOCl: 230.0373; found: 230.0367.

2-(4-Nitrophenyl)benzoxazole [¹¹b] (Table 3, Entry 11)

Yellow solid; mp 268-269 ˚C (Lit. [¹¹b] 269-270 ˚C); R f  = 0.5 (hexanes-EtOAc, 8:2).

IR (neat): 736, 1025, 1269, 1480, 2944 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 7.43 (s, 2 H), 7.64 (d, J = 6 Hz, 1 H), 7.83 (d, J = 5.2 Hz, 1 H), 8.31-8.51 (m, 4 H).

HRMS: m/z [M + H+] calcd for C13H9N2O3: 241.0613; found: 214.0615.

2-[1-( tert -Butoxycarbonyl)pyrrolidin-2-yl]benzoxazole (Table 3, Entry 12)

White solid; mp 65-70 ˚C; R f  = 0.25 (hexanes-EtOAc, 8:2).

IR (neat): 1163, 1693, 2134, 2928, 2973 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 1.20 (s, 6 H), 1.50 (s, 3 H), 1.95-2.44 (m, 4 H), 3.45-3.80 (m, 2 H), 4.9-5.2 (m, 1 H), 7.27-7.35 (m, 2 H), 7.45-7.52 (m, 1 H), 7.69 (dd, J = 3.2, 5.6 Hz, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 23.9, 24.5, 28.6, 31.6, 46.7, 55.5, 80.1, 110.6, 120.0, 120.2, 124.5, 124.9, 141.3, 154.0, 167.5.

HRMS: m/z [M + H+] calcd for C16H21N2O3: 289.1552; found: 289.1555.

2- tert -Butylbenzoxazole [¹¹a] (Table 3, Entry 13)

Brown oil; R f  = 0.6 (hexanes-EtOAc, 9:1).

IR (neat): 1098, 1243, 1564, 2974 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 1.40 (s, 9 H), 7.16-7.22 (m, 2 H), 7.35-7.40 (m, 1 H), 7.57-7.64 (m, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 28.6, 34.2, 110.4, 119.8, 124.1, 124.5, 141.4, 150.9, 173.6.

HRMS: m/z [M + H+] calcd for C11H14NO: 176.1075; found: 176.1073.

6-Methyl-2-phenylbenzoxazole [²¹] (Table 3, Entry 18)

White solid; mp 90-93 ˚C (Lit. [²¹] 90-92 ˚C); R f  = 0.57 (hexanes-EtOAc, 9:1).

IR (neat): 760, 1248, 1555, 2921, 3056 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 2.50 (s, 3 H), 7.16 (d, J = 8.0 Hz, 1 H), 7.38 (s, 1 H), 7.49-7.54 (m, 3 H), 7.63 (d, J = 8 Hz, 1 H), 8.21-8.26 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 21.8, 110.8, 119.4, 125.8, 127.4, 127.5, 128.9, 131.3, 135.6, 140.0, 151.1, 162.6.

HRMS: m/z [M + H+] calcd for C14H12NO: 210.0919; found: 210.0920.

2-(4-Methoxyphenyl)-6-methylbenzoxazole [²²] (Table 3, Entry 19)

White solid; mp 90 ˚C (Lit. [²²a] 91 ˚C); R f  = 0.65 (hexanes-EtOAc, 9:1).

IR (neat): 731, 836, 1246, 1581, 2839, 2919, 3100 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 2.50 (s, 3 H), 3.90 (s, 3 H), 6.99 (d, J = 8.4 Hz, 2 H), 7.13 (d, J = 8.0 Hz, 1 H), 7.32 (s, 1 H), 7.59 (d, J = 8 Hz, 1 H), 8.15 (d, J = 8.4 Hz, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 21.8, 55.4, 110.6, 114.3, 118.9, 119.9, 125.6, 129.2, 134.9, 140.1, 150.9, 162.2, 162.7.

HRMS: m/z [M + H+] calcd for C15H14NO2: 240.1025; found: 240.1021.

2-(3-Methoxyphenyl)-6-methylbenzoxazole (Table 3, Entry 20)

White solid; mp 80-82 ˚C; R f  = 0.43 (hexanes-EtOAc, 9:1).

IR (neat): 726, 1225, 1556, 2983 cm-¹.

¹H NMR (400 MHz, CDCl3): δ = 2.40 (s, 3 H), 3.80 (s, 3 H), 6.93 (dd, J = 2.4, 8.4 Hz, 1 H), 7.03 (d, J = 8.4 Hz, 1 H), 7.23 (s, 1 H), 7.28 (t, J = 8 Hz, 1 H), 7.52 (d, J = 8.0 Hz, 1 H), 7.62-7.64 (m, 1 H), 7.70 (d, J = 8 Hz, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 21.8, 55.5, 110.8, 111.8, 118.1, 119.4, 120.0, 125.9, 128.6, 130.0, 135.7, 140.0, 151.1, 160.0, 162.5.

HRMS: m/z [M + H+] calcd for C15H14NO2: 240.1025; found: 240.1021.

Supporting Information for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/ejournals/toc/synthesis.

Acknowledgment

We thank DST (Project No. SR/S1/OC-06/2008), New Delhi for financial support. A.B.N. thanks UGC, New Delhi for SRF. We thank DST, New Delhi for funding towards the 400-MHz NMR machine to the Department of Chemistry, IIT-Madras under the IRPHA Scheme and for funding to the ESI-MS facility under the FIST Programme.

17

BINAM with Cu(OTf)2 gives a 1:2 complex. The X-ray crystal structure of (R)-BINAM-Cu(OTf)2 complex was solved; see ref. 15d.

18

BINAM is irritating to the skin, eyes, and respiratory tract, and is an equivocal tumorigenic agent by RTECS criteria (as per the Material Safety Data Sheet of Strem Chemicals, Inc.).

17

BINAM with Cu(OTf)2 gives a 1:2 complex. The X-ray crystal structure of (R)-BINAM-Cu(OTf)2 complex was solved; see ref. 15d.

18

BINAM is irritating to the skin, eyes, and respiratory tract, and is an equivocal tumorigenic agent by RTECS criteria (as per the Material Safety Data Sheet of Strem Chemicals, Inc.).

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Scheme 1

Figure 1 BINAM-based ligands for Ullmann-type intramolecular C(aryl)-O bond-forming cyclization