Palladium Cascade Catalysis: Construction of

Jan 10, 2018 - The cascade catalysis involving N-heterocyclic carbene (NHC) and palladium/ligand was demonstrated. In the presence of a triazolium sal...
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Article Cite This: J. Org. Chem. 2018, 83, 1913−1923

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N‑Heterocyclic Carbene/Palladium Cascade Catalysis: Construction of 2,2-Disubstitiuted Benzofuranones from the Reaction of 3‑(2Formylphenoxy)propenoates with Allylic Esters Yu-Jie Liu, Ya-Li Ding, Shuang-Shuo Niu, Jin-Tao Ma, and Ying Cheng* College of Chemistry, Beijing Normal University, Beijing 100875, China S Supporting Information *

ABSTRACT: The cascade catalysis involving N-heterocyclic carbene (NHC) and palladium/ligand was demonstrated. In the presence of a triazolium salt, palladium catalyst, and base, the reaction of 3-(2-formylphenoxy)propenoates and allylic esters proceeded efficiently under mild conditions to afford 2-allylbenzofuran-3-one-2-acetates in moderated to good yields. An asymmetric cascade catalysis was achieved when (R)-BINAP was employed as a chiral ligand, producing enantiomerically enriched 2,2-disubstitiuted benzofuran-3-one derivatives with an ee up to 81%.

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INTRODUCTION Over the past decade, the multicatalysis including cooperative catalysis and cascade catalysis by means of the combination of an organocatalyst and a transition-metal catalyst has emerged as a powerful and very promising strategy for the development of new reactions, which cannot be achieved by either of them individually.1,2 Despite the great achievement of organocatalysis of N-heterocyclic carbenes (NHCs) in organic reactions, especially in the Umpolung reactions of carbonyl compounds,3 the successful merger of a NHC with a late transition-metal catalyst in one-pot multicatalytic reactions still remains a challenge due to the strong donor property of NHCs to many transition metals, which as a general consequence results in the inhibition of either or both catalysts. Only a few satisfactory integrations of NHCs with metal catalysts have been reported to date. For example, the cooperative NHC/palladium catalysis has been realized in the intramolecular and intermolecular reactions between an α,β-unsaturated aldehyde and an allylic esters species.4 The cascade Benzoin/allylation and allylic amination/Stetter reactions have been achieved by the combination of NHC and palladium catalysis.5 In addition, the cooperative NHC/Ru(II) and NHC/Fe(II) redox catalysis has been utilized in the esterification of aldehydes,6 while the photoredox α-acylation of tertiary amines with aldehydes has been carried out by the cooperative NHC and Ru(II)-based catalysis.7 Furthermore, the direct synthesis of acyloins from olefins has been effected by the tandem NHC/rhodium catalysis.8 Since N-heterocyclic carbenes and late transition© 2018 American Chemical Society

metal catalysts can activate various and totally different substrates, the NHC/transition-metal tandem catalysis would provide chemists with great opportunities and unique tools in organic synthesis. Benzofuran-3-one derivatives, especially the 2,2-disubstituted benzofuran-3-ones, are known to exhibit a strong and broad spectrum of biological activities, such as anticancer,9a−c antipsychotic (Alzheimer’s disease),9d antiviral,9e antibacterial, and antifungal properties.9f The 2,2-disubstituted benzofuran-3one core is also found in various natural products including Griseofulvin10a (antifungal agent), spiroapplanatumines (kinase inhibitors),10b and armeniaspirols A−C (antibiotic activity)10c (Figure 1). Because of their potential applications in medicinal chemistry, the synthesis of benzofuran-3-one derivatives has been drawing great attention. A number of methods, including the N-heterocyclic carbene-catalyzed reactions, have been developed for the construction of benzofuran-3-ones containing a quaternary stereocenter at C2.11,12 Although many of the known methods provide access to 2,2-disubstituted benzofuran3-one products in good yields, most of them need multiple steps to prepare the substrates. To address this problem, multicatalytic cascade reactions starting from simple materials is a good choice. In 2010, Rovis and co-workers, for instance, developed an efficient and enantioselective synthesis of 2Received: November 10, 2017 Published: January 10, 2018 1913

DOI: 10.1021/acs.joc.7b02849 J. Org. Chem. 2018, 83, 1913−1923

Article

The Journal of Organic Chemistry

Figure 1. Some biologically active synthetic and natural 2,2-disubstituted benzofuran-3-one derivatives.

Scheme 1. Examples for the Synthesis of 2,2-Disubstituted Benzofuran-3-ones via the Multicatalytic Cascade Reactions

synthesis of 2-((aryl)(carbonylamino)methyl)benzofuran-3one-2-acetates (Scheme 1, equ 4).12f We envisioned that the combination of the NHC-catalyzed benzofuranone formation with the C2-substitution reactions of benzofuranones might provide new route to various 2,2-disubstituted benzofuran-3one derivatives. As a continuation of our research on the development of highly efficient cascade catalysis methods for the construction of multifunctional complexed molecules, we undertook the current study on the NHC/Pd-catalyzed reaction of 3-(2-formylphenoxy)propenoates with allylic esters.

(carboxylmethyl)benzofuran-3-one-2-carboxylates via a cascade tert-amine/NHC-catalyzed reaction of salicyladehydes with electron-deficient alkynes (Scheme 1, equ 1).12d Later on, Glorius and co-workers reported a NHC and base cascade catalyzed reaction of o-propargyloxybenzaldehydes with aldehydes, leading to the formation of 2-(carbonylmethyl)-2methyl-benzofuran-3-one derivatives (Scheme 1, equ 2).12e Recently, Xu and co-workers reported an asymmetric rhodium/ palladium relay catalysis for the synthesis of 2,2-diaryl benzofuran-3-ones from the reaction of 1,2-diaryl-α-diketones with arylboronic acids (Scheme 1, equ 3).11b In these cascade catalytic methods, the 2,2-disubstituted benzofuran-3-one products were not derived from benzofuranone intermediates. 3-(2-Formylphenoxy)propenoates are known to undergo a NHC-catalyzed intramolecular Stetter reaction to form benzofuran-3-one-2-acetates.13 Inspired by this benzofuran-3one formation reaction, we have recently developed a cascade NHC/base-catalyzed reaction between 3-(2-formylphenoxy)propenoates and N-bocarylimines, furnishing the high yield

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RESULTS AND DISCUSSION As a prelude of the investigation, 3-(2-formylphenoxy)propenoate 1a and cinnamyl acetate 2a were chosen as the model substrates. We commenced our study by the treatment of 3-(2-formylphenoxy)propenoate 1a with cinnamyl acetate 2a under the catalysis of a variety of N-heterocyclic carbenes 3′ in combination with Pd(PPh3)4 in dichloromethane at an ambient 1914

DOI: 10.1021/acs.joc.7b02849 J. Org. Chem. 2018, 83, 1913−1923

Article

The Journal of Organic Chemistry Table 1. Optimization of Reaction Conditions

entry

3 (mol %)

base (equiv)

MLn (mol %)

solvent

T (°C)

time (h)

yield of 4aa

4a/5a/6ab

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

3a (20) 3b (20) 3c (20) 3d (20) 3e (20) 3f (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20) 3g (20)

Cs2CO3 (2) Cs2CO3 (2) Cs2CO3 (2) Cs2CO3 (2) Cs2CO3 (2) Cs2CO3 (2) Cs2CO3 (2) K2CO3 (2) K2CO3 (1.5) t-BuOK (2) NaH (2) DBU (2) K2CO3 (2) K2CO3 (2) K2CO3 (2) K2CO3 (2) K2CO3 (2) K2CO3 (2) K2CO3 (2) K2CO3 (2) K2CO3 (2) K2CO3 (2) K2CO3 (2) K2CO3 (2) K2CO3 (2) K2CO3 (2)

Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) [Pd(C3H5)Cl)]2 (10) Pd2(dba)3 (10) Pd2(dba)3/dpppc (10) Pd2(dba)3/dppbd (10) Pd2(dba)3/dppfe (10) [Pd(C3H5)Cl)]2/dppfe (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (10) Pd(PPh3)4 (5)

DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM DCE toluene dioxane CH3CN DCM DCM DCM DCM

25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 40 0 25−30 25−30

8 8 8 8 8 24 8 8 12 8 8 11 24 24 8 8 8 8 8 8 8 8 8 8 8 24

26 62 56 52 55 9 70 80 37 20 45 11

72:14:14 85:7:8 83:9:8 82:9:8 87:7:6 80:10:10 81:10:9 83:9:8 80:10:10 70:13:17 76:8:16 78:10:12

43 69 67 73 77 71 26 80 15 61f 70

76:12:12 76:13:11 76:12:12 81:9:10 84:6:10 82:7:11 73:11:8 86:7:7 69:15:16 89:5:6 81:9:10

a

Isolated yields. bDetermined by 1H NMR. cdppp = 1,3-bis(diphenylphosphino) propane. ddppb = 1,4-bis(diphenylphosphino)butane. edppf = 1,1′bis(diphenyphosphino)ferrocene. fIn this reaction, the loading of cinnamyl acetate 2a was 1.5 equiv.

temperature (about 25−30 °C). The N-heterocyclic carbenes were generated in situ from deprotonation of the corresponding azolium salts 3 with Cs2CO3. It was found that, in the presence of thiazolium salt 3a (20 mol %), Pd(PPh3)4 (10 mol %), and Cs2CO3 (2 equiv), the reaction of aldehyde 1a (1 equiv) with allylacetate 2a (2 equiv) afforded the expected 2cinnamylbenzofuran-3-one-2-acetate 4a in a low yield (26%) along with a trace amount of isomers 5a and 6a (Table 1, entry 1). The replacement of thiazolium 3a by cyclohepta[d]thiazolium salt 3b increased the yield of 4a to 62% (Table 1, entry 2). Under the same reaction conditions, the reaction using imidazolinium 3c as the NHC precatalyst provided product 4a in 56% yield. When triazolium salts 3d−3g were employed as NHC precursors, 1,3,4-triphenyltriazolium 3d and N-phenylpyrrolo[2,1-c]triazoium 3e worked similarly to give product 4a in 52−55% yields (Table 1, entries 4 and 5). In contrast, N-mesitylpyrrolo[2,1-c]triazolium 3f was virtually ineffective. Gratifyingly, N-perfluorophenylpyrrolo[2,1-c]triazolium 3g acted as the most efficient and suitable NHC precatalyst. Combined with Pd(PPh3)4 and Cs2CO3, it catalyzed the reaction of 3-(2-formylphenoxy)propenoate 1a

with cinnamyl acetate 2a to produce 4a in a good yield (70%) (Table 1, entry 7). With the use of triazolium 3g as an optimized NHC precatalyst, we found the action of the base used in this cascade catalysis was crucial, dictating not only for the generation of the carbene catalyst but also for the allylation of benzofuran-3-one intermediates. As summarized in entries 10−12 in Table 1, bases such as t-BuOK, NaH, and DBU led to reduced yields of product 4a. Replacement of Cs2CO3 by K2CO3 significantly improved the yield of 4a to 80% (entry 8). It should be noted that, however, the decrease of base loading of K2CO3 to 1.5 equiv dramatically decreased the yield of 4a to 37% (entry 9). The outcome indicated clearly that the excess of base was necessary for this reaction. To seek an optimal metal catalyst, different palladium catalysts were then examined. Varying Pd(PPh3)4 to [Pd(C3H5)Cl)]2, Pd2(dba)3, and Pd2(dba)3/dppp resulted in the inhibition of the reaction. However, Pd2(dba)3/dppb, Pd2(dba)3/dppf, and [Pd(C3H5)Cl)]2/dppf were able to catalyze the formation of 4a but in diminished yields (43−69%) (Table 1, entries 13−18). It was also noteworthy that the reaction media and temperature played decisive roles on the cascade catalysis in question. While 1915

DOI: 10.1021/acs.joc.7b02849 J. Org. Chem. 2018, 83, 1913−1923

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The Journal of Organic Chemistry Table 2. Scope of the Developed Protocol on Various Substrates

a

Isolated yields. bThe ratios of 4/5/6 were determined by 1H NMR. Except for 5a, 6a, 5e, and 6e that were isolated and characterized, other byproducts were detected by TLC and 1H NMR without isolation. cIn this reaction, 11% yield of intermediate 10a was detected in the crude products determined by 1H NMR.

changing the solvent from dichloromethane to dichloroethane, 1,4-dioxane and toluene under the otherwise identical conditions did not show a beneficial effect; the yield of product 4a was heavily decreased when a polar solvent, acetonitrile, was

tested (Table 1, entries 19−22). The reaction conducted in refluxing dichloromethane and at room temperature gave similar results. In stark contrast, the reaction at 0 °C only yielded 15% of product. Finally, under the conditions of 1916

DOI: 10.1021/acs.joc.7b02849 J. Org. Chem. 2018, 83, 1913−1923

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The Journal of Organic Chemistry optimized catalysts, base, solvent, and temperature, respectively reducing the loading of cinnamyl acetate 2a to 1.5 equiv and Pd(PPh3)4 to 5 mol % led to diminished yields of product 4a (Table 1, entries 25 and 26). In addition to the major product 4a, two diastereoisomeric byproducts 5a and 6a were also detected both below 10% yields (4a/5a/6a 69:15:16−87:7:6) in most of the aforementioned reactions. X-ray diffraction analysis confirmed that the major product 4 and the minor 6 were constitutional isomers that were derived from two different regioselective reactions between 1 and 2. (See X-ray structures of 4a and 6e in the Supporting Information.) The 1H NMR spectra indicated that the two minor products 5a an 6a were the syn- and anti-stereoisomers. With the optimized conditions established, we surveyed the scope of the reaction by employing various 3-(2formylphenoxy)propenoates 1 and allylic esters 2 as reaction substrates (Table 2). It was revealed that the substituents on the aldehydes 1 have a negligible effect on the outcomes of the reaction. Substrates 1b−1g bearing an electron-donating (methoxy and methyl) or an electron-withdrawing group (bromine atom) on the para- or meta-position of aldehyde underwent highly regioselective cascade reactions with cinnamyl acetate 2a, affording the corresponding products 4b−4g in good yields (69−87%), and only a trace amount of minor isomers 5b−5g and 6b−6g were formed (4/5/6 81:10:9−86:9:5) (Table 2, entries 2−7). In sharp contrast to the substrates 1, the structures of allylic esters 2 significantly influenced the reactivity and regioselectivity of the reaction. For instance, cinnamyl acetates 2b and 2c bearing an electronwithdrawing bromine and carboxylate groups on the paraposition of phenyl ring reacted with aldehyde 1a to produce 4h and 4i in 61−65% yields with excellent regioselectivity (4/5/6 87:4:9−93:2:5) (Table 2, entries 8 and 9). Meanwhile, the reactions of electron-donating p-methoxy and p-methyl substituted cinnamyl acetates 2d and 2f with aldehyde 1a yielded products 4j and 4l also in moderate yields (50−62%) but exhibited a lower regioselectivity (4/5/6 68:16:6− 74:12:14) (Table 2, entries 10 and 12). When ortho-substituted cinnamyl acetate was used, however, the reaction of omethylcinnamyl 2e with 1a provided product 4k in a good yield (73%) with an excellent regioselectivity (4/5/6 93:3:4) (Table 2, entry 11). However, the reaction of nonsubstituted allylic ester 2g with 1a produced 4m as the sole product in 79% yield (Table 2, entry 13). In addition, when alkyl substituted allylic esters were employed, the reaction was obviously less efficient than that of aryl substituted allylic esters. After reacting with 1a for 24 h, 2-hexenyl acetate 2h provided 63% yield of 4n with an excellent regioselectivity (4n/5n/6n 90:5:5), whereas 2-cyclohexenyl acetate 2i produced the sole product 4o in only 40% yield (Table 2, entries 14 and 15). Finally, different esters of cinnamic alcohol were employed in the reaction with aldehyde 1a. It was found that the cinnamyl carbonate 2j gave product 4a in a similar yield and regioselectivity (83% yield, 4a/ 5a/6a 82:6:12) as that of cinnamyl acetate 2a, whereas the cinnamyl benzoate 2k produced 4a in a lower yield with a higher regioselectivity (70% yield, 4a/5a/6a 89:7:4) (Table 2, entries 1, 16, and 17). The most plausible catalytic cycle for the NHC/Pd-catalyzed tandem reaction of 3-(2-formylphenoxy)propenoates 1 with allylic esters 2 is depicted in Figure 2. The addition of a NHC catalyst to aldehydes 1 forms the Breslow intermediates 7. An intramolecular Stetter reaction of intermediates 7 yields the carbanion intermediates 8. Carbanions 8 undergo a proton

Figure 2. Proposed mechanism for the tandem reaction.

transformation followed by the elimination of a NHC species to produce the benzofuran-3-one-2-acetates 10. In the presence of a base catalyst, deprotonation of intermediates 10 forms the enolates 11. The enolates 11 undergo nucleophilic attack to the palladium π-allyl complexes derived from allylic esters 2 and the palladium catalyst to provide 2,2-disubstituted benzofuran-3one products. The major products 4 and the minor ones 5 and 6 were derived respectively from the regioselective addition to the terminal and substituted carbons of palladium π-allyl complexes. This cascade catalytic mechanism has been confirmed by the Pd(PPh3)4/K2CO3-catalyzed reaction of benzofuran-3-one-2-acetate 10a with cinnamyl acetate 2a to produce 2,2-disubstituted benzofuran-3-ones 4a, 5a,and 6a. To achieve asymmetric synthesis of 2,2-disubstituted benzofuranones, the reaction between 3-(2-formylphenoxy)propenoates 1 and allylic esters 2 was then examined under the catalysis of chiral catalysts. It was found that the reaction catalyzed by a combination of a chiral NHC and Pd(PPh3)4 showed no enantioselectivity in the formation of products 4 due to the racemization of the monosubstituted benzofuranone intermediates 10 in the allylation step. Thus, we focused on the asymmetric reaction of 1a with 2a under the catalysis of triazole carbene and chiral palladium catalysts (Table 3). Since both Pd2(bda)3 and [Pd(C3H5)Cl]2 have been frequently used as palladium precatalysts in various asymmetric allylic alkylation reactions of nucleophiles with allylic esters,14 we first tried the reaction under the catalysis of NHC/Pd2(bda)3/(R)-BINAP (L1) and NHC/[Pd(C3H5)Cl]2/(R)-BINAP, respectively. In dichloromethane and at 25−30 °C, the combination of triazolium salt 3g, K2CO3, and Pd2(bda)3/BINAP did not appear as an efficient catalytic system. A high catalytic activity was observed when [Pd(C3H5)Cl]2/BINAP was applied in the reaction promoted by the same NHC. Although product 4a was yielded in 82%, unfortunately, the enantioselectivity was rather low (33% ee) (Table 3, entry 2). To improve the enantioselectivity, the solvent effect was investigated. The reaction in dichloroethane gave similar results as that in dichloremethane; however, the use of 1,4-dioxane and toluene as solvents nearly doubled the ee values of the product 4a (Table 3, entries 3−5). Different chiral bidentate phosphine ligands L1−L8 were then studied in toluene at 25−30 °C. It was found that the DIFLUORPHOS (L3) gave a comparable yield and enantioselectivity as BINAP (L1), whereas SEGPHOS (L2) and SYNPHOS (L4) gave slightly worse chiral inductions than that of BINAP (Table 3, entries 5−8). 1917

DOI: 10.1021/acs.joc.7b02849 J. Org. Chem. 2018, 83, 1913−1923

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The Journal of Organic Chemistry Table 3. Optimization of Reaction Conditions for Enantioselective Synthesis

a

entry

PdLn

ligand

base

solvent

T (°C)

time (h)

yield of 4a (%)a

ee (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Pd2(dba)3 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2 [Pd(C3H5)Cl]2

L1 L1 L1 L1 L1 L2 L3 L4 L5 L6 L7 L8 L1 L1 L1

K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 Cs2CO3 K2CO3 Cs2CO3

DCM DCM DCE 1,4-dioxane toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene

25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 25−30 0 0

12 12 12 12 12 12 12 12 12 12 12 12 12 12 12

c 82 74 80 87 90 83 87 76 50 91 76 84 77 82

33 32 63 65 59 64 51 61 62 2 67 63 73 75

Isolated yields. bDetermined by chiral HPLC. cOnly benzofuran-3-one-2-acetate intermediate 10a was isolated under these conditions.

Table 4. Enantioselective Synthesis of 2,2-Disubstituted Benzofuran-3-ones

entry

1: X

2: Ar

T (°C)

time (h)

yield of 4a (%)a,b

ee (%)c

1 2 3 4 5 6 7 8 9 10 11

1a: H 1b: Br 1c: Me 1c: Me 1c: Me 1d: OMe 1d: OMe 1a: H 1a: H 1a: H 1a: H

2a: Ph 2a: Ph 2a: Ph 2a: Ph 2a: Ph 2a: Ph 2a: Ph 2b: p-BrC6H4 2c: p-MeC6H4 2c: p-MeC6H4 2d: p-OMeC6H4

0 0 0 0 25−30 0 25−30 0 0 0 0

12 12 12 24 24 24 24 12 12 24 12

4a: 82 4b: 90 4c: 61d 4c: 82 4c: 85 4d: 46d 4d: 84 4i: 77 4j: 55d 4j: 79 4l: 54

75 68 72 81 72 74 75 79 67 73 73

a

Isolated yields. bA trace amount of byproducts 5 and 6 was detected by TLC without isolation. cDetermined by chiral HPLC. dIn these reactions, the intermediates 10 were detected in 20−46% yields in the products determined by 1H NMR. The yields of products 4 were calculated based on the total yields and the ratios of 4/8 in the products.

(R)-5-Cl-6-MeO-BIPHEP (L5) and (S)-P-PHOS (L6) led to the formation of product 4a in lower yields with similar enantioselectivity as that of BINAP (Table 3, entries 9 and 10). On the contrary, the bulky ligand (S)-DTBM-SEGPHOS (L7)

gave an excellent yield of product, but with no enantioselectivity (Table 3, entry 11). In addition to the 2,2′bis(diarylphosphino)-1,1′-biaryl ligands L1−L7, the (R,R)Trost Ligand (L8) was also examined, which gave product in 1918

DOI: 10.1021/acs.joc.7b02849 J. Org. Chem. 2018, 83, 1913−1923

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The Journal of Organic Chemistry Scheme 2. Transformations of 2-Cinnamylbenzofuran-3-one-2-acetates 4

was recovered with 77% ee, and no isomerized product was observed under these conditions. In addition, the asymmetric reactions of 1c with 2a and 1a with 2c have been carried out at 0 °C for 12 h and 24 h, respectively, and both reactions gave higher chemical yields and ee values in 24 h than 12 h (Table 4, entries 3, 4, 9, and 10). All of these results indicated that the products 4 did not undergo racemization and isomerization under our chiral catalysis conditions. To demonstrate the synthetic utility of the resulting products, different transformations of the racemic 2-cinnamylbenzofuran-3-one-2-acetates 4 were explored. For example, the oxidative cleavage of CC bonds of 4a and 4b with PhI(OAc)2 and catalytic OsO4 yielded aldehydes 12a and 12b in 61% and 51% yields, respectively (Scheme 2, equ 1).15 The epoxidation of 4 with m-CPBA provided a pair of diastereomeric epoxides 13 and 14 in 42−45% and 43−47% yields (Scheme 2, equ 2).16 In the presence of DBU, dihydrobenzofuran-3-ones 4 underwent a base-catalyzed isomerization to form the anti-substituted 2-styrylchroman-4one-3-acetates 15 in 41−47% yields (Scheme 2, equ 3). Although different bases, the loading of DBU, solvents, temperature, and reaction time were varied, and the dihydrobenzofuranones 4 were not completely transformed into chromanones 15, with 4 being recovered in 26−56% yields. This was most probably due to the equilibrium between benzofuran-3-ones 4 and chroman-4-ones 15 under the reaction conditions used. The relative configurations of compounds 13a, 14a, and 15a were determined by singlecrystal X-ray diffraction analysis. (See the Supporting Information.)

a lower yield with an ee value similar as that of BINAP (Table 3, entries 5 and 12). At 25−30 °C, the change of a base catalyst from K2CO3 to Cs2CO3 did not benefit the reaction. Delightfully, decreasing the reaction temperature to 0 °C improved the enantioselectivity to 73% ee (77% yield) and 75% ee (82% yield) by using K2CO3 and Cs2CO3 as the base catalyst, respectively (Table 3, entries 14 and 15). Under the asymmetric catalytic conditions using (R)-BINAP as a chiral ligand, reactions of a number of aldehydes 1 and cinnamyl acetates 2 were studied in order to synthesize enantiomerically enriched 2,2-disubstituted benzofuran-3-ones 4. It was found that, in the presence of triazolium salt 3g, Cs2CO3, and [Pd(C3H5)Cl]2/(R)-BINAP in toluene at 0 °C, the reaction of 3-(5-bromo-2-formylphenoxy)propenoate 1b with cinnamyl acetate 2a proceeded efficiently to give product 4b in 90% yield with 68% ee in 12 h (Table 4, entry 2). Under the same conditions, however, 3-(2-formyl-5-methylphenoxy)propenoate 1c and 3-(2-formyl-5-methoxyphenoxy)propenoate 1d were less reactive than 1a and 1b, as their reactions with 2a produced 4c and 4d in 61% and 46% yields with 72% ee and 74% ee, respectively (Table 4, entries 3 and 6). An appreciable amount of benzofuran-3-one-2-acetate intermediates 10c and 10d (20−46%) remained unconverted. By prolonging the reaction time at 0 °C or both prolonging time and elevating temperature to 25−30 °C, the reaction of 1c and 2a was completed within 24 h to give 4c in 82% yield (81% ee) or 85% yield (72% ee), respectively (Table 4, entries 4 and 5). At 25− 30 °C, the reaction between 1d and 2a also completed in 24 h to provide product 4d in 84% yield with 75% ee (Table 4, entry 7). However, the reactions of p-bromo-, p-methyl-, and pmethoxy-substituted cinnamyl acetates 2c, 2d, and 2f with aldehyde 1a proceeded analogously, affording products 4i, 4j, and 4l in 54−79% yields with 73−79% ee in 12−24 h at 0 °C (Table 4, entries 8, 10, and 11). The absolute configurations of the major enantiomers have not been determined by X-ray analysis because a pair of enantiomers precipitated from the enantioenriched products 4 during the process of recrystallization, although different products 4 and different solvents have been tried. Glorius and co-workers have reported a DBU-catalyzed rearrangement from chroman-4-ones to 2,2-disubstituted benzofuran-3-ones.12e In this work, we also found a DBUcatalyzed isomerization between benzofuran-3-ones 4 and chroman-4-ones 15 (vide infra Scheme 2, equ 3). To examine the stability of the optically active products 4 under basic reaction conditions, we stirred the enantiomerically enriched benzofuran-3-one product 4h (79% ee) with 2 equiv of Cs2CO3 in dry toluene for 12 h at room temperature. The product 4h

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CONCLUSION In summary, we have developed a novel and efficient NHC/ base/Pd cascade catalytic method for the synthesis of 2,2disubstituted benzofuran-3-ones from the reaction of 3-(2formylphenoxy)propenoates with allylic esters. In the presence of a combination of a triazole carbene, K2CO3 or Cs2CO3, and Pd(PPh3)4, the 3-(2-formylphenoxy)propenoates and allylic esters undergo a cascade Stetter reaction and regioselective allylation to produce 2-allylbenzofuran-3-one-2-acetates in 40− 87% yields. By using [Pd(C3H5)Cl]2/(R)-BINAP as the chiral palladium catalyst, optically active 2-allylbenzofuran-3-one-2acetates were obtained in 54−90% yields with 68−81% ee. The resulting products were easily converted into different polyfunctionalized compounds. This work has provided not only a simple and efficient strategy for the construction of 2,2disubstituted benzofuran-3-ones but also demonstrated an 1919

DOI: 10.1021/acs.joc.7b02849 J. Org. Chem. 2018, 83, 1913−1923

Article

The Journal of Organic Chemistry

39.9, 39.8; HRMS (TOF-APCI) [M + H]+ calcd for C20H18BrO4 401.0382, found 401.0385. (E)-Methyl 2-Cinnamyl-6-methylbenzofuran-3-one-2-acetate (4c): white solid, 145 mg, 86%; mp 124−125 °C (recrystallization from AcOEt/n-hexane); IR v (cm−1) 1738, 1713, 1616; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.57 (d, J = 8.0 Hz, 1H), 7.20−7.29 (m, 5H), 6.90 (s, 1H), 6.89 (d, J = 7.0 Hz, 1H), 6.48 (d, J = 15.8 Hz, 1H), 6.04− 6.11 (m, 1H), 3.53 (s, 3H), 3.04 (d, J = 16.8 Hz, 1H), 3.00 (d, J = 16.6 Hz, 1H), 2.62−2.72 (m, 2H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 201.5, 171.8, 169.1, 149.9, 136.8, 135.1, 128.5, 127.6, 126.3, 124.0, 123.7, 121.7, 118.9, 113.2, 88.4, 51.9, 39.9, 39.8, 22.6; HRMS (TOF-APCI) [M + H]+ calcd for C21H21O4 337.1434, found 337.1439. (E)-Methyl 2-Cinnamyl-6-methoxybenzofuran-3-one-2-acetate (4d): white solid, 153 mg, 87%; mp 149−150 °C (recrystallization from AcOEt/n-hexane); IR v (cm−1) 1742, 1705, 1611; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.58 (d, J = 8.6 Hz, 1H), 7.20−7.29 (m, 5H), 6.63 (d, J = 8.6 Hz, 1H), 6.53 (s, 1H), 6.49 (d, J = 15.8 Hz, 1H), 6.04− 6.11 (m, 1H), 3.86 (s, 3H), 3.54 (s, 3H), 3.03 (d, J = 17.2 Hz, 1H), 2.98 (d, J = 17.2 Hz, 1H), 2.64−2.75 (m, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 199.7, 173.7, 169.1, 168.2, 136.8, 135.1, 128.5, 127.6, 126.3, 125.4, 121.7, 114.3, 111.6, 96.1, 89.1, 55.8, 51.9, 39.9, 39.7; HRMS (TOF-APCI) [M + H]+ calcd for C21H21O5 353.1383, found 353.1387. (E)-Methyl 5-Bromo-2-cinnamylbenzofuran-3-one-2-acetate (4e): white solid, 147.8 mg, 74%; mp 104−105 °C (without recrystallization); IR v (cm−1) 1744, 1719, 1607; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.81 (s, 1H), 7.67 (d, J = 8.8 Hz, 1H), 7.21− 7.30 (m, 5H), 7.01 (d, J = 8.7 Hz, 1H), 6.49 (d, J = 15.8 Hz, 1H), 6.01−6.08 (m, 1H), 3.54 (s, 3H), 3.10 (d, J = 16.9 Hz, 1H), 3.04 (d, J = 16.9 Hz, 1H), 2.62−2.74 (m, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 200.8, 169.9, 169.0, 140.3, 136.6, 135.6, 128.6, 127.8, 126.9, 126.3, 123.2, 120.9, 114.8, 114.5, 89.1, 52.0, 40.0, 39.8; HRMS (TOFAPCI) [M + H]+ calcd for C20H18BrO4 401.0382, found 401.0387. syn-Methyl 5-Bromo-2-(1-phenylallyl)benzofuran-3-one-2-acetate (5e): white solid, 7.5 mg, 3.7%; mp 112−113 °C (recrystallization from AcOEt/n-hexane); IR v (cm−1) 1743, 1727, 1609; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.75 (d, J = 1.8 Hz, 1H), 7.65 (dd, J = 8.7, 2.0 Hz, 1H), 7.36 (d, J = 7.0 Hz, 2H), 7.32 (t, J = 7.6 Hz, 2H), 7.26 (t, J = 8.2 Hz, 1H), 7.02 (d, J = 8.7 Hz, 1H), 5.86 (dt, J = 16.9, 9.6 Hz, 1H), 5.06 (d, J = 16.9 Hz, 1H), 4.94 (d, J = 10.1 Hz, 1H), 3.67 (d, J = 9.2 Hz, 1H), 3.44 (s, 3H), 2.99 (d, J = 17.0 Hz, 1H), 2.70 (d, J = 17.0 Hz, 1H); 13C NMR (100 MHz, CD3Cl) δ (ppm) 201.1, 170.5, 168.9, 140.0, 138.0, 133.6, 128.9, 128.8, 127.7, 126.4, 124.8, 119.2, 114.5, 114.3, 91.2, 56.9, 51.8, 40.4; HRMS (TOF-ESI) [M + Na]+ calcd for C20H17O4BrNa 423.0202, found 423.0195. anti-Methyl 5-Bromo-2-(1-phenylallyl)benzofuran-3-one-2-acetate (6e): white solid, 8.7 mg, 4.3%; mp 129−130 °C (recrystallization from AcOEt); IR v (cm−1) 1732, 1720, 1607; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.49 (dd, J = 8.7, 2.1 Hz, 1H), 7.44 (d, J = 2.1 Hz, 1H), 7.00−7.10 (m, 5H), 6.87 (d, J = 8.7 Hz, 1H), 6.35 (dt, J = 17.0, 10.1 Hz, 1H), 5.34 (d, J = 10.1 Hz, 1H), 5.29 (d, J = 17.0 Hz, 1H), 3.66 (d, J = 10.1 Hz, 1H), 3.49 (s, 3H), 3.23 (d, J = 16.9 Hz, 1H), 3.09 (d, J = 16.9 Hz, 1H); 13C NMR (100 MHz, CD3COCD3) δ (ppm) 199.8, 170.7, 168.7, 139.4, 137.0, 135.3, 129.1, 127.9, 127.1, 125.3, 124.9, 119.2, 114.7, 113.1, 90.6, 55.8, 51.1, 40.0; HRMS (TOF-ESI) [M + H]+ calcd for C20H18O4Br 401.0382, found 401.0387. (E)-Methyl 2-Cinnamyl-5-methylbenzofuran-3-one-2-acetate (4f): white solid; mp 66−67 °C (without recrystallization), 130 mg, 77%; IR v (cm−1) 1745, 1717, 1620; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.46 (s, 1H), 7.41 (dd, J = 8.5, 1.8 Hz, 1H), 7.18−7.29 (m, 5H), 7.00 (d, J = 8.4 Hz, 1H), 6.48 (d, J = 15.8 Hz, 1H), 6.04−6.11 (m, 1H), 3.52 (s, 3H), 3.05 (d, J = 16.5 Hz, 1H), 3.00 (d, J = 16.5 Hz, 1H), 2.62−2.72 (m, 2H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 202.2, 169.7, 169.1, 139.1, 136.8, 135.1, 131.6, 128.5, 127.5, 126.3, 123.8, 121.6, 121.2, 112.6, 88.3, 51.8, 39.9, 39.8, 20.6; HRMS (TOF-APCI) [M + H]+ calcd for C21H20O4Na 359.1253, found 359.1259. (E)-Methyl 2-Cinnamyl-5-methoxybenzofuran-3-one-2-acetate (4g): colorless oil, 136.9 mg, 78%; IR v (cm−1) 1744, 1715, 1602;

interesting example of a N-heterocyclic carbene and transitionmetal cascade catalysis in organic synthesis.

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EXPERIMENTAL SECTION

General Procedure for the Synthesis of 2-Allylbenzofuran-3one-2-acetates 4 from NHC/Pd(PPh3)4-Catalyzed Reaction of 3-(2-Formylphenoxy)propenoates with Allylic Esters. At an ambient temperature (around 25 °C), Pd(PPh3)4 (57.8 mg, 0.05 mmol, 10 mol %), triazolium salt 3g (36.3 mg, 0.1 mmol, 20 mol %), and 3-(2-formylphenoxy)propenoates 1 (0.5 mmol) were added to an oven-dried Schlenk tube. The test tube was then evacuated and backfilled with nitrogen (3×). The dry dichloromethane (5 mL) was added using a microsyringe, and the mixture was stirred for 5 min. Then allylic esters (1 mmol) and K2CO3 (1 mmol) were added to the mixture under N2. The reaction mixture was then stirred for 8−24 h at room temperature under a nitrogen atmosphere. The K2CO3 was filtrated and washed with dichloromethane (10 mL × 3). The filtrate was concentrated under reduced pressure. The residue was chromatographed on a silica gel column eluting with a mixture of petroleum ether and ethyl acetate (PE/EA from 15:1 to 10:1) to give a mixture of isomeric products 4, 5, and 6. After the ratios of 4/5/6 by 1H NMR were determined, the crude products were chromatographed again on a silica gel column to give the major products 4 in 40−87% yields. Except for 5a, 6a, 5e, and 6e that were isolated and characterized, other minor products 5 and 6 were determined in 3−10% yields by 1H NMR without isolation. (E)-Methyl 2-Cinnamylbenzofuran-3-one-2-acetate (4a): white solid, 129/134/113 mg, 80/83/70% from 1a and cinnamyl acetate 2a/ cinnamyl carbonate 2j/cinnamyl benzoate 2k, respectively; mp 104− 105 °C (recrystallization from AcOEt/n-hexane); IR v (cm−1) 1740, 1717, 1611; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.69 (d, J = 7.6 Hz, 1H), 7.60 (t, J = 7.4 Hz, 1H), 7.20−7.28 (m, 5H), 7.10 (d, J = 7.7 Hz, 1H), 7.08 (t, J = 7.5 Hz, 1H), 6.49 (d, J = 15.8 Hz, 1H), 6.03−6.11 (m, 1H), 3.52 (s, 3H), 3.08 (d, J = 17.0 Hz, 1H), 3.03 (d, J = 16.8 Hz, 1H), 2.64−2.73 (m, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 202.2, 171.4, 169.1, 137.9, 136.9, 135.3, 128.6, 127.7, 126.4, 124.4, 122.1, 121.6, 121.4, 113.2, 88.3, 51.9, 40.0, 39.9; HRMS (TOF-APCI) [M + H]+ calcd for C20H19O4 323.1277, found 323.1272. syn-Methyl 2-(1-Phenylallyl)benzofuran-3-one-2-acetate (5a): white solid, 7.4 mg, 4.6% from cinnamyl acetate 2a; mp 79−80 °C (without recrystallization); IR v (cm−1) 1741, 1729, 1617; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.65 (t, J = 7.7 Hz, 1H), 7.59 (d, J = 7.4 Hz, 1H), 7.40 (d, J = 7.8 Hz, 2H), 7.33 (t, J = 7.5 Hz, 2H), 7.24−7.27 (m, 1H), 7.12 (d, J = 8.3 Hz, 1H), 7.07 (t, J = 7.4 Hz, 1H), 5.83−5.92 (m, 1H), 5.06 (d, J = 16.9 Hz, 1H), 4.91 (d, J = 10.1 Hz, 1H), 3.70 (d, J = 9.2 Hz, 1H), 3.41 (s, 3H), 2.98 (d, J = 16.7 Hz, 1H), 2.69 (d, J = 16.7 Hz, 1H); 13C NMR (100 MHz, CD3Cl) δ (ppm) 202.5, 171.9, 169.0, 138.3, 137.6, 133.9, 129.0, 128.7, 127.5, 123.8, 122.9, 122.0, 118.8, 112.6, 90.3, 56.8, 51.8, 40.3; HRMS (TOF-APCI) [M + H]+ calcd for C20H19O4 323.1277, found 323.1283. anti-Methyl 2-(1-Phenylallyl)benzofuran-3-one-2-acetate (6a): white solid, 8.6 mg, 5.3%; mp 65−66 °C (recrystallization from AcOEt/n-hexane); IR v (cm−1) 1745, 1722, 1614; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.43 (t, J = 8.2 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 7.12 (d, J = 7.6 Hz, 2H), 6.96−7.04 (m, 4H), 6.83 (t, J = 7.3 Hz, 1H), 6.39 (dt, J = 16.9, 10.1 Hz, 1H), 5.33 (d, J = 11.5 Hz, 1H), 5.29 (d, J = 18.2 Hz, 1H), 3.68 (d, J = 10.1 Hz, 1H), 3.46 (s, 3H), 3.23 (d, J = 16.6 Hz, 1H), 3.10 (d, J = 16.6 Hz, 1H); 13C NMR (100 MHz, CD3Cl) δ (ppm) 202.2, 172.0, 169.1, 137.4, 136.8, 135.1, 129.1, 128.1, 127.2, 123.7, 122.7, 121.6, 119.8, 112.4, 89.8, 56.2, 51.9, 40.2; HRMS (TOF-ESI) [M + Na]+ calcd for C20H18O4Na 345.1097, found 345.1093. (E)-Methyl 6-Bromo-2-cinnamylbenzofuran-3-one-2-acetate (4b): white solid, 137 mg, 69%; mp 126−127 °C (recrystallization from AcOEt/n-hexane); IR v (cm−1) 1738, 1717, 1605; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.54 (d, J = 8.2 Hz, 1H), 7.21−7.31 (m, 7H), 6.49 (d, J = 15.8 Hz, 1H), 6.00−6.08 (m, 1H), 3.54 (s, 3H), 3.08 (d, J = 16.9 Hz, 1H), 3.04 (d, J = 16.8 Hz, 1H), 2.62−2.71 (m, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 200.9, 171.3, 169.0, 136.6, 135.5, 132.6, 128.6, 127.7, 126.3, 125.8, 125.1, 121.0, 120.5, 116.7, 89.1, 52.0, 1920

DOI: 10.1021/acs.joc.7b02849 J. Org. Chem. 2018, 83, 1913−1923

Article

The Journal of Organic Chemistry H NMR (400 MHz, CDCl3) δ (ppm) 7.18−7.29 (m, 6H), 7.08 (d, J = 2.8 Hz, 1H), 7.03 (d, J = 8.9 Hz, 1H), 6.49 (d, J = 15.8 Hz, 1H), 6.04−6.11 (m, 1H), 3.80 (s, 3H), 3.53 (s, 3H), 3.06 (d, J = 16.5 Hz, 1H), 3.01 (d, J = 16.6 Hz, 1H), 2.62−2.73 (m, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 202.4, 169.1, 166.6, 154.9, 136.8, 135.1, 128.5, 127.7, 127.6, 126.3, 121.6, 121.2, 114.0, 104.2, 88.8, 55.8, 51.8, 40.0, 39.9; HRMS (TOF-APCI) [M + Na]+ calcd for C21H20O5Na 375.1202, found 375.1204. (E)-Methyl 2-(3-(p-(Methoxycarbonyl)phenyl)allyl)benzofuran-3one-2-acetate (4h): white solid, 124 mg, 65%; mp 95−96 °C (recrystallization from CH2Cl2/petroleum ether); IR v (cm−1) 1742, 1719, 1612; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.92 (d, J = 8.4 Hz, 2H), 7.69 (dd, J = 7.6, 0.7 Hz, 1H), 7.60 (td, J = 8.4, 1.4 Hz, 1H), 7.27 (d, J = 9.0 Hz, 2H), 7.07−7.12 (m, 2H), 6.52 (d, J = 15.8 Hz, 1H), 6.14−6.22 (m, 1H), 3.89 (s, 3H), 3.53 (s, 3H), 3.08 (d, J = 16.5 Hz, 1H), 3.02 (d, J = 16.6 Hz, 1H), 2.66−2.77 (m, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 202.0, 171.2, 168.9, 166.8, 141.1, 138.0, 134.3, 129.8, 129.0, 126.1, 124.4, 124.3, 122.1, 121.2, 113.1, 88.0, 52.1, 51.9, 39.9, 39.7; HRMS (TOF-ESI) [M + H]+ calcd for C22H21O6 381.1332, found 381.133. (E)-Methyl 2-(3-(p-Bromophenyl)allyl)benzofuran-3-one-2-acetate (4i): white solid, 121.5 mg, 61%; mp 80−81 °C (recrystallization from AcOEt/n-hexane); IR v (cm−1) 1743, 1721, 1614; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.68 (d, J = 7.6 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.37 (d, J = 8.3 Hz, 2H), 7.07−7.11 (m, 4H), 6.42 (d, J = 15.8 Hz, 1H), 6.01−6.08 (m, 1H), 3.52 (s, 3H), 3.06 (d, J = 16.5 Hz, 1H), 3.01 (d, J = 16.4 Hz, 1H), 2.63−2.73 (m, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 202.1, 171.2, 169.0, 137.9, 135.6, 134.0, 131.6, 127.8, 124.3, 122.4, 122.1, 121.4, 121.3, 113.1, 88.0, 51.9, 39.9, 39.7; HRMS (TOF-ESI) [M + Na]+ calcd for C20H17BrO4Na 423.0202, found 423.0208. (E)-Methyl 2-(3-(p-Methylphenyl)allyl)benzofuran-3-one-2-acetate (4j): colorless oil, 83.5 mg, 50%; IR v (cm−1) 1745, 1722, 1614; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.69 (d, J = 7.6 Hz, 1H), 7.60 (t, J = 7.5 Hz, 1H), 7.06−7.15 (m, 6H), 6.45 (d, J = 15.7 Hz, 1H), 5.98−6.05 (m, 1H), 3.51 (s, 3H), 3.07 (d, J = 17.0 Hz, 1H), 3.03 (d, J = 18.9 Hz, 1H), 2.62−2.71 (m, 2H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 202.2, 171.3, 169.0, 137.8, 137.4, 135.1, 134.0, 129.1, 126.2, 124.3, 121.9, 121.4, 120.4, 113.0, 88.2, 51.8, 39.9, 39.8, 21.1; HRMS (TOF-ESI) [M + Na]+ calcd for C21H20O4Na 359.1253, found 359.1258. (E)-Methyl 2-(3-(o-Methylphenyl)allyl)benzofuran-3-one-2-acetate (4k): white solid, 123 mg, 73%; mp 61−62 °C (recrystallization from acetone/n-hexane); IR v (cm−1) 1744, 1721, 1612; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.69 (d, J = 7.6 Hz, 1H), 7.60 (td, J = 8.5, 1.4 Hz, 1H), 7.04−7.13 (m, 6H), 6.67 (d, J = 15.6 Hz, 1H), 5.85−5.92 (m, 1H), 3.53 (s, 3H), 3.09 (d, J = 16.5 Hz, 1H), 3.03 (d, J = 16.5 Hz, 1H), 2.67−2.78 (m, 2H), 2.26 (s, 3H); 13C NMR (100 MHz, CD3COCD3) δ (ppm) 201.2, 171.3, 168.8, 137.6, 136.2, 135.0, 133.0, 130.0, 127.4, 125.9, 125.6, 123.7, 123.2, 121.9, 121.8, 112.9, 88.2, 51.0, 39.8, 39.7, 18.9; HRMS (TOF-ESI) [M + H]+ calcd for C21H21O4 337.1434, found 337.1436. (E)-Methyl 2-(3-(p-Methoxyphenyl)allyl)benzofuran-3-one-2-acetate (4l): white solid, 109.2 mg, 62%; mp 78−79 °C (without recrystallization); IR v (cm−1) 1736, 1722, 1614; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.69 (d, J = 7.6 Hz, 1H), 7.59 (t, J = 8.4 Hz, 1H), 7.17 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.2 Hz, 1H), 7.07 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.7 Hz, 2H), 6.42 (d, J = 15.8 Hz, 1H), 5.88−5.96 (m, 1H), 3.78 (s, 3H), 3.51 (s, 3H), 3.07 (d, J = 16.6 Hz, 1H), 3.02 (d, J = 16.6 Hz, 1H), 2.61−2.70 (m, 2H); 13C NMR (100 MHz, CD3COCD3) δ (ppm) 201.2, 171.2, 168.8, 159.4, 137.6, 134.3, 129.7, 127.3, 123.7, 121.8, 121.7, 119.2, 113.8, 112.9, 88.2, 54.6, 51.0, 39.7, 39.6; HRMS (TOF-ESI) [M + Na]+ calcd for C21H20O5Na 375.1202, found 375.1208. (E)-Methyl 2-Allylbenzofuran-3-one-2-acetate (4m): colorless oil, 97.2 mg, 79%; IR v (cm−1) 1747, 1722, 1614; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.69 (d, J = 7.8 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.09 (t, J = 7.1 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 5.62−5.72 (m, 1H), 5.15 (d, J = 17.0 Hz, 1H), 5.09 (d, J = 10.1 Hz, 1H), 3.51 (s, 3H), 3.03 (d, J = 16.6 Hz, 1H), 2.98 (d, J = 16.6 Hz, 1H), 2.49−2.59 (m, 2H);

C NMR (100 MHz, CDCl3) δ (ppm) 202.2, 171.3, 169.0, 137.8, 130.0, 124.2, 121.9, 121.4, 120.5, 113.0, 87.9, 51.8, 40.5, 39.9; HRMS (TOF-ESI) [M + H]+ calcd for C14H15O4 247.0964, found 247.0963. (E)-Methyl 2-(2-Hexen-1-yl)benzofuran-3-one-2-acetate (4n): colorless oil, 90.2 mg, 63%; IR v (cm−1) 1746, 1722, 1614; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.67 (dd, J = 8.1, 1.4 Hz, 1H), 7.58 (td, J = 8.0, 1.4 Hz, 1H), 7.04−7.08 (m, 2H), 5.52−5.56 (m, 1H), 5.24−5.28 (m, 1H), 3.51 (s, 3H), 3.01 (d, J = 16.5 Hz, 1H), 2.96 (d, J = 16.4 Hz, 1H), 2.46−2.49 (m, 2H), 1.87 (q, J = 7.2 Hz, 2H), 1.21− 1.26 (m, 2H), 0.76 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 202.4, 171.3, 169.1, 137.6, 136.6, 124.1, 121.7, 121.6, 121.3, 112.9, 88.3, 51.7, 40.0, 39.5, 34.4, 22.1, 13.4; HRMS (TOF-ESI) [M + H]+ calcd for C17H21O4 289.1434, found 289.1432. (E)-Methyl 2-(2-Cyclohex-1-yl)benzofuran-3-one-2-acetate (4o): colorless oil, 58 mg, 40%; IR v (cm−1) 1746, 1721, 1614; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.68 (dd, J = 7.9, 1.2 Hz, 1H), 7.58 (td, J = 7.4, 1.4 Hz, 1H), 7.07 (t, J = 7.1 Hz, 1H), 7.08 (d, J = 8.6 Hz, 1H), 5.79−5.83 (m, 1H), 5.50 (d, J = 10.2 Hz, 1H), 3.47 (s, 3H), 3.10 (d, J = 16.2 Hz, 1H), 3.04 (d, J = 16.2 Hz, 1H), 2.59−2.62 (m, 1H), 1.91− 1.98 (m, 3H), 1.76−1.84 (m, 1H), 1.39−1.52 (m, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 202.4, 171.5, 169.3, 137.5, 131.4, 124.5, 124.0, 122.2, 121.7, 112.9, 89.9, 51.7, 42.2, 38.0, 24.9, 23.2, 21.6; HRMS (TOF-ESI) [M + Na]+ calcd for C17H18O4Na 309.1097, found 309.1093. General Procedure for the Enantioselective Synthesis of 2Cinnamylbenzofuran-3-one-2-acetates 4. The palladium catalyst was first prepared in a glovebox by mixing [Pd(C3H5)Cl]2 (0.04 mmol) and (R)-BINAP (0.08 mmol) in dry toluene (1 mL) in an oven-dried test tube for 1 h at room temperature. To a separate Schlenk tube were added 3-(2-formylphenoxy)propenoates 1 (0.4 mmol), triazolium salt 3g (0.08 mmol), and Cs2CO3 (0.8 mmol). After the mixture in the Schlenk tube was evacuated and backfilled with nitrogen (3×), dry toluene (2 mL) and cinnamyl acetates 2 (0.8 mmol) were added using a microsyringe. This Schlenk tube was then moved into the glovebox, and a pre-prepared palladium-BINAP complex solution was added. To ensure the complete transfer of the Pd-catalyst, the test tube was washed with 1 mL of dry toluene and added to the reaction mixture. The resulting reaction mixture was kept stirring for 12−24 h at 0 °C or at 25−30 °C (Table 4) under a nitrogen atmosphere. After the reaction, the Cs2CO3 was filtrated and washed with toluene (10 mL × 3). The filtrate was concentrated under a vacuum. The residue was chromatographed on a silica gel column eluting with a mixture of petroleum ether and ethyl acetate (PE/EA from 15:1 to 10:1) to give products 4 in 54−90% yields with 68−81% ee. 4a: 82% yield, 75% ee (HPLC data = OD-H column, 95:5 hexane/ IPA, flow rate 1 mL/min, 254 nm, 25 °C, tR 22.067 min), [α]20 D −99.8 (c 0.50, CH2Cl2). 4b: 90% yield, 68% ee (HPLC data = AD-H column, 95:5 hexane/ IPA, flow rate 1 mL/min, 254 nm, 25 °C, tR 13.851 min), [α]20 D −39.6 (c 0.50, CH2Cl2). 4c: 82% yield, 81% ee (HPLC data = OD-H column, 95:5 hexane/ IPA, flow rate 1 mL/min, 254 nm, 25 °C, tR 20.862 min), [α]20 D −78.6 (c 0.50, CH2Cl2). 4d: 84% yield, 75% ee (HPLC data = AD-H column, 95:5 hexane/ IPA, flow rate 1 mL/min, 254 nm, 25 °C, tR 37.974 min), [α]20 D −26.2 (c 0.50, CH2Cl2). 4i: 77% yield, 79% ee (HPLC data = AD-H column, 95:5 hexane/ IPA, flow rate 1 mL/min, 254 nm, 25 °C, tR 20.013 min), [α]20 D −91 (c 0.50, CH2Cl2). 4j: 79% yield, 73% ee (HPLC data = OD-H column, 95:5 hexane/ IPA, flow rate 1 mL/min, 254 nm, 25 °C, tR 16.135 min), [α]20 D −106.8 (c 0.50, CH2Cl2). 4l: 54% yield, 73% ee (HPLC data = OD-H column, 95:5 hexane/ IPA, flow rate 1 mL/min, 254 nm, 25 °C, tR 29.669 min), [α]20 D −90.8 (c 0.50, CH2Cl2). Oxidation of 2-Cinnamylbenzofuran-3-one-2-acetates 4 with PhI(OAc) 2 and Catalytic OsO 4 . In a flask, the 2cinnamylbenzofuran-3-one-2-acetates 4 (0.3 mmol) were dissolved in a mixture of THF (3 mL) and water (0.1 mL) with stirring. To this

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DOI: 10.1021/acs.joc.7b02849 J. Org. Chem. 2018, 83, 1913−1923

Article

The Journal of Organic Chemistry

Hz, 1H), 2.09 (dd, J = 14.5, 4.9 Hz, 1H); 13C NMR (100 MHz, CD3Cl) δ (ppm) 200.5, 171.1, 168.8, 136.3, 132.7, 128.4, 128.3, 126.0, 125.4, 125.1, 120.1, 116.7, 88.2, 57.8, 57.5, 52.0, 39.9, 39.0; HRMS (TOF-ESI) [M + H]+ calcd for C20H18O5Br 417.0332, found 417.0330. Epoxide 14b: white solid, 40 mg, 47%; mp 146−147 °C (recrystallization from AcOEt/petroleum ether); IR v (cm−1) 1736, 1721, 1605; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.52 (d, J = 8.2 Hz, 1H), 7.26−7.31 (m, 4H), 7.19 (dd, J = 8.2, 1.4 Hz, 1H), 7.08−7.10 (m, 2H), 3.60 (d, J = 1.9 Hz, 1H), 3.57 (s, 3H), 3.11 (d, J = 16.7 Hz, 1H), 3.03 (d, J = 16.7 Hz, 1H), 2.95 (td, J = 6.0, 2.0 Hz, 1H), 2.25 (dd, J = 14.4, 6.2 Hz, 1H), 2.19 (dd, J = 14.4, 5.7 Hz, 1H); 13C NMR (100 MHz, CD3Cl) δ (ppm) 200.1, 171.1, 168.6, 136.2, 132.7, 128.4, 128.3, 126.0, 125.4, 125.2, 120.2, 116.7, 87.8, 58.3, 56.8, 52.0, 40.3, 39.1; HRMS (TOF-ESI) [M + H]+ calcd for C20H18O5Br 417.0332, found 417.0334. Base-Catalyzed Isomerization of 2-Cinnamylbenzofuran-3one-2-acetates 4 to 2-Styrylchroman-4-one-3-acetates 15. Under a nitrogen atmosphere, the 2-cinnamylbenzofuran-3-one-2acetates 4 (0.2 mmol) and DBU (0.2 mmol) were dissolved in dry dichloroethane (2 mL). The reaction mixture was stirred at room temperature for 24 h. After the removal of the solvent, the residue was chromatographed on a silica gel column eluting with a mixture of petroleum ether and ethyl acetate (PE/EA 15:1) to give anti-2styrylchroman-4-one-3-acetates 15 in 41−47% yields, along with 26− 56% of recovered reactants 4. (anti and E)-Methyl 2-Styrylchroman-4-one-3-acetate (15a): white solid, 28 mg, 44%; mp 114−115 °C (recrystallization from AcOEt/petroleum ether); IR v (cm−1) 1728, 1695, 1605; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.90 (dd, J = 7.8, 1.6 Hz, 1H), 7.50 (td, J = 8.6, 1.7 Hz, 1H), 7.43 (d, J = 7.0 Hz, 2H), 7.28−7.38 (m, 3H), 7.05 (t, J = 7.3 Hz, 1H), 7.02 (d, J = 8.3 Hz, 1H), 6.74 (d, J = 15.9 Hz, 1H), 6.36 (dd, J = 15.9, 8.4 Hz, 1H), 4.99 (dd, J = 15.9, 12.1 Hz, 1H), 3.58 (s, 3H), 3.32−3.38 (m, 1H), 2.90 (dd, J = 17.0, 5.1 Hz, 1H), 2.58 (dd, J = 17.0, 6.3 Hz, 1H); 13C NMR (100 MHz, CD3Cl) δ (ppm) 192.4, 172.2, 161.1, 136.1, 135.7, 135.5, 128.7, 128.7, 127.3, 126.9, 125.0, 121.6, 120.3, 117.9, 82.8, 51.9, 47.3, 30.1; HRMS (TOF-ESI) [M + H]+ calcd for C20H19O4 323.1277, found 323.1276. (anti and E)-Methyl 7-Bromo-2-styrylchroman-4-one-3-acetate (15b): white solid, 38 mg, 47%; mp 118−119 °C (recrystallization from DCM/n-hexane); IR v (cm−1) 1726, 1697, 1591; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.75 (d, J = 8.4 Hz, 1H), 7.43 (d, J = 8.6 Hz, 2H), 7.29−7.38 (m, 3H), 7.23 (d, J = 2.0 Hz, 1H), 7.18 (dd, J = 8.8, 1.6 Hz, 1H), 6.74 (d, J = 16.0 Hz, 1H), 6.32 (dd, J = 16.0, 8.4 Hz, 1H), 5.01 (dd, J = 12.0, 8.8 Hz, 1H), 3.59 (s, 3H), 3.28−3.34 (m, 1H), 2.87 (dd, J = 17.2, 4.8 Hz, 1H), 2.60 (dd, J = 16.8, 6.0 Hz, 1H); 13C NMR (100 MHz, CD3Cl) δ (ppm) 191.7, 172.1, 161.4, 136.2, 135.4, 130.7, 128.9, 128.8, 128.6, 127.0, 125.4, 124.6, 121.2, 119.3, 83.2, 52.0, 47.3, 30.1; HRMS (TOF-ESI) [M + H]+ calcd for C20H18O4Br 401.0382, found 401.0384. (anti and E)-Methyl 2-(p-Bromostyryl)chroman-4-one-3-acetate (15l): white solid, 33 mg, 41%; mp 109−110 °C (recrystallization from DCM/n-hexane); IR v (cm−1) 1724, 1697, 1607; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.90 (dd, J = 8.4, 2.0 Hz, 1H), 7.50 (td, J = 6.8, 1.6 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.05 (t, J = 8.0 Hz, 1H), 7.01 (d, J = 8.0 Hz, 1H), 6.68 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.4 Hz, 1H), 4.97 (dd, J = 12.0, 8.4 Hz, 1H), 3.0 (s, 3H), 3.31−3.37 (m, 1H), 2.92 (dd, J = 16.8, 4.4 Hz, 1H), 2.56 (dd, J = 16.8, 6.4 Hz, 1H); 13C NMR (100 MHz, CD3Cl) δ (ppm) 191.2, 172.2, 161.0, 136.3, 134.6, 134.4, 132.0, 128.4, 127.5, 126.0, 122.7, 121.8, 120.3, 117.9, 82.6, 52.0, 47.4, 30.2; HRMS (TOF-ESI) [M + H]+ calcd for C20H18O4Br 401.0382, found 401.0380.

solution, 2,6-lutidine (0.75 mmol), OsO4 (0.012 mmol), and PhI(OAc)2 (0.69 mmol) were added. The reaction mixture was stirred at room temperature until the substrates 4 were consumed (about 12 h). The reaction was quenched by adding a saturated aqueous solution of Na2S2O3 (10 mL). The reaction mixture was then extracted with ethyl acetate (10 mL × 3). The extract was washed by a saturated aqueous solution of CuSO4 (10 mL × 2) and then was dried over anhydrous Na2SO4. After the removal of Na2SO4, the solvent was evaporated under a vacuum. The residue was chromatographed on a silica gel column eluting with a mixture of petroleum ether and ethyl acetate (PE/EA 5:1) to give the aldehydes 12 in 51−61% yields. Methyl 2-(2-Oxoethyl)benzofuran-3-one-2-acetate (12a): colorless oil, 45 mg, 61%, IR v (cm−1) 1724, 1614; 1H NMR (400 MHz, CDCl3) δ (ppm) 9.64 (t, J = 0.9 Hz, 1H), 7.73 (d, J = 7.7 Hz, 1H), 7.64 (td, J = 7.1, 1.4 Hz, 1H), 7.14 (t, J = 7.4 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 3.58 (s, 3H), 3.18 (dd, J = 17, 2.2 Hz, 1H), 3.03 (d, J = 16.2 Hz, 1H), 2.97 (dd, J = 16.9, 0.7 Hz, 1H), 2.95 (d, J = 16.2 Hz, 1H); 13 C NMR (100 MHz, CD3Cl) δ (ppm) 200.8, 196.6, 170.9, 168.6, 138.1, 124.6, 122.5, 120.6, 113.3, 85.0, 52.1, 48.2, 39.9; HRMS (TOFESI) [M + H]+ calcd for C13H13O5 249.0757, found 249.0758. Methyl 6-Bromo-2-(2-oxoethyl)benzofuran-3-one-2-acetate (12b): colorless oil, 50 mg, 51%, IR v (cm−1) 1724, 1605; 1H NMR (400 MHz, CDCl3) δ (ppm) 9.62 (d, J = 1.0 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.27−7.30 (m, 2H), 3.61 (s, 3H), 3.21 (dd, J = 17.3, 2.0 Hz, 1H), 2.93−3.05 (m, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 199.5, 196.0, 170.9, 168.4, 132.8, 126.3, 125.3, 119.9, 116.8, 85.7, 52.1, 48.2, 39.9; HRMS (TOF-ESI) [M + H]+ calcd for C13H12 BrO5 326.9862, found 326.9865. Epoxidation of 2-Cinnamylbenzofuran-3-one-2-acetates 4 with m-CPBA. In a flask, the 2-cinnamylbenzofuran-3-one-2-acetates 4 (0.2 mmol) were dissolved in dry dichloromethane (1 mL). The solution of m-CPBA (85% by wt, 0.4 mmol) in DCM (1 mL) was added dropwise to the flask cooled in an ice-bath. The resultant mixture was stirred at room temperature for 8−10 h until the substrates 4 were consumed. The reaction was quenched by the addition of a saturated aqueous solution of NaHCO3 (10 mL). The organic layer was separated. The aqueous phase was extracted with DCM (10 mL × 2). The combined organic solution was dried over anhydrous Mg2SO4. After the removal of Mg2SO4, the solvent was evaporated under a vacuum. The residue was chromatographed on a silica gel column eluting with a mixture of petroleum ether and ethyl acetate (PE/EA 10:1) to give a pair of diastereomeric epoxides 13 and 14 in 42−45% and 43−47% yields. Epoxide 13a: white solid, 30 mg, 45%; mp 73−74 °C (recrystallization from DCM/n-hexane); IR v (cm−1) 1744, 1721, 1611; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.67 (d, J = 7.8 Hz, 1H), 7.56 (td, J = 8.4, 1.8 Hz, 1H), 7.22−7.28 (m, 3H), 7.12 (d, J = 7.2 Hz, 2H), 7.06 (d, J = 9 Hz, 1H), 7.04 (t, J = 7.2 Hz, 1H), 3.57 (s, 1H), 3.54 (s, 3H), 3.24 (d, J = 16.8 Hz, 1H), 3.12 (d, J = 16.8 Hz, 1H), 3.02 (td, J = 7.2, 1.2 Hz, 1H), 2.22 (dd, J = 14.4, 6.0 Hz, 1H), 2.09 (dd, J = 14.4, 5.4 Hz, 1H); 13C NMR (100 MHz, CD3Cl) δ (ppm) 201.9, 171.2, 169.0, 138.1, 136.6, 128.4, 128.3, 125.5, 124.5, 122.3, 121.0, 113.2, 87.5, 57.9, 57.8, 52.0, 40.1, 39.1; HRMS (TOF-ESI) [M + H]+ calcd for C20H19O5 339.1227, found 339.1228. Epoxide 14a: white solid, 29 mg, 43%; mp 133−134 °C (recrystallization from DCM/n-hexane); IR v (cm−1) 1738, 1721, 1612; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.68 (d, J = 8 Hz, 1H), 7.58 (t, J = 7.6 Hz, 1H), 7.22−7.28 (m, 3H), 7.04−7.12 (d, 4H), 3.62 (s, 1H), 3.55 (s, 3H), 3.14 (d, J = 16.4 Hz, 1H), 3.03 (d, J = 15.6 Hz, 1H), 2.99 (d, J = 5.6 Hz, 1H), 2.28 (dd, J = 14.4, 6.0 Hz, 1H), 2.20 (dd, J = 14.4, 5.6 Hz, 1H); 13C NMR (100 MHz, CD3Cl) δ (ppm) 201.5, 171.2, 168.8, 138.0, 136.5, 128.4, 128.3, 125.6, 124.6, 122.3, 121.0, 113.2, 86.9, 58.5, 57.1, 52.0, 40.4, 39.1; HRMS (TOF-ESI) [M + H]+ calcd for C20H19O5 339.1227, found 339.1226. Epoxide 13b: white solid, 35 mg, 42%; mp 109−110 °C (recrystallization from AcOEt/petroleum ether); IR v (cm−1) 1738, 1715, 1601; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.52 (d, J = 8.2 Hz, 1H), 7.27−7.31 (m, 4H), 7.19 (dd, J = 8.2, 1.3 Hz, 1H), 7.12−7.14 (m, 2H), 3.57 (s, 1H), 3.56 (s, 3H), 3.26 (d, J = 17.0 Hz, 1H), 3.14 (d, J = 17.0 Hz, 1H), 3.01 (td, J = 6.6, 2.0 Hz, 1H), 2.17 (dd, J = 14.5, 6.6

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02849. Copies of 1H and 13C NMR spectra for the products 4a− 4o, 5a, 5e, 6a, 6e, 12a, 12b, 13a, 13b, 14a, 14b, 15a, 1922

DOI: 10.1021/acs.joc.7b02849 J. Org. Chem. 2018, 83, 1913−1923

Article

The Journal of Organic Chemistry

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Xu, D. Org. Biomol. Chem. 2017, 15, 4191−4198. (d) Dhokale, R. A.; Mhaske, S. B. J. Org. Chem. 2017, 82, 4875−4882. (e) Coe, J. W.; Bianco, K. E.; Boscoe, B. P.; Brooks, P. R.; Cox, E. D.; Vetelino, M. G. J. Org. Chem. 2003, 68, 9964−9970. (f) Fu, J.; Shang, H.; Wang, Z.; Chang, L.; Shao, W.; Yang, Z.; Tang, Y. Angew. Chem., Int. Ed. 2013, 52, 4198−4202. (g) Li, Q.-B.; Hu, X.-C. Chem. Lett. 2012, 41, 1633− 1635. (h) Luo, Q.; Wei, X.-Y.; Yang, J.; Luo, J.-F.; Liang, R.; Tu, Z.-C.; Cheng, Y.-X. J. Nat. Prod. 2017, 80, 61−70. (12) For NHC-catalyzed reactions to the 2,2-disubstituted benzofuran-3-ones, see: (a) Kerr, M. S.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 8876−8877. (b) He, J.; Zheng, J.; Liu, J.; She, X.; Pan, X. Org. Lett. 2006, 8, 4637−4640. (c) He, J.; Tang, S.; Liu, J.; Su, Y.; Pan, X.; She, X. Tetrahedron 2008, 64, 8797−8800. (d) Filloux, C. M.; Lathrop, S. P.; Rovis, T. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 20666−20671. (e) Padmanaban, M.; Biju, A. T.; Glorius, F. Org. Lett. 2011, 13, 5624−5627. (f) Zhao, Y.; Wang, Z.-T.; Cheng, Y. Adv. Synth. Catal. 2014, 356, 2580−2590. (13) (a) Ciganek, E. Synthesis 1995, 1995, 1311−1314. (b) Rong, Z.Q.; Li, Y.; Yang, G.-Q.; You, S.-L. Synlett 2011, 2011, 1033−1037. (c) Kerr, M. S.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 8876−8877. (d) Moore, J. L.; Kerr, M. S.; Rovis, T. Tetrahedron 2006, 62, 11477− 11482. (14) For the reviews for Pd-catalyzed allylation reactions, see: (a) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921−2943. (b) Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258−297. (15) Nicolaou, K. C.; Adsool, V. A.; Hale, C. R. H. Org. Lett. 2010, 12, 1552−1555. (16) For examples of epoxidation of CC bonds with m-CPBA, see: (a) Brennan, M. B.; Csatayová, K.; Davies, S. G.; Fletcher, A. M.; Green, W. D.; Lee, J. A.; Roberts, P. M.; Russell, A. J.; Thomson, J. E. J. Org. Chem. 2015, 80, 6609−6618. (b) Brambilla, M.; Brennan, M. B.; Csatayová, K.; Davies, S. G.; Fletcher, A. M.; Kennett, A. M. R.; Lee, J. A.; Roberts, P. M.; Russell, A. J.; Thomson, J. E. J. Org. Chem. 2017, 82, 10297−10309. (c) Abbasov, M. E.; Hudson, B. M.; Kong, W.; Tantillo, D. J.; Romo, D. Org. Biomol. Chem. 2017, 15, 3179− 3183.

15b, and 15i and HPLC chromatographs for enantiomerically enriched 4a−4d, 4i, 4j, and 4l (PDF) Single crystal data of rac-4a (CIF) Single crystal data of rac-6e (CIF) Single crystal data of rac-13a (CIF) Single crystal data of rac-14a (CIF) Single crystal data of rac-15a (CIF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Ying Cheng: 0000-0002-2598-2974 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (no. 21772015). REFERENCES

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DOI: 10.1021/acs.joc.7b02849 J. Org. Chem. 2018, 83, 1913−1923