KR100614546B1 - Tetrahydrofuran cyclic compounds having high stereoselectivity, and Process for preparing them - Google Patents
Tetrahydrofuran cyclic compounds having high stereoselectivity, and Process for preparing them Download PDFInfo
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Abstract
본 발명은 입체선택성이 높은 테트라하이드로퓨란 고리화합물과 이의 제조방법에 관한 것으로서, 트리메틸실라닐펜탄인올을 출발물질로 하고 루이스산(Lewis acid) 촉매를 이용한 분자간 프린스 고리화 반응을 수행하여 알렌(allene)을 포함하고 있는 입체선택성이 높은 다음 화학식 1로 표시되는 신규의 테트라하이드로퓨란 고리화합물과 이 화합물의 제조방법에 관한 것이다.The present invention relates to a tetrahydrofuran cyclic compound having high stereoselectivity and a method for preparing the same. It relates to a novel tetrahydrofuran cyclic compound represented by the following formula (1) having high stereoselectivity containing allene) and a method for preparing the compound.
상기 화학식 1에서, R1은 탄소수 1 내지 8의 알킬기, 또는 방향족기를 나타내고, R2 및 R3는 각각 수소원자, 탄소수 1 내지 8의 알킬기, 또는 방향족기를 나타내고, 상기 R2 및 R3는 서로 결합하여 5 내지 7각형의 고리를 형성한다.In Formula 1, R 1 represents an alkyl group having 1 to 8 carbon atoms, or an aromatic group, R 2 and R 3 each represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or an aromatic group, wherein R 2 and R 3 are each other Combine to form a 5-7 hexagonal ring.
입체선택성, 테트라하이드로퓨란, 트리메틸실라닐펜탄인올, 알렌(allene), 루이스산 촉매, 분자간 프린스 고리화Stereoselectivity, tetrahydrofuran, trimethylsilanylpentaneinol, allene, Lewis acid catalyst, intermolecular prince cyclization
Description
본 발명은 입체선택성이 높은 테트라하이드로퓨란 고리화합물과 이의 제조방법에 관한 것으로서, 트리메틸실라닐펜탄인올을 출발물질로 하고 루이스산(Lewis acid) 촉매를 이용한 분자간 프린스 고리화 반응을 수행하여 알렌(allene)을 포함하고 있는 입체선택성이 높은 다음 화학식 1로 표시되는 신규의 테트라하이드로퓨란 고리화합물과 이 화합물의 제조방법에 관한 것이다.The present invention relates to a tetrahydrofuran cyclic compound having high stereoselectivity and a method for preparing the same. It relates to a novel tetrahydrofuran cyclic compound represented by the following formula (1) having high stereoselectivity containing allene) and a method for preparing the compound.
[화학식 1][Formula 1]
상기 화학식 1에서, R1은 탄소수 1 내지 8의 알킬기, 또는 방향족기를 나타내고, R2 및 R3는 각각 수소원자, 탄소수 1 내지 8의 알킬기, 또는 방향족기를 나타내고, 상 기 R2 및 R3는 서로 결합하여 5 내지 7각형의 고리를 형성한다.In Formula 1, R 1 represents an alkyl group having 1 to 8 carbon atoms or an aromatic group, R 2 and R 3 each represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or an aromatic group, wherein R 2 and R 3 are They combine with each other to form a 5-7 hexagonal ring.
테트라하이드로퓨란 계열의 고리화합물은 생체 활성을 가지는 천연물이나 의약품을 합성하는 데 있어 중요하게 사용되어지는 중간체 화합물로 잘 알려져 있다 [Tetrahedron, 1987, 43, 3309~3362]. 따라서, 본 발명이 합성한 상기 화학식 1로 표시되는 화합물 역시 테트라하이드로퓨란 계열의 고리화합물로서 산업적 유용성이 클 것으로 기대된다. 특히, 본 발명이 합성한 테트라하이드로퓨란 고리화합물은 알렌(allene)을 포함하고 있는 구조적 특징을 가지고 있어, 알렌 구조를 이용한 분자내 반응을 통해 또 다른 고리를 확장시킬 수 있을 것으로 기대된다.Tetrahydrofuran-based cyclic compounds are well known as intermediate compounds that are important for the synthesis of natural or pharmaceutical products with bioactivity [ Tetrahedron , 1987 , 43 , 3309-3362]. Therefore, the compound represented by Chemical Formula 1 synthesized in the present invention is also expected to be of great industrial utility as a tetrahydrofuran-based ring compound. In particular, the tetrahydrofuran ring compound synthesized according to the present invention has a structural feature including an allene, and is expected to expand another ring through an intramolecular reaction using an allene structure.
본 발명의 발명자들은 천연물이나 의약품을 합성용 중간체 또는 다중 고리화합물 합성용 중간체로서 그 산업작 용도가 큰 테트라하이드로퓨란 고리화합물을 보다 효율적으로 합성할 수 있는 제조방법을 개발하고자 연구 노력한 결과로 본 발명을 완성하게 되었다.The inventors of the present invention, as a result of research efforts to develop a method for more efficiently synthesizing a tetrahydrofuran cyclic compound having a large industrial use as a natural intermediate or a pharmaceutical compound as an intermediate for synthesizing a compound or a polycyclic compound. To complete.
따라서, 본 발명은 고 입체선택성의 테트라하이드로퓨란 고리화합물을 제공하는데 그 목적이 있다.Accordingly, an object of the present invention is to provide a high stereoselective tetrahydrofuran ring compound.
또한, 본 발명은 고 입체선택성의 테트라하이드로퓨란 고리화합물의 제조방법을 제공하는데 그 목적이 있다.
It is another object of the present invention to provide a method for preparing a high stereoselective tetrahydrofuran ring compound.
본 발명은 다음 화학식 1로 표시되는 테트라하이드로퓨란 고리화합물을 그 특징으로 한다 :The present invention is characterized by a tetrahydrofuran cyclic compound represented by the following formula (1):
[화학식 1][Formula 1]
상기 화학식 1에서, R1은 탄소수 1 내지 8의 알킬기, 또는 방향족기를 나타내고, R2 및 R3는 각각 수소원자, 탄소수 1 내지 8의 알킬기, 또는 방향족기를 나타내고, 상기 R2 및 R3는 서로 결합하여 5 내지 7각형의 고리를 형성한다.In Formula 1, R 1 represents an alkyl group having 1 to 8 carbon atoms, or an aromatic group, R 2 and R 3 each represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or an aromatic group, wherein R 2 and R 3 are each other Combine to form a 5-7 hexagonal ring.
상기 화학식 1로 표시되는 화합물에 있어, 바람직하기로는 R1은 탄소수 1 내지 8의 알킬기, 페닐기, 나프탈렌기, 퓨란기, 또는 싸이오펜기를 나타내고, R2 및 R3는 각각 수소원자, 탄소수 1 내지 8의 알킬기, 벤질기, 또는 페닐기를 나타내고, 또는 상기 R2 및 R3는 서로 결합하여 5 내지 7각형의 고리를 형성하거나 또는 산소원자 또는 황원자와 함께 5 내지 7각형의 헤테로고리를 형성하는 화합물의 경우이다.In the compound represented by Chemical Formula 1, preferably, R 1 represents an alkyl group having 1 to 8 carbon atoms, a phenyl group, a naphthalene group, a furan group, or a thiophene group, and R 2 and R 3 each represent a hydrogen atom or 1 to C carbon. An alkyl group, a benzyl group, or a phenyl group of 8 or R 2 and R 3 combine with each other to form a 5 to 7 hexagonal ring or a 5 to 7 heterocyclic ring together with an oxygen atom or a sulfur atom; Is the case.
또한, 본 발명은 다음 반응식 1에 나타낸 바와 같이, 다음 화학식 2로 표시되는 트리메틸실라닐펜탄인올과 다음 화학식 3으로 표시되는 카보화합물을, 루이스산(Lewis acid) 촉매의 존재 하에서 분자간 프린스 고리화 반응을 수행하여 다음 화학식 1로 표시되는 테트라하이드로퓨란 고리화합물의 제조방법을 포함한다 :In addition, the present invention, as shown in the following scheme 1, trimethylsilanylpentaninol represented by the following formula (2) and carbo compound represented by the following formula (3), intermolecular Prince cyclization in the presence of Lewis acid catalyst (Lewis acid) catalyst A method for preparing a tetrahydrofuran cyclic compound represented by the following Chemical Formula 1 by performing a reaction is included:
상기 반응식 1에서, R1은 탄소수 1 내지 8의 알킬기, 또는 방향족기를 나타내고, R2 및 R3는 각각 수소원자, 탄소수 1 내지 8의 알킬기, 또는 방향족기를 나타내고, 상기 R2 및 R3는 서로 결합하여 5 내지 7각형의 고리를 형성한다.In Reaction Scheme 1, R 1 represents an alkyl group having 1 to 8 carbon atoms, or an aromatic group, R 2 and R 3 each represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or an aromatic group, and R 2 and R 3 each other Combine to form a 5-7 hexagonal ring.
본 발명에 따른 분자간 프린스 고리화 반응을 수행함에 있어, 반응촉매로는 루이스산 촉매를 사용한다. 루이스산 촉매는 BF3·Et2O, InCl3, SnCl 4, 트라이메틸실라닐 트라이플루오로메탄설포네이트(TMSOTf) 등 중에서 선택하며, 그 중에서도 특히 바람직하기로는 트라이메틸실라닐 트라이플루오로메탄설포네이트(TMSOTf)를 사용하는 것이다. 상기한 루이스산 촉매는 반응물질에 대하여 1.0 내지 1.5 당량비 범위 내에서 사용하도록 한다.In performing the intermolecular prince cyclization reaction according to the present invention, a Lewis acid catalyst is used as the reaction catalyst. The Lewis acid catalyst is selected from BF 3 · Et 2 O, InCl 3 , SnCl 4 , trimethylsilanyl trifluoromethanesulfonate (TMSOTf), and the like, and particularly preferably trimethylsilanyl trifluoromethanesulfo Nate (TMSOTf) is used. The Lewis acid catalyst may be used in the range of 1.0 to 1.5 equivalent ratios with respect to the reactants.
반응 용매로는 통상의 유기용매를 사용하도록 하며, 그 중에서도 바람직하기로는 다이에틸에테르, 다이클로로메탄 등 중에서 선택 사용하는 것이며, 특히 바람직하기로는 다이에틸에테르를 사용하는 것이다.As the reaction solvent, a conventional organic solvent is used, and among these, diethyl ether, dichloromethane and the like are preferably used, and particularly preferably diethyl ether is used.
또한, 반응온도는 -78 ℃ 내지 상온(대략 25 ℃) 범위를 유지하도록 한다.In addition, the reaction temperature is -78 Maintain a range of ℃ to room temperature (about 25 ℃).
상기한 바와 같이, 본 발명에 따른 제조방법은 비교적 온화한 반응 조건하에 서 진행되며, 목적물에 대한 제조 수율도 매우 높아 산업적으로 유용하게 적용이 가능하다.As described above, the production method according to the present invention proceeds under relatively mild reaction conditions, and the production yield for the target is also very high, and thus industrially usefully applicable.
또한, 본 발명에 따른 제조방법에 의해 제조된 상기 화학식 1로 표시되는 화합물은 신규 화합물로서 높은 입체선택성을 가지고 있어 의약품의 중간체 등 그 응용범위가 매우 광범위하다.In addition, the compound represented by the formula (1) prepared by the manufacturing method according to the present invention has a high stereoselectivity as a novel compound, and its application range, such as intermediates of pharmaceutical products is very wide.
이상에서 설명한 바와 같은 본 발명은 다음의 실시예에 의거하여 더욱 상세히 설명하겠는 바, 본 발명이 다음의 실시예에 의해 한정되는 것은 아니다.The present invention as described above will be described in more detail based on the following examples, but the present invention is not limited by the following examples.
실시예 1. 2,5-다이페닐-3-바이닐리덴-테트라하이드로-퓨란Example 1 2,5-Diphenyl-3-vinylidene-tetrahydro-furan
질소 대기 하에서 1-페닐-5-트라이메틸실라닐-펜타-3-인-1-올(51 mg, 0.22 mmol)과 벤즈 알데하이드(23 μL, 0.23 mmol)에 에테르 2.0 mL를 넣고 -78 ℃에서 교반하다가, 트라이메틸실라닐 트라이플루오로메탄설포네이트(TMSOTf; 53 μL, 0.24 mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 3시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 48 mg(91%, diastereomer ratio 35:1)을 얻었다. 2.0 mL of ether was added to 1-phenyl-5-trimethylsilanyl-penta-3-yn-1-ol (51 mg, 0.22 mmol) and benzaldehyde (23 μL, 0.23 mmol) under nitrogen atmosphere at -78 ° C. While stirring, trimethylsilanyl trifluoromethanesulfonate (TMSOTf; 53 μL, 0.24 mmol) was added. While stirring the reaction mixture, the reaction temperature was gradually raised to room temperature for about 3 hours, and then stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 48 mg (91%, diastereomer ratio 35: 1) of the product.
1H NMR(300MHz, CDCl3) δ 7.62-7.34(m, 10H), 5.62(s, 1H), 5.14(q, 2H, J=5.1Hz), 4.96-4.89(m, 1H), 4.83-4.76(m, 1H), 3.22-3.13(m, 1H), 2.92-2.83(m, 1H); 13C NMR(75MHz, CDCl3) δ 200.97, 141.21, 141.01, 128.75, 128.48, 128.15, 128.06, 126.99, 126.49, 105.44, 81.60, 81.38, 79.58, 40.35 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.62-7.34 (m, 10H), 5.62 (s, 1H), 5.14 (q, 2H, J = 5.1 Hz), 4.96-4.89 (m, 1H), 4.83-4.76 (m, 1H), 3.22-3.13 ( m, 1H), 2.92-2.83 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 200.97, 141.21, 141.01, 128.75, 128.48, 128.15, 128.06, 126.99, 126.49, 105.44, 81.60, 81.38, 79.58, 40.35 ppm
실시예 2. 2-사이클로헥실-5-페닐-3-바이닐리덴-테트라하이드로-퓨란Example 2. 2-cyclohexyl-5-phenyl-3-vinylidene-tetrahydro-furan
질소 대기 하에서 출발 물질 1-페닐-5-트라이메틸실라닐-펜타-3-인-1-올(80 mg, 0.34 mmol)과 사이클로헥산카르보 알데하이드(48 μL, 0.40 mmol)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(72 μL, 0.40 mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 3시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 75 mg(86%, diastereomer ratio >99:1)을 얻었다. Starter 1-phenyl-5-trimethylsilanyl-penta-3-yn-1-ol (80 mg, 0.34 mmol) and cyclohexanecarboaldehyde (48 μL, 0.40 mmol) in 2.0 mL of ether under nitrogen atmosphere. It melt | dissolved and stirred at -78 degreeC, and added TMSOTf (72 microliters, 0.40 mmol). While stirring the reaction mixture, the reaction temperature was gradually raised to room temperature for about 3 hours, and then stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to yield 75 mg (86%, diastereomer ratio> 99: 1) of the product.
1H NMR(300MHz, CDCl3) δ 7.46-7.30(m, 5H), 4.97-4.83(m, 3H), 4.51-4.47(m, 1H), 3.00-2.92(m, 1H), 2.64-2.53(m, 1H), 1.88-1.65(m, 6H), 1.48-1.21(m, 4H); 13C NMR(75MHz, CDCl3) δ 199.94, 141.47, 128.68, 128.00, 126.39, 102.96, 83.76, 80.91, 78.41, 42.94, 41.40, 29.72, 27.75, 26.86, 26.71 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.46-7.30 (m, 5H), 4.97-4.83 (m, 3H), 4.51-4.47 (m, 1H), 3.00-2.92 (m, 1H), 2.64-2.53 (m, 1H), 1.88-1.65 (m , 6H), 1.48-1.21 (m, 4H); 13 C NMR (75 MHz, CDCl 3 ) δ 199.94, 141.47, 128.68, 128.00, 126.39, 102.96, 83.76, 80.91, 78.41, 42.94, 41.40, 29.72, 27.75, 26.86, 26.71 ppm
실시예 3. 2-펜틸-5-페닐-3-바이닐리덴-테트라하이드로-퓨란Example 3. 2-pentyl-5-phenyl-3-vinylidene-tetrahydro-furan
질소 대기 하에서 출발 물질 1-페닐-5-트라이메틸실라닐-펜타-3-인-1-올(81 mg, 0.35 mmol)과 헥산 알데하이드(46 μL, 0.38 mmol)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(69 μL, 0.38 mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 3시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 59 mg(70%, diastereomer ratio >99:1)을 얻었다. Starting material 1-phenyl-5-trimethylsilanyl-penta-3-yn-1-ol (81 mg, 0.35 mmol) and hexane aldehyde (46 μL, 0.38 mmol) were dissolved in 2.0 mL of ether under nitrogen atmosphere. Stir at C and add TMSOTf (69 μL, 0.38 mmol). While stirring the reaction mixture, the reaction temperature was gradually raised to room temperature for about 3 hours, and then stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 59 mg (70%, diastereomer ratio> 99: 1) of the product.
1H NMR(300MHz, CDCl3) δ 7.46-7.30(m, 5H), 4.95-4.89(m, 3H), 4.62(t, 1H, J=5.1Hz), 3.08-2.99(m, 1H), 2.72-2.62(m, 1H), 1.84-1.73(m, 2H), 1.60-1.37(m, 6H), 0.98-0.94(q, 3H, J=7.2Hz); 13C NMR(75MHz, CDCl3) δ 199.71, 141.51, 128.68, 128.00, 126.40, 104.47, 80.89, 79.88, 78.84, 40.43, 34.88, 32.31, 25.35, 22.89 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.46-7.30 (m, 5H), 4.95-4.89 (m, 3H), 4.62 (t, 1H, J = 5.1 Hz), 3.08-2.99 (m, 1H), 2.72-2.62 (m, 1H), 1.84- 1.73 (m, 2H), 1.60-1.37 (m, 6H), 0.98-0.94 (q, 3H, J = 7.2 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ 199.71, 141.51, 128.68, 128.00, 126.40, 104.47, 80.89, 79.88, 78.84, 40.43, 34.88, 32.31, 25.35, 22.89 ppm
실시예 4. 아세틱엑시드-2-(5-페닐-3-바이닐리덴-테트라하이드로-퓨란-2-일)-프로필에스터 Example 4 Acetic Acid-2- (5-phenyl-3-vinylidene-tetrahydro-furan-2-yl) -propylester
질소 대기 하에서 출발 물질 1-페닐-5-트라이메틸실라닐-펜타-3-인-1-올(214 mg, 0.92 mmol)과 아세틱엑시드4-옥소-부틸에스터(100 mg, 0.77 mmol)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(167 μL, 0.92 mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 3시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 182 mg(87%, diastereomer ratio >99:1)을 얻었다. Starting material 1-phenyl-5-trimethylsilanyl-penta-3-yn-1-ol (214 mg, 0.92 mmol) and acetic acid 4-oxo-butylester (100 mg, 0.77 mmol) under nitrogen atmosphere It was dissolved in 2.0 mL of ether, stirred at -78 ° C, and then TMSOTf (167 μL, 0.92 mmol) was added thereto. While stirring the reaction mixture, the reaction temperature was gradually raised to room temperature for about 3 hours, and then stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 182 mg (87%, diastereomer ratio> 99: 1) of the product.
1H NMR(300MHz, CDCl3) δ 7.45-7.30(m, 5H), 4.94-4.89(m, 3H), 4.64(s, 1H), 4.20-4.15(q, 2H, J=6.0Hz), 3.09-3.00(m, 1H), 2.72-2.59(m, 1H), 2.09, 3H), 1.98-1.75(m, 4H); 13C NMR(75MHz, CDCl3) δ 199.64, 171.50, 141.20, 128.71, 128.06 126.32, 104.02, 80.92, 79.20, 64.81, 40.26, 31.01, 24.78, 21.28 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.45-7.30 (m, 5H), 4.94-4.89 (m, 3H), 4.64 (s, 1H), 4.20-4.15 (q, 2H, J = 6.0 Hz), 3.09-3.00 (m, 1H), 2.72- 2.59 (m, 1 H), 2.09, 3 H), 1.98-1.75 (m, 4 H); 13 C NMR (75 MHz, CDCl 3 ) δ 199.64, 171.50, 141.20, 128.71, 128.06 126.32, 104.02, 80.92, 79.20, 64.81, 40.26, 31.01, 24.78, 21.28 ppm
실시예 5. 2-(2-아이요도-벤질)-5-페닐-3-바이닐리덴-테트라하이드로-퓨란Example 5. 2- (2-Iodo-benzyl) -5-phenyl-3-vinylidene-tetrahydro-furan
질소 대기 하에서 출발 물질 1-페닐-5-트라이메틸실라닐-펜타-3-인-1-올(33 mg, 0.14 mmol)과 (2-아이요도-페닐)-아세트알데하이드(35 mg, 0.14 mmol)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(31 μL, 0.17 mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 3시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 45 mg(82%, diastereomer ratio >99:1)을 얻었다. Starting material 1-phenyl-5-trimethylsilanyl-penta-3-yn-1-ol (33 mg, 0.14 mmol) and (2- iodo-phenyl) -acetaldehyde (35 mg, 0.14 mmol) under nitrogen atmosphere ) Was dissolved in 2.0 mL of ether, stirred at −78 ° C., and TMSOTf (31 μL, 0.17 mmol) was added thereto. While stirring the reaction mixture, the reaction temperature was gradually raised to room temperature for about 3 hours, and then stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 45 mg (82%, diastereomer ratio> 99: 1) of the product.
1H NMR(300MHz, CDCl3) δ 7.90-7.87(q, 1H, J=6.6Hz), 7.48-7.29(m, 5H), 6.98-6.93(m, 1H), 4.99-4.87(m, 4H), 3.33-3.18(m, 2H), 3.11-3.01(m, 1H), 2.76-2.66(m, 1H); 13C NMR(75MHz, CDCl3) δ 199.92, 141.42, 139.61, 131.43, 128.63 128.49, 128.32, 127.94, 126.32, 103.70, 101.58, 81.24, 79.46, 79.14, 46.13, 40.12 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.90-7.87 (q, 1H, J = 6.6 Hz), 7.48-7.29 (m, 5H), 6.98-6.93 (m, 1H), 4.99-4.87 (m, 4H), 3.33-3.18 (m, 2H), 3.11-3.01 (m, 1 H), 2.76-2.66 (m, 1 H); 13 C NMR (75 MHz, CDCl 3 ) δ 199.92, 141.42, 139.61, 131.43, 128.63 128.49, 128.32, 127.94, 126.32, 103.70, 101.58, 81.24, 79.46, 79.14, 46.13, 40.12 ppm
실시예 6. 2-부틸-2-메틸-5-페닐-3-바이닐리덴-테트라하이드로-퓨란Example 6. 2-butyl-2-methyl-5-phenyl-3-vinylidene-tetrahydro-furan
질소 대기 하에서 출발 물질 1-페닐-5-트라이메틸실라닐-펜타-3-인-1-올(65 mg, 0.28 mmol)과 헥산-2-온(38 μL, 0.31 mmol)를 에테르 2.0 mL에 녹여 -78 ℃에 서 교반하다가, TMSOTf(56 μL, 0.31 mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 4시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 61 mg(90%, diastereomer ratio 3:2)을 얻었다. Starter 1-phenyl-5-trimethylsilanyl-penta-3-yn-1-ol (65 mg, 0.28 mmol) and hexane-2-one (38 μL, 0.31 mmol) in 2.0 mL of ether under nitrogen atmosphere. Melt and stirred at -78 ℃, TMSOTf (56 μL, 0.31 mmol) was added. While slowly stirring the reaction mixture to room temperature for about 4 hours, the mixture was stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 61 mg (90%, diastereomer ratio 3: 2) of the product.
1H NMR(300MHz, CDCl3) δ 7.47-7.29(m, 5H), 5.08-4.95(m, 1H), 4.94-4.86(m, 2H), 3.10-2.97(m, 1H), 2.82-2.65(m, 1H), 1.83-1.64(m, 2H), 1.52-1.36(m, 7H), 1.36-0.96(m, 3H); 13C NMR(75MHz, CDCl3) δ 199.80, 199.66, 142.40, 141.67, 128.69, 127.98, 127.89, 126.45, 126.39, 108.66, 108.46, 100.22, 84.18, 84.09, 79.60, 78.87, 41.42, 40.26, 26.98, 26.81, 26.72, 26.24, 23.48, 23.37, 14.44 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.47-7.29 (m, 5H), 5.08-4.95 (m, 1H), 4.94-4.86 (m, 2H), 3.10-2.97 (m, 1H), 2.82-2.65 (m, 1H), 1.83-1.64 (m , 2H), 1.52-1.36 (m, 7H), 1.36-0.96 (m, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 199.80, 199.66, 142.40, 141.67, 128.69, 127.98, 127.89, 126.45, 126.39, 108.66, 108.46, 100.22, 84.18, 84.09, 79.60, 78.87, 41.42, 40.26, 26.98, 26.81, 26.72, 23.24, 23.24, 23.24, 23.24.
실시예 7. 2-메틸-2,5-다이페닐-3-바이닐리덴-테트라하이드로-퓨란Example 7. 2-Methyl-2,5-diphenyl-3-vinylidene-tetrahydro-furan
질소 대기 하에서 출발 물질 1-페닐-5-트라이메틸실라닐-펜타-3-인-1-올(70 mg, 0.30 mmol)과 1-페닐-에탄온(41 μL, 0.35 mmol)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(63 μL, 0.35 mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 4시간동안 상온으로 올린 후, 상온에서 30분간 교반 하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 43 mg(55%, diastereomer ratio 7:1)을 얻었다. 2.0 mL of starting material 1-phenyl-5-trimethylsilanyl-penta-3-yn-1-ol (70 mg, 0.30 mmol) and 1-phenyl-ethanone (41 μL, 0.35 mmol) under nitrogen atmosphere Was dissolved in the solution and stirred at -78 ° C, and TMSOTf (63 L, 0.35 mmol) was added thereto. While stirring the reaction mixture, the reaction temperature was gradually raised to room temperature for about 4 hours, and then stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 43 mg (55%, diastereomer ratio 7: 1) of the product.
1H NMR(300MHz, CDCl3) δ 7.70-7.62(m, 2H), 7.53-7.28(m, 8H), 5.25-5.20(q, 1H, J=5.4Hz), 5.12-5.07(m, 1H), 5.01-4.94(m, 1H), 3.06-2.99(m, 1H), 2.81-2.71(m, 1H), 1.79(d, 3H, J=4.2Hz); 13C NMR(75MHz, CDCl3) δ 201.21, 147.21, 142,91, 141.20, 128.75, 128.51, 128.26, 128.14, 127.09, 126.71, 126.26, 125.46, 125.78, 109.74, 84.21, 79.89, 79.69, 40.72, 29.98, 28.64 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.70-7.62 (m, 2H), 7.53-7.28 (m, 8H), 5.25-5.20 (q, 1H, J = 5.4 Hz), 5.12-5.07 (m, 1H), 5.01-4.94 (m, 1H), 3.06-2.99 (m, 1 H), 2.81-2.71 (m, 1 H), 1.79 (d, 3H, J = 4.2 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ 201.21, 147.21, 142,91, 141.20, 128.75, 128.51, 128.26, 128.14, 127.09, 126.71, 126.26, 125.46, 125.78, 109.74, 84.21, 79.89, 79.69, 40.72, 29.98, 28.64 ppm
실시예 8. 2-페닐-4-바이닐리덴-1-옥사-스파이로[4,5]데칸Example 8. 2-phenyl-4-vinylidene-1-oxa-spiro [4,5] decane
질소 대기 하에서 출발 물질 1-페닐-5-트라이메틸실라닐-펜타-3-인-1-올(70 mg, 0.30 mmol)과 사이클로헥산온(32 μL, 0.35 mmol)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(63 μL, 0.35 mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 4시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 69 mg(95%)을 얻었다. Dissolve starting material 1-phenyl-5-trimethylsilanyl-penta-3-yn-1-ol (70 mg, 0.30 mmol) and cyclohexanone (32 μL, 0.35 mmol) in 2.0 mL of ether under nitrogen atmosphere. After stirring at 78 ° C., TMSOTf (63 μL, 0.35 mmol) was added. While slowly stirring the reaction mixture to room temperature for about 4 hours, the mixture was stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 69 mg (95%) of product.
1H NMR(300MHz, CDCl3) δ 7.49-7.30(m, 5H), 5.07-4.95(m, 1H), 4.94-4.89(m, 2H), 3.10-3.01(m, 1H), 2.80-2.68(m, 1H), 1.96-1.93(d, 2H, J=12Hz), 1.87-1.50(m, 7H), 1.42-1.29(m, 1H); 13C NMR(75MHz, CDCl3) δ 200.20, 142.37, 128.66, 127.82, 127.12, 127.09, 126.37, 109.34, 82.79, 78.87, 78.64, 40.51, 37.99, 35.59, 25.71, 23.03, 22.86 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.49-7.30 (m, 5H), 5.07-4.95 (m, 1H), 4.94-4.89 (m, 2H), 3.10-3.01 (m, 1H), 2.80-2.68 (m, 1H), 1.96-1.93 (d , 2H, J = 12 Hz), 1.87-1.50 (m, 7H), 1.42-1.29 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 200.20, 142.37, 128.66, 127.82, 127.12, 127.09, 126.37, 109.34, 82.79, 78.87, 78.64, 40.51, 37.99, 35.59, 25.71, 23.03, 22.86 ppm
실시예 9. 2-페닐-4-바이닐리덴-1,8-다이옥사-스파이로[4,5]데칸Example 9. 2-phenyl-4-vinylidene-1,8-dioxa-spiro [4,5] decane
질소 대기 하에서 출발 물질 1-페닐-5-트라이메틸실라닐-펜타-3-인-1-올(70 mg, 0.30 mmol)과 테트라하이드로-하이란-4-온(32 μL, 0.35 mmol)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(62 μL, 0.35 mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 4시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 52 mg(71%)을 얻었다. Start nitrogen 1-phenyl-5-trimethylsilanyl-penta-3-yn-1-ol (70 mg, 0.30 mmol) and tetrahydro-hyran-4-one (32 μL, 0.35 mmol) under nitrogen atmosphere. It was dissolved in 2.0 mL of ether, stirred at -78 ° C, and TMSOTf (62 μL, 0.35 mmol) was added thereto. While slowly stirring the reaction mixture to room temperature for about 4 hours, the mixture was stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 52 mg (71%) of product.
1H NMR(300MHz, CDCl3) δ 7.47-7.30(m, 5H), 5.08-5.00(m, 1H), 4.99-4.97(m, 2H), 3.98-3.82(m, 4H), 3.12-3.03(m, 1H), 2.81-2.69(m, 1H), 2.05-1.84(m, 4H); 13C NMR(75MHz, CDCl3) δ 200.23, 141.83, 128.74, 128.03, 126.31, 108.43, 79.95, 79.77, 78.91, 77.80, 77.37, 76.95, 65.06, 64.93, 40.09, 38.08, 35.85 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.47-7.30 (m, 5H), 5.08-5.00 (m, 1H), 4.99-4.97 (m, 2H), 3.98-3.82 (m, 4H), 3.12-3.03 (m, 1H), 2.81-2.69 (m , 1H), 2.05-1.84 (m, 4H); 13 C NMR (75 MHz, CDCl 3 ) δ 200.23, 141.83, 128.74, 128.03, 126.31, 108.43, 79.95, 79.77, 78.91, 77.80, 77.37, 76.95, 65.06, 64.93, 40.09, 38.08, 35.85 ppm
실시예 10. 2,10-다이페닐-4,12-다이바이닐리덴-1,9-다이옥사-다이스파이로[4,2,4,2] 테트라데칸Example 10. 2,10-Diphenyl-4,12-divinylidene-1,9-dioxa-diispyro [4,2,4,2] tetradecane
질소 대기 하에서 출발 물질 1-페닐-5-트라이메틸실라닐-펜타-3-인-1-올(100 mg, 0.43 mmol)과 사이클로헥산-1,4-다이온(27 mg, 0.24 mmol)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(86 μL, 0.47 mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 5시간동안 상온으로 올린 후, 상온에서 50분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 44.7 mg(48%, mp 168 ℃)을 얻었다.Starting material 1-phenyl-5-trimethylsilanyl-penta-3-yn-1-ol (100 mg, 0.43 mmol) and cyclohexane-1,4-dione (27 mg, 0.24 mmol) under nitrogen atmosphere It was dissolved in 2.0 mL of ether, stirred at -78 ° C, and then TMSOTf (86 μL, 0.47 mmol) was added thereto. While stirring the reaction mixture, the reaction temperature was gradually raised to room temperature for about 5 hours, and then stirred at room temperature for 50 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 44.7 mg (48%, mp 168) of the product. C) was obtained.
1H NMR(300MHz, CDCl3) δ 7.49-7.30(m, 10H), 5.04(q, 2H, J= 6Hz), 4.93-4.85(m, 4H), 3.10-3.01(m, 2H), 2.77-2.65(m, 2H), 2.17-1.85(m, 8H); 13C NMR(75MHz, CDCl3) δ 199.60, 142.65, 128.63, 127.79, 127.11, 126.32, 109.02, 82.13, 79.43, 78.61, 40.28, 34.10, 33.96, 31.58, 31.44 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.49-7.30 (m, 10H), 5.04 (q, 2H, J = 6 Hz), 4.93-4.85 (m, 4H), 3.10-3.01 (m, 2H), 2.77-2.65 (m, 2H), 2.17-1.85 (m, 8 H); 13 C NMR (75 MHz, CDCl 3 ) δ 199.60, 142.65, 128.63, 127.79, 127.11, 126.32, 109.02, 82.13, 79.43, 78.61, 40.28, 34.10, 33.96, 31.58, 31.44 ppm
실시예 11. 5-페닐-4-바이닐리덴-2,3,4,5,-테트라하이드로-[2,2']바이퓨란일Example 11. 5-phenyl-4-vinylidene-2,3,4,5, -tetrahydro- [2,2 '] bifuranyl
질소 대기 하에서 출발 물질 1-퓨란-2-일-5-트라이메틸실라닐-펜타-3-인-1-올(50 mg, 0.23 mmol)과 벤즈 알데하이드(24 mg, 0.23 mmole)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(51 μL, 0.28mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 3시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 40 mg(73%, diastereomer ratio > 99:1)을 얻었다.2.0 mL of starting material 1-furan-2-yl-5-trimethylsilanyl-penta-3-yn-1-ol (50 mg, 0.23 mmol) and benzaldehyde (24 mg, 0.23 mmole) under nitrogen atmosphere It was dissolved in the solution and stirred at -78 ° C, and TMSOTf (51 µL, 0.28 mmol) was added thereto. While stirring the reaction mixture, the reaction temperature was gradually raised to room temperature for about 3 hours, and then stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 40 mg (73%, diastereomer ratio> 99: 1) of the product.
1H NMR (300MHz, CDCl3) δ 7.44-7.39(m 1H), 7.37-7.22(m, 5H), 6.38-6.35(q, 1H, J=6.2Hz), 6.28-6.25(q, 1H, J=6.2Hz), 5.58-5.56(m, 1H), 5.14-5.04(m, 3H), 3.03-2.89(m, 1H), 2.83-2.73(m, 1H); 13C NMR (75MHz, CDCl3) δ 204.04, 152.16, 142.23, 142.41, 129.06, 127.56, 126.70, 110.86, 109.19, 82.59, 76.92, 73.13, 44.08 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.44-7.39 (m 1 H), 7.37-7.22 (m, 5H), 6.38-6.35 (q, 1H, J = 6.2 Hz), 6.28-6.25 (q, 1H, J = 6.2 Hz), 5.58-5.56 (m, 1 H), 5.14-5.04 (m, 3 H), 3.03-2.89 (m, 1 H), 2.83-2.73 (m, 1 H); 13 C NMR (75 MHz, CDCl 3 ) δ 204.04, 152.16, 142.23, 142.41, 129.06, 127.56, 126.70, 110.86, 109.19, 82.59, 76.92, 73.13, 44.08 ppm
실시예 12. 2-페닐-5-싸이오펜-2-일-3-바이닐리덴-테트라하이드로-퓨란Example 12. 2-phenyl-5-thiophen-2-yl-3-vinylidene-tetrahydro-furan
질소 대기 하에서 출발 물질 1-싸이오펜-2-일-5-트라이메틸실라닐-펜타-3-인-1-올(50 mg, 0.21 mmol)과 벤즈 알데하이드(22 mg, 0.21 mmole)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(46 μL, 0.25 mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 3시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 43 mg(81%, diastereomer ratio > 99:1)을 얻었다.Starting material 1-thiophen-2-yl-5-trimethylsilanyl-penta-3-yn-1-ol (50 mg, 0.21 mmol) and benzaldehyde (22 mg, 0.21 mmole) under nitrogen atmosphere were converted to ether 2.0. After dissolving in mL and stirring at -78 ° C, TMSOTf (46 μL, 0.25 mmol) was added thereto. While stirring the reaction mixture, the reaction temperature was gradually raised to room temperature for about 3 hours, and then stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 43 mg (81%, diastereomer ratio> 99: 1) of the product.
1H NMR(300MHz, CDCl3) δ 7.49-7.46(m, 1H), 7.31-7.20(m, 5H), 7.00-6.94(m, 2H), 5.66-5.64(m, 1H), 5.05(t, 1H, J=6.06Hz), 4.85-4.81(m, 2H), 2.97-2.89(m, 1H), 2.77-2.68(m, 1H); 13C NMR(75MHz, CDCl3) δ 206.32, 143.88, 143.37, 129.06, 127.34, 126.78, 125.70, 107.30, 83.55, 82.75, 76.59, 45.67 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.49-7.46 (m, 1H), 7.31-7.20 (m, 5H), 7.00-6.94 (m, 2H), 5.66-5.64 (m, 1H), 5.05 (t, 1H, J = 6.06 Hz), 4.85-4.81 (m, 2H), 2.97-2.89 (m, 1H), 2.77-2.68 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 206.32, 143.88, 143.37, 129.06, 127.34, 126.78, 125.70, 107.30, 83.55, 82.75, 76.59, 45.67 ppm
실시예 13. 5-에틸-2-페닐-3-바이닐리덴-테트라하이드로-퓨란Example 13. 5-ethyl-2-phenyl-3-vinylidene-tetrahydro-furan
질소 대기 하에서 출발 물질 8-트라이메틸실라닐-옥타-6-인-4-올(45 mg, 0.23 mmol)과 벤즈 알데하이드(24 mg, 0.23 mmole)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(51 μL, 0.25mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 3시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 40mg (87%, diastereomerratio > 99:1)을 얻었다.Under nitrogen atmosphere, the starting material 8-trimethylsilanyl-octa-6-yn-4-ol (45 mg, 0.23 mmol) and benzaldehyde (24 mg, 0.23 mmole) were dissolved in 2.0 mL of ether, and stirred at -78 ° C. , TMSOTf (51 μL, 0.25 mmol) was added. While stirring the reaction mixture, the reaction temperature was gradually raised to room temperature for about 3 hours, and then stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 40 mg (87%, diastereomerratio> 99: 1) of the product.
1H NMR(300MHz, CDCl3) δ 7.44-7.24(m, 5H), 5.50(s, 1H), 4.93-4.90(m, 2H), 4.16-4.07(m, 1H), 2.53-2.45(m, 1H), 2.37-2.31(m, 1H), 1.68-1.56(m, 2H), 0.96(t, 3H, J=6.00Hz); 13C NMR(75MHz, CDCl3) δ 206.93, 142.66, 128.92, 127.64, 126.95, 107.99, 81.90, 79.53, 78.56, 38.42, 26.53, 10.23 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.44-7.24 (m, 5H), 5.50 (s, 1H), 4.93-4.90 (m, 2H), 4.16-4.07 (m, 1H), 2.53-2.45 (m, 1H), 2.37-2.31 (m, 1H), 1.68-1.56 (m, 2H), 0.96 (t, 3H, J = 6.00 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ 206.93, 142.66, 128.92, 127.64, 126.95, 107.99, 81.90, 79.53, 78.56, 38.42, 26.53, 10.23 ppm
실시예 14. 5-나프탈렌-2-일-2-페닐-3-바이닐리덴-테트라하이드로-퓨란Example 14. 5-naphthalen-2-yl-2-phenyl-3-vinylidene-tetrahydro-furan
질소 대기 하에서 출발 물질 1-나프탈렌-2-일-5-트라이메틸실라닐-펜트-3-인-1-올(48 mg, 0.17 mmol)과 벤즈 알데하이드(18 mg, 0.17 mmole)를 에테르 2.0 mL에 녹여 -78 ℃에서 교반하다가, TMSOTf(37 μL, 0.20mmol)를 넣었다. 반응 혼합물을 교반하면서 반응 온도를 서서히 약 3시간동안 상온으로 올린 후, 상온에서 30분간 교반하였다. 반응이 완결되면 NaHCO3를 넣어주고 5분 정도 교반하다가, 반응 혼합물을 EtOAc에 묽혀서 물과 포화 소금물로 씻어준 후 혼합물에서 유기층을 분리하여 무수 MgSO4로 건조하였다. 감압 하에 용매를 제거하고 남겨진 물질을 관크로마토그래피(EtOAc:n-Hexane=1:10)로 정제하여 생성물 35 mg(68%, diastereomer ratio>99:1)을 얻었다.2.0 mL of starting material 1-naphthalen-2-yl-5-trimethylsilanyl-pent-3-yn-1-ol (48 mg, 0.17 mmol) and benzaldehyde (18 mg, 0.17 mmole) under nitrogen atmosphere It was dissolved in the solution and stirred at -78 ° C, and TMSOTf (37 µL, 0.20 mmol) was added thereto. While stirring the reaction mixture, the reaction temperature was gradually raised to room temperature for about 3 hours, and then stirred at room temperature for 30 minutes. After completion of the reaction, NaHCO 3 was added and stirred for about 5 minutes. The reaction mixture was diluted with EtOAc, washed with water and saturated brine, and the organic layer was separated from the mixture and dried over anhydrous MgSO 4 . The solvent was removed under reduced pressure and the remaining material was purified by column chromatography (EtOAc: n-Hexane = 1: 10) to give 35 mg (68%, diastereomer ratio> 99: 1) of the product.
1H NMR(300MHz, CDCl3) δ 7.81-7.73(m, 3H), 7.41-7.22(m, 4H), 5.58(s, 1H), 5.23(t, 1H, J=6.06Hz), 4.74-4.71(m, 2H), 2.95-2.86(m, 1H), 2.80-2.75(m, 1H); 13C NMR(75MHz, CDCl3) δ 206.25, 143.23, 137.15, 133.19, 132.00, 129.06, 128.00, 127.73, 126.08, 125.83, 124.52, 100.99, 82.99, 81.36, 80.42, 45.22 ppm 1 H NMR (300 MHz, CDCl 3 ) δ 7.81-7.73 (m, 3H), 7.41-7.22 (m, 4H), 5.58 (s, 1H), 5.23 (t, 1H, J = 6.06 Hz), 4.74-4.71 (m, 2H), 2.95-2.86 (m, 1H), 2.80-2.75 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 206.25, 143.23, 137.15, 133.19, 132.00, 129.06, 128.00, 127.73, 126.08, 125.83, 124.52, 100.99, 82.99, 81.36, 80.42, 45.22 ppm
이상에서 설명한 바와 같이, 본 발명은 상기 화학식 1로 표시되는 테트라하이드로퓨란 고리화합물과 이의 제조방법을 제공한다.As described above, the present invention provides a tetrahydrofuran cyclic compound represented by Chemical Formula 1 and a preparation method thereof.
본 발명이 제공하는 상기 화학식 1로 표시되는 신규 화합물은 높은 입체 선택성을 가지고 있어 산업적으로의 응용성이 매우 높다.The novel compounds represented by the general formula (1) provided by the present invention have high stereoselectivity and have high industrial applicability.
또한, 본 발명이 제공하는 제조방법은 비교적 반응조건이 온화하고 수율도 높으며, 특히 목적물의 입체선택성이 높으므로 의약품 합성 등의 정밀화학 분야에서의 유용성이 크다.In addition, the manufacturing method provided by the present invention has relatively high reaction conditions, high yield, and particularly high stereoselectivity of the target, so that it is useful in the field of fine chemicals such as pharmaceutical synthesis.
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| US5510326A (en) | 1994-12-23 | 1996-04-23 | Givaudan-Roure Corporation | Multi-substituted tetrahydrofurans |
| JPH0977758A (en) * | 1995-09-11 | 1997-03-25 | Kuraray Co Ltd | Production of tetrahydrofuran derivative |
| JPH09227542A (en) * | 1996-02-27 | 1997-09-02 | Sumitomo Chem Co Ltd | Production of tetrahydrofuran derivative |
| JPH09227541A (en) * | 1996-02-27 | 1997-09-02 | Sumitomo Chem Co Ltd | Production of tetrahydrofuran derivative |
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| US5510326A (en) | 1994-12-23 | 1996-04-23 | Givaudan-Roure Corporation | Multi-substituted tetrahydrofurans |
| JPH0977758A (en) * | 1995-09-11 | 1997-03-25 | Kuraray Co Ltd | Production of tetrahydrofuran derivative |
| JPH09227542A (en) * | 1996-02-27 | 1997-09-02 | Sumitomo Chem Co Ltd | Production of tetrahydrofuran derivative |
| JPH09227541A (en) * | 1996-02-27 | 1997-09-02 | Sumitomo Chem Co Ltd | Production of tetrahydrofuran derivative |
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