KR100915095B1 - β- boration of α, β-alkyne ester compound - Google Patents
β- boration of α, β-alkyne ester compoundInfo
- Publication number
- KR100915095B1 KR100915095B1 KR1020080006571A KR20080006571A KR100915095B1 KR 100915095 B1 KR100915095 B1 KR 100915095B1 KR 1020080006571 A KR1020080006571 A KR 1020080006571A KR 20080006571 A KR20080006571 A KR 20080006571A KR 100915095 B1 KR100915095 B1 KR 100915095B1
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- present
- compound
- beta
- ester compound
- Prior art date
Links
- 238000005885 boration reaction Methods 0.000 title 1
- -1 alkene ester Chemical class 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 18
- 239000003054 catalyst Substances 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052802 copper Inorganic materials 0.000 claims abstract description 15
- 239000010949 copper Substances 0.000 claims abstract description 15
- 229910052796 boron Inorganic materials 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 5
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 10
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 claims description 6
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 150000003138 primary alcohols Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 abstract description 15
- 239000003446 ligand Substances 0.000 abstract description 13
- 229910000073 phosphorus hydride Inorganic materials 0.000 abstract description 7
- 238000002360 preparation method Methods 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 abstract description 3
- 150000002148 esters Chemical class 0.000 abstract description 3
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 229910052723 transition metal Inorganic materials 0.000 abstract description 2
- 150000003624 transition metals Chemical class 0.000 abstract description 2
- 150000001336 alkenes Chemical class 0.000 abstract 1
- 239000000047 product Substances 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- IVDFJHOHABJVEH-UHFFFAOYSA-N HOCMe2CMe2OH Natural products CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 3
- RYXZOQOZERSHHQ-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenoxy)phenyl]-diphenylphosphane Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1OC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RYXZOQOZERSHHQ-UHFFFAOYSA-N 0.000 description 3
- 238000006197 hydroboration reaction Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 150000003333 secondary alcohols Chemical class 0.000 description 2
- 150000003509 tertiary alcohols Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- HAKVNWBUOCSHTR-UHFFFAOYSA-N (9,9-dimethylxanthen-1-yl)-diphenylphosphane Chemical compound C=12C(C)(C)C3=CC=CC=C3OC2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 HAKVNWBUOCSHTR-UHFFFAOYSA-N 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000220324 Pyrus Species 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 150000001638 boron Chemical class 0.000 description 1
- 125000005621 boronate group Chemical group 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- PYTMYKVIJXPNBD-UHFFFAOYSA-N clomiphene citrate Chemical compound [H+].[H+].[H+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.C1=CC(OCCN(CC)CC)=CC=C1C(C=1C=CC=CC=1)=C(Cl)C1=CC=CC=C1 PYTMYKVIJXPNBD-UHFFFAOYSA-N 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- LCGITQAMTPXTBS-UHFFFAOYSA-N copper;copper(1+) Chemical compound [Cu+].[Cu+2] LCGITQAMTPXTBS-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 235000021017 pears Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/08—Halides
- B01J27/122—Halides of copper
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
본 발명은 전이금속촉매인 구리를 이용한 알파, 베타-알킨 에스터 화합물 (α,β-alkyne ester compound)의 β-보론화 방법에 관한 것으로, 하기 반응식 (1)에 나타낸 바와 같이 구리 촉매 및 포스핀리간드의 존재 하에서, 용매 중 화학식 (I)의 알파, 베타-알킨 에스터 화합물과 화학식 (II)의 비스피나콜라토다이보론을 반응시켜 화학식 (III)의 β-위치에 보론이 첨가된 알켄 에스터 (alkene ester)를 제조하는 방법에 관한 것이다. 본 발명의 제조방법은 다양한 알파, 베타-알킨 에스터 화합물에 선택적으로 β-위치에 피나콜보론 에스터를 첨가할 수 있으며, 이로부터 β-보론이 첨가된 알켄 화합물의 제조와 그 생성물의 응용이 가능하다. 따라서, 본 발명에 의해 생성된 화학식(III)의 화합물은 유기합성의 관점에서 새로운 탄소-탄소 결합반응 또는 다른 작용기로의 변환이 가능하여 유용한 중간체로 쓰일 수 있다.The present invention relates to a β-boronation method of alpha, beta-alkyne ester compound using a transition metal catalyst, copper, and a copper catalyst and phosphine, as shown in the following scheme (1). In the presence of a ligand, an alkene ester having boron added to the β-position of formula (III) by reacting the alpha, beta-alkyne ester compound of formula (I) with bispinacolatodiborone of formula (II) in a solvent esters). The production method of the present invention can selectively add pinacolboron ester to the β-position to various alpha, beta-alkyne ester compounds, from which the preparation of alkenes to which β-boron is added and its application are possible. Do. Therefore, the compound of formula (III) produced by the present invention can be used as a useful intermediate because it can be converted to a new carbon-carbon bond reaction or other functional group in view of organic synthesis.
반응식 1Scheme 1
상기 식에서, Where
R1 및 R2 는 명세서에 기재된 바와 같다.R 1 and R 2 Is as described in the specification.
Description
본 발명은 알파, 베타-알킨 에스터 화합물의 β-보론화 방법으로 구리촉매를 사용하여 β-위치에 피나콜보로네이트 에스터를 첨가하는 반응을 수행하여 알파,베타-알킨 에스터 화합물에 효과적인 β-보론화 방법에 관한 것이다.The present invention is a β-boron method of alpha, beta-alkyne ester compound by using a copper catalyst to add the pinacol boronate ester at the β-position to be effective in the alpha, beta-alkyne ester compound It is about how to get angry.
β-보론화로 수득되는 알켄 에스터 화합물은 유기합성의 중간체로 아주 유용하고, 다양한 유기 전환반응에 이용되고 있다. 지난 수년간 전이금속에 의하여 촉매화되는 탄소-탄소 다중결합의 첨가반응에 대한 연구가 광범위하게 진행되어 왔다. 하지만 전자가 부족한 삼중결합을 가지고 있는 알파, 베타-알킨 에스터 화합물에 보론 유도체의 첨가반응은 현재로는 하이드로보레이션(hydroboration)방법만이 알려져 있으며 적용 범위도 아주 제한적이다. 일례로 R1 의 치환체가 수소인 프로피올릭산 에스터 (R1= H, R2= Me)인 경우 안정한 피나콜 보로네이트를 형성하기 위해서는, 전자가 풍부한 알킬보레인(참고문헌: a와 b)과의 하이드로보레이션 후 여러 단계의 반응스텝을 거쳐야 하는 단점이 있다[참고문헌: (a) E.-i. Negishi, T. Yoshida, J. Am . Chem . Soc. 1973, 95, 6837-6838; (b) P. Martinez-Fresneda, M. Vauliter, Tetrahedron Lett . 1989, 30, 2929-2932]. 또한 치환체가 있는 알킨 화합물(R1≠ H)의 경우 화합물의 하이드로보레이션 반응은 알킬그룹의 치환체에 따른 입체장애에 의해서 위치 선택적으로 알킨 화합물의 β-위치에 보로네이트기를 도입할 수 없다는 것이 알려져 있다. [참고문헌: J. Plamondon, J. T. Snow, G. Zweifel, Organomet . Chem . Synth. 1971, 1, 249-252]. 따라서 알킨 에스터 (alkyne ester) 화합물로부터 알켄 에스터 (alkene ester) 화합물을 제조하는 일반적이고, 위치 및 입체 선택적인 β-보론화 방법의 효과적인 개발이 요구되어 지고 있다.Alkene ester compounds obtained by β-boronation are very useful as intermediates of organic synthesis and are used in various organic conversion reactions. Over the years, extensive research has been conducted on the addition of carbon-carbon multiple bonds catalyzed by transition metals. However, the addition reaction of boron derivatives to alpha, beta-alkyne ester compounds having triple bonds lacking electrons is currently known only as a hydroboration method and its application range is very limited. For example, when the substituent of R 1 is propiolic acid ester of hydrogen (R 1 = H, R 2 = Me), an electron-rich alkylboraine (refs. A and b) may be used to form a stable pinacol boronate. There is a drawback to undergoing several reaction steps after hydroboration with [Ref: (a) E.-i. Negishi, T. Yoshida, J. Am . Chem . Soc . 1973, 95 , 6837-6838; (b) P. Martinez-Fresneda, M. Vauliter, Tetrahedron Lett . 1989, 30 , 2929-2932. It is also known that in the case of alkyne compounds with substituents (R 1 ≠ H), the hydroboration reaction of the compounds cannot introduce a boronate group at the β-position of the alkyne compound positionally due to steric hindrance due to substituents of alkyl groups. have. [References: J. Plamondon, JT Snow, G. Zweifel, Organomet . Chem . Synth . 1971, 1 , 249-252. Therefore, there is a need for an effective development of a general, positional and stereoselective β-boronation method for preparing alkene ester compounds from alkyne ester compounds.
본 발명의 목적은 알파, 베타-알킨 에스터 화합물의 β-보론화 방법을 제공하는 것이다. It is an object of the present invention to provide a β-boronated method of alpha, beta-alkyne ester compounds.
본 발명의 목적은 β-위치에 보론이 첨가된 알켄 에스터 화합물의 제조방법을 제공하는 것이다. It is an object of the present invention to provide a method for preparing an alkene ester compound having boron added at the β-position.
상기한 목적을 달성하기 위하여, 본 발명의 목적은 구리 촉매 및 포스핀리간드의 존재 하에서, 용매 중 하기 화학식 (I)의 알파,베타-알킨 에스터 화합물과 비스피나콜라토다이보론 화합물을 반응시켜 β-위치에 보론이 첨가된 알켄 에스터 화합물을 제조하는 방법을 제공한다.In order to achieve the above object, it is an object of the present invention to react the alpha, beta-alkyne ester compound of formula (I) with a bispinacolatodiborone compound in a solvent in the presence of a copper catalyst and phosphine ligand, Provided is a method for preparing an alkene ester compound having boron added in position.
또한, 본 발명은 하기 반응식 1에 나타낸 바와 같이, 구리 촉매 및 포스핀리간드의 존재 하에서, 용매 중 화학식 (I)의 알파,베타-알킨 에스터 화합물과 화학식 (II)의 비스피나콜라토다이보론을 반응시켜 화학식 (III)의 β-위치에 보론이 첨가된 알켄 에스터 화합물을 제조하는 방법을 제공한다.In addition, the present invention reacts the alpha, beta-alkyne ester compound of formula (I) with bispinacolatodiborone of formula (II) in a solvent, in the presence of a copper catalyst and phosphine ligand, as shown in Scheme 1 below. To provide an alkene ester compound having boron added at the β-position of formula (III).
본 발명에 따른 화학식(I)의 알파, 베타-알킨 에스터 화합물과 비스피나콜라토다이보론화합물을 반응시켜 β-위치에 보론이 첨가된 알켄 에스터 화합물을 제조하는 방법은 하기 반응식 1로 도식화될 수 있다.A method of preparing an alkene ester compound having boron added at the β-position by reacting an alpha, beta-alkyne ester compound of formula (I) and a bispinacolato diborone compound according to the present invention may be illustrated in Scheme 1 below. .
상기 식에서, Where
R1은 수소, C1~C10 알킬, 페닐 또는 치환되거나 비치환된 C6~C14 방향족을 나타내며,R 1 is hydrogen, C 1 -C 10 alkyl, phenyl or substituted or unsubstituted C 6 -C 14 Aromatic,
R2는 C1~C6 알킬, 페닐 또는 치환된 C6~C14 방향족을 나타낸다.R 2 represents C 1 -C 6 alkyl, phenyl or substituted C 6 -C 14 aromatic.
본 발명에 따른 반응식 1로 표시되는 화합물의 제조방법은 다음과 같다. 먼저 출발물질로 사용되는 알파, 베타-알킨 에스터 화합물은 종래 공지된 방법에 따라 제조하며, 이렇게 제조된 다양한 화학식(I)의 화합물들을 구리촉매를 사용하여 반응시킨다. The preparation method of the compound represented by Scheme 1 according to the present invention is as follows. First, the alpha, beta-alkyne ester compound used as a starting material is prepared according to a conventionally known method, and various compounds of formula (I) thus prepared are reacted using a copper catalyst.
본 발명에서는 촉매로서 구리촉매를 사용한다. 사용 가능한 구리촉매로서는 염화(I)구리/나트륨 3차-부톡사이드 (CuCl/NaOt-Bu)의 조합 또는 구리(I)싸이펜2-카르복실레이트 (CuTc)를 포함한다. 구리촉매는 화학식(I)의 화합물에 대하여 0.01 내지 0.10 당량으로 사용할 수 있다. 바람직하게는 염화(I)구리를 사용하는 경우, 필수성분으로 첨가되는 염기인 나트륨 3차-부톡사이(NaOt-Bu)의 당량 대 구리염(CuCl)의 당량은 약 1 : 1 내지 1 : 5배로 사용될 수 있으며, 보다 바람직하게는 1 : 1 내지 1 : 3배 당량으로 사용될 수 있다. 염기를 포함한 구리촉매의 함량이 하한치 미만인 경우, 촉매 첨가에 따른 반응속도 및 수율을 얻을 수 없으며, 상기 상한치를 초과한 경우, 제조시 경제적 효과를 얻을 수 없다.In the present invention, a copper catalyst is used as the catalyst. Copper catalysts that can be used include (I) copper chloride / sodium tert-butoxide (CuCl / NaOt-Bu) or copper (I) siphene 2-carboxylate (CuTc). The copper catalyst may be used in an amount of 0.01 to 0.10 equivalents based on the compound of formula (I). Preferably, when copper (I) copper is used, the equivalent of sodium tert-butoxide (NaOt-Bu) to the equivalent of copper salt (CuCl) is about 1: 1 to 1: 5, which is added as an essential ingredient. It may be used in pears, more preferably 1: 1 to 1: 3 times the equivalent. If the content of the copper catalyst containing the base is less than the lower limit, the reaction rate and yield according to the addition of the catalyst can not be obtained, and if the upper limit is exceeded, economic effects in the production cannot be obtained.
본 발명에서는 리간드로서, 적당한 반응성을 갖는 포스핀리간드를 사용한다. 사용 가능한 포스핀리간드로는 모노포스핀 리간드, 다이포스핀 리간드를 포함하며, 바람직하게는 잔포스(Xantphos; 비스(디페닐포스피노-9,9-디메틸잔텐)), DPE포스(DPEphos; 비스(2-디페닐포스피노페닐)에테르), dppf(1,1-비스(디페닐포스피노)페로신)을 포함한다. In the present invention, phosphine ligands having appropriate reactivity are used as ligands. Usable phosphine ligands include monophosphine ligands, diphosphine ligands, preferably Xantphos (bis (diphenylphosphino-9,9-dimethylxanthene)), DPE phos (DPEphos; bis) (2-diphenylphosphinophenyl) ether), dppf (1,1-bis (diphenylphosphino) ferrocine).
본 발명에서는 구리촉매 존재하에서 알킬보레인 대신 비스피나콜라토다이보론을 사용하고, 반응 온도는 70℃로 하여 반응을 진행시켜 50%의 수득률을 얻을 수 있다. In the present invention, bispinacolatodiborone is used in place of alkyl borane in the presence of a copper catalyst, and the reaction temperature is 70 ° C. to allow the reaction to proceed to obtain a yield of 50%.
하지만, 더 나은 반응성과 수득률을 위하여 본 발명에서는 반응속도 촉진제인 알코올을 사용하여 당량에 따라 리간드를 선택적으로 사용하는 것이 필수적이다. 본 발명에서 알코올은 C1~C6의 1차 내지 3차 알코올을 화학식(I)의 화합물에 대하여 1 내지 3 당량으로 사용할 수 있다. 보론이 2번 첨가된 생성물의 생성을 배제하기 위해서 알코올(C1~C6의 1차, 2차, 3차 알코올)을 2 당량 내지 3 당량 사용시 잔포스리간드를, 반응성이 좋은 알코올(1차, 2차 알코올)을 1 당량 사용시에는 잔포스(Xantphos), DPE포스(DPEphos), dppf 중 선택된 리간드를 사용하는 것이 바람직하다.However, for the better reactivity and yield, it is essential in the present invention to selectively use the ligand according to the equivalent weight by using an alcohol which is a reaction rate accelerator. In the present invention, the alcohol may use C 1 to C 6 primary to tertiary alcohols in an amount of 1 to 3 equivalents based on the compound of formula (I). To eliminate the production of boron-added product twice, xanthose ligand is used when 2 to 3 equivalents of alcohols (primary, secondary and tertiary alcohols of C 1 to C 6 ) are used. , Secondary alcohol), it is preferable to use a ligand selected from Xantphos, DPEphos, dppf.
본 발명에서는 보론이 2번 첨가된 생성물(diboronated product)의 생성을 배제하기 위해서 비스피나콜라토다이보론의 양을 조절하는 것이 중요하며, 비스피나콜라토다이보론은 화학식(I)의 화합물에 대하여 과량을 쓰지 않고 1.1 당량으로 사용하는 것이 바람직하다.In the present invention, it is important to control the amount of bispinacolatodiborone in order to exclude the production of a diboronated product in which boron is added twice. It is preferable to use 1.1 equivalents, without using.
본 발명에 따른 제조방법에서 '실온'은 당업계에서 통상적으로 사용하는 20 ~ 30℃의 온도로서, 온도를 상승시킬 필요가 없다는 의미이며, 상기 실온의 온도범위를 제한하지 아니한다. In the manufacturing method according to the present invention, 'room temperature' is a temperature of 20 to 30 ° C. which is commonly used in the art, and means that there is no need to increase the temperature, and does not limit the temperature range of the room temperature.
본 발명에 따른 생성물, 바람직하게는 화학식 (III)의 알켄 에스터 화합물은 화학물질 제조분야에서 통상적으로 사용될 수 있는 세척, 여과, 정제 등의 과정을 수행할 수 있으며, 본 발명에서는 이에 대해 한정하지 않는다.The product according to the invention, preferably the alkene ester compound of formula (III), can carry out processes of washing, filtration, purification and the like, which can be commonly used in the chemical preparation field, but the present invention is not limited thereto. .
본 발명에서는 β-위치에 보론이 첨가된 화학식 (III)의 알켄 에스터 화합물을 빠른 시간 안에 높은 수율로 얻을 수 있으며, 생성물이 비교적 안정하여 반응 후 용이하게 분리 가능하다. 이러한 화합물은 유기합성의 중간체로 많이 사용될 수 있다.In the present invention, the alkene ester compound of formula (III) having boron added at the β-position can be obtained in a high yield in a short time, and the product is relatively stable and can be easily separated after the reaction. Such compounds can be used as intermediates in organic synthesis.
일구체예에서, 본 발명은 알파, 베타-알킨 에스터 화합물의 β-보론화 방법을 제공한다. In one embodiment, the present invention provides a method of β-boronation of alpha, beta-alkyne ester compounds.
상기한 과제 해결 수단에 의한 본 발명에 따르면, 알파, 베타-알킨 에스터 화합물의 β-보론화 방법은 구리 촉매와 포스핀리간드, 알코올의 존재 하에 비스피나콜라토다이보론 화합물을 사용함으로써, 위치 및 입체 선택적인 β-보론화 방법에 효율적이다. 또한, 본 발명에 따른 반응 생성물은 탄소-탄소 결합반응 또는 다른 작용기로의 변환이 가능한 유용한 중간체로 사용가능하다. According to the present invention by the above-mentioned means for solving the problem, the β-boronation method of alpha, beta-alkyne ester compound by using a bispinacolatodiborone compound in the presence of a copper catalyst, phosphine ligand, alcohol, Efficient for selective β-boronation methods. In addition, the reaction products according to the invention can be used as useful intermediates capable of converting carbon-carbon bonds or other functional groups.
이하, 본 발명을 하기 실시 예에 의거하여 더욱 상세히 설명한다. 하기 실시예는 단지 본 발명을 예시하고자 하는 것으로, 본 발명을 제한하고자 하는 것은 아니다.Hereinafter, the present invention will be described in more detail based on the following examples. The following examples are merely intended to illustrate the invention, not to limit the invention.
실시예Example 1: 본 발명의 β-위치에 1: at β-position of the present invention 보론이Boron 첨가된 화합물의 제조 Preparation of Added Compound
질소 대기 하, 실온에서 염화(I)구리 (0.0015 g, 0.015 mmol), 잔포스 (0.0087 g, 0.015 mmol) 및 나트륨 3차-부톡사이드 (0.0029 g, 0.030 mmol)를 첨가한 다음 테트라히드로퓨란 (0.4 mL)을 첨가하였다. 30분 후 비스피나콜라토다이보론 (0.1397 g, 0.55 mmol)을 테트라히드로퓨란에 녹여서 첨가하고, 10분 후 화학식(I)에 해당하는 반응물 (0.5 mmol)을 첨가하였다. 후속하여, 반응속도 촉진제인 1차 알코올 (0.04 mL, 1.0 mmol)을 첨가하여 반응을 진행시켰다. 따라서, 생성물을 에틸아세테이트(Ethyl acetate)를 이용하여 셀라이트 필터(Celite filter)로 여과한 후에 여과액을 모아서 농축하고, 이를 실리카겔 컬럼을 이용하여 정제하여, 하기 표 1과 표 2에 기재된 바와 같은 수율에 상응하는 화합물(Ⅲ)을 수득하였다.Copper chloride (0.0015 g, 0.015 mmol), xantose (0.0087 g, 0.015 mmol) and sodium tert-butoxide (0.0029 g, 0.030 mmol) are added at room temperature under nitrogen atmosphere, followed by tetrahydrofuran ( 0.4 mL) was added. After 30 minutes, bispinacolatodiborone (0.1397 g, 0.55 mmol) was dissolved in tetrahydrofuran and added, and after 10 minutes, a reactant corresponding to formula (I) (0.5 mmol) was added. Subsequently, primary alcohol (0.04 mL, 1.0 mmol), which is a reaction rate accelerator, was added to proceed with the reaction. Thus, the product was filtered through a Celite filter using ethyl acetate, and the filtrates were collected and concentrated, and purified using a silica gel column, as shown in Tables 1 and 2 below. Compound (III) was obtained corresponding to the yield.
또한, 상기 표 1 및 표 2에 기재된 화합물 중 샘플번호 1 내지 6에 해당되는 화학식 (III)의 화합물에 대한 물리화학적 데이터는 하기와 같다.In addition, the physicochemical data of the compound of formula (III) corresponding to Sample Nos. 1 to 6 among the compounds described in Table 1 and Table 2 are as follows.
상기 표 1에 나타낸 바와 같이, 본 발명의 제조방법을 통하여 빠른 시간 안에 높은 수율을 얻는 화학식(Ⅲ)의 화합물을 수득할 수 있음을 알 수 있다.As shown in Table 1, it can be seen that through the production method of the present invention it is possible to obtain a compound of the formula (III) to obtain a high yield in a short time.
본 발명에서는 기존에 보고된 바 없는 알킨의 β-보론화 방법을 최초로 성공적으로 수행하였으며, 샘플 1, 2, 3(표 2)의 경우 높은 수율로 원활하게 생성물을 얻을 수 있었다. In the present invention, the β-boronation method of alkynes, which has not been reported previously, was successfully performed for the first time, and in the case of samples 1, 2, and 3 (Table 2), the product was smoothly obtained in high yield.
일반적으로 신 첨가(syn addition) 형태의 생성물을 얻는 반면에 샘플 5의 터트-부틸이 치환된 에스터의 경우 (E)와 (Z)이성질체가 형성되는 것을 확인할 수 있었다.In general, while the product in the form of syn addition was obtained, the tere-butyl-substituted ester of Sample 5 was found to form (E) and (i) isomers.
상기에서는 본 발명의 바람직한 실시예를 참조하여 설명하였지만, 해당기술 분야의 숙련된 당업자는 하기의 특허 청구의 범위에 기재된 본 발명의 사상 및 영역으로부터 벗어나지 않는 범위 내에서 본 발명을 다양하게 수정 및 변경시킬 수 있음을 이해할 수 있을 것이다.Although the above has been described with reference to a preferred embodiment of the present invention, those skilled in the art will be variously modified and changed within the scope of the invention without departing from the spirit and scope of the invention described in the claims below. I can understand that you can.
본 발명은 구리 촉매 및 포스핀리간드의 존재 하에서, 용매 중 알파, 베타-알킨 에스터 화합물과 비스피나콜라토다이보론을 반응시켜 β-위치에 보론이 첨가된 알켄 에스터 (alkene ester)를 제조하는 방법에 관한 것이다. 이에 의해 한번의 반응스텝으로 손쉽게 제조가 가능하여 다양한 유기합성 및 정밀 화학제품 생산에 응용이 가능하다. The present invention relates to a method for preparing an alkene ester in which boron is added at β-position by reacting an alpha, beta-alkyne ester compound and bispinacolatodiborone in a solvent in the presence of a copper catalyst and phosphine ligand. It is about. This makes it easy to manufacture in one reaction step, which makes it possible to apply to various organic synthesis and fine chemical production.
Claims (11)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020080006571A KR100915095B1 (en) | 2008-01-22 | 2008-01-22 | β- boration of α, β-alkyne ester compound |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020080006571A KR100915095B1 (en) | 2008-01-22 | 2008-01-22 | β- boration of α, β-alkyne ester compound |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20090080677A KR20090080677A (en) | 2009-07-27 |
KR100915095B1 true KR100915095B1 (en) | 2009-09-02 |
Family
ID=41291749
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020080006571A KR100915095B1 (en) | 2008-01-22 | 2008-01-22 | β- boration of α, β-alkyne ester compound |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR100915095B1 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113354671B (en) * | 2021-05-28 | 2023-08-04 | 西北大学 | Method for synthesizing olefin compound containing boron and sulfur or olefin compound containing boron and selenium by copper catalysis |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003026692A (en) * | 2001-07-06 | 2003-01-29 | Japan Science & Technology Corp | 1-boryl-4-stannyl-1,3-diene compound and method for producing the same |
WO2006132896A2 (en) * | 2005-06-08 | 2006-12-14 | Wyeth | Stereoselective synthesis of (e)-vinylboronic esters via a zr mediated hydroboration of alkynes |
-
2008
- 2008-01-22 KR KR1020080006571A patent/KR100915095B1/en not_active IP Right Cessation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003026692A (en) * | 2001-07-06 | 2003-01-29 | Japan Science & Technology Corp | 1-boryl-4-stannyl-1,3-diene compound and method for producing the same |
WO2006132896A2 (en) * | 2005-06-08 | 2006-12-14 | Wyeth | Stereoselective synthesis of (e)-vinylboronic esters via a zr mediated hydroboration of alkynes |
Non-Patent Citations (2)
Title |
---|
Chem. Eur. J. 2007, 13, 2614-2621 |
Soungyun Mun et al, Copper-Catalyzed β-Boration of α,β-Unsaturated Carbonyl Compounds, Organic Letters, 2006, Vol.8, No.21, 4887-4889 |
Also Published As
Publication number | Publication date |
---|---|
KR20090080677A (en) | 2009-07-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103962183B (en) | A kind of PNN ligand-metal complex Catalysts and its preparation method and application | |
US7754902B2 (en) | Ruthenium(II) catalysts for use in stereoselective cyclopropanations | |
CN111420709B (en) | Application of N-heterocyclic carbene-based mixed nickel (II) complex in synthesis of 2-linear alkyl benzothiazole compound | |
CN111217848B (en) | Spiro-dihydrobenzothiole diphenol compound, synthesis method and application thereof | |
EP2678304B1 (en) | Hydrogenation of dienals with rhodium complexes under carbon monoxide free atmosphere | |
CN100430139C (en) | Application of substituted bidentate amido phosphite ligand on binaphthol skeleton in hydroformylation of olefin | |
Cunningham et al. | On the use of mixtures of organotin species for catalytic enantioselective ketone allylation—A detective story | |
JP6054108B2 (en) | Process for producing optically active 2,3-dihydrofarnesal | |
CN108002966B (en) | Method for synthesizing 1, 2-diarylethane compounds | |
Chang et al. | Pyridine N-oxide promoted hydrosilylation of carbonyl compounds catalyzed by [PSiP]-pincer iron hydrides | |
KR100915095B1 (en) | β- boration of α, β-alkyne ester compound | |
CN110156832A (en) | Bisacetal base Phenylphosphine, their preparation method and the purposes in coupling reaction | |
CN111468183A (en) | Polyfluoro triaryl chiral spiro phosphoric acid catalyst, and preparation method and application thereof | |
CN1042128C (en) | Process for preparation of alcohols | |
JP3631070B2 (en) | Optically active fluorinated binaphthol derivatives | |
JP5102505B2 (en) | Process for producing optically active dialkylphosphinomethane derivatives | |
CN117321041A (en) | Catalytic cannabinol synthesis and precursors | |
CN114907404A (en) | 5- (2- (disubstituted phosphino) phenyl) -1-alkyl-1H-pyrazolylphosphine ligand and preparation method and application thereof | |
JP5493346B2 (en) | Ferrocene derivatives and uses thereof | |
CN113583046A (en) | Bidentate phosphine ligand, preparation method and application thereof | |
CN103748065A (en) | Production method for 2-alkenylamine compound | |
CN112250709A (en) | Synthesis method of ortho-aryl substituted tertiary phosphine compound | |
Fan et al. | Rhodium catalyzed asymmetric Pauson-Khand reaction using SDP ligands | |
CN111690009A (en) | Phosphine pyridine oxazoline compound, metal complex, preparation method and application thereof | |
EP1698609B1 (en) | Process for producing an alcohol or its silyl ether |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant | ||
FPAY | Annual fee payment |
Payment date: 20120724 Year of fee payment: 4 |
|
FPAY | Annual fee payment |
Payment date: 20130530 Year of fee payment: 5 |
|
LAPS | Lapse due to unpaid annual fee |