Method for constructing bicyclo [2.1. 1] hexane compound through cycloaddition reaction of allyl silane and bicyclo [1.1. 1] butane

Abstract

The invention discloses a method for constructing a bicyclo [2.1. 1] hexane compound through cycloaddition reaction of allyl silane and bicyclo [1.1. 1] butane. The preparation method comprises the following steps: carrying out intermolecular cycloaddition reaction in an organic solvent by taking allyl silane and bicyclo [1.1. 1] butanone as raw materials under the action of lewis acid as a catalyst to obtain the bicyclo [2.1. 1] hexane compound. And purifying to obtain the bicyclo [2.1. 1] hexane compound. Raw materials are easy to obtain, stability is high, reaction operation is simple, conditions are mild, substrate applicability is good, atom economy is achieved, the method has the advantage of being suitable for industrial production, and a novel and diversified skeleton structure has very important value for research and development of new drugs.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a method for constructing bicyclo[2.1.1]hexane compounds by the cycloaddition reaction of allylsilanes and bicyclo[1.1.0]butane. Background Art

[0002] In new drug research and development, chemists often prefer to introduce saturated cyclic compounds to replace aromatic backbone structures to modify the physicochemical properties of compounds, including activity, metabolic stability, water solubility, and lipophilicity, etc., thereby increasing the success rate of drug research and development. Therefore, the development of novel synthetic strategies for constructing new benzene ring bioisosteres has received extensive attention from synthetic chemists. In recent years, bicyclo[2.1.1]hexane compounds have been considered as bioisosteres of ortho- or meta-disubstituted benzene rings, and their synthesis has become a research hotspot. Bicyclo[1.1.0]butane molecules are very practical synthons, and based on the internal ring strain of the molecules, they can participate in radical or ionic cyclization reactions to construct bicyclo[2.1.1]hexane compounds. Previously, we have developed a formal cycloaddition reaction of indole and enol silyl ethers with bicyclo[1.1.0]butane molecules catalyzed by Lewis acid to construct bicyclo[2.1.1]hexane compounds. This new catalytic mode of using Lewis acid-catalyzed bicyclo[1.1.0]butane as an electrophile has very broad substrate generality. However, this strategy has only been extended to active nucleophiles, and more inert nucleophiles remain to be further developed, which is expected to further expand the scope of application of this catalytic system and provide new synthetic methods for new drug research and development. Allylsilane compounds are very important reaction reagents and can undergo a series of addition reactions (Hosomi-Sakurai) and (2+2) or (3+2) cycloaddition reactions with some carbonyl or unsaturated carbonyl compounds to construct a series of novel compounds. However, the cycloaddition reaction of allylsilane compounds with σ-bonds has rarely been reported. It is worth mentioning that allylsilane compounds are simple to obtain and extremely stable, and can tolerate conditions such as oxygen and water. In addition, the silyl functional group can be simply converted into a series of other active functional groups through subsequent reactions, further enriching the compound library. Therefore, developing the cycloaddition reaction of allylsilane compounds and bicyclo[1.1.0]butane to construct silyl-substituted bicyclo[2.1.1]hexane compounds has important scientific research value and application value. Summary of the Invention

[0003] The object of the present invention is to provide a method for constructing bicyclo[2.1.1]hexane compounds by the cycloaddition reaction of allylsilanes and bicyclo[1.1.0]butane. In the present invention, the allylsilane compound undergoes an intermolecular cycloaddition reaction with bicyclo[1.1.0]butane activated by a Lewis acid to directly prepare bicyclo[2.1.1]hexane compounds.

[0004] The object of the present invention is achieved by the following technical solutions:

[0005] A method for constructing bicyclo[2.1.1]hexane compounds through the cycloaddition reaction of allylsilanes and bicyclo[1.1.0]butane uses allylsilane compound I and bicyclo[1.1.0]butanone compound II as raw materials, a Lewis acid as a catalyst, and undergoes an intermolecular cycloaddition reaction in an organic solvent, and the bicyclo[2.1.1]hexane compound III is obtained through purification;

[0006] The specific reaction equation is as follows:

[0007]

[0008] In the formula, R of the silyl substituent in allylsilane compound I 1 , R 2 , R 3 are selected from alkyl or aryl, including trimethylsilyl (TMS), dimethylphenylsilyl (DMPS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS); R 4 is selected from any one of aryl, alkenyl, alkynyl, or alkyl substituents; R 5 is selected from hydrogen or an alkyl substituent; R in bicyclo[1.1.0]butanone compound II 6 is selected from aryl or alkyl; R of the bicyclo[2.1.1]hexane compound III 1 ~R 6 is the same as the two raw materials;

[0009] The organic solvent is selected from any one of halogenated solvents, aromatic solvents, ether solvents, nitrile solvents, and ester solvents.

[0010] Furthermore, the allylsilane compound I is selected from one of the following compounds:

[0011]

[0012] Furthermore, the bicyclo[1.1.0]butanone compound II is selected from one of the following compounds:

[0013]

[0014] Furthermore, the organic solvent is at least one of dichloromethane, toluene, tetrahydrofuran, acetonitrile, and ethyl acetate.

[0015] Furthermore, the Lewis acid is Yb(OTf) 3 , Sc(OTf) 3 , Cu(OTf) 2, AgOTf, Al(OTf) 3 , Ga(OTf) 3 , Fe(OTf) 3 , Bi(OTf) 3 , B(C 6 F 5 ) 3 and InI 3 Any one of; in Yb(OTf) 3 , Sc(OTf) 3 and B(C 6 F 5 ) 3 Under the catalysis of these Lewis acids, the reaction yield is high.

[0016] Furthermore, the molar ratio of the allylsilane compound I to the bicyclo[1.1.0]butanone compound II is 1:(1-1.5). Specifically, within this reaction molar ratio range, the allylsilane compound can be completely converted. When it is higher than 1:1, the allylsilane compound will remain. When it is lower than 1:1.5, a large amount of bicyclo[1.1.0]butane will remain, causing waste. The further preferred reaction molar ratio is 1:1.3.

[0017] Furthermore, the reaction time is 0.5 - 12 hours. Specifically, within 2 hours, the reaction raw materials will remain, and within 12 hours, the raw materials will completely react. The reaction temperature is room temperature. Specifically, the reaction conversion rate is high between 20°C and 30°C.

[0018] A bicyclo[2.1.1]hexane compound prepared by the above method.

[0019] Furthermore, the structural formula of the bicyclo[2.1.1]hexane compound III is selected from:

[0020]

[0021]

[0022] Furthermore, after the reaction, the separation of the final product is completed by column chromatography. The eluent for column chromatography is a mixed solvent of ethyl acetate / petroleum ether. Furthermore, the percentage of ethyl acetate in petroleum ether is 0% - 10%.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] (1) Under the catalysis of Lewis acid in the present invention, the allylsilane compound and bicyclo[1.1.0]butane undergo an intermolecular cycloaddition reaction to obtain a bicyclo[2.1.1]hexane compound, with good functional group compatibility and high atom economy.

[0025] (2) The reaction substrate of the present invention has good stability, mild conditions, simple operation and is easy to industrialize.

[0026] (3) The allylsilane compound used in the present invention is simple to prepare, and the starting materials are inexpensive, greatly reducing the preparation cost of the final product.

[0027] (4) The present invention has a wide range of applications and can rapidly and diversely synthesize a series of structurally novel bicyclo[2.1.1]hexane compounds, which will be of great significance for new drug screening. Detailed implementation manners

[0028] The present invention will be specifically described below through examples. It is necessary to point out here that the following examples are only used to further illustrate the present invention and cannot be construed as limiting the protection scope of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the above content of the present invention all fall within the protection scope of the present invention.

[0029] Examples 1-10

[0030] Using allylsilane compound I-1 and bicyclo[1.1.0]butane II-1 as raw materials, dichloromethane as the solvent, and 10 kinds of Lewis acids as catalysts, a cycloaddition reaction occurs to obtain bicyclo[2.1.1]hexane compound III-1. The reaction formula is as follows:

[0031]

[0032] I-1 (0.1 mmol), II-1 (0.13 mmol) and Lewis acid (0.01 mmol) were added to a 5 mL reaction flask, the rubber stopper was plugged, and nitrogen was evacuated and replaced three times. Under a nitrogen atmosphere, the solvent dichloromethane (1 mL) was added, and then the rubber stopper was quickly replaced with a screw cap. After stirring at 25 °C for 2-8 hours, it was filtered through a short silica gel column, the filtrate was concentrated, and the residual mixture was separated and purified by silica gel column chromatography to obtain bicyclo[2.1.1]hexane compound III-1.

[0033] Table 1: Influence of Lewis acid on the reaction

[0034]

[0035] a. NMR yield using mesitylene as the internal standard.

[0036] Examples 11-15

[0037] Using allylsilane compound I-1 and bicyclo[1.1.0]butane II-1 as raw materials, with Sc(OTf) 3Using [catalyst] as the catalyst, a cycloaddition reaction occurs in four solvents to obtain the bicyclo[2.1.1]hexane compound III-1. The reaction formula is as follows:

[0038]

[0039] I-1 (0.1 mmol), II-1 (0.13 mmol) and Lewis acid (0.01 or 0.005 mmol) were added to a 5 mL reaction flask, the rubber stopper was inserted, and nitrogen was evacuated and replaced three times. Under a nitrogen atmosphere, the solvent (1 mL) was added, and then the rubber stopper was quickly replaced with a screw cap. After stirring at 25 °C for 0.5 or 3 hours, it was filtered through a short silica gel column, the filtrate was concentrated, and the residual mixture was separated and purified by silica gel column chromatography to obtain the bicyclo[2.1.1]hexane compound III-1.

[0040] Table 2: Influence of solvents and catalyst amounts on the reaction

[0041]

[0042] a. NMR yield using mesitylene as the internal standard.

[0043] Examples 16 - 19

[0044] Using allylsilane compounds I-1 - I-4 with different silyl substituents and bicyclo[1.1.0]butane II-1 as raw materials, a cycloaddition reaction occurs in toluene as the solvent using scandium trifluoromethanesulfonate as the catalyst to obtain bicyclo[2.1.1]hexane compounds III-1 - III-4. The reaction formula is as follows:

[0045]

[0046] I-1 - I-4 (0.1 mmol), II-1 (0.13 mmol) and scandium trifluoromethanesulfonate (0.01 mmol) were added to a 5 mL reaction flask, the rubber stopper was inserted, and nitrogen was evacuated and replaced three times. Under a nitrogen atmosphere, toluene (1 mL) was added, and then the rubber stopper was quickly replaced with a screw cap. After stirring at 25 °C for 2 hours, it was filtered through a short silica gel column, the filtrate was concentrated, and further separated and purified by silica gel column chromatography to obtain bicyclo[2.1.1]hexane compounds III-1 - III-4.

[0047] Table 3: Influence of silyl substituents on the reaction

[0048]

[0049] a. Isolated yield

[0050] The characterization of the bicyclo[2.1.1]hexane compound products is as follows:

[0051] (rac - )((1S,2R,4R)-2-((tert - butyldiphenylsilyl)methyl)-2 - methylbicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 1)

[0052]

[0053] Colorless oil, 91 mg, 90%(0.2 mmol scale), R f = 0.60(10% EA in PE). 1 H NMR(500 MHz, CDCl 3 ) δ 8.40(s, 1H), 8.01(dd, J = 8.5, 1.6 Hz, 1H), 7.93(d, J = 8.1 Hz, 1H), 7.90(d, J = 8.6 Hz, 1H), 7.87(d, J = 8.1 Hz, 1H), 7.72(d, J = 7.1 Hz, 2H), 7.58(t, J = 7.4 Hz, 1H), 7.54(dd, J = 7.8, 3.4 Hz, 3H), 7.41(t, J = 7.2 Hz, 1H), 7.36(t, J = 7.2 Hz, 2H), 7.32(t, J = 7.4 Hz, 1H), 7.25(t, J = 7.4 Hz, 2H), 2.30–2.23(m, 2H), 2.09–2.00(m, 3H), 1.89(d, J = 14.9 Hz, 1H), 1.58(d, J = 11.1 Hz, 1H), 1.32(d, J = 14.9 Hz, 1H), 1.08(d, J = 12.2 Hz, 1H), 0.94(d, J = 17.3 Hz, 12H). 13 C NMR(125 MHz, CDCl 3 ) δ 204.1, 136.9, 136.8, 136.6, 135.6, 135.3, 135.2, 132.6, 130.6, 129.6, 129.1, 129.0, 128.3, 128.2, 127.8, 127.6, 127.3, 126.7, 124.9, 68.8, 43.9, 43.6, 43.5, 42.6, 35.6, 28.0, 26.8, 20.4, 18.4. ATR - IR ν(cm -1): 2962 (m), 2928 (m), 2856 (m), 1648 (s), 1626 (m), 1426 (m), 1305 (m), 1194 (m), 1100 (s), 787 (s), 735 (s), 701 (s). HRMS (ESI): Calc for C 35 H 39 OSi + (M + H + ): 503.2765, Found: 503.2763.

[0054] (rac - )((1S,2R,4R)-2 - methyl - 2 - ((triisopropylsilyl)methyl)bicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone (III - 2)

[0055]

[0056] Colourless oil, 72 mg, 86% (0.2 mmol scale), R f =0.55 (10% EA in PE). 1 HNMR (500 MHz, CDCl 3 ) δ 8.37 (s, 1H), 7.95 (d, J = 8.5 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 8.7 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 2.43 (s, 1H), 2.27 (dd, J = 9.8, 6.9 Hz, 1H), 2.18 (dd, J = 9.9, 6.9 Hz, 1H), 2.12 (dt, J = 6.4, 2.8 Hz, 1H), 2.06 (dt, J = 6.6, 3.0 Hz, 1H), 1.86 (dd, J = 10.6, 2.4 Hz, 1H), 1.75 (dd, J = 10.4, 2.3 Hz, 1H), 1.26 (m, 4H), 1.07–1.02 (m, 3H), 1.00–0.92 (m, 18H), 0.72 (d, J = 15.0 Hz, 1H). 13 C NMR (125 MHz, CDCl 3)δ204.1,136.7,135.2,132.5,130.6,129.6,128.2,128.1,127.8,126.7,124.9,69.0,44.3,43.9,43.3,42.9,35.5,26.5,20.7,19.1,19.1,12.0.ATR-IRν(cm -1 ):2964(s),2942(s),2865(s),1652(s),1627(m),1463(s),1307(s),1194(s),881(s),787(s),745(s).HRMS(ESI):Calc forC 28 H 41 OSi + (M+H + ):421.2921,Found:421.2927.

[0057] (rac - )((1S,2R,4R)-2 - ((dimethyl(phenyl)silyl)methyl)-2 - methylbicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 3)

[0058]

[0059] Colourless oil,56 mg,69%(0.2 mmol scale),Rf=0.55(10% EA in PE). 1 HNMR(500 MHz,CDCl 3)δ8.38(s,1H),7.97(d,J=8.5 Hz,1H),7.93(d,J=8.1 Hz,1H),7.87(d,J=8.2 Hz,2H),7.59(t,J=7.5 Hz,1H),7.54(t,J=7.4 Hz,1H),7.46(dd,J=6.4,2.1Hz,2H),7.32–7.26(m,3H),2.38(s,1H),2.17(qd,J=9.7,6.3 Hz,2H),2.10(dd,J=6.3,3.1 Hz,1H),2.03(dd,J=6.5,3.1 Hz,1H),1.78(d,J=10.8 Hz,1H),1.61(d,J=12.9Hz,1H),1.51(d,J=14.5Hz,1H),1.19(s,3H),0.94(d,J=14.5Hz,1H),0.33(d,J=15.6Hz,6H). 13 C NMR(125MHz,CDCl 3 )(one carbon in aromatic region is overlapped)δ203.7,140.4,136.2,135.3,133.6,132.5,130.8,129.7,128.8,128.4,128.2,127.8,126.7,125.0,68.2,44.3,43.8,43.3,42.9,35.5,27.1,26.9.ATR-IRν(cm -1 ):2962(s),2926(m),1649(s),1626(s),1462(m),1306(s),1113(s),832(s),817(s),786(s).HRMS(ESI):Calcfor C 27 H 31 OSi + (M+H + ):399.2139,Found:399.2140.

[0060] (rac-)((1S,2R,4R)-2-methyl-2-((trimethylsilyl)methyl)bicyclo[2.1.1]hexan-1-yl)(na phthalen-2-yl)methanone(III-4)

[0061]

[0062] White solid, 37 mg, 55% (0.2 mmol scale), Rf = 0.55 (10% EA in PE). m.p.: 94 °C. 1 H NMR (500 MHz, CDCl 3 ) δ 8.38 (s, 1H), 7.98 (dd, J = 8.7, 1.7 Hz, 1H), 7.94 (dd, J = 8.1, 1.2 Hz, 1H), 7.86 (d, J = 8.4 Hz, 2H), 7.58 (ddd, J = 8.2, 6.9, 1.4 Hz, 1H), 7.53 (ddd, J = 8.1, 6.8, 1.4 Hz, 1H), 2.42 (br s, 1H), 2.22 (dd, J = 9.8, 6.7 Hz, 1H), 2.17 (dd, J = 9.8, 6.8 Hz, 1H), 2.11 (dt, J = 6.7, 2.8 Hz, 1H), 2.04 (dt, J = 6.8, 2.8 Hz, 1H), 1.84–1.80 (m, 1H), 1.70 (m, 1.4 Hz, 1H), 1.23 (m, 4H), 0.65 (d, J = 14.1 Hz, 1H), 0.02 (d, J = 0.8 Hz, 9H). 13 C NMR (125 MHz, CDCl 3 ) δ 203.7, 136.2, 135.3, 132.5, 130.9, 129.8, 128.4, 128.1, 127.8, 126.7, 125.0, 68.2, 44.4, 43.9, 43.3, 43.0, 35.5, 27.7, 26.6. ATR-IR ν (cm -1 ): 2963 (s), 1651 (s), 1627 (m), 1307 (m), 1248 (s), 1195 (m), 864 (s), 842 (s), 786 (s). HRMS (ESI): Calc for C 22 H 29 OSi + (M + H + ): 337.1982, Found: 337.1988.

[0063] Examples 20 - 52

[0064] Using tert-butyldiphenylsilyl allyl silane compounds I-5 to I-37 with different substituents and bicyclo[1.1.0]butane II-1 as raw materials, in toluene as a solvent, with scandium trifluoromethanesulfonate as a catalyst, a cycloaddition reaction occurs to obtain bicyclo[2.1.1]hexane compounds III-5 to III-37. The reaction formula is as follows:

[0065]

[0066] Table 4: Influence of substituents on the vinyl group of allylsilane compounds on the reaction

[0067]

[0068]

[0069]

[0070]

[0071] a. Isolated yield; b. rr: regioselectivity ratio (3 + 2) / (4 + 3)

[0072] The product characterization of the bicyclo[2.1.1]hexane compound is as follows:

[0073] (rac - )((1S,2R,4R)-2-butyl-2-((tert-butyldiphenylsilyl)methyl)bicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone (III-5)

[0074]

[0075] White foam, 78 mg, 72% yield (0.2 mmol scale), Rf = 0.70 (10% EA in PE). 1 1H NMR (600 MHz, CDCl 3)δ8.34(d, J = 1.7 Hz, 1H), 7.95–7.89(m, 2H), 7.89–7.85(m, 2H), 7.71–7.67(m, 2H), 7.66–7.63(m, 2H), 7.58(ddd, J = 8.2, 6.8, 1.3 Hz, 1H), 7.54–7.51(m, 1H), 7.43–7.33(m, 4H), 7.28(t, J = 7.5 Hz, 2H), 2.41(ddd, J = 8.5, 6.8, 1.4 Hz, 1H), 2.26(d, J = 1.7 Hz, 1H), 2.07(dd, J = 6.6, 3.1 Hz, 1H), 2.05–1.95(m, 4H), 1.46(tt, J = 14.2, 2.4 Hz, 1H), 1.37(d, J = 15.2 Hz, 1H), 1.26–1.21(m, 1H), 1.01–0.95(m, 1H), 0.92(s, 9H), 0.83–0.76(m, 1H), 0.71–0.52(m, 3H), 0.39(t, J = 7.2 Hz, 3H). 13 C NMR(150 MHz, CDCl 3 )δ204.6, 137.0, 136.9, 136.3, 136.2, 135.6, 135.2, 132.5, 130.4, 129.6, 129.2, 129.0, 128.3, 128.1, 127.8, 127.5, 127.4, 126.7, 125.0, 68.2, 48.2, 45.5, 44.3, 41.9, 37.9, 34.9, 29.0, 28.0, 23.0, 18.7, 15.6, 13.8. ATR - IR ν(cm -1 ): 2959(s), 2929(s), 1651(s), 1464(m), 1303(m), 1102(s), 817(m), 701(s). HRMS(ESI): Calc for C 38 H 45 OSi + (M + H + ): 545.3235, Found: 545.3244.

[0076] (rac - )((1S,2R,4R) - 2 - (but - 3 - en - 1 - yl) - 2 - ((tert - butyldiphenylsilyl)methyl)bicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 6)

[0077]

[0078] White foam,90mg,82%yield(0.2mmol scale),Rf=0.65(10% EA in PE). 1 HNMR(500MHz,CDCl 3 )δ8.35(d,J=1.7Hz,1H),7.95(dd,J=8.6,1.7Hz,1H),7.93–7.84(m,3H),7.70(dt,J=6.6,1.6Hz,2H),7.69–7.64(m,2H),7.58(ddd,J=8.1,6.8,1.3Hz,1H),7.56–7.49(m,1H),7.46–7.34(m,4H),7.30(dd,J=8.0,6.8Hz,2H),5.10(dddd,J=17.3,10.1,7.4,6.0Hz,1H),4.56–4.50(m,1H),4.28(dd,J=17.2,1.9Hz,1H),2.42(td,J=6.7,3.8Hz,1H),2.28(s,1H),2.11–1.97(m,5H),1.80–1.71(m,1H),1.60–1.49(m,1H),1.49–1.40(m,1H),1.36(d,J=15.3 Hz,1H),1.28–1.22(m,1H),0.94(s,9H),0.90–0.82(m,1H). 13 C NMR(125 MHz,CDCl 3 )δ204.3,138.4,136.9,136.9,136.1,136.0,135.5,135.3,132.5,130.5,129.7,129.3,129.1,128.4,128.2,127.8,127.6,127.5,126.8,124.9,113.9,68.1,47.9,45.6,44.3,42.0,37.4,35.0,31.1,28.0,18.7,15.2.ATR-IRν(cm -1 ):2961(m),2929(m),1650(s),1470(m),1427(m),1302(m),1101(s),913(m),816(m),736(s),701(s).HRMS(ESI):Calc for C 38 H 43 OSi + (M+H + ):543.3078,Found:543.3085.

[0079] (rac-)((1S,2R,4R)-2-(2-(1,3-dioxolan-2-yl)ethyl)-2-((tert-butyldiphenylsilyl)methyl)bicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III-7)

[0080]

[0081] Colorless oil,68 mg,58%yield(0.2 mmol scale),Rf=0.3(10% EA in PE). 1 H NMR(500 MHz,CDCl 3 )δ8.37(d,J=1.7 Hz,1H),7.97(dd,J=8.6,1.8 Hz,1H),7.92(d,J=8.1 Hz,1H),7.85(dd,J=8.5,6.6 Hz,2H),7.69(ddt,J=11.1,6.7,1.5 Hz,4H),7.56(ddd,J=8.2,6.8,1.3 Hz,1H),7.51(ddd,J=8.2,6.8,1.3 Hz,1H),7.39(dtd,J=13.3,7.1,5.2 Hz,4H),7.30(dd,J=8.0,6.6 Hz,2H),4.09(dd,J=6.7,3.3 Hz,1H),3.53–3.40(m,2H),3.35(td,J=6.8,5.3 Hz,1H),3.24(dt,J=7.0,5.8 Hz,1H),2.40(dd,J=9.7,7.0Hz,1H),2.29–2.23(m,1H),2.11–1.98(m,5H),1.75–1.66(m,1H),1.41–1.32(m,2H),1.31–1.23(m,1H),1.03–0.97(m,1H),0.95(s,9H),0.92–0.82(m,1H). 13 C NMR(125 MHz,CDCl 3)δ204.2,137.0,136.9,136.0,135.8,135.5,135.3,132.5,131.0,129.8,129.3,129.1,128.3,128.1,127.8,127.6,127.5,126.6,125.1,104.8,67.9,64.5,64.4,47.5,45.7,44.2,42.0,35.0,32.3,31.4,28.1,18.6,15.2.ATR-IRν(cm -1 ):2962(s),2930(m),1650(s),1463(m),1427(m),1303(m),1102(s),815(m),738(s),702(s).HRMS(ESI):Calc forC 39 H 45 O 3 Si + (M+H + ):589.3133,Found:589.3146.

[0082] (rac-)((1S,2R,4R)-2-(3-((tert-butyldimethylsilyl)oxy)propyl)-2-((tert-butyldiphenylsilyl)methyl)bicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III-8)

[0083]

[0084] Light yellow oil,88 mg,67%yield(0.2 mmol scale),Rf=0.60(10% EA inPE). 1 HNMR(600 MHz,CDCl 3)δ8.36(s,1H),7.97–7.89(m,2H),7.86(dd,J=8.5,3.8Hz,2H),7.72–7.67(m,2H),7.66–7.61(m,2H),7.60–7.54(m,1H),7.55–7.49(m,1H),7.44–7.33(m,4H),7.28(t,J=7.5 Hz,2H),2.94(td,J=8.8,8.3,4.9 Hz,1H),2.86(dt,J=9.6,7.1 Hz,1H),2.41(td,J=6.5,4.0 Hz,1H),2.27(s,1H),2.08(dt,J=6.4,2.8 Hz,1H),2.05–1.95(m,4H),1.55–1.46(m,1H),1.39(d,J=15.3Hz,1H),1.22(ddd,J=18.2,11.9,3.9 Hz,2H),1.08–0.98(m,1H),0.95–0.90(m,9H),0.79–0.70(m,1H),0.75(s,9H),-0.19(s,3H),-0.22(s,3H). 13 C NMR(150MHz,CDCl 3 )δ204.4,137.0,136.8,136.3,136.1,135.6,135.2,132.6,130.4,129.7,129.3,129.1,128.3,128.1,127.8,127.6,127.5,126.7,125.1,68.1,63.5,47.7,45.6,44.3,41.8,35.0,34.0,30.0,28.0,26.0,18.6,18.3,15.9,-5.3,-5.3.ATR-IRν(cm -1 ):2956(m),2928(m),1652(s),1471(m),1427(m),1255(m),1101(s),835(s),776(m),701(s).HRMS(ESI):Calc for C 43 H 57 O 2 Si 2 + (M+H + ):661.3892,Found:661.3895.

[0085] (rac-)((1S,2R,4R)-2-((tert-butyldiphenylsilyl)methyl)-2-phenethylbicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III-9)

[0086]

[0087] White foam,91 mg,77%yield(0.2 mmol scale),Rf=0.50(10% EA in PE). 1 HNMR(600 MHz,CDCl 3 )δ8.42(d,J=1.7 Hz,1H),8.06(dd,J=8.6,1.7 Hz,1H),7.92(dd,J=12.8,8.4 Hz,2H),7.87(d,J=8.2 Hz,1H),7.76(d,J=6.6 Hz,2H),7.73–7.69(m,2H),7.61(ddd,J=8.2,6.9,1.2 Hz,1H),7.54(ddd,J=8.1,6.8,1.2Hz,1H),7.46–7.38(m,4H),7.35(t,J=7.5 Hz,2H),7.01–6.96(m,1H),6.93(t,J=7.4 Hz,2H),6.33–6.27(m,2H),2.51(dd,J=9.7,7.0 Hz,1H),2.36(td,J=12.8,6.2 Hz,1H),2.31(t,J=2.7 Hz,1H),2.19–2.02(m,5H),1.99(td,J=13.2,2.8 Hz,1H),1.77(td,J=13.3,12.0,2.3 Hz,1H),1.48(d,J=15.3 Hz,1H),1.37(dd,J=14.0,6.2 Hz,1H),1.35–1.30(m,1H),0.98(s,9H). 13 C NMR(150 MHz,CDCl 3)δ204.3,142.5,137.1,136.9,136.2,136.1,135.4,135.4,132.6,130.8,129.7,129.4,129.1,128.4,128.4,128.1,127.9,127.8,127.8,127.5,126.8,125.4,125.0,68.3,48.2,45.5,44.4,42.1,40.2,34.9,32.9,27.9,18.7,15.5.ATR-IRν(cm -1 ):2961(m),2929(m),1650(s),1470(m),1427(m),1304(m),1102(m),818(m),739(s),702(s).HRMS(ESI):Calc for C 42 H 45 OSi + (M+H + ):593.3235,Found:593.3242.

[0088] (rac - )((1S,2R,4R)-2-((tert - butyldiphenylsilyl)methyl)-2-(2-(thiophen - 2 - yl)ethyl)bicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 10)

[0089]

[0090] White foam, 97 mg, 80% yield (0.2 mmol scale), Rf=0.70 (10% EA in PE). 1 HNMR(500 MHz, CDCl 3)δ8.38(d, J = 1.7 Hz, 1H), 8.01(dd, J = 8.6, 1.7 Hz, 1H), 7.93–7.84(m, 3H), 7.71(ddd, J = 8.2, 4.4, 1.6 Hz, 4H), 7.59(ddd, J = 8.1, 6.8, 1.3Hz, 1H), 7.52(ddd, J = 8.1, 6.8, 1.2 Hz, 1H), 7.44–7.37(m, 4H), 7.32(dd, J = 8.0, 6.7 Hz, 2H), 6.88(dd, J = 5.1, 1.2 Hz, 1H), 6.62(dd, J = 5.2, 3.4 Hz, 1H), 5.95(dd, J = 3.5, 1.2 Hz, 1H), 2.56(dt, J = 13.3, 6.7 Hz, 1H), 2.45(t, J = 8.1 Hz, 1H), 2.31–2.21(m, 2H), 2.15–2.00(m, 5H), 1.92–1.80(m, 1H), 1.46(d, J = 15.4 Hz, 1H), 1.37–1.24(m, 2H), 0.98(s, 9H). 13 C NMR(125 MHz, CDCl 3 )(one carbon in aromatic region is overlapped)δ204.2, 144.9, 137.0, 136.9, 135.9, 135.4, 135.2, 132.6, 130.6, 129.8, 129.4, 129.2, 128.5, 128.5, 127.9, 127.8, 127.6, 126.8, 126.3, 124.9, 123.8, 122.6, 68.0, 48.2, 45.6, 44.3, 42.2, 40.6, 35.0, 28.0, 27.4, 18.7, 15.3. ATR-IR ν(cm -1 ): 2961(m), 2929(m), 1650(s), 1462(m), 1427(m), 1303(m), 1101(m), 816(m), 738(s), 700(s). HRMS(ESI): Calc for C 40 H 43 OSi + (M + H + ): 599.2799, Found: 599.2796.

[0091] (rac-)((1S,2R,4R)-2-((tert-butyldiphenylsilyl)methyl)-2-(4-(trimethylsilyl)but-3-yn-1-yl)bicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III-11)

[0092]

[0093] White foam,72 mg,59%yield(0.2 mmol scale),Rf=0.70(10% EA in PE). 1 HNMR(600 MHz,CDCl 3 )δ8.33(s,1H),7.95–7.90(m,2H),7.90–7.85(m,2H),7.73–7.67(m,2H),7.62(dt,J=8.0,1.3 Hz,2H),7.59(d,J=1.3 Hz,1H),7.55–7.50(m,1H),7.45–7.35(m,4H),7.33–7.28(m,2H),2.42–2.35(m,1H),2.30–2.25(m,1H),2.10(dt,J=6.5,2.9 Hz,1H),2.04–1.85(m,5H),1.83–1.75(m,1H),1.68(ddd,J=15.9,12.9,3.4 Hz,1H),1.28–1.21(m,1H),1.16(d,J=15.4 Hz,1H),1.05(td,J=13.7,4.5 Hz,1H),0.89(d,J=1.2 Hz,9H),0.02(d,J=1.2 Hz,9H). 13 CNMR(150 MHz,CDCl 3 )δ204.4,136.9,136.6,136.0,135.6,135.3,135.0,132.6,130.5,129.8,129.4,129.2,128.4,128.4,127.9,127.8,127.6,126.8,124.8,107.0,83.7,68.1,47.6,45.5,43.9,41.7,37.3,35.0,28.0,18.6,17.4,15.4,0.2.ATR-IRν(cm -1): 2960(m), 2929(m), 2175(m), 1650(s), 1462(m), 1427(m), 1302(m), 1248(m), 1102(s), 841(s), 738(s), 701(s). HRMS(ESI): Calc for C 41 H 49 OSi 2 + (M + H + ): 613.3317, Found: 613.3319.

[0094] (rac - )((1S,2R,4R)-2-((tert - butyldiphenylsilyl)methyl)-2 - isobutylbicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 12)

[0095]

[0096] White foam, 62 mg, 57% yield(0.2 mmol scale), Rf=0.70(10% EA in PE). 1 HNMR(600 MHz, CDCl 3 ) δ 8.38(d, J=1.7 Hz, 1H), 7.95(dt, J=8.4, 2.0 Hz, 2H), 7.88(t, J=8.6 Hz, 2H), 7.69–7.65(m, 2H), 7.64–7.61(m, 2H), 7.60–7.56(m, 1H), 7.56–7.51(m, 1H), 7.43–7.33(m, 4H), 7.29(t, J=7.5 Hz, 2H), 2.43(td, J=6.9, 2.5 Hz, 1H), 2.26(s, 1H), 2.14(dt, J=6.1, 2.7 Hz, 1H), 2.10(d, J=15.1 Hz, 1H), 2.03–1.95(m, 3H), 1.41(td, J=15.3, 13.7, 5.9 Hz, 4H), 1.04(dd, J=14.6, 5.0 Hz, 1H), 0.88(s, 9H), 0.46(d, J=6.3 Hz, 3H), 0.43(d, J=6.3 Hz, 3H). 13 C NMR(150 MHz, CDCl 3)(one carbon in aromatic region is overlapped) δ204.5, 137.2, 137.0, 136.9, 136.3, 135.3, 135.1, 132.5, 130.6, 129.6, 129.1, 129.0, 128.3, 128.1, 127.8, 127.4, 126.8, 125.2, 68.8, 48.4, 47.5, 45.8, 45.2, 41.6, 35.0, 28.0, 26.0, 25.1, 24.6, 18.7, 18.2. ATR-IR ν(cm -1 ): 2960(s), 2930(m), 1651(s), 1469(m), 1427(m), 1303(m), 1101(m), 818(m), 738(s), 702(s). HRMS(ESI): Calc for C 38 H 45 OSi + (M + H + ): 545.3235, Found: 545.3235.

[0097] (rac - )((1R,2S,4S)-2-((tert - butyldiphenylsilyl)methyl)-2 - isopropylbicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 13)

[0098]

[0099] White foam, 48 mg, 45% yield(0.2 mmol scale), Rf=0.70(10% EA in PE). 1 1H NMR(600 MHz, CDCl 3)δ8.38–8.35(m,1H),7.96–7.91(m,2H),7.91–7.85(m,2H),7.76(dt,J=6.7,1.5 Hz,2H),7.68–7.62(m,2H),7.61–7.51(m,2H),7.43–7.32(m,4H),7.29(dd,J=8.0,6.7 Hz,2H),2.31(dd,J=10.0,6.8 Hz,1H),2.20–2.16(m,1H),2.11(d,J=15.7 Hz,1H),2.07(dd,J=10.0,7.3 Hz,1H),2.02(p,J=6.9 Hz,1H),1.94(td,J=6.9,3.2 Hz,2H),1.74(dt,J=11.4,2.0 Hz,1H),1.57–1.52(m,2H),0.92(s,9H),0.77(d,J=6.8 Hz,3H),0.59(d,J=7.0 Hz,3H). 13 C NMR(150 MHz,CDCl 3 )δ205.4,137.3,137.2,136.8,135.9,135.8,135.1,132.5,130.4,129.7,129.1,129.0,128.3,128.1,127.8,127.4,127.3,126.7,125.3,68.4,53.1,46.8,41.7,41.4,35.7,34.8,28.2,21.2,20.8,19.2,15.0.ATR-IRν(cm -1 ):2962(m),2929(m),1652(s),1469(m),1427(m),1289(m),1101(m),815(m),738(s),702(s).HRMS(ESI):Calc for C 37 H 43 OSi + (M+H + ):531.3078,Found:531.3086.

[0100] (rac - )((1R,2S,4S)-2-((tert - butyldiphenylsilyl)methyl)-2 - cyclopentylbicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 14)

[0101]

[0102] White foam,62 mg,57%yield(0.2 mmol scale),Rf=0.70(10% EA in PE). 1 HNMR(500 MHz,CDCl 3 )δ8.37(s,1H),7.97–7.90(m,2H),7.91–7.85(m,2H),7.73–7.67(m,2H),7.62–7.50(m,4H),7.43–7.29(m,4H),7.27–7.21(m,2H),2.42(dd,J=10.1,6.8 Hz,1H),2.26–2.21(m,1H),2.14–2.07(m,2H),2.04(d,J=15.4 Hz,1H),1.95(dt,J=7.3,2.9Hz,1H),1.87(ddd,J=11.1,2.7,1.5 Hz,1H),1.81(ddd,J=11.4,6.9,4.5 Hz,1H),1.57(dt,J=11.2,1.9 Hz,2H),1.37–1.28(m,3H),1.29–1.20(m,2H),1.09(dtd,J=21.0,7.8,7.3,3.8 Hz,2H),0.99(ddt,J=9.3,6.9,2.1 Hz,1H),0.82(s,9H). 13 C NMR(125 MHz,CDCl 3 )δ205.6,137.3,137.1,136.9,136.0,135.8,135.1,132.5,130.4,129.6,129.1,129.1,128.2,128.1,127.8,127.4,127.4,126.7,125.3,69.2,50.4,49.5,46.0,42.5,41.9,34.9,30.0,29.7,28.1,25.5,23.8,18.9,17.9.ATR-IRν(cm -1 ):2960(m),1653(s),1464(m),1427(m),1286(m),1101(m),818(m),739(s),702(s).HRMS(ESI):Calc forC 39 H 45 OSi + (M+H + ):557.3235,Found:557.3237.

[0103] (rac-)((1R,2S,4S)-2-((tert-butyldiphenylsilyl)methyl)-2-cyclohexylbicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III-15)

[0104]

[0105] White foam,70 mg,61%yield(0.2 mmol scale),Rf=0.70(10% EA in PE). 1 HNMR(600 MHz,CDCl 3 )δ8.35(s,1H),7.94(d,J=8.2 Hz,1H),7.92–7.85(m,3H),7.77–7.73(m,2H),7.64(dd,J=7.8,1.5 Hz,2H),7.61–7.51(m,2H),7.43–7.33(m,4H),7.29(t,J=7.4 Hz,2H),2.34(dd,J=10.1,6.9 Hz,1H),2.20(t,J=2.5Hz,1H),2.11(d,J=15.6Hz,1H),2.07(dd,J=10.1,7.2 Hz,1H),1.98–1.89(m,2H),1.70–1.61(m,3H),1.53–1.34(m,6H),1.15–1.09(m,1H),0.93(s,9H),0.85–0.69(m,4H). 13 C NMR(150 MHz,CDCl 3 )(Onecarbon in aromatic region isoverlapped)δ205.4,137.3,137.2,136.8,136.1,135.8,135.1,132.5,130.4,129.6,129.0,128.2,128.0,127.8,127.4,127.4,126.7,125.2,68.3,52.7,47.2,46.9,41.3,40.4,34.7,32.1,30.4,28.1,27.5,27.5,26.4,19.0,17.0.ATR-IRν(cm -1 ):2927(s),1651(s),1464(m),1427(m),1288(m),1101(m),817(m),701(s).HRMS(ESI):Calc for C40 H 47 OSi + (M + H + ): 571.3391, Found: 571.3395.

[0106] (rac - )((1R,3R,3aR,6aR)-6a - ((tert - butyldiphenylsilyl)methyl)hexahydro - 1,3 - methanopentalen - 1(2H)-yl)(naphthalen - 2 - yl)methanone(III - 16)

[0107]

[0108] White foam, 95 mg, 89% yield (0.2 mmol scale), Rf=0.70 (10% EA in PE). 1 HNMR(500 MHz, CDCl 3 ) δ 8.41 (d, J=1.7 Hz, 1H), 8.02–7.95 (m, 2H), 7.91 (dd, J=13.9, 8.3Hz, 2H), 7.75 (dt, J=6.9, 1.5 Hz, 2H), 7.63–7.50 (m, 4H), 7.44–7.39 (m, 1H), 7.36 (dd, J=8.0, 6.4 Hz, 2H), 7.33–7.28 (m, 1H), 7.24 (t, J=7.5 Hz, 2H), 2.34 (dd, J=9.8, 6.8 Hz, 1H), 2.26 (dd, J=6.8, 2.9 Hz, 1H), 2.18–2.09 (m, 2H), 2.06 (dd, J=9.8, 7.5 Hz, 1H), 1.92 (dt, J=7.6, 2.3 Hz, 1H), 1.85 (d, J=15.2 Hz, 1H), 1.80–1.73 (m, 1H), 1.56 (d, J=15.2Hz, 1H), 1.41 (tq, J=9.2, 5.7, 4.6 Hz, 2H), 1.08 (ddt, J=18.9, 8.4, 2.8 Hz, 1H), 0.99–0.91 (m, 1H), 0.85 (s, 9H), 0.82–0.75 (m, 1H). 13 C NMR(125 MHz, CDCl 3)δ204.8,137.0,136.8,136.6,135.2,135.1,134.7,132.6,130.4,129.6,129.2,129.1,128.3,128.3,127.9,127.6,127.3,126.8,124.9,68.5,58.4,54.8,46.5,40.6,39.4,35.3,29.8,29.7,28.0,19.5,18.8.ATR-IRν(cm -1 ):2960(m),2929(m),1650(s),1470(m),1427(m),1298(m),1103(s),818(m),739(s),702(s).HRMS(ESI):Calc for C 37 H 41 OSi + (M+H + ):529.2922,Found:529.2916.

[0109] (rac - )((1R,3R,3aR)-7a - ((tert - butyldiphenylsilyl)methyl)octahydro - 1H - 1,3 - methanoinden - 1 - yl)(naphthalen - 2 - yl)methanone(III - 17)

[0110]

[0111] White foam, 93 mg, 86% yield(0.2 mmol scale), Rf=0.70(10% EA in PE). 1 HNMR(500 MHz, CDCl 3)δ8.42(d, J = 1.6 Hz, 1H), 7.98(ddd, J = 16.6, 8.3, 1.6 Hz, 2H), 7.93–7.86(m, 2H), 7.81–7.76(m, 2H), 7.63–7.53(m, 4H), 7.43–7.27(m, 4H), 7.25–7.19(m, 2H), 2.28(dd, J = 10.0, 6.7 Hz, 1H), 2.18(dd, J = 10.0, 7.4 Hz, 1H), 2.08(dd, J = 6.7, 3.0 Hz, 1H), 2.07–2.03(m, 1H), 1.89(dt, J = 7.4, 2.5 Hz, 1H), 1.83(dd, J = 14.9, 1.5 Hz, 1H), 1.79–1.74(m, 1H), 1.68–1.60(m, 1H), 1.44(d, J = 14.9 Hz, 1H), 1.39(dt, J = 14.2, 4.2 Hz, 1H), 1.11–0.93(m, 3H), 0.90–0.76(m, 3H), 0.74(s, 9H).

[0112] 13 C NMR(125 MHz, CDCl 3 )(one carbon in aromatic region is overlapped)δ204.5, 137.1, 136.8, 136.4, 135.3, 135.0, 134.3, 132.6, 130.6, 129.7, 129.2, 129.0, 128.3, 127.9, 127.5, 127.2, 126.8, 125.0, 69.6, 46.2, 44.8, 42.8, 42.3, 41.2, 32.3, 28.0, 26.1, 22.3, 21.0, 20.8, 19.0. ATR-IR ν(cm -1 ): 2957(m), 2927(m), 1650(s), 1467(m), 1427(m), 1306(m), 1103(s), 815(m), 740(m), 702(s). HRMS(ESI): Calc for C 38 H 43 OSi + (M + H + ): 543.3078, Found: 543.3079.

[0113] (rac-)((3aS,9bR)-9b-((tert-butyldiphenylsilyl)methyl)-2,3,3a,4,5,9b-hexahydro-1H-1,3-methanocyclopenta[a]naphthalen-1-yl)(naphthalen-2-yl)methanone(III-18)

[0114]

[0115] White foam,111 mg,93%yield(0.2 mmol scale),Rf=0.60(10% EAin PE). 1 HNMR(600 MHz,CDCl 3 )δ7.80(d,J=8.1 Hz,1H),7.73(d,J=8.6 Hz,1H),7.62(dd,J=8.0,1.5 Hz,1H),7.57–7.49(m,3H),7.44(dd,J=7.4,4.0 Hz,3H),7.38–7.33(m,1H),7.29–7.23(m,2H),7.20–7.14(m,1H),7.12(d,J=7.4 Hz,2H),7.05–6.99(m,3H),6.96(t,J=7.4 Hz,1H),6.88(d,J=7.5 Hz,1H),6.58(t,J=7.5 Hz,1H),2.62(ddd,J=17.0,11.9,5.7 Hz,1H),2.35(d,J=15.4 Hz,1H),2.32–2.21(m,3H),2.23–2.15(m,1H),2.12(s,1H),1.95(dd,J=6.9,2.9 Hz,1H),1.83(dd,J=10.0,7.6 Hz,1H),1.72(dt,J=7.5,2.3 Hz,1H),1.40(ddt,J=13.4,6.4,3.7 Hz,1H),1.06–0.96(m,1H),0.89(s,9H). 13 C NMR(150MHz,CDCl 3)δ204.0,141.7,138.8,136.8,136.5,135.8,135.5,135.1,134.4,132.1,131.6,129.9,129.6,129.0,128.9,128.4,128.2,127.6,127.6,127.4,126.9,126.4,126.1,125.7,125.2,70.1,50.0,45.7,41.1,40.2,28.0,27.9,24.2,21.2,18.7.ATR-IRν(cm -1 ):2960(m),2928(m),1650(s),1470(m),1427(m),1297(m),1102(m),738(s),702(s).HRMS(ESI):Calc forC 42 H 43 OSi + (M+H + ):591.3078,Found:591.3073.

[0116] (rac - )((1R,2S,4S)-2 - ((tert - butyldiphenylsilyl)methyl)-2 - phenylbicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 19)

[0117]

[0118] White solid,105 mg,92% yield(0.2 mmol scale),Rf=0.55(10% EA in PE).m.p.:82℃. 1 H NMR(500 MHz,CDCl 3) δ 7.74 (dd, J = 8.2, 1.1 Hz, 1H), 7.65 (d, J = 8.7 Hz, 1H), 7.51–7.45 (m, 4H), 7.43–7.37 (m, 3H), 7.31 (m, 2H), 7.23–7.18 (m, 3H), 7.14 (d, J = 1.8 Hz, 1H), 7.04 (t, J = 7.6 Hz, 2H), 6.92–6.80 (m, 3H), 6.76 (t, J = 7.7 Hz, 2H), 2.47 (dd, J = 9.8, 7.2 Hz, 1H), 2.44–2.34 (m, 4H), 2.02 (dt, J = 7.3, 2.8 Hz, 1H), 1.89–1.82 (m, 2H), 1.75 (dt, J = 7.2, 2.7 Hz, 1H), 0.96 (s, 9H). 13 C NMR (125 MHz, CDCl 3 ) δ 204.0, 143.9, 136.9, 136.5, 135.6, 135.2, 135.0, 134.7, 132.0, 131.4, 129.8, 128.8, 128.4, 128.3, 128.1, 127.5, 127.4, 127.3, 127.3, 126.9, 126.2, 125.6, 124.8, 68.3, 52.4, 45.8, 41.4, 38.8, 34.9, 28.0, 18.9, 18.6. ATR-IR ν (cm -1 ): 2958 (s), 2926 (s), 2855 (s), 1649 (s), 1626 (m), 1463 (m), 1426 (m), 1302 (m), 1101 (s), 737 (s), 699 (s). HRMS (ESI): Calc for C 40 H 41 OSi + (M + H + ): 565.2921, Found: 565.2921. (rac-) ((1R,2S,4S)-2-((tert-butyldiphenylsilyl)methyl)-2-(4-fluorophenyl)bicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone (III-20)

[0119]

[0120] White solid, 97 mg, 84% yield (0.2 mmol scale), Rf=0.60 (10% EA in PE). m.p.: 231℃. 1 1H NMR (500 MHz, CDCl 3 ) δ 7.77 (d, J=8.1 Hz, 1H), 7.68 (d, J=8.7 Hz, 1H), 7.53–7.51 (m, 3H), 7.50–7.47 (m, 2H), 7.44–7.39 (m, 2H), 7.33 (t, J=7.3 Hz, 2H), 7.30 (s, 1H), 7.24–7.20 (m, 3H), 7.07 (t, J=7.6 Hz, 2H), 6.79 (m, 2H), 6.43 (t, J=8.5 Hz, 2H), 2.49 (tt, J=7.1, 4.1 Hz, 1H), 2.44–2.38 (m, 2H), 2.34 (d, J=12.1 Hz, 1H), 2.28 (d, J=15.3 Hz, 1H), 2.06 (dt, J=7.3, 2.8 Hz, 1H), 1.92 (d, J=11.9 Hz, 1H), 1.80 (m, 2H), 0.96 (s, 9H). 13 13C NMR (125 MHz, CDCl 3 ) δ 203.6, 160.9 (d, J=245.0 Hz), 139.9 (d, J=3.2 Hz), 136.9, 136.4, 135.5, 135.2, 135.0, 134.7, 132.1, 131.3, 129.8 (q, J=7.5, 7.1 Hz), 129.7, 129.0, 128.5, 128.3, 127.6, 127.4, 127.0, 126.5, 124.7, 113.8, 113.7, 68.3, 52.0, 45.7, 41.4, 39.2, 34.9, 28.0, 19.3, 18.5. 19 19F NMR (471 MHz, CDCl 3 ) δ -118.3. ATR-IR ν (cm -1 ): 2959 (s), 2927 (s), 2856 (s), 1651 (s), 1626 (m), 1511 (s), 1470 (m), 1427 (m), 1302 (m), 1238 (s), 1167 (m), 1101 (s), 823 (m), 739 (s), 700 (s). HRMS (ESI): Calc for C 40 1H 40 FOSi + (M+H +):583.2827,Found:583.2833.

[0121] (rac-)((1R,2S,4S)-2-((tert-butyldiphenylsilyl)methyl)-2-(4-chlorophenyl)bicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III-21)

[0122]

[0123] White solid,100 mg,83%yield(0.2 mmol scale),Rf=0.60(10% EAin PE).m.p.:239℃. 1 H NMR(500 MHz,CDCl 3 )δ7.78(d,J=8.2 Hz,1H),7.69(d,J=8.7 Hz,1H),7.55–7.49(m,5H),7.46–7.39(m,2H),7.33(t,J=7.4 Hz,2H),7.28(s,1H),7.25–7.19(m,3H),7.07(t,J=7.5 Hz,2H),6.83–6.63(m,4H),2.49(t,J=8.2 Hz,1H),2.44–2.38(m,2H),2.35(d,J=11.6 Hz,1H),2.26(d,J=15.3 Hz,1H),2.09–2.04(m,1H),1.93(d,J=12.0 Hz,1H),1.82–1.75(m,2H),0.95(s,9H). 13 C NMR(125 MHz,CDCl 3 )δ203.5,142.8,136.8,136.4,135.4,135.1,135.0,134.5,132.0,131.4,131.4,129.7,129.6,129.0,128.5,128.4,127.6,127.6,127.4,127.1,127.0,126.5,124.6,68.2,52.1,45.7,41.4,38.9,34.9,27.9,19.1,18.5.ATR-IRν(cm -1): 2959 (s), 2926 (s), 2856 (s), 1649 (s), 1626 (m), 1497 (m), 1426 (s), 1300 (s), 1119 (s), 1100 (s), 1010 (m), 700 (s). HRMS (ESI): Calc for C 40 H 40 ClOSi + (M + H + ): 599.2532, Found: 599.2543.

[0124] (rac - )((1R,2S,4S)-2-(4-(tert - butyl)phenyl)-2-((tert - butyldiphenylsilyl)methyl)bicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone (III - 22)

[0125]

[0126] White solid, 107 mg, 86% yield (0.2 mmol scale), Rf = 0.55 (10% EA in PE). m.p.: 208℃. 1 H NMR (500 MHz, CDCl 3 ) δ 7.73 (d, J = 8.5 Hz, 1H), 7.62 (d, J = 8.6 Hz, 1H), 7.52 (dd, J = 8.0, 1.4 Hz, 2H), 7.50–7.45 (m, 2H), 7.40–7.37 (m, 1H), 7.36–7.33 (m, 2H), 7.31 (t, J = 7.4 Hz, 2H), 7.18–7.14 (m, 3H), 7.10 (d, J = 1.6 Hz, 1H), 6.99 (t, J = 7.6 Hz, 2H), 6.72 (m, 4H), 2.46 (dd, J = 9.9, 7.1 Hz, 1H), 2.41–2.35 (m, 3H), 2.32 (d, J = 15.3 Hz, 1H), 2.01 (dt, J = 7.2, 2.8 Hz, 1H), 1.91–1.85 (m, 2H), 1.76 (dt, J = 7.2, 2.7 Hz, 1H), 1.12 (s, 9H), 0.95 (s, 9H). 13 C NMR (125 MHz, CDCl 3)δ204.0,148.2,140.7,136.9,136.5,135.9,135.2,134.9,134.8,132.0,131.6,130.0,128.8,128.2,128.1,128.0,127.5,127.3,127.3,126.9,126.1,124.8,123.9,68.4,51.9,45.7,41.5,38.7,34.9,34.1,31.4,28.1,18.8,18.6.ATR-IRν(cm -1 ):2960(s),2927(s),2857(s),1650(s),1627(m),1463(m),1426(m),1304(m),1196(m),1101(s),808(s),737(s),699(s).HRMS(ESI):Calc for C 44 H 49 OSi + (M+H + ):621.3547,Found:621.3551.

[0127] (rac - )((1R,2S,4S)-2-(4-((tert - butyldimethylsilyl)oxy)phenyl)-2-((tert - butyldiphenylsilyl)methyl)bicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 23)

[0128]

[0129] White solid, 123 mg, 89% yield(0.2 mmol scale), Rf=0.55(10% EA in PE). m.p.: 79℃. 1 H NMR(500 MHz, CDCl 3) δ 7.74 (dd, J=8.4, 1.1 Hz, 1H), 7.64 (d, J=8.5 Hz, 1H), 7.53 (dd, J=8.3, 1.1 Hz, 1H), 7.51–7.45 (m, 3H), 7.42–7.37 (m, 4H), 7.30 (dd, J=8.0, 6.8 Hz, 2H), 7.26 (d, J=1.5 Hz, 1H), 7.24 (d, J=1.4 Hz, 1H), 7.23–7.19 (m, 1H), 7.08 (t, J=7.6 Hz, 2H), 6.71 (d, J=8.4 Hz, 2H), 6.22 (d, J=8.2 Hz, 2H), 2.42 (dd, J=9.8, 7.2 Hz, 1H), 2.38–2.30 (m, 3H), 2.25 (dt, J=12.0, 2.1 Hz, 1H), 1.99 (dt, J=7.2, 2.8 Hz, 1H), 1.86–1.78 (m, 2H), 1.76 (dt, J=7.1, 2.7 Hz, 1H), 0.96 (s, 9H), 0.92 (s, 9H), 0.03 (s, 6H). 13 C NMR (125 MHz, CDCl 3 ) δ 204.2, 153.5, 137.1, 136.7, 136.6, 135.7, 135.3, 134.9, 134.9, 132.1, 131.4, 130.0, 129.5, 128.9, 128.4, 128.2, 127.5, 127.4, 127.2, 126.9, 126.3, 124.9, 118.5, 68.3, 51.9, 45.9, 41.5, 39.3, 34.9, 28.0, 25.8, 19.3, 18.6, 18.3, -4.4, -4.4. ATR-IR ν (cm -1 ): 2957 (s), 2927 (s), 2856 (s), 1651 (s), 1606 (m), 1511 (s), 1471 (m), 1265 (s), 1196 (m), 1102 (m), 917 (s), 809 (s), 781 (s), 700 (s). HRMS (ESI): Calc for C 46 H 55 O 2 Si 2 + (M + H + ): 695.3735, Found: 695.3741.

[0130] (rac - )((1R,2S,4S)-2-((tert - butyldiphenylsilyl)methyl)-2-(4-(trifluoromethyl)phenyl)bicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III - 24)

[0131]

[0132] White solid, 90 mg, 71% yield (0.2 mmol scale), Rf=0.55 (10% EA in PE). m.p.: 200℃. 1 H NMR (500 MHz, CDCl 3 ) δ 7.76 (dd, J=8.3, 1.0 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H), 7.56–7.53 (m, 2H), 7.52–7.47 (m, 2H), 7.43–7.39 (m, 3H), 7.33 (dd, J=8.0, 6.7 Hz, 2H), 7.22–7.17 (m, 2H), 7.16–7.12 (m, 2H), 7.00 (t, J=7.6 Hz, 2H), 6.96 (d, J=8.2 Hz, 2H), 6.90 (d, J=8.6 Hz, 2H), 2.54–2.40 (m, 4H), 2.26 (d, J=15.4 Hz, 1H), 2.09 (dt, J=7.4, 2.8 Hz, 1H), 2.00–1.94 (m, 1H), 1.82 (dt, J=7.5, 2.7 Hz, 1H), 1.76 (dd, J=9.8, 7.4 Hz, 1H), 0.94 (s, 9H). 13 C NMR (125 MHz, CDCl 3 )(one carbon in aromatic region is overlapped) δ 203.2, 148.4, 136.8, 136.3, 135.3, 135.1, 134.4, 132.0, 131.3, 129.6, 129.1, 128.6, 128.5, 128.4, 127.9 (q, J=32.7 Hz), 127.7, 127.6, 127.5, 127.2, 126.6, 124.5, 125.3 (q, J=271.0 Hz), 124.0 (q, J=3.4 Hz), 68.2, 52.5, 45.7, 41.3, 38.7, 35.0, 28.0, 19.0, 18.5. 1919F NMR (471 MHz, CDCl 3 ) δ -62.5. ATR-IR ν(cm -1 ): 2961 (m), 2928 (m), 2857 (m), 1650 (s), 1626 (m), 1427 (m), 1329 (s), 1122 (s), 1072 (m), 701 (m). HRMS (ESI): Calc for C 41 H 40 19F 3 OSi + (M + H + ): 633.2795, Found: 633.2795.

[0133] (rac -) ((1S,2R,4R)-2 - ((tert - butyldiphenylsilyl)methyl)-2-(2 - fluorophenyl)bicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone (III - 25)

[0134]

[0135] White solid, 86 mg, 74% yield (0.2 mmol scale), Rf = 0.65 (10% EA in PE). m.p.: 67℃. 1 1H NMR (500 MHz, CDCl 3 ) δ 7.81–7.73 (m, 3H), 7.57 (t, J = 7.1 Hz, 3H), 7.52–7.47 (m, 2H), 7.41 (d, J = 7.3 Hz, 2H), 7.35 (t, J = 7.4 Hz, 2H), 7.27 (d, J = 7.3 Hz, 2H), 7.20 (t, J = 7.4 Hz, 1H), 7.04 (t, J = 7.4 Hz, 2H), 6.90 (t, J = 7.0 Hz, 1H), 6.65 (p, J = 7.8 Hz, 2H), 6.34 (dd, J = 13.1, 8.0 Hz, 1H), 2.68 (d, J = 15.3 Hz, 1H), 2.54 (t, J = 8.6 Hz, 1H), 2.45 (d, J = 12.1 Hz, 1H), 2.39–2.34 (m, 2H), 2.06 (s, 1H), 1.88–1.81 (m, 2H), 1.69 (t, J = 8.5 Hz, 1H), 0.93 (s, 9H). 13 13C NMR (125 MHz, CDCl 3)δ201.7,161.4(d,J=247.4 Hz),137.0,136.5,135.8,135.1,134.4,132.2,130.6,130.5,129.7,129.0,128.5,128.1,127.9(d,J=9.2 Hz),127.6,127.6,127.4,127.0,126.3,124.8,123.1,116.4(d,J=25.2 Hz),67.7,51.4,45.2,42.3,40.0,34.5,27.8,18.6,16.9.ATR-IRν(cm -1 ):2960(s),2927(s),2856(m),1655(s),1426(m),1306(m),1216(m),1102(s),700(s).HRMS(ESI):Calc for C 40 H 40 FOSi + (M+H + ):583.2827,Found:583.2833.

[0136] (rac-)((1R,2S,4S)-2-((tert-butyldiphenylsilyl)methyl)-2-(3-fluorophenyl)bicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III-26)

[0137]

[0138] White solid,111 mg,95%yield(0.2 mmol scale),Rf=0.55(10% EAin PE).m.p.:202℃. 1 H NMR(500 MHz,CDCl 3) δ 7.76 (d, J = 8.1 Hz, 1H), 7.67 (d, J = 8.6 Hz, 1H), 7.53 (d, J = 8.0 Hz, 2H), 7.52–7.46 (m, 3H), 7.41 (t, J = 7.5 Hz, 2H), 7.33 (dd, J = 16.0, 8.6 Hz, 3H), 7.22 (d, J = 7.6 Hz, 3H), 7.06 (t, J = 7.5 Hz, 2H), 6.73–6.62 (m, 2H), 6.58 (td, J = 8.3, 2.4 Hz, 1H), 6.43 (d, J = 11.6 Hz, 1H), 2.48 (td, J = 7.2, 2.9 Hz, 1H), 2.44–2.38 (m, 2H), 2.28 (dd, J = 13.8, 7.5 Hz, 2H), 2.05 (dd, J = 6.9, 3.4 Hz, 1H), 1.92 (d, J = 12.0 Hz, 1H), 1.81 (d, J = 6.6 Hz, 2H), 0.96 (s, 9H). 13 C NMR (125 MHz, CDCl 3 ) δ 203.5, 162.1 (d, J = 244.2 Hz), 147.1 (d, J = 6.3 Hz), 136.9, 136.5, 135.3, 135.2 (d, J = 43.7 Hz), 134.4, 132.1, 131.2, 129.7, 129.0, 128.6, 128.5, 128.3, 127.6, 127.4, 127.0, 126.4, 124.7, 124.3, 115.4 (d, J = 22.5 Hz), 112.4 (d, J = 20.8 Hz), 68.2, 52.30 (d, J = 1.7 Hz), 45.8, 41.4, 39.1, 34.9, 28.0, 19.1, 18.5. 19 F NMR (471 MHz, CDCl 3 ) δ -114.6. ATR-IR ν (cm -1 ): 2960 (m), 2927 (m), 1648 (s), 1586 (m), 1426 (s), 1304 (s), 1101 (s), 738 (s), 699 (s). HRMS (ESI): Calc for C 40 H 40 FOSi + (M + H + ): 583.2827, Found: 583.2833.

[0139] (rac-)((1R,2S,4S)-2-((tert-butyldiphenylsilyl)methyl)-2-(3-chlorophenyl)bicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III-27)

[0140]

[0141] White solid,117 mg,98%yield(0.2 mmol scale),Rf=0.50(10% EAin PE).m.p.:197℃. 1 H NMR(500 MHz,CDCl 3 )δ7.77(d,J=8.1 Hz,1H),7.68(d,J=8.7 Hz,1H),7.53–7.49(m,5H),7.44–7.40(m,2H),7.36–7.31(m,3H),7.24(t,J=7.4 Hz,1H),7.22–7.19(m,2H),7.06(t,J=7.5 Hz,2H),6.85(d,J=7.9 Hz,1H),6.83–6.66(m,2H),6.61(t,J=7.9 Hz,1H),2.47(t,J=8.2 Hz,1H),2.41–2.37(m,2H),2.31–2.23(m,2H),2.08–2.04(m,1H),1.89(d,J=12.5 Hz,1H),1.82–1.77(m,2H),0.96(s,9H). 13 C NMR(125 MHz,CDCl 3 )δ203.4,146.3,136.9,136.4,135.3,135.2,135.1,134.1,133.4,132.1,131.3,129.7,129.0,128.7,128.4,128.3,127.6,127.6,127.4,127.0,126.5,125.8,124.6,68.2,52.4,45.6,41.4,38.9,34.9,27.9,18.9,18.5.ATR-IRν(cm -1 ):2959(s),2926(s),2856(s),1649(s),1469(m),1426(m),1302(m),1211(m),1101(s),781(s),738(s),697(s).HRMS(ESI):Calc forC40 H 40 ClOSi + (M + H + ): 599.2531, Found: 599.2526.

[0142] (rac - )((1R,2S,4S)-2-((tert - butyldiphenylsilyl)methyl)-2-(3,5 - dimethylphenyl)bicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 28)

[0143]

[0144] White solid, 115 mg, 97% yield (0.2 mmol scale), Rf = 0.55 (10% EA in PE). m.p.: 156℃. 1 H NMR (500 MHz, CDCl 3 ) δ 7.63 (d, J = 8.2 Hz, 1H), 7.53 (d, J = 8.6 Hz, 1H), 7.40–7.35 (m, 2H), 7.33–7.24 (m, 5H), 7.16 (t, J = 7.4 Hz, 2H), 7.13–7.06 (m, 4H), 6.93 (t, J = 7.4 Hz, 2H), 6.40–6.17 (m, 3H), 2.33 (dd, J = 9.8, 7.1 Hz, 1H), 2.25–2.17 (m, 4H), 1.91–1.88 (m, 1H), 1.86–1.39 (m, 9H), 0.84 (s, 9H). 13 C NMR (125 MHz, CDCl 3 )(one carbon in aromatic region is overlapped) δ 204.1, 143.3, 137.1, 136.6, 136.2, 135.5, 135.3, 134.9, 134.7, 132.0, 131.5, 129.7, 128.7, 128.2, 128.1, 127.5, 127.2, 127.2, 127.1, 126.7, 126.2, 124.8, 68.3, 52.2, 45.5, 41.5, 39.0, 34.9, 28.0, 21.1, 18.8, 18.6. ATR - IR ν (cm -1): 2925(m), 2856(m), 1648(s), 1469(m), 1426(m), 1101(s), 737(s), 699(s). HRMS(ESI): Calc for C 42 H 45 OSi + (M + H + ): 593.3234, Found: 593.3231.

[0145] (rac - )((1R,2S,4S) - 2 - (benzo[d][1,3]dioxol - 5 - yl) - 2 - ((tert - butyldiphenylsilyl)methyl)bicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 29)

[0146]

[0147] White solid, 111 mg, 91% yield(0.2 mmol scale), Rf=0.50(10% EA in PE). m.p.: 78℃. 1 H NMR(500 MHz, CDCl 3 )δ 7.77(d, J = 8.1 Hz, 1H), 7.69(d, J = 8.6 Hz, 1H), 7.56–7.49(m, 5H), 7.45–7.36(m, 3H), 7.32(t, J = 7.3 Hz, 2H), 7.26–7.19(m, 3H), 7.08(t, J = 7.4 Hz, 2H), 6.36(d, J = 7.7 Hz, 1H), 6.29–6.14(m, 2H), 5.89–5.17(m, 2H), 2.44(dd, J = 9.8, 7.2 Hz, 1H), 2.39–2.33(m, 2H), 2.28–2.19(m, 2H), 2.03(dt, J = 7.2, 2.8 Hz, 1H), 1.91–1.84(m, 2H), 1.79(dt, J = 7.3, 2.7 Hz, 1H), 0.95(s, 9H). 13 C NMR(125 MHz, CDCl 3)δ203.8,146.6,145.3,138.4,136.9,136.5,135.6,135.3,135.0,134.8,132.1,131.4,129.7,128.9,128.4,128.2,127.6,127.5,127.3,126.8,126.4,124.8,121.8,109.4,106.9,100.6,68.5,52.2,45.7,41.5,39.3,34.9,28.0,19.4,18.6.ATR-IRν(cm -1 ):2960(s),2927(s),2856(s),1648(s),1486(s),1427(s),1236(s),1102(s),1041(s),739(s),700(s).HRMS(ESI):Calc forC 41 H 41 O 3 Si + (M+H + ):609.2819,Found:609.2825.

[0148] (rac-)((1R,2S,4S)-2-((tert-butyldiphenylsilyl)methyl)-2-(naphthalen-2-yl)bicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III-30)

[0149]

[0150] White foam,116 mg,94%yield(0.2 mmol scale),Rf=0.60(10% EAin PE). 1 HNMR(600 MHz,CDCl 3)δ7.67(d, J = 8.2 Hz, 1H), 7.54(t, J = 8.4 Hz, 2H), 7.48(d, J = 7.4 Hz, 2H), 7.42(ddd, J = 8.3, 4.0, 2.6 Hz, 2H), 7.40–7.27(m, 4H), 7.23(dd, J = 10.7, 6.8 Hz, 4H), 7.20–7.13(m, 2H), 7.13–7.04(m, 4H), 7.02–6.95(m, 1H), 6.79(t, J = 7.4 Hz, 2H), 2.57–2.50(m, 2H), 2.51–2.39(m, 3H), 2.08(dt, J = 6.4, 2.8 Hz, 1H), 1.96(dd, J = 12.0, 2.5 Hz, 1H), 1.89(dd, J = 9.8, 7.2 Hz, 1H), 1.79(dt, J = 6.6, 2.8 Hz, 1H), 0.94(s, 9H). 13 C NMR(150 MHz, CDCl 3 )(One aromatic carbon is overlapped)δ204.0, 141.4, 136.9, 136.4, 135.5, 135.2, 134.9, 134.4, 132.6, 131.9, 131.7, 131.3, 129.5, 128.9, 128.6, 128.3, 128.1, 127.4, 127.4, 127.3, 127.1, 127.0, 126.7, 126.6, 126.2, 125.4, 125.3, 124.8, 68.3, 52.8, 45.8, 41.6, 39.1, 35.0, 28.0, 18.7, 18.6. ATR-IR ν(cm -1 ): 2960(m), 2927(m), 1650(s), 1469(m), 1427(m), 1102(m), 805(m), 739(s), 700(s). HRMS(ESI): Calc for C 41 H 43 OSi + (M + H + ): 615.3078, Found: 615.3079.

[0151] (rac - )((1S,2R,4R)-2-((tert - butyldiphenylsilyl)methyl)-2-(furan - 2 - yl)bicyclo[2.1.1]hexan - 1 - yl)(naphthalen - 2 - yl)methanone(III - 31)

[0152]

[0153] White solid, 106 mg, 96% yield (0.2 mmol scale), Rf=0.50 (10% EA in PE). m.p.: 58℃. 1 1H NMR (500 MHz, CDCl 3 ) δ 7.78 (d, J=8.2 Hz, 1H), 7.72 (d, J=8.6 Hz, 1H), 7.63–7.57 (m, 4H), 7.52 (t, J=7.5 Hz, 1H), 7.45–7.39 (m, 3H), 7.35 (dt, J=7.5, 3.6 Hz, 4H), 7.25–7.21 (m, 1H), 7.12 (t, J=7.4 Hz, 2H), 6.71–6.64 (m, 1H), 5.92 (s, 1H), 5.56 (d, J=3.2 Hz, 1H), 2.33–2.28 (m, 2H), 2.23 (d, J=15.2 Hz, 1H), 2.17 (d, J=15.2 Hz, 1H), 2.04–2.00 (m, 2H), 1.93–1.90 (m, 1H), 1.88 (s, 2H), 0.98 (s, 9H). 13 13C NMR (125 MHz, CDCl 3 ) δ 202.8, 158.2, 139.9, 136.9, 136.5, 135.6, 135.1, 134.7, 134.5, 132.4, 130.5, 130.0, 129.0, 128.5, 128.1, 127.6, 127.6, 127.3, 126.9, 126.3, 124.6, 110.3, 107.9, 67.9, 48.7, 44.7, 42.4, 41.2, 34.5, 27.9, 18.6, 16.4. ATR-IR ν (cm -1 ): 2959 (m), 2927 (m), 1651 (s), 1426 (m), 1307 (m), 1101 (s), 1107 (m), 725 (s), 699 (s). HRMS (ESI): Calc for C 38 H 39 O 2 Si + (M + H + ): 555.2714, Found: 555.2715.

[0154] (rac-)tert-butyl 3-((1R,2S,4S)-1-(2-naphthoyl)-2-((tert-butyldiphenylsilyl)methyl)-bicyclo[2.1.1]hexan-2-yl)-1H-pyrrole-1-carboxylate(III-32)

[0155]

[0156] White solid,124 mg,95%yield(0.2 mmol scale),Rf=0.65(10% EAin PE).m.p.:81℃. 1 H NMR(500 MHz,CDCl 3 )δ7.79(d,J=8.2 Hz,1H),7.72(d,J=8.5 Hz,1H),7.68(d,J=9.8 Hz,2H),7.62(d,J=8.2 Hz,1H),7.57(d,J=7.3 Hz,2H),7.52(t,J=7.5Hz,1H),7.44(t,J=7.5 Hz,1H),7.39(d,J=7.3 Hz,1H),7.34–7.29(m,4H),7.22(t,J=7.4 Hz,1H),7.07(t,J=7.4 Hz,2H),6.67(s,1H),6.13(s,1H),5.60(s,1H),2.40–2.35(m,1H),2.34(s,1H),2.28(d,J=15.1 Hz,1H),2.08–2.05(m,1H),2.00–1.96(m,1H),1.94–1.82(m,4H),1.46(s,9H),0.94(s,9H). 13 C NMR(125 MHz,CDCl 3 )δ203.5,148.6,136.9,136.5,135.7,135.3,135.1,135.0,132.5,132.2,131.5,129.7,128.9,128.4,128.2,127.6,127.5,127.2,126.6,126.4,125.0,118.6,118.3,113.4,82.9,68.2,47.3,44.8,42.4,41.2,34.8,28.0,18.8,18.6.ATR-IRν(cm -1): 2959 (s), 2926 (s), 2856 (m), 1742 (s), 1650 (m), 1391 (m), 1369 (s), 1280 (m), 1158 (m), 977 (m), 700 (m). HRMS (ESI): Calc for C 43 H 47 NO 3 Si + (M + H + ): 654.3398, Found: 654.3403.

[0157] (rac - )tert - butyl - 5 - ((1R,2S,4S) - 1 - (2 - naphthoyl) - 2 - ((tert - butyldiphenylsilyl)methyl)bicyclo[2.1.1]hexan - 2 - yl) - 1H - indole - 1 - carboxylate (III - 33)

[0158]

[0159] Colourless gel, 128 mg, 91% yield (0.2 mmol scale), Rf=0.50 (10% EA in PE). 1 HNMR (500 MHz, CDCl 3 ) δ 7.70 (d, J=8.2 Hz, 1H), 7.61 (d, J=8.6 Hz, 1H), 7.51 (dd, J=8.7, 1.7 Hz, 1H), 7.46–7.35 (m, 6H), 7.29–7.25 (m, 3H), 7.17–7.15 (m, 2H), 7.14–7.08 (m, 3H), 6.95–6.86 (m, 4H), 6.12 (s, 1H), 2.49 (dd, J=9.8, 7.1 Hz, 1H), 2.43–2.38 (m, 4H), 2.06 (dd, J=6.3, 3.5 Hz, 1H), 1.92–1.88 (m, 2H), 1.77 (dd, J=6.5, 3.3 Hz, 1H), 1.58 (s, 9H), 0.95 (s, 9H). 13 C NMR (125 MHz, CDCl 3)δ204.1,149.8,138.3,137.0,136.5,135.5,135.3,134.9,134.7,133.3,131.9,131.5,129.8,129.5,128.8,128.3,128.0,127.4,127.4,127.2,126.6,126.0,125.5,125.3,124.7,120.8,113.6,107.6,83.3,68.6,52.5,45.6,41.6,39.4,34.9,28.2,28.0,19.3,18.6.ATR-IRν(cm -1 ):2963(m),2928(m),1732(s),1647(s),1368(s),1246(m),737(s),701(s).HRMS(ESI):Calc for C 47 H 50 NO 3 Si + (M+H + ):704.3554,Found:704.3560.(rac-)((1S,2R,4R)-2-((tert-butyldiphenylsilyl)methyl)-2-((trimethylsilyl)ethynyl)bicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III-34)

[0160]

[0161] White solid,66 mg,57%yield(0.2 mmol scale),Rf=0.65(10% EA in PE).m.p.:138℃. 1 H NMR(500 MHz,CDCl 3)δ8.49(s,1H),8.10(dd,J=8.6,1.7 Hz,1H),7.94(d,J=8.1 Hz,1H),7.88(d,J=8.4 Hz,2H),7.83(d,J=7.3 Hz,2H),7.58(t,J=7.5 Hz,1H),7.53(dd,J=7.9,4.3 Hz,3H),7.41(t,J=7.3 Hz,1H),7.35(t,J=7.4Hz,2H),7.25(d,J=8.7 Hz,1H),7.18(t,J=7.4 Hz,2H),2.36(t,J=6.8 Hz,1H),2.25(d,J=2.7 Hz,1H),2.23–2.19(m,1H),1.99–1.91(m,2H),1.88(d,J=15.0Hz,1H),1.68(d,J=15.0 Hz,1H),1.47(s,2H),1.04(s,9H),-0.42(s,9H). 13 C NMR(125 MHz,CDCl 3 )δ203.0,137.5,136.9,136.1,135.4,135.1,135.0,132.4,131.3,129.9,129.1,128.7,128.3,127.8,127.8,127.3,127.0,126.5,125.4,112.9,87.9,77.4,68.2,46.9,44.1,42.6,41.9,35.4,28.1,18.5,18.0.ATR-IRν(cm -1 ):2959(s),2857(m),2159(m),1651(s),1427(m),1248(m),1105(m),842(s),700(s).HRMS(ESI):Calc for C 39 H 45 OSi 2 + (M+H + ):585.3003,Found:585.3009.

[0162] (rac - )((1R,2S,4S)-2-((tert - butyldiphenylsilyl)methyl)-2-vinylbicyclo[2.1.1]hexan-1-yl)(naphthalen-2-yl)methanone(III - 35)

[0163]

[0164] White foam, 99 mg, 96% yield, 5:1 rr(0.2 mmol scale)(rr: (3 + 2) / (4 + 3)), Rf=0.50(10% EA in PE). 1 1H NMR(500 MHz, CDCl 3 ) δ 8.33(d, J=1.8 Hz, 1H), 7.98(dd, J=8.6, 1.7 Hz, 1H), 7.88(dd, J=13.3, 8.3 Hz, 3H), 7.70–7.64(m, 2H), 7.59(ddd, J=8.1, 6.8, 1.3 Hz, 1H), 7.53(ddd, J=8.0, 6.7, 1.3 Hz, 1H), 7.51–7.45(m, 2H), 7.43–7.37(m, 1H), 7.34(dd, J=8.0, 6.6 Hz, 2H), 7.33–7.26(m, 1H), 7.21(t, J=7.3 Hz, 2H), 5.54(dd, J=17.4, 10.8 Hz, 1H), 4.68(d, J=10.9 Hz, 1H), 4.53(d, J=17.4 Hz, 1H), 2.29–2.21(m, 2H), 2.03(dt, J=7.1, 2.8 Hz, 1H), 1.97(d, J=15.1 Hz, 1H), 1.96–1.89(m, 2H), 1.66(dt, J=11.5, 2.1 Hz, 1H), 1.53(d, J=15.0 Hz, 1H), 1.40(dd, J=11.6, 2.2 Hz, 1H), 0.94(s, 9H). 13 13C NMR(125 MHz, CDCl 3 ) δ 203.2, 143.5, 137.2, 137.0, 135.8, 135.4, 135.3, 135.0, 132.5, 131.5, 129.7, 129.1, 128.9, 128.4, 128.0, 127.8, 127.3, 127.0, 126.7, 125.1, 114.5, 67.5, 50.3, 43.5, 42.3, 37.7, 34.9, 28.0, 18.6, 18.5.

[0165] ATR-IR ν(cm -1 ): 2961(s), 2928(m), 1650(s), 1469(m), 1427(m), 1306(m), 1103(s), 912(m), 815(m), 738(s), 701(s). HRMS(ESI): Calc for C 36H 39 OSi + (M + H + ): 515.2765, Found: 515.2765.

[0166] (rac -)6 - ((1R,2S,4S)-1-(2 - naphthoyl)-2 - ((tert - butyldiphenylsilyl)methyl)bicyclo[2.1.1]hexan - 2 - yl)-2H - chromen - 2 - one (III - 36)

[0167]

[0168] White foam, 97 mg, 76% yield (0.2 mmol scale), Rf = 0.30 (10% EA in PE). 1 HNMR(500 MHz, CDCl 3 ) δ 7.73 (d, J = 8.1 Hz, 1H), 7.64 (d, J = 8.6 Hz, 1H), 7.49 (dd, J = 8.6, 2.0 Hz, 2H), 7.46–7.35 (m, 6H), 7.29 (d, J = 7.4 Hz, 2H), 7.17–7.08 (m, 3H), 6.97 (t, J = 7.6 Hz, 4H), 6.74–6.67 (m, 2H), 6.16–6.02 (m, 1H), 2.49 (dd, J = 9.9, 7.3 Hz, 1H), 2.47–2.42 (m, 1H), 2.43–2.33 (m, 2H), 2.20 (d, J = 15.4 Hz, 1H), 2.11 (dt, J = 7.4, 2.7 Hz, 1H), 1.95 (d, J = 12.8 Hz, 1H), 1.89 (dt, J = 7.4, 2.7 Hz, 1H), 1.76 (dd, J = 9.8, 7.4 Hz, 1H), 0.91 (s, 9H). 13 C NMR(125 MHz, CDCl 3)δ203.0,160.9,151.9,143.4,140.5,136.8,136.4,135.2,135.1,135.0,134.6,132.0,131.8,131.2,129.4,129.1,128.7,128.6,127.9,127.8,127.6,127.4,127.0,126.8,124.5,117.2,116.0,115.2,68.4,52.1,45.3,41.6,39.2,35.1,27.9,19.3,18.5.ATR-IRν(cm -1 ):2961(m),2928(m),1732(s),1650(s),1469(m),1427(m),1306(m),1101(m),822(m),738(m),701(m).HRMS(ESI):Calc for C 43 H 41 O 3 Si + (M+H + ):633.2820,Found:633.2823.

[0169] (8R,9S,13S,14S)-3-((1R,2S,4S)-1-(2-naphthoyl)-2-((tert-butyldiphenylsilyl)methyl)bicyclo[2.1.1]hexan-2-yl)-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one(III-37)

[0170]

[0171] White foam,110mg,74%yield(0.2mmol scale),Rf=0.25(10% EA in PE). 1 HNMR(600MHz,CDCl 3) δ 7.75 (s, 1H), 7.74 (s, 1H), 7.70–7.63 (m, 4H), 7.51–7.41 (m, 6H), 7.39–7.32 (m, 5H), 7.30–7.26 (m, 5H), 7.21–7.13 (m, 6H), 7.05–6.94 (m, 6H), 6.53 (d, J=51.5 Hz, 6H), 2.53–2.19 (m, 16H), 2.11 (ddd, J=19.1, 14.5, 9.3 Hz, 4H), 2.03–1.73 (m, 16H), 1.62–1.51 (m, 2H), 1.49–1.30 (m, 8H), 1.21–1.04 (m, 2H), 0.95 (s, 9H), 0.93 (s, 9H), 0.91 (s, 3H), 0.88 (s, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 221.0, 203.8, 203.7, 140.9, 140.8, 137.0, 136.9, 136.8, 136.7, 136.5, 136.5, 135.7, 135.5, 135.2, 135.2, 135.0, 134.9, 134.9, 134.9, 134.6, 134.4, 132.1, 132.0, 131.9, 131.9, 129.8, 129.7, 128.8, 128.1, 128.1, 128.0, 127.6, 127.3, 127.2, 127.2, 126.6, 126.6, 126.1, 126.0, 124.8, 124.7, 123.9, 123.8, 68.5, 51.9, 50.6, 50.5, 48.1, 48.0, 45.3, 44.4, 44.2, 41.7, 41.7, 38.9, 38.7, 38.4, 38.1, 36.0, 35.9, 34.9, 34.9, 31.7, 31.7, 28.0, 26.5, 26.4, 25.9, 25.6, 21.6, 21.6, 18.6, 18.6, 18.4, 14.1, 14.1. ATR-IR ν (cm -1 ): 2960 (m), 2928 (s), 1739 (s), 1648 (s), 1470 (m), 1427 (m), 1307 (m), 1102 (m), 819 (m), 738 (s), 700 (s). HRMS (ESI): Calc for C 52 H 57 O 2 Si + (M + H + ): 741.4123, Found: 741.4122.

[0172] Examples 53 - 59

[0173] Using tert-butyldiphenylsilylmethylallylsilane compound I-I and bicyclo[1.1.0]butanes II-1 to II-8 with different substituents as raw materials, in toluene as the solvent, and scandium trifluoromethanesulfonate as the catalyst, a cycloaddition reaction occurs to obtain bicyclo[2.1.1]hexane compounds III-38 to III-44. The reaction formula is as follows:

[0174]

[0175] Table 5: Influence of Substituents in Bicyclo[1.1.0]butane on the Reaction

[0176]

[0177]

[0178] a. Isolated Yield (rac-) ((1S,2R,4R)-2-((tert-butyldiphenylsilyl)methyl)-2-methylbicyclo[2.1.1]hexan-1-yl)(phenyl)methanone (III-38)

[0179]

[0180] Colourless gel, 58 mg, 64% yield (0.2 mmol scale), Rf = 0.70 (10% EA in PE). 1 HNMR(500MHz,CDCl 3 )δ7.88(d,J = 7.4Hz,2H),7.70(d,J = 6.6Hz,2H),7.56–7.50(m,3H),7.45(t,J = 7.0Hz,2H),7.42–7.39(m,1H),7.38–7.32(m,3H),7.31–7.26(m,2H),2.24–2.15(m,2H),2.01(dt,J = 6.9,2.8Hz,1H),1.94–1.88(m,2H),1.79(d,J = 15.1Hz,1H),1.53(dt,J = 11.0,1.9Hz,1H),1.23(d,J = 14.9Hz,1H),1.04(d,J = 11.7Hz,1H),0.93(s,9H),0.89(d,J = 1.1Hz,3H). 13 C NMR(125MHz,CDCl 3)δ204.4,139.6,136.9,136.8,135.6,135.3,132.4,129.2,129.1,128.9,128.4,127.6,127.4,68.6,43.8,43.5,43.3,42.2,35.6,28.0,26.7,20.3,18.4.ATR-IRν(cm -1 ):2962(m),2927(m),2857(m),1655(s),1427(m),1319(m),1101(s),700(s).HRMS(ESI):Calc for C 31 H 37 OSi + (M+H + ):453.2608,Found:453.2614.

[0181] (rac - )((1S,2R,4R)-2-((tert - butyldiphenylsilyl)methyl)-2 - methylbicyclo[2.1.1]hexan - 1 - yl)(4-(trifluoromethyl)phenyl)methanone(III - 39)

[0182]

[0183] White foam,87mg,84% yield(0.2mmol scale),Rf=0.60(10% EA in PE). 1 HNMR(600MHz,CDCl 3 )δ7.95(d,J=8.1Hz,2H),7.71(d,J=8.1Hz,2H),7.69(d,J=6.8Hz,2H),7.54(d,J=7.0Hz,2H),7.44–7.38(m,1H),7.36(t,J=7.3Hz,3H),7.29(t,J=7.4Hz,2H),2.25(d,J=3.1Hz,1H),2.21–2.15(m,1H),2.01(dt,J=6.4,2.8Hz,1H),1.94(dt,J=5.6,2.7Hz,1H),1.91(dd,J=9.6,7.1Hz,1H),1.77(d,J=14.9Hz,1H),1.55(dt,J=10.9,2.3Hz,1H),1.16(d,J=14.9Hz,1H),1.06(dt,J=11.0,1.8Hz,1H),0.93(s,9H),0.86(s,3H).13 C NMR (150 MHz, CDCl 3 ) δ 203.7, 142.3, 136.9, 136.8, 135.4, 135.1, 133.7 (q, J = 32.6 Hz), 129.2, 129.2, 129.0, 127.6, 127.5, 125.5 (q, J = 3.8 Hz), 123.8 (q, J = 272.6 Hz), 68.7, 44.1, 43.4, 43.3, 42.2, 35.7, 28.0, 26.7, 20.4, 18.4. 19 F NMR (565 MHz, CDCl 3 ) δ -63.1. ATR-IR ν (cm -1 ): 2964 (m), 2930 (m), 1662 (s), 1427 (m), 1427 (m), 1323 (s), 1289 (m), 1169 (m), 1130 (s), 1066 (s), 818 (m), 736 (m), 701 (s). HRMS (ESI): Calc for C 32 H 36 F 3 OSi + (M + H + ): 521.2483, Found: 521.2488.

[0184] (rac-)Benzo[d][1,3]dioxol-5-yl((1S,2R,4R)-2-((tert-butyldiphenylsilyl)methyl)-2-methylbicyclo[2.1.1]hexan-1-yl)methanone (III-40)

[0185]

[0186] White foam, 91 mg, 91% yield (0.2 mmol scale), Rf = 0.50 (10% EA in PE). 1 HNMR (600 MHz, CDCl 3) δ 7.71 (dt, J = 6.8, 1.4 Hz, 2H), 7.58–7.53 (m, 2H), 7.49 (dd, J = 8.2, 1.7 Hz, 1H), 7.44–7.37 (m, 2H), 7.38–7.32 (m, 3H), 7.32–7.26 (m, 2H), 6.83 (d, J = 8.2 Hz, 1H), 6.03 (dd, J = 1.4 Hz, 2H), 2.19 (t, J = 1.5 Hz, 1H), 2.18–2.12 (m, 1H), 1.96 (dt, J = 6.9, 2.8 Hz, 1H), 1.92–1.85 (m, 2H), 1.80 (dd, J = 15.0, 1.4 Hz, 1H), 1.52 (dt, J = 11.1, 1.8 Hz, 1H), 1.27 (d, J = 15.1 Hz, 1H), 1.03 (ddd, J = 11.1, 2.7, 1.4 Hz, 1H), 0.95 (s, 9H), 0.91 (s, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 201.8, 151.3, 148.0, 136.9, 136.9, 135.6, 135.3, 133.9, 129.2, 129.1, 127.6, 127.4, 125.5, 108.9, 107.7, 101.8, 68.4, 43.7, 43.5, 43.5, 42.5, 35.5, 28.1, 26.7, 20.2, 18.5. ATR-IR ν (cm -1 ): 2963 (m), 1647 (m), 1604 (m), 1486 (m), 1436 (m), 1241 (s), 1102 (m), 1038 (m), 933 (m), 701 (m). HRMS (ESI): Calc for C 32 H 37 O 3 Si + (M + H + ): 497.2507, Found: 497.2516.

[0187] (rac - )((1S,2R,4R)-2-((tert - butyldiphenylsilyl)methyl)-2 - methylbicyclo[2.1.1]hexan - 1 - yl)(furan - 2 - yl)methanone (III - 41)

[0188]

[0189] Colourless gel, 82 mg, 93% yield (0.2 mmol scale), Rf=0.50 (10% EA in PE). 1 HNMR (500 MHz, CDCl 3 ) δ 7.72 (dd, J=6.6, 1.5 Hz, 2H), 7.63–7.57 (m, 3H), 7.44–7.37 (m, 1H), 7.38–7.33 (m, 3H), 7.33–7.27 (m, 2H), 7.13 (d, J=3.5 Hz, 1H), 6.52 (dd, J=3.5, 1.7 Hz, 1H), 2.19 (d, J=2.8 Hz, 1H), 2.14 (dd, J=9.2, 7.1 Hz, 1H), 1.92 (dt, J=7.1, 2.9 Hz, 1H), 1.90–1.81 (m, 3H), 1.51 (d, J=11.1 Hz, 1H), 1.32 (d, J=15.0 Hz, 1H), 1.04 (d, J=11.1 Hz, 1H), 0.99–0.93 (m, 12H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.0, 153.7, 146.2, 136.9, 136.9, 135.7, 135.3, 129.1, 129.1, 127.5, 127.4, 118.2, 112.1, 67.0, 44.2, 43.3, 42.6, 41.6, 35.5, 28.0, 26.4, 19.8, 18.5. ATR-IR ν (cm -1 ): 2963 (s), 2928 (s), 2857 (m), 1650 (s), 1464 (s), 1317 (m), 1101 (s), 808 (s), 722 (s). HRMS (ESI): Calc for C 29 H 35 O 2 Si + (M + H + ): 443.2401, Found: 443.2405.

[0190] (rac - )((1S,2R,4R)-2-((tert - butyldiphenylsilyl)methyl)-2 - methylbicyclo[2.1.1]hexan - 1 - yl)(thiophen - 2 - yl)methanone (III - 42)

[0191]

[0192] Light yellow foam, 90 mg, 98% yield (0.2 mmol scale), Rf=0.50 (10% EA in PE). 1 HNMR (500 MHz, CDCl 3 ) δ 7.76–7.69 (m, 2H), 7.65 (dd, J=3.8, 1.1 Hz, 1H), 7.62 (dd, J=5.0, 1.1 Hz, 1H), 7.61–7.56 (m, 2H), 7.43–7.27 (m, 6H), 7.11 (dd, J=5.0, 3.8 Hz, 1H), 2.21 (d, J=2.6 Hz, 1H), 2.16 (td, J=6.8, 4.4 Hz, 1H), 1.97 (dt, J=7.0, 2.9 Hz, 1H), 1.93–1.87 (m, 2H), 1.86–1.80 (m, 1H), 1.52 (dt, J=11.1, 1.8 Hz, 1H), 1.37 (d, J=15.0 Hz, 1H), 1.04 (ddd, J=11.1, 2.5, 1.4 Hz, 1H), 0.96 (s, 12H). 13 CNMR (125 MHz, CDCl 3 ) δ 196.1, 145.6, 136.9, 136.9, 135.6, 135.3, 133.4, 132.9, 129.2, 129.1, 128.0, 127.6, 127.4, 68.0, 43.9, 43.4, 43.1, 42.1, 35.5, 28.1, 26.6, 20.1, 18.5. ATR-IR ν (cm -1 ): 2962 (m), 2928 (m), 1633 (m), 1413 (m), 1356 (m), 1240 (m), 1101 (m), 792 (m), 702 (s). HRMS (ESI): Calc for C 29 H 35 OSSi + (M + H + ): 459.2173, Found: 459.2187.

[0193] (rac-)1-((1S,2R,4R)-2-((tert-butyldiphenylsilyl)methyl)-2-methylbicyclo[2.1.1]hexan-1-yl)pentan-1-one (III-43)

[0194]

[0195] Colourless gel, 85 mg, 98% yield (0.2 mmol scale), Rf=0.75 (10% EA in PE). 1 HNMR(500 MHz, CDCl 3 ) δ 7.72 (dd, J=6.5, 1.3 Hz, 2H), 7.67 (dd, J=6.4, 1.3 Hz, 2H), 7.43–7.36 (m, 2H), 7.39–7.31 (m, 4H), 2.49–2.34 (m, 2H), 2.13 (d, J=2.7Hz, 1H), 1.90 (t, J=8.6 Hz, 1H), 1.77–1.69 (m, 2H), 1.65–1.55 (m, 4H), 1.51–1.43 (m, 2H), 1.34 (h, J=7.4Hz, 2H), 1.01 (s, 9H), 0.98–0.91 (m, 7H). 13 C NMR(125 MHz, CDCl 3 ) δ 213.9, 136.9, 136.9, 135.7, 135.4, 129.1, 129.1, 127.5, 127.4, 68.5, 43.5, 43.0, 41.4, 41.3, 40.6, 34.7, 28.1, 26.3, 25.6, 22.7, 19.6, 18.5, 14.2. ATR-IR ν(cm -1 ): 2959 (m), 2929 (m), 2857 (m), 1691 (s), 1426 (m), 1101 (s), 818 (s), 735 (s), 700 (s). HRMS(ESI): Calc for C 29 H 41 OSi + (M + H + ): 433.2921, Found: 433.2923.

[0196] (rac-)1-((1S,2R,4R)-2-((tert-butyldiphenylsilyl)methyl)-2-methylbicyclo[2.1.1]hexan-1-yl)pent-4-en-1-one (III-44)

[0197]

[0198] Colourless oil, 30mg, 35% yield (0.2mmol scale), Rf=0.60 (10% EA in PE).1 HNMR (600 MHz, CDCl 3 ) δ 7.74–7.69 (m, 2H), 7.66 (dd, J=6.8, 1.4 Hz, 2H), 7.42–7.32 (m, 6H), 5.85 (ddt, J=16.9, 10.1, 6.6 Hz, 1H), 5.06 (d, J=17.1 Hz, 1H), 5.00 (d, J=10.2 Hz, 1H), 2.60–2.45 (m, 2H), 2.40–2.31 (m, 2H), 2.15–2.11 (m, 1H), 1.89 (dd, J=9.1, 7.1 Hz, 1H), 1.76–1.68 (m, 2H), 1.65–1.57 (m, 2H), 1.45 (dd, J=13.0, 7.2 Hz, 2H), 1.03–0.98 (m, 9H), 0.96 (s, 3H), 0.96–0.91 (m, 1H). 13 C NMR (150 MHz, CDCl 3 ) δ 212.8, 137.8, 137.0, 136.9, 135.7, 135.4, 129.2, 129.1, 127.6, 127.4, 115.3, 68.4, 43.5, 43.1, 41.4, 40.9, 40.6, 34.8, 28.1, 27.6, 26.3, 19.6, 18.5. ATR-IR ν (cm -1 ): 2963 (m), 2929 (m), 1693 (s), 1427 (m), 1289 (m), 1102 (s), 818 (m), 736 (m), 701 (s). HRMS (ESI): Calc for C 29 H 39 OSi + (M + H + ): 431.2765, Found: 431.2774.

[0199] Those of ordinary skill in the art can understand that the above are only preferred examples of the invention and are not used to limit the invention. Although the invention has been described in detail with reference to the foregoing examples, those skilled in the art can still modify the technical solutions described in the foregoing examples or make equivalent replacements for some of the technical features. Any modifications, equivalent replacements, etc. made within the spirit and principle of the invention shall be included within the protection scope of the invention.

Claims

1. A method for constructing a bicyclo[2.1.1]hexane compound by a cycloaddition reaction of allylsilane and bicyclo[1.1.0]butane, characterized in that: Using allylsilane compound I and bicyclo[1.1.0]butanyl ketone compound II as raw materials and Lewis acid as catalyst, an intermolecular cycloaddition reaction occurs in an organic solvent, and after purification, a bicyclo[2.1.1]hexane compound III is obtained. The specific reaction equation is as follows: In the formula, R of the silicon-based substituent in the allylsilane compound I is 1 , R 2 , R 3 are all selected from alkyl or aryl; the alkyl or aryl groups include trimethylsilyl, dimethylphenylsilyl, tert-butyldiphenylsilyl and triisopropylsilyl; R 4 Any one selected from aryl, alkenyl, alkynyl or alkyl substituents; R 5 R in the bicyclo[1.1.0]butanyl ketone compound II is selected from hydrogen or an alkyl substituent; 6 is selected from aryl or alkyl; R of the bicyclo[2.1.1]hexane compound III is 1 ~R 6 Same with both ingredients; The organic solvent is selected from any one of a halogenated solvent, an aromatic solvent, an ether solvent, a nitrile solvent or an ester solvent.

2. The method for constructing a bicyclo[2.1.1]hexane compound by a cycloaddition reaction of allylsilane and bicyclo[1.1.0]butane according to claim 1, characterized in that: The allylsilane compound I is selected from one of the following compounds:

3. The method for constructing a bicyclo[2.1.1]hexane compound by a cycloaddition reaction of allylsilane and bicyclo[1.1.0]butane according to claim 1, characterized in that: The bicyclo[1.1.0]butanyl ketone compound II is selected from one of the following compounds:

4. The method for constructing a bicyclo[2.1.1]hexane compound by a cycloaddition reaction of allylsilane and bicyclo[1.1.0]butane according to claim 1, characterized in that: The organic solvent is at least one of dichloromethane, toluene, tetrahydrofuran, acetonitrile and ethyl acetate.

5. The method for constructing a bicyclo[2.1.1]hexane compound by a cycloaddition reaction of allylsilane and bicyclo[1.1.0]butane according to claim 1, characterized in that: The Lewis acid is any one of Yb(OTf)3, Sc(OTf)3, Cu(OTf)2, AgOTf, Al(OTf)3, Ga(OTf)3, Fe(OTf)3, Bi(OTf)3, B(C6F5)3 and InI3.

6. The method for constructing a bicyclo[2.1.1]hexane compound by a cycloaddition reaction of allylsilane and bicyclo[1.1.0]butane according to claim 1, characterized in that: The molar ratio of the allylsilane compound I to the bicyclo[1.1.0]butanyl ketone compound II is 1:(1-1.5).

7. The method for constructing a bicyclo[2.1.1]hexane compound by a cycloaddition reaction of allylsilane and bicyclo[1.1.0]butane according to claim 6, characterized in that: The molar ratio of the allylsilane compound I to the bicyclo[1.1.0]butanyl ketone compound II is 1:1.

3.

8. The method for constructing a bicyclo[2.1.1]hexane compound by a cycloaddition reaction of allylsilane and bicyclo[1.1.0]butane according to claim 1, characterized in that: The reaction time is 0.5-12 hours, and the reaction temperature is 20-30°C.

9. A bicyclo[2.1.1]hexane compound prepared by the method according to any one of claims 1 to 8.

10. The bicyclo[2.1.1]hexane compound according to claim 9, characterized in that The bicyclo[2.1.1]hexane compound is selected from one of the following compounds:

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