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Cite This: J. Org. Chem. 2017, 82, 11691-11702

Hypervalent-Iodine-Mediated Formation of Epoxides from Carbon(sp2)−Carbon(sp3) Single Bonds Shan Jiang, Tai-Shan Yan, Yong-Chao Han, Li-Qian Cui, Xiao-Song Xue,* and Chi Zhang* State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, College of Chemistry, Nankai University, Tianjin 300071, China S Supporting Information *

ABSTRACT: We have developed an efficient method for direct formation of epoxide groups from carbon(sp2)− carbon(sp3) single bonds of β-keto esters; the reaction is mediated by the water-soluble hypervalent iodine(V) reagent AIBX (5-trimethylammonio-1,3-dioxo-1,3-dihydro-1λ5-benzo[d][1,2]iodoxol-1-ol anion). On the basis of the results of density functional theory calculations and experimental studies, we propose that the reaction proceeds by a two-stage mechanism involving dehydrogenation of the β-keto ester substrates and epoxidation of the resulting enone intermediates. The rate-limiting step is abstraction of the β′-C−H (calculated free energy of activation, 24.5 kcal/mol).

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INTRODUCTION Epoxides are versatile intermediates that are widely used as building blocks for the synthesis of valuable chemicals, such as 1,2-diols, β-amino alcohols, and halohydrins.1 In addition, epoxides have been proposed as intermediates in the biosyntheses of several complex natural products.2 The epoxide group is widespread in bioactive molecules, including the anticholinergic drug Spiriva, which is used for maintenance treatment of chronic obstructive pulmonary disease; the potential anticancer drug epothilone B, which has been investigated in several clinical trials; and the natural product triptolide, which has potent immunosuppressive activity (Figure 1).3 Owing to the importance of the epoxide group,

Figure 1. Selected epoxide-bearing molecules.

many methods, both oxidative and nonoxidative, for its formation have been developed. For nonoxidative methods, halohydrins, aldehydes, and ketones often serve as precursors for efficient formation of epoxide groups (Figure 2A−C).4 Nearly all of the currently available oxidative methods involve treatment of olefins with various oxidants (Figure 2D).5 The development of oxidative methodology for the efficient formation of epoxide groups directly from carbon−carbon single bonds rather than double bonds is highly desirable. There have been a few scattered reports of such transformations, and they can be divided into two categories: direct © 2017 American Chemical Society

Figure 2. Methods for efficient formation of epoxides.

transformations of carbon(sp2)−carbon(sp3) (Csp2−Csp3) single bonds and transformations of carbon(sp3)−carbon(sp3) single bonds, which are more challenging. Two cases of epoxide formation from Csp2−Csp3 single bonds have been reported, Special Issue: Hypervalent Iodine Reagents Received: April 13, 2017 Published: June 3, 2017 11691

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702

Article

The Journal of Organic Chemistry Table 1. Screening of Organic Solvents and Organic Solvent/H2O Ratiosa

entry

solvent (v/v)

time (h)

conv. (%)

yield (%) of 2a

yield (%) of 3

1 2b 3 4c 5c 6d 7 8 9 10 11e 12e 13c

diglyme/H2O (1/3) diglyme/H2O (1/3) DME/H2O (1/3) THF/H2O (1/3) DMF/H2O (1/3) DMSO/H2O (1/3) PEG400/H2O (1/3) PEG2000/H2O (1g/3 mL) CCl4/H2O (1/3) PEG400/H2O (1/1) PEG400/H2O (1/3) PEG400/H2O (1/1) H2O

7 36 24 36 24 24 7 8 24 6 23 9 24

100 100 100 49 100 90 100 100 25 100 100 100 90

82 60 49 20 49 50 84 83 14 83 72f 79f 26

11 4 8

yield (%) of 4

17 34 11 11 8 19 12 4

50

Reaction conditions: 1a (0.3 mmol), AIBX (0.45 mmol), solvent (4 mL), 90 °C. The reaction was carried out at 70 °C. Decarboxylated product 4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one (4) was obtained. dDehydrogenation product methyl 4,4-dimethyl-1-oxo-1,4-dihydronaphthalene-2carboxylate (I) was obtained in 25% yield. eCompound 1b was used as the substrate. fEpoxide 2b was obtained. a

b

both of which involved molecular oxygen as the oxidant:6 (1) photochemical reactions of a six-membered-ring enolic 1,3diketone generated an epoxide in up to 15% yield, and (2) Mn(OAc)2-catalyzed oxidation of a cyclic β-keto ester afforded the corresponding epoxide in 45% yield after 3 days. Neither of these processes is practical, owing to either low yield or sluggish reaction. Formation of an epoxide group directly from a carbon(sp3)−carbon(sp3) single bond is one of the most challenging oxidative processes. To date, no systematic study of this transformation has been reported in the literature. The only reported direct formation of epoxide groups from carbon(sp3)−carbon(sp3) single bonds was observed in oxidative studies of several hydrocarbons; the major oxidative products were alcohols and/or carbonyl compounds,7 and only low yields of epoxides (6−26%) were obtained. Therefore, an efficient method for epoxide formation directly from carbon− carbon single bonds is highly desirable. Hypervalent iodine reagents, due to their safety, ready availability, environmental friendliness, and regenerability, are preferred organo-oxidants in the organic synthesis.8 In this study, as part of our ongoing exploration of the reactivity of AIBX (5-trimethylammonio-1,3-dioxo-1,3-dihydro-1λ5-benzo[d][1,2]iodoxol-1-ol anion), a water-soluble hypervalent iodine(V) reagent that was first synthesized in our laboratory,9 we developed an efficient method for oxidative formation of epoxide groups directly from Csp2−Csp3 single bonds in a single step using AIBX as an oxidant in the absence of a catalyst (Figure 2E).

c

hydroxylated product 3a (Table 1, entry 1). Lowering the reaction temperature to 70 °C decreased the yield of 2a (entry 2). To improve the efficiency of the reaction, we screened various other organic solvents. Neither DME/H2O nor THF/ H2O improved the results (entries 3−4), among them, the reaction in THF/H2O produced 20% yield of 2a and 17% yield of the decarboxylated product 4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one (4). Reactions in DMF/H2O and DMSO/ H2O afforded 2a in moderate yields (49 and 50%, respectively; entries 5 and 6). Epoxide formation reactions in polyethylene glycols (PEGs) PEG400 and PEG2000 gave better yields of 2a (84% and 83%, respectively; entries 7 and 8). The biphasic solvent system of CCl4/H2O was a poor choice, providing 2a in a low yield (entry 9). Because PEG400 was the best of the organic solvents we evaluated, we examined the effect of the PEG400/H2O volume ratio. Reactions of 1a in 1/3 (v/v) PEG400/H2O and 1/1 (v/ v) PEG400/H2O gave comparable yields of 2a (Table 1, compare entries 7 and 10), but the reaction of methyl 6-bromo4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1b) was much slower in 1/3 PEG400/H2O than in 1/1 PEG400/H2O, and the yield of 2b was lower in the former than in the latter, owing to the better solubility of 1b in 1/1 PEG400/H2O (compare entries 11 and 12). Reaction in water alone resulted in a very low yield of 2a along with 50% yield of 4 after 24 h (entry 13). On the basis of these results, we used the conditions shown in entry 10 of Table 1 for further study. Note that when 2-iodoxybenzoic acid (IBX), the widely used hypervalent iodine(V) reagent that is the parent compound of AIBX, was employed as the oxidant under the otherwise identical reaction conditions as described in entry 10, epoxide 2a was not detected; α-hydroxylation product 3a was obtained as the sole product in 53% yield, and conversion of 1a was only 80%. The derivatives of IBX, including FIBX and mIBX,10 were also tried and gave α-hydroxylation product 3a in 94 and 82% yields, respectively, without detecting epoxidation product.

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RESULTS AND DISCUSSION We began by investigating epoxide formation from β-keto ester 1a, methyl 4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2carboxylate, using 1.5 equiv of AIBX in a 1/3 (v/v) mixture of diglyme and water at 90 °C. After 7 h, the desired epoxide product, methyl 7,7-dimethyl-2-oxo-1a,2,7,7atetrahydronaphtho[2,3-b]oxirene-1a-carboxylate (2a), was obtained in 82% yield along with a small amount of α11692

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702

Article

The Journal of Organic Chemistry

Figure 3. Substrate scope of epoxide formation reaction. The reactions were carried out with 0.3 mmol of substrates in 1/1 (v/v) PEG400/H2O. Reaction times and yields of products are shown, along with yields of α-hydroxylated products (in parentheses). (b) Carried out in 1/3 (v/v) PEG400/H2O. (c) The yield in parentheses is the yield of methyl 3,3-dimethyl-6-oxocyclohex-1-ene-1-carboxylate (5s).

Figure 4. Synthesis of 2a from I.

We conducted some experiments to investigate the mechanism of this new reaction. Specifically, the reaction of 1a with AIBX in 1/3 (v/v) DMSO/H2O at 90 °C gave enone I as a byproduct, and the reaction of substrate 1s under the standard conditions gave enone 5s as a byproduct (Table 1, entry 6; Figure 3). On the basis of these results, our previous work9 on AIBX-mediated dehydrogenation reactions of cyclic β-keto esters, and the reported iodosobenzene-mediated epoxidation of electron-deficient olefins, such as enones,11 we propose a two-stage reaction mechanism for the present AIBXmediated epoxide formation reaction directly from Csp2−Csp3 single bonds. First, the β-keto ester substrate is oxidatively dehydrogenated to the corresponding dehydrogenated enone by AIBX, which is reduced to AIBA (3-oxo-5-(trimethylammonio)-1λ3-benzo[d][1,2]iodaoxol-1(3H)-olate), a hypervalent iodine(III) reagent. Second, the enone is transformed to the corresponding epoxide by the AIBA generated in situ. To verify this mechanism, we performed the following control experiment shown in Figure 4. When enone I, the product of dehydrogenation of 1a, was synthesized12 and treated with AIBA, desired epoxide 2a was obtained in 63% yield (for preparation of AIBA, see Experimental Section). This control experiment showed that the epoxide formation reaction occurred in two stages with enone I as an intermediate. It was worth noting that 1-hydroxy-1l3-benzo[d][1,2]iodaoxol3(1H)-one (IBA), the reduced form of IBX, was used in the reaction under the otherwise same reaction conditions of AIBA, affording only 8% yield of epoxide product (2a) along with 70% yield of starting material being recovered. To gain a better understanding of the mechanistic details of this AIBX-mediated epoxide formation reaction, we carried out density functional theory calculations at the M06-2X/[6-311+ +G(2df,2p) + SDD(I)](SMD)//M06-2X/[6-31+G(d) +

To test the generality of this epoxide formation reaction, we evaluated a variety of β-keto esters and a β-diketone in which gem-dimethyl groups are installed at the γ-site of carbonyl to prevent aromatization9a as substrates (Figure 3). Like 1a, ethyl 4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1c) was readily oxidized to corresponding epoxides 2c (83% yield). Substrates bearing either an electron-withdrawing substituent (F, Cl, Br, I, NO2) or an electron-donating substituent [Me, OMe, N(CO2Me)Me] on the phenyl ring were also smoothly converted to the desired epoxides in good to high yields (2d−l). Note that the reaction of 1i, with a methyl group on the phenyl ring, yielded desired epoxide 2i in 81% yield without undergoing benzylic oxidation. A substrate with a readily oxidizable naphthalene ring was also compatible with the reaction conditions, providing 2m in 75% yield. A compound with a spiro cyclopentyl group at the benzylic position afforded corresponding epoxide 2n in 86% yield. A thiophene substituent was also well tolerated under the standard conditions: 1o yielded the corresponding epoxide (2o) in 80% yield. This success in converting Csp2−Csp3 single bonds of benzo-fused β-keto esters into epoxide groups encouraged us to explore the feasibility of changing the phenyl moiety to a simple carbon−carbon double bond. Under the standard reaction conditions, epoxides 2p−r were produced in 59, 63, and 72% yields, respectively. Furthermore, epoxidation could be accomplished even with a fully saturated substrate: 1s afforded epoxide 2s in 32% yield. β-Diketone 1t was also smoothly transformed into its corresponding epoxide (2t) in 75% yield. Note that because AIBX is highly water-soluble (0.38 M),9a it can be regenerated readily after the reaction as exemplified in the oxidation of 1o in which AIBX could be regenerated in 86% yield (for the detailed procedure, see Experimental Section). 11693

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702

Article

The Journal of Organic Chemistry

Figure 5. Energy diagram for AIBX-mediated epoxide formation calculated at the M06-2X/[6-311++G(2df,2p) + SDD(I)](SMD)//M06-2X/[631+G(d) + Lanl2dz(I)](SMD) level. Free energies are in kilocalories per mole, and bond lengths are in angstroms.14

Figure 6. Kinetic isotope effect experiment.

was predicted to lie 54.7 kcal/mol above IM1. In contrast, the calculated free energy of activation for direct hydride transfer via TS2 was only 24.5 kcal/mol. That is, direct hydride transfer was calculated to be preferred by nearly 30 kcal/mol relative to SET. Therefore, although the SET mechanism has been widely proposed for 2-iodoxybenzoic acid−induced dehydrogenation of aldehydes and ketones, this mechanism is highly unlikely for our AIBX-mediated dehydrogenation of β-keto esters. A possible reason for this difference may be that compared to aldehyde and ketone enolates, β-keto ester enolates are more

Lanl2dz(I)](SMD) level of theory (Figure 5). The energy difference between substrate 1a and enol form 1a′ was calculated to be only 0.2 kcal/mol. Deprotonation of the O− H bond of 1a′ by the oxygen atom of AIBX was found to be a facile process with an energy barrier of only 9.4 kcal/mol; this step was calculated to be 7.3 kcal/mol endergonic in water. Subsequent formation of enone intermediate I can proceed via either single electron transfer13 or direct hydride transfer. Our calculations indicated that the energy barrier for SET was prohibitively high: the hypothetical diradical intermediate IM2 11694

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702

Article

The Journal of Organic Chemistry

Figure 7. Proposed mechanism.

reluctant to release an electron. The dehydrogenation process leading to enone intermediate I and AIBA was predicted to be exothermic by 61.2 kcal/mol. The epoxidation of I by AIBA was found to be a stepwise process. Michael-type addition of AIBA to enone intermediate I via TS3 was calculated to require an activation free energy of 11.9 kcal/mol, and subsequent ring closure through TS4 to generate epoxy product 2a was calculated to have a barrier of only 12.0 kcal/mol. Reviewing the calculated energy profile of the overall reaction pathway, we found that the overall reaction was exergonic by 105.2 kcal/mol and that abstraction of the β′C−H of enolate 1a′ to give enone intermediate I was the ratelimiting step. To validate our calculation-based prediction that β′-C−H abstraction was the rate-limiting step, a kinetic isotope effect (KIE) experiment was undertaken. First, β′-double deuterated substrate β′-[D2]-1a (deuteration ratio: > 95%) was prepared from β-tetralone by introduction of two deuterium atoms from NaBD4 and from D2 generated in situ from NaBD4 and CD3OD, respectively (for the preparation of β′-[D2]-1a, see Experimental Section). Then a KIE experiment was conducted with 1a and β′-[D2]-1a as the substrates under the standard reaction conditions, except that only 0.5 equiv of AIBX was employed (Figure 6). Analysis of the reaction products by 1H NMR indicated that the KIE value for the intermolecular competition experiment was 2.9, suggesting that β′-C−H abstraction was the rate-limiting step. Thus, the result of this KIE experiment was in agreement with the results of our calculations indicating that abstraction of the β′−C-H was the rate-limiting step. On the basis of all the above-described results, we propose the reaction mechanism shown in Figure 7. First, substrate 1a is deprotonated by AIBX to give corresponding enolate A. Enolate A tautomerizes to the corresponding keto form, which then combines with protonated AIBX to yield intermediate B.

Intermediate B yields dehydrogenated intermediate I via hydride transfer via transition state TS2, which contains a seven-membered I(V) heterocycle. Epoxidation of I by Michael-type addition of AIBA to the double bond produces intermediate IM3, which gives epoxide 2a through intramolecular cyclization.

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CONCLUSION In summary, we have developed an AIBX-mediated method for forming epoxide groups directly from Csp2−Csp3 single bonds. This method offers an alternative to the traditional methods for epoxide formation. Experimental and theoretical results revealed that the reaction proceeds via a two-stage mechanism. By calculating the energy profile of the overall reaction pathway, we found that abstraction of the β′-C−H of enolate 1a′ to give enone intermediate I is the rate-limiting step. Investigation of the use of this method for transformations of light alkanes is underway in our laboratory.

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EXPERIMENTAL SECTION

General Information. All the reactions were carried out under atmosphere without any special protection. The PEG400 and deionized water were used as solvents. The 1H NMR spectra were recorded at 400 MHz and 13C{1H}NMR spectra were measured at 100 MHz using Bruker AV 400 as instrument; CDCl3 or D2O was used as the solvent. 1H NMR spectra are reported as follows: chemical shift in ppm (δ) relative to the chemical shift of CDCl3 at 7.26 ppm or D2O at 4.70 ppm, multiplicities, coupling constants (Hz), and integration. 13C{1H}NMR spectra are reported in ppm (δ) relative to the central line of triplet of CDCl3 at 77.00 ppm. IR spectra were recorded with a FT-IR Bruker EQUINOX55 spectrometer in KBr pellets. High-resolution mass spectroscopy (HRMS) was performed with a high-resolution ESI−FTICR mass spectrometer (Varian 7.0 T). Preparation and Characterization of Substrates. Methyl 4,4Dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1a). To the suspension of NaH (960 mg, 40 mmol) in dried dimethyl carbonate (10 mL) was added a solution of 4,4-dimethyl-3,411695

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702

Article

The Journal of Organic Chemistry

δ 173.0, 162.9, 146.0, 132.3, 130.8, 130.2, 125.5, 124.7, 96.3, 51.8, 35.4, 33.5, 28.4; IR (KBr) ν = 2980, 1668, 1633, 1559, 1449, 1400, 1355, 1268, 1100, 1053, 1010, 889, 821, 777, 531 cm−1; HRMS(ESI): calcd. for C14H16ClO3 [M+H]+ 267.0788, found 267.0782. Methyl 7-Bromo-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1f). To a cooled (0 °C) stirred solution of sodium nitrate (2.18 g, 13.92 mmol) in concentrated sulfuric acid (28.4 mL) and glacial acetic acid (26.27 mL) was added a solution of 4,4-dimethyl-7-amino-1-tetralone (5.0 g, 26.46 mmol) in glacial acetic acid (89 mL) over 10 min. The resulting solution was added slowly (over 10 min) to a cooled solution of copper(I) bromide (16.66 g) in concentrated hydrobromic acid (159 mL). The mixture was stirred at 0 °C overnight. After the reaction completed, the reaction mixture was diluted with water (250 mL) and extracted with ethyl acetate (200 mL × 2). The combined organic phases were concentrated in vacuo to give 7-bromo-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one. Compound 1f was obtained in 87% yield (674 mg) following the procedure for the preparation of 1a with 7-bromo-4,4-dimethyl-3,4-dihydronaphthalen1(2H)-one (2.5 mmol) and dimethyl carbonate as the starting material. White solid; m.p.: 55−57 °C; 1H NMR (400 MHz, CDCl3) δ 12.26 (s, 1H), 7.95 (d, J = 2.4 Hz, 1H), 7.49 (dd, J = 8.0, 2.4 Hz, 1H), 7.19 (d, J = 8.0 Hz, 1H), 3.83 (s, 3H), 2.47 (s, 2H), 1.27 (s, 6H); 13 C{1H}NMR (100 MHz, CDCl3) δ 173.0, 162.8, 146.5, 133.8, 130.5, 127.6, 125.8, 120.2, 96.3, 51.8, 35.3, 33.6, 28.3; IR (KBr) ν = 2967, 2939, 1666, 1632, 1575, 1448, 1387, 1277, 1129, 1020, 849, 750, 677 cm−1; HRMS(ESI): calcd. for C14H16BrO3 [M+H]+ 311.0283, found 311.0288. Methyl 7-iodo-4,4-Dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1g). To a solution of 4,4-dimethyl-7-amino-1tetralone (1.82 g, 10.0 mmol) in concentrated hydrochloric acid (4.69 mL) was added ice cold water (3.13 mL). The reaction mixture was then cooled to 0 °C by use of an ice−water bath. The reaction mixture was then diazotized by the dropwise addition with stirring of a solution of sodium nitrite (0.76 g, 11.0 mmol) in water (3.13 mL), keeping temperature between 0−5 °C. After stirring for 15 min, the reaction mixture was added to a solution of potassium iodide (3.63 g, 21.9 mmol) in water (18.8 mL). After stirring for 30 min, the reaction mixture was extracted with ethyl acetate. The organic phase was then concentrated in vacuo to give 7-iodo-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one. Compound 1g was obtained in 81% yield (667 mg) following the procedure for the preparation of 1a with 7-iodo-4,4dimethyl-3,4-dihydronaphthalen-1(2H)-one (2.3 mmol) and dimethyl carbonate as the starting material. White solid; m.p.: 58−60 °C; 1H NMR (400 MHz, CDCl3) δ 12.26 (s, 1H), 8.14 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H), 3.83 (s, 3H), 2.46 (s, 2H), 1.26 (s, 6H); 13C{1H}NMR (100 MHz, CDCl3) δ 173.0, 162.8, 147.2, 139.8, 133.5, 130.5, 126.1, 96.2, 91.3, 51.8, 35.3, 33.6, 28.3; IR (KBr) ν = 2922, 1666, 1625, 1455, 1375, 1324, 1240, 1167, 1012, 823, 766, 710 cm−1; HRMS(ESI): calcd. for C14H16IO3 [M+H]+ 359.0144, found 359.0140. Ethyl 4,4-Dimethyl-7-nitro-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1h). 4,4-Dimethyl-7-nitro-3,4-dihydronaphthalen-1(2H)-one was prepared following the literature procedure.17 To a freshly prepared solution of LDA (11 mmol using 1.44 mL of iPr2NH and 4.58 mL of n-BuLi 2.4 M) in THF (5 mL) at −78 °C, a solution of 4,4-dimethyl-7-nitro-3,4-dihydronaphthalen-1(2H)-one (2.19 g, 10 mmol) in THF (5 mL) was added dropwise and the solution was stirred at this temperature during 30 min. Then DMPU (1.2 mL, 10 mmol) was added to the resulted solution followed by adding a solution of ethyl carbonocyanidate (2.0 g, 20 mmol) in THF (5 mL). After the resulting solution was stirred at −78 °C for 4 h, the reaction was quenched with aqueous NH4Cl (20 mL) and extracted with EtOAc (50 mL × 3). The combined organic layer was dried over MgSO4 and concentrated in vacuo to afford the crude product, which was purified by silica gel flash chromatography to give 1h in 51% yield (1.48 g). White solid; m.p.: 71−73 °C; 1H NMR (400 MHz, CDCl3) δ 12.36 (s, 1H), 8.64 (d, J = 4.0 Hz, 1H), 8.21 (dd, J = 8.0, 4.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 4.31 (q, J = 8.0 Hz, 2H), 2.53 (s, 2H), 1.37 (t, J = 8.0 Hz, 3H), 1.33 (s, 6H); 13C{1H}NMR (100 MHz, CDCl3) δ 172.4, 161.6, 154.5, 146.7, 130.2, 125.4, 125.2, 119.8, 97.4, 61.0, 35.0,

dihydronaphthalen-1(2H)-one (1.46 g, 5 mmol) in dried dimethyl carbonate (10 mL) dropwise at room temperature. The mixture was heated to reflux until the starting material was totally consumed. After cooling to room temperature, the reaction mixture was poured into ice water and extracted with EtOAc (50 mL × 3). The combined organic layer was dried with MgSO4 and concentrated in vacuo. The residue was purified by column chromatography to give the title compound in 87% yield (1.01 g). Colorless oil; 1H NMR (400 MHz, CDCl3) enol and keto form, δ 12.34 (s, 0.85H), 8.02 (d, J = 8.0 Hz, 0.11H), 7.84 (d, J = 8.0 Hz, 0.83H), 7.56 (t, J = 8.0 Hz, 0.13H), 7.47−7.23 (m, 3.28H), 3.83 (s, 3H), 2.48 (s, 1.88H), 1.47 (s, 0.36H), 1.37 (s, 0.38H), 1.29 (s, 5.67H); 13C{1H}5NMR (100 MHz, CDCl3) enol and keto form, δ 173.2, 164.4, 147.8, 134.4, 131.2, 128.5, 127.8, 126.6, 126.2, 126.0, 124.7, 123.90, 95.3, 52.3, 51.6, 51.4, 40.0, 35.5, 33.6, 30.3, 29.7, 28.5; IR (KBr) ν = 2974, 1676, 1635, 1333, 1124, 884, 861, 745 cm−1; HRMS(ESI): calcd. for C14H17O3 [M+H]+ 233.1178, found 233.1182. Methyl 6-Bromo-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1b). 6-Bromo-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one was prepared following the literature procedure.15 Compound 1b was obtained in 79% yield (1.23 g) following the procedure for the preparation of 1a with 6-bromo-4,4-dimethyl-3,4dihydronaphthalen-1(2H)-one (5 mmol) and dimethyl carbonate as the starting material. White solid; m.p.: 60−61 °C; 1H NMR (400 MHz, CDCl3) enol and keto form, δ 12.28 (s, 0.85H), 7.87 (d, J = 12.0 Hz, 0.19H), 7.69 (d, J = 8.0 Hz, 1H), 7.56 (s, 0.18H), 7.45 (s, 1.20H), 7.41 (d, J = 8.0 Hz, 0.94H), 3.83 (s, 3.18H), 3.81 (s, 0.51H), 2.47 (s, 2.00H), 1.46 (s, 0.55H), 1.37 (s, 0.51H), 1.28 (s, 6.29H); 13C{1H}NMR (100 MHz, CDCl3) enol and keto form, δ 173.1, 163.5, 149.8, 130.2, 129.4, 127.5, 127.4, 126.4, 125.8, 95.7, 52.4, 51.7, 51.2, 39.8, 35.4, 33.9, 30.1, 29.6, 28.3; IR (KBr) ν = 2977, 1666, 1630, 1595, 1393, 1247, 1199, 1140, 1100, 783, 764 cm−1; HRMS(ESI): calcd. for C14H16BrO3 [M+H]+ 311.0283, found 311.0286. Ethyl 4,4-Dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1c). Compound 1c was obtained in 86% yield (1.06 g) following the procedure for the preparation of 1a with 4,4-dimethyl3,4-dihydronaphthalen-1(2H)-one (5 mmol) and diethyl carbonate as the starting material. Slightly yellow oil; 1H NMR (400 MHz, CDCl3) enol and keto form, δ 12.47 (s, 0.63H), 7.96 (m, 0.90H), 7.63−7.24 (m, 3.03H), 4.37−4.21 (m, 1.92H), 3.84 (dd, J = 14.1, 4.5 Hz, 0.20H), 2.51 (s, 1.60H), 2.12 (m, 0.33H), 1.50 (s, 0.80H), 1.44−1.35 (m, 3.39H), 1.32 (s, 4.76H); 13C{1H}NMR (100 MHz, CDCl3) enol and keto form, δ 193.4, 172.94, 170.5, 164.3, 151.5, 147.7, 131.1, 128.6, 127.7, 126.5, 126.1, 125.9, 124.7, 123.9, 95.5, 61.2, 60.5, 51.5, 39.9, 35.5, 33.6, 30.3, 29.7, 28.4, 14.3, 14.2; IR (KBr) ν = 2947, 1680, 1630, 1257, 1205, 1145, 874, 734 cm−1; HRMS(ESI): calcd. for C15H19O3 [M+H]+ 247.1334, found 247.1339. Methyl 7-Fluoro-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1d). 7-Fluoro-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one was prepared following the literature procedure.16 Compound 1d was obtained in 85% yield (1.06 g) following the procedure for the preparation of 1a with 7-fluoro-4,4-dimethyl-3,4dihydronaphthalen-1(2H)-one (5 mmol) and dimethyl carbonate as the starting material. Slightly yellow oil; 1H NMR (400 MHz, CDCl3) δ 12.28 (s, 1H), 7.50 (d, J = 9.2 Hz, 1H), 7.33−7.20 (m, 1H), 7.04 (t, J = 8.4 Hz, 1H), 3.83 (s, 3H), 2.46 (s, 2H), 1.26 (s, 6H); 13C{1H}NMR (100 MHz, CDCl3) δ 173.0, 163.0, 161.3 (d, J = 242.7 Hz), 143.3 (d, J = 3.1 Hz), 130.4 (d, J = 7.8 Hz), 125.6 (d, J = 7.6 Hz), 117.5 (d, J = 21.0 Hz), 111.4 (d, J = 23.0 Hz), 96.4, 51.7, 35.5, 33.4, 28.5; IR (KBr) ν = 2943, 1673, 1622, 1433, 1382, 1222, 1188, 823, 719 cm−1; HRMS(ESI): calcd. for C14H16FO3 [M+H]+ 251.1083, found 251.1090. Methyl 7-Chloro-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1e). Compound 1e was prepared following the procedure for the preparation of 1f and using freshly prepared CuCl and HCl to replace the CuBr and HBr, 1e was obtained in the yield of 90% (479 mg) with 6-chloro-4,4-dimethyl-3,4-dihydronaphthalen1(2H)-one (2 mmol) and dimethyl carbonate as the starting material.. Slightly yellow oil; 1H NMR (400 MHz, CDCl3) δ 12.27 (s, 1H), 7.80 (d, J = 2.0 Hz, 1H), 7.36−7.30 (m, 1H), 7.25 (d, J = 8.4 Hz, 1H), 3.83 (s, 3H), 2.47 (s, 2H), 1.27 (s, 6H); 13C{1H}NMR (100 MHz, CDCl3) 11696

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702

Article

The Journal of Organic Chemistry 34.4, 28.3, 14.3. IR (KBr) ν = 2969, 1654, 1623, 1524, 1400, 1347, 1224, 1066, 1025, 909, 834, 743 cm−1; HRMS(ESI): calcd. for C15H18NO5 [M+H]+ 292.1185, found 292.1186. Methyl 4,4,6-Trimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2carboxylate (1i). 4,4,6-Trimethyl-3,4-dihydronaphthalen-1(2H)-one was prepared following the literature procedure.18 Compound 1i was obtained in 79% yield (972 mg) following the procedure for the preparation of 1a with 4,4,6-trimethyl-3,4-dihydronaphthalen-1(2H)one (5 mmol) and dimethyl carbonate as the starting material. Slightly yellow oil; 1H NMR (400 MHz, CDCl3) enol and keto form, δ 12.33 (s, 1H), 7.92 (d, J = 8.0 Hz, 0.23H), 7.73 (d, J = 8.0 Hz, 1H), 7.20 (s, 0.23H), 7.14 (s, 1H), 7.09 (d, J = 8.0 Hz, 1H), 3.82 (s, 3H), 3.81 (s, 0.55H), 2.46 (s, 2H), 2.41 (s, 0.75H), 2.39 (s, 3H), 1.46 (s, 0.77H), 1.36 (s, 0.74H), 1.27 (s, 6H); 13C{1H}NMR (100 MHz, CDCl3) enol and keto form, δ 192.9, 173.3, 171.1, 164.8, 147.9, 141.5, 128.0, 127.7, 126.9, 126.4, 125.9, 124.8, 124.7, 94.5, 52.3, 51.6, 51.4, 40.1, 35.7, 33.6, 30.3, 29.7, 28.5, 22.0, 21.9; IR (KBr) ν = 2981, 1666, 1625, 1365, 1124, 888, 810, 762 cm−1; HRMS(ESI): calcd. for C15H19O3 [M+H]+ 247.1334, found 247.1338. Methyl 6-Methoxy-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1j). 6-Methoxy-3,4-dihydronaphthalen1(2H)-one was prepared following the procedure for the preparation of 1i and using anisole to replace toluene. Compound 1j was obtained in 88% yield (784 mg) following the procedure for the preparation of 1a with 6-methoxy-3,4-dihydronaphthalen-1(2H)-one and (3.4 mmol) dimethyl carbonate as the starting material. White solid; m.p.: 64−65 °C; 1H NMR (400 MHz, CDCl3) enol and keto form, δ 12.39 (s, 0.72H), 8.02 (d, J = 8.0 Hz, 0.23H), 7.79 (d, J = 8.0 Hz, 0.76H), 6.85 (m, 1.15H), 6.79 (m, 0.83H), 3.87 (s, 0.73H), 3.85 (s, 2.32H), 3.81 (s, 2.05H), 3.81 (s, 0.73H), 2.45 (s, 1.62H), 2.06 (dd, J = 13.5, 4.7 Hz, 0.24H), 1.45 (s, 0.77H), 1.35 (s, 0.78H), 1.26 (s, 4.88H); 13C{1H}NMR (100 MHz, CDCl3) enol and keto form, δ 191.9, 173.3, 171.2, 164.8, 164.4, 162.1, 154.0, 150.2, 130.6, 126.7, 123.8, 121.5, 112.2, 110.9, 110.6, 110.4, 93.4, 55.4, 55.3, 52.3, 51.5, 51.2, 40.1, 35.5, 33.9, 33.9, 30.2, 29.6, 28.4; IR (KBr) ν = 2978, 2931, 1733, 1669, 1637, 1609, 1540, 1437, 1382, 1353, 1325, 1284, 1224, 1177, 1156, 1121, 1037, 910, 878, 827, 777, 684 cm−1; HRMS(ESI): calcd. For C15H19O4 [M+H]+ 263.1283, found 263.1288. Methyl 7-Methoxy-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (1k). 7-Methoxy-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one was prepared following the literature procedure.19 Compound 1k was obtained in 79% yield (1.03 g) following the procedure for the preparation of 1a with 7-methoxy-4,4-dimethyl3,4-dihydronaphthalen-1(2H)-one (5 mmol) and dimethyl carbonate as the starting material. White solid; m.p.: 53−54 °C; 1H NMR (400 MHz, CDCl3) δ 12.38 (s, 0.83H), 7.48 (d, J = 2.8 Hz, 0.14H), 7.38 (d, J = 2.8 Hz, 0.87H), 7.34 (m, 0.14H), 7.24 (m, 0.93H), 7.13 (m, 0.12H), 6.94 (m, 0.91H), 3.84 (s, 3H), 3.83 (s, 3H), 2.46 (s, 2H), 1.26 (s, 6H); 13C{1H}NMR (100 MHz, CDCl3) δ 173.3, 164.2, 158.0, 140.1, 129.5, 125.2, 117.5, 109.0, 95.8, 55.4, 51.7, 35.8, 33.2, 28.6. IR (KBr) ν = 2935, 1666, 1621, 1536, 1377, 1234, 1179, 1130, 1072, 831, 772, 580 cm−1; HRMS(ESI): calcd. for C15H19O4 [M+H]+ 263.1283, found 263.1288. Methyl 7-((Methoxycarbonyl) (methyl)amino)-4,4-dimethyl-1oxo-1,2,3,4-tetrahydro-naphthalene-2-carboxylate (1l). A solution of 2.3 g (10.5 mmol) 3,4-dihydro-4,4-dimethyl-7-nitro-1(2H)naphthalenone in 50 mL of EtOAc was stirred at room temperature with 0.23 g of 10% Pd−C under 1 atm of H2 for 24 h. The catalyst was removed by filtration through a pad of Celite, and the filtrate concentrated under reduced pressure to give 7-amino-4,4-dimethyl3,4-dihydronaphthalen-1(2H)-one as a dark green oil. To the solution of crude 7-amino-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one in CH2Cl2 (20 mL) at 0 °C was added AcCl (1.1 mL, 15 mmol) and Et3N (4.3 mL, 30 mmol). The resulting mixture was stirred at 0 °C for 2 h. The resulting mixture was diluted with CH2Cl2 and washed with H2O, dilute HCl, and brine. The organic layer was dried over MgSO4 and concentrated in vacuo to afford the crude N-(5,5-dimethyl-8-oxo5,6,7,8-tetrahydronaphthalen-2-yl)benzamide. Compound 1l was obtained in 80% yield (664 mg) following the procedure for the preparation of 1a with N-(5,5-dimethyl-8-oxo-5,6,7,8-tetrahydronaph-

thalen-2-yl)benzamide (2.6 mmol) and dimethyl carbonate as the starting material. Slightly yellow oil; 1H NMR (400 MHz, CDCl3) δ 12.32 (s, 1H), 7.74 (m, 1H), 7.45−7.26 (m, 2H), 3.83 (s, 3H), 3.71 (s, 3H), 3.31 (s, 3H), 2.47 (s, 2H), 1.28 (s, 6H); 13C{1H}NMR (100 MHz, CDCl3) δ 173.2, 163.7, 156.1, 145.5, 141.5, 129.3, 128.5, 124.6, 121.6, 95.9, 53.0, 51.7, 37.7, 35.5, 33.5, 28.4; IR (KBr) ν = 2981, 1701, 1652, 1623, 1481, 1453, 1351, 1303, 1152, 1066, 769, 669 cm−1; HRMS(ESI): calcd. for C17H22NO5 [M+H]+ 320.1498, found 320.1500. Methyl 7-(N,4-Dimethylphenylsulfonamido)-4,4-dimethyl-1-oxo1,2,3,4-tetrahydro-naphthalene-2-carboxylate (1m). 1,1-Dimethyl1,2,3,4-tetrahydroanthracene was prepared following the literature procedure.20 4,4-Dimethyl-3,4-dihydroanthracen-1(2H)-one was prepared following the literature procedure.21 Compound 1m was obtained in 86% yield (1.21 g) following the procedure for the preparation of 1a with 4,4-dimethyl-3,4-dihydroanthracen-1(2H)-one (5 mmol) and dimethyl carbonate as the starting material. White solid; mp: 88−89 °C. 1H NMR (400 MHz, CDCl3): δ 1.39 (s, 6 H), 2.55 (s, 2 H), 3.86 (s, 3 H), 7.44−7.52 (m, 2 H), 7.71 (s, 1 H), 7.80 (d, J = 8.0 Hz, 1 H), 7.89 (d, J = 8.0 Hz, 1 H), 8.37 (s, 1 H), 12.42 (s, 1 H); 13 C{1H}NMR (100 MHz, CDCl3): δ 28.9, 34.0, 35.8, 51.7, 96.7, 122.4, 125.2, 125.9, 127.0, 127.4, 127.5, 128.8, 131.6, 134.8, 144.4, 164.3, 173.3.; IR (KBr) ν = 2978, 2913, 1711, 1633, 1542, 1379, 1261, 1174, 1048, 977, 815, 742 cm−1; HRMS(ESI): calcd. for C18H19O3 [M+H]+ 283.1334, found 283.1330. Methyl 4′-oxo-3′,4′-Dihydro-2′H-spiro[cyclopentane-1,1′-naphthalene]-3′-carboxylate (1n). 2′H-spiro[cyclopentane-1,1′-naphthalen]-4′(3′H)-one was prepared following the literature procedure.22 Compound 1n was obtained in 78% yield (282 mg) following the procedure for the preparation of 1a with 2′H-spiro[cyclopentane-1,1′naphthalen]-4′(3′H)-one (1.4 mmol) and dimethyl carbonate as the starting material. Slightly yellow oil; 1H NMR (400 MHz, CDCl3) δ 12.35 (s, 0.71H), 8.03 (d, J = 7.6 Hz, 0.18H), 7.86 (d, J = 7.6 Hz, 0.76H), 7.57 (t, J = 7.6 Hz, 0.19H), 7.41 (t, J = 7.6 Hz, 1.02H), 7.31 (t, J = 14.0 Hz, 1.88H), 3.85 (s, 3H), 2.56 (s, 2H), 2.03−1.68 (m, 8H); 13 C{1H}NMR (100 MHz, CDCl3) δ 193.5, 173.2, 171.0, 165.1, 152.1, 147.6, 134.3, 131.0, 129.0, 127.5, 126.4, 126.3, 126.0, 124.7, 124.0, 96.1, 52.4, 52.3, 51.6, 45.5, 45.3, 41.8, 40.4, 38.4, 38.3, 33.7, 25.7, 25.5, 24.9; IR (KBr) ν = 2965, 2927, 1662, 1632, 1600, 1457, 1420, 1318, 1277, 1230, 1149, 977, 758, 702 cm−1; HRMS(ESI): calcd. for C16H19O3 [M+H]+ 259.1334, found 259.1332. Methyl 4,4-Dimethyl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-6-carboxylate (1o). 4,4-Dimethyl-5,6-dihydrobenzo[b]thiophen-7(4H)-one was prepared following the literature procedure.23 Compound 1o was obtained in 87% yield (1.04 g) following the procedure for the preparation of 1a with 4,4-dimethyl-5,6dihydrobenzo[b]thiophen-7(4H)-one (5 mmol) and dimethyl carbonate as the starting material. Slightly yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 4.8 Hz, 1H), 7.04 (d, J = 4.8 Hz, 1H), 3.81 (dd, J = 13.2, 4.8 Hz, 1H), 3.80 (s, 3H), 2.53 (t, J = 13.2 Hz, 1H), 2.10 (dd, J = 13.2, 4.8 Hz, 1H), 1.42 (s, 3H), 1.33 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 186.6, 170.8, 160.5, 135.6, 134.0, 126.1, 52.4, 51.8, 41.7, 33.9, 29.7, 28.2; IR (KBr) ν = 2967, 1760, 1676, 1462, 1429, 1342, 1290, 1236, 1150, 1060, 974, 770, 671 cm−1; HRMS(ESI): calcd. for C12H15O3S [M+H]+ 239.0742, found 239.0746. Ethyl 5,5-Dimethyl-2-oxocyclohex-3-enecarboxylate (1p). 4,4Dimethylcyclohex-2-enone was prepared following the literature procedure.24 Compound 1p was obtained in 76% yield (1.5 g) following the procedure for the preparation of 1h with 4,4dimethylcyclohex-2-enone (10 mmol) as the starting material. Slightly yellow oil; 1H NMR (400 MHz, CDCl3) keto form, δ 6.67 (dd, J = 8.4, 1.6 Hz, 1H), 5.87 (dd, J = 10.0, 1.6 Hz, 1H), 4.29−4.16 (m, 2H), 3.53 (m, 1H), 2.31 (m, 2H), 1.30 (t, J = 7.0 Hz, 3H), 1.31 (s, 3H), 1.20 (s, 3H), enol form, δ 11.95 (s, 1H), 6.04 (d, J = 9.8 Hz, 1H), 5.83 (dd, J = 9.8, 1.5 Hz, 1H), 4.34−4.14 (m, 2H), 1.98 (m, 2H), 1.33−1.26 (t, J = 7.0 Hz, 3H), 1.05 (s, 6H); 13C{1H}NMR (100 MHz, CDCl3) keto and enol form, δ 194.0, 170.4, 159.5, 149.6, 126.0, 121.2, 61.2, 60.2, 50.8, 38.9, 34.4, 33.0, 32.5, 30.0, 27.7, 25.7, 14.3, 14.1; IR (KBr) ν = 2975, 2938, 2851, 1774, 1722, 1680, 1638, 1584, 1542, 1488, 1435, 1389, 1340, 1278, 1240, 1211, 1183, 1152, 1068, 1025, 944, 878, 825, 751, 11697

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702

Article

The Journal of Organic Chemistry 689, 662, 556, 488 cm−1, HRMS(ESI): calcd. for C11H17O3 [M+H]+ 197.1178, found 197.1180. Ethyl 3-Methoxy-5,5-dimethyl-2-oxocyclohex-3-enecarboxylate (1q). To an ice-cold solution of 4,4-dimethyl-cyclohex-2-enone (1.00 g, 8.05 mmol) in methanol (8 mL) was added 35% hydrogen peroxide (3.5 mL, 40.86 mmol) followed by 0.5 N NaOH (2.2 mL, 1.1 mmol). The mixture was stirred at 0 °C for 1 h, stored in a freezer (−15 °C) overnight and then stirred at 0 °C for another 6 h. After this time, water (15 mL) was added, and the mixture was extracted with dichloromethane (30 mL × 9). The organic layers were combined, washed with 10% Na2SO3 (40 mL × 2) and brine, dried over Na2SO4, filtered, and concentrated at reduced pressure to afford 5,5-dimethyl-7oxabicyclo[4.1.0]heptan-2-one as a colorless oil. To a solution of KOH (0.49 g, 7.4 mmol) in methanol (15 mL) was added a solution of 5,5dimethyl-7-oxabicyclo[4.1.0]heptan-2-one (1.04 g, 7.42 mmol) in methanol (5 mL). The mixture was stirred overnight at room temperature and then heated at reflux for 20 min. After cooling to room temperature, water (40 mL) was added, and the mixture was extracted with diethyl ether (20 mL × 3). The organics were combined, washed with brine, dried over Na2SO4, filtered, and concentrated at reduced pressure. The residue was stirred with hexane for 30 min. The resulting solid was removed by filtration, and the filtrate was concentrated at reduced pressure to afford 2-methoxy-4, 4dimethyl-cyclohex-2-enone as an oil. Compound 1q was obtained in 54% yield (268 mg) following the procedure for the preparation of 1h with 2-methoxy-4,4-dimethyl-cyclohex-2-enone (2.2 mmol) as the starting material. Slightly yellow oil; 1H NMR (400 MHz, CDCl3) enol and keto form, δ 12.36 (s, 0.08H), 5.56 (s, 0.87H), 4.92 (s, 0.08H), 4.21 (dd, J = 8.0, 4.0 Hz, 2H), 3.63−3.57 (m, 1H), 3.56 (d, J = 4.0 Hz, 3H), 2.26 (t, J = 16.0 Hz, 1H), 1.94 (d, J = 12.0 Hz, 1H), 1.28 (dd, J = 12.0, 8.0 Hz, 3H), 1.20 (s, 5.52H), 1.06 (s, 0.65H); 13 C{1H}NMR (100 MHz, CDCl3) enol and keto form, δ 188.8, 170.0, 161.3, 148.6, 126.1, 115.1, 61.2, 60.5, 55.0, 51.2, 39.0, 34.7, 32.1, 31.5, 28.9, 27.2, 14.2, 14.1. IR (KBr) ν = 2967, 1768, 1674, 1488, 1410, 1324, 1281, 1248, 1188, 1060, 977, 768, 671 cm−1; HRMS(ESI): calcd. for C12H19O4 [M+H]+ 227.1283, found 227.1288. Ethyl 8-oxo-1,4-Dioxaspiro[4.5]dec-9-ene-7-carboxylate (1r). To the solution of cyclohexane-1,4-dione (5.6 g, 50 mmol) in benzene (25 mL) was added ethylene glycol (4.03g, 65 mmol) and p-TsOH (855 mg, 4.5 mmol) and the solution was refluxed for 15 h. After the solution was cooled to rt, benzene was removed at reduced pressure and the crude product was diluted with EtOAc and washed with NaOH. The organic layer was dried with over Na2SO4, filtered, and concentrated at reduced pressure to give crude 1,4-dioxaspiro[4.5]decan-8-one. At −5 °C, to a solution of crude 1,4-dioxaspiro[4.5]decan-8-one (1.34g, 8.6 mmol) in CH2Cl2 (70 mL) was added Et3N (3.6 mL, 25.7 mmol) followed by adding a solution of TMSOTf (1.72 mL, 9.46 mmol) in CH2Cl2 (20 mL). The mixture was stirred at −5 °C for 1 h. The resulting mixture was diluted with CH2Cl2 (100 mL) and washed with saturated NaHCO3 (10 mL). The organic layer was dried with over Na2SO4, filtered, and concentrated at reduced pressure to give crude (1,4-dioxaspiro[4.5]dec-7-en-8-yloxy)trimethylsilane. To the solution of resulted crude (1,4-dioxaspiro[4.5]dec-7-en-8-yloxy)trimethylsilane in CH3CN was added Pd(OAc)2 (1.49 g 6.7 mmol). The mixture was stirred at rt for 12 h. The resulting mixture was filtered, and concentrated at reduced pressure to give crude 1,4dioxaspiro[4.5]dec-6-en-8-one. Compound 1r was obtained in 61% yield (414 mg) following the procedure for the preparation of 1h with 1,4-dioxaspiro[4.5]dec-6-en-8-one (3 mmol) as the starting material. Slightly yellow oil; 1H NMR (400 MHz, CDCl3) enol and keto form, δ 11.89 (s, 0.38H), 6.62 (d, J = 12.0 Hz, 0.55H), 6.12 (q, J = 8.0 Hz, 0.82H), 6.04 (d, J = 8.0 Hz, 0.51H), 4.23 (m, 2H), 4.13−3.94 (m, 4H), 3.72 (m, 0.55H), 2.79 (s, 0.85H), 2.62 (t, J = 12.4 Hz, 0.6H), 2.31 (m, 0.59H), 1.30 (m 3H); 13C{1H}NMR (100 MHz, CDCl3) enol and keto form, δ 193.6, 171.6, 169.2, 163.2, 146.5, 136.2, 129.7, 126.4, 105.1, 103.3, 94.4, 65.4, 65.1, 64.7, 61.4, 60.6, 51.8, 35.8, 31.9, 14.2, 14.1; IR (KBr) ν = 3055, 2983, 2921, 2848, 2832, 1778, 1679, 1628, 1598, 1556, 1494, 1463, 1374, 1324, 1281, 1250, 1150, 1033, 977, 873, 766, 688, 559 cm−1; HRMS(ESI): calcd. for C11H15O5 [M +H]+ 227.0919, found 227.0922.

Methyl 5,5-Dimethyl-2-oxocyclohexanecarboxylate (1s). Compound 1s was prepared following the literature procedure in 78% yield (9.6 g).24 colorless oil; 1H NMR (400 MHz, CDCl3) δ 12.14 (s, 1H), 3.75 (s, 3H), 2.29 (t, J = 8.0 Hz, 2H), 2.03 (s, 2H), 1.44 (t, J = 8.0 Hz, 2H), 0.95 (s, 6H); 13C{1H}NMR (100 MHz, CDCl3) δ 173.2, 171.2, 96.3, 51.3, 36.1, 34.3, 28.9, 27.8, 26.5. 2-Acetyl-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one (1t). Under N2, to the solution of 4,4-dimethyl-3,4-dihydronaphthalen1(2H)-one (870 mg, 5 mmol) in Ac2O (1.8 mL) was added BF3·Et2O (0.9 mL, 1.56 mmol). The resulting mixture was heated at 60 °C for 2 h followed by reflux for 1.5 h. The resulting mixture was cooled to rt and filtered. The resulting solid was washed by Et2O and dissolved in acetone (10 mL). A solution of 10% NaOAc (10 mL) was added to the above solution and the mixture was stirred at reflux for 24 h. The mixture was cooled to rt and extracted with EtOAc (50 mL × 3). The combined organic layer was dried with MgSO4 and concentrated in vacuo. The residue was purified by column chromatography to give the compound 1t in 78% yield (842 mg). Yellow solid, m.p.: 52−54 °C; 1 H NMR (400 MHz, CDCl3) δ 16.32 (s, 1H), 7.99−7.97 (d, 8.0 Hz, 1H), 7.48−7.46 (d, 8.0 Hz, 1H), 7.37−7.30 (m, 2H), 2.52 (s, 2H), 2.23 (s, 3H), 1.32 (s, 6H); 13C{1H}NMR (100 MHz, CDCl3)193.5, 176.8, 149.2, 132.5, 129.7, 126.4, 126.3, 124.0, 104.7, 37.9, 34.1, 28.8, 23.7. IR (KBr) ν = 2933, 1612, 1582, 1445, 1288, 1266, 963, 870, 758 cm−1; HRMS(ESI): calcd. for C14H17O2 [M+H]+ 217.1229, found 217.1232. Typical Procedure for Synthesis of Epoxide Functionality Directly from Carbon−Carbon Single Bond. To the solution of 1a (69.6 mg, 0.3 mmol) in PEG400 and water (4 mL, v/v = 1/1) was added AIBX (151 mg, 0.45 mmol). The reaction mixture was heated to 90 °C with stirring and monitored by TLC. After 1a was completely consumed, the reaction mixture was allowed to cool to room temperature and extracted with EtOAc (50 mL × 3). The organic layer was combined and washed with brine and dried over anhydrous MgSO4. The solvent was evaporated and the residue was purified by column chromatography to provide product 2a in 83% yield (68 mg). Characterization of the Products. Methyl 7,7-Dimethyl-2-oxo1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene-1a-carboxylate (2a). 83%, 68 mg; colorless oil; 1H NMR (CDCl3, 400 MHz) δ 8.01(dd, J = 1.2 Hz, 8.0 Hz, 1H), 7.59−7.63 (m, 1H), 4.35−7.40 (m, 2H), 3.91 (s, 3H), 3.68 (s, 1H), 1.68 (s, 3H), 1.38 (s, 3H); 13C{1H}NMR (CDCl3, 100 MHz) δ 189.0, 165.8, 146.5, 134.8, 128.2, 127.8, 127.3, 126.2, 67.1, 60.0, 53.0, 35.6, 30.3, 25.2. IR (KBr) ν = 2963, 1760, 1688, 1484, 1434, 1329, 1263, 1222, 1131, 1018, 903, 836, 775, 724, 634 cm−1; HRMS(ESI): calcd. for C14H15O4 [M+H]+ 247.0970, found 247.0972. Methyl 2-Hydroxy-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (3a). 8%, 6 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.02 (dd, J = 8.0, 1.2 Hz, 1H), 7.65−7.55 (m, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.39−7.30 (m, 1H), 4.21 (s, 1H), 3.76 (s, 3H), 2.66 (d, J = 16.0 Hz, 1H), 2.15 (d, J = 12.0 Hz, 1H), 1.45 (s, 3H), 1.39 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.9, 172.6, 151.9, 134.8, 129.0, 128.2, 126.7, 126.2, 76.9, 53.1, 45.5, 33.5, 32.9, 30.6; IR (KBr) ν = 3524, 2937, 1748, 1685, 1574, 1259, 1162, 1101, 924, 833 cm−1; HRMS(ESI): calcd. for C14H17O4 [M+H]+ 249.1127, found 249.1123. Methyl 5-Bromo-7,7-dimethyl-2-oxo-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene-1a-carboxylate (2b). 79%, 76.8 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.4 Hz, 1H), 7.54− 7.49 (m, 2H), 3.91 (s, 3H), 3.67 (s, 1H), 1.66 (s, 3H), 1.38 (s, 3H); 13 C{1H}NMR (100 MHz, CDCl3) δ 188.2, 165.5, 148.2, 130.8, 130.2, 129.8, 129.5, 126.7, 66.9, 59.8, 53.1, 35.7, 30.1, 25.1; IR (KBr) ν = 2961, 1751, 1697, 1587, 1479, 1442, 1398, 1313, 1237, 1165, 1092, 1042, 938, 796, 736 cm−1; HRMS(ESI): calcd. for C14H14BrO4 [M +H]+ 325.0075, found 325.0080. Methyl 6-Bromo-2-hydroxy-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (3b). 12%, 11.7 mg; colorless oil; 1 H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.4 Hz, 1H), 7.59 (s, 1H), 7.48 (d, J = 8.4 Hz, 1H), 4.17 (s, 1H), 3.76 (s, 3H), 2.63 (d, J = 14.4 Hz, 1H), 2.14 (d, J = 14.4 Hz, 1H), 1.44 (s, 3H), 1.39 (s, 3H); 13 C{1H}NMR (100 MHz, CDCl3) δ 194.0, 172.4, 153.6, 130.4, 130.3, 11698

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702

Article

The Journal of Organic Chemistry

35.6, 30.1, 25.0. IR (KBr) ν = 2936, 1777, 1687, 1455, 1328, 1279, 1129, 890, 833, 777, 720 cm−1; HRMS(ESI): calcd. for C14H14BrO4 [M+H]+ 325.0075, found 325.0079. Ethyl 7-Bromo-2-hydroxy-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (3f). 8%, 7.8 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 2.2 Hz, 1H), 7.68 (dd, J = 8.0, 4.0 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 3.95 (s, 1H), 3.76 (s, 3H), 2.62 (d, J = 16.0 Hz, 1H), 2.14 (d, J = 12.0 Hz, 1H), 1.43 (s, 3H), 1.37 (s, 3H). 13 C{1H}NMR (100 MHz, CDCl3) δ 193.6, 172.3, 150.7, 137.5, 130.7, 130.6, 128.2, 120.8, 76.9, 53.3, 45.2, 33.4, 32.7, 30.5; IR (KBr) ν = 3520, 2946, 1751, 1688, 1428, 1360, 1321, 1291, 1203, 1079, 1055, 862, 774, 711 cm−1; HRMS(ESI): calcd. for C14H16BrO4 [M+H]+ 327.0232, found 327.0235. Methyl 4-iodo-7,7-Dimethyl-2-oxo-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene-1a-carboxylate (2g). 77%, 85.9 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.30 (s, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H), 3.91 (s, 3H), 3.67 (s, 1H), 1.65 (s, 3H), 1.36 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 187.6, 165.4, 145.9, 143.3, 136.7, 129.4, 128.2, 92.3, 66.9, 59.8, 53.1, 35.6, 30.0, 24.9. IR (KBr) ν = 2960, 1755, 1692, 1584, 1476, 1440, 1398, 1313, 1237, 1164, 1097, 1063, 991, 931, 790, 731, 715 cm−1; HRMS(ESI): calcd. for C14H14IO4 [M+H]+ 372.9937, found 372.9933. Methyl 2-Hydroxy-7-iodo-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (3g). 11%, 12.3 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.21 (d, J = 8.4 Hz, 1H), 4.16 (s, 1H), 3.78 (s, 3H), 2.63 (d, J = 14.4 Hz, 1H), 2.15 (d, J = 14.4 Hz, 1H), 1.44 (s, 3H), 1.38 (s, 3H); 13 C{1H}NMR (100 MHz, CDCl3) δ 193.5, 172.4, 151.3, 143.2, 136.8, 130.7, 128.3, 91.8, 76.9, 53.3, 45.2, 33.5, 32.7, 30.5; IR (KBr) ν = 3468, 2958, 1754, 1688, 1574, 1468, 1422, 1388, 1331, 1248, 1195, 1155, 1054, 857, 790, 742 cm−1; HRMS(ESI): calcd. for C14H16IO4 [M+H]+ 375.0093, found 375.0095. Ethyl 7,7-Dimethyl-4-nitro-2-oxo-7,7a-dihydronaphtho[2,3-b]oxirene-1a(2H)-carboxylate (2h). 62%, 56.9 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.82 (d, J = 2.4 Hz, 1H), 8.42 (dd, J = 8.0, 4.0 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 4.49−4.30 (m, 2H), 3.74 (s, 1H), 1.73 (s, 3H), 1.43 (s, 3H), 1.38 (t, J = 8.0 Hz, 3H). 13 C{1H}NMR (100 MHz, CDCl3) δ 187.2, 164.4, 152.7, 147.1, 129.2, 128.4, 128.1, 123.4, 66.9, 62.6, 59.8, 36.4, 29.8, 25.1, 14.1; IR (KBr) ν = 2935, 1759, 1688, 1469, 1336, 1263, 1218, 1125, 1095, 829, 762, 729, 592 cm−1; HRMS(ESI): calcd. for C15H16NO6 [M+H]+ 306.0978, found 306.0982. Ethyl 2-Hydroxy-4,4-dimethyl-7-nitro-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (3h). 12%, 11.1 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.83 (d, J = 4.0 Hz, 1H), 8.41 (dd, J = 8.0, 4.0 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 4.27 (m, 2H), 4.16 (s, 1H), 2.66 (d, J = 12.0 Hz, 1H), 2.20 (d, J = 14.0 Hz, 1H), 1.51 (s, 3H), 1.48 (s, 3H), 1.26 (t, J = 8.0 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 192.8, 171.7, 158.3, 146.8, 130.2, 128.3, 128.0, 123.4, 76.8, 63.0, 44.6, 34.3, 32.6, 30.8, 13.9; IR (KBr) ν = 3438, 2936, 1739, 1666, 1393, 1313, 1254, 1184, 1029, 852, 694 cm−1; HRMS(ESI): calcd. for C15H18NO6 [M+H]+ 308.1134, found 308.1130. Methyl 5,7,7-Trimethyl-2-oxo-1a,2,7,7a-tetrahydronaphtho[2,3b]oxirene-1a-carboxylate (2i). 81%, 63.2 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.4 Hz, 1H), 7.17 (m, 2H), 3.90 (s, 3H), 3.65 (s, 1H), 2.41 (s, 3H), 1.66 (s, 3H), 1.36 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 188.5, 165.9, 146.5, 145.8, 128.2, 128.2, 126.7, 125.3, 67.1, 59.9, 52.9, 35.4, 30.2, 25.1, 22.0; IR (KBr) ν = 2972, 2929, 1750, 1686, 1600, 1456, 1339, 1297, 1233, 1160, 982, 919, 788, 718 cm−1; HRMS(ESI): calcd. for C15H17O4 [M +H]+ 261.1127, found 261.1129. Methyl 2-Hydroxy-4,4,7-trimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (3i). 9%, 7.1 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.0 Hz, 1H), 7.23 (s, 1H), 7.17 (d, J = 8.0 Hz, 1H), 4.18 (s, 1H), 3.76 (s, 3H), 2.65 (d, J = 14.4 Hz, 1H), 2.43 (s, 3H), 2.14 (d, J = 14.4 Hz, 1H), 1.44 (s, 3H), 1.39 (s, 3H); 13 C{1H}NMR (100 MHz, CDCl3) δ 194.5, 172.7, 152.0, 145.8, 128.3, 127.9, 126.7, 126.6, 76.9, 53.1, 45.6, 33.4, 32.9, 30.6, 22.1; IR (KBr) ν = 3585, 2947, 1758, 1685, 1587, 1497, 1447, 1388, 1314, 1158, 1080,

129.9, 129.5, 127.9, 76.8, 53.2, 45.2, 33.6, 32.8, 30.5; IR (KBr) ν = 3529, 2955, 1755, 1671, 1547, 1497, 1432, 1377, 1308, 1237, 1146, 1088, 947, 786, 716 cm−1; HRMS(ESI): calcd. for C14H16BrO4 [M +H]+ 327.0232, found 327.0238. Ethyl 7,7-Dimethyl-2-oxo-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene-1a-carboxylate (2c). 83%, 64.7 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.01 (dd, J = 8.0, 1.2 Hz, 1H), 7.65−7.56 (m, 1H), 7.43−7.32 (m, 2H), 4.38 (m, 2H), 3.67 (s, 1H), 1.68 (s, 3H), 1.37 (t, J = 7.2 Hz, 3H), 1.38 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 189.1, 165.4, 146.6, 134.7, 128.1, 127.9, 127.2, 126.2, 67.1, 62.2, 60.1, 35.6, 30.2, 25.2, 14.1; IR (KBr) ν = 2928, 1758, 1697, 1490, 1428, 1315, 1260, 1220, 1125, 1010, 925, 830, 768, 729 cm−1; HRMS(ESI): calcd. for C15H17O4 [M+H]+ 261.1127, found 261.1122. Ethyl 2-Hydroxy-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (3c). 8%, 6.3 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.02 (dd, J = 8.0, 1.2 Hz, 1H), 7.60 (td, J = 8.0, 1.2 Hz, 1H), 7.45 (d, J = 7.6 Hz, 1H), 7.38−7.30 (m, 1H), 4.28−4.19 (m, 2H), 4.18 (s, 1H), 2.66 (d, J = 14.4 Hz, 1H), 2.14 (d, J = 14.4 Hz, 1H), 1.46 (s, 3H), 1.41 (s, 3H), 1.23 (t, J = 7.2 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.9, 172.2, 151.9, 134.7, 129.2, 128.1, 126.7, 126.1, 76.9, 62.4, 45.4, 33.5, 33.0, 30.8, 13.9; IR (KBr) ν = 3328, 2952, 1759, 1689, 1450, 1355, 1308, 1281, 1233, 1128, 1022, 830, 788, 733 cm−1; HRMS(ESI): calcd. for C15H19O4 [M+H]+ 263.1283, found 263.1285. Methyl 4-Fluoro-7,7-dimethyl-2-oxo-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene-1a-carboxylate (2d). 79%, 62.6 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.8 Hz, 1H), 7.44− 7.36 (m, 1H), 7.32 (t, J = 8.4 Hz, 1H), 3.92 (s, 3H), 3.69 (s, 1H), 1.67 (s, 3H), 1.37 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 187.9, 165.5, 161.5 (d, J = 246.7 Hz), 142.3, 129.7, 128.5 (d, J = 7.3 Hz), 122.1 (d, J = 21.8 Hz), 114.1 (d, J = 22.4 Hz), 67.1, 59.8, 53.1, 35.4, 30.3, 25.3. IR (KBr) ν = 2959, 1755, 1692, 1494, 1443, 1322, 1263, 1205, 1145, 1002, 910, 836, 774 cm−1; HRMS(ESI): calcd. for C14H14FO4 [M+H]+ 265.0876, found 265.0879. Methyl 7-Fluoro-2-hydroxy-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (3d). 11%, 8.8 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.66 (dd, J = 8.8, 2.8 Hz, 1H), 7.44 (dd, J = 8.8, 5.2 Hz, 1H), 7.30 (td, J = 8.4, 2.8 Hz, 1H), 4.18 (s, 1H), 3.77 (s, 3H), 2.63 (d, J = 14.4 Hz, 1H), 2.15 (d, J = 14.4 Hz, 1H), 1.44 (s, 3H), 1.38 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 193.8, 172.5, 161.2 (d, J = 245.9 Hz), 147.8, 130.7, 128.4 (d, J = 7.1 Hz), 122.1 (d, J = 22.0 Hz), 113.8 (d, J = 22.1 Hz), 53.2, 45.4, 33.3, 32.9, 30.8; IR (KBr) ν = 3436, 2944, 1758, 1688, 1472, 1384, 1300, 1254, 1203, 1131, 1008, 836, 756 cm−1; HRMS(ESI): calcd. for C14H16FO4 [M+H]+ 267.1033, found 267.1038. Methyl 4-Chloro-7,7-dimethyl-2-oxo-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene-1a-carboxylate (2e). 81%, 68.1 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 2.4 Hz, 1H), 7.55 (dd, J = 8.8, 2.4 Hz, 1H), 7.34 (d, J = 8.8 Hz, 1H), 3.91 (s, 3H), 3.68 (s, 1H), 1.65 (s, 3H), 1.36 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 187.8, 165.4, 144.8, 134.7, 133.6, 129.2, 128.0, 127.7, 67.0, 59.9, 53.1, 35.5, 30.1, 25.1. IR (KBr) ν = 2935, 1759, 1688, 1469, 1336, 1292, 1125, 940, 829, 762, 729, 592 cm−1; HRMS(ESI): calcd. for C14H14ClO4 [M+H]+ 281.0581, found 281.0586. Ethyl 7-Chloro-2-hydroxy-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (3e). 11%, 9.3 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 2.4 Hz, 1H), 7.51 (dd, J = 8.0, 2.4 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 4.28 (s, 1H), 3.74 (s, 3H), 2.60 (d, J = 12.0 Hz, 1H), 2.12 (d, J = 12.0 Hz, 1H), 1.41 (s, 3H), 1.35 (s, 3H). 13 C{1H}NMR (100 MHz, CDCl3) δ 193.5, 172.3, 150.1, 134.5, 132.8, 130.3, 127.9, 127.5, 76.9, 53.1, 45.1, 33.3, 32.6, 30.5; IR (KBr) ν = 3490, 2955, 1748, 1679, 1433, 1349, 1310, 1260, 1088, 852, 764, 705 cm−1; HRMS(ESI): calcd. for C14H16ClO4 [M+H]+ 283.0737, found 283.0733. Methyl 4-Bromo-7,7-dimethyl-2-oxo-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene-1a-carboxylate (2f). 83%, 80.7 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 1.6 Hz, 1H), 7.71 (dd, J = 8.4, 1.6 Hz, 1H), 7.28 (d, J = 8.4 Hz, 1H), 3.92 (s, 3H), 3.69 (s, 1H), 1.66 (s, 3H), 1.37 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 187.7, 165.4, 145.3, 137.5, 130.8, 129.5, 128.2, 121.4, 67.0, 59.9, 53.1, 11699

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702

Article

The Journal of Organic Chemistry 987, 766, 710 cm−1; HRMS(ESI): calcd. for C15H19O4 [M+H]+ 263.1283, found 263.1287. Methyl 5-Methoxy-7,7-dimethyl-2-oxo-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene-1a-carboxylate (2j). 88%, 72.9 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.8 Hz, 1H), 6.87 (d, J = 8.4 Hz, 1H), 6.82 (s, 1H), 3.89 (s, 3H), 3.86 (s, 3H), 3.63 (s, 1H), 1.64 (s, 3H), 1.36 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 187.5, 166.1, 164.9, 149.0, 130.8, 121.0, 112.5, 111.8, 67.0, 59.8, 55.5, 52.9, 35.7, 30.2, 25.2; IR (KBr) ν = 2956, 1754, 1692, 1492, 1440, 1321, 1251, 1207, 1148, 1061, 893, 834, 786 cm−1; HRMS(ESI): calcd. for C15H17O5 [M+H]+ 277.1076, found 277.1083. Methyl 4-Methoxy-7,7-dimethyl-2-oxo-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene-1a-carboxylate (2k). 83%, 68.7 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 2.9 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.17 (dd, J = 8.0, 4.0 Hz, 1H), 3.91 (s, 3H), 3.83 (s, 3H), 3.66 (s, 1H), 1.63 (s, 3H), 1.35 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 188.8, 165.9, 158.5, 139.1, 128.7, 127.7, 122.9, 110.1, 67.2, 60.0, 55.5, 53.0, 35.1, 30.3, 25.3; IR (KBr) ν = 2958, 1758, 1699, 1558, 1425, 1382, 1319, 1208, 1184, 1077, 907, 820, 739, 709 cm−1; HRMS(ESI): calcd. for C15H17O5 [M+H]+ 277.1076, found 277.1071. Methyl 2-Hydroxy-7-methoxy-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate (3k). 6%, 5.0 mg; colorless oil; 1 H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 2.8 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.17 (dd, J = 8.4, 2.8 Hz, 1H), 4.23 (s, 1H), 3.83 (s, 3H), 3.75 (s, 3H), 2.62 (d, J = 14.4 Hz, 1H), 2.13 (d, J = 14.4 Hz, 1H), 1.41 (s, 3H), 1.35 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 192.8, 171.7, 146.6, 134.8, 128.2, 127.9, 126.2, 76.8, 63.0, 59.4, 41.1, 33.1, 32.9, 30.4; IR (KBr) ν = 3327, 3053, 1728, 1707, 1591, 1489, 1259, 1058, 1029, 941, 860 cm−1; HRMS(ESI): calcd. for C15H19O5 [M+H]+ 279.1232, found 279.1230. Methyl 4-((Methoxycarbonyl) (methyl)amino)-7,7-dimethyl-2oxo-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene-1a-carboxylate (2l). 68%, 67.9 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 2.4 Hz, 1H), 7.56 (s, 1H), 7.36 (d, J = 8.8 Hz, 1H), 3.90 (s, 3H), 3.71 (s, 3H), 3.68 (s, 1H), 3.30 (s, 3H), 1.66 (s, 3H), 1.38 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 188.3, 165.6, 155.7, 143.8, 142.4, 132.1, 128.3, 127.0, 123.7, 67.1, 59.9, 53.0, 53.0, 37.3, 35.4, 30.1, 25.1. IR (KBr) ν = 2981, 2961, 1777, 1701, 1681, 1610, 1497, 1445, 1361, 1303, 1260, 1062, 1020, 920, 792, 634 cm−1; HRMS(ESI): calcd. for C17H20NO6 [M+H]+ 334.1291, found, 334.1285. Methyl 9,9-Dimethyl-2-oxo-1a,2,9,9a-tetrahydroanthra[2,3-b]oxirene-1a-carboxylate (2m). 75%, 66.6 mg; colorless oil; 1H NMR (400 MHz, CDCl3): δ 1.42 (s, 3 H), 1.82 (s, 3 H), 3.76 (s, 1 H), 3.94 (s, 3 H), 7.51 (td, J = 8.4, 1.2 Hz, 1 H), 7.60 (td, J = 8.4, 1.2 Hz, 1 H), 7.81 (s, 1 H), 7.84 (d, J = 8.0 Hz, 1 H), 7.96 (d, J = 8.4 Hz, 1 H), 8.58 (s, 1 H); 13C{1H}NMR (100 MHz, CDCl3): δ 25.4, 30.7, 35.8, 53.0, 60.4, 67.4, 125.2, 126.4, 126.7, 127.5, 129.0, 129.6, 130.2, 131.5, 136.4, 141.5, 165.8, 189.5; IR (KBr) ν = 2977, 1758, 1682, 1600, 1528, 1450, 1343, 1286, 1210, 1148, 921, 787, 701 cm−1; HRMS(ESI): calcd. for C18H17O4 [M+H]+ 297.1127, found 297.1120. Methyl 7′-oxo-7′,7a′-Dihydro-1a′H-spiro[cyclopentane-1,2′naphtho[2,3-b]oxirene]-7a′-carboxylate (2n). 86%, 70.2 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 7.2 Hz, 1H), 7.59 (t, J = 7.2 Hz, 1H), 7.34 (d, J = 6.0 Hz, 2H), 3.90 (s, 3H), 3.73 (s, 1H), 2.38 (m, 2H), 2.14−1.98 (m, 3H), 1.89 (m, 2H), 1.75 (m, 1H); 13 C{1H}NMR (100 MHz, CDCl3) δ 189.0, 166.0, 147.1, 134.8, 128.4, 127.7, 126.9, 126.5, 66.0, 60.3, 53.0, 46.2, 42.0, 38.5, 26.7, 25.9; IR (KBr) ν = 2956, 1755, 1685, 1601, 1455, 1409, 1333, 1296, 1239, 1161, 934, 789, 715 cm−1; HRMS(ESI): calcd. for C16H17O4 [M+H]+ 273.1127, found 273.1118. Methyl 6,6-Dimethyl-2-oxo-1a,2,6,6a-tetrahydrothieno[2′,3′:4,5]benzo[1,2-b]oxirene-1a-carboxylate (2o). 80%, 60.5 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 5.2 Hz, 1H), 7.02 (d, J = 5.2 Hz, 1H), 3.88 (s, 3H), 3.59 (s, 1H), 1.58 (s, 3H), 1.40 (s, 3H); 13 C{1H}NMR (100 MHz, CDCl3) δ 181.6, 165.9, 155.0, 136.3, 131.1, 126.5, 67.7, 59.7, 53.0, 35.9, 29.0, 25.0. IR (KBr) ν = 2968, 1755, 1668, 1474, 1440, 1336, 1278, 1248, 1162, 1060, 913, 778, 680 cm−1; HRMS(ESI): calcd. for C12H13O4S [M+H]+ 253.0535, found 253.0533.

Ethyl 5,5-Dimethyl-2-oxo-7-oxabicyclo[4.1.0]hept-3-ene-1-carboxylate (2p). 59%, 37.2 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 6.38 (dd, J = 10.4, 2.4 Hz, 1H), 5.88 (dd, J = 10.4, 2.4 Hz, 1H), 4.39−4.24 (m, 2H), 3.56−3.43 (m, 1H), 1.37−1.27 (m, 9H); 13 C{1H}NMR (100 MHz, CDCl3) δ 188.8, 165.5, 153.9, 123.3, 66.0, 62.2, 58.7, 35.0, 26.4, 24.4, 14.0. IR (KBr) ν = 2961, 1763, 1685, 1493, 1342, 1234, 1151, 1088, 1005, 935, 880, 809, 637, 602 cm−1; HRMS(ESI): calcd. for C11H15O4 [M+H]+ 211.0970, found 211.0977. Ethyl 1-Hydroxy-5,5-dimethyl-2-oxocyclohex-3-enecarboxylate (3p). 19%, 12.1 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 6.74 (d, J = 10.4 Hz, 1H), 6.01 (d, J = 10.4 Hz, 1H), 4.38−4.14 (m, 2H), 4.02 (d, J = 0.4 Hz, 1H), 2.50 (d, J = 14.4 Hz, 1H), 1.98 (dd, J = 14.4, 0.8 Hz, 1H), 1.34−1.23 (m, 6H), 1.17 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.5, 172.2, 160.6, 124.0, 76.2, 62.4, 44.2, 33.4, 29.9, 29.2, 13.9; IR (KBr) ν = 3562, 2988, 1749, 1679, 1483, 1327, 1243, 1115, 1088, 1015, 935, 877, 635 cm−1; HRMS(ESI): calcd. for C11H17O4 [M+H]+ 213.1127, found 213.1121. Ethyl 3-Methoxy-5,5-dimethyl-2-oxo-7-oxabicyclo[4.1.0]hept-3ene-1-carboxylate (2q). 63%, 45.4 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 5.27 (d, J = 2.3 Hz, 1H), 4.39−4.22 (m, 2H), 3.57 (s, 3H), 3.46 (d, J = 2.3 Hz, 1H), 1.31 (m, 9H); 13C{1H}NMR (100 MHz, CDCl3) δ 184.0, 164.9, 146.6, 120.7, 65.8, 62.2, 59.5, 55.1, 34.3, 28.3, 25.8, 14.0, IR (KBr) ν = 2967, 2929, 1752, 1697, 1498, 1444, 1325, 1255, 1207, 1142, 1067, 907, 837, 744 cm−1; HRMS(ESI): calcd. for C12H17O5 [M+H]+ 241.1076, found 241.1080. Ethyl 1-Hydroxy-3-methoxy-5,5-dimethyl-2-oxocyclohex-3-enecarboxylate (3q). 21%, 15.2 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 5.67 (s, 1H), 4.25 (m, 2H), 4.02 (s, 1H), 3.62 (s, 3H), 2.45 (d, J = 12.0 Hz, 1H), 1.96 (d, J = 16.0 Hz, 1H), 1.32 (s, 3H), 1.28 (t, J = 8.0 Hz, 3H), 1.19 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 189.6, 172.0, 147.5, 127.6, 77.1, 62.6, 55.1, 44.0, 32.0, 31.4, 31.0, 13.9; IR (KBr) ν = 3588, 2974, 1746, 1682, 1443, 1317, 1282, 1209, 1095, 1033, 901, 855, 633 cm−1; HRMS(ESI): calcd. for C12H19O5 [M+H]+ 243.1232, found 243.1229. Ethyl 5-oxo-7-Oxaspiro[bicyclo[4.1.0]hept[3]ene-2,2′-[1,3]dioxolane]-6-carboxylate (2r). 72%, 51.8 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 6.32 (dd, J = 12.0, 4.0 Hz, 1H), 6.03 (d, J = 12.0 Hz, 1H), 4.36−4.26 (m, 2H), 4.24−4.12 (m, 4H), 3.69 (d, J = 4.0 Hz, 1H), 1.32 (t, J = 8.0 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 187.2, 164.1, 141.6, 127.6, 100.1, 66.4, 66.2, 62.5, 59.2, 56.5, 14.0; IR (KBr) ν = 2964, 1754, 1690, 1585, 1448, 1394, 1315, 1271, 1237, 1165, 1096, 999, 922, 793, 738, 710 cm−1; HRMS(ESI): calcd. for C11H13O6 [M+H]+ 241.0712, found 241.0709. Methyl 5,5-Dimethyl-2-oxo-7-oxabicyclo[4.1.0]heptane-1-carboxylate (2s). 32%, 19.0 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 3.82 (s, 3H), 3.28 (s, 1H), 2.50−2.39 (m, 1H), 2.36−2.24 (m, 1H), 1.80 (m, 1H), 1.47−1.37 (m, 1H), 1.23 (s, 3H), 1.17 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 199.3, 166.4, 68.0, 59.5, 52.8, 34.0, 30.6, 29.9, 27.1, 22.7; IR (KBr) ν = 2952, 1733, 1687, 1602, 1457, 1410, 1331, 1292, 1252, 1165, 921, 794, 719 cm−1; HRMS(ESI): calcd. for C10H15O4 [M+H]+ 199.0970, found 199.0965. Methyl 3,3-Dimethyl-6-oxocyclohex-1-ene-1-carboxylate (5s). 21%, 11.5 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.35 (s, 1H), 3.80 (s, 3H), 2.59−2.48 (m, 2H), 1.96−1.83 (m, 2H), 1.23 (s, 6H). 13C{1H}NMR (100 MHz, CDCl3) δ 194.4, 165.3, 164.5, 130.0, 52.2, 35.4, 35.2, 33.5, 27.3. 1a-Acetyl-7,7-dimethyl-7,7a-dihydronaphtho[2,3-b]oxiren-2(1aH)-one (2t). 75%, 51.8 mg; colorless oil; 1H NMR (CDCl3, 400 MHz) δ 7.97−8.00 (m 1H), 7.59−7.63 (m, 1H), 7.36−7.41 (m, 2H), 3.54 (s, 1H), 2.44 (s, 3H), 1.67 (s, 3H),1.35 (s, 3H); 13C{1H}NMR (CDCl3, 100 MHz) δ 200.6, 190.9, 146.6, 134.8, 128.2, 128.0, 127.3, 126.2, 67.6, 64.0, 35.8, 30.3, 28.3, 25.11; IR (KBr) ν = 2966, 1761, 1688, 1492, 1343, 1286, 1155, 1082, 1068, 1004, 886, 777, 602 cm−1; HRMS(ESI): calcd. for C14H15O3 [M+H]+ 231.1021, found 231.1026. Methyl 4,4-Dimethyl-1-oxo-1,4-dihydronaphthalene-2-carboxylate (I). 1.08g, 94%; colorless oil; 1H NMR (400 MHz, CDCl3): δ 1.54 (s, 6 H), 3.90 (s, 3 H), 7.41 (td, J = 7.2, 1.2 Hz, 1 H), 7.52 (dd, J = 8.0, 0.8 Hz, 1 H), 7.60 (td, J = 7.2, 1.2 Hz, 1 H), 7.63 (s, 1 H), 8.21 (dd, J = 8.0, 1.2 Hz, 1 H); 13C{1H}NMR (100 MHz, CDCl3): δ = 29.3, 37.5, 52.4, 125.9, 127.1, 127.5, 129.3, 130.6, 133.0, 148.2, 162.2, 165.6, 180.8; IR (KBr) ν = 2927, 1730, 1715, 1458, 1327, 1219, 1058, 11700

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702

Article

The Journal of Organic Chemistry 907, 772 cm−1; calcd. for C14H15O3 [M+H]+ 231.1021, found 231.1019. Preparation of AIBA. At 0 °C, a stream of O3/O2 was continually introduced to the suspension of 2-iodo-5-(trimethylammonio)benzoate (500 mg, 1.64 mmol) in acetone (80 mL). The suspension was stirred at 0 °C for 12 h. The product was collected by filtration, washed with diethyl ether, and dried under reduced pressure to give the title compound (490 mg, 93%). White solid; m.p.: 97−100 °C (decomp.). 1H NMR (400 MHz, D2O) δ 8.42 (s, 1H), 8.31 (dd, J = 8.0, 4.0 Hz, 1H), 8.00 (d, J = 8.0 Hz, 1H), 3.64 (s, 9H); 13C{1H}NMR (100 MHz, D2O) δ 169.8, 149.1, 132.4, 128.4, 126.6, 122.9, 122.4, 57.2; IR (KBr): ν = 1771, 1655, 1483, 1455, 1413, 1315, 1301, 1176, 1150, 1017, 960, 940, 893, 859, 821, 788, 744, 561, 484, 452 cm−1; HRMS(ESI): calcd. for C10H13NO3I [M+H]+ 321.9935, found 321.9931. Regeneration of AIBX. AIBX (151 mg, 1.5 equiv) was added to the solution of substrate 1o (0.3 mmol, 75.6 mg) in the mixed solvent of PEG400 and water (4 mL, v/v = 1/3). The mixture was heated to 90 °C for 6 h. After the reaction was completed as determined by TLC, the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (50 mL × 3). The aqueous phase was evaporated under reduced pressure. Then, acetone was added to the residue, and precipitated reduced form of AIBX was filtered off, washed with acetone, and dried in vacuo. The reduced form of AIBX was added to dimethyldioxirane solution (80 mL, 0.1 M in acetone) at 0 °C in an ice bath and the mixture was stirred for 12 h. AIBX was collected by filtration, washed with diethyl ether, and dried in vacuo (130 mg, 86%, white solid). Epoxidation of Enone I to 2a. AIBA (96 mg, 0.3 mmol) was added to the mixture of enone I (46 mg, 0.2 mmol) in PEG400 and water (4 mL, v/v = 1/1). The reaction mixture was heated to 90 °C with stirring. After 24 h, the reaction mixture was allowed to cool to room temperature and extracted with EtOAc (50 mL × 3). The combined organic layer was washed with brine and dried over anhydrous MgSO4. The solvent was evaporated and the residue was purified by column chromatography to provide product 2a in 63% yield (31 mg). Preparation of β-[D2]-1a. 1,1-Dimethyl-1,2,3,4-tetrahydronaphthalen-2-d-2-ol. 1,1-Dimethyl-3,4-dihydronaphthalen-2(1H)one was prepared following the literature procedure.25 To the solution of 1,1-dimethyl-3,4-dihydronaphthalen-2(1H)-one (696 mg, 4 mmol) in THF (10 mL) was added NaBD4 (252 mg, 6 mmol). The reaction mixture was stirred at reflux overnight. After cooling to room temperature, the reaction mixture was quenched with D2O (5 mL) and extracted with EtOAc (50 mL × 3). The combined organic layer was dried over MgSO4 and concentrated in vacuo to afford the crude product, which was purified by silica gel flash chromatography to give 1,1-dimethyl-1,2,3,4-tetrahydronaphthalen-2-d-2-ol (605 mg, 85%). 1H NMR (400 MHz, CDCl3) δ 7.35 (dd, J = 8.0, 4.0 Hz, 1H), 7.21−7.15 (m, 1H), 7.11 (m, 1H), 7.07 (m, 1H), 2.97 (m, 1H), 2.91−2.81 (m, 1H), 2.03 (m, 1H), 1.98−1.89 (m, 1H), 1.35 (s, 3H), 1.30 (s, 3H); 13 C{1H}NMR (100 MHz, CDCl3) δ 144.2, 134.5, 128.7, 126.9, 126.2, 125.6, 75.3, 75.1, 74.9, 39.0, 28.9, 27.0, 26.7, 25.0. 4,4-Dimethyl-3,4-dihydronaphthalen-1(2H)-one-2,3,3-d3. 4,4-Dimethylnaphthalen-1(4H)-one-3-d was prepared following the literature procedure.26 NiCl2·2H2O (650 mg, 5 mmol) was added to 0.5 mL of dry CD3OD. The resulting suspension was cooled to 0 °C and NaBD4 (210 mg, 5 mmol) was added to it with concurrent gas evolution. The resulting black suspension was stirred at 0 °C for an additional 15 min and then a solution of 4,4-dimethylnaphthalen1(4H)-one-3-d (173 mg, 1 mmol) in CD3OD (0.5 mL) was transferred into it. The cooling bath was removed immediately after the addition and the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with ether (50 mL), the black residue was filtered off, and the crude product was purified on a silica gel column to produce 4,4-dimethyl-3,4-dihydronaphthalen1(2H)-one-2,3,3-d3 as a colorless oil (161 mg, 91%). Methyl 4,4-Dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2carboxylate-3,3-d2. Methyl 4,4-dimethyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate-3,3-d2 was obtained following the proce-

dure for the preparation of 1a with 4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one-2,3,3-d3 (89 mg, 0.5 mmol) and dimethyl carbonate (5 mL) as the starting material. Yield: 85%, 75 mg. 1H NMR (400 MHz, CDCl3) δ 12.33 (s, 0.86H), 8.02 (d, J = 8.0 Hz, 0.10H), 7.84 (d, J = 8.0 Hz, 0.87H), 7.56 (t, J = 8.0 Hz, 0.12H), 7.46−7.23 (m, 3H), 7.21−7.10 (m, 0.12 H), 3.83 (s, 2.70 H), 3.82 (s, 0.30H), 3.80 (s, 0.14H), 2.46 (s, 0.07H), 1.47 (s, 0.34H), 1.37 (s, 0.40H), 1.29 (s, 5.49H); 13C{1H}NMR (100 MHz, CDCl3) δ 193.3, 173.3, 170.9, 164.5, 151.5, 147.8, 134.4, 131.2, 130.2, 129.4, 128.8, 128.5, 127.8, 126.6, 126.2, 126.0, 125.9, 124.7, 123.9, 95.2, 54.6, 52.3, 51.6, 51.3, 35.4, 35.4, 35.2, 35.0, 34.8, 34.6, 34.4, 33.6, 33.5, 31.4, 31.4, 31.2, 31.0, 30.3, 29.7, 28.4. Procedure for the KIE Experiment. The reaction was conducted in the presence of 1a and β-[D2]-1a, according to the standard procedure except that the amount of AIBX was reduced to 0.5 equiv in order to make a proper conversion. To the solution of 1a (23 mg, 0.1 mmol) and β-[D2]-1a (23 mg, 0.1 mmol) in the mixed solvent of PEG400/H2O (4 mL, V/V = 1/1) was added AIBX (34 mg, 0.1 mmol). The reaction mixture was stirred at 90 °C for 6 h. After cooling to room temperature, the reaction mixture was diluted with water, extract with EtOAc (50 mL × 3). The combined organic layer was dried over MgSO4 and concentrated in vacuo to afford the crude product, which was purified by silica gel flash chromatography to give I and β-[D1]-I (7 mg, I/β-[D1]-I = 9/1) in combination with 2a and β[D1]-2a (8 mg, 2a/β-[D1]-2a = 3/2). kH/kD = (I + 2a)/(β-[D1]-I + β-[D1]-2a) = 2.9.

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COMPUTATIONAL DETAILS Truhlar et al.’s M06-2X density functional has been shown to provide accurate predictions for main group kinetics and thermodynamics.27 More recently, this functional has been successfully applied to hypervalent iodine chemistry. 28 Accordingly, the M06-2X functional in conjugation with a mixed basis set of the Lanl2dz29 pseudopotential for iodine and 6-31+G(d)30 for all other atoms was used for optimizing the geometry of all the minima and transition states in solution. The universal solvation model (SMD) was employed to account for the effects of water solution.31 All the optimized structures were confirmed by frequency calculations to be either minima or transition states at the same level of theory. To obtain more accurate electronic energies, single point energy calculations were performed at the M06-2X/[6-311+ +G(2df,2p) + SDD(I)](SMD) level with the M06-2X/[631+G(d) + Lanl2dz(I)](SMD) structures. Computed structures were illustrated with CYLView.32All quantum mechanical calculations were performed using Gaussian 09 packages.33

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b00883. Copies of NMR spectra and computational details (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Xiao-Song Xue: 0000-0003-4541-8702 Chi Zhang: 0000-0001-9050-076X Notes

The authors declare no competing financial interest. 11701

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702

Article

The Journal of Organic Chemistry

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(13) Nicolaou, K. C.; Montagnon, T.; Baran, P. S.; Zhong, Y. L. J. Am. Chem. Soc. 2002, 124, 2245−2258. (14) (a) For bimolecular processes, translational and rotational entropy losses in the transition state will be overestimated. Therefore, we corrected the calculated free energies by −2.6 kcal/mol to account for this; the correction value was based on “the theory of free volume”. (b) Liu, Q.; Lan, Y.; Liu, J.; Li, G.; Wu, Y.-D.; Lei, A.-W. J. Am. Chem. Soc. 2009, 131, 10201−10210. (c) Schoenebeck, F.; Houk, K. N. J. Am. Chem. Soc. 2010, 132, 2496−2497. (d) Zhou, Q.-H.; Li, Y.-X. J. Am. Chem. Soc. 2015, 137, 10182−10189. (15) Mathur, N. C.; Snow, M. S.; Young, K. M.; Pincock, J. A. Tetrahedron 1985, 41, 1509−1516. (16) Allinger, N. L.; Jones, E. S. J. Org. Chem. 1962, 27, 70−76. (17) Weinberg, L. R.; Albom, M. S.; Angeles, T. S.; Husten, J.; Lisko, J. G.; McHugh, R. J.; Milkiewicz, K. L.; Murthy, S.; Ott, G. R.; Theroff, J. P.; Tripathy, R.; Underiner, T. L.; Zificsak, C. A.; Dorsey, B. D. Bioorg. Med. Chem. Lett. 2011, 21, 164−167. (18) Mathur, N. C.; Snow, M. S.; Young, K. M.; Pincock, J. A. Tetrahedron 1985, 41, 1509−1516. (19) Winstein, S.; Heck, R. F. J. Org. Chem. 1972, 37, 825−836. (20) Morin, F. G.; Horton, W. J.; Grant, D. M.; Dalling, D. K.; Pugmire, R. J. J. Am. Chem. Soc. 1983, 105, 3992−3998. (21) Cui, L.-Q.; Liu, K.; Zhang, C. Org. Biomol. Chem. 2011, 9, 2258−2265. (22) Adkins, H.; Davis, J. W. J. Am. Chem. Soc. 1949, 71, 2955−2957. (23) Romanski, S.; Kraus, B.; Guttentag, M.; Schlundt, W.; Ruecker, H.; Adler, A.; Neudoerfl, J.-M.; Alberto, R.; Amslinger, S.; Schmalz, H.G. Dalton Trans. 2012, 41, 13862−13875. (24) Madder, A.; De Clercq, P. J.; Declercq, J.-P. J. Org. Chem. 1998, 63, 2548−2559. (25) Soni, R.; Collinson, J.-M.; Clarkson, G. C.; Wills, M. Org. Lett. 2011, 13, 4304−4307. (26) Gorka-Kereskenyi, Á .; Hazai, L.; Szántay, C.; Háda, V.; Szabó, L.; Szántay, C. Heterocycles 2005, 65, 1359−1371. (27) Zhao, Y.; Truhlar, D. G. Acc. Chem. Res. 2008, 41, 157−167. (28) For selected examples, see: (a) Zhu, C.; Liang, Y.; Hong, X.; Sun, H.; Sun, W.-Y.; Houk, K. N.; Shi, Z. J. Am. Chem. Soc. 2015, 137, 7564−7567. (b) Beaulieu, S.; Legault, C. Y. Chem. - Eur. J. 2015, 21, 11206−11211. (c) Sreenithya, A.; Sunoj, R. B. Org. Lett. 2014, 16, 6224−6227. (d) Li, M.; Xue, X.-S.; Guo, J.; Wang, Y.; Cheng, J.-P. J. Org. Chem. 2016, 81, 3119−3126. (e) Li, M.; Wang, Y.; Xue, X.-S.; Cheng, J.-P. Asian J. Org. Chem. 2017, 6, 235−240. (f) Sreenithya, A.; Patel, C.; Hadad, C. M.; Sunoj, R. B. ACS Catal. 2017, 7, 4189−4196. (29) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299−310. (30) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio Molecular Orbital Theory; Wiley: New York, 1986. (31) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2009, 113, 6378−6396. (32) Legault, C. Y. CYLview, 1.0b; Université de Sherbrooke: Sherbrooke (Québec) Canada, 2009; http://www.cylview.org. (33) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, revision B.01; Gaussian Inc.: Wallingford, CT, 2010.

ACKNOWLEDGMENTS This work was financially supported by The National Natural Science Foundation of China (21472094, 21421062, 21390400, and 21402099). We thank Mr. L.-H. Zuo and Mr. H.-D. Xia for assistance with the preparation of some substrates.

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REFERENCES

(1) (a) Smith, J. G. Chem. Informationsdienst 1984, 15, 629−656. (b) Lauret, C. Tetrahedron. Tetrahedron: Asymmetry 2001, 12, 2359− 2383. (c) Schneider, C. Synthesis 2006, 2006, 3919−3944. (d) Nielsen, L. P. C.; Jacobsen, E. N. Catalytic Asymmetric Epoxide Ring-opening Chemistry. In Aziridines and Epoxides in Organic Synthesis; Yudin, A. K., Eds.; Wiley-VCH: Weinheim, 2006; pp 229−270. (e) Olofsson, B.; Somfai, P. Vinylepoxides in Organic Synthesis. In Aziridines and Epoxides in Organic Synthesis; Yudin, A. K., Eds.; Wiley-VCH: Weinheim, 2006; pp 315−348. (2) (a) Cane, D. E.; Celmer, W. D.; Westley, J. W. J. Am. Chem. Soc. 1983, 105, 3594−3600. (b) Lee, M. S.; Qin, G.-W.; Nakanishi, K.; Zagorski, M. G. J. Am. Chem. Soc. 1989, 111, 6234−6241. (c) Valentine, J. C.; McDonald, F. E. Synlett 2006, 2006, 1816−1828. (3) (a) Zheng, J.-R.; Gu, K.-X.; Xu, L.-F.; Gao, J.-W.; Yu, Y.-H.; Tang, M.-Y. Acta Acad. Med. Sin. 1991, 13, 391−397. (b) Gu, W.-Z.; Chen, R.; Brandwein, S.; McAlpine, J.; Burres, N. Int. J. Immunopharmacol. 1995, 17, 351−356. (c) Yang, S.-X.; Gao, H.-L.; Xie, S.-S.; Zhang, W.R.; Long, Z.-Z. Int. J. Immunopharmacol. 1992, 14, 963−969. (d) Qiu, D.-M.; Zhao, G.-H.; Aoki, Y.; Shi, L.-F.; Uyei, A.; Nazarian, S.; Ng, J. C.-H.; Kao, P. N. J. Biol. Chem. 1999, 274, 13443−13450. (e) Huinink, W. W. T.; Sufliarsky, J.; Smit, W. M.; Spanik, S.; Wagnerova, M.; Hirte, H. W.; Kaye, S.; Johri, A. R.; Oza, A. M. J. Clin. Oncol. 2009, 27, 3097− 3103. (f) Forster, M.; Kaye, S.; Oza, A.; Sklenar, I.; Johri, A.; Cheung, W.; Zaknoen, S.; Gore, M. Clin. Cancer Res. 2007, 13, 4178−4184. (4) (a) Smith, M. B. Aliphatic Substitution, Nucleophilic and Organometallic. In March’s advanced organic chemistry: reactions, mechanisms, and structure, 7th ed.; John Wiley & Sons: NJ, 2013; pp 461. (b) Newman, M. S.; Magerlein, B. J. Org. React. 1949, 5, 413− 440. (c) Herrera, F. J. L.; Garcia, F. R. S.; Gonzalez, M. S. P. Rec. Res. Dev. Org. Chem. 2000, 4, 465−490. (d) Lakeev, S. N.; Maydanova, I. O.; Galin, F. Z.; Tolstikov, G. A. Russ. Chem. Rev. 2001, 70, 655−672. (5) (a) Carey, F. A.; Sundberg, R. J. Oxidations. In Advanced organic chemistry. Part B: reactions and synthesis, 5th ed.; Springer: Berlin, 2007; pp1091−1103. (b) Swern, D. Chem. Rev. 1949, 45, 1−68. (6) (a) Yoshioka, M.; Sawada, H.; Saitoh, M.; Hasegawa, T. J. Chem. Soc., Perkin Trans. 1 1990, 1097−1110. (b) Christoffers, J. J. Org. Chem. 1999, 64, 7668−7669. (7) (a) Rebelo, S. L. H.; Simões, M. M. Q.; Neves, M. G. P. M. S.; Cavaleiro, J. A. S. J. Mol. Catal. A: Chem. 2003, 201, 9−22. (b) Połtowicz, J.; Pamin, K.; Haber, J. J. Mol. Catal. A: Chem. 2006, 257, 154−157. (c) Bianchini, G.; Crucianelli, M.; Canevali, C.; Crestini, C.; Morazzoni, F.; Saladino, R. Tetrahedron 2006, 62, 12326− 12333. (8) (a) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523− 2584. (b) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299− 5358. (c) Yoshimura, A.; Zhdankin, V. V. Chem. Rev. 2016, 116, 3328−3435. (d) Zhdankin, V. V. Hypervalent Iodine Chemistry: preparation, structure and synthetic applications of polyvalent iodine compounds, 2th ed.; John Wiley & Sons, 2014. (e) Duan, Y.-N.; Jiang, S.; Han, Y.-C.; Sun, B.; Zhang, C. Youji Huaxue 2016, 36, 1973−1984. (9) (a) Cui, L.-Q.; Dong, Z.-L.; Liu, K.; Zhang, C. Org. Lett. 2011, 13, 6488−6491. (b) Duan, Y.-N.; Cui, L.-Q.; Zuo, L.-H.; Zhang, C. Chem. - Eur. J. 2015, 21, 13052−13057. (c) Duan, Y.-N.; Zhang, Z.; Zhang, C. Org. Lett. 2016, 18, 6176−6179. (10) (a) Richardson, R. R.; Zayed, J. M.; Altermann, S.; Smith, D.; Wirth, T. Angew. Chem., Int. Ed. 2007, 46, 6529−6532. (b) Thottumkara, A. P.; Vinod, T. K. Tetrahedron Lett. 2002, 43, 569−572. (11) McQuaid, K. M.; Pettus, T. R. R. Synlett 2004, 13, 2403−2405. (12) Hogberg, T.; Khanna, I.; Drake, S. D.; Mitscher, L. A.; Shen, L. L. J. Med. Chem. 1984, 27, 306−310. 11702

DOI: 10.1021/acs.joc.7b00883 J. Org. Chem. 2017, 82, 11691−11702