Hypervalent-Iodine-Mediated Formation of Epoxides from Carbon(sp2)-Carbon(sp3) Single Bonds

Article abstract of DOI:10.1021/acs.joc.7b00883

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).

Full text of DOI:10.1021/acs.joc.7b00883

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Article
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
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 03 Jun 2017
Downloaded from http://pubs.acs.org on June 3, 2017
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Hypervalent-Iodine-Mediated Formation of Epoxides from Car-
bon(sp2)–Carbon(sp3) Single Bonds
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Shan Jiang, TaiꢀShan Yan, YongꢀChao Han, LiꢀQian Cui, XiaoꢀSong Xue,* and Chi Zhang*
State Key Laboratory of ElementoꢀOrganic Chemistry, Collaborative Innovation Center of Chemical Science and Engineerꢀ
ing, College of Chemistry, Nankai University, Tianjin 300071, China
ABSTRACT: We have developed an efficient method for direct formation of epoxide groups from carbon(sp2)–carbon(sp3) single
bonds of βꢀketo esters; the reaction is mediated by the waterꢀsoluble hypervalent iodine(V) reagent AIBX (5ꢀtrimethylammonioꢀ
1,3ꢀdioxoꢀ1,3ꢀdihydroꢀ1λ5ꢀbenzo[d][1,2]iodoxolꢀ1ꢀol anion). On the basis of the results of density functional theory calculations
and experimental studies, we propose that the reaction proceeds by a twoꢀstage mechanism involving dehydrogenation of the βꢀketo
ester substrates and epoxidation of the resulting enone intermediates. The rateꢀlimiting step is abstraction of the β′ꢀC–H (calculated
free energy of activation, 24.5 kcal/mol).
Introduction
Epoxides are versatile intermediates that are widely used as building blocks for the synthesis of valuable chemicals such as 1,2ꢀ
diols, βꢀamino 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, many methods, both oxidative and nonꢀoxidative, for its
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formation have been developed. For nonꢀoxidative methods, halohydrins, aldehydes, and ketones often serve as precursors for
efficient formation of epoxide groups (Figure 2, A–C).4 Nearly all of the currently available oxidative methods involve treatment of
olefins with various oxidants (Figure 2D).5
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Figure 1. Selected epoxideꢀbearing molecules.
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 diꢀ
vided into two categories: direct transformations of carbon(sp2)–carbon(sp3) (Csp2–Csp3) single bonds and transformations of carꢀ
bon(sp3)–carbon(sp3) single bonds, which are more challenging. Two cases of epoxide formation from Csp2–Csp3 single bonds have
been reported, both of which involved molecular oxygen as the oxidant6: (1) photochemical reactions of a sixꢀmemberedꢀring enolꢀ
ic 1,3ꢀdiketone generated an epoxide in up to 15% yield, and (2) Mn(OAc)2ꢀcatalyzed oxidation of a cyclic βꢀketo ester afforded the
corresponding epoxide in 45% yield after 3 days. Neither of these processes is practical, owing to either low yield or sluggish reacꢀ
tion. 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.
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Figure 2. Methods for efficient formation of epoxides.
Hypervalent iodine reagents, due to their safety, ready availability, environmental friendliness, and regenerability, are preferred
organoꢀoxidants in the organic synthesis.8 In this study, as part of our ongoing exploration of the reactivity of AIBX (5ꢀ
trimethylammonioꢀ1,3ꢀdioxoꢀ1,3ꢀdihydroꢀ1λ5ꢀbenzo[d][1,2]iodoxolꢀ1ꢀol anion), a waterꢀsoluble 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).
Results and Discussion
We began by investigating epoxide formation from βꢀketo ester 1a, methyl 4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀ
carboxylate, using 1.5 equiv of AIBX in a 1/3 (v/v) mixture of diglyme and water at 90 oC. After 7 h, the desired epoxide product,
methyl 7,7ꢀdimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (2a), was obtained in 82% yield along with a
o
small amount of αꢀhydroxylated 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 4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(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).
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Because PEG400 was the best of the organic solvents we evaluated, we examined the effect of the PEG400/H2O volume ratio. Reꢀ
actions 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 6ꢀbromoꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (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 soluꢀ
bility 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 2ꢀiodoxybenzoic 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; αꢀhydroxylation product 3a was obtained as the sole product in 53% yield, and conversion of 1a was only 80%. The deꢀ
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rivatives of IBX, including FIBX and mIBX,10 were also tried and gave αꢀhydroxylation product 3a in 94% and 82% yields respecꢀ
tively without detecting epoxidation product.
Table 1. Screening of organic solvents and organic solvent/H2O ratios.a
O
O
O
O
O
O
O
O
1.5 equiv of AIBX
Solvent, 90 oC
O
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(1)
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1b (R = Br)
3a (R = H)
3b (R = Br)
2a (R = H)
2b (R = Br)
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Yield (%)
of 2a
Yield (%)
Yield (%)
Entry
1
Solvent (v/v)
Time (h)
Conv. (%)
of 4
of 3
diglyme/H2O (1/3)
diglyme/H2O (1/3)
DME/H2O (1/3)
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100
90
THF/H2O (1/3)
DMF/H2O (1/3)
DMSO/H2O (1/3)
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PEG400/H2O (1/3)
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100
100
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PEG2000/H2O (1g/3 mL)
CCl4/H2O (1/3)
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72f
PEG400/H2O (1/1)
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100
100
8
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PEG400/H2O (1/3)
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12e
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100
90
79f
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PEG400/H2O (1/1)
H2O
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aReaction conditions: 1a (0.3 mmol), AIBX (0.45 mmol), solvent (4 mL), 90 C. The reaction was carried out at 70 oC. Decarboxylated
product 4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone (4) was obtained. dDehydrogenation product methyl 4,4ꢀdimethylꢀ1ꢀoxoꢀ1,4ꢀ
dihydronaphthaleneꢀ2ꢀcarboxylate (I) was obtained in 25% yield. eCompound 1b was used as the substrate. fEpoxide 2b was obtained.
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To test the generality of this epoxide formation reaction, we evaluated a variety of βꢀketo esters and a βꢀdiketone in which gemꢀ
dimethyl groups are installed at the γꢀsite of carbonyl to prevent aromatization[9a] as substrates (Figure 3). Like 1a, ethyl 4,4ꢀ
dimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (1c) was readily oxidized to corresponding epoxides 2c (83% yield).
Substrates bearing either an electronꢀwithdrawing substituent (F, Cl, Br, I, NO2) or an electronꢀdonating 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 oxidaꢀ
tion. 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 thiꢀ
ophene 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 benzoꢀfused βꢀketo 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. βꢀDiketone 1t was also smoothly transformed into its corresponding epoxꢀ
ide (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).
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Figure 3. Substrate scope of epoxide formation reaction.a
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aThe 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 αꢀhydroxylated products (in parentheses). bCarried out in 1/3 (v/v) PEG400/H2O. cThe yield in parentheses is the yield
of methyl 3,3ꢀdimethylꢀ6ꢀoxocyclohexꢀ1ꢀeneꢀ1ꢀcarboxylate (5s).
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We conducted some experiments to investigate the mechanism of this new reaction. Specifically, the reaction of 1a with AIBX in
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1/3 (v/v) DMSO/H2O at 90 C gave enone I as a byꢀproduct, and the reaction of substrate 1s under the standard conditions gave
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enone 5s as a byꢀproduct (Table 1, entry 6; Figure 3). On the basis of these results, our previous work9 on AIBXꢀmediated dehydroꢀ
genation reactions of cyclic βꢀketo esters, and the reported iodosobenzeneꢀmediated epoxidation of electronꢀdeficient olefins such
as enones,11 we propose a twoꢀstage reaction mechanism for the present AIBXꢀmediated epoxide formation reaction directly from
Csp2–Csp3 single bonds. First, the βꢀketo ester substrate is oxidatively dehydrogenated to the corresponding dehydrogenated enone
by AIBX, which is reduced to AIBA (3ꢀoxoꢀ5ꢀ(trimethylammonio)ꢀ1λ3ꢀbenzo[d][1,2]iodaoxolꢀ1(3H)ꢀolate), a hypervalent ioꢀ
dine(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 Experiꢀ
mental 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 1ꢀhydroxyꢀ1l3ꢀbenzo[d][1,2]iodaoxolꢀ3(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.
Figure 4. Synthesis of 2a from I.
To gain a better understanding of the mechanistic details of this AIBXꢀmediated epoxide formation reaction, we carried out density
functional theory calculations at the M06ꢀ2X/[6ꢀ311++G(2df,2p) + SDD(I)](SMD)//M06ꢀ2X/[6ꢀ31+G(d) + 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. Deproꢀ
tonation 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 proꢀ
ceed via either single electron transfer13 or direct hydride transfer. Our calculations indicated that the energy barrier for SET was
prohibitively high: the hypothetical diꢀradical intermediate IM2 was predicted to lie 54.7 kcal/mol above IM1. In contrast, the calꢀ
culated free energy of activation for direct hydride transfer via TS2 was only 24.5 kcal/mol. That is, direct hydride transfer was
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calculated to be preferred by nearly 30 kcal/mol relative to SET. Therefore, although the SET mechanism has been widely proposed
for 2ꢀiodoxybenzoic acid–induced dehydrogenation of aldehydes and ketones, this mechanism is highly unlikely for our AIBXꢀ
mediated dehydrogenation of βꢀketo esters. A possible reason for this difference may be that compared to aldehyde and ketone enoꢀ
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lates, βꢀketo ester enolates are more reluctant to release an electron. The dehydrogenation process leading to enone intermediate I
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and AIBA was predicted to be exothermic by 61.2 kcal/mol.
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The epoxidation of I by AIBA was found to be a stepwise process. Michaelꢀtype 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 rateꢀlimiting step.
Figure 5. Energy diagram for AIBXꢀmediated epoxide formation calculated at the M06ꢀ2X/[6ꢀ311++G(2df,2p) +
SDD(I)](SMD)//M06ꢀ2X/[6ꢀ31+G(d) + Lanl2dz(I)](SMD) level. Free energies are in kilocalories per mole, and bond lengths
are in angstroms.14
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To validate our calculationꢀbased prediction that β′ꢀC–H abstraction was the rateꢀlimiting step, a kinetic isotope effect (KIE) experꢀ
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iment was undertaken. First, β′ꢀdouble deuterated substrate β′ꢀ[D2]ꢀ1a (deuteration ratio: >95%) was prepared from βꢀtetralone 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 subꢀ
strates under the standard reaction conditions, except that only 0.5 equiv of AIBX was employed (Figure 6). Analysis of the reacꢀ
tion 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 rateꢀlimiting step. Thus, the result of this KIE experiment was in agreement with the results of our calculaꢀ
tions indicating that abstraction of the β′ꢀCꢀH was the rateꢀlimiting step.
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Figure 6. Kinetic isotope effect experiment.
On the basis of all the aboveꢀdescribed results, we propose the reaction mechanism shown in Figure 7. First, substrate 1a is deproꢀ
tonated 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 transiꢀ
tion state TS2, which contains a sevenꢀmembered I(V) heterocycle. Epoxidation of I by Michaelꢀtype addition of AIBA to the douꢀ
ble bond produces intermediate IM3, which gives epoxide 2a through intramolecular cyclization.
Figure 7. Proposed mechanism.
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In summary, we have developed an AIBXꢀmediated 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 twoꢀstage mechanism. By calculating the energy profile of the overall reaction pathway, we found that abꢀ
straction of the β′ꢀC–H of enolate 1a′ to give enone intermediate I is the rateꢀlimiting step. Investigation of the use of this method
for transformations of light alkanes is underway in our laboratory.
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
FTꢀIR Bruker EQUINOX55 spectrometer in KBr pellets. Highꢀresolution mass spectroscopy (HRMS) was performed with a high resoluꢀ
tion ESI–FTICR mass spectrometer (Varian 7.0 T).
Preparation and characterization of substrates
Methyl 4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (1a): To the suspension of NaH (960 mg, 40 mmol) in dried
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dimethyl carbonate (10 mL) was added a solution of 4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(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,
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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 ;
HRMS(ESI): calcd. for C14H17O3 [M+H]+ 233.1178, found 233.1182.
Methyl
6ꢀbromoꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate
(1b):
6ꢀBromoꢀ4,4ꢀdimethylꢀ3,4ꢀ
dihydronaphthalenꢀ1(2H)ꢀone was prepared following the literature procedure.15 Compound 1b was obtained in 79% yield (1.23 g) followꢀ
ing the procedure for the preparation of 1a with 6ꢀbromoꢀ4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone (5 mmol) and dimethyl carbonate
as the starting material. White solid; m.p.: 60ꢀ61 oC; 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,
－
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1393, 1247, 1199, 1140, 1100, 783, 764 cm ; HRMS(ESI): calcd. for C14H16BrO3 [M+H]+ 311.0283, found 311.0286.
Ethyl 4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (1c): Compound 1c was obtained in 86% yield (1.06 g) followꢀ
ing the procedure for the preparation of 1a with 4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(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,
－
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1630, 1257, 1205, 1145, 874, 734 cm ; HRMS(ESI): calcd. for C15H19O3 [M+H]+ 247.1334, found 247.1339.
Methyl 7ꢀfluoroꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (1d): 7ꢀFluoroꢀ4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ
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 7ꢀfluoroꢀ4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(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 cmꢀ1; HRMS(ESI): calcd. for C14H16FO3 [M+H]+ 251.1083, found 251.1090.
Methyl 7ꢀchloroꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (1e): Compound 1e was prepared following the
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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
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90% (479 mg) with 6ꢀchloroꢀ4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone (2 mmol) and dimethyl carbonate as the starting material..
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Slightly yellow oil; H 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),
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3.83 (s, 3H), 2.47 (s, 2H), 1.27 (s, 6H); 13C{1H}NMR (100 MHz, CDCl3) 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 cmꢀ1;
HRMS(ESI): calcd. for C14H16ClO3 [M+H]+ 267.0788, found 267.0782.
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Methyl 7ꢀbromoꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (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 4,4ꢀ
dimethylꢀ7ꢀaminoꢀ1ꢀtetralone (5.0 g, 26.46 mmol) in glacial acetic acid (89 mL) over 10 minutes. The resulting solution was added slowly
(over 10 minutes) 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 7ꢀbromoꢀ4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone. Comꢀ
pound 1f was obtained in 87% yield (674 mg) following the procedure for the preparation of 1a with 7ꢀbromoꢀ4,4ꢀdimethylꢀ3,4ꢀ
dihydronaphthalenꢀ1(2H)ꢀone (2.5 mmol) and dimethyl carbonate as the starting material. White solid; m.p.: 55ꢀ57 oC; 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); 13C{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 cmꢀ1; HRMS(ESI): calcd. for C14H16BrO3 [M+H]+ 311.0283,
found 311.0288.
Methyl 7ꢀiodoꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (1g): To a solution of 4,4ꢀdimethylꢀ7ꢀaminoꢀ1ꢀ
tetralone (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 iceꢀwater bath. The reaction mixture was then diazotized by the dropwise addition with stirring of a soluꢀ
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tion of sodium nitrite (0.76 g, 11.0 mmol) in water (3.13 mL), keeping temperature between 0 Cꢀ5 C. After stirring for 15 minutes, 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 minutes, the
reaction mixture was extracted with ethyl acetate. The organic phase was then concentrated in vacuo to give 7ꢀiodoꢀ4,4ꢀdimethylꢀ3,4ꢀ
dihydronaphthalenꢀ1(2H)ꢀone. Compound 1g was obtained in 81% yield (667 mg) following the procedure for the preparation of 1a with
7ꢀiodoꢀ4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone (2.3 mmol) and dimethyl carbonate as the starting material. White solid; m.p.: 58ꢀ
60 oC; 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 cmꢀ1; HRMS(ESI): calcd. for C14H16IO3 [M+H]+ 359.0144,
found 359.0140.
Ethyl 4,4ꢀdimethylꢀ7ꢀnitroꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (1h): 4,4ꢀDimethylꢀ7ꢀnitroꢀ3,4ꢀdihydronaphthalenꢀ
1(2H)ꢀone was prepared following the literature procedure.17 To a freshly prepared solution of LDA (11 mmol using 1.44 mL of iꢀPr2NH
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and 4.58 mL of nꢀBuLi 2.4 M) in THF (5 mL) at ꢀ78 C, a solution of 4,4ꢀdimethylꢀ7ꢀnitroꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone (2.19 g, 10
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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 oC 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
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silica gel flash chromatography to give 1h in 51% yield (1.48 g). White solid; m.p.: 71ꢀ73 oC; 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, 34.4, 28.3,
14.3. IR (KBr) ν = 2969, 1654, 1623, 1524, 1400, 1347, 1224, 1066, 1025, 909, 834, 743 cmꢀ1; HRMS(ESI): calcd. for C15H18NO5 [M+H]+
292.1185, found 292.1186.
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Methyl 4,4,6ꢀtrimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (1i): 4,4,6ꢀTrimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone
was prepared following the literature procedure.18 Compound 1i was obtained in 79% yield (972 mg) following the procedure for the prepꢀ
aration of 1a with 4,4,6ꢀtrimethylꢀ3,4ꢀdihydronaphthalenꢀ1(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,
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1124, 888, 810, 762 cm ; HRMS(ESI): calcd. for C15H19O3 [M+H]+ 247.1334, found 247.1338.
Methyl 6ꢀmethoxyꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (1j): 6ꢀMethoxyꢀ3,4ꢀdihydronaphthalenꢀ1(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 6ꢀmethoxyꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone and (3.4 mmol) dimeꢀ
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thyl carbonate as the starting material. White solid; m.p.: 64ꢀ65 C; H 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 cmꢀ1; HRMS(ESI): calcd. For C15H19O4 [M+H]+
263.1283, found 263.1288.
Methyl
7ꢀmethoxyꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate
(1k):
7ꢀMethoxyꢀ4,4ꢀdimethylꢀ3,4ꢀ
dihydronaphthalenꢀ1(2H)ꢀone was prepared following the literature procedure.19 Compound 1k was obtained in 79% yield (1.03 g) followꢀ
ing the procedure for the preparation of 1a with 7ꢀmethoxyꢀ4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone (5 mmol) and dimethyl carꢀ
bonate as the starting material. White solid; m.p.: 53ꢀ54 oC; 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),
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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 cmꢀ1; HRMS(ESI): calcd. for C15H19O4 [M+H]+
263.1283, found 263.1288.
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Methyl 7ꢀ((methoxycarbonyl)(methyl)amino)ꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydroꢀ naphthaleneꢀ2ꢀcarboxylate (1l): A solution of
2.3 g (10.5 mmol) 3,4ꢀdihydroꢀ4,4ꢀdimethylꢀ7ꢀnitroꢀ1(2H)ꢀnaphthalenone in 50 ml of EtOAc was stirred at room temperature with 0.23 g
of 10% PdꢀC under 1 atm of H2 for 24 hours. The catalyst was removed by filtration through a pad of Celite, and the filtrate concentrated
under reduced pressure to give 7ꢀaminoꢀ4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone as a dark green oil. To the solution of crude 7ꢀ
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aminoꢀ4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone in CH2Cl2 (20 mL) at 0 C was added AcCl (1.1 mL, 15 mmol) and Et3N (4.3 mL,
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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 Nꢀ(5,5ꢀdimethylꢀ8ꢀoxoꢀ5,6,7,8ꢀ
tetrahydronaphthalenꢀ2ꢀyl)benzamide. Compound 1l was obtained in 80% yield (664 mg) following the procedure for the preparation of 1a
with Nꢀ(5,5ꢀdimethylꢀ8ꢀoxoꢀ5,6,7,8ꢀtetrahydronaphthalenꢀ2ꢀyl)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 cmꢀ1; HRMS(ESI): calcd.
for C17H22NO5 [M+H]+ 320.1498, found 320.1500.
Methyl 7ꢀ(N,4ꢀdimethylphenylsulfonamido)ꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2, 3,4ꢀtetrahydro naphthaleneꢀ2ꢀcarboxylate (1m): 1,1ꢀDimethylꢀ
1,2,3,4ꢀtetrahydroanthracene was prepared following the literature procedure.20 4,4ꢀDimethylꢀ3,4ꢀdihydroanthracenꢀ1(2H)ꢀone was preꢀ
pared following the literature procedure.21 Compound 1m was obtained in 86% yield (1.21 g) following the procedure for the preparation
of 1a with 4,4ꢀdimethylꢀ3,4ꢀdihydroanthracenꢀ1(2H)ꢀone (5 mmol) and dimethyl carbonate as the starting material. White solid; mp: 88ꢀ89
oC. 1H NMR (400 MHz, CDCl3): δ 1.39 (s, 6 H), 2.55 (s, 2 H), 3.86 (s, 3 H), 7.44ꢀ7.52 (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); 13C{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 cmꢀ1; HRMS(ESI): calcd. for C18H19O3 [M+H]+ 283.1334, found 283.1330.
Methyl 4'ꢀoxoꢀ3',4'ꢀdihydroꢀ2'Hꢀspiro[cyclopentaneꢀ1,1'ꢀnaphthalene]ꢀ3'ꢀcarboxylate (1n) : 2'Hꢀspiro[cyclopentaneꢀ1,1'ꢀ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'Hꢀspiro[cyclopentaneꢀ1,1'ꢀnaphthalen]ꢀ4'(3'H)ꢀone (1.4 mmol) and dimethyl carbonate as the starting mateꢀ
rial. 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); 13C{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 cmꢀ1; HRMS(ESI): calcd. for C16H19O3 [M+H]+ 259.1334, found 259.1332.
Methyl 4,4ꢀdimethylꢀ7ꢀoxoꢀ4,5,6,7ꢀtetrahydrobenzo[b]thiopheneꢀ6ꢀcarboxylate (1o): 4,4ꢀDimethylꢀ5,6ꢀdihydrobenzo[b]thiophenꢀ
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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 4,4ꢀdimethylꢀ5,6ꢀdihydrobenzo[b]thiophenꢀ7(4H)ꢀone (5 mmol) and dimethyl carbonate as the starting mateꢀ
rial. 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 cmꢀ1; HRMS(ESI): calcd. for C12H15O3S [M+H]+ 239.0742, found 239.0746.
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Ethyl 5,5ꢀdimethylꢀ2ꢀoxocyclohexꢀ3ꢀenecarboxylate (1p): 4,4ꢀDimethylcyclohexꢀ2ꢀenone was prepared following the literature proceꢀ
dure.24 Compound 1p was obtained in 76% yield (1.5 g) following the procedure for the preparation of 1h with 4,4ꢀdimethylcyclohexꢀ2ꢀ
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, 689, 662, 556, 488 cmꢀ1, HRMS(ESI): calcd. for C11H17O3 [M+H]+ 197.1178,
found 197.1180.
Ethyl 3ꢀmethoxyꢀ5,5ꢀdimethylꢀ2ꢀoxocyclohexꢀ3ꢀenecarboxylate (1q): To an iceꢀcold solution of 4,4ꢀdimethylꢀcyclohexꢀ2ꢀenone (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 5,5ꢀdimethylꢀ7ꢀ
oxabicyclo[4.1.0]heptanꢀ2ꢀone as a colorless oil. To a solution of KOH (0.49 g, 7.4 mmol) in methanol (15 mL) was added a solution of
5,5ꢀdimethylꢀ7ꢀoxabicyclo[4.1.0]heptanꢀ2ꢀone (1.04 g, 7.42 mmol) in methanol (5 mL). The mixture was stirred overnight at room temperꢀ
ature 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 2ꢀmethoxyꢀ4, 4ꢀdimethylꢀcyclohexꢀ2ꢀenone as an oil. Compound 1q was obtained in 54% yield (268 mg) folꢀ
lowing the procedure for the preparation of 1h with 2ꢀmethoxyꢀ4,4ꢀdimethylꢀcyclohexꢀ2ꢀenone (2.2 mmol) as the starting material. Slightꢀ
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ly yellow oil; H 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); 13C{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 cmꢀ1; HRMS(ESI): calcd. for C12H19O4 [M+H]+ 227.1283, found 227.1288.
Ethyl 8ꢀoxoꢀ1,4ꢀdioxaspiro[4.5]decꢀ9ꢀeneꢀ7ꢀcarboxylate (1r) : To the solution of cyclohexaneꢀ1,4ꢀdione (5.6g, 50 mmol) in benzene (25
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mL) was added ethylene glycol (4.03g, 65 mmol) and pꢀTsOH (855 mg, 4.5 mmol) and the solution was reflux 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 1,4ꢀdioxaspiro[4.5]decanꢀ8ꢀone. At ꢀ
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followed by adding a solution of TMSOTf (1.72 mL, 9.46 mmol) in CH2Cl2 (20 mL). The mixture was stirred at ꢀ5 oC for 1 h. The resultꢀ
ing 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 (1,4ꢀdioxaspiro[4.5]decꢀ7ꢀenꢀ8ꢀyloxy)trimethylsilane. To the solution
of resulted crude (1,4ꢀdioxaspiro[4.5]decꢀ7ꢀenꢀ8ꢀyloxy)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 1,4ꢀdioxaspiro[4.5]decꢀ6ꢀ
enꢀ8ꢀone. Compound 1r was obtained in 61% yield (414 mg) following the procedure for the preparation of 1h with 1,4ꢀ
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dioxaspiro[4.5]decꢀ6ꢀenꢀ8ꢀone (3 mmol) as the starting material. Slightly yellow oil; H 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 cmꢀ1; HRMS(ESI): calcd. for C11H15O5 [M+H]+ 227.0919, found 227.0922.
Methyl 5,5ꢀdimethylꢀ2ꢀoxocyclohexanecarboxylate (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.
2ꢀAcetylꢀ4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone (1t): Under N2, to the solution of 4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀ
one (870 mg, 5 mmol) in Ac2O (1.8 mL) was added BF3ꢁEt2O (0.9 mL, 1.56 mmol). The resulting mixture was heated at 60 oC for 2 h folꢀ
lowed 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.: 52ꢀ54 oC;
1H NMR (400 MHz, CDCl3) δ 16.32 (s, 1H), 7.99ꢀ7.97 (d, 8.0 Hz, 1H), 7.48ꢀ7.46 (d, 8.0 Hz, 1H), 7.37ꢀ7.30 (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 cmꢀ1; HRMS(ESI): calcd. for C14H17O2 [M+H]+ 217.1229, found 217.1232.
Typical procedure for synthesis of epoxide functionality directly from carbonꢀcarbon 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 oC 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
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anhydrous MgSO4. The solvent was evaporated and the residue was purified by column chromatography to provide product 2a in 83%
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The characterization of the products
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Methyl 7,7ꢀdimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (2a): 83%, 68 mg; colorless oil; 1H NMR
(CDCl3, 400MHz) δ 8.01(dd, J = 1.2 Hz, 8.0 Hz, 1H), 7.59ꢀ7.63 (m, 1H), 4.35ꢀ7.40 (m, 2H), 3.91 (s, 3H), 3.68 (s, 1H), 1.68 (s, 3H), 1.38
(s, 3H); 13C{1H}NMR (CDCl3, 100MHz) 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 cmꢀ1; HRMS(ESI): calcd. for C14H15O4
[M+H]+ 247.0970, found 247.0972.
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Methyl 2ꢀhydroxyꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (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 cmꢀ1;
HRMS(ESI): calcd. for C14H17O4 [M+H]+ 249.1127, found 249.1123.
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Methyl 5ꢀbromoꢀ7,7ꢀdimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (2b): 79%, 76.8 mg; colorless oil; H
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);
13C{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 cmꢀ1; HRMS(ESI): calcd. for C14H14BrO4 [M+H]+
325.0075, found 325.0080.
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Methyl 6ꢀbromoꢀ2ꢀhydroxyꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (3b): 12%, 11.7 mg; colorless oil; 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); 13C{1H}NMR (100 MHz, CDCl3) δ 194.0, 172.4, 153.6, 130.4, 130.3, 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 cmꢀ1; HRMS(ESI): calcd. for C14H16BrO4 [M+H]+ 327.0232, found 327.0238.
Ethyl 7,7ꢀdimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (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 cmꢀ1; HRMS(ESI):
calcd. for C15H17O4 [M+H]+ 261.1127, found 261.1122.
Ethyl 2ꢀhydroxyꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (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,
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1759, 1689, 1450, 1355, 1308, 1281, 1233, 1128, 1022, 830, 788, 733 cmꢀ1; HRMS(ESI): calcd. for C15H19O4 [M+H]+ 263.1283, found
263.1285.
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Methyl 4ꢀfluoroꢀ7,7ꢀdimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (2d): 79%, 62.6 mg; colorless oil; H
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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 cmꢀ1; HRMS(ESI): calcd. for C14H14FO4 [M+H]+ 265.0876, found 265.0879.
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Methyl 7ꢀfluoroꢀ2ꢀhydroxyꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (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 cmꢀ1; HRMS(ESI): calcd. for C14H16FO4 [M+H]+
267.1033, found 267.1038.
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Methyl 4ꢀchloroꢀ7,7ꢀdimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (2e):81%, 68.1 mg; colorless oil; H
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 cmꢀ1; HRMS(ESI): calcd. for C14H14ClO4
[M+H]+ 281.0581, found 281.0586.
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Ethyl 7ꢀchloroꢀ2ꢀhydroxyꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (3e):11%, 9.3 mg; colorless oil; H 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). 13C{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
cmꢀ1; HRMS(ESI): calcd. for C14H16ClO4 [M+H]+ 283.0737, found 283.0733.
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Methyl 4ꢀbromoꢀ7,7ꢀdimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (2f): 83%, 80.7 mg; colorless oil; H
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, 35.6,
30.1, 25.0. IR (KBr) ν = 2936, 1777, 1687, 1455, 1328, 1279, 1129, 890, 833, 777, 720 cmꢀ1; HRMS(ESI): calcd. for C14H14BrO4 [M+H]+
325.0075, found 325.0079.
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Ethyl 7ꢀbromoꢀ2ꢀhydroxyꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (3f): 8%, 7.8 mg; colorless oil; H 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). 13C{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 cmꢀ1; HRMS(ESI): calcd. for C14H16BrO4 [M+H]+ 327.0232, found 327.0235.
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Methyl 4ꢀiodoꢀ7,7ꢀdimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (2g): 77%, 85.9 mg; colorless oil; H
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 cmꢀ1; HRMS(ESI): calcd. for
C14H14IO4 [M+H]+ 372.9937, found 372.9933.
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Methyl 2ꢀhydroxyꢀ7ꢀiodoꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (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); 13C{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 cmꢀ1; HRMS(ESI): calcd. for C14H16IO4 [M+H]+ 375.0093, found 375.0095.
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Ethyl 7,7ꢀdimethylꢀ4ꢀnitroꢀ2ꢀoxoꢀ7,7aꢀdihydronaphtho[2,3ꢀb]oxireneꢀ1a(2H)ꢀcarboxylate (2h): 62%, 56.9 mg; colorless oil; H 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). 13C{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 cmꢀ
1; HRMS(ESI): calcd. for C15H16NO6 [M+H]+ 306.0978, found 306.0982.
Ethyl 2ꢀhydroxyꢀ4,4ꢀdimethylꢀ7ꢀnitroꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (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 cmꢀ1; HRMS(ESI): calcd. for C15H18NO6 [M+H]+ 308.1134, found 308.1130.
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Methyl 5,7,7ꢀtrimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (2i): 81%, 63.2 mg; colorless oil; H 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 cmꢀ1; HRMS(ESI): calcd. for C15H17O4 [M+H]+
261.1127, found 261.1129.
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Methyl 2ꢀhydroxyꢀ4,4,7ꢀtrimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (3i): 9%, 7.1 mg; colorless oil; H 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); 13C{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, 987,
766, 710 cmꢀ1; HRMS(ESI): calcd. for C15H19O4 [M+H]+ 263.1283, found 263.1287.
Methyl 5ꢀmethoxyꢀ7,7ꢀdimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (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,
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30.2, 25.2; IR (KBr) ν = 2956, 1754, 1692, 1492, 1440, 1321, 1251, 1207, 1148, 1061, 893, 834, 786cmꢀ1; HRMS(ESI): calcd. for
C15H17O5 [M+H]+ 277.1076, found 277.1083.
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Methyl 4ꢀmethoxyꢀ7,7ꢀdimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (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 cmꢀ1;
HRMS(ESI): calcd. for C15H17O5 [M+H]+ 277.1076, found 277.1071.
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Methyl 2ꢀhydroxyꢀ7ꢀmethoxyꢀ4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylate (3k): 6%, 5.0 mg; colorless oil; 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 cmꢀ1; HRMS(ESI): calcd. for C15H19O5 [M+H]+ 279.1232, found 279.1230.
Methyl 4ꢀ((methoxycarbonyl)(methyl)amino)ꢀ7,7ꢀdimethylꢀ2ꢀoxoꢀ1a,2,7,7aꢀtetrahydronaphtho[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (2l):
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68%, 67.9 mg; colorless oil; H 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 cmꢀ1; HRMS(ESI): calcd. for C17H20NO6 [M+H]+ 334.1291, found, 334.1285.
Methyl 9,9ꢀdimethylꢀ2ꢀoxoꢀ1a,2,9,9aꢀtetrahydroanthra[2,3ꢀb]oxireneꢀ1aꢀcarboxylate (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 cmꢀ1; HRMS(ESI): calcd. for C18H17O4 [M+H]+ 297.1127, found 297.1120.
Methyl 7'ꢀoxoꢀ7',7a'ꢀdihydroꢀ1a'Hꢀspiro[cyclopentaneꢀ1,2'ꢀnaphtho[2,3ꢀb]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); 13C{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 cmꢀ1; HRMS(ESI): calcd. for C16H17O4 [M+H]+ 273.1127, found 273.1118.
Methyl 6,6ꢀdimethylꢀ2ꢀoxoꢀ1a,2,6,6aꢀtetrahydrothieno[2',3':4,5]benzo[1,2ꢀb]oxireneꢀ1aꢀcarboxylate (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);
13C{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 cmꢀ1; HRMS(ESI): calcd. for C12H13O4S [M+H]+ 253.0535, found
253.0533.
Ethyl 5,5ꢀdimethylꢀ2ꢀoxoꢀ7ꢀoxabicyclo[4.1.0]heptꢀ3ꢀeneꢀ1ꢀcarboxylate (2p): 59%, 37.2 mg; colorless oil; 1H NMR (400 MHz, CDCl3) δ
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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);
13C{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 cmꢀ1; HRMS(ESI): calcd. for C11H15O4 [M+H]+ 211.0970, found 211.0977.
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Ethyl 1ꢀhydroxyꢀ5,5ꢀdimethylꢀ2ꢀoxocyclohexꢀ3ꢀenecarboxylate (3p): 19%, 12.1 mg; colorless oil; H NMR (400 MHz, CDCl3) δ 6.74
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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 cmꢀ1; HRMS(ESI): calcd. for
C11H17O4 [M+H]+ 213.1127, found 213.1121.
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Ethyl 3ꢀmethoxyꢀ5,5ꢀdimethylꢀ2ꢀoxoꢀ7ꢀoxabicyclo[4.1.0]heptꢀ3ꢀeneꢀ1ꢀcarboxylate (2q): 63%, 45.4 mg; colorless oil; H 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 cmꢀ1; HRMS(ESI): calcd. for C12H17O5 [M+H]+ 241.1076, found 241.1080.
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Ethyl 1ꢀhydroxyꢀ3ꢀmethoxyꢀ5,5ꢀdimethylꢀ2ꢀoxocyclohexꢀ3ꢀenecarboxylate (3q): 21%, 15.2 mg; colorless oil; H 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 cmꢀ1; HRMS(ESI): calcd. for C12H19O5 [M+H]+
243.1232, found 243.1229.
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Ethyl 5ꢀoxoꢀ7ꢀoxaspiro[bicyclo[4.1.0]hept[3]eneꢀ2,2'ꢀ[1,3]dioxolane]ꢀ6ꢀcarboxylate (2r): 72%, 51.8 mg; colorless oil; H NMR (400
MHz, CDCl3) δ 6.32 (dd, J = 12.0, 4.0Hz, 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 cmꢀ1; HRMS(ESI): calcd. for
C11H13O6 [M+H]+ 241.0712, found 241.0709.
Methyl 5,5ꢀdimethylꢀ2ꢀoxoꢀ7ꢀoxabicyclo[4.1.0]heptaneꢀ1ꢀcarboxylate (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 cmꢀ1; HRMS(ESI): calcd. for C10H15O4 [M+H]+ 199.0970, found 199.0965.
1
Methyl 3,3ꢀdimethylꢀ6ꢀoxocyclohexꢀ1ꢀeneꢀ1ꢀcarboxylate (5s): 21%, 11.5 mg; colorless oil; H 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.
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1aꢀAcetylꢀ7,7ꢀdimethylꢀ7,7aꢀdihydronaphtho[2,3ꢀb]oxirenꢀ2(1aH)ꢀone (2t): 75%, 51.8 mg; colorless oil; H NMR (CDCl3, 400MHz) δ
7.97ꢀ8.00 (m 1H), 7.59ꢀ7.63 (m, 1H), 7.36ꢀ7.41 (m, 2H), 3.54 (s, 1H), 2.44 (s, 3H), 1.67 (s, 3H),1.35 (s, 3H); 13C{1H}NMR (CDCl3,
100MHz) 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 cmꢀ1; HRMS(ESI): calcd. for C14H15O3 [M+H]+ 231.1021, found 231.1026.
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Methyl 4,4ꢀdimethylꢀ1ꢀoxoꢀ1,4ꢀdihydronaphthaleneꢀ2ꢀcarboxylate (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, 907, 772 cmꢀ1; calcd. for C14H15O3 [M+H]+ 231.1021, found 231.1019.
Preparation of AIBA
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At 0 oC, a stream of O3/O2 was continually introduced to the suspension of 2ꢀiodoꢀ5ꢀ(trimethylammonio)benzoate (500 mg, 1.64 mmol) in
o
acetone (80 mL). The suspension was stirred at 0 C for 12 hours. 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.: 97ꢀ100 oC (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 cmꢀ1; HRMS(ESI): calcd. for C10H13NO3I [M+H]+ 321.9935, found 321.9931.
The 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,
o
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
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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
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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 βꢀ[D2]ꢀ1a
1,1ꢀDimethylꢀ1,2,3,4ꢀtetrahydronaphthalenꢀ2ꢀdꢀ2ꢀol: 1,1ꢀDimethylꢀ3,4ꢀdihydronaphthalenꢀ2(1H)ꢀone was prepared following the literaꢀ
ture procedure.25 To the solution of 1,1ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ2(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 1,1ꢀdimethylꢀ1,2,3,4ꢀ
tetrahydronaphthalenꢀ2ꢀdꢀ2ꢀol (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); 13C{1H}NMR (100
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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.
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4,4ꢀDimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀoneꢀ2,3,3ꢀd3: 4,4ꢀDimethylnaphthalenꢀ1(4H)ꢀoneꢀ3ꢀd was prepared following the literature
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procedure.26 NiCl2 2H2O (650 mg, 5 mmol) was added to 0.5 mL of dry CD3OD. The resulting suspension was cooled to 0 oC and NaBD4
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(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
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min and then a solution of 4,4ꢀdimethylnaphthalenꢀ1(4H)ꢀoneꢀ3ꢀd (173 mg, 1 mmol) in CD3OD (0.5 mL) was transferred into it. The coolꢀ
ing bath was removed immediately after the addition and the reaction mixture was stirred at room temperature for 1 h. The reaction mixꢀ
ture 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
4,4ꢀdimethylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀoneꢀ2,3,3ꢀd3 as a colorless oil (161 mg, 91%).
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Methyl
4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀtetrahydronaphthaleneꢀ2ꢀcarboxylateꢀ3,3ꢀd2:
Methyl
4,4ꢀdimethylꢀ1ꢀoxoꢀ1,2,3,4ꢀ
tetrahydronaphthaleneꢀ2ꢀcarboxylateꢀ3,3ꢀd2 was obtained following the procedure for the preparation of 1a with 4,4ꢀdimethylꢀ3,4ꢀ
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dihydronaphthalenꢀ1(2H)ꢀoneꢀ2,3,3ꢀd3 (89 mg, 0.5 mmol) and dimethyl carbonate (5 mL) as the starting material. Yield: 85%, 75 mg. H
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.
The procedure for the KIE experiment
The reaction was conducted in the presence of 1a and βꢀ[D2]ꢀ1a, according3u to the standard procedure except that the amount of AIBX
was reduced to 0.5 equiv in order to make sure a proper conversion. To the solution of 1a (23 mg, 0.1 mmol) and βꢀ[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
o
90 C for 6 h. After cooling to room temperature, the reaction mixture was diluted with water, extract with EtOAc (50 mL×3). The comꢀ
bined 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 βꢀ[D1]ꢀI (7mg, I/βꢀ[D1]ꢀI = 9/1) in combination with 2a and βꢀ[D1]ꢀ2a (8mg, 2a/βꢀ[D1]ꢀ2a = 3/2). kH/kD =
(I + 2a)/(βꢀ[D1]ꢀI + βꢀ[D1]ꢀ2a) = 2.9.
Computational Details
Truhlar et al.’s M06ꢀ2X 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 M06ꢀ2X functional in conꢀ
jugation with a mixed basis set of the Lanl2dz29 pseudopotential for iodine and 6ꢀ31+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.31All 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 M06ꢀ2X/[6ꢀ
311++G(2df,2p) + SDD(I)](SMD) level with the M06ꢀ2X/[6ꢀ31+G(d) + Lanl2dz(I)](SMD) structures. Computed structures were illustratꢀ
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AUTHOR INFORMATION
Corresponding Author
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*Eꢀmail: xuexs@nankai.edu.cn.
* Eꢀmail: zhangchi@nankai.edu.cn.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
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.
Supporting Information
Copies of NMR spectra and computational details. This material is available free of charge via the Internet at http://pubs.acs.org.
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14. (a) For bimolecular processes, translational and rotational entropy losses in the transition state will be overestimated. Therefore, we
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