JP2000511922A - Chiral organoborane - Google Patents
Chiral organoboraneInfo
- Publication number
- JP2000511922A JP2000511922A JP10501309A JP50130998A JP2000511922A JP 2000511922 A JP2000511922 A JP 2000511922A JP 10501309 A JP10501309 A JP 10501309A JP 50130998 A JP50130998 A JP 50130998A JP 2000511922 A JP2000511922 A JP 2000511922A
- Authority
- JP
- Japan
- Prior art keywords
- compound represented
- formula
- compound
- general formula
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 46
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 125000005843 halogen group Chemical group 0.000 claims abstract description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
- 229930195734 saturated hydrocarbon Natural products 0.000 claims abstract description 5
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims abstract 2
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 6
- 239000012433 hydrogen halide Substances 0.000 claims description 6
- 150000002576 ketones Chemical class 0.000 claims description 5
- 150000002466 imines Chemical class 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000000962 organic group Chemical group 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 150000001721 carbon Chemical class 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 150000002900 organolithium compounds Chemical class 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 229940125782 compound 2 Drugs 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 229940125904 compound 1 Drugs 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- FPEQNDQUWPJCKZ-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1B2.C1CCC2CCCC1B2 FPEQNDQUWPJCKZ-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 240000005125 Myrtus communis Species 0.000 description 1
- 235000013418 Myrtus communis Nutrition 0.000 description 1
- PGZLEZYONDNZTC-UHFFFAOYSA-N S(=O)(=O)=C1SSCCC1 Chemical compound S(=O)(=O)=C1SSCCC1 PGZLEZYONDNZTC-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001925 cycloalkenes Chemical class 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- 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
- C07F5/027—Organoboranes and organoborohydrides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
(57)【要約】 本発明は、次の一般式(Ｉ)及び(II) （式中、Ｒ1及びＲ2は独立して水素原子又はアルキル基もしくはシクロアルキル基を表すか、あるいはＲ1及びＲ2は一緒になって二価の飽和炭化水素基を表し；Ｘ1はハロゲン原子を表し；且つＸ2は水素原子又はハロゲン原子を表す）で示されるキラルオルガノボランに関する。本発明はまたかかる化合物の製造方法及びその使用、特に不斉還元剤としての使用に関する。 (57) [Summary] The present invention relates to the following general formulas (I) and (II): (Wherein R 1 and R 2 independently represent a hydrogen atom or an alkyl group or a cycloalkyl group, or R 1 and R 2 together represent a divalent saturated hydrocarbon group; X 1 represents A halogen atom; and X 2 represents a hydrogen atom or a halogen atom). The invention also relates to a process for the preparation of such compounds and their use, especially as asymmetric reducing agents.
Description
【発明の詳細な説明】 キラルオルガノボラン 本発明はキラルオルガノボラン(chiral organoboranes)、その製造方法及びそ の使用特に不斉還元剤としての使用に関する。 すなわち、本発明は次の一般式Ｉ及びII （式中、Ｒ1及びＲ2は独立して水素原子又はアルキル基もしくはシクロアルキル 基を表すか、あるいはＲ1及びＲ2は一緒になって二価の飽和炭化水素基を表し； Ｘ1はハロゲン原子を表し；且つＸ2は水素原子又はハロゲン原子を表す）で示さ れる化合物を主題とする。 前記の定義において、ハロゲン原子という用語は、弗素原子、塩素原子、臭素 原子又は沃素原子を表し、好ましくは弗素原子、塩素原子及び臭素原子を表す。 アルキル基という用語は、炭素原子を１〜６個有する直鎖又は分岐鎖のアルキル 基を表し、特に炭素原子を１〜４個有するアルキル基、例えばメチル基、エチル 基、プロピル基、イソプロピル基、ブチル基、イソブチル基、sec-ブチル基及び tert-ブチル基を表す。 前記の飽和シクロアルキル基は、炭素原子を３〜７個有する基、例えばシクロ プロピル基、シクロブチル基、シクロペンチル基、シクロヘキシル基、シクロヘ プチル基又はシクロオクチル基から選択し得、これらの基は低級アルキル基で置 換されていてもよい。 前記の二価の飽和炭化水素基という用語は、炭素原子を６〜８個有し、二環式 の基すなわちビシクロ[5,1,1]、[4,1,2]、［3,1,3]、[4,1,1]、[3,1,2]、[3,1,1 ]、又は[2,1,2]型の基、好ましくはビシクロ[3,1,3]型 の基を表し得る。 また、本発明は、前記の一般式Ｉで示される化合物の製造方法であって、次の 一般式III で示される化合物を適当な不飽和水素化化合物と反応させて次の式IV （式中、Ｒ1及びＲ2は前記の意義を有する）で示される化合物を製造し、式で示 される化合物を式Ｒ'Li（式中、Ｒ’は有機基を表す）で示される有機リチウム 化合物と反応させて前記の式Ｉで示される化合物を製造することを特徴とする前 記の一般式Ｉで示される化合物の製造方法を主題とする。 前記の適当な不飽和水素化化台物という用語は、二重結合を１個又は２個有す る炭化水素化合物を表す。 前記の有機基という用語は、アルキル基又はアリール基、好ましくはtert-ブ チル基のようなアルキル基を表す。 従って、炭素原子を６〜８個有するシクロアルキルジエンと式IIIで示される 化合物との反応は、前記の式Ｉで示される化合物であって式中のＲ1及びＲ2が一 緒になって炭素原子を６〜８個有する二価の飽和炭化水素基を表す化合物の製造 を可能にする。同様に前記の式Ｉで示される化合物のホウ素原子上のアルキル基 及び／又はシクロアルキル基は、対 応するアルケン及び／又はシクロアルケンそれぞれを前記の式IIIで示される化 合物と反応させることによって得られる。このことは、式Ｉで示される化合物で あって式中のＲ1がアルキル基を表し且つＲ2がシクロアルキル基を表す化合物が 、前記の式IIIで示される化合物を、所望のシクロアルキル基と同じ個数の炭素 原子を有するアルケンと反応させることによって得られること意味する。もちろ ん、Ｒ1とＲ2は同じ基を表し得る。 さらにまた、本発明は前記の一般式IIで示される化合物の製造方法を主題とす る。前記の一般式IIで示される化合物であって式中のＸ1が前記の意義を有し且 つＸ2が水素原子を表す場合の化合物の製造方法は、前記の一般式IIIで示される 化合物を式ＨＸ1（式中、Ｘ1は前記の意義を有ずする）で示されるハロゲン化水 素１モルと反応させることを特徴とする。前記の一般式IIで示される化合物であ って、式中のＸ1が前記の意義を有し且つＸ2がハロゲン原子を表す場合の化合物 の製造方法は、前記の一般式IIIで示される化合物を式ＨＸ1で示されるハロゲン 化水素１モル及び式ＨＸ2で表されるハロゲン化水素１モルと反応させることを 特徴とする。勿論、Ｘ1とＸ2は同じハロゲン原子を表し得る。 出発化合物IIIは公知であり、ジボランによるか又はジボランとルイス酸との 錯体による2-ミルテニル-1,3-ジチアン(2-myrtenyl 1,3-dithiane)の水素化ホウ 素化(hydroboration)により製造し得る（欧州特許第61408号明細書)。 前記の式Ｉ及びIIで示される化合物はこのようにして光学活性形の化合物物II Iから出発して光学活性形で製造し得る。 本発明の化合物は不斉還元剤として有用である。さらにまた、本発明は不斉還 元における前記の式Ｉ及びIIで示される化合物の使用を主題とする。本発明の化 合物はケトン又はイミン官能基の立体特異的還元に使用される。ケトン又はイミ ンの立体特異的還元は、該ケトン又はイミンを一般式Ｉ又はIIで示される化合物 の鏡像異性体と反応させることからなる。 以下の実施例は本発明を例証することを目的として示すものであり、本発明の 範囲を限定するものではない。実施例１ (-)-化合物II（式中、Ｘ1＝Ｘ2＝Cl）の製造 (-)-化合物III３g(11ミリモル)を窒素雰囲気下に100mlフラスコ中の無水エー テル60mlに縣濁した。次いで、得られた縣濁液を冷却浴中で−610℃に冷却し、4 .5Ｎ塩化水素エーテル5.6ml(25ミリモル)を迅速に加えた。冷却浴を取り除き、 次いで温度を−10℃で２時間30分保持した。標記化合物が白色粉末の形で沈殿し た。溶媒を減圧除去した。全収率は2-ミルテニル-1,3-ジチアンボランを基準と して計算して83.7％であった。得られた白色固体は無水テトラヒドロフラン20ml に溶解し、そのまま還元に使用した。実施例２ (-)-化合物III 37gを無水テトラヒドロフラン140mlに注加した。温度を０℃に し、シクロオクタジエン20mlをテトラヒドロフラン20mlに溶解した溶液を30分間 にわたって加えた。次いで、反応混合物を還流下で一夜加熱した。反応混合物を −70±５℃に冷却した後に、ペンタンに溶解したt-ブチルリチウムの1.7Ｍ溶液8 1mlを45分間にわたって加えた。反応混合物を−70±５℃でさらに２時間保持し 、次いで種々の溶媒と過剰量のシクロオクタジエンとを減圧下に周囲温度で除去 した。得られた残留物をMTBE 100mlに溶解した。この溶液を周囲温度で２時間攪 拌した後に−20℃でデカント(decanting)し、液層を分離した。得られた白色固 体状残留物を周囲温度でヘプタン100mlで洗浄し、次いで直ちに濾過して除去し た。最後にさらに周囲温度でMTBE100mlで洗浄した後に、減圧下で乾燥し、白色 結晶45.9gを得た(収率86.4％)。これらの結晶をアルゴン雰囲気下に４℃で保持 し、遮光した。実施例３ 実施例１で得られた化合物IIの下記に示す還元反応における使用 無水テトラヒドロフラン10mlに溶解した化合物１ １ｇ（3.15ミリモル）を、 実施例１で得られた(-)-化合物113.7g(11ミリモル)を無水テトラビドロフラン20 mlに溶解した溶液に、窒素雰囲気下に０℃で加えた。得られた溶液を25℃で48時 間攪拌した。次いで、溶媒を減圧下で除去した。得られた残留物をエチルエーテ ル60mlに溶解し、ジエタノールアミン2.6g(25ミリモル)を加えた。不溶物を濾過 して除去し、得られた濾液を濃縮乾固した。 得られた残留物は化合物２ 0.6gであり、これは（+）-体75％、(-)-体25％の 鏡像異性体組成を有していた。実施例４ 実施例２で得られた化合物Ｉの前記の化合物１→化合物２の還元反応における 使用 前記で得られた化合物Ｉ 10gを不活性雰囲気下で無水テトラヒドロフラン45ml に溶解した。次いで得られた反応混合物をサーモスタット制御を使用して約−78 ℃の温度に保持し、次いでテトラヒドロフラン10mlに希釈した化合物１ 0.5当量 を30分間にわたって加えた。反応を約−78℃で２時問続けた。過剰量の水素化ホ ウ素すなわち化合物Ｉをアルコールで中和した。得られた反応混合物を減圧乾燥 した。得られた残留物をエチルエーテル25mlに再溶解し、有機層を中性のpHにな るまで水洗した。得られた有機層を硫酸ナトリウムを用いて脱水した後に、濾過 し、減圧乾燥して混合物8.9gを得、これをシリカカラムを用いてクロマ トグラフィーにより分離した。得られた化合物２の鏡像異性体比は(+)-体96％、 (-)-体４％であった。実施例５ れる化合物の化合物１→化合物２の還元反応における使用 ａ） (+)- 化合物２の製造 THF(1280ml)に溶解した(-)-ミルテニルジチアン214.2gを9-ボラビシクロ[3,3, 1]ノナン(9-bora bicyclo[3,3,1]nonane)に加えた。溶解した後に、得られた反 応混合物を還流下で一夜加熱して反応を完結させ、次いで−80℃に冷却した。次 いで、tert-ブチルリチウムを−60〜−80℃の温度を維持しながら１時間以内に 加えた。次いで、化合物１(100g)を15分未満内に徐々に加えた。得られた混合物 を−60℃で２時間保持した。この時点で化合物１は完全に転化した。 前記の実施例のようにして処理した後に、(+)-化合物２をヘキサン(530ml)か ら再結晶して(-)-体98.2％／(+)-体1.8％の組成をもつ化合物２ 52.1gを得た。 ｂ） (-)- 化合物２の製造 (+)-化合物III39.5gをTHF(240ml)に溶解した。得られた溶液を０℃に冷却し、 1,5-シクロオクタジエン(15.9g)をTHF(45・ml)に溶解した溶液に加えた。 得られた溶液を還流下で一夜加熱して、次いでt-BuLiを用いて前記のようにし て処理して化合物１(21g)を還元し、常用の処理をした後に(-)-化合物２(10g-ee 100％)を得た。DETAILED DESCRIPTION OF THE INVENTION Chiral organoborane invention chiral organoborane (chiral organoboranes), their use as their preparation and their use particularly asymmetric reduction agent. That is, the present invention relates to the following general formulas I and II (Wherein R 1 and R 2 independently represent a hydrogen atom or an alkyl group or a cycloalkyl group, or R 1 and R 2 together represent a divalent saturated hydrocarbon group; X 1 represents A halogen atom; and X 2 represents a hydrogen atom or a halogen atom). In the above definition, the term halogen atom represents a fluorine, chlorine, bromine or iodine atom, preferably a fluorine, chlorine and bromine atom. The term alkyl group denotes a straight-chain or branched alkyl group having 1 to 6 carbon atoms, particularly an alkyl group having 1 to 4 carbon atoms, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, Represents a butyl group, an isobutyl group, a sec-butyl group and a tert-butyl group. Said saturated cycloalkyl group may be selected from groups having 3 to 7 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, these groups being lower alkyl. May be substituted with a group. The term divalent saturated hydrocarbon group refers to a bicyclic group having from 6 to 8 carbon atoms, ie, bicyclo [5,1,1], [4,1,2], [3,1 , 3], [4,1,1], [3,1,2], [3,1,1], or [2,1,2] type groups, preferably bicyclo [3,1,3] May represent a type group. The present invention also provides a method for producing a compound represented by the above general formula I, which comprises the following general formula III Is reacted with a suitable unsaturated hydrogenated compound to give the following formula IV Wherein R 1 and R 2 have the same meaning as described above, and the compound represented by the formula is converted to an organic compound represented by the formula R′Li (where R ′ represents an organic group). The subject of the present invention is a method for producing a compound represented by the above general formula I, which comprises reacting a compound represented by the above formula I with a lithium compound. The term suitable unsaturated hydrogenation platform described above refers to a hydrocarbon compound having one or two double bonds. The term organic group refers to an alkyl or aryl group, preferably an alkyl group such as a tert-butyl group. Accordingly, the reaction of a cycloalkyldiene having 6 to 8 carbon atoms with a compound represented by the formula III is a compound represented by the above formula I, wherein R 1 and R 2 are combined to form a carbon atom. It enables the production of compounds representing divalent saturated hydrocarbon groups having 6 to 8 atoms. Similarly, the alkyl group and / or cycloalkyl group on the boron atom of the compound of the formula I is obtained by reacting each of the corresponding alkene and / or cycloalkene with the compound of the formula III. . This means that the compound of the formula I wherein R 1 represents an alkyl group and R 2 represents a cycloalkyl group can be obtained by converting the compound of the formula III into a desired cycloalkyl group. Is obtained by reacting with an alkene having the same number of carbon atoms. Of course, R 1 and R 2 can represent the same group. Furthermore, the present invention is directed to a process for preparing a compound of the above general formula II. A method for producing a compound represented by the above general formula II, wherein X 1 has the above-mentioned meaning and X 2 represents a hydrogen atom, comprises a compound represented by the above general formula III. It is characterized by reacting with 1 mol of hydrogen halide represented by the formula HX 1 (wherein X 1 has the above-mentioned meaning). A method for producing a compound represented by the above general formula II, wherein X 1 has the above-mentioned meaning and X 2 represents a halogen atom, is a compound represented by the above general formula III the is characterized in that is reacted with hydrogen halide to 1 mole of the represented by hydrogen halide to 1 mole and formula HX 2 of the formula HX 1. Of course, X 1 and X 2 may represent the same halogen atom. The starting compound III is known and is prepared by hydroboration of 2-myrtenyl-1,3-dithiane with diborane or with a complex of diborane and a Lewis acid. (EP 61408). The compounds of the above formulas I and II can thus be prepared in optically active form starting from the optically active compound III. The compounds of the present invention are useful as asymmetric reducing agents. Furthermore, the invention is directed to the use of the compounds of formulas I and II above in asymmetric reduction. The compounds of the present invention are used for stereospecific reduction of a ketone or imine function. Stereospecific reduction of a ketone or imine comprises reacting the ketone or imine with an enantiomer of a compound of general formula I or II. The following examples are provided for the purpose of illustrating the invention and are not intended to limit the scope of the invention. Example 1 Preparation of (-)-Compound II (where X 1 = X 2 = Cl) 3 g (11 mmol) of (-)-Compound III was suspended in 60 ml of anhydrous ether in a 100 ml flask under a nitrogen atmosphere. The resulting suspension was then cooled to -610 ° C in a cooling bath and 5.6 ml (25 mmol) of 4.5N hydrogen chloride ether was added quickly. The cooling bath was removed, then the temperature was kept at -10 ° C for 2 hours 30 minutes. The title compound precipitates in the form of a white powder. The solvent was removed under reduced pressure. The overall yield was 83.7%, calculated based on 2-miltenyl-1,3-dithiamborane. The obtained white solid was dissolved in anhydrous tetrahydrofuran (20 ml) and used as it was for reduction. Example 2 37 g of (-)-Compound III was poured into 140 ml of anhydrous tetrahydrofuran. The temperature was brought to 0 ° C. and a solution of 20 ml of cyclooctadiene in 20 ml of tetrahydrofuran was added over 30 minutes. The reaction mixture was then heated under reflux overnight. After cooling the reaction mixture to -70 ± 5 ° C., 81 ml of a 1.7 M solution of t-butyllithium in pentane was added over 45 minutes. The reaction mixture was kept at -70 ± 5 ° C. for a further 2 hours, then the various solvents and excess cyclooctadiene were removed under reduced pressure at ambient temperature. The obtained residue was dissolved in 100 ml of MTBE. The solution was stirred at ambient temperature for 2 hours, then decanted at -20 ° C, and the liquid layer was separated. The white solid residue obtained was washed with 100 ml of heptane at ambient temperature and then immediately filtered off. Finally, after further washing with 100 ml of MTBE at ambient temperature, it was dried under reduced pressure to obtain 45.9 g of white crystals (86.4% yield). These crystals were kept at 4 ° C. under an argon atmosphere to protect them from light. Example 3 Use of the compound II obtained in Example 1 in the following reduction reaction Under a nitrogen atmosphere, 1 g (3.15 mmol) of compound 11 dissolved in 10 ml of anhydrous tetrahydrofuran was added to a solution of 113.7 g (11 mmol) of the (-)-compound obtained in Example 1 in 20 ml of anhydrous tetrahydrofuran. Added at 0 ° C. The resulting solution was stirred at 25 C for 48 hours. Then the solvent was removed under reduced pressure. The obtained residue was dissolved in 60 ml of ethyl ether, and 2.6 g (25 mmol) of diethanolamine was added. The insoluble matter was removed by filtration, and the obtained filtrate was concentrated to dryness. The obtained residue was Compound 2 ( 0.6 g), which had an enantiomeric composition of (+)-isomer 75% and (-)-isomer 25%. Example 4 Use of Compound I Obtained in Example 2 in Reduction Reaction of Compound 1 → Compound 2 10 g of Compound I obtained above was dissolved in 45 ml of anhydrous tetrahydrofuran under an inert atmosphere. The resulting reaction mixture was then held at a temperature of about -78 ° C. using thermostatically controlled, followed by addition of Compound 1 0.5 equivalent diluted in tetrahydrofuran 10ml for 30 minutes. The reaction was continued at about -78 ° C for 2 hours. Excess borohydride, compound I, was neutralized with alcohol. The obtained reaction mixture was dried under reduced pressure. The obtained residue was redissolved in 25 ml of ethyl ether, and the organic layer was washed with water until a neutral pH was reached. After the obtained organic layer was dehydrated using sodium sulfate, it was filtered and dried under reduced pressure to obtain 8.9 g of a mixture, which was separated by chromatography using a silica column. The enantiomer ratio of the obtained compound 2 was 96% for the (+)-isomer and 4% for the (-)-isomer. Example 5 Is a use in the reduction of the compound 1 → Compound 2 compounds) (+) - was dissolved in the preparation THF Compound 2 (1280 mls) (-) - a myrtle sulfonyl dithiane 214.2 g 9-borabicyclo [3,3, 1 ] Nonane (9-bora bicyclo [3,3,1] nonane). After dissolution, the resulting reaction mixture was heated under reflux overnight to complete the reaction, and then cooled to -80 ° C. Then tert-butyllithium was added within one hour while maintaining the temperature between -60 and -80C. Compound 1 (100 g) was then added slowly within less than 15 minutes. The resulting mixture was kept at -60 ° C for 2 hours. At this point, compound 1 was completely converted. After treatment as in the previous example, (+)-compound 2 was recrystallized from hexane (530 ml) to give compound 2 having a composition of (-)-form 98.2% / (+)-form 1.8%. g was obtained. b) Preparation of (-)- Compound 2 39.5 g of (+)-Compound III were dissolved in THF (240 ml). The resulting solution was cooled to 0 ° C. and added to a solution of 1,5-cyclooctadiene (15.9 g) dissolved in THF (45 · ml). The resulting solution was heated under reflux overnight and then treated as above with t-BuLi to reduce compound 1 (21 g) and after conventional treatment, (-)-compound 2 ( 10g-ee 100%).
───────────────────────────────────────────────────── フロントページの続き (81)指定国 ＥＰ(ＡＴ，ＢＥ，ＣＨ，ＤＥ， ＤＫ，ＥＳ，ＦＩ，ＦＲ，ＧＢ，ＧＲ，ＩＥ，ＩＴ，Ｌ Ｕ，ＭＣ，ＮＬ，ＰＴ，ＳＥ)，ＯＡ(ＢＦ，ＢＪ，ＣＦ ，ＣＧ，ＣＩ，ＣＭ，ＧＡ，ＧＮ，ＭＬ，ＭＲ，ＮＥ， ＳＮ，ＴＤ，ＴＧ)，ＡＰ(ＧＨ，ＫＥ，ＬＳ，ＭＷ，Ｓ Ｄ，ＳＺ，ＵＧ，ＺＷ)，ＥＡ(ＡＭ，ＡＺ，ＢＹ，ＫＧ ，ＫＺ，ＭＤ，ＲＵ，ＴＪ，ＴＭ)，ＡＬ，ＡＭ，ＡＴ ，ＡＵ，ＡＺ，ＢＡ，ＢＢ，ＢＧ，ＢＲ，ＢＹ，ＣＡ， ＣＨ，ＣＮ，ＣＵ，ＣＺ，ＤＥ，ＤＫ，ＥＥ，ＥＳ，Ｆ Ｉ，ＧＢ，ＧＥ，ＧＨ，ＨＵ，ＩＬ，ＩＳ，ＪＰ，ＫＥ ，ＫＧ，ＫＰ，ＫＲ，ＫＺ，ＬＣ，ＬＫ，ＬＲ，ＬＳ， ＬＴ，ＬＵ，ＬＶ，ＭＤ，ＭＧ，ＭＫ，ＭＮ，ＭＷ，Ｍ Ｘ，ＮＯ，ＮＺ，ＰＬ，ＰＴ，ＲＯ，ＲＵ，ＳＤ，ＳＥ ，ＳＧ，ＳＩ，ＳＫ，ＴＪ，ＴＭ，ＴＲ，ＴＴ，ＵＡ， ＵＧ，ＵＳ，ＵＺ，ＶＮ，ＹＵ (72)発明者 フオレ，ミシエル フランス国 エフ―84000 アヴィヨン, リュ ヌーヴ サン シヤルレ，３ (72)発明者 カマンカ，ジヤン―マルク フランス国 エフ―34090 モンペリエ, アヴニュ デュ シヤトー ドー，19────────────────────────────────────────────────── ─── Continuation of front page (81) Designated countries EP (AT, BE, CH, DE, DK, ES, FI, FR, GB, GR, IE, IT, L U, MC, NL, PT, SE), OA (BF, BJ, CF) , CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG), AP (GH, KE, LS, MW, S D, SZ, UG, ZW), EA (AM, AZ, BY, KG) , KZ, MD, RU, TJ, TM), AL, AM, AT , AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, F I, GB, GE, GH, HU, IL, IS, JP, KE , KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, M X, NO, NZ, PL, PT, RO, RU, SD, SE , SG, SI, SK, TJ, TM, TR, TT, UA, UG, US, UZ, VN, YU (72) Inventor Huore, Michel France-84000 Avillon, Ryu Neuve Saint-Cierre, 3 (72) Inventors Kamanka, Jean-Marc FR-34090 Montpellier, France, Avenue du Chateau d'Or, 19
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR96/07331 | 1996-06-13 | ||
| FR9607331A FR2749847B1 (en) | 1996-06-13 | 1996-06-13 | CHIRAL ORGANOBORANES |
| PCT/FR1997/001050 WO1997047628A1 (en) | 1996-06-13 | 1997-06-12 | Chiral organoboranes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000511922A true JP2000511922A (en) | 2000-09-12 |
Family
ID=9493012
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10501309A Pending JP2000511922A (en) | 1996-06-13 | 1997-06-12 | Chiral organoborane |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0918779A1 (en) |
| JP (1) | JP2000511922A (en) |
| AU (1) | AU714166B2 (en) |
| CA (1) | CA2257678A1 (en) |
| FR (1) | FR2749847B1 (en) |
| NO (1) | NO985832L (en) |
| NZ (1) | NZ333451A (en) |
| WO (1) | WO1997047628A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1144419B1 (en) * | 1999-01-19 | 2004-09-08 | Basf Ag | Synthesis of alkali metal substituted borohydride reagents |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA821644B (en) * | 1981-03-25 | 1983-01-26 | Expansia Sa | Borane complexes |
-
1996
- 1996-06-13 FR FR9607331A patent/FR2749847B1/en not_active Expired - Fee Related
-
1997
- 1997-06-12 CA CA 2257678 patent/CA2257678A1/en not_active Abandoned
- 1997-06-12 EP EP97928339A patent/EP0918779A1/en not_active Withdrawn
- 1997-06-12 WO PCT/FR1997/001050 patent/WO1997047628A1/en not_active Application Discontinuation
- 1997-06-12 AU AU32669/97A patent/AU714166B2/en not_active Ceased
- 1997-06-12 JP JP10501309A patent/JP2000511922A/en active Pending
- 1997-06-12 NZ NZ333451A patent/NZ333451A/en unknown
-
1998
- 1998-12-11 NO NO985832A patent/NO985832L/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0918779A1 (en) | 1999-06-02 |
| NZ333451A (en) | 1999-08-30 |
| FR2749847B1 (en) | 1998-11-06 |
| CA2257678A1 (en) | 1997-12-18 |
| WO1997047628A1 (en) | 1997-12-18 |
| NO985832D0 (en) | 1998-12-11 |
| AU714166B2 (en) | 1999-12-23 |
| FR2749847A1 (en) | 1997-12-19 |
| NO985832L (en) | 1998-12-14 |
| AU3266997A (en) | 1998-01-07 |
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