Method for preparing chiral spirosteroid compounds using chiral aryl iodide catalyst derived from chloramphenicol

Abstract

The present invention discloses a method for preparing a chiral spirosteroid compound by using a chiral aryl iodide catalyst derived from chloramphenicol. The method comprises the following steps: adding a naphthol derivative to an organic solvent; sequentially adding an additive, a chiral aryl iodide catalyst, and an oxidant at an appropriate temperature to carry out a reaction; quenching the reaction with a quencher to obtain a product; and finally recovering the catalyst. The reaction process includes the following steps: reaction 1: #imgabs0# reaction 2: #imgabs1# reaction 3: #imgabs2# H on the benzene ring is replaced by a substituent R 1 , R 2 , R 3 , R 4 and R 5 Substituted or unsubstituted, when substituted R 1 , R 2 are each independently selected from alkyl, halogen, phenyl, alkyl acyl or phenyl acyl; R 3 is selected from halogen or alkoxy; R 4 and R 5 The present invention has mild reaction conditions, cheap and readily available raw materials, good catalyst catalytic effect, high product stereoselectivity, simple reaction operation, high yield, economical and practical, and environmentally friendly.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound synthesis, and particularly relates to a method for preparing chiral spirosteroid compounds by using a chiral aryl iodide catalyst derived from chloramphenicol. Background Art

[0002] Spirosteroids possess unique chemical structures, making the synthesis of these compounds with high stereoselectivity a challenging task in organic synthesis. Hypervalent iodine catalysts have garnered considerable attention in recent years, emerging as versatile, low-toxic, easy-to-handle, stable, and environmentally friendly oxidants in organic synthesis. These catalysts have led to numerous "metalloid" oxidative transformations of important scaffolds in comparable or even comparable timeframes, in some cases even exceeding the efficiency levels of various transition metals. Asymmetric reactions utilizing these chiral organoiodides have become state-of-the-art, offering high applicability and versatility in modern organic synthesis. The past decade has witnessed tremendous progress in enantioselective hypervalent iodide catalysis for asymmetric organocatalytic oxidations, a field that has proven challenging due to the difficulty in achieving high stereoselectivity at the relevant transition states compared to metal-catalyzed and enzymatic oxidations. Therefore, the development of organoiodine catalysts that efficiently achieve a variety of asymmetric transformations and afford enantiomerically pure structures remains highly desirable.

[0003] In terms of application, existing reported methods for synthesizing chiral spirosteroids, particularly those using high-iodine catalysts as catalytic precursors, provide only a single chiral center, potentially reducing the richness and tunability of the catalyst's chiral environment, thereby inhibiting its synthetic diversity and reactivity. Furthermore, most reported catalysts are difficult to effectively recover using simple methods, often requiring the use of chromatography columns. Therefore, a new library of conformationally flexible catalysts that are readily accessible and highly reactive would be highly desirable. Summary of the Invention

[0004] The present invention overcomes many shortcomings of traditional methods for constructing chiral hypervalent iodine catalysts, innovatively develops a method for preparing chiral spirosteroid compounds using a chiral aryl iodine catalyst derived from chloramphenicol, and completes a green, low-toxic, and environmentally friendly method for synthesizing spirosteroid compounds from 1-naphthol and 2-naphthol using a chiral hypervalent iodine catalyst, and a method for recovering the catalyst.

[0005] A method for preparing chiral spirosteroid compounds using a chiral aryl iodide catalyst derived from chloramphenicol comprises the following steps: adding a naphthol derivative to an organic solvent; sequentially adding an additive, a chiral aryl iodide catalyst, and an oxidant at an appropriate temperature to carry out a reaction; after completion of the reaction, quenching the reaction with a quencher to obtain a product; and finally recovering the catalyst. The reaction process includes the following steps:

[0006] Reaction 1:

[0007]

[0008] The H on the benzene ring is substituted by R 1 , R 2 , R 3 , R 4 and R 5 Substituted or unsubstituted, when substituted R 1 , R 2 are each independently selected from alkyl, halogen, phenyl, alkyl acyl or phenyl acyl; R 3 is selected from halogen or alkoxy; R 4 and R 5 Selected from alkoxy,

[0009] The structural formula of the chiral aryl iodide catalyst derived from chloramphenicol is as follows: 6 , R 7 and R 8 Each is independently selected from phenyl, substituted phenyl, the substituent on the substituted phenyl is methyl, methoxy, tert-butyl, halogen or nitro:

[0010]

[0011] Furthermore, the oxidant in the reaction is potassium peroxymonosulfonate, a selective fluorine reagent, N-fluorobisbenzenesulfonamide or m-chloroperbenzoic acid.

[0012] Furthermore, the amount of the catalyst used in reaction 1 is 1-20 mol% of the 1-naphthol derivative shown in formula (1), the amount of the oxidant used is 1.0-3.0 equivalents of the 1-naphthol derivative shown in formula (1), the additive is methanol, ethanol or n-butanol, and the solvent is dichloromethane, toluene or ethyl acetate.

[0013] Furthermore, the amount of the catalyst used in Reaction 2 is 1-20 mol% of the 1-naphthol derivative shown in formula (3), the amount of the oxidant used is 1.0-3.0 equivalents of the 1-naphthol derivative shown in formula (3), the additive is methanol, ethanol or n-butanol, and the solvent is dichloromethane, toluene or ethyl acetate.

[0014] Furthermore, the amount of the catalyst used in Reaction 3 is 1-20 mol% of the 2-naphthol derivative shown in formula (5), the amount of the oxidant used is 1.0-3.0 equivalents of the 1-naphthol derivative shown in formula (5), the additive is methanol, ethanol or n-butanol, and the solvent is dichloromethane, toluene or ethyl acetate.

[0015] Furthermore, the reaction temperatures of reaction 1, reaction 2, and reaction 3 are all -40-10°C, the reaction times are all 8-30 hours, and the quenching agents are saturated sodium thiosulfate aqueous solution and sodium bicarbonate aqueous solution.

[0016] Furthermore, the catalyst recovery process includes the following steps:

[0017] 1) adding dichloromethane to the quenched system for extraction;

[0018] 2) The organic phase was dried by adding anhydrous sodium sulfate and evaporated under reduced pressure;

[0019] 3) Dissolve the residue with a good solvent;

[0020] 4) adding an inert solvent to the solution of step 3) to produce a white solid;

[0021] 5) Filter with a Buchner funnel to obtain a white solid, which is the recovered catalyst.

[0022] Furthermore, the benign solvent in step 3) is ether, methanol or ethanol, and the volume of the benign solvent is 1:0.05 to the molar mass of the naphthol derivative, the volume unit is mL, and the molar mass unit is mmol.

[0023] Furthermore, the inert solvent in step 4) is water or petroleum ether, and the amount of the inert solvent is 0.2-1 times the amount of the benign solvent.

[0024] The beneficial effects of the present invention are:

[0025] 1) The compound preparation of the present invention realizes a gram-scale reaction, is practical, has broad application prospects, and is suitable for industrial-scale production.

[0026] 2) The present invention has high reaction efficiency, high yield, simple and stable preparation, no irritating odor, and mild reaction conditions.

[0027] 3) The present invention adopts a simple, safe and green method to efficiently and repeatedly recover the catalyst. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a diagram showing the effect of the catalyst after recycling and recovery of the present invention. DETAILED DESCRIPTION

[0029] The present invention is further described in detail below in conjunction with the following specific examples, and the protection content of the present invention is not limited to the following examples. Without departing from the spirit and scope of the inventive concept, changes and advantages that those skilled in the art can think of are included in the present invention, and are protected by the appended claims. The process, conditions, reagents, experimental methods, etc. for implementing the present invention, except for the contents specifically mentioned below, are common knowledge and common common sense in the art, and the present invention has no special restrictions. The data given in the following examples include specific operations and reaction conditions and products. Product purity is identified by nuclear magnetic resonance.

[0030] The structural formula of the catalyst used in the reaction is shown below:

[0031]

[0032] Example 1

[0033] Synthesis of (R)-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0034]

[0035] Under nitrogen atmosphere, 1a (43.2 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 2a (39.5 mg, 92% yield, 98% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0036] 1H NMR (400MHz, CDCl3) δ8.03(d,J=7.6Hz,1H),7.65(t,J=7.4Hz,1H),7.43(t,J=7.5Hz,1H),7.29(d,J=7.6Hz,1H),6.68(d,J=9.9Hz,1H),6.23(d,J=9.9Hz ,1H),2.92(ddd,J=9.7,11.2,17.6Hz,1H),2.62(ddd,J=2.0,9.6,17.6Hz,1 H), 2.44 (ddd, J=2.0, 9.6, 13.2Hz, 1H), 2.22 (ddd, J=9.8, 11.2, 13.2Hz, 1H). 13 CNMR(100MHz, CDCl3)δ196.7,176.7,136.9,135.8,132.3,129.0,128.1,128.0,127.8,127.4,83.6,31.3,26.6.HRMS(ESI)m / z Calcd for[C 13 H 10 O3,M+H] + :215.0703; Found:215.0701.Optical Rotation:[α] 25 D 186.2 (c = 1.0, CHCl3).

[0037] Example 2

[0038] Synthesis of (R)-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0039]

[0040] Under nitrogen atmosphere, a dry schlenk tube was charged with 1a (43.2 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.), followed by the addition of catalyst (10 (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at 0°C. After reacting at 0°C for 24 hours, the reaction was quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 2a (39.5 mg, 87% yield, 98% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0041] Example 3

[0042] Synthesis of (R)-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0043]

[0044] Under nitrogen atmosphere, 1a (43.2 mg, 0.2 mmol, 1.0 equiv.) and anhydrous DCM (10.0 mL) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic phase was separated and the solvent was removed under reduced pressure. The product 2a (35.1 mg, 82% yield, 98% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0045] Example 4

[0046] Synthesis of (R)-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0047]

[0048] Under nitrogen atmosphere, 1a (43.2 mg, 0.2 mmol, 1.0 equiv.) and anhydrous EA (10.0 mL) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate solution and aqueous sodium bicarbonate solution, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 2a (18.8 mg, 44% yield, 87% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0049] Example 5

[0050] Synthesis of (R)-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0051]

[0052] Under nitrogen atmosphere, 1a (43.2 mg, 0.2 mmol, 1.0 equiv.) and anhydrous toluene (10.0 mL) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic phase was separated, the solvent was removed under reduced pressure, and the product 2a (32.9 mg, yield 77%, ee value 96%) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0053] Example 6

[0054] Synthesis of (R)-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0055]

[0056] Under nitrogen atmosphere, 1a (43.2 mg, 0.2 mmol, 1.0 equiv.) and anhydrous DCM (10.0 mL) were added to a dry schlenk tube, followed by the addition of catalyst (11) (35.6 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic phase was separated and the solvent was removed under reduced pressure. The product 2a (28.2 mg, yield 66%, ee value 79%) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0057] Example 7

[0058] Synthesis of (R)-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0059]

[0060] Under nitrogen atmosphere, 1a (43.2 mg, 0.2 mmol, 1.0 equiv.) and anhydrous DCM (10.0 mL) were added to a dry schlenk tube, followed by the addition of catalyst (13) (42.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -30°C. The mixture was reacted at -30°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic phase was separated and the solvent was removed under reduced pressure. The product 2a (14.9 mg, 35% yield, 75% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0061] Example 8

[0062] Synthesis of (R)-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0063]

[0064] Under nitrogen atmosphere, 1a (43.2 mg, 0.2 mmol, 1.0 equiv.) and anhydrous DCM (10.0 mL) were added to a dry schlenk tube, followed by the addition of catalyst (14) (39.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -30°C. The mixture was reacted at -30°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic phase was separated and the solvent was removed under reduced pressure. The product 2a (20.1 mg, 47% yield, 86% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0065] Example 9

[0066] Synthesis of (R)-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0067]

[0068] Under nitrogen atmosphere, 1a (43.2 mg, 0.2 mmol, 1.0 equiv.) and anhydrous DCM (10.0 mL) were added to a dry schlenk tube, followed by the addition of catalyst (15) (30.1 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -30°C. The mixture was reacted at -30°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic phase was separated and the solvent was removed under reduced pressure. The product 2a (34.2 mg, 80% yield, 92% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0069] Example 10

[0070] Synthesis of (R)-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0071]

[0072] Under nitrogen atmosphere, 1a (43.2 mg, 0.2 mmol, 1.0 equiv.) and anhydrous DCM (10.0 mL) were added to a dry schlenk tube, followed by the addition of catalyst (16) (40.1 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -30°C. The mixture was reacted at -30°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic phase was separated and the solvent was removed under reduced pressure. The product 2a (23.9 mg, 56% yield, 86% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0073] Example 11

[0074] Synthesis of (R)-4'-bromo-3,4-dihydro-1'-H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0075]

[0076] Under nitrogen atmosphere, 1b (58.8 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 h, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 2b (49.6 mg, 85% yield, 97% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0077] 1 H NMR (400MHz, CDCl3) δ8.03(d,J=7.7Hz,1H),7.79–7.70(m,2H),7.50(m,1H),6.39(s,1H),2.88(ddd,J=17.6,11.2,9. 5Hz,1H),2.61(ddd,J=17.7,9.6,2.3Hz,1H),2.44(ddd,J=13.5,9.6,2.3Hz,1H),2.24(ddd,J=13.4,11.1,9.6Hz,1H). 13 C NMR(100MHz, CDCl3)δ194.9,176.0,135.9,134.6,131.8,130.2,129.2,128.1,127.3,126.2,83.6,31.5,26.6.HRMS(ESI)m / z Calcd for[C 13 H9O3Br,M+H] + :292.9808,294.9793; Found:292.9804,294.9786.Optical Rotation:[α] 25 D 101.1 (c=1, CHCl3).

[0078] Example 12

[0079] Synthesis of (R)-4'-benzoyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0080]

[0081] Under nitrogen atmosphere, 1c (64.0 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 2c (54.1 mg, 85% yield, 92% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0082] 1 H NMR(400MHz, CDCl3)δ8.09(dd,J=7.8,1.5Hz,1H),8.02–7.88(m,2H),7.66–7.56(m,2H),7.53–7.42(m,3H),7.39(d,J=7.8Hz,1H),6.38(s,1H),2 .89(ddd,J=17.6,11.3,9.6Hz,1H), 2.60(ddd,J=17.6,9.6,2.2Hz,1H), 2.51(ddd,J=13.5,9.5,2.2Hz,1H), 2.28(ddd,J=13.4,11.3,9.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ195.4,194.6,176.0,137.5,136.1,135.8,134.4,134.3,1 34.2,130.1,129.9,129.0,128.5,127.4,127.0,82.8,31.2,26.3.HRMS(ESI)m / z Calcd for[C 20 H 14 O4,M+H] + :319.0965; Found:319.0964.OpticalRotation:[α] 25 D -36.8 (c=1.0, CHCl3).

[0083] Example 13

[0084] Synthesis of (R)-4'-acetyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0085]

[0086] Under nitrogen atmosphere, 1d (51.6 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 h, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 2d (36.4 mg, 71% yield, 94% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0087] 1 H NMR (400MHz, CDCl3) δ8.03(dd,J=7.7,1.6Hz,1H),7.91(d,J=8.0Hz,1H),7.65(td,J=7.7,1.4Hz,1H),7.45(t,J=7.6Hz,1H),6.82(s,1H),2. 83(ddd,J=17.7,11.4,9.4Hz,1H),2.65–2.58(m,1H),2.54(s,3H),2.44(ddd,J=13.7,9.3,2.1Hz,1H),2.28(ddd,J=13.4,11.5,9.5Hz,1H). 13 C NMR (100MHz, CDCl3) δ199.1,195.2,175.8,137.3,137.0,135.7,133.2,129.7,128.4,127.7,127.5,83.3,31.1,29.0,26.2.MS(EI)m / z:256.06[M] + .Optical Rotation:[α] 25 D 180.1 (c = 1.0, CHCl3).

[0088] Example 14

[0089] Synthesis of (R)-4'-phenylacyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0090]

[0091] Under nitrogen atmosphere, 1e (58.4 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 2e (34.8 mg, 60% yield, 96% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0092] 1 H NMR (400MHz, CDCl3) δ8.09 (dd, J=7.7, 1.5Hz, 1H), 7.56 (td, J=7.7, 1.5Hz, 1H ),7.48–7.41(m,4H),7.35(dd,J=7.4,2.2Hz,2H),7.16(d,J=7.8Hz,1H),6.12 (s,1H),2.92(ddd,J=17.6,11.3,9.6Hz,1H),2.63(ddd,J=17.6,9.6,2.2Hz, 1H), 2.53 (ddd, J=13.4, 9.5, 2.2Hz, 1H), 2.28 (ddd, J=13.4, 11.3, 9.6Hz, 1H). 13 C NMR (100MHz, CDCl3) δ196.6,176.6,140.0,137.7,137.5,135.5,130.7,129. 1,128.9,128.8,128.6,128.3,127.7,127.5,83.9,31.6,26.9.HRMS(ESI)m / z Calcd for[C 19 H 14 O3,M+H] + :291.1016; Found:291.1015.Optical Rotation:[α] 25 D 76 (c = 0.2, CHCl3).

[0093] Example 15

[0094] Synthesis of (R)-4'-benzyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0095]

[0096] Under nitrogen atmosphere, 1f (61.2 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 h, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 2f (48.6 mg, 80% yield, 96% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0097] 1 H NMR (400MHz, CDCl3) δ7.96(d,J=7.7Hz,1H),7.51(t,J=7.7Hz,1H),7.31(dd,J=12.9,7.2Hz,2H),7.24(t,J=7.5Hz ,2H),7.17(d,J=7.5Hz,3H),5.82(s,1H),3.81(s,2H),2.79(m,1H),2.48(m,1H),2.36(m,1H),2.18–2.03(m,1H). 13 C NMR (100MHz, CDCl3) δ196.7,176.6,137.5,137.2,135.9,135.6,130.9,128.9,128 .9,128.8,128.1,127.7,126.9,125.2,83.8,38.8,31.6,26.8.HRMS(ESI)m / zCalcd for[C 20 H 16 O3,M+H] + :305.1172; Found:305.1176.Optical Rotation:[α] 25 D 104.2 (c=1, CHCl3).

[0098] Example 16

[0099] Synthesis of (R)-4'-methyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0100]

[0101] Under nitrogen atmosphere, 1 g (46.0 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate solution and aqueous sodium bicarbonate solution, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product was purified by column chromatography to give 2 g (28.7 mg, yield 63%, ee value 93%) (eluent polarity: PE:EA 3:1).

[0102] 1 H NMR(400MHz, CDCl3)δ8.02(d,J=7.6Hz,1H),7.67(td,J=7.6,1.6Hz,1H),7.47–7.37(m,2H),6.01(s,1H),2.87(ddd,J=17.6 ,11.2,9.7Hz,1H),2.57(ddd,J=17.6,9.5,1.9Hz,1H),2.39(ddd,J=13.5,9.6,2.3Hz,1H),2.18(s,3H),2.22–2.08(m,1H). 13 CNMR(100MHz, CDCl3)δ196.9,176.8,138.0,135.7,133.2,129.0,128.8,127.9,127.4,125.0,83.7,31.6,26.9,19.4.HRMS(ESI)m / z Calcd for[C 14 H 12 O3,M+H] + :229.0859; Found:229.0861.Optical Rotation:[α] 25 D 104.2 (c=1, CHCl3).

[0103] Example 17

[0104] Synthesis of (R)-4'-n-propyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0105]

[0106] Under nitrogen atmosphere, 1h (51.6 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 2h (32.2 mg, yield 63%, ee value 94%) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0107] 1 H NMR (400MHz, CDCl3) δ8.01 (dd, J=7.7, 1.5Hz, 1H), 7.65 (td, J=7.6, 1.5Hz, 1H), 7.46–7.34 (m, 2H), 5.97 (s 1H),2.85(ddd,J=17.6,11.4,9.5Hz,1H),2.63–2.53(m,1H),2.55–2.45(m,2H),2.39(ddd,J=13. 5,9.5,2.1Hz,1H),2.15(ddd,J=13.5,11.4,9.5Hz,1H),1.69–1.55(m,2H),1.00(t,J=7.4Hz,3H). 13 CNMR(100MHz, CDCl3)δ197.0,176.7,137.4,136.8,135.6,128.6,128.3,128.1,127.7,124.7,83.9,34.3,31.6,26.8,21.2,14.0.HRMS(ESI)m / z Calcd for[C 16 H 16 O3,M+H] + :257.1172; Found:257.1175.OpticalRotation:[α] 25 D 169.8 (c=1.0, CHCl3).

[0108] Example 18

[0109] Synthesis of (R)-6'-methoxy-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0110]

[0111] Under nitrogen atmosphere, 1i (49.2 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 h, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 2i (46.3 mg, 95% yield, 97% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0112] 1 H NMR (400MHz, CDCl3) δ7.98(d,J=8.6Hz,1H),6.88(dd,J=8.7,2.5Hz,1H),6.70(d,J=2.5Hz,1H),6.59(d,J=9.9Hz,1H),6.20(d ,J=9.9Hz,1H),3.89(s,3H),2.93(m,1H),2.58(ddd,J=17.6,9.6,2.1Hz,1H),2.39(ddd,J=12.2,9.6,2.2Hz,1H),2.16(m,1H). 13 C NMR(100MHz, CDCl3)δ195.0,176.9,165.7,139.2,133.4,130.6,128.0,120.7,114.5,113.0,83.1,55.9,31.7,26.9.HRMS(ESI)m / zCalcd for[C 14 H 12 O4,M+H] + :245.0808; Found:245.0809.Optical Rotation:[α] 25 D 138.3 (c=1, CHCl3).

[0113] Example 19

[0114] Synthesis of (R)-4,5-dihydro-1'H,3H-spiro[furan-2,2'-naphthalene]-1'-one:

[0115]

[0116] Under nitrogen atmosphere, 3a (40.4 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 4a (30.4 mg, yield 76%, ee value 96%) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0117] 1 H NMR (400MHz, CDCl3) δ7.95 (dd, J=7.8, 1.4Hz, 1H), 7.53 (td, J=7.5, 1.4Hz, 1H), 7.32 (td, J=7.6, 1.2Hz, 1H), 7.17 (dd, J=7.6, 1.1Hz, 1H), 6. 49(d,J=9.9Hz,1H),6.16(d,J=9.9Hz,1H),4.36–4.26(m,1H),4.19–4.09(m,1H),2.27–2.16(m,2H),2.08–1.99(m,1H),1.96–1.85(m,1H). 13 C NMR(100MHz, CDCl3)δ202.0,137.5,136.7,134.8,129.0,128.1,127.4,127.2,125.7,84.3,70.7,36.6,25.3.HRMS(ESI)m / z Calcd for[C 13 H 12 O2,M+H] + :201.0910; Found:201.0907.Optical Rotation:[α] 25 D 247.2 (c = 0.5, CHCl3).

[0118] Example 20

[0119] Synthesis of (R)-4'-methyl-4,5-dihydro-1'H,3H-spiro[furan-2,2'-naphthalene]-1'-one:

[0120]

[0121] Under nitrogen atmosphere, 3b (43.2 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 4b (22.2 mg, 52% yield, 89% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0122] 1 H NMR (400MHz, CDCl3) δ7.97(dd,J=7.7,1.5Hz,1H),7.59(td,J=7.6,1.5Hz,1H),7.34(td,J=7.7,6.3Hz,2H),5.97(s,1H),4. 30–4.21(m,1H),4.17–4.06(m,1H),2.19(ddd,J=11.8,7.7,3.9Hz,2H),2.12(s,3H),2.07–1.99(m,1H),1.92–1.82(m,1H). 13 C NMR(100MHz, CDCl3)δ202.1,138.5,134.7,133.2,130.6,129.0,127.9,127.4,124.4,84.1,70.4,36.4,25.4,19.4.HRMS(ESI)m / z Calcd for[C 14 H 14 O2,M+H] + :215.1067; Found:215.1070.Optical Rotation:[α] 25 D 216.2 (c = 0.5, CHCl3).

[0123] Example 21

[0124] Synthesis of (R)-4'-ethyl-4,5-dihydro-1'H,3H-spiro[furan-2,2'-naphthalene]-1'-one:

[0125]

[0126] Under nitrogen atmosphere, 3c (46.0 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 h, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 4c (28.7 mg, 63% yield, 91% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0127] 1 H NMR (400MHz, CDCl3) δ7.97(dd,J=7.7,1.5Hz,1H),7.58(td,J=7.6,1.5Hz,1H),7.39–7.31(m,2H),5.96(s,1H),4.32–4.25(m ,1H),4.17–4.11(m,1H),2.55–2.47(m,2H),2.24–2.16(m,2H),2.07–1.99(m,1H),1.91–1.83(m,1H),1.21(t,J=7.4Hz,3H). 13 CNMR(100MHz, CDCl3)δ202.3,138.0,135.9,134.6,131.3,129.3,127.8,127.5,123.9,84.4,70.5,36.5,25.3,25.1,12.6.HRMS(ESI)m / z Calcd for[C 15 H 16 O2,M+H] + :229.1223; Found:229.1225.Optical Rotation:[α] 25 D 176.6 (c=1, CHCl3).

[0128] Example 22

[0129] Synthesis of (R)-4'-n-butyl-4,5-dihydro-1'H,3H-spiro[furan-2,2'-naphthalene]-1'-one:

[0130]

[0131] Under nitrogen atmosphere, 3d (51.6 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 4d (31.2 mg, 61% yield, 88% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0132] 1 H NMR(400MHz, CDCl3)δ7.97(dd,J=7.7,1.5Hz,1H),7.57(td,J=7.6,1.5Hz,1H),7.39–7.30(m,2H),5.95(s,1H),4.31–4.25(m,1H),4.17–4.10(m ,1H),2.51–2.43(m,2H),2.24–2.15(m,2H),2.06–1.98(m,1H),1.92–1. 83(m,1H),1.60–1.52(m,2H),1.46–1.36(m,2H),0.94(t,J=7.3Hz,3H). 13 C NMR (100MHz, CDCl3) δ202.3,137.9,134.6,134.6,132.4,129.4,127.7,127.5,124.1,84.4,70.4,36.6,32.1,30.4,25.3,22.7,14.1.HRMS (ESI) m / z Calcd for[C 15 H 12 O4,M+H] + :257.0807; Found:257.0808.Optical Rotation:[α] 25 D 176.4 (c = 0.5, CHCl3).

[0133] Example 23

[0134] Synthesis of (R)-4'-phenyl-4,5-dihydro-1'H,3H-spiro[furan-2,2'-naphthalene]-1'-one:

[0135]

[0136] Under nitrogen atmosphere, 3e (57.4 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 4e (38.6 mg, 70% yield, 86% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0137] 1 H NMR(400MHz, CDCl3)δ8.03(dd,J=7.7,1.5Hz,1H),7.51–7.33(m,7H),7.09(d,J=7.8Hz,1H),6.11(s, 1H),4.36–4.29(m,1H),4.22–4.10(m,1H),2.37–2.30(m,1H),2.28–2.19(m,1H),2.12–1.97(m,2H). 13 C NMR (100MHz, CDCl3) δ201.8,138.7,137.9,137.6,135.2,134.4,129.3,129. 0,128.6,128.2,128.0,127.6,126.8,84.5,70.6,36.8,25.5.HRMS(ESI)m / z Calcd for[C 19 H 16 O2,M+H] + :277.1223; Found:277.1223.OpticalRotation:[α] 25 D 98.0 (c = 0.5, CHCl3).

[0138] Example 24

[0139] Synthesis of (R)-4'-phenyl-4,5-dihydro-1'H,3H-spiro[furan-2,2'-naphthalene]-1'-one:

[0140]

[0141] Under nitrogen atmosphere, 3f (58.4 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 h, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 4f (41.1 mg, 71% yield, 92% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0142] 1 H NMR (400MHz, CDCl3) δ7.99–7.87(m,1H),7.43(td,J=7.6,1.3Hz,1H),7.28–7.14(m,7H),5.91(s,1H),4.25(td ,J=7.7,5.3Hz,1H),4.12–4.03(m,1H),3.79(s,2H),2.25–2.10(m,2H),2.04–1.94(m,1H),1.92–1.81(m,1H). 13 CNMR(100MHz, CDCl3)δ=202.0,138.4,137.6,135.4,134.6,133.1,129.3,128.7,12 8.7,127.9,127.5,126.6,124.8,84.5,70.6,38.9,36.7,25.2.HRMS(ESI)m / zCalcd for[C 20 H 18 O2,M+H] + :291.1380; Found:291.1382.Optical Rotation:[α] 25 D 136.0 (c=1, CHCl3).

[0143] Example 25

[0144] Synthesis of (R)-6'-methoxy-4,5-dihydro-1'H,3H-spiro[furan-2,2'-naphthalene]-1'-one:

[0145]

[0146] Under nitrogen atmosphere, 3 g (46.4 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 3 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate solution and aqueous sodium bicarbonate solution, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product was purified by column chromatography to give 4 g (33.5 mg, yield 73%, ee value 94%) (eluent polarity: PE:EA 3:1).

[0147] 1 H NMR (400MHz, CDCl3) δ8.37(d,J=8.6Hz,1H),7.25(dd,J=8.6,2.5Hz,1H),7.06(d,J=2.5Hz,1H),6.87(d,J=9.8Hz,1H),6.60( d,J=9.8Hz,1H),4.78–4.67(m,1H),4.62–4.51(m,1H),4.29(s,3H),2.73–2.59(m,2H),2.51–2.41(m,1H),2.39–2.25(m,1H). 13 C NMR(100MHz, CDCl3)δ200.4,164.9,139.7,137.7,129.9,125.6,122.4,113.7,112.1,83.6,70.8,55.7,37.0,25.5.HRMS(ESI)m / zCalcd for[C 14 H 14 O3,M+H] + :231.1016; Found:231.1016.Optical Rotation:[α] 25 D 172.5 (c = 0.5, CHCl3).

[0148] Example 26

[0149] Synthesis of (R)-3,4-dihydro-2'H,5Hspiro[furan-2'-naphthalene]-2',5-dione:

[0150]

[0151] Under nitrogen atmosphere, 5a (43.2 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 6a (31.2 mg, 73% yield, 95% ee) was purified by column chromatography (eluent polarity: PE:EA 1:1) was obtained.

[0152] 1 H NMR (400MHz, CDCl3) δ7.55(d,J=7.7Hz,1H),7.47(dd,J=9.3,6.7Hz,2H),7.43–7.33(m,2H),6.17(d,J=9 .9Hz,1H),2.84(ddd,J=17.1,11.6,9.3Hz,1H),2.71–2.60(m,2H),2.15(ddd,J=14.0,11.6,9.7Hz,1H). 13 C NMR (100MHz, CDCl3) δ197.7,176.6,146.2,140.7,131.2,129.9,129.3,129.3,125.9,122.7,86.0,35.9,26.7.MS(EI)m / z:214.06[M] + .Optical Rotation:[α] 25 D 264.2 (c = 1.0, CHCl3).

[0153] Example 27

[0154] Synthesis of (R)-7'-methoxy-3,4-dihydro-2'H,5Hspiro[furan-2'-naphthalene]-2',5-dione:

[0155]

[0156] Under nitrogen atmosphere, 5b (49.2 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 6b (41.4 mg, 85% yield, 95% ee) was purified by column chromatography (eluent polarity: PE:EA 1:1) was obtained.

[0157] 1 H NMR (400MHz, CDCl3) δ7.40(d,J=9.9Hz,1H),7.24(d,J=2.7Hz,1H),7.05(d,J=2.6Hz,1H),6.85(dd,J=8.4,2.6Hz,1H),5.99 (d,J=9.9Hz,1H),3.83(s,3H),2.80(ddd,J=17.4,11.7,9.4Hz,1H),2.66–2.57(m,2H),2.11(ddd,J=13.8,11.7,9.6Hz,1H). 13 C NMR(100MHz, CDCl3)δ197.6,176.7,162.3,146.2,143.1,131.7,122.3,119.9,114.5,111.7,86.1,55.8,36.2,26.7.HRMS(FAB)m / zcalcd for[C 14 H 12 O4+H] + :245.0814,found:245.0808.Optical Rotation:[α] 25 D 232.2 (c = 1.0, CHCl3).

[0158] Example 28

[0159] Synthesis of (R)-6'-bromo-3,4-dihydro-2'H,5Hspiro[furan-2'-naphthalene]-2',5-dione:

[0160]

[0161] Under nitrogen atmosphere, 5c (58.8 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of the preferred catalyst (10) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 hours, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure and purified by column chromatography to give the product 6c (35.6 mg, 61% yield, 94% ee) (eluent polarity: PE:EA 1:1).

[0162] 1 H NMR (400MHz, CDCl3) δ7.58(dd,J=8.3,2.0Hz,1H),7.49(d,J=2.0Hz,1H),7.45–7.37(m,2H),6.20(d,J=1 0.0Hz,1H),2.82(ddd,J=16.9,11.6,9.0Hz,1H),2.68–2.59(m,2H),2.11(ddd,J=14.3,11.6,9.7Hz,1H). 13 C NMR(100MHz, CDCl3)δ196.9,176.2,144.5,139.4,133.8,132.4,131.1,127.6,123.9,123.2,85.5,35.7,26.6.HRMS(FAB)m / zcalcd for[C 13 H9BrO3+H] + :292.9813,found:292.9814.Optical Rotation:[α] 25 D 172.5 (c = 0.5, CHCl3).

[0163] Example 29

[0164] Synthesis of (S)-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione:

[0165]

[0166] Under nitrogen atmosphere, 1a (43.2 mg, 0.2 mmol, 1.0 equiv.), anhydrous DCM (10.0 mL) and ethanol (46.1 mg, 5 equiv.) were added to a dry schlenk tube, followed by the addition of catalyst (18) (41.2 mg, 0.03 mmol, 15 mol%) and mCPBA (61.1 mg, 3 mmol, 1.5 equiv.) at -20°C. The mixture was reacted at -20°C for 24 h, quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate, extracted with ethyl acetate, and the organic phase was separated. The solvent was removed under reduced pressure, and the product 2a' (39.5 mg, 92% yield, -98% ee) was purified by column chromatography (eluent polarity: PE:EA 3:1) was obtained.

[0167] Optical Rotation:[α] 25 D -143.5 (c = 0.5, CHCl3).

[0168] Example 30

[0169] Catalyst recovery:

[0170]

[0171] Under nitrogen atmosphere, 1a (648.1 mg, 3 mmol, 1.0 equiv.), anhydrous DCM (210.0 mL) and ethanol (690.8 mg, 5 equiv.) were added to a dry Schlenk tube. Then, the preferred catalyst (10) (417.2 mg, 0.3 mmol, 10 mol%) and mCPBA (732.7 mg, 3.6 mmol, 1.2 equiv.) were added at -20°C and reacted for 48 hours at -20°C. The reaction was quenched with saturated aqueous sodium thiosulfate and aqueous sodium bicarbonate. The organic layer was extracted with DCM, washed with saturated brine, dried over anhydrous Na2SO4, and evaporated under reduced pressure. The residue was dissolved in 30 mL of MeOH, and then 10 mL of H2O was added to obtain a precipitated catalyst that could be used in the next cycle. The solution was evaporated under reduced pressure to obtain a crude product, which could be further purified by ethyl acetate and petroleum ether. The crude product can be further recrystallized from a mixture of ethyl acetate and petroleum ether (10 mL, 1:300 volume ratio) to obtain 2a (558.7 mg, 87% yield, 96% ee value), 405.8 mg of catalyst is recovered, and the catalyst recovery rate is 97%; the above operation is repeated for a second cycle, and the product 2a (545.9 mg, 85% yield, 96% ee value) is obtained for the second recrystallization and purification, and 393.6 mg of catalyst is recovered, and the catalyst recovery rate is 97%; the above operation is repeated for ten cycles, and the product 2a (526.6 mg, 82% yield, 97% ee value) is obtained for the tenth recrystallization and purification, and the catalyst recovery rate is 98%. After completing ten catalytic reactions, 330.4 mg of catalyst is obtained, and the total recovery rate is 79.9%. The catalyst recovery experiment yield, ee value, and recovery rate are shown as follows: Figure 1 shown.

Claims

1. A method for preparing chiral spirosteroid compounds using a chiral aryl iodide catalyst derived from chloramphenicol, characterized in that: The method comprises the following steps: adding a naphthol derivative to an organic solvent; sequentially adding an additive, a chiral aryl iodide catalyst, and an oxidant at an appropriate temperature to carry out a reaction; quenching the reaction with a quenching agent to obtain a product; and finally recovering the catalyst. The reaction process includes the following steps: Reaction 1: Reaction 2: Reaction 3: The H on the benzene ring is substituted by R 1 , R 2 , R 3 , R 4 and R 5 Substituted or unsubstituted, when substituted R 1 , R 2 are each independently selected from alkyl, halogen, phenyl, alkyl acyl or phenyl acyl; R 3 is selected from halogen or alkoxy; R 4 and R 5 Selected from alkoxy, The structural formula of the chiral aryl iodide catalyst derived from chloramphenicol is as follows: 6 , R 7 and R 8 Each is independently selected from phenyl, substituted phenyl, the substituent on the substituted phenyl is methyl, methoxy, tert-butyl, halogen or nitro: The oxidant in the reaction is potassium peroxymonosulfonate, a selective fluorine reagent, N-fluorobisbenzenesulfonamide or m-chloroperbenzoic acid; the additive is methanol, ethanol or n-butanol; The catalyst recovery process includes the following steps: 1) adding dichloromethane to the quenched system for extraction; 2) The organic phase was dried by adding anhydrous sodium sulfate and evaporated under reduced pressure; 3) Dissolve the residue with a good solvent; 4) adding an inert solvent to the solution of step 3) to produce a white solid; 5) Filter with a Buchner funnel to obtain a white solid, which is the recovered catalyst; The benign solvent in step 3) is ether, methanol or ethanol; The inert solvent in step 4) is water or petroleum ether.

2. A method according to claim 1, characterized in that The amount of the catalyst used in reaction 1 is 1-20 mol% of the 1-naphthol derivative shown in formula (1), the amount of the oxidant used is 1.0-3.0 equivalents of the 1-naphthol derivative shown in formula (1), and the solvent is dichloromethane, toluene or ethyl acetate.

3. The method according to claim 1, wherein The amount of the catalyst used in reaction 2 is 1-20 mol% of the 1-naphthol derivative shown in formula (3), the amount of the oxidant used is 1.0-3.0 equivalents of the 1-naphthol derivative shown in formula (3), and the solvent is dichloromethane, toluene or ethyl acetate.

4. The method according to claim 1, wherein The amount of the catalyst used in reaction 3 is 1-20 mol% of the 2-naphthol derivative shown in formula (5), the amount of the oxidant used is 1.0-3.0 equivalents of the 1-naphthol derivative shown in formula (5), and the solvent is dichloromethane, toluene or ethyl acetate.

5. The method according to claim 1, wherein The reaction temperatures of reaction 1, reaction 2 and reaction 3 are all -40-10°C, the reaction times are all 8-30h, and the quenching agents are saturated sodium thiosulfate aqueous solution and sodium bicarbonate aqueous solution.

6. The method according to claim 1, wherein The volume dosage of the benign solvent is 1:0.05 to the molar mass dosage of the naphthol derivative. The volume unit is mL, and the molar mass unit is mmol.

7. The method according to claim 6, wherein The dosage of inert solvent is 0.2-1 times that of benign solvent.

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