AU714166B2 - Chiral organoboranes - Google Patents
Chiral organoboranes Download PDFInfo
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- AU714166B2 AU714166B2 AU32669/97A AU3266997A AU714166B2 AU 714166 B2 AU714166 B2 AU 714166B2 AU 32669/97 A AU32669/97 A AU 32669/97A AU 3266997 A AU3266997 A AU 3266997A AU 714166 B2 AU714166 B2 AU 714166B2
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- 150000001875 compounds Chemical class 0.000 claims description 41
- -1 cycloalkyl radical Chemical class 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 12
- 230000009467 reduction Effects 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 6
- 239000012433 hydrogen halide Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 150000002576 ketones Chemical class 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 150000002466 imines Chemical class 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000000962 organic group Chemical group 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 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
- 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
- 150000002431 hydrogen Chemical class 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
- 150000002900 organolithium compounds Chemical class 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
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- IIVWHGMLFGNMOW-UHFFFAOYSA-N 2-methylpropane Chemical compound C[C](C)C IIVWHGMLFGNMOW-UHFFFAOYSA-N 0.000 claims 1
- 235000009917 Crataegus X brevipes Nutrition 0.000 claims 1
- 235000013204 Crataegus X haemacarpa Nutrition 0.000 claims 1
- 235000009685 Crataegus X maligna Nutrition 0.000 claims 1
- 235000009444 Crataegus X rubrocarnea Nutrition 0.000 claims 1
- 235000009486 Crataegus bullatus Nutrition 0.000 claims 1
- 235000017181 Crataegus chrysocarpa Nutrition 0.000 claims 1
- 235000009682 Crataegus limnophila Nutrition 0.000 claims 1
- 235000004423 Crataegus monogyna Nutrition 0.000 claims 1
- 240000000171 Crataegus monogyna Species 0.000 claims 1
- 235000002313 Crataegus paludosa Nutrition 0.000 claims 1
- 235000009840 Crataegus x incaedua Nutrition 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- NQOJWOIPQBVKKX-UHFFFAOYSA-N cyclooctane Chemical compound [CH]1CCCCCCC1 NQOJWOIPQBVKKX-UHFFFAOYSA-N 0.000 claims 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 229940125782 compound 2 Drugs 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 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 3
- 238000001914 filtration Methods 0.000 description 3
- 229910052740 iodine 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
- WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical compound C1CSCSC1 WQADWIOXOXRPLN-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-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
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-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 compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000001925 cycloalkenes Chemical class 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 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
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 1
- BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 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
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
-
- 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)
Description
Chiral oranoboranes The invention relates to chiral organoboranes, the processes for their preparation and their use in particular as an asymmetrical reducing agent.
Thus, a subject of the invention is the compounds of general formulae I and II 1 B- X RB/R1 LiI m"R 2 X 2
H
I II in which either R 1 and R 2 represent, independently, a hydrogen atom or an alkyl or cycloalkyl radical, or R 1 and R 2 represent together a saturated divalent hydrocarbon group; Xi represents a halogen atom; and
X
2 represents a hydrogen or halogen atom.
In the definitions indicated above, the expression halogen represents a fluorine, chlorine, bromine or iodine atom, preferably fluorine, chlorine and bromine. The expression alkyl preferably represents a linear or branched alkyl radical having 1 to 6 carbon atoms, and in particular an alkyl radical having 1 to 4 carbon atoms such as the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl radicals.
The saturated cycloalkyl radicals can be chosen from the radicals having 3 to 7 carbon atoms such as the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl radicals, optionally substituted by a lower alkyl group.
The expression saturated divalent hydrocarbon group contains 6 to 8 carbon atoms and can be represented by a group of bicyclo type or and preferably the type A subject of the invention is also a preparation process for the compounds of general formula I as defined above, characterized in that a compound of general formula III B H 2 is reacted with an appropriate unsaturated hydrogenated hydrogen compound in order to obtain a compound of formula IV in which R 1 and R 2 are as defined above, which product of formula IV is reacted with an organolithium compound of formula R'Li in which R' represents an organic group, in order to obtain the compound of formula I.
The expression an appropriate unsaturated hydrogenated hydrogen compound represents a hydrocarbon compound containing one or two double bond(s).
The expression organic group represents an alkyl or aryl radical, and preferably an alkyl radical such as tert-butyl.
Thus, the reaction of a cycloalkyldiene containing 6 to 8 carbon atoms with the compound of formula III, allows a compound of formula I to be obtained in which Ri M
M
and R 2 represent together a saturated divalent hydrocarbon group of 6 to 8 atoms respectively. Similarly, the obtaining of an alkyl and/or cycloalkyl radical on the boron atom of the compound of formula I, is achieved by reacting the corresponding alkene and/or cycloalkene respectively, with the compound of formula III. This means that a compound of formula I in which Ri represents an alkyl radical and R 2 a cycloalkyl radical is obtained by reacting the compound of formula III with an alkene having the same number of carbon atoms as the desired cycloalkyl radical. Of course, Ri and R 2 can represent the same radical.
A subject of the invention is also a preparation process for the compounds of general formula II as defined above. The preparation process for a compound of formula II in which Xi has the meaning indicated above and X 2 represents hydrogen, is characterized in that a compound of general formula III as defined above, is reacted with one mole of a hydrogen halide of formula HX 1 in which XI has the meaning indicated above. The preparation process for a compound of formula II in which X 1 has the meaning indicated above and X 2 represents a halogen, is characterized in that a compound of general formula III as defined above is reacted with one mole of a hydrogen halide HXI and with one mole of a hydrogen halide HX 2 Of course, Xi and X 2 can represent the same halogen atom.
The starting compound III is known, it can be prepared by the hydroboration of 2myrtenl 1,3-dithiane by diborane or by a complex of diborane with a Lewis acid (Patent EP 61408).
The compounds of formula I and II can thus be prepared in optically active form, starting from compound III in optically active form.
The compositions of the present invention are useful as an asymmetrical reducing agent.
A subject of the invention is also the use of the compounds of formulae I and II for asymmetrical reductions. Preferably, the compounds of the present invention are used for the stereospecific reduction of ketone or imine function(s). The stereospecfic reduction of a ketone or of an imine, consists in reacting the ketone or the imine with an enantiomer of a compound of general formula I or II.
The following examples are presented in order to illustrate the invention and should in no event be considered to limit the scope of the invention.
Example 1 Preparation of compound in which Xi X2 Cl 3 g (11 mmol) of compound is suspended in 60 ml of anhydrous ethyl ether in a 100 ml flask under nitrogen atmosphere. The suspension is then cooled down in a refrigerating bath to -60 0 C and 5.6 ml (25 mmol) of 4.5N hydrochloric ether is rapidly introduced. The bath is removed, then the temperature is maintained at -10 0 C for 2 hours 30 minutes. The product precipitates in the form of a white powder. The solvent is eliminated under vacuum. The overall yield is 83.7%, calculated on the basis of 2myrtenyl-1,3-dithiane borane.
The white solid is recovered in 20 ml of anhydrous tetrahydrofuran and used as it is in the reductions.
Example 2.
Preparation of a compound of formula I, in which B--R 1 represents B R2 37 g of compound is poured into 140 ml of anhydrous tetrahydrofuran. The temperature is taken to 0°C and 20 ml of cyclooctadiene in 20 ml of tetrahydrofuran is added over 30 minutes. The reaction mixture is then heated under reflux overnight. After cooling down to -70 5 0 C, 81 ml of a 1.7M solution of t-butyllithium in pentane is added over 45 minutes. The reaction mixture is maintained at 70 5 0 C for another two hours, then the different solvents as well as the excess cyclooctadiene are eliminated Sunder reduced pressure and at ambient temperature. The residue obtained is taken up in 100 ml of MTBE. After agitation for 2 hours at ambient temperature, then decanting at 0 C, the liquid phase is separated. The white solid residue is washed with 100 ml of heptane at ambient temperature which is then immediately eliminated by filtering. After a last additional washing at ambient temperature with 100 ml of MTBE and drying under reduced pressure, 45.9 g of white crystals is obtained (yield These crystals are kept at 4°C under argon and sheltered from light.
Example 3.
Use of compound II obtained in Example 1 for the reduction shown below: o o O ,H e °T~i1
TTY)
CH
3 Cl CH3 N S 1 g (3.15 mmol) of compound I solubilized in 10 ml of anhydrous tetrahydrofuran is added, at 0°C under nitrogen atmosphere, to a solution of 3.7 g (11 mmol) of compound as obtained in Example 1, solubilized in 20 ml of anhydrous tetrahydrofuran. The solution is agitated for 48 hours at 25 0 C. The solvent is then eliminated under reduced pressure. The residue is taken up in 60 ml of ethyl ether and 2.6 g (25 mmol) of diethanolamine is added. The insoluble part is removed by filtering and the filtrate is Sconcentrated to dryness.
The residue represents 0.6 g of compound 2 with an enantiomeric composition of Example 4 Use of compound I obtained in Example 2, for the reduction of I 2 as defined above.
g of compound I as obtained above is dissolved in 45 ml of anhydrous tetrahydrofuran Sunder an inert atmosphere. The reaction mixture is then held at a temperature of approximately -78 0 C using thermostat control, and 0.5 equivalent of compound I diluted in 10 ml of tetrahydrofuran is added over 30 minutes. The reaction is continued for 2 hours at approximately -78 0 C. The excess borohydride is neutralized with alcohol. The reaction mixture is dried under vacuum. The residue obtained is redissolved in 25 ml of ethyl ether and the organic phase is washed with water to a neutral pH. After dehydration with sodium sulphate, filtering and drying under vacuum, 8.9 g of a mixture is recovered which is separated by chromotography on a silica column. The ratio of the enantiomers of compound 2 is 96% Example Use of compound of formula I, in which B-RI represents B R2 prepared in situ for the reduction of 1>2 as defined above.
a) Preparation of compound 214.2 g myrtenyl dithiane dissolved in THF (1280 ml) is added to 9-bora bicyclco nonane. After dissolution, the reaction mixture is heated under reflux overnight, in order to complete the reaction, then cooled down to -80 0 C. Then tert butyl lithium is added over less than one hour, while maintaining the temperature between -60 and 800C.
Then, compound 1 )100 g) is added by portions over less than 15 minutes. The mixture is maintained for two hours at -60 0 C. At this precise moment compound 1 is entirely converted.
After treating as in the previous example, compound 2 is crystallized from hexane (530 ml), in order to produce 52.1 g with a composition 98.2% b) Preparation of compound 2 39.5 g of compound III is dissolved in THF (240 ml). The solution is cooled down to 0 C and incorporated in a solution of 1,5 cyclo octadien (15.9 g) in THF (45 ml).
-L
7 The resulting solution is heated at reflux overnight, then treated as above with tBuLi in order to reduce compound 1 (21 g) and produces, after usual treatment, compound 2 g ee 100%).
Claims (10)
1. The compounds of general formula I and II BeRIB-X B, R I Li I 'R2 x 2 H I II in which either RI and R 2 represent, independently, a hydrogen atom or an alkyl or cycloalkyl radical, or R, and R 2 represent together a.saturated divalent hydrocarbon group; X, represents a halogen atom; and X 2 represents a hydrogen or halogen atom.
2. The compounds of general formula I as defined in claim 1, characterized in that R, and R 2 independently, a hydrogen atom or a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-buytl, tert-butyl radical, or a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 20 cycloheptyl or cyclooctyl radical, optionally substituted by a lower alkyl group.
3. The compounds of general formula I as defined in claim 1 in which R, and R 2 represent together a saturated divalent hydrocarbon group containing 8 carbon atoms, and preferably a group such as B-RI B represents
4. The compounds of general formula II as defined in claim 1, in which X, and X 2 represent a halogen atom and preferably a chlorine atom. ii i; i i ii i Process for the preparation of the products of general formula I as defined in one of claims 1 to 2, characterized in that a compound of general formula I11 BH 2 is reacted with an appropriate unsaturated hydrogenated compound, in order to obtain a compound of formula IV B-RI Rz IV in which R, and R 2 are as defined above, which product of formula IV is reacted with an organolithium compound of formula R'Li 20 in which R' represents an organic group, in order to obtain the compound of formula I. C
6. Process for the preparation of the products of general formula 11 as defined in claim 1, in which X, has the meaning indicated in claim 1 and X 2 represents hydrogen, characterized in that a compound of general formula III as defined in claim 5 is reacted 25 with one mole of a hydrogen halide of formula HX, in which X, has the meaning indicated above. Co C*
7. Process for the preparation of the products of general formula II as defined in claim 1, in which Xi has the meaning indicated in claim 1 and X 2 represents a halogen, characterized in that a compound of general formula III as defined in claim 5 is reacted with one mole of a hydrogen halide of formula HXI in which X, has the meaning indicated above and one mole of a hydrogen halide of formula HX 2 in which X 2 has the meaning indicated above.
8. Use of the products of formula I or II as defined in any one of claims I to 4, as an asymmetrical reducing agent and in particular for the asymmetrical reduction of ketones or imines.
9. Use according to claim 8, in which the ketone is the compound of formula 1 CH 3 0 a. .0. .0a 0 a a a. a a. a Compounds according to claim 1 and as herein described with reference to the examples.
11. The process according to claim 5 and as herein described with reference to the examples.
12. The process according to claim 6 and as herein described with reference to the examples. DATED this 28th day of October 1999 SOCIETE D'EXPANSION SCIENTIFIQUE EXPANSIA WATERMARK PATENT TRADEMARK ATTORNEYS 290 BURWOOD ROAD HAWTHORN VICTORIA 3122 AUSTRALIA VAX DOC029 AU3266997: IAS/CLR/RES
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9607331A FR2749847B1 (en) | 1996-06-13 | 1996-06-13 | CHIRAL ORGANOBORANES |
| FR96/07331 | 1996-06-13 | ||
| PCT/FR1997/001050 WO1997047628A1 (en) | 1996-06-13 | 1997-06-12 | Chiral organoboranes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU3266997A AU3266997A (en) | 1998-01-07 |
| AU714166B2 true AU714166B2 (en) | 1999-12-23 |
Family
ID=9493012
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU32669/97A Ceased AU714166B2 (en) | 1996-06-13 | 1997-06-12 | Chiral organoboranes |
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 |
|---|---|---|---|---|
| AU2236499A (en) * | 1999-01-19 | 2000-08-07 | Mine Safety Appliances Company | 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 AU AU32669/97A patent/AU714166B2/en not_active Ceased
- 1997-06-12 EP EP97928339A patent/EP0918779A1/en not_active Withdrawn
- 1997-06-12 NZ NZ333451A patent/NZ333451A/en unknown
- 1997-06-12 CA CA 2257678 patent/CA2257678A1/en not_active Abandoned
- 1997-06-12 JP JP10501309A patent/JP2000511922A/en active Pending
- 1997-06-12 WO PCT/FR1997/001050 patent/WO1997047628A1/en not_active Application Discontinuation
-
1998
- 1998-12-11 NO NO985832A patent/NO985832L/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NZ333451A (en) | 1999-08-30 |
| AU3266997A (en) | 1998-01-07 |
| CA2257678A1 (en) | 1997-12-18 |
| WO1997047628A1 (en) | 1997-12-18 |
| FR2749847A1 (en) | 1997-12-19 |
| JP2000511922A (en) | 2000-09-12 |
| NO985832D0 (en) | 1998-12-11 |
| NO985832L (en) | 1998-12-14 |
| FR2749847B1 (en) | 1998-11-06 |
| EP0918779A1 (en) | 1999-06-02 |
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| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |