HETEROCYCLES

Paper | Regular issue | Vol. 83, No. 8, 2011, pp. 1783-1805
Received, 20th April, 2011, Accepted, 16th June, 2011, Published online, 20th June, 2011.
DOI: 10.3987/COM-11-12241

■ Synthesis of Peroxylactones Using Mn(III)-Catalyzed Aerobic Oxidation

Md. Aminul Haque and Hiroshi Nishino*

Graduate School of Science and Technology, Kumamoto University, Kurokami 2-39-1, Kumamoto 860-8555, Japan

Abstract

The aerobic oxidation of tetronic acid in the presence of 1,1-disubstituted alkenes afforded hydroperoxyethyl-peroxylactones, while a similar reaction using 3-alkyl-substituted tetronic acids gave stable crystalline peroxylactones in good to excellent yields. The oxidation using a stoichiometric amount of manganese(III) acetate did not give the bicyclic lactone but the ethenyl- and/or ethyl-tetronic acid derivatives.

INTRODUCTION
Many cyclic peroxides have been isolated from marine metabolites, terrestrial sources, steroids, and fatty acids.1 These cyclic peroxides have various biological activities, for example, cytotoxic, antitumor, antimalarial, antifungal, antagonistic, antimicrobial, ichthyotoxic, antibacterial, etc. These activities seem to be attributable to the active decomposition products derived from the cleavage of the peroxy bond in vivo.2 Although the peroxide linkage generally appears to be weak since the dissociation energy is estimated to be only 34 kcal/mol,3 six-membered cyclic peroxides are unexpectedly stable in neutral and basic media, even in acidic solution, based on our experience.4,5 Recently, Taylor et al. reported the synthesis of peroxylactones6 and conversion into building blocks of Hagen’s gland lactones7 and natural products.8 Plakortolides having a cytotoxic property were isolated from marine sponges9 and used as the starting material of the building blocks.6 The plakortolides consist of a 2,3,7-trioxabicyclo- [4.3.0]nonan-8-one skeleton, so we conceived the reaction of tetronic acids, a kind of cyclic β-keto esters, with alkenes under Mn(III)-catalyzed aerobic oxidation conditions to synthesize a similar trioxabicyclo[4.3.0]nonanone scaffold (Scheme 1).4c,10 A commercially available tetronic acid (4-hydroxy-2(5H)-furanone) and its derivatives are also important as a core of the biologically active natural products such as the antibiotic, antiviral, antineoplastic, anticoagulant, insecticidal, acaricidal, antioxidant, and anti-inflammatory agents.11 In this paper, we describe the synthesis of new 2,3,8-trioxabicyclo[4.3.0]nonan-7-ones, their characterization, and related reaction.

RESULTS AND DISCUSSION
Reaction of Tetronic Acid (1a) with 1,1-Disubstituted Alkenes 2a-j. We initially examined the reaction of a commercially available tetronic acid (1a) with crystalline 1,1-bis(4-chlrorophenyl)ethene (2a) in the presence of manganese(III) acetate in acetic acid at room temperature in order to evaluate the aerobic oxidation. When the reaction was carried out at the molar ratio of 1a:2a:Mn(OAc)3 = 2:0.5:0.5, the desired peroxylactone 3a was fortunately isolated in 8% yield (Scheme 2 and Table 1, Entry 1). Since the 1:1 stoichiometric product was not isolated, but the hydroperoxyethyl-peroxylactone 3a was produced by the reaction of 1a with double 2a,12 we focused on the synthesis of the hydroperoxyethyl- peroxylactone 3a. After the optimization of the reaction conditions, the yield of 3a was improved up to 58% (Entry 6).

The structure of 3a was deduced by spectroscopic methods. The characteristic hydroperoxy group in the 1H NMR spectrum appeared at 11.44 ppm which shifted downfield in DMSO-d6 because of the intramolecular hydrogen-bond with the ester carbonyl group,12 and three pairs of the geminal AB quartet appeared at 4.48 and 3.84 ppm (J = 10.1 Hz), 3.18 and 2.87 ppm (J = 14.7 Hz), and 3.00 and 2.43 ppm (J = 14.4 Hz), respectively, assigned to the three methylene protons. In the 13C NMR spectrum, only one carbonyl carbon appeared at 172.8 ppm due to the ester carbonyl group, and three characteristic quaternary carbons attached to the peroxy bonds were revealed at 103.2, 85.3, and 82.9 ppm. Therefore,

the structure of 3a was determined to be 6-[2,2-bis(4-chlorophenyl)-2-hydroperoxyethyl]-4,4-bis(4-chlorophenyl)-1-hydroxy-2,3,8-trioxabicyclo[4.3.0]nonan-7-one based on the spectroscopic data including the HMQC spectrum and the elemental analysis.
With the optimized conditions in hand, we applied the reaction to various 1,1-disubstituted alkenes 2b-j, and the desired hydroperoxyethyl-peroxylactones 3b-d,f-i were obtained in moderate to good yields (Scheme 1 and Table 1, Entries 7-9,11-14). From the reaction with 2a-c, only one isomer each 3a-c probably due to energetically advantageous cis-fused peroxylactones was produced (Entries 6-8).13,14 The product 3d (Entry 9) existed as an equilibrium mixture of hydroperoxyethyl-peroxylactone 3d and bishydroperoxide 3d’ in both CDCl3 and DMSO-d6 on the NMR time scale (Scheme 3). The reaction with 2f-i also gave a stereoisomeric mixture of the corresponding hydroperoxyethyl-peroxylactones 3f-i in good yields (Entries 11-14), one of which could be isolated. Surprisingly, the reaction with 2e having

electron-donating substituents did not proceed and the alkene 2e was recovered (Entry 10). The reaction with 2-ethyl-1-butene (2j) resulted in an intractable mixture (Entry 15).
Reaction of 3-Substituted Tetronic Acids 1b-g with Various Alkenes 2a-l. In order to prevent the double attack of the alkenes 2 on the tetronic acid (1a), we planned the reaction using 3-substituted tetronic acids. The 3-substituted tetronic acids 1b-g were prepared by bromination of the corresponding 2-alkyl-3-oxobutanoates with bromine followed by cyclization.15 With the 3-substituted tetronic acids 1b-g in hand, we explored the aerobic oxidation of 3-methyltetronic acid (1b) using 1,1-diphenylethene (2c) (Scheme 4). When the reaction was carried out using one equivalent of manganese(III) acetate, the desired peroxylactone 4bc was obtained in 85% yield (Table 2, Entry 3). After optimizing the reaction conditions, the highest yield of 4bc (95%) was achieved using a catalytic amount of manganese(III) acetate (Entry 5). The structure of 4bc was assigned by the spectroscopic method. The 1H NMR spectrum showed two specific pairs of geminal AB quartets at 4.22 and 3.95 ppm (J = 10.5 Hz), 3.41 and 2.40 ppm (J = 14.4 Hz), respectively, and the characteristic two quaternary carbons attached to an endoperoxy group appeared at 103.1 and 84.3 ppm in the 13C NMR spectrum. Therefore, the structure was determined to be 1-hydroxy-6-methyl-4,4-diphenyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one, and the elemental analysis also agreed with the structure. Since we were delighted to obtain the desired peroxylactone, we examined the reaction using other 3-alkyl-substituted tetronic acids 1c-g and alkenes 2a-l. All the reactions gave the

desired peroxylactones 4 in good to excellent yields except for 2-ethyl-1-butene (2j) which afforded an inseparable mixture (Table 2, Entries 1, 2, 6-19). When the 1,1-disubstututed alkenes 2g, 2h, 2i, 2k, and 2l having a different substituent were used in the reaction, two diastereomers were isolated and characterized (Entries 8-10, 13, and 14). Surprisingly, 3-benzyltetronic acid was consumed within 3 h, giving the peroxylactone 4fc in 80% yield (Entry 18).
Reaction at Elevated Temperature. Concave bicyclic lactones, such as Hagen’s gland lactones, are structurally and biologically interesting,7,16 therefore, it was speculated that the bicyclic lactones such as A in Scheme 5 would be formed by the Mn(III)-based oxidative addition of tetronic acids to alkenes in the absence of molecular oxygen. We then explored the teronic acids with alkenes using a stoichiometric amount of manganese(III) acetate at elevated temperature. As a result, the reaction of tetronic acid (1a) with the 1,1-disubstituted alkenes 2a and 2c did not give the bicyclic lactone A, but the teronic acid (1a) underwent double alkylation to afford the diethyl- and/or ethenyl-ethyl-substituted tetronic acids 5 and/or 6 along with peroxypropellane 7 when 2c was used (Scheme 5 and Table 3, Entries 1 and 2).4c,12,14,17 The formation of the peroxypropellane 7 could be avoided by the reaction under an argon atmosphere.17 The 3-alkyl-substituted tetronic acids 1b-g also underwent substitution to produce the corresponding ethyl- 8 and/or ethenyl-tetronic acids 9 (Table 3, Entries 3-9).

Reaction Pathway. Although the mechanism for the formation of the endoperoxides 3 and 4 in the Mn(III)-catalyzed aerobic oxidation and the ethenyl- 6, 9 and/or ethyl-tetronic acid derivatives 5, 8 in the Mn(III)-mediated oxidation is well-documented in the literature,18 in order to comprehend the present reactions, the reaction pathway is outlined in Schemes 6 and 7. The tetronic acid 1 underwent complexation with Mn(III) catalyst to produce enolate complex B followed by single electron-transfer oxidation and addition with the alkene 2, giving radical D (Scheme 6). The radical D would be trapped by the dissolved molecular oxygen to form peroxy radical E, which would be reduced by Mn(II) species followed by cyclization and protonation to produce the peroxylactone 4, when the substituent R3 is an alkyl group. On the other hand, when the R3 group is hydrogen, the peroxy radical E would prefer to undergo hydrogen abstraction to produce hydroperoxyethyl radical H, and finally, the hydroperoxyethyl-peroxylactone 3 would be obtained via similar steps from E to 4 (Scheme 6). Although it is not clear the reaction of 1a with 2e did not occur at this moment (Table 1, Entry 10), the equilibrium

from C to I in Scheme 6 might lie so far to the left since the electron-rich alkene 2e might be considerably stable under the conditions. In addition, the radical reaction would not be controlled in the reaction with 2j since the radical intermediate D would not be sufficiently stabilized by the inductive effect of the alkyl substituent (R1 = R2 = Et). Therefore, the reaction gave an intractable mixture (Table 1, Entry 15 and Table 2, Entry 12).
When the reaction was carried out at elevated temperature using a stoichiometric amount of the oxidant, the radical D would be preferentially oxidized to produce the corresponding cation L (Scheme 7). The cation L did not cyclize with the keto-carbonyl oxygen probably because of the steric strain and the instability of the hemiacetal A in boiling acetic acid, but predominantly would be attacked by the solvent or deprotonate to produce 8 or 9. When the R3 group is hydrogen, a similar oxidation would be repeated to afford 5 and 6.

CONCLUSION
We achieved the synthesis of the peroxylactones 3 and 4 which might be important building blocks of some synthetic targets. The peroxylactones could be used for the construction of Hagen’s gland lactone analogues,19 or converted into the corresponding diols as a building block.6 The direct synthesis of the concave bicyclic lactones A failed. Since the peroxylactones are stable and handy, the biological screening of the peroxylactones 3 and 4 are underway.

EXPERIMENTAL
General Information. Melting points were taken using a Yanagimoto micromelting point apparatus and were not corrected. The NMR spectra were recorded using a JNM AL300 or ECX 500 FT-NMR spectrometer at 300 or 500 MHz for 1H and 75 or 125 MHz for 13C, with tetramethylsilane as the internal standard. The chemical shifts are reported in δ values (ppm) and the coupling constants in Hz. The IR spectra were measured in chloroform or KBr using a Shimadzu 8400 FT IR spectrometer and expressed in cm-1. The EI MS spectra were measured by a Shimadzu QP-5050A gas chromatograph-mass spectrometer with the ionizing voltage of 70 eV. The high-resolution mass spectra and the elemental analysis were performed at the Instrumental Analysis Center, Kumamoto University, Kumamoto, Japan. Manganese(II) acetate tetrahydrate, Mn(OAc)2•4H2O, was purchased from Wako Pure Chemical Ind., Ltd. Manganese(III) acetate dehydrate, Mn(OAc)3•2H2O, was prepared according to the modified method described in the literature.20 The 1,1-disubstituted ethenes 2a-2i and 2k were prepared by the reaction of the corresponding acetophenones with arylmagnesium bromides followed by dehydration. Tetronic acid (1a), 2-ethyl-1-butene (2j) and styrene (2l) were purchased from Tokyo Chemical Industry Co., Ltd., and used as received.
Preparation of 3-Substituted Tetronic Acids (1b-g).
4-Hydroxy-3-methyl-2(5H)-furanone (1b) was prepared as follows.15a Bromine (5.85g, 36.5 mmol) in CHCl3 (5 mL) was dropwise added to a stirred solution of ethyl α-methylacetoacetate (5g, 34.5 mmol) in CHCl3 (17 mL) at 0 °C, and the reaction mixture was further stirred for 1 h at rt. Evaporation of the solvent gave the residue, which was heated for 2 h at 130 °C. After cooling, the solid residue was washed with hexane and then recrystallized from methanol to give 1b (2.7 g; 68%) as colorless needles. The other 3-substituted tetronic acids 1c-g were prepared by a method similar to that already described.
4-Hydroxy-3-methyl-2(5H)-furanone (1b): Colorless needles (from MeOH); mp 190-191 °C (lit.15a mp 190-191 °C); IR (KBr) ν 1749, 1681 (C=O); 1H NMR (DMSO-d6) δ = 11.81 (1H, br s, OH), 4.57 (2H, s, CH2-C=O), 1.59 (3H, s, Me); 13C NMR (DMSO-d6); δ = 175.2 (C-4), 172.9 (C-2, C=O), 94.4 (C-3), 66.5 (C-5, CH2), 5.9 (Me).
3-Ethyl-4-hydroxy-2(5H)-furanone (1c): Colorless needles (from CHCl3/hexane); mp 126-127 °C (lit.15e,f mp 127-129 °C); IR (KBr) ν 1730, 1654 (C=O); 1H NMR (DMSO-d6) δ = 10.62 (1H, br s, OH), 4.62 (2H, s, CH2-C=O), 2.17 (2H, q, J = 7.8 Hz, CH2), 1.01(3H, t, J = 7.8 Hz, Me); 13C NMR (DMSO-d6) δ = 179.2 (C-4), 174.4 (C-2, C=O), 102.7 (C-3), 67.9 (C-5, CH2), 14.4 (CH2), 12.4 (Me).
3-Isopropyl-4-hydroxy-2(5H)-furanone (1d): Colorless needles (from EtOAc/hexane); mp 121-123 °C (lit.15c mp 120-123 °C); IR (KBr) ν 1724, 1662 (C=O); 1H NMR (DMSO-d6) δ = 10.48 (1H, br s, OH), 4.64 (2H, s, CH2-C=O), 2.74 (1H, m, CH), 1.19 (6H, d, J = 6.9 Hz, 2Me); 13C NMR (DMSO-d6) δ = 178.4 (C-4), 173.8 (C-2, C=O), 106.1 (C-3), 67.5 (C-5, CH2), 22.8 (CH), 20.2 (2Me).
3-Butyl-4-hydroxy-2(5H)-furanone (1e): Colorless needles (from CHCl3/hexane); mp 121-122 °C (lit.15d 121-123 °C); IR (KBr) ν 1732, 1658 (C=O); 1H NMR (DMSO-d6) δ = 10.66 (1H, br s, OH), 4.62 (2H, s, CH2-C=O), 2.14 (2H, t, J = 7.2 Hz, CH2), 1.30 (4H, m, 2CH2), 0.83(3H, t, J = 7.2 Hz, Me); 13C NMR (DMSO-d6) δ = 179.5 (C-4), 174.8 (C-2, C=O), 101.4 (C-3), 67.9 (C-5, CH2), 29.9, 22.4, 20.6 (CH2), 13.7 (Me).
3-Benzyl-4-hydroxy-2(5H)-furanone (1f): Colorless amorphous solid15g; IR (KBr) ν 1747, 1672 (C=O); 1H NMR (DMSO-d6) δ = 12.14 (1H, br s, OH), 7.29-7.14 (5H, m, arom H), 4.66 (2H, s, CH2-C=O), 3.42 (2H, s, PhCH2); 13C NMR (DMSO-d6) δ = 174.8 (C-4), 174.1 (C-2, C=O), 139.6, 128.3, 128.1, 125.9 (arom C), 98.4 (C-3), 66.6 (C-5, CH2), 26.6 (CH2).
4-Hydroxy-3-pentyl-2(5H)-furanone (1g): Colorless needles (from CHCl3/hexane); mp 112-113 °C (lit.15d mp 112-113 °C); IR (KBr) ν 1737, 1662 (C=O); 1H NMR (DMSO-d6) δ = 11.74 (1H, br s, OH), 4.56 (2H, s, CH2-C=O), 2.10-1.99 (2H, br, CH2), 1.38-1.23 (6H, br, 3CH2), 0.86-0.84 (3H, br, Me); 13C NMR (DMSO-d6) δ = 174.9 (C-4), 173.13 (C-2, C=O), 99.0 (C-3), 66.3 (C-5, CH2), 30.9, 27.1, 21.8, 20.7 (CH2), 13.9 (Me).
Reaction of Tetronic Acid (1a) with 1,1-Disubstituted Alkenes 2a-j. To a solution of the tetronic acid (1a) (0.5 mmol) and 1,1-disubstituted alkene 2 (1 mmol) in glacial acetic acid (20 mL), manganese(III) acetate dehydrate (0.25 mmol) was added. The mixture was stirred at rt in air for 11-15 h, and then the reaction was quenched by adding water (20 mL) to the mixture. The aqueous reaction mixture was extracted three times with CH2Cl2 (30 mL) and the combined extracts were washed with water, then a saturated aqueous solution of NaHCO3, dried over anhydrous MgSO4, and concentrated to dryness. The residue was purified by silica gel column chromatography while eluting with the appropriate solvent. The results are shown in Table 1. The products 3f-i were obtained as a stereoisomeric mixture. Although we could not determine the diastereomeric ratio, one of the diastereomers was isolated and characterized after chromatographic separation. The data of the isolated diastereomers 3f-i were described (vide infra).
6-[2,2-Bis(4-chlorophenyl)-2-hydroperoxyethyl]-4,4-bis(4-chlorophenyl)-1-hydroxy-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (3a): Yield (190.5 mg, 58%); Rf = 0.65 (Et2O/hexane 7:3 v/v); colorless needles (from CHCl3/hexane); mp 177-178 °C; IR (KBr) ν 3600-3100 (OOH, OH), 1757 (C=O); 1H NMR (DMSO-d6) δ = 11.44 (1H, s, OOH), 8.16 (1H, s, OH), 7.44-7.11 (16H, m, arom H), 4.48 (1H, d, J = 10.1 Hz, Ha-9), 3.84 (1H, d, J = 10.1 Hz, Hb-9), 3.18 (1H, d, J = 14.7 Hz, Ha-5), 3.00 (1H, d, J = 14.4, aCH2), 2.87 (1H, d, J = 14.7 Hz, Hb-5), 2.43 (1H, d, J = 14.4 Hz, bCH2); 13C NMR (DMSO-d6) δ = 172.8 (C=O), 143.4, 143.3, 142.7, 139.9, 132.5, 131.8, 131.6, 131.5 (arom C), 128.6, 128.4, 128.1, 127.8, 127.6, 126.8 (arom CH), 103.2 (C-1), 85.3 (quart C), 82.9 (C-4), 69.3 (CH2), 44.3 (C-6), 38.4, 35.1 (CH2). Anal. Calcd for C32H24Cl4O7•1/3H2O: C, 57.51; H, 3.72. Found: C, 57.57; H, 3.81.
6-[2,2-Bis(4-fluorophenyl)-2-hydroperoxyethyl]-4,4-bis(4-fluorophenyl)-1-hydroxy-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (3b): Yield (152 mg, 51%); Rf = 0.49 (Et2O/hexane 7:3 v/v); colorless microcrystals (from CHCl3/hexane); mp 121-122 °C; IR (KBr) ν 3600-3100 (OOH, OH), 1774 (C=O); 1H NMR (CDCl3) δ = 8.95 (1H, s, OOH), 7.38-6.88 (16H, m, arom H), 4.46 (1H, s, OH), 4.32 (1H, d, J = 10.5 Hz, Ha-9), 3.87 (1H, d, J = 10.5 Hz, Hb-9), 3.21 (1H, d, J = 15.6 Hz, Ha-5), 3.03 (1H, d, J = 14.7 Hz, aCH2), 2.96 (1H, d, J = 15.6 Hz, Hb-5), 2.27 (1H, d, J = 14.7 Hz, bCH2); 13C NMR (CDCl3) δ = 175.0 (C=O), 163.6, 163.5, 160.5, 139.9, 139.5, 137.7, 134.9 (arom C), 128.7, 128.6, 127.9, 127.9, 127.8, 127.7, 127.0, 126.9, 115.6, 115.5, 115.4, 115.3, 115.2, 115.1, 114.8 (arom CH), 103.3 (C-1), 86.1 (quart C), 84.5 (C-4), 70.6 (CH2), 44.9 (C-6), 40.7, 37.0 (CH2). Anal. Calcd for C32H24F4O7: C, 64.43; H, 4.06. Found: C, 64.72; H, 4.27.
6-(2-Hydroperoxy-2,2-diphenylethyl)-1-hydroxy-4,4-diphenyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (3c): Yield (150.9 mg, 58%); Rf = 0.29 (Et2O/hexane 7:3 v/v); colorless microcrystals (from CHCl3/hexane); mp 112-114 °C; IR (KBr) ν 3600-3100 (OOH, OH), 1786 (C=O); 1H NMR (CDCl3) δ = 8.99 (1H, s, OOH), 7.59-6.92 (20H, m, arom H), 4.67 (1H, s, OH), 4.30 (1H, d, J = 10.5 Hz, Ha-9), 3.84 (1H, d, J = 10.5 Hz, Hb-9), 3.21 (1H, d, J = 15.6 Hz, Ha-5), 3.11 (1H, d, J = 14.7 Hz, aCH2), 3.05 (1H, d, J = 15.6 Hz, Hb-5), 2.32 (1H, d, J = 14.7 Hz, bCH2); 13C NMR (CDCl3) 175.4 (C=O), 144.6, 144.0, 142.2, 139.8 (arom C), 130.2, 128.6, 128.2, 127.8, 127.4, 127.3, 127.2, 126.7, 126.4, 126.0, 125.2, 124.9 (arom CH), 103.4 (C-1), 86.7 (quart C), 84.9 (C-4), 70.6 (CH2), 45.0 (C-6), 40.6, 36.7 (CH2). Anal. Calcd for C32H28O7•1/2 H2O: C, 72.03; H, 5.48. Found: C, 72.19; H, 5.73.
6-[2-Hydroperoxy-2,2-bis(4-methylphenyl)ethyl]-1-hydroxy-4,4-bis(4-methylphenyl)-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (3d): Yield (101.6 mg, 35%); IR (KBr) ν 3600-3100 (OOH, OH), 1786 (C=O); 1H NMR (CDCl3) the OOH group did not appeared; δ = 7.67-7.65 (4H, m, arom H), 7.28-6.99 (12H, m, arom H), 5.83 (1H, s, OH), 4.22 (1H, d, J = 10.2 Hz, Ha-9), 4.09 (1H, d, J = 10.2 Hz, Hb-9), 3.52 (1H, d, J = 18.0 Hz, Ha-5), 3.09 (1H, d, J = 18.0 Hz, Hb-5), 2.97 (1H, d, J = 14.4 Hz, aCH2), 2.87 (1H, d, J = 14.4 Hz, bCH2), 2.30 (3H, s, Me), 2.22 (9H, s, 3Me); 13C NMR (CDCl3) 198.1 (C-4 keto carbonyl), 177.3 (C=O), 145.4, 141.6, 138.6, 137.5, 137.0, 133.3, 124.6 (arom C), 129.4, 129.2, 129.1, 128.8, 128.5, 126.2, 125.3, 124.5 (arom CH), 104.0 (C-1), 85.0 (quart C), 76.6 (C-4), 73.2 (C-9), 46.0 (C-6), 42.0 (CH2), 36.7 (C-5), 31.7, 27.5 (Me); 13C NMR (DMSO-d6) 196.7 (C-4 keto carbonyl), 177.1 (C=O), 144.1, 139.1, 136.4, 136.1, 133.4 (arom C), 129.8, 129.3, 129.1, 128.8, 128.5, 128.2, 125.7, 124.9 (arom CH), (C-1 missing), 84.1 (quart C), (C-4 missing), (C-9 missing), 44.7 (C-6), 43.8 (CH2), (C-5 missing), 21.7, 21.0 (Me). Anal. Calcd for C36H36O7•1/2H2O: C, 73.33; H, 6.33. Found: C, 73.10; H, 6.03.
6-[2-(4-Bromophenyl)-2-(4-chlorophenyl)-2-hydroperoxyethyl]-4-(4-bromophenyl)-4-(4-chlorophenyl)-1-hydroxy-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (3f): Yield (161.5 mg, 43%); Rf = 0.48 (EtOAc/hexane 4:6 v/v); colorless needles (from CHCl3/hexane); mp 160-162 °C; IR (KBr) ν 3550-3100 (OOH, OH), 1757 (C=O); 1H NMR (DMSO-d6) δ = 11.46 (1H, s, OOH), 8.18 (1H, s, OH), 7.62-7.03 (16H, m, arom H), 4.48 (1H, d, J = 10.5 Hz, Ha-9), 3.83 (1H, d, J = 10.5 Hz, Hb-9), 3.18 (1H, d, J = 15.0 Hz, Ha-5), 3.00 (1H, d, J = 14.1 Hz, aCH2), 2.87 (1H, d, J = 15.0 Hz, Hb-5), 2.42 (1H, d, J = 14.1 Hz, bCH2); 13C NMR (DMSO-d6) δ = 172.8 (C=O), 143.8, 143.2, 143.1, 142.6, 140.4, 139.9, 120.4, 120.2 (arom C), 131.3, 130.8, 130.5, 128.9, 128.7, 128.5, 128.4, 128.0, 127.8, 127.6, 127.0, 126.9, 126.7, 126.7 (arom CH), 103.2 (C-1), 85.3 (quart C), 82.8 (C-4), 69.3 (CH2), 44.3 (C-6), 38.3, 35.0 (CH2). Anal. Calcd for C32H24Br2Cl2O7•1/2H2O: C, 50.56; H, 3.31. Found: C, 50.67; H, 3.53.
6-[2-(4-Chlorophenyl)-2-hydroperoxypropyl]-4-(4-chlorophenyl)-1-hydroxy-4-methyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (3g): Yield (94 mg, 40%); Rf = 0.21 (EtOAc/hexane 3:7 v/v); colorless microcrystals (from CHCl3/hexane); mp 81-83 °C; IR (KBr) ν 3600-3100 (OOH), 1770 (C=O); 1H NMR (CDCl3) δ = 8.92 (1H, s, OOH), 7.38-7.21 (8H, m, arom H), 4.37 (1H, d, J = 10.5 Hz, Ha-9), 4.16 (1H, s, OH), 3.79 (1H, d, J = 10.5 Hz, Hb-9), 2.92 (1H, d, J = 14.7 Hz, Ha-5), 2.49 (1H, d, J = 15.6 Hz, aCH2), 2.31 (1H, d, J = 15.6 Hz, bCH2), 1.92 (1H, d, J = 14.7 Hz, Hb-5), 1.67 (3H, s, Me), 1.29 (3H, s, Me); 13C NMR (CDCl3) δ = 174.7 (C=O), 140.4, 139.3, 133.6, 133.1, (arom C), 128.4, 128.1, 127.2, 126.7, (arom CH), 103.2 (C-1), 84.5 (quart C), 82.1 (C-4), 70.3 (CH2), 44.7 (C-6), 43.4, 36.9 (CH2), 31.6, 27.6 (Me). Anal. Calcd for C22H22Cl2O7•1/3H2O: C, 55.59; H, 4.81. Found: C, 55.83; H, 5.06.
6-[2-Hydroperoxy-2-phenylpropyl]-1-hydroxy-4-methyl-4-phenyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (3h): Yield (161 mg, 80%); Rf = 0.26 (EtOAc/Hexane 3:7 v/v); colorless microcrystals (from CHCl3/hexane); mp 89-91 °C; IR (KBr) ν 3650-3100 (OOH, OH), 1766 (C=O); 1H NMR (CDCl3) δ = 8.88 (1H, s, OOH), 7.40-7.08 (10H, m, arom H), 4.43 (1H, s, OH), 4.27 (1H, d, J = 10.2 Hz, Ha-9), 3.69 (1H, d, J = 10.2 Hz, Hb-9), 2.88 (1H, d, J = 14.7 Hz, Ha-5), 2.43 (1H, d, J = 15.9 Hz, aCH2), 2.28 (1H, d, J = 15.9 Hz, bCH2), 1.84 (1H, d, J = 14.7 Hz, Hb-5), 1.63 (3H, s, Me), 1.21 (3H, s, Me); 13C NMR (CDCl3) δ = 174.8 (C=O), 142.1, 140.9, (arom C), 128.2, 127.7, 127.6, 127.1, 125.6, 125.1, (arom CH), 103.1 (C-1), 84.9 (quart C), 82.3 (C-4), 70.3 (CH2), 44.8 (C-6), 43.6, 36.8 (CH2), 31.7, 27.5 (Me). Anal. Calcd for C22H24O7•1/3H2O: C, 65.01; H, 6.12. Found: C, 65.12; H, 6.06.
6-[2-Hydroperoxy-2-(4-methylphenyl)propyl]-1-hydroxy-4-(4-methylphenyl)-4-methyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (3i): Yield (124.3 mg, 58%); Rf = 0.35 (EtOAc/hexane 4:6 v/v); colorless microcrystals (from CHCl3/hexane); mp 209-211 °C; IR (KBr) ν 3600-3100 (OOH, OH), 1766 (C=O); 1H NMR (CDCl3) δ = 8.84 (1H, s, OOH), 7.26-7.05 (8H, m, arom H), 4.37 (1H, d, J = 10.8 Hz, Ha-9), 4.11 (1H, s, OH), 3.77 (1H, d, J = 10.8 Hz, Hb-9), 3.03 (1H, d, J = 14.7 Hz, Ha-5), 2.33 (8H, m, 2CH3, 1H (Hb-5), 1H (aCH2)), 1.96 (1H, d, J = 14.7 Hz, bCH2), 1.68, (3H, s, Me), 1.30 (3H, s, Me); 13C NMR (CDCl3) δ = 174.7 (C=O), 138.9, 137.9, 137.3, 136.7, (arom C), 128.9, 128.5, 125.6, 125.0, (arom CH), 103.2 (C-1), 84.9 (quart C), 82.3 (C-4), 70.3 (CH2), 44.7 (C-6), 43.6, 37.1 (CH2), 31.8, 27.7, 21.1, 20.9 (Me). Anal. Calcd for C24H28O7•4/5H2O: C, 65.09; H, 6.74. Found: C, 64.72; H, 6.46.
Reaction of 3-Substituted Tetronic Acids 1b-g with Various Alkenes 2a-l. To a solution of the 3-substituted tetronic acid 1 (1 mmol) and alkene 2 (1 mmol) in glacial acetic acid (20 mL), manganese(III) acetate dehydrate (0.2 mmol) was added. The mixture was stirred at rt in air until the alkene 2 was completely consumed, and then the reaction was quenched by adding water (20 mL) to the mixture. The aqueous reaction mixture was extracted three times with CH2Cl2 (30 mL) and the combined extracts were washed with water, then a saturated aqueous solution of NaHCO3, dried over anhydrous MgSO4, and concentrated to dryness. The residue was purified by silica gel column chromatography while eluting with the appropriate solvent. The results are shown in Table 2.
4,4-Bis(4-chlorophenyl)-1-hydroxy-6-methyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4ba): Yield (329.1 mg, 83%); Rf = 0.32 (EtOAc/hexane 4:7 v/v); colorless needles (from CHCl3/hexane); mp 222-223 °C; IR (KBr) ν 3550-3150 (OH), 1762 (C=O); 1H NMR (DMSO-d6) δ = 8.03 (1H, s, OH), 7.55-7.32 (8H, m, arom H), 4.25 (1H, d, J = 10.5 Hz, Ha-9), 3.97 (1H, d, J = 10.5 Hz, Hb-9), 3.40 (1H, d, J = 14.4 Hz, Ha-5), 2.39 (1H, d, J = 14.4 Hz, Hb-5), 1.25 (3H, s, Me); 13C NMR (DMSO-d6) δ = 176.7 (C=O), 142.9, 139.3, 132.5, 131.74 (arom C), 128.8 (2C), 128.3 (2C), 127.6 (2C), 127.0 (2C), (arom CH), 100.2 (C-1), 83.7 (C-4), 70.4 (CH2), 42.5 (C-6), 35.5 (CH2), 20.9 (Me). Anal. Calcd for C19H16Cl2O5: C,57.74; H, 4.08. Found: C, 57.57; H, 4.26.
4,4-Bis(4-fluorophenyl)-1-hydroxy-6-methyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4bb): Yield (304.4 mg, 84%); Rf = 0.49 (EtOAc/hexane 4:6 v/v); colorless needles (from CHCl3/hexane); mp 210-211 °C; IR (KBr) ν 3550-3200 (OH), 1762 (C=O); 1H NMR (DMSO-d6) δ = 8.03 (1H, s, OH), 7.57-7.07 (8H, m, arom H), 4.24 (1H, d, J = 10.5 Hz, Ha-9), 3.96 (1H, d, J = 10.5 Hz, Hb-9), 3.39 (1H, d, J = 14.4 Hz, Ha-5), 2.41 (1H, d, J = 14.4 Hz, Hb-5), 1.25 (3H, s, Me); 13C NMR (DMSO-d6) δ = 176.8 (C=O), 162.7, 159.5, 140.7, 136.6 (arom C), 129.2 (1C), 129.1 (2C), 127.6 (1C), 127.5 (1C), 115.3 (1C), 115.0 (1C), 114.6 (1C), 114.3 (1C) (arom CH), 103.2 (C-1), 83.9 (C-4), 70.5 (CH2), 42.6 (C-6), 35.9 (CH2), 21.1 (Me). Anal. Calcd for C19H16F2O5: C, 62.98; H, 4.45. Found: C, 62.95; H, 4.61.
1-Hydroxy-6-methyl-4,4-diphenyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4bc): Yield (310 mg, 95%); Rf = 0.51 (Et2O/hexane 7:3 v/v); colorless needles (from CHCl3/hexane); mp 205 °C; IR (KBr) ν 3550-3150 (OH), 1762 (C=O); 1H NMR (DMSO-d6) δ = 7.96 (1H, s, OH), 7.53-7.15 (10H, m, arom H), 4.22 (1H, d, J = 10.5 Hz, Ha-9), 3.95 (1H, d, J = 10.5 Hz, Hb-9), 3.41 (1H, d, J = 14.4 Hz, Ha-5), 2.40 (1H, d, J = 14.4 Hz, Hb-5), 1.24 (3H, s, Me); 13C NMR (DMSO-d6) δ = 176.8 (C=O), 144.8, 140.8 (arom C), 128.2 (2C), 127.6 (1C), 127.5 (1C), 126.7 (2C), 124.9 (2C) (arom CH), 103.1 (C-1), 84.3 (C-4), 70.5 (CH2), 42.4 (C-6), 35.8 (CH2), 21.1 (Me). Anal. Calcd for C19H18O5: C, 69.93; H, 5.56. Found: C, 69.69; H, 5.55.
1-Hydroxy-4,4-bis(4-methylphenyl)-6-methyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4bd): Yield (294.2 mg, 83%); Rf = 0.54 (EtOAc/hexane 3:7 v/v); colorless needles (from CHCl3/hexane); mp 209-210 °C; IR (KBr) ν 3550-3200 (OH), 1762 (C=O); 1H NMR (DMSO-d6) δ = 7.88 (1H, s, OH), 7.35-7.02 (8H, m, arom H), 4.19 (1H, d, J = 10.5 Hz, Ha-9), 3.91 (1H, d, J = 10.5 Hz, Hb-9), 3.28 (1H, d, J = 14.4 Hz, Ha-5), 2.35 (1H, d, J = 14.4 Hz, Hb-5), 2.22 (3H, s, Me), 2.20 (3H, s, Me), 1.22 (3H, s, Me); 13C NMR (DMSO-d6) δ = 176.9 (C=O), 142.1, 137.9, 136.8, 135.7 (arom C), 128.7 (2C), 128.2 (2C), 126.8 (2C), 125.1 (2C) (arom CH), 102.9 (C-1), 84.3 (C-4), 70.6 (CH2), 42.5 (C-6), 35.9 (CH2), 21.2, 20.6, 20.5 (Me). Anal. Calcd for C21H22O5: C, 71.17; H, 6.26. Found: C, 70.88; H, 6.37.
1-Hydroxy-4,4-bis(4-methoxyphenyl)-6-methyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4be): Yield (309.1 mg, 80%); Rf = 0.32 (EtOAc/hexane 4:7 v/v); colorless needles (from EtOAc/hexane); mp 173-174 °C; IR (KBr) ν 3500-3200 (OH), 1743 (C=O); 1H NMR (DMSO-d6) δ = 7.91 (1H, s, OH), 7.38-6.79 (8H, m, arom H), 4.20 (1H, d, J = 10.8 Hz, Ha-9), 3.92 (1H, d, J = 10.8 Hz, Hb-9), 3.24 (1H, d, J = 14.7 Hz, Ha-5), 3.72(3H, s, Me), 3.69(3H, s, Me), 2.38 (1H, d, J = 14.7 Hz, Hb-5), 1.23 (3H, s, Me); 13C NMR (DMSO-d6) δ = 176.9 (C=O), 158.5, 157.9, 137.1, 132.7 (arom C), 128.3 (2C), 126.9 (2C), 113.5 (2C), 112.9 (2C) (arom CH), 102.9 (C-1), 84.2 (C-4), 70.6 (CH2), 42.5 (C-6), 55.1, 54.9 MeO), 36.1 (CH2), 21.3 (Me). Anal. Calcd for C21H22O7: C, 65.28; H, 5.74. Found: C, 65.25; H, 5.97.
4-(4-Bromophenyl)-4-(4-chlorophenyl)-1-hydroxy-6-methyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4bf): Yield (382.5 mg, 87%); Rf = 0.56 (EtOAc/hexane 3:7 v/v); colorless needles (from EtOAc/hexane), mp 229-231 °C; IR (KBr) ν 3500-3200 (OH), 1762 (C=O); 1H NMR (DMSO-d6) δ = 8.06 (1H, s, OH), 8.05-7.32 (4H, m, arom H), 4.25 (1H, d, J = 6.6 Hz, Ha-9), 3.95 (1H, d, J = 6.6 Hz, Hb-9), 3.38 (1H, d, J = 8.7 Hz, Ha-5), 2.38 (1H, d, J = 8.7 Hz, Hb-5), 1.24 (3H, s, Me); 13C NMR (DMSO-d6) δ = 176.8 (C=O), 143.4, 142.9, 139.8, 139.4 (arom C), 131.4, 130.7, 129.2, 128.9, 128.4, 127.7, 127.4, 127.1 (arom CH), 103.3 (C-1), 83.9 (C-4), 70.5 (CH2), 42.5 (C-6), 35.5 (CH2), 20.9 (Me). Anal. Calcd for C19H16BrClO5: C, 51.90; H, 3.67. Found: C, 51.70; H, 3.69.
4-(4-Chlorophenyl)-1-hydroxy-4,6-dimethyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4bg): Yield (254.2 mg, 85%); dr = 81:19.
Major Diastereomer: Rf = 0.62 (EtOAc/hexane 4:6 v/v); colorless blocks (from CHCl3/hexane); mp 206 °C; IR (KBr) ν 3500-3100 (OH), 1726 (C=O); 1H NMR (CDCl3) δ = 7.40-7.26 (4H, m, arom H), 4.13 (1H, d, J = 6.3 Hz, Ha-9), 3.93 (1H, d, J = 6.3 Hz, Hb-9), 3.81 (1H, s, OH), 3.00 (1H, d, J = 8.7 Hz, Ha-5), 1.98 (1H, d, J = 8.7 Hz, Hb-5), 1.37 (3H, s, Me), 1.31 (3H, s, Me); 13C NMR (CDCl3) δ = 176.7 (C=O), 139.4, 133.2 (arom C), 128.2 (2C), 127.4(2C), (arom CH), 103.2 (C-1), 82.3 (C-4), 70.3 (CH2), 42.3 (C-6), 36.5 (CH2), 31.4, 21.7 (Me). Anal. Calcd for C14H15ClO5: C, 56.29; H, 5.06. Found: C, 56.00; H, 5.02.
Minor Diastereomer: Rf = 0.81 (EtOAc/hexane 4:6 v/v); colorless needles (from CHCl3/hexane); mp 185-187 °C; IR (KBr) ν 3500-3200 (OH), 1764 (C=O); 1H NMR (CDCl3) δ = 7.36-7.26 (4H, m, arom H), 4.31 (1H, d, J = 6.3 Hz, Ha-9), 4.24 (1H, d, J = 6.3 Hz, Hb-9), 3.58 (1H, s, OH), 2.63 (1H, d, J = 8.4 Hz, Ha-5), 2.04 (1H, d, J = 8.4 Hz, Hb-5), 1.61 (3H, s, Me), 1.57 (3H, s, Me); 13C NMR (CDCl3) 178.0 (C=O), 142.9, 134.1 (arom C), 128.7 (2C), 125.6 (2C) (arom CH), 103.7 (C-1), 81.1 (C-4), 70.7 (CH2), 42.6 (C-6), 38.4 (CH2), 24.7, 21.4 (Me). Anal. Calcd for C14H15ClO5: C, 56.29; H, 5.06. Found: C, 55.99; H, 5.05.
1-Hydroxy-4,6-dimethyl-4-phenyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4bh): Yield (256.3 mg, 97%); dr = 54:46.
Major Diastereomer: Rf = 0.26 (EtOAc/hexane 3:7 v/v); colorless needles (from CHCl3/hexane); mp 177-178 °C; IR (KBr) ν 3500-3100 (OH), 1766 (C=O); 1H NMR (CDCl3) δ = 7.39-7.16 (5H, m, arom H), 4.04 (1H, d, J = 10.5 Hz, Ha-9), 3.85 (1H, d, J = 10.5 Hz, Hb-9), 3.68 (1H, s, OH), 2.99 (1H, d, J = 14.4 Hz, Ha-5), 1.91 (1H, d, J = 14.4 Hz, Hb-5), 1.33 (3H, s, Me), 1.24 (3H, s, Me); 13C NMR (CDCl3) δ = 176.7 (C=O), 140.8 (arom C), 127.9 (2C), 127.3 (1C), 125.8 (2C) (arom CH), 103.1 (C-1), 82.7 (C-4), 70.3 (CH2), 42.4 (C-6), 36.7 (CH2), 31.5, 21.8 (Me). Anal. Calcd for C14H16O5: C, 63.63; H, 6.10. Found: C, 63.47; H, 6.08.
Minor Diastereomer: Rf = 0.45 (EtOAc/hexane 3:7 v/v); colorless blocks (from CHCl3/hexane), mp 168-170 °C; IR (KBr) ν 3500-3200 (OH), 1762 (C=O); 1H NMR (CDCl3) δ = 7.29-7.19 (5H, m, arom H), 4.22 (1H, d, J = 10.2 Hz, Ha-9), 4.14 (1H, d, J = 10.2 Hz, Hb-9), 3.69 (1H, s, OH), 2.57 (1H, d, J = 14.1 Hz, Ha-5), 2.02 (1H, d, J = 14.1 Hz, Hb-5), 1.51 (3H, s, Me), 1.22 (3H, s, Me); 13C NMR (CDCl3) δ = 178.4 (C=O), 144.4 (arom C), 128.6 (2C), 127.9 (1C), 124.0 (2C) (arom CH), 103.7 (C-1), 81.4 (C-4), 70.7 (CH2), 42.7 (C-6), 38.3 (CH2), 24.8, 21.4 (Me). Anal. Calcd for C14H16O5•1/8 H2O: C, 63.09; H, 6.15. Found: C, 63.23; H, 6.31.
1-Hydroxy-4-(4-methylphenyl)-4,6-dimethyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4bi): Yield (235.6 mg, 84%); dr = 50:50.
Diastereomer: Rf = 0.52 (EtOAc/hexane 3:7 v/v); colorless microcrystals (from CHCl3/hexane); mp 172 °C; IR (KBr) ν 3550-3200 (OH), 1759 (C=O); 1H NMR (CDCl3) δ = 7.26-7.15 (4H, m, arom H), 4.26 (1H, d, J = 6.6 Hz, Ha-9), 4.25 (1H, s, OH), 4.19 (1H, d, J = 6.6 Hz, Hb-9), 2.58 (1H, d, J = 8.7 Hz, Ha-5), 2.33 (3H, s, Me), 2.08 (1H, d, J = 8.7 Hz, Hb-5), 1.55 (3H, s, Me), 1.27 (3H, s, Me); 13C NMR (CDCl3) δ = 178.6 (C=O), 141.4, 137.7 (arom C), 129.1 (2C), 124.1 (2C) (arom CH), 103.5 (C-1), 81.2 (C-4), 70.8 (CH2), 42.7 (C-6), 38.3 (CH2), 24.6, 21.3, 20.9 (Me). Anal. Calcd for C15H18O5: C, 64.74; H, 6.52. Found: C, 64.50; H, 6.50.
The Other Diastereomer: Rf = 0.36 (EtOAc/hexane 3:7 v/v); colorless needles (from CHCl3/hexane); mp 198-199 °C; IR (KBr) ν 3500-3100 (OH), 1759 (C=O); 1H NMR (CDCl3) δ = 7.34-7.12 (4H, m, arom H), 4.11 (1H, d, J = 6.6 Hz, Ha-9), 3.92 (1H, d, J = 6.6 Hz, Hb-9), 3.76 (1H, s, OH), 3.05 (1H, d, J = 8.7 Hz, Ha-5), 2.31 (3H, s, Me), 1.96 (1H, d, J = 8.7 Hz, Hb-5), 1.38 (3H, s, Me), 1.31 (3H, s, Me); 13C NMR (CDCl3) δ = 176.8 (C=O), 137.8, 136.8 (arom C), 128.7 (2C), 125.7 (2C) (arom CH), 103.1 (C-1), 82.6 (C-4), 70.3 (CH2), 42.3 (C-6), 36.6 (CH2), 31.6, 21.8, 21.0 (Me). Anal. Calcd for C15H18O5•1/6H2O: C, 64.05; H, 6.57. Found: C, 64.20; H, 6.43.
1-Hydroxy-6-methyl-4-phenyl-4-(2-thienyl)-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4bk): Yield (255.9 mg, 77%); dr = 54:46.
Major Diastereomer: Rf = 0.42 (EtOAc/hexane 3:7 v/v); colorless cubes (from CHCl3/hexane); mp 154-156 °C; IR (KBr) ν 3600-3200 (OH), 1772 (C=O); 1H NMR (CDCl3) δ = 7.52-6.66 (9H, m, arom H, thienyl H), 4.08 (1H, d, J = 10.5 Hz, CH2a), 3.90 (1H, d, J = 10.5 Hz, CH2b), 3.62 (1H, s, OH), 3.32 (1H, d, J = 14.7 Hz, Ha-5), 2.54 (1H, d, J = 14.7 Hz, Hb-5), 1.31(3H, s, Me); 13C NMR (CDCl3) δ = 176.3 (C=O), 146.5 (arom C), 138.5 (thienyl C), 128.2, 127.8, 127.2, 127.1, 126.7 (arom CH, thienyl CH), 103.4 (C-1), 83.9 (C-4), 70.2 (CH2), 42.9 (C-6), 37.6 (CH2), 21.8 (Me). Anal. Calcd for C17H16O5S•1/4H2O: C, 60.61; H, 4.94. Found: C, 60.73; H, 4.69.
Minor Diastereomer: Rf = 0.46 (EtOAc/hexane 3:7 v/v); colorless needles (from CHCl3/hexane); mp 158-160 °C; IR (KBr) ν 3550-3200 (OH), 1755 (C=O); 1H NMR (CDCl3) δ = 7.31-6.91 (9H, m, arom H, thienyl H), 4.22 (1H, d, J = 10.5 Hz, Ha-9), 4.07 (1H, d, J = 10.5 Hz, Hb-9), 3.57 (1H, s, OH), 3.32 (1H, d, J = 14.7 Hz, Ha-5), 2.40 (1H, d, J = 14.7 Hz, Hb-5), 1.36 (3H, s, Me); 13C NMR (CDCl3) δ = 177.2 (C=O), 144.4 (arom C), 143.9 (thienyl C), 128.5, 128.3, 127.4, 126.6, 126.2, 124.8 (arom CH, thienyl CH), 103.5 (C-1), 84.3 ( C-4), 70.6 (CH2), 42.6 (C-6), 38.3 (CH2), 21.9 (Me). Anal. Calcd for C17H16O5S•2/3H2O: C, 59.29; H, 5.07. Found: C, 59.17; H, 5.26.
1-Hydroxy-6-methyl-4-phenyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4bl): Yield (235.2 mg, 94%); dr = 50:50).
Diastereomer: Rf = 0.42 (EtOAc/hexane 3:7 v/v); colorless microcrystals (from CHCl3/hexane); mp 157 °C; IR (KBr) ν 3550-3100 (OH), 1751 (C=O); 1H NMR (CDCl3) δ = 7.39-7.26 (5H, m, arom H), 5.26 (1H, t, J = 6.3 Hz, CH), 4.27 (1H, d, J = 10.2 Hz, Ha-9), 4.23 (1H, d, J = 10.2 Hz, Hb-9), 3.97 (1H, s, OH), 2.48 (1H, dd, J = 15.0, 6.3 Hz, Ha-5), 2.36 (1H, dd, J = 15.0, 6.3 Hz, Hb-5), 1.42 (3H, s, Me); 13C NMR (CDCl3) δ = 177.6 (C=O), 137.8 (arom C), 128.5 (2C), 128.2 (1C), 126.1 (2C) (arom CH), 104.5 (C-1), 78.4 (CH, C-4), 71.8 (CH2), 42.3 (C-6), 33.5 (CH2), 17.8 (Me). Anal. Calcd for C13H14O5•1/4H2O: C, 61.29; H, 5.74. Found: C, 61.48; H, 5.72.
The Other Diastereomer: Rf = 0.39 (EtOAc/hexane 3:7 v/v); colorless microcrystals (from CHCl3/hexane); mp 148-149 °C; IR (KBr) ν 3550-3100 (OH), 1751 (C=O); 1H NMR (CDCl3) δ = 7.29-7.19 (5H, m, arom H), 4.99 (1H, dd, J = 12.0, 2.4 Hz, CH), 4.21 (1H, d, J = 10.4 Hz, Ha-9), 4.01 (1H, d, J = 10.4 Hz, Hb-9), 3.87 (1H, s, OH), 2.41 (1H, dd, J = 12.0. 2.4 Hz, Ha-5), 2.00 (1H, dd, J = 12.0, 12.0 Hz, Hb-5), 1.29 (3H, s, Me); 13C NMR (CDCl3) δ = 177.4 (C=O), 136.4 (arom C), 129.2 (1C), 128.7(2C), 126.9(2C) (arom CH), 103.8 (C-1), 81.1 (CH, C-4), 69.9 (CH2), 44.1 (C-6), 34.1 (CH2), 20.5 (Me). Anal. Calcd for C13H14O5•1/6H2O: C, 61.65; H, 5.70. Found: C, 61.95; H, 5.60.
6-Ethyl-1-hydroxy-4,4-diphenyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4cc): Yield (279.1 mg, 82%); Rf = 0.51 (EtOAc/hexane 3:7 v/v); colorless blocks (from CHCl3/hexane); mp 208 °C; IR (KBr) ν 3550-3200 (OH), 1759 (C=O); 1H NMR (DMSO-d6) δ = 7.95 (1H, s, OH), 7.53-7.13 (10H, m, arom H), 4.15 (1H, d, J = 10.8 Hz, Ha-9), 3.93 (1H, d, J = 10.8 Hz, Hb-9), 3.44 (1H, d, J = 14.1 Hz, Ha-5), 2.31 (1H, d, J = 14.1 Hz, Hb-5), 1.72 (2H, m, CH2), 0.93 (3H, t, J = 7.2 Hz, Me); 13C NMR (DMSO-d6) δ = 175.4 (C=O), 145.2, 141.0 (arom C), 128.3 (2C), 127.6 (2C), 127.5 (2C), 126.8 (2C), 125.0 (2C) (arom CH), 103.2 (C-1), 84.4 (C-4), 71.2 (CH2), 45.9 (C-6), 34.6, 27.9 (CH2), 7.8 (Me). Anal. Calcd for C20H20O5: C, 70.57; H, 5.92. Found: C, 70.39; H, 5.72.
1-Hydroxy-6-isopropyl-4,4-diphenyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4dc): Yield (276.4 mg, 78%); Rf = 0.58 (EtOAc/hexane 3:7 v/v); colorless blocks (from EtOAc/hexane); mp 227-228 °C; IR (KBr) ν 3500-3200 (OH), 1751 (C=O); 1H NMR (DMSO-d6) δ = 7.99 (1H, s, OH), 7.48-7.14 (10H, m, arom H), 4.11 (1H, d, J = 6.6 Hz, Ha-9), 3.47 (1H, d, J = 8.4 Hz, Ha-5), 3.36 (1H, d, J = 6.6 Hz, Hb-9), 2.33 (1H, d, J = 8.4 Hz, Hb-5), 2.08 (1H, m, CH), 1.07 (3H, d, J = 4.2 Hz, Me), 0.95 (3H, d, J = 4.2 Hz, Me); 13C NMR (DMSO-d6) δ = 174.7 (C=O), 145.8, 141.33 (arom C), 128.3 (2C), 127.7 (2C), 127.4 (1C), 126.8 (1C), 126.4 (1C), 124.9 (2C) (arom CH), 103.7 (C-1), 84.4 (C-4), 72.88 (CH2), 48.8 (C-6), 35.8 (CH2), 33.7 (CH), 18.8, 17.3 (Me). Anal. Calcd for C21H22O5: C, 71.17; H, 6.26. Found: C, 71.12; H, 6.14.
6-Butyl-1-hydroxy-4,4-diphenyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4ec): Yield (261.6 mg, 71%); Rf = 0.56 (EtOAc/hexane 3:7 v/v); colorless needles (from CHCl3/hexane); mp 184 °C; IR (KBr) ν 3550-3200 (OH), 1759 (C=O); 1H NMR (CDCl3) δ = 7.47-7.11 (10H, m, arom H), 4.18 (1H, s, OH), 3.99 (1H, d, J = 10.8 Hz, Ha-9), 3.76 (1H, d, J = 10.8 Hz, Hb-9), 3.33 (1H, d, J = 14.4 Hz, Ha-5), 2.28 (1H, d, J = 14.4 Hz, Hb-5), 1.64-1.57 (2H, m, CH2), 1.40-1.15 (4H, m, 2CH2), 0.83 (3H, t, J = 7.2 Hz, Me); 13C NMR (CDCl3) δ = 176.1 (C=O), 144.3, 139.4 (arom C), 128.4, 128.3, 127.9, 127.9, 127.4, 127.1, 125.2 (arom CH), 103.3 (C-1), 85.5 (C-4), 70.9 (CH2), 45.9 (C-6), 35.9, 35.7, 25.2, 22.9 (CH2), 13.8 (Me). Anal. Calcd for C22H24O5: C, 71.72; H, 6.57. Found: C, 71.69; H, 6.37.
6-Benzyl-1-hydroxy-4,4-diphenyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4fc): Yield (321.94 mg, 80%), Rf = 0.33 (EtOAc/hexane 2:8 v/v); colorless needles (from CHCl3/hexane); mp 215 °C; IR (KBr) ν 3500-3200 (OH), 1739 (C=O); 1H NMR (DMSO-d6) δ = 8.24 (1H, s, OH), 7.48-7.15 (15H, m, arom H), 3.73 (1H, d, J = 10.8 Hz, Ha-9), 3.39 (1H, d, J = 10.8 Hz, Hb-9), 3.34 (1H, d, J = 14.1 Hz, Ha-5), 3.12 (1H, d, J = 13.5 Hz, CH2), 2.88 (1H, d, J = 13.5 Hz, CH2), 2.56 (1H, d, J = 14.1 Hz, Hb-5); 13C NMR (DMSO-d6) δ = 175.2 (C=O), 145.0, 141.0, 135.1 (arom C), 130.6, 128.4, 128.0, 127.6, 127.2, 126.8, 126.7, 125.0 (arom CH), 102.8 (C-1), 84.5 (C-4), 70.7 (CH2), 48.1 (C-6), 40.9, 35.6 (CH2). Anal. Calcd for C25H22O5: C, 74.61; H, 5.51. Found: C, 74.31; H, 5.55.
4,4-Bis(4-chlorophenyl)-1-hydroxy-6-pentyl-2,3,8-trioxabicyclo[4.3.0]nonan-7-one (4ga): Yield (401.7 mg, 89%); Rf = 0.94 (EtOAc/hexane 4:6 v/v); colorless needles (from CHCl3/hexane); mp 188 °C; IR (KBr) ν 3550-3200 (OH), 1747 (C=O); 1H NMR (CDCl3) δ = 7.47-7.12 (8H, m, arom H), 4.14 (1H, d, J = 10.5 Hz, Ha-9), 3.93 (1H, d, J = 10.5 Hz, Hb-9), 3.87 (1H, s, OH), 3.34 (1H, d, J = 14.7 Hz, Ha-5), 2.29 (1H, d, J = 14.7 Hz, Hb-5), 1.72-1.66 (2H, m, CH2), 1.37-1.23 (6H, m, 3CH2), 0.88 (3H, t, J = 7.2 Hz, Me); 13C NMR (CDCl3) δ = 175.8 (C=O), 142.3, 137.6, 134.1, 133.7 (arom C), 128.7, 128.6, 128.4, 126.6 (arom CH), 103.4 (C-1), 84.9 (C-4), 71.0 (CH2), 46.0 (C-6), 36.0, 35.5, 31.9, 22.8, 22.3 (CH2), 13.9 (Me). Anal. Calcd for C23H24Cl2O5•1/2H2O: C, 60.01; H, 5.47. Found: C, 60.18; H, 5.22.
Reaction at Elevated Temperature. The 1,1-diarylethene 2a or 2c (0.5 mmol) was placed in a 100 mL volumetric flask with a magnetic stirrer. Glacial acetic acid (20 mL) and the tetronic acid derivatives 1a-g (2 mmol) were added to the flask. Manganese(III) acetate (2 mmol) was then added to the mixture. The flask was installed an argon balloon and degassing in the flask was performed under reduced pressure using an ultrasonic bath for 15 minutes. For the tetronic acid (1a), the reaction was carried out in air (Table 3, Entries 1 and 2). The mixture was then heated under reflux until the dark-brown color of manganese(III) disappeared. After reaction, the acetic acid was removed in vacuo and the residue was triturated with water (25 mL) followed by extraction three times with CH2Cl2 (30 mL). The combined extracts were washed with water (30 mL) followed by saturated aqueous NaHCO3 solution (30 mL), dried over anhydrous MgSO4, filtered and then concentrated to dryness. The products were separated by silica gel column chromatography while eluting with EtOAc/hexane 3:7 v/v. The results are shown in Table 3.
3,3-Bis[2-acetoxy-2,2-bis(4-chlorophenyl)ethyl]tetrahydrofuran-2,4-dione (5aa): Yield (229 mg, 32%); Rf = 0.49 (EtOAc/hexane 4:6 v/v); colorless microcrystals (from CHCl3); mp 155-156 °C; IR (KBr) ν 1807, 1759 (C=O); 1H NMR (CDCl3) δ = 7.26-7.09 (16H, m, arom H), 3.65 (2H, d, J = 8.7 Hz, CH2), 3.52 (2H, s, CH2), 3.42 (2H, d, J = 8.7 Hz, CH2), 2.04 (6H, s, 2OAc); 13C NMR (CDCl3) δ = 208.2, 173.7, 168.9 (C=O), 141.2, 140.9, 134.0, 133.9 (arom C), 128.6, 128.5, 127.7, 126.9 (arom CH), 82.0 (quart C), 72.8 (CH2), 46.8 (C-3), 44.1 (CH2), 22.1 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C36H2835Cl4O7Na 735.0487 (M+Na). Found 735.0468.
3,3-Bis(2-acetoxy-2,2-diphenylethyl)tetrahydrofuran-2,4-dione (5ac): Yield (184 mg, 20%); Rf = 0.49 (EtOAc/hexane 4:6 v/v); colorless microcrystals (from CHCl3); mp 222-223 °C; IR (KBr) ν 1805, 1759 (C=O); 1H NMR (CDCl3) δ = 7.26-7.18 (20H, m, arom H), 3.77 (2H, d, J = 14.4 Hz, CH2), 3.34 (2H, s, CH2), 3.51 (2H, d, J = 14.4 Hz, CH2), 2.04 (6H, s, 2OAc); 13C NMR (CDCl3) δ = 208.7, 174.1, 169.1 (C=O), 143.2, 142.7 (arom C), 128.2, 128.1, 127.6, 127.5,126.4, 125.6 (arom CH), 82.8 (quart C), 72.6 (CH2), 46.9 (C-3), 44.8 (CH2), 22.2 (Me). Anal. Calcd for C36H32O7•1/3H2O: C, 74.21; H, 5.65. Found: C, 74.48; H, 5.44.
3-[2,2-Bis(4-chlorophenyl)ethenyl]-3-[2-acetoxy-2,2-bis(4-chlorophenyl)ethyl]-tetrahydrofuran-2,4-dione (6): Yield (85 mg, 13%); Rf = 0.49 (EtOAc/hexane 4:6 v/v); colorless microcrystals (from CHCl3); mp 231-233 °C; IR (KBr) ν 1801, 1757 (C=O); 1H NMR (CDCl3) δ = 7.39-6.92 (16H, m, arom H), 6.0 (1H, s, CH=), 3.95 (1H, d, J = 8.4 Hz, CH2), 3.70 (1H, d, J = 8.4 Hz, CH2), 3.54 (1H, d, J = 9.9 Hz, CH2), 2.93 (1H, d, J = 9.9 Hz, CH2), 2.08 (3H, s, OAc); 13C NMR (CDCl3) δ = 208.2, 174.2, 168.9 (C=O), 144.7, 141.2, 140.7, 138.2, 135.3, 134.9, 134.7, 133.9 (arom C), 129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 128.1, 127.6, 126.8, 126.5 (arom CH and CH=), 134.1 (quart C), 82.1 (quart C), 73.2 (CH2), 50.4 (C-3), 43.9 (CH2), 21.9 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C34H2435Cl4O5Na 675.0276 (M+Na). Found 675.0320.
4,4,11,11-Tetraphenyl-2,3,8,10-tetraoxatricyclo[4.3.3.01,6]tridecan-7-one (7): Yield (59 mg, 12%); Rf = 0.53 (CHCl3); colorless needles (from CHCl3/hexane); mp 203-205 °C; IR (KBr) ν 1774 (C=O); 1H NMR (CDCl3) δ = 7.44-7.15 (20H, m, arom H), 4.41 (1H, d, J = 10.2 Hz, CH2), 4.32 (1H, d, J = 10.2 Hz, CH2), 3.26 (1H, d, J = 14.4 Hz, CH2), 3.10 (1H, d, J = 13.5 Hz, CH2), 2.82 (1H, d, J = 13.5 Hz, CH2), 2.64 (1H, d, J = 14.4 Hz, CH2); 13C NMR (CDCl3) δ = 176.3 (C=O), 145.0, 144.1, 143.2, 142.5 (arom C), 128.9, 128.5, 128.4, 128.1, 127.8, 127.7, 127.5, 127.2, 125.9,125.8, 125.4, 125.3 (arom CH), 113.6, 91.6, 83.8 (quart C), 72.9 (CH2), 50.9 (quart C), 44.0, 35.6 (CH2). FAB HRMS (acetone/NBA/NaI) calcd for C32H26O5Na 513.1678 (M+Na). Found 513.1733.
3-[2-Acetoxy-2,2-bis(4-chlorophenyl)ethyl]-3-methyltetrahydrofuran-2,4-dione (8ba): Yield (125 mg, 60%); Rf = 0.88 (EtOAc/hexane 4:6 v/v); colorless microcrystals (from CHCl3); mp 191-192 °C; IR (KBr) ν 1801, 1755 (C=O); 1H NMR (CDCl3) δ = 7.25-7.18 (8H, m, arom H), 4.33 (1H, d, J = 10.5 Hz, CH2), 3.83 (1H, d, J = 10.5 Hz, CH2), 3.69 (1H, d, J = 8.7 Hz, CH2), 3.31 (1H, d, J = 8.7 Hz, CH2), 2.12 (OAc), 1.34 (3H, s, Me); 13C NMR (CDCl3) δ = 208.5, 175.8, 169.1 (C=O), 141.7, 141.0, 134.2, 133.9 (arom C), 128.6, 127.9, 127.2 (arom CH), 82.3 (quart C), 71.9, 41.4 (CH2), 45.1 (C-3), 24.7, 22.2 (Me). Anal. Calcd for C21H18Cl2O5•1/3H2O: C, 59.03; H, 4.40. Found: C, 59.16; H, 4.29.
3-(2-Acetoxy-2,2-diphenylethyl)-3-methyltetrahydrofuran-2,4-dione (8bc): Yield (56.4 mg, 32%); Rf = 0.33 (EtOAc/hexane 3:7 v/v); colorless blocks (from CHCl3/hexane); mp 193-194 °C; IR (KBr) ν 1805, 1757, 1739 (C=O); 1H NMR (CDCl3) δ = 7.22-7.16 (10H, m, arom H), 4.16 (1H, d, J = 16.8 Hz, CH2), 3.69 (1H, , d, J = 15.0 Hz, CH2), 3.51 (1H, d, J = 16.8 Hz, CH2), ), 3.31 (1H, d, J = 15.0 Hz, CH2), 2.06 (3H, s, OAc), 1.26 (3H, s, Me); 13C NMR (CDCl3) δ = 208.8, 176.1, 169.2 (C=O), 143.5, 142.8 (arom C), 128.3, 128.2, 127.9, 127.7, 126.5, 125.7 (arom CH), 83.1 (quart C), 71.7 (CH2), 45.2 (C-3), 41.9 (CH2), 24.6, 22.2 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C21H20O5Na 375.1208 (M+Na). Found 375.1275.
3-(2-Acetoxy-2,2-diphenylethyl)-3-ethyltetrahydrofuran-2,4-dione (8cc): Yield (93 mg, 51%); Rf = 0.49 (EtOAc/hexane 3:7 v/v); colorless microcrystals (from CHCl3); mp 155-156 °C; IR (CHCl3) ν 1803, 1755 (C=O); 1H NMR (CDCl3) δ = 7.29-7.21 (10H, m, arom H), 4.03 (1H, d, J = 10.2 Hz, CH2), 3.76 (1H, , d, J = 9.0 Hz, CH2), 3.59 (1H, d, J = 10.2 Hz, CH2), 3.37 (1H, d, J = 9.0 Hz, CH2), 2.13 (3H, s, OAc), 1.85 (2H, q, J = 4.5 Hz, CH2), 0.79 (3H, t, J = 4.5 Hz, Me); 13C NMR (CDCl3) δ = 209.6, 175.5, 169.2 (C=O), 143.6, 142.8 (arom C), 128.2, 128.1, 127.8, 127.5, 126.5, 125.7 (arom CH), 82.9 (quart C), 72.7 (CH2), 50.4 (C-3), 41.3, 32.9 (CH2), 22.2, 8.0 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C22H22O5Na 389.1365 (M+Na). Found 389.1398.
3-(2-Acetoxy-2,2-diphenylethyl)-3-isopropyltetrahydrofuran-2,4-dione (8dc): Yield (132 mg, 72%); Rf = 0.44 (EtOAc/hexane 3:7 v/v); colorless microcrystals (from CHCl3); mp 157 °C; IR (CHCl3) ν 1799, 1753 (C=O); 1H NMR (CDCl3) δ = 7.31-7.21 (10H, m, arom H), 3.95 (1H, d, J = 10.5 Hz, CH2), 3.86 (1H, d, J = 8.7, CH2), 3.44 (1H, d, J = 10.5 Hz, CH2), 3.42 (1H, d, J = 8.7, CH2), 2.15 (3H, s, CH3), 2.11 (1H, m, CH), 1.00 (3H, d, J = 4.2 Hz, Me), 0.98 (3H, d, J = 4.2 Hz, Me); 13C NMR (CDCl3) δ = 209.6, 175.3, 169.3 (C=O), 143.9, 142.7 (arom C), 128.2, 128.1, 127.8, 127.6, 126.8, 125.7 (arom CH), 82.9 (quart C), 72.7 (CH2), 52.6 (C-3), 39.7 (CH2), 22.3 (CH), 38.0, 17.4, 16.4 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C22H21O5Na 403.1521 (M+Na). Found 403.1500.
3-[2-Acetoxy-2,2-bis(4-chlorophenyl)ethyl]-3-benzyltetrahydrofuran-2,4-dione (8fa): Yield (132 mg, 53%); Rf = 0.56 (EtOAc/hexane 3:7 v/v); colorless microcrystals (from CHCl3); mp 206-207 °C; IR (KBr) ν 1799, 1743 (C=O); 1H NMR (CDCl3) δ = 7.19-6.89 (13H, m, arom H), 3.76 (1H, d, J = 9.0 Hz, CH2), 3.45 (1H, d, J = 10.4 Hz, CH2), 3.35 (1H, d, J = 9.0 Hz, CH2), 3.09 (1H, d, J = 7.4 Hz, CH2), 2.954 (1H, d, J = 10.4 Hz, CH2), 2.945 (1H, d J = 7.4 Hz, CH2), 2.06 (OAc). 13C NMR (CDCl3) δ = 209.0, 174.9, 169.1 (C=O), 141.8, 141.0, 134.1, 133.8, 132.1 (arom C), 129.8, 128.7, 128.6, 128.4, 128.0, 127.9, 127.2 (arom CH), 82.1 (quart C), 72.8 (CH2), 52.7 (C-3), 45.5, 41.3 (CH2), 22.1 (OAc). FAB HRMS (acetone/NBA/NaI) calcd for C27H2235Cl2O5Na 519.0742 (M+Na). Found 519.0753.
3-(2-Acetoxy-2,2-diphenylethyl)-3-pentyltetrahydrofuran-2,4-dione (8gc): Yield (6 mg, 3%); Rf = 0.73 (EtOAc/hexane 3:7 v/v); colorless needles (from CHCl3); mp 96-97 °C; IR (CHCl3) ν 1797, 1755 (C=O); 1H NMR (CDCl3) δ = 7.29-7.21 (10H, m, arom H), 4.04 (1H, d, J = 10.5 Hz, CH2), 3.77 (1H, d, J = 9.0 Hz, CH2 ), 3.58 (1H, d, J = 10.5 Hz, CH2), 3.38 (1H, d, J = 9.0 Hz, CH2 ), 2.13 ( 3H, s, OAc), 1.80-1.77 (2H, m, CH2), 1.25-1.12 (6H, m, 3CH2), 0.82 (3H, t, J = 4.5 Hz, Me); 13C NMR (CDCl3) δ = 209.7, 175.7, 169.2 (C=O), 143.6, 142.8 (arom C), 128.2, 127.8, 127.5, 126.6, 125.7 (arom CH), 83.0 (quart C), 72.7 (CH2), 49.9 (C-3), 41.7, 39.7, 31.4, 23.0, 21.9 (CH2), 22.2, 13.7 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C25H28O5Na 431.1834 (M+Na). Found 431.1820.
3-[2,2-Bis(4-chlorophenyl)ethenyl]-3-methyltetrahydrofuran-2,4-dione (9ba): Yield (13.4 mg, 8%); Rf = 0.72 (EtOAc/hexane 4:6 v/v); colorless microcrystals (from CHCl3); mp 150-151 °C; IR (KBr) ν 1801, 1751 (C=O); 1H NMR (CDCl3) δ = 7.34-6.93 (8H, m, arom H), 6.00 (1H, s, CH=), 4.31 (1H, d, J = 10.2 Hz, CH2), 3.38 (1H, d, J = 10.2 Hz, CH2), 1.53 (3H, s, Me); 13C NMR (CDCl3) δ = 208.6, 176.1 (C=O), 137.8, 136.0, 134.9 (arom C), 131.5, 130.3, 129.1, 128.9, 128.8, 128.7, 128.5, 128.2 (arom CH), 145.3 ( quart C), 126.5 (CH), 72.2 (CH2), 49.0 (C-3), 23.6 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C19H14Cl2O3Na 383.0218 (M+Na). Found 383.0210.
3-Methyl-3-(2,2-diphenylethenyl)tetrahydrofuran-2,4-dione (9bc): Yield (36.7 mg, 25%); Rf = 0.50 (EtOAc/hexane 3:7 v/v); colorless liquid; IR (CHCl3) ν 1805, 1757 (C=O); 1H NMR (CDCl3) δ = 7.38-7.06 (10H, m, arom H), 6.08 (1H, s, CH=), 4.25 (1H, d, J = 16.8 Hz, CH2), 3.19 (1H, d, J = 16.8 Hz, CH2), 1.57 (3H, s, Me); 13C NMR (CDCl3) δ = 209.1, 176.6 (C=O), 147.4, 139.8 (arom C), 128.7, 128.4, 128.3, 128.2, 126.9, 125.9 (arom CH), 138.2 ( quart C), 130.2 (CH), 72.1 (CH2), 48.8 (C-3), 23.6 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C19H16O3Na 315.0997 (M+Na). Found 315.1035.
3-Ethyl-3-(2,2-diphenylethenyl)tetrahydrofuran-2,4-dione (9cc): Yield (17.6 mg, 11%); Rf = 0.59 (EtOAc/hexane 3:7 v/v); colorless liquid; IR (CHCl3) ν 1803, 1755 (C=O); 1H NMR (CDCl3) δ = 7.39-7.09 (10H, m, arom H), 6.09 (1H, s, CH=), 4.09 (1H, d, J = 10.2 Hz, CH2), 3.14 (1H, d, J = 10.2 Hz, CH2 ), 2.11 (2H, q, J = 4.5 Hz, CH2), 0.97 (3H, t, J = 4.5 Hz, Me); 13C NMR (CDCl3) δ = 209.6, 176.1 (C=O), 139.9, 138.4, (arom C), 130.3, 128.7, 128.4, 128.3, 128.2, 126.9 (arom CH), 147.3 (quart C), 125.6 (CH), 73.0 (CH2), 53.9 (C-3), 31.9(CH2), 8.4 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C20H18O3Na 329.1154 (M+Na). Found 329.1168.
3-Isopropyl-3-(2,2-diphenylethenyl)tetrahydrofuran-2,4-dione (9dc): Yield (30 mg, 18%); Rf = 0.65 (EtOAc/hexane 3:7 v/v); colorless liquid; IR (CHCl3) ν 1799, 1753 (C=O); 1H NMR (CDCl3) δ = 7.38-7.09 (10H, m, arom H), 6.18 (1H, s, CH=), 4.02 (1H, d, J = 9.9 Hz, CH2), 3.13 (1H, d, J =9.9 Hz, CH2), 2.43-2.40 (1H, m, CH), 1.09 (3H, d, J = 7.5 Hz, Me), 1.06 (3H, d, J = 7.5 Hz, Me); 13C NMR (CDCl3) δ = 209.1, 175.7 (C=O), 140.3, 138.4 (arom C), 130.4, 128.6, 128.3, 128.2, 128.1, 126.9 (arom CH), 147.1 quart C), 125.5 (CH), 73.2 (CH2), 56.9 (C-3), 37.2 (CH), 17.5, 16.8 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C21H20O3Na 321.1491 (M+Na). Found 321.1510.
3-Butyl-3-(2,2-diphenylethenyl)tetrahydrofuran-2,4-dione (9ec): Yield (232 mg, 70%); Rf = 0.54 (EtOAc/hexane 3:7 v/v); colorless liquid; IR (CHCl3) ν 1801, 1753 (C=O); 1H NMR (CDCl3) δ = 7.39-7.09 (10H, m, arom H), 6.09 (1H, s, CH=), 4.09 (1H, d, J = 10.5 Hz, CH2), 3.13 (1H, d, J = 10.5 Hz, CH2), 2.06-2.03 (2H, m, CH2), 1.33-1.17 (4H, m, 2CH2), 0.89 (3H, t, J = 4.2 Hz, Me); 13C NMR (CDCl3) δ = 209.6, 176.1 (C=O), 139.9, 138.4 (arom C), 130.3, 128.6, 128.4, 128.2, 126.9 (arom CH), 147.2 ( quart C), 125.9 (CH), 72.9 (CH2), 53.5 (C-3), 38.6, 25.9, 22.6 (CH2), 13.6 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C22H22O3Na 357.1467 (M+Na). Found 357.1472.
3-Benzyl-3-[2,2-bis(4-chlorophenyl)ethenyl]tetrahydrofuran-2,4-dione (9fa): Yield (27.5 mg, 13%); Rf = 0.59 (EtOAc /hexane 3:7 v/v); colorless microcrystals (from CHCl3); mp 180-181 °C; IR (KBr) ν 1793, 1755 (C=O); 1H NMR (CDCl3) δ = 7.28-6.92 (13H, m, arom H), 6.10 (1H, s, CH=), 3.40 (1H, d, J = 7.8 Hz, CH2), 3.28 (1H, d, J =7.5 Hz, CH2), 3.00 (2H, s, CH2); 13C NMR (CDCl3) δ = 209.5, 175.4 (C=O), 145.1, 138.0, 136.2, 134.9, 134.7, 132.4 (arom C), 131.5, 129.7, 129.1, 128.9, 128.6, 128.2, 128.2, (arom CH), 128.7 (quart C), 126.4 (CH), 73.2 (CH2), 56.4 (C-3), 44.9 (CH2). FAB HRMS (acetone/NBA/NaI) calcd for C25H18Cl2O3Na 459.0531 (M+Na). Found 459.0566.
3-Pentyl-3-(2,2-diphenylethenyl)tetrahydrofuran-2,4-dione (9gc): Yield (61 mg, 35%); Rf = 0.81 (EtOAc/hexane 3:7 v/v); colorless needles (from CHCl3); mp 111-113 °C; IR (CHCl3) ν 1799, 1755 (C=O); 1H NMR (CDCl3) δ = 7.39-7.08 (10H, m, arom H), 6.09 (1H, s, CH=), 4.09 (1H, d, J = 10.5 Hz, CH2), 3.13 (1H, d, J = 10.5 Hz, CH2 ), 2.06-2.02 (2H, m, CH2), 1.36-1.27 (6H, m, 3CH2), 0.87 (3H, t, J = 4.2 Hz, Me); 13C NMR (CDCl3) δ = 209.6, 176.1 (C=O), 147.1 (quart C), 139.9, 138.4 (arom C), 130.3, 128.6, 128.4, 128.2, 126.9 (arom CH), 125.9 (CH=), 72.9 (CH2), 53.6 (C-3), 38.7, 31.6, 23.4, 22.1 (CH2), 13.8 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C23H24O3Na 371.1623 (M+Na). Found 371.1644.

ACKNOWLEDGEMENTS
This research was supported by Grants-in-Aid for Scientific Research (C), No. 19550046 and No. 22550041, from the Japan Society for the Promotion of Science.

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