ISSN 1477-0520

1477-0520(2013)11:36;1-4

Organic & Biomolecular Chemistry www.rsc.org/obc Volume 11 | Number 36 | 28 September 2013 | Pages 5965–6226

PAPER Wei Zeng et al. An unusual 1,2-aryl shift in palladium-catalyzed cross-coupling ethoxycarbonylation of arylboronic acids with α-iminoesters

Organic &Biomolecular Chemistry

PAPER

Cite this: Org. Biomol. Chem., 2013, 11,6013

Received 15th May 2013,Accepted 12th July 2013

DOI: 10.1039/c3ob41011k

www.rsc.org/obc

An unusual 1,2-aryl shift in palladium-catalyzedcross-coupling ethoxycarbonylation of arylboronicacids with α-iminoesters†

Cheng Qian,a Jiayan Chen,a Meiqin Fu,a Shiya Zhu,a Wen-Hua Chen,b

Huanfeng Jianga and Wei Zeng*a

The Pd-catalyzed cross-coupling ethoxycarbonylation of aryl boronic acids with N-aryl-α-iminoesters

affords aryl carboxylic esters via carbonyl-imino σ bond cleavage. This unprecedented mode of reaction

allows regioselective installation of the ethoxycarbonyl group into target molecules. Mechanism studies

have revealed that an unusual 1,2-aryl shift process is involved in the transformation.

Introduction

Arylcarboxylic derivatives are important structural buildingblocks and synthetic intermediates in biologically activenatural products and medicinal chemistry. Transition metal-catalyzed carbonylation of aryl halides,1 tosylates2 and borates3

and decarboxylation of aryl halides4 have emerged as powerfulalternatives to the traditional synthetic method of these com-pounds. Although much progress toward achieving this trans-formation has been made, in most cases, the drawbacks ofusing toxic carbon monoxide and high pressure reaction con-ditions often limit the scope of this reaction. The developmentof a new metal-catalyzed carbonylation transformation undermild and practical conditions is therefore highly desirable.

Recently, much research on carbonylation of aryl halideshas focused on identifying various carbonylating agents.Although gas carbon monoxide and metal CO complexes couldbe employed as traditional carbonyl (CvO) sources,5 car-boxylic acid derivatives have also attracted particular attention,and have already been studied and used extensively by manygroups.1d,e,4,6 Related typical studies include the work of Liu4a

and Goossen,4b who realized that successively Pd-catalyzedcross-coupling carbonylation of aryl halides with potassiumcarboxylates (RCOCO2K) affords the corresponding α-aryl car-bonyl compounds. More recently, Skrydstrup also developed aPd-catalyzed aminocarbonylation and hydroxycarbonylation ofaryl halides using pivaloyl chloride and potassium formate as

CO-precursors, respectively.1d,e On the other hand, acylimineshave served as versatile acceptors of nucleophiles due to theirmultiple reactive sites, and their corresponding addition reac-tions with organometallic reagents, Mannich donors, radicalregents, etc. are commonly utilized in many crucial steps.7 Forexample, Ellman8 and other researchers9 found that transitionmetal salts could efficiently catalyze the arylation of N-sulfonylimine (S2) via the addition of aryl boronic acid (S1) to CvNbonds of S2 to yield the corresponding amide derivatives (P1)(Scheme 1a). Nevertheless, transition metal-catalyzed regio-selective installation of the carbonyl group into target moleculesusing iminoester (RO2CCvNR1) as a carbonylating agent wasunprecedented. We recently reported the palladium-catalyzedasymmetric addition of arylboronic acids to α-imino esters.Using an appropriate bis(oxazoline) ligand, protected α-aminoesters P2 could be prepared in up to 95% yield and 99% ee.7i

During the course of these studies we noticed that, undermore vigorous conditions, aryl carboxylates P3 were theobserved products (Scheme 1b). Assuming that P2 remains theprimary product, the formation of P3 implies the occurrenceof a 1,2-aryl shift and extrusion of (unstable) methylene imineP4. Such a rearrangement is, to our knowledge, unprece-dented. Therefore we undertook a two-part study (1) to explore

Scheme 1 Two different reactions of aryl metal species with N-acylimines andC-acylimines.

†Electronic supplementary information (ESI) available: Detailed experimentalprocedures and characterization of products. See DOI: 10.1039/c3ob41011k

aSchool of Chemistry and Chemical Engineering, South China University of

Technology, Guangzhou 510641, P. R. China. E-mail: zengwei@scut.edu.cnbSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou

510515, P. R. China

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the scope of this transformation to identify any potential syn-thetic utility and (2) to gain a mechanistic understanding ofthe reaction.

Results and discussion

The Pd(OAc)2-catalyzed cross-coupling ethoxycarbonylation ofvarious coupling partners (0.18 mmol) including aryl halidesand aryl boronic acid derivatives with α-imino ester 1a(0.18 mmol) was first investigated in CH3NO2 (3.0 mL) at110 °C for 48 h (Table 1, entries 1–4), and we soon found thatonly phenylboronic acid could provide 8% yield of ethyl benzo-ate (3a) (entry 4). Although the yield of 3a is very poor, thispositive result encouraged us to conduct further carbonylationtransformation to screen the reaction conditions for achievingsatisfying yields. Then, we investigated the effect of variouspalladium salts on the cross-coupling ethoxylcarbonylation ofphenylboronic acid (2a) with N-(4-methoxy-phenyl)-α-imino-ester (1a). Among the tested palladium salts (entries 4–8),PdCl2(CH3CN)2 and PdCl2(PhCN)2 were effective catalysts forthis transformation, and could increase the yield of 3a byaround 30% (compare entries 4 and 7–8). Considering thatsuitable ligands can increase the nucleophilicity of arylpalla-dium species and accelerate the arylation reaction,9e we triedto employ various phosphine- or nitrogen-containing ligandsto improve the reaction yield. To our delight, bidentate nitro-gen-containing ligands (L1, L7–L8) could significantly enhancethe catalytic activity of Pd(TFA)2 (compare entries 5 with 11,16–18). Further optimization of these reaction conditionsdemonstrated that the cross-coupling ethoxylcarbonylationof phenylboronic acid 2a with α-imino ester 1a was mostproductive using L7 as a ligand under 110 °C within 48 h, pro-viding 3a in 91% yield (entry 17) (see ESI† for more details).Unfortunately, other α-imino esters such as isopropyl [(4-meth-oxyphenyl)imino] acetate 1b and benzyl [(4-methoxyphenyl)-imino] acetate 1c gave a little lower yield of benzoate esters 3band 3c (compare entries 17 with 19–20). Notably, evaluatingphosphine-containing ligands (L2–L5) could not enhanceefficiently the transformation to occur in the presence of Pd(TFA)2 (entries 12–15). When the reaction temperature waslowered from 110 °C to 90 °C, diminished chemical selectivi-ties were observed, and the arylation product (4-methoxy-phe-nylamino)-phenyl-acetic acid ethyl ester (P2a) (45% yield) wasformed (compare entries 17 and 21). It is interesting that whenwe switch substrate N-(4-methoxy-phenyl)-α-iminoester 1a toN-(4-methoxy-phenyl)-α-iminoketone 1d, we got 51% yield of1,2-diphenylethanedione (3a–1) instead of benzophenone(entry 22).

Having established an efficient reaction protocol thatenables the smooth cross-coupling transformation of a par-ticular phenyl boronic acid, we next investigated its scope withregard to the N-aryl iminoester coupling partner. As shown inTable 2, aryl substitution on the imine nitrogen (R1) showedsignificant electronic effects, the substrates with a para-electron-donating group (4-MeO, 4-Me) on the phenyl ring

afforded the ethyl benzoate ester in good to excellent yields(76–91% yield of 3a, compare entries 5 and 1–2), and electron-withdrawing (such as 4-Cl, 4-Br, 4-NO2, 3-CO2Et) α-iminoestersincluding N-cyclohexyl α-iminoester underwent slightly worseconversion and provided lower yield of 3a (16–59%, entries 3–4and 6–8).

The scope of the procedure with regard to the aryl boronicacid coupling partner was then explored with N-(4-methoxyl-phenyl)-α-iminoester as the carbon electrophile (see Table 3).Electron-rich and halide-substituted aryl boronic acids under-went a smooth conversion when common functionalities, suchas methyl, methoxyl, chloro, fluoro and aryl groups, werepresent as para or meta-substituents on the aromatic ring, withthe formation of 42–94% yield of compounds 3a, 3d–3e, and3k–3n (entries 1–3 and 9–12). But electron-poor aryl boronicacid (4-CF3 and 3-NO2) gave lower yield of esters (entries 7 and 8).Of particular note, the cross-coupling reaction of 1a with3-nitrophenylboronic acid also produced unexpectedly4′-methoxy-3-nitro-biphenyl (3j–1) in 35% yield (entry 8).10

Also, benzo-fused aryl boronic acids could also be convertedinto the corresponding carboxylic esters in good yields (entries13 and 14); especially for 3p, we could make it with 75% yieldjust in one step (entry 14). Previously, Tomioka reported thesynthesis of 3p from anthranilic acid in a route that is 5 stepslonger.11 Compared with the para-substituted aryl boronicacids, ortho-substituted aryl boronic acid led to a substantialdecrease in product yield presumably due to the increasedsteric hindrance around arylpalladium species (compareentries 2 with 4). Furthermore, several sensitive functionalgroup-containing arylboronic acids could also give the desiredproducts in 45–79% yields (entries 15–18).12 It is worth notingthat heterocyclic aryl boronic acids such as 2-thienyl, 3-thienyland 2-benzothiophenyl boronic acids could also be usedin this transformation and gave the corresponding arylcarboxylic esters in up to 74% yield (entries 19–21). Unfortu-nately, no reaction occurred for the alkenyl boronic acid (2v),and α-iminoester 1a was completely recovered (entry 22).13

We further conducted several control experiments toexplore the reaction mechanism. At first, considering that theN-aryl-α-iminoester is not stable, and produces ethyl glyoxalate(1aa) via reversible reaction in the presence of trace amountsof H2O (Scheme 2a),14 we used 1aa and 4-methylphenylboronicacid (2e) as starting materials to run the reaction, but onlytrace amounts of 3g were obtained (Scheme 2b). This resultexcludes the possibility that 1aa was directly involved in thecoupling carbonylation with arylboronic acid 2e. On the otherhand, when the coupling reaction between N-(4-methoxyphe-nyl)-α-iminoester (1a) and 2e was carried out at 110 °C for 24 hand monitored by TLC and GC-MS methods, we found andseparated the intermediate 2aa (25% yield), which could befurther converted into 3g in 85% yield under the Pd(TFA)2(5 mol%)/bipy (5 mol%)/phenylboronic acid 2a (20 mol%) cata-lytic system (Scheme 2c).15,16 It is worth noting that 2aa couldalso be converted into 3g in 65% yield in the presence of Lewisacid FeCl3 (2.0 equiv.); this result indicated that the Pd(TFA)2/L7/arylboronic acid system possibly plays a key role of a Lewis

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Table 1 Optimisation results for the alkoxycarbonylation of arylboronic acid with Pd(II)/ligand as the catalysta

Entry PdX2 (5 mol%) 1 2 L Product Yieldb (%)

1 Pd(OAc)2 L2 0

2 Pd(OAc)2 1a L2 3a 0

3 Pd(OAc)2 1a — 3a 0

4 Pd(OAc)2 1a — 3a 8

5 Pd(TFA)2 1a 2a — 3a 136 PdCl2 1a 2a — 3a 277 PdCl2(CH3CN)2 1a 2a — 3a 358 PdCl2(PhCN)2 1a 2a — 3a 379 PdCl2 1a 2a L1 3a 2710 PdCl2(CH3CN)2 1a 2a L1 3a 5311 Pd(TFA)2 1a 2a L1 3a 6112 Pd(TFA)2 1a 2a L2 3a 1613 Pd(TFA)2 1a 2a L3 3a 1114 Pd(TFA)2 1a 2a L4 3a 1715 Pd(TFA)2 1a 2a L5 3a <1016 Pd(TFA)2 1a 2a L6 3a 3517 Pd(TFA)2 1a 2a L7 3a 9118 Pd(TFA)2 1a 2a L8 3a 8119 Pd(TFA)2 2a L7 82

20 Pd(TFA)2 2a L7 12

21 Pd(TFA)2 1a 2a L7 3a 37c

45c

22 Pd(TFA)2 2a L7 51

a All the reactions were run with imine 1 (0.18 mmol), aryl compound 2 (0.18 mmol), palladium catalyst (5 mol%), L (5 mol%), CH3NO2 (3.0 mL)at 110 °C under Ar for 48 h in a sealed reaction tube, followed by flash chromatography on SiO2.

b Isolated yield. c The reaction temperature was90 °C. L = ligand.

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acid catalyst during the transformation of 2aa into 3g(Scheme 2c and 2d). By the way, 2aa could not be convertedinto 3g in the absence of phenylboronic acid 2a or 2e(Scheme 2e) (see ESI† for more details).

After we confirmed that 2aa was the key intermediate whichcould lead to the final ethoxycarbonylation product 3i(Scheme 2c), we further investigated the electronic effect ofsubstituent (R) in the N-substituted benzene ring of arylationintermediate (P2a–P2f ) on this transformation using the Pd(II)/L7/2a catalytic system. As shown in Table 4, compared with theelectron-donating group (R = OMe, Me and H, entries 1–3), theelectron-withdrawing group (R = Cl, Br and NO2, entries 4–6)resulted in lower yield of ethyl benzoate (3a), possibly due tothat the electron-withdrawing group decreased the electrondensity at the amino nitrogen, and cannot efficiently promotethe 1,2-aryl shift to occur. Moreover, simple Hammett

Table 2 The effect of the α-imino esters on the Pd(II)-catalyzed ethoxycarbony-lation of arylboronic acid 2aa

Entry α-Imino esters (1) Yieldb (%)

1 91

2 76c

3 26

4 18

5 64c

6 59

7 41

8 16

a All the reactions were run with α-imino ester (1) (0.18 mmol), arylboronic acid (2a) (0.18 mmol), Pd(TFA)2 (5 mol%), L7 (5 mol%), inCH3NO2 (3.0 mL) at 110 °C under Ar for 48 h unless otherwise noted.b Isolated yield after flash chromatography on SiO2.

c The reactiontime: 72 h.

Table 3 Pd(II)-catalyzed ethoxycarbonylation of arylboronic acids 2a

Entry Aryl boronic acid 2 Product Yieldb (%)

1 91

2 94

3 81

4 42

5 88

6 88

7 29

8 21

35

9 68

10 68

11 57

12 82

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correlation studies about various N-substituted arylglycines P2(R = MeO, Me, H, Cl, Br, NO2) also showed a linear free energyrelationship (R = 0.96) with the Hammett constant σp

+ and thevalue ρ+ was found to be −0.64 (Fig. 1).

On the basis of the above-mentioned experimental resultsand the corresponding GC-MS analysis about the reaction pro-gress of α-iminoesters (1a) and phenylboronic acid (2a) (seeESI† for more details), a possible mechanism for this reactionis outlined in Fig. 2. For the first step, the coordination of aryl

Table 3 (Contd.)

Entry Aryl boronic acid 2 Product Yieldb (%)

13 53

14 75

15 70c

16 45

17 67

18 79

19 71

20 74

21 25

22 0

a All the reactions were run with 1a (0.18 mmol), aryl boronic acid 2(0.18 mmol), Pd(TFA)2 (5 mol%), L7 (5 mol%), in CH3NO2 (3.0 mL) at110 °C under Ar for 48 h unless otherwise noted. b Isolated yield afterflash chromatography on SiO2.

c The reaction temperature was 120 °C.

Scheme 2 Mechanism exploration of the Pd-catalyzed cross-coupling ethoxy-carbonylation of arylboronic acids with α-iminoesters.

Table 4 The electronic effect of substituents in the N-substituted benzene ringof arylation intermediate (P2) on the 1,2-aryl shift processa

Entry Arylation intermediate (P2) Yieldb (%)

1 89

2 73

3 68

4 39

5 35

6 20

a All the reactions were run with the arylation intermediate (P2)(0.18 mmol), phenylboronic acid (2a) (20 mol%), Pd(TFA)2 (5 mol%),L7 (5 mol%), in CH3NO2 (3.0 mL) at 110 °C under Ar for 48 h.b Isolated yield after flash chromatography on SiO2.

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palladium active species B with the N-aryl-α-iminoester 1a ledto intermediate C, and then the addition of aryl group (Ar) toimine furnished the formation of adduct E upon proto-nation.7i,17 Subsequently, bpy-aryl Pd complexes B could possiblycontinue to serve as a Lewis acid to activate the ester carbonylgroup; and the transfer of a lone electron pair on the N atomof intermediate F triggers the 1,2-aryl shift18 and affords theintermediate G, which could provide the aryl carboxylic ester3a via a further cleavage of Csp2–Csp3 bonds. The other frag-ment of G is (4-methoxy-phenyl)-methylene-amine which isnot stable and could be further partially trapped by the solventCH3NO2 to form 4-methoxy-N-(2-nitroethyl) benzenamine (4b,28% yield).19,20

Conclusions

In summary, we have reported a novel 1,2-aryl shift process inPd-catalyzed cross-coupling esterification of arylboronic acidswith N-aryl-α-iminoesters. Further studies on expanding thescope of the reaction to more complex substrates are currentlyunderway in our laboratory.

ExperimentalGeneral synthetic procedures

Unless otherwise noted, all other commercially availablereagents and solvents were used without further purification.Purifications of reaction products were carried out by flashchromatography using silica gel (40–63 mm). Infrared spectra(IR) are reported as wavelength numbers (cm−1). 1H and 13CNMR spectra were recorded using a 400 MHz NMR spectro-meter. Splitting patterns are denoted as singlet (s), broadsinglet (bs), doublet (d), and triplet (t). Splitting patterns thatcould not be interpreted or easily visualized are denoted asmultiplet (m). Mass spectra were acquired using a quadrupoleMS instrument in the ESI (+) mode for low resolution spectraand in the ESI (−) mode for high resolution analysisrespectively.

General procedures for the synthesis of 3a–3x

A mixture containing ethyl glyoxylate (0.18 mmol, 1.0 equiv.),substituted amine (0.18 mmol, 1.0 equiv.), anhydrous sodiumsulfate (0.87 mmol, 5.0 equiv.) and 3 mL of toluene was stirredat room temperature for 0.5 hour to afford C-acylimines 1a, 1b,1c, 1d, 1f, 1 h, or refluxed at 110 °C for 2 hours to afford C-acyl-imines 1i, 1j, 1k. The mixture was then filtered and thesolvent was removed under reduced pressure, and the corres-ponding crude products were directly used for synthetic pur-poses without purification.7g Then, to the solution ofC-acylimine (0.18 mmol, 1.0 equiv.) in CH3NO2 (3.0 mL) wasadded arylboronic acid (0.18 mmol, 1.0 equiv.), Pd(TFA)2(0.009 mmol, 5 mol%) and bipy (0.009 mmol, 5 mol%), andthen the corresponding mixture was stirred at 110 °C under Arfor 48 h. After the reaction was completed (monitored by TLC),the reaction mixture was cooled to room temperature, thenconcentrated under vacuum and purified by flash chromato-graphy (eluting with an eluent consisting of hexane–EtOAc,from 20 : 1 to 10 : 1) to give the corresponding pure products.

Ethyl benzoate (3a).21 Yellow oil; 24.5 mg, 91% yield;1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.1 Hz, 2 H), 7.70–7.63(m, 1 H), 7.52 (t, J = 7.7 Hz, 2 H), 4.46 (q, J = 7.1 Hz, 2 H), 1.43(t, J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 186.44,163.84, 134.90, 132.49, 130.04, 128.90, 62.35, 14.12; MS (EI, 70eV) m/z: 150.09 (M+); IR (KBr): 2925, 2854, 1734, 1689, 1452,1195, 1071, 751, 691, 565 cm−1.

Isopropyl benzoate (3b).22 Yellow oil; 24.1 mg, 82% yield;1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.4 Hz, 2 H), 7.70–7.63(m, 1 H), 7.53 (t, J = 7.8 Hz, 2 H), 5.35 (dt, J = 12.5, 6.3 Hz,1 H), 1.43 (d, J = 6.3 Hz, 6 H); 13C NMR (100 MHz, CDCl3)δ 186.73, 163.65, 134.81, 132.54, 129.95, 128.89, 70.68, 21.72;MS (EI, 70 eV) m/z: 163.88 (M+); IR (KBr): 2984, 1736, 1691,1597, 1451, 1375, 1244, 1205, 1177, 1102, 1050, 988, 913, 844,744, 687 cm−1.

Benzyl benzoate (3c).23 Yellow oil; 4.5 mg, 12% yield; 1HNMR (400 MHz, CDCl3) δ 7.99–7.94 (m, 2 H), 7.63 (t, J = 7.4 Hz,1 H), 7.49 (d, J = 7.9 Hz, 2 H), 7.44 (dd, J = 8.2, 1.9 Hz, 2 H),7.40–7.36 (m, 3H), 5.41 (s, 2 H); 13C NMR (100 MHz, CDCl3)δ 186.08, 163.67, 134.97, 134.56, 132.45, 130.05, 128.93, 128.84,

Fig. 1 Log(Y/Y0) as a function of the Hammett constant for this 1,2-aryl shiftprocess. Y refers to the yield from para-substituted arylamines (P2a–P2b, P2d–P2f ), and Y0 refers to the yield from P2c.

Fig. 2 The proposed mechanism for the Pd(II)-catalyzed cross-couplingcarbonylation of α-iminoester (1a) with arylboronic acid (2a).

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128.77, 128.63, 67.79; MS (EI, 70 eV) m/z: 212.10 (M+); IR (KBr):2983, 1739, 1690, 1598, 1520, 1451, 1373, 1343, 1244, 1195,1173, 1048, 992, 749, 698 cm−1.

Ethyl 2-(4-methoxyphenylamino)-2-phenylacetate (P2a).7i

Yellow oil; 23.1 mg, 45% yield; 1H NMR (400 MHz, CDCl3)δ 7.49 (d, J = 7.5 Hz, 2 H), 7.36–7.30 (m, 3 H), 6.72 (d, J = 8.8 Hz,2 H), 6.53 (d, J = 8.7 Hz, 2 H), 5.00 (s, 1 H), 4.67 (s, 1 H),4.25–4.11 (m, 2 H), 3.70 (s, 3 H), 1.20 (t, J = 7.1 Hz, 3 H); 13CNMR (100 MHz, CDCl3) δ (ppm) 172.1, 152.5, 140.3, 137.9,128.8, 128.2, 127.3, 114.8, 61.7, 61.6, 55.7, 14.1; MS (ESI): m/z =286.6 [M+], 324.6 [M + K+]; IR (KBr): 3399, 2927, 2854, 1734,1513, 1457, 1370, 1305, 1239, 1178, 1029, 820, 732, 688,523 cm−1.

2-Diphenyl-ethane-1,2-dione (3a–1).24 Oil; 19.3 mg, 51%yield; 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 7.4 Hz, 4 H),7.65 (t, J = 7.4 Hz, 2 H), 7.51 (t, J = 7.7 Hz, 4 H); 13C NMR(100 MHz, CDCl3) δ 194.61, 134.91, 133.01, 129.91, 129.04. MS(EI, 70 eV) m/z: 210.12 (M+); IR (KBr): 3063, 1660, 1594, 1448,1321, 1275, 1209, 1173, 1071, 793, 750, 718, 641, 464 cm−1.

Ethyl 4-methoxybenzoate (3d).21 Yellow oil; 30.5 mg, 94%yield; 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.8 Hz, 2 H),6.97 (d, J = 8.8 Hz, 2 H), 4.43 (q, J = 7.1 Hz, 2 H), 3.89 (s, 3 H),1.42 (t, J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 184.90,165.03, 164.18, 132.57, 125.51, 114.24, 62.16, 55.64, 14.12; MS(EI, 70 eV) m/z: 179.18 (M+); IR (KBr): 2933, 2846, 1736, 1676,1599, 1572, 1463, 1308, 1266, 1207, 1164, 1021, 976, 841, 617,514 cm−1.

Ethyl 3-methoxybenzoate (3e).25 Yellow oil; 26.3 mg, 81%yield; 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 7.6 Hz, 1 H),7.53 (s, 1 H), 7.41 (t, J = 7.9 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H),4.45 (q, J = 7.1 Hz, 2 H), 3.86 (s, 3 H), 1.42 (t, J = 7.1 Hz, 3 H);13C NMR (100 MHz, CDCl3) δ 186.33, 163.87, 133.70, 129.91,123.11, 121.84, 113.28, 62.34, 55.51, 14.11; MS (ESI): m/z =200.09 [M + Na+]; IR (KBr): 2936, 2840, 1736, 1687, 1598, 1582,1519, 1486, 1369, 1311, 1290, 1155, 1020, 875, 787, 677,559 cm−1.

Ethyl 2-methoxybenzoate (3f ).21 Yellow oil; 13.6 mg, 42%yield; 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 7.7 Hz, 1 H),7.59 (t, J = 7.9 Hz, 1 H), 7.07 (t, J = 7.5 Hz, 1 H), 6.99 (d, J =8.4 Hz, 1 H), 4.39 (q, J = 7.1 Hz, 2 H), 3.87 (s, 3 H), 1.39 (t, J =7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 186.60, 165.30,136.27, 130.81, 121.32, 112.04, 61.76, 56.01, 14.13; MS (EI,70 eV) m/z: 178.94 (M+); IR (KBr): 2929, 2843, 1739, 1674, 1599,1511, 1484, 1466, 1442, 1272, 1246, 1162, 1112, 1022, 979, 757,665, 530 cm−1.

Ethyl 4-methylbenzoate (3g).21 Yellow oil; 26.0 mg, 88%yield; 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.0 Hz, 2 H),7.32 (d, J = 8.0 Hz, 2 H), 4.45 (q, J = 7.1 Hz, 3 H), 2.45 (s, 3 H),1.43 (t, J = 7.1 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ 186.11,164.05, 146.24, 130.15, 129.62, 62.22, 21.89, 14.11; MS (EI,70 eV) m/z: 164.10 (M+); IR (KBr): 2984, 2928, 1737, 1683, 1605,1448, 1412, 1371, 1304, 1203, 1173, 1118, 1017, 976, 867, 828,749, 618, 480 cm−1.

Ethyl 3-methylbenzoate (3h).21 Yellow oil; 26.0 mg, 88%yield; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.0 Hz, 2 H),7.47 (d, J = 7.4 Hz, 1 H), 7.39 (t, J = 7.7 Hz, 1 H), 4.45 (q, J =

7.1 Hz, 2 H), 2.42 (s, 3 H), 1.42 (t, J = 7.1 Hz, 3 H); 13C NMR(100 MHz, CDCl3) δ 186.70, 164.02, 138.85, 135.77, 130.29,128.78, 127.36, 62.28, 21.27, 14.11; MS (EI, 70 eV) m/z: 164.13(M+); IR (KBr): 2925, 2854, 1737, 1686, 1602, 1459, 1373, 1309,1231, 1154, 1093, 1031, 750, 674, 463 cm−1.

Ethyl 4-(trifluoromethyl)benzoate (3i).21 Yellow oil; 11.4 mg,29% yield; 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.0 Hz,2 H), 7.80 (d, J = 8.1 Hz, 2 H), 4.49 (q, J = 7.1 Hz, 2 H), 1.46 (t,J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 184.98, 162.80,136.02, 135.69, 135.28, 130.43, 125.91, 125.87, 62.76, 14.06; MS(ESI): m/z = 219.0 [M+]; IR (KBr): 2924, 2854, 2388, 2287, 1734,1697, 1603, 1411, 1374, 1323, 1202, 1170, 1016, 980, 843, 741,591 cm−1.

Ethyl 3-nitrobenzoate (3j).26 Yellow oil; 7.4 mg, 21% yield;1H NMR (400 MHz, CDCl3) δ 8.90 (s, 1 H), 8.58–8.46 (m, 2 H),7.76 (t, J = 8.1 Hz, 1 H), 4.51 (q, J = 7.1 Hz, 2 H), 1.46 (t, J = 7.1Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 183.54, 162.19, 137.59,135.45, 130.20, 128.84, 125.02, 63.06, 14.05; MS (ESI): m/z =219.0 [M + Na+]; IR (KBr): 3087, 2925, 2854, 1732, 1696, 1611,1531, 1407, 1343, 1311, 1196, 1099, 1021, 884, 857, 813, 700,673 cm−1.

4′-Methoxy-3-nitro-1,1′-biphenyl (3j–1).27 Yellow oil; 14.5 mg,35% yield; 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1 H), 8.19–8.14(m, 1 H), 7.89 (d, J = 7.8 Hz, 1 H), 7.62–7.57 (m, 3 H), 7.04 (d,J = 8.7 Hz, 2 H), 3.90 (s, 3 H); 13C NMR (100 MHz, CDCl3)δ 160.10, 148.78, 142.49, 132.51, 131.10, 129.63, 128.28,121.40, 121.37, 114.60, 55.43; MS (EI, 70 eV) m/z: 229.28 (M+);IR (KBr): 2924, 2853, 1765, 1607, 1512, 1461, 1346, 1253, 1179,1044, 898, 875, 831, 749, 680, 570 cm−1.

Ethyl 4-chlorobenzoate (3k).21 Yellow oil; 22.5 mg, 68%yield; 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.3 Hz, 2 H),7.49 (d, J = 8.3 Hz, 2 H), 4.45 (q, J = 7.1 Hz, 2 H), 1.43 (t, J =7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 184.86, 163.01,135.25, 134.80, 134.07, 130.22, 129.87, 128.24, 62.66, 14.09; MS(EI, 70 eV) m/z: 184.10 (M+); IR (KBr): 2925, 2854, 1736, 1689,1590, 1519, 1462, 1402, 1340, 1200, 1170, 1089, 1014, 976, 833,769, 673, 544, 482 cm−1.

Ethyl 3-chlorobenzoate (3l).25 Yellow oil; 22.5 mg, 68%yield; 1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1 H), 7.92 (d, J =7.7 Hz, 1 H), 7.63 (d, J = 8.0 Hz, 1 H), 7.46 (t, J = 7.9 Hz, 1 H),4.46 (q, J = 7.1 Hz, 2 H), 1.43 (t, J = 7.1 Hz, 3 H); 13C NMR(100 MHz, CDCl3) δ 184.86, 163.01, 135.25, 134.80, 130.22,129.87, 128.24, 62.66, 14.09; MS (EI, 70 eV) m/z: 184.11 (M+); IR(KBr): 2926, 2854, 1737, 1693, 1510, 1570, 1424, 1370, 1343,1308, 1192, 1023, 900, 782, 742 cm−1.

Ethyl 4-fluorobenzoate (3m).21 Yellow oil; 17.3 mg, 57%yield; 1H NMR (400 MHz, CDCl3) δ 8.12–8.06 (m, 2 H), 7.19 (t,J = 8.5 Hz, 2 H), 4.45 (q, J = 7.1 Hz, 2 H), 1.43 (t, J = 7.1 Hz,3 H); 13C NMR (100 MHz, CDCl3) δ 184.90, 163.22, 141.63,131.44, 129.31, 62.56, 14.09; MS (ESI): m/z = 192.9 [M + Na+];IR (KBr): 2926, 2854, 2361, 1736, 1689, 1598, 1507, 1414, 1372,1238, 1197, 1155, 1099, 1018, 978, 845, 747, 636, 549,506 cm−1.

Ethyl [1,1′-biphenyl]-4-carboxylate (3n).28 Yellow oil;33.4 mg, 82% yield; 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J =8.2 Hz, 2 H), 7.72 (d, J = 8.2 Hz, 2 H), 7.62 (d, J = 8.0 Hz, 2 H),

Organic & Biomolecular Chemistry Paper

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7.47 (t, J = 7.5 Hz, 2 H), 7.43–7.38 (m, 1 H), 4.46 (q, J = 7.1 Hz,2 H), 1.43 (t, J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3)δ 185.96, 163.87, 147.60, 139.45, 131.23, 130.68, 129.07,128.68, 127.52, 127.37, 62.39, 14.16; MS (EI, 70 eV) m/z: 226.30(M+); IR (KBr): 3059, 3032, 2983, 2934, 1733, 1681, 1600, 1556,1483, 1447, 1369, 1303, 1207, 1176, 1023, 1009, 976, 759, 740,694, 632, 506, 479 cm−1.

Ethyl 1-naphthoate (3o).29 Yellow oil; 19.1 mg, 53% yield;1H NMR (400 MHz, CDCl3) δ 9.04 (d, J = 8.6 Hz, 1 H), 8.12 (d,J = 8.2 Hz, 1 H), 7.98 (d, J = 7.3 Hz, 1 H), 7.91 (d, J = 8.1 Hz,1 H), 7.69 (dd, J = 8.3, 7.2 Hz, 1 H), 7.57 (dt, J = 15.8, 7.9 Hz,2 H), 4.48 (q, J = 7.1 Hz, 2 H), 1.44 (t, J = 7.1 Hz, 3 H); 13C NMR(100 MHz, CDCl3) δ 188.87, 164.64, 135.83, 133.96, 130.99,129.28, 128.76, 128.23, 127.05, 125.63, 124.31, 62.41, 14.15; MS(EI, 70 eV) m/z: 200.11 (M+); IR (KBr): 3052, 2925, 2853, 1734,1677, 1509, 1461, 1301, 1259, 1218, 1173, 1090, 1074, 1011,943, 851, 802, 774, 738, 662, 614, 506 cm−1.

Ethyl phenanthrene-9-carboxylate (3p).30 Oil; 29.3 mg, 65%yield; 1H NMR (400 MHz, CDCl3) δ 9.03 (dq, J = 6.8, 3.4 Hz,1 H), 8.68–8.62 (m, 1 H), 8.59 (d, J = 8.4 Hz, 1 H), 8.25 (s, 1 H),7.91 (d, J = 7.8 Hz, 1 H), 7.78–7.71 (m, 1 H), 7.68 (dq, J = 6.9,3.5 Hz, 2 H), 7.59 (dd, J = 11.1, 3.9 Hz, 1 H), 4.52 (q, J = 7.1 Hz,2 H), 1.49 (t, J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3)δ 188.73, 164.58, 137.40, 133.01, 130.78, 130.67, 130.45,129.42, 128.33, 128.19, 127.63, 127.33, 126.46, 122.87, 122.80,62.49, 14.18; MS (ESI): m/z = 250.1 [M+]; IR (KBr): 2951, 2920,2850, 1732, 1672, 1616, 1529, 1450, 1244, 1148, 1011, 912, 742,539 cm−1.

Ethyl 4-(benzyloxy)-3-fluorobenzoate (3q). Oil; 34.5 mg, 70%yield; 1H NMR (400 MHz, CDCl3) δ 7.85–7.75 (m, 2 H), 7.39 (m,5 H), 7.07 (t, J = 8.4 Hz, 1 H), 5.24 (s, 2 H), 4.43 (q, J = 7.1 Hz,2 H), 1.41 (t, J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3)δ 163.42, 153.58, 152.66, 152.55, 151.10, 135.29, 128.81,128.54, 128.07, 128.04, 127.37, 117.51, 117.32, 114.29, 71.22,62.41, 14.09; HR-MS (ESI) calcd for [M + 1]+ C16H15FO3:275.1005, found: 275.1009; IR (KBr): 3451, 3120, 2108, 1758,1634, 1432, 1268, 1030, 935, 749, 735 cm−1.

4-Ethyl 1-methyl 2-methoxyterephthalate (3r). Oil; 19.7 mg,45% yield; 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 7.9 Hz,1H), 7.65 (s, 1H), 7.60 (d, J = 7.9 Hz, 1H), 4.47 (q, J = 7.1 Hz,2H), 3.97 (s, 3H), 3.93 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H); 13CNMR (100 MHz, CDCl3) δ 165.87, 163.15, 158.90, 136.09,131.66, 126.17, 122.38, 112.06, 62.61, 56.28, 52.48, 14.09;HR-MS (ESI) calcd for [M + 1]+ C12H14O5: 239.0841, found:239.0846; IR (KBr): 3456, 3105, 1635, 1261, 1254, 950, 790,735 cm−1.

Ethyl 4-acetylbenzoate (3s).21 Oil; 23.2 mg, 67% yield; 1HNMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.4 Hz, 2H), 8.07 (d, J =8.4 Hz, 2H), 4.48 (q, J = 7.1 Hz, 2H), 2.66 (s, 3H), 1.44 (t, J =7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 185.51, 163.08,141.31, 135.64, 130.31, 128.55, 62.68, 26.95, 14.10. MS (EI,70 eV) m/z: 192.2 (M+).

Ethyl benzo[d][1,3]dioxole-5-carboxylate (3t).21 Oil; 27.6 mg,79% yield; 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.2 Hz,1H), 7.48 (s, 1H), 6.89 (d, J = 8.2 Hz, 1H), 6.09 (s, 2H), 4.43 (q,J = 7.1 Hz, 2H), 1.42 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,

CDCl3) δ 184.56, 164.01, 153.53, 148.51, 127.84, 108.74, 108.31,102.25, 62.26, 14.10. MS (EI, 70 eV) m/z: 194.1 (M+).

Ethyl thiophene-3-carboxylate (3u).31 Yellow oil; 19.9 mg,71% yield; 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 2.4 Hz,1 H), 7.69 (d, J = 5.1 Hz, 1 H), 7.36 (dd, J = 4.6, 2.9 Hz, 1 H),4.43 (q, J = 7.1 Hz, 2 H), 1.43 (t, J = 7.1 Hz, 3 H); 13C NMR(100 MHz, CDCl3) δ 178.19, 162.42, 137.75, 127.87, 126.68,62.52, 14.08; MS (EI, 70 eV) m/z: 156.09 (M+); IR (KBr): 3112,2926, 2854, 1733, 1676, 1508, 1416, 1302, 1219, 1161, 1080,1023, 875, 832, 787, 746, 623 cm−1.

Ethyl thiophene-2-carboxylate (3v).32 Yellow oil; 20.8 mg,74% yield; 1H NMR (400 MHz, CDCl3) δ 8.2–8.13 (m, 1 H), 7.83(d, J = 4.5 Hz, 1 H), 7.20 (t, J = 3.5 Hz, 1 H), 4.44 (q, J = 7.0 Hz,2 H), 1.43 (t, J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ176.41, 161.67, 137.44, 137.21, 128.65, 62.77, 14.05; MS (EI,70 eV) m/z: 156.09 (M+); IR (KBr): 3114, 2934, 2853, 1736, 1659,1503, 1423, 1306, 1214, 1152, 1075, 869, 839, 781, 735,634 cm−1.

Ethyl benzo[b]thiophene-2-carboxylate (3w).33 Pink oil;9.3 mg, 25% yield; 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1 H),7.94 (d, J = 8.0 Hz, 1 H), 7.89 (d, J = 8.2 Hz, 1 H), 7.54–7.49 (m,1 H), 7.45–7.41 (m, 1 H), 4.48 (q, J = 7.2 Hz, 2 H), 1.45 (t, J =7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 178.28, 161.44,143.85, 138.92, 135.13, 128.62, 126.85, 125.37, 122.95, 62.88,14.07; MS (EI, 70 eV) m/z: 206.16 (M+); IR (KBr): 2925, 2853,1732, 1666, 1593, 1507, 1459, 1424, 1370, 1297, 1210, 1146,1014, 922, 867, 748, 658, 556, 480 cm−1.

Ethyl 2-(4-methoxyphenylamino)-2-p-tolylacetate (2aa).7i

The mixture of ethyl 2-(4-methoxyphenylimino) acetate(0.1 mmol, 1 equiv.), p-tolylboronic acid (0.1 mmol, 1 equiv.),Pd(OAc)2 (0.005 mmol, 5 mol%), bipy (0.005 mmol, 5 mol%)and CH3NO2 (2.0 mL) in a sealed tube was stirred at 60 °C inan oil bath under Ar for 24 h. After the crude mixture wascooled to room temperature, it was concentrated undervacuum and purified by flash chromatography (eluting with aneluent consisting of hexane–EtOAc, 15 : 1) to give the pureproduct. 26 mg, 86% yield; Yellow oil; 1H NMR (400 MHz,CDCl3) δ 7.38 (d, J = 7.8 Hz, 2 H), 7.16 (d, J = 7.8 Hz, 2 H), 6.73(d, J = 8.7 Hz, 2 H), 6.55 (d, J = 8.7 Hz, 2 H), 4.98 (s, 1 H), 4.65(s, 1 H), 4.25–4.11 (m, 2 H), 3.71 (s, 3 H), 2.34 (s, 3 H), 1.22 (t,J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ (ppm) 172.2,152.4, 140.4, 137.9, 134.9, 129.5, 127.1, 114.8, 114.7, 61.6, 61.4,55.7, 21.2, 14.1; MS (ESI): m/z = 300.6 [M+], 322.6 [M + Na+];IR (KBr): 3400, 2925, 2855, 1735, 1615, 1514, 1462, 1371, 1307,1240, 1179, 1097, 1023, 807, 731, 698, 509 cm−1.

General procedures for mechanism exploration

Scheme 2c. 2aa (0.18 mmol, 1 equiv.), phenylboronic acid2a (0.036 mmol, 0.2 equiv.), Pd(TFA)2 (0.009 mmol, 5 mol%)and bipy (0.009 mmol, 5 mol%) were added in 3.0 mL ofCH3NO2 under Ar, and then the corresponding mixture wasstirred at 110 °C for 48 h. After the reaction mixture wascooled to room temperature, it was concentrated undervacuum and purified by flash chromatography (eluting with aneluent consisting of hexane–EtOAc, 20 : 1) to give the pureproduct of 3i (25.1 mg, 85% yield).

Paper Organic & Biomolecular Chemistry

6020 | Org. Biomol. Chem., 2013, 11, 6013–6022 This journal is © The Royal Society of Chemistry 2013

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Scheme 2d. 2aa (0.18 mmol, 1 equiv.) and FeCl3(0.36 mmol, 2.0 equiv.) were added into 3.0 mL of CH3NO2

under Ar, and then the corresponding mixture was stirred at120 °C under Ar for 48 h. After the reaction mixture was cooledto room temperature, it was filtrated and the corresponding fil-trate was concentrated under vacuum and purified by flashchromatography (eluting with an eluent consisting of hexane–EtOAc, 20 : 1) to give the pure product of 3i (19.2 mg, 65%yield).

General procedures for the synthesis of P2a–P2f

The mixture of C-acylimine 1a, 1e, 1g, 1f, 1j (0.1 mmol,1 equiv.), arylboronic acid (0.1 mmol, 1 equiv.), Pd(OAc)2(0.005 mmol, 5 mol%), bipy (0.005 mmol, 5 mol%) andCH3NO2 (2.0 mL) in a sealed tube was stirred at 60 °C in an oilbath under Ar for 24 h. After the crude mixture was cooled toroom temperature, it was concentrated under vacuum and pur-ified by flash chromatography (hexane–EtOAc, 15 : 1) to givethe pure product P2a–P2f.

Ethyl 2-(p-toluidino)-2-phenyl acetate (P2b).7i 15.3 mg, 71%yield. 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 7.4 Hz, 2 H),7.37–7.28 (m, 3 H), 6.94 (d, J = 8.1 Hz, 2 H), 6.50 (d, J = 8.2 Hz,2 H), 5.05 (s, 1 H), 4.83 (s, 1 H), 4.26–4.12 (m, 2 H), 2.21 (s,3 H), 1.22 (t, J = 8.0 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ(ppm) 172.0, 143.7, 137.9, 129.7, 128.8, 128.2, 127.3, 127.2,113.6, 61.8, 61.1, 20.4, 14.1; MS (ESI): m/z = 270.6 [M+], 292.5[M + Na+], 308.6 [M + K+]; IR (KBr): 3408, 2959, 2925, 2862,1736, 1618, 1521, 1456, 1371, 1307, 1259, 1179, 1097, 1023,807, 731, 698, 509 cm−1.

Ethyl 2-phenyl-2-(phenylamino)acetate (P2c).7i 17.1 mg.64% yield. 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.7 Hz,2 H), 7.37–7.26 (m, 3 H), 7.14 (t, J = 7.7 Hz, 2 H), 6.73–6.70 (m,1 H), 6.58 (d, J = 8.4 Hz, 2 H), 5.09 (d, J = 5.6 Hz, 1 H), 4.99 (s,1H), 4.31–4.09 (m, 2 H), 1.23 (t, J = 12.0 Hz, 8.0 Hz, 3 H); 13CNMR (100 MHz, CDCl3) δ (ppm) 171.9, 146.0, 137.8, 129.3,128.8, 128.2, 127.2, 118.1, 113.4, 61.8, 60.8, 14.1; MS (ESI): m/z= 256.5 [M+], 278.5 [M + Na+], 294.5 [M + K+]; IR (KBr): 3406,3055, 3028, 2983, 2931, 1735, 1603, 1504, 1453, 1369, 1313,1257, 1178, 1075, 1023, 872, 747, 695, 508 cm−1.

Ethyl 2-(4-chlorophenylamino)-2-phenyl acetate (P2d).7i

26.7 mg, 92% yield. 1H NMR (400 MHz, CDCl3) δ 7.51–7.48 (m,2 H), 7.42–7.29 (m, 3 H), 7.11–7.04 (m, 2 H), 6.52–6.44 (m,2 H), 5.08–5.00 (m, 2 H), 4.30–4.09 (m, 2 H), 1.23 (t, J = 8.0,4.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 171.6, 144.5,137.3, 129.0, 128.4, 127.2, 122.7, 114.5, 62.0, 60.8, 14.1; MS(ESI): m/z = 290.5 [M+], 328.5 [M + K+]; IR (KBr): 3404, 2926,2856, 1736, 1600, 1500, 1458, 1371, 1315, 1256, 1177, 1094,1022, 816, 734, 698, 503 cm−1.

Ethyl 2-(4-bromophenylamino)-2-phenyl acetate (P2e).7i

18.6 mg, 91% yield. 1H NMR (400 MHz, CDCl3) δ 7.50–7.48 (m,2 H), 7.39–7.30 (m, 3H), 7.22–7.18 (m, 2 H), 6.46–6.42 (m, 2 H),5.07 (s, 1 H), 5.03 (s, 1 H), 4.29–4.11 (m, 2 H), 1.22 (t, J = 8 Hz,3 H); 13C NMR (100 MHz, CDCl3) δ (ppm) 171.5, 144.9, 137.2,132.0, 128.9, 128.4, 127.2, 115.0, 109.8, 62.0, 60.7, 14.1; MS(ESI): m/z = 334.5 [M+]; IR (KBr): 3400, 2926, 2855, 1735, 1652,1595, 1457, 1369, 1309, 1240, 1021, 878, 772, 697, 502 cm−1.

Ethyl 2-(4-nitrophenylamino)-2-phenyl acetate (P2f).7i

27.1 mg, 89% yield. 1H NMR (400 MHz, CDCl3) δ 8.03–7.99 (m,2 H), 7.47–7.44 (m, 2 H), 7.39–7.31 (m, 3 H), 6.52–6.48 (m,2 H), 5.87 (d, J = 5.3 Hz, 1 H), 5.12 (d, J = 5.7 Hz, 1 H),4.31–4.11 (m, 2 H), 1.22 (t, J = 8.0 Hz, 3 H); 13C NMR(100 MHz, CDCl3) δ (ppm) 170.7, 150.9, 138.8, 136.1, 129.1,128.8, 127.0, 126.2, 112.1, 62.5, 60.0, 14.0; MS (ESI): m/z =301.6 [M+], 339.5 [M + K+]; IR (KBr): 3779, 3403, 2923, 2853,1734, 1668, 1604, 1513, 1460, 1373, 1307, 1240, 1179, 1031,821, 754, 700, 506 cm−1.

Acknowledgements

The authors thank the NCET (no. 10-0371), NSFC (no.21072063), SRF for ROCS (no. 2010-1174), RFDP (no.20100172120020) and GNSF (no. 10351064101000000) forfinancial support.

Notes and references

1 Selected examples: (a) A. Correa and R. Martín, J. Am.Chem. Soc., 2009, 131, 15974; (b) Y. Hu, J. Liu, Z. Lü,X. Luo, H. Zhang, Y. Lan and A. Lei, J. Am. Chem. Soc.,2010, 132, 3153; (c) S. D. Friis, R. H. Taaning,A. T. Lindhardt and T. Skrydstrup, J. Am. Chem. Soc., 2011,133, 18114; (d) S. Korsager, R. H. Taaning andT. Skrydstrup, J. Am. Chem. Soc., 2013, 135, 2891;(e) P. Hermange, A. T. Lindhardt, R. H. Taaning,K. Bjerglund, D. Lupp and T. Skrydstrup, J. Am. Chem. Soc.,2011, 133, 6061; (f ) T. Fujihara, K. Nogi, T. Xu, J. Terao andY. Tsuji, J. Am. Chem. Soc., 2012, 134, 9106.

2 Selected examples: (a) C. Cai, N. R. Rivera, J. Balsells,R. R. Sidler, J. C. McWilliams, C. S. Shultz and Y. Sun, Org.Lett., 2006, 8, 5161; (b) R. H. Munday, J. R. Martinelli andS. L. Buchwald, J. Am. Chem. Soc., 2008, 130, 2754.

3 (a) Y. Z. Duan and M. Z. Deng, Synlett, 2005, 355; (b) Q. Liu,G. Li, J. He, J. Liu, P. Li and A. Lei, Angew. Chem., Int. Ed.,2010, 49, 3371; (c) C. S. Cho, T. Ohe and S. Uemora, J. Organo-met. Chem., 1995, 496, 221; (d) A. Correa and R. Martin,Angew. Chem., Int. Ed., 2009, 48, 6201; (e) K. Ukai, M. Aoki,J. Takaya and N. Iwasawa, J. Am. Chem. Soc., 2006, 128,8706; (f ) T. Ohishi, M. Nishiura and Z. Hou, Angew. Chem.,Int. Ed., 2008, 47, 5792; (g) J. Takaya, S. Tadami, K. Ukaiand N. Iwasawa, Org. Lett., 2008, 10, 2697.

4 (a) R. Shang, Y. Fu, J. B. Li, S. L. Zhang, Q. X. Guo andL. Liu, J. Am. Chem. Soc., 2009, 131, 5738; (b) L. J. Goossen,F. Rudolphi, C. Oppel and N. Rodríguez, Angew. Chem., Int.Ed., 2008, 47, 3043.

5 For recent reviews: (a) I. Omae, Coord. Chem. Rev., 2011,255, 139; (b) C. F. J. Barnard, Organometallics, 2008, 27,5402.

6 L. J. Goossen and K. Ghosh, Chem. Commun., 2001, 2084.7 For selected reviews, see: (a) R. Bloch, Chem. Rev., 1998, 98,

1407; (b) J. S. Dickstein and M. C. Kozlowski, Chem. Soc.

Organic & Biomolecular Chemistry Paper

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Rev., 2008, 37, 1166; (c) S. Kobayashi and H. Ishitahi, Chem.Rev., 1999, 99, 1069; For selected examples, see:(d) Y. Suto, M. Kanai and M. Shibasaki, J. Am. Chem. Soc.,2007, 129, 500; (e) S. Ueno, M. Ohtsubo and R. Kuwano,J. Am. Chem. Soc., 2009, 131, 12904; (f ) B. Qian, S. Guo,J. Shao, Q. Zhu, L. Yang, C. Xia and H. Huang, J. Am. Chem.Soc., 2010, 132, 3650; (g) S. Zhu, J. Dong, S. Fu, H. Jiangand W. Zeng, Org. Lett., 2011, 13, 4914; (h) Y. Luo, X. Lu,Y. Ye, Y. Guo, H. Jiang and W. Zeng, Org. Lett., 2012, 14,5640; (i) J. Chen, X. Lu, W. Lou, Y. Ye, H. Jiang andW. Zeng, J. Org. Chem., 2012, 77, 8541.

8 M. A. Beenen, D. J. Weix and J. A. Ellman, J. Am. Chem.Soc., 2006, 128, 6304.

9 For selected examples: (a) Z. Q. Wang, C. G. Feng, M. H. Xuand G. Q. Lin, J. Am. Chem. Soc., 2007, 129, 5336;(b) R. Shintani, M. Takeda, T. Tsuji and T. Hayashi, J. Am.Chem. Soc., 2010, 132, 13168; (c) T. Nishimura, A. Noishiki,G. C. Tsui and T. Hayashi, J. Am. Chem. Soc., 2012, 134,5056; (d) J. A. Bishop, S. Lou and S. E. Schaus, Angew.Chem., Int. Ed., 2009, 48, 4337; (e) H. X. Dai and X. Y. Lu,Org. Lett., 2007, 9, 3077.

10 Because nucleophile 3-nitrophenyl palladium species (NPS)is easily formed via the transmetalation of 3-phenylboronic acid with palladium(II) salts (see Fig. 2), 3j–lis possibly derived from the nucleophilic substituted reac-tion in which 3-nitrophenyl from the NPS displaces theimino group bonded to the aromatic carbon of the mole-cule 1a.

11 H. Tomioka, A. Okuno, T. Sugiyama and S. Murata, J. Org.Chem., 1995, 60, 2344.

12 It should be noted that 4-acetamide or 4-trimethylsilanyl-oxy aryl boronic acid did not afford the desired compoundsunder our reaction conditions.

13 Also, n-butylboronic acid or 3-pyridylboronic acid did notreact with α-imino ester 1a under our reaction conditions.

14 E. Borrione, M. Prato, G. Scorrano, M. Stivanello andV. Lucchini, J. Heterocycl. Chem., 1988, 25, 1831.

15 Under the same reaction conditions, the Pd(TFA)2 (5 mol%)/bipy (5 mol%)/phenylboronic acid 2a (10 mol%) catalyticsystem gave 65% yield of 3i, and the Pd(TFA)2 (5 mol%)/bipy (5 mol%)/phenylboronic acid 2a (50 mol%) catalyticsystem gave 90% yield of 3i.

16 We also investigated the electronic effect of substituents inthe aryl boronic acids on this transformation under thesame reaction conditions, and found that Pd(TFA)2 (5 mol%)/bipy (5 mol%)/4-methylphenylboronic acid 2e (20 mol%),Pd(TFA)2 (5 mol%)/bipy (5 mol%)/phenylboronic acid2a (20 mol%), Pd(TFA)2 (5 mol%)/bipy (5 mol%)/4-chloro-phenylboronic acid 2i (20 mol%), Pd(TFA)2 (5 mol%)/bipy(5 mol%)/4-(trifluoromethyl) phenylboronic acid 2g

(20 mol%) catalytic system gave the 82%, 85%, 84% and64% yield of 3i, respectively (see ESI† for more details).

17 F. J. Williams and E. R. Jarvo, Angew. Chem., Int. Ed., 2011,50, 4459.

18 For examples about the 1,2-aryl shift which is triggered bythe transfer of the lone electron-pair in the oxygen atom,see: (a) V. C. Giordano, G. Castaldi and F. Uggeri, Angew.Chem., Int. Ed. Engl., 1984, 96, 413; (b) T. Pei, C. Chen,P. G. Dormer and I. W. Davies, Angew. Chem., Int. Ed., 2008,47, 4231; (c) P. Levesques and P. A. Fournier, J. Org. Chem.,2010, 75, 7033.

19 We have already characterized this byproduct by using1H NMR, 13C NMR and HR-MS spectra; 4b: oil; 10 mg, 28%yield; 1H NMR (400 MHz, CDCl3) δ 6.80 (d, J = 8.8 Hz, 2 H),6.61 (d, J = 8.8 Hz, 2 H), 4.59–4.54 (m, 2 H), 3.75 (d, J =3.9 Hz, 6 H); 13C NMR (100 MHz, CDCl3) δ 153.12, 140.11,115.14, 114.92, 74.34, 55.76, 42.44; HR-MS (ESI) calcd for[M + 1]+ C9H12N2O3: 197.0848, found: 197.0843; IR (KBr):3457, 2924, 1637, 1551, 1511, 1237, 1031, 749 cm−1.

20 We also tried to use other solvents such as CH3CN orCH3OH to trap this intermediate (4-methoxy-phenyl)-methylene-amine; unfortunately, the major product wasthe arylation product P2a, and the yield of ethoxycarbonyl-ation product 3a was not more than 23% (seeESI† fordetails). Basically, no desired 4-(4-methoxy-phenylamino)-butyronitrile or methoxymethyl-(4-methoxy-phenyl)-aminewas detected.

21 R. Shang, Y. Fu, J. B. Li, S. L. Zhang, Q. X. Guo and L. Liu,J. Am. Chem. Soc., 2009, 131, 5738.

22 J. G. Lukas, M. Filipe, A. K. Bilal and R. Nuria, J. Org.Chem., 2009, 74, 2620.

23 G. R. Murray and B. Udo, J. Org. Chem., 2010, 68, 4819.24 S. Velusamy, M. Ahamed and T. Punniyamurthy, Org. Lett.,

2004, 6, 4821.25 Y. S. Zhao, L. Q. Jin, P. Li and A. W. Lei, J. Am. Chem. Soc.,

2008, 130, 9429.26 M. Bhuiyan, H. Delower, K. X. Zhu, P. L. Jensen and

A. C. Try, Eur. J. Org. Chem., 2010, 4662.27 W. J. Zhou, K. H. Wang, J. X. Wang and D. F. Huang,

Eur. J. Org. Chem., 2010, 416.28 K. Ueura, T. Satoh and M. Miura, Org. Lett., 2005, 7, 2229.29 T. Yoshino, S. Imori and H. Togo, Tetrahedron, 2006, 62,

1309.30 N. Koji, Y. Hiroki, E. Naoki, M. Naoya and H. Tetsutaro,

J. Org. Chem., 2010, 75, 7855.31 G. D. Yin, M. Gao, Z. H. Wang, Y. Y. Wu and A. X. Wu, Bull.

Chem. Soc. Jpn., 2008, 81, 369.32 X. F. Wu and C. Darcel, Eur. J. Org. Chem., 2009, 1144.33 V. Guilarte, M. A. Fernandez-Rodriguez, P. Garcia-Garcia,

E. Hernando and R. Sanz, Org. Lett., 2011, 13, 5100.

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