CN101250091B - Synthesis of polysubstitution 2-fluorin allyl alcohol compounds - Google Patents
Synthesis of polysubstitution 2-fluorin allyl alcohol compounds Download PDFInfo
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- CN101250091B CN101250091B CN2008100590840A CN200810059084A CN101250091B CN 101250091 B CN101250091 B CN 101250091B CN 2008100590840 A CN2008100590840 A CN 2008100590840A CN 200810059084 A CN200810059084 A CN 200810059084A CN 101250091 B CN101250091 B CN 101250091B
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- allyl alcohol
- alcohol compound
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- fluorine
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- 150000004808 allyl alcohols Chemical class 0.000 title abstract description 3
- 238000003786 synthesis reaction Methods 0.000 title description 2
- 230000015572 biosynthetic process Effects 0.000 title 1
- XXROGKLTLUQVRX-UHFFFAOYSA-N hydroxymethylethylene Natural products OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 21
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 17
- 239000011737 fluorine Substances 0.000 claims abstract description 17
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- -1 allyl alcohol compound Chemical class 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 30
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 11
- 150000001336 alkenes Chemical class 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 4
- QVCUKHQDEZNNOC-UHFFFAOYSA-N 1,2-diazabicyclo[2.2.2]octane Chemical compound C1CC2CCN1NC2 QVCUKHQDEZNNOC-UHFFFAOYSA-N 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000004334 fluoridation Methods 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 239000012141 concentrate Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 125000001424 substituent group Chemical group 0.000 abstract description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract 1
- 150000001361 allenes Chemical class 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000003682 fluorination reaction Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000012363 selectfluor Substances 0.000 description 14
- 239000007788 liquid Substances 0.000 description 12
- 239000000758 substrate Substances 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000003905 agrochemical Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- DYHZACXDGYGUBZ-UHFFFAOYSA-N CCCCC(=C=C)C1=CC=C(C)C=C1 Chemical compound CCCCC(=C=C)C1=CC=C(C)C=C1 DYHZACXDGYGUBZ-UHFFFAOYSA-N 0.000 description 1
- MCWBAEYMPNWDNS-UHFFFAOYSA-N CCCCC(=C=C)C1=CC=CC=C1C Chemical compound CCCCC(=C=C)C1=CC=CC=C1C MCWBAEYMPNWDNS-UHFFFAOYSA-N 0.000 description 1
- KCHYGHWBOOGWAZ-UHFFFAOYSA-N CCCCCCC(=C=C)C1=CC=CC=C1 Chemical compound CCCCCCC(=C=C)C1=CC=CC=C1 KCHYGHWBOOGWAZ-UHFFFAOYSA-N 0.000 description 1
- OGXMDFMCXMZVRV-UHFFFAOYSA-N CCCCCCC(=C=C)C1=CC=CC=C1C Chemical compound CCCCCCC(=C=C)C1=CC=CC=C1C OGXMDFMCXMZVRV-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- CXWIPHRBYYENRX-UHFFFAOYSA-N penta-1,2-dien-3-ylbenzene Chemical compound CCC(=C=C)C1=CC=CC=C1 CXWIPHRBYYENRX-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- DOKHEARVIDLSFF-UHFFFAOYSA-N prop-1-en-1-ol Chemical class CC=CO DOKHEARVIDLSFF-UHFFFAOYSA-N 0.000 description 1
- WEHMXWJFCCNXHJ-UHFFFAOYSA-N propa-1,2-dienylbenzene Chemical compound C=C=CC1=CC=CC=C1 WEHMXWJFCCNXHJ-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Abstract
The invention relates to a method for synthesizing polysubstituted 2-fluo allyl alcohol compound, which uses the high area and stereo selectivity hydroxyl fluorination reaction of allenes and electrophilic reagent containing fluorine to synthesize the 2-fluo allyl alcohol compound. The reactive style is represented as follows. The invention has simple operation and easily accessible materials and agents, the reaction has high area and stereo selectivity and can lead in multiple substituents, and the product is easily to be separated and purified. The invention is suitable for synthesizing various substituted 2-fluo allyl alcohol compounds.
Description
Technical field
The present invention relates to a kind of method of synthetic polysubstituted 2-fluorine allyl alcohol compound, i.e. regional the and synthetic alpha-functional group multi-substituted propenol method of Stereoselective by the hydroxyl fluoridation height of connection alkene.
Background technology
Multi-substituted allyl alcohol is one of most important intermediate in the organic synthesis, also is one of modal structural unit in the natural product, has multiple important physical activity, and at biological technical field, there is huge value of exploiting and utilizing aspects such as medicine and agricultural chemicals.And fluorochemical does not also have bibliographical information because its unique physiologically active has obtained using widely in fields such as medicine and agricultural chemicals and generate the method that replaces 2-fluorine allyl alcohol compound by single step reaction.Therefore can introduce a plurality of substituting group Synthetic 2s-fluorine vinyl carbinol a step and very quantum jump be arranged than reaction in the past.
Summary of the invention
Purpose of the present invention just provides a kind of effectively synthetic polysubstituted 2-fluorine allyl alcohol compound method.
The present invention is based on the high zone and the stereoselective hydroxyl fluoridation of connection alkene and fluorine-containing electrophilic reagent, Synthetic 2-fluorine allyl alcohol compound, reaction formula is as follows:
Productive rate: 37-88%
R can be the alkyl of H or different carbon chain length, and wherein alkyl is C
nH
2n+1, n=2-6 wherein, Ar can be phenyl or ortho position, a position, contraposition by the aryl that different substituents replaces, the steps include:
(1) at room temperature will join alkene 1 and join in acetonitrile and the water mixed solvent, stir adding 1-chloromethyl-4-fluoro-1 down, 4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) 2, reaction is 2-20 hour under the room temperature, adds water.
(2) use extracted with diethyl ether, anhydrous sodium sulfate drying filters, and concentrates, and rapid column chromatography obtains 2-fluorine allyl alcohol compound 3.
The volume ratio of acetonitrile and water is 10: 1 in the mixed solvent of the present invention.
Reaction raw materials 1-chloromethyl of the present invention-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) is 1.2～1.5: 1 with the mol ratio of connection alkene.
It is 10 milliliters that the α of 1 mmole of the present invention-Lian alkene needs the amount of solubilizing agent acetonitrile.
Present method is simple to operate, and raw material and reagent are easy to get, and reaction has the zone and the stereoselectivity of height, can introduce a plurality of substituting groups simultaneously, and the easily separated purifying of product is applicable to the 2-fluorine vinyl carbinol that synthesizes various replacements
The invention reside in the method that has developed a kind of convenient and practical synthetic polysubstituted 2-fluorine allyl alcohol compound.
The corresponding 2-fluorine allyl alcohol compound productive rate of the inventive method gained is 37-88%.
Embodiment
Following examples help to understand the present invention, but are not limited to content of the present invention.
Embodiment 1
Add 3-phenyl-1 in the reaction tubes, and the 2-heptadiene (86.0mg, 0.5mmol), 5.0mL acetonitrile (MeCN) and 0.5mL H
2The O dissolving, stir and add 212.4mg (0.60mmol) 1-chloromethyl-4-fluoro-1 down, 4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor), stir 2h react completely (tracking of TLC point plate) under the room temperature, adding the 10mL shrend goes out, extracted with diethyl ether three times (30+25 * 2mL), the saturated nacl aqueous solution washing, anhydrous sodium sulfate drying, concentrated solution, rapid column chromatography, petrol ether/ethyl acetate=20: 1, get product 64.8mg 3-phenyl-2-fluoro-1-teracrylic acid-alcohol, productive rate 62%, product are colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.50(d，J＝7.5Hz，2H)，7.39-7.23(m，3H)，4.81(dd，J＝7.8?&2.4Hz，1H)，4.70(dd，J＝24.0?&?3.0Hz，1H)，2.30(s，1H)，2.07-1.87(m，2H)，1.44-1.17(m，4H)，0.88(t，J＝6.9Hz，3H)；
13C?NMR(75MHz，CDCl
3)δ167.9(d，J＝259.7Hz)，142.7，128.2，127.6，125.5，90.4(d，J＝19.1Hz)，76.6(d，J＝28.3Hz)，38.6，25.4，22.9，14.0；
19F?NMR(288MHz，CDCl
3)δ-107.1；
IR(neat)v(cm
-1)3471，2958，2871，1670，1495，1447，1377，1233，1137；
MS(70eV，EI)m/z(％)：208(M
+，7.37)，151(100)；
HRMS?Calcd?for?C
13H
17OF(M
+)：208.1263，Found：208.1269。
Embodiment 2
Press embodiment 1 described method, different is that used substrate and reagent are: 1-phenyl-1,2-propadiene (58.0mg, 0.5mmol), 1-chloromethyl-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) (212.4mg, 0.60mmol), 5.0mL MeCN and 0.5mL H
2O gets product 28.2mg, and productive rate is 37%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.48-7.31(m，5H)，5.22(dd，J＝9.0?&?4.5Hz，1H)，4.82-4.58(m，2H)，2.31(d，J＝4.5Hz，1H)；
13C?NMR(75MHz，CDCl
3)δ165.5(d，J＝258.2Hz)，139.1，128.63，128.57，126.7，91.2(d，J＝17.1Hz)，72.4(d，J＝33.7Hz)；
19F?NMR(288MHz，CDCl
3)δ-1?08.5；
IR(neat)v(cm
-1)3376，1677，1495，1456，，1119，1048；
MS(70eV，EI)m/z(％)：152(M
+，64.47)，77(100)。
Embodiment 3
Press embodiment 1 described method, different is that used substrate and reagent are: 3-phenyl-1,2-pentadiene (72.0mg, 0.5mmol), 1-chloromethyl-4-fluoro-1,-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) (212.4mg, 0.60mmol), 5.0mL MeCN and 0.5mL H
2O gets product 56.8mg, and productive rate is 65%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.52-7.44(m，2H)，7.42-7.27(m，3H)，4.80(dd，J＝6.0?&?3.3Hz，1H)，4.68(dd，J＝26.7?&?3.3Hz，1H)，2.28(s，1H)，1.87-2.15(m，2H)，0.90(t，J＝7.2Hz，3H)；
13C?NMR(75MHz，CDCl
3)δ167.7(d，J＝259.7Hz)，142.4，128.2，127.6，125.5，90.59(d，J＝18.8Hz)，76.65，31.55，7.60；
19F?NMR(288MHz，CDCl
3)δ-107.2；
IR(neat)v(cm
-1)3473，2958，2931，2870，1670，1607，1464，1379，1234，1135；
MS(70eV，EI)m/z(％)：180(M
+，4.21)，73(100)；
HRMS?Calcd?for?C
11H
13OF(M
+)：180.0950，Found：180.0959。
Embodiment 4
Press embodiment 1 described method, different is that used substrate and reagent are: 3-phenyl-1,2-nonadiene (100.0mg, 0.5mmol), 1-chloromethyl-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) (212.4mg, 0.60mmol), 5.0mL MeCN and 0.5mL H
2O gets product 67.6mg, and productive rate is 57%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.50(d，J＝7.5Hz，2H)，7.24-7.39(m，3H)，4.81(dd，J＝7.8?&2.7Hz，1H)，4.70(dd，J＝24.3?&?2.7Hz，1H)，2.25(s，1H)，2.05-1.87(m，2H)，1.48-1.21(m，8H)，0.86(t，J＝6.3Hz，3H)；
13C?NMR(75MHz，CDCl
3)δ167.9(d，J＝259.7Hz)，142.7，128.2，127.6，125.5，90.4(d，J＝18.5Hz)，76.6(d，J＝28.4Hz)，38.8，31.7，29.4，23.2，22.6，14.0；
19F?NMR(288MHz，CDCl
3)δ-107.1；
IR(neat)v(cm
-1)3580，3472，3063，2928，2958，1670，1597，1486，1451，1376，12301182，1131，1068；
MS(70eV，EI)m/z(％)：236(M
+，2.70)，151(100)；
HRMS?Calcd?for?C
15H
21OF(M
+)：236.1576，Found：236.1566。
Embodiment 5
Press embodiment 1 described method, different is that used substrate and reagent are: 1,1-phenylbenzene-1,2-propadiene (57.6mg, 0.3mmol), 1-chloromethyl-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) (127.4mg, 0.36mmol), 3.0mL MeCN and 0.3mL H
2O gets product 33.5mg, and productive rate is 49%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.50-7.41(m，4H)，7.40-7.28(m，6H)，4.95(dd，J＝17.4?&?3.0Hz，1H)，4.49(dd，J＝18.9?&?3.0Hz，1H)，2.91(s，1H)；
13C?NMR(75MHz，CDCl
3)δ166.9(d，J＝261.3Hz)，142.7，128.2，128.0，127.4，94.2(d，J＝18.8Hz)，79.7(d，J＝27.7Hz)；
19F?NMR(288MHz，CDCl
3)δ-104.4；
IR(neat)v(cm
-1)3582，3459，3061，3030，1669，1597，1492，1449，1365，1335，1235，1168，1135，1031；
MS(70eV，EI)m/z(％)：228(M
+，8.49)，105(100)；
HRMS?Calcd?for?C
15H
13OF(M
+)：228.0950，Found：228.0950。
Embodiment 6
Press embodiment 1 described method, different is that used substrate and reagent are: aminomethyl phenyl between 3--1,2-heptadiene (93.0mg, 0.5mmol), 1-chloromethyl-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) (212.4mg, 0.60mmol), 5.0mL MeCN and 0.5mL H
2O gets product 81.8mg, and productive rate is 74%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.32-7.20(m，3H)，7.10(d，J＝6.9Hz，1H)，4.81(dd，J＝9.9?&2.7Hz，1H)，4.69(dd，J＝22.5?&?3.0Hz，1H)，2.36(s，3H)，2.24(s，1H)，2.09-1.87(m，2H)，1.44-1.16(m，4H)，0.88(t，J＝6.9Hz，3H)；
13C?NMR(75MHz，CDCl
3)δ168.0(d，J＝260.0Hz)，142.7，137.9，128.3，128.1，126.1，122.5，90.3(d，J＝18.9Hz)，76.6(d，J＝27.6Hz)，38.6，25.4，22.9，21.6，14.0；
19F?NMR(288MHz，CDCl
3)δ-107.0；
IR(neat)v(cm
-1)3473，3029，2958，2931，2870，1670，1607，1487，1464，1379，1234，1210，1135，1078，1057；
MS(70eV，EI)m/z(％)：222(M
+，3.97)，73(100)；
HRMS?Calcd?for?C
14H
19OF(M
+)：222.1420，Found：222.1421。
Embodiment 7
Press embodiment 1 described method, different is that used substrate and reagent are: aminomethyl phenyl between 3--1,2-nonadiene (107.1mg, 0.5mmol), 1-chloromethyl-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) (212.4mg, 0.60mmol), 5.0mL MeCN and 0.5mL H
2O gets product 88.2mg, and productive rate is 71%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.32-7.20(m，3H)，7.09(d，J＝7.2Hz，1H)，4.80(dd，J
1＝10.2Hz，J
2＝3.0Hz，1H)，4.69(dd，J
1＝22.2Hz，J
1＝3.0Hz，1H)，2.36(s，3H)，2.27(s，1H)，2.05-1.90(m，2H)，1.44-1.22(m，8H)，0.86(t，J＝6.0Hz，3H)；
13C?NMR(75MHz，CDCl
3)δ168.0(d，J＝260.0Hz)，142.7，137.8，128.3，128.1，126.1，122.5，90.3(d，J＝18.8Hz)，76.6(d，J＝28.8Hz)，38.8，31.7，29.5，23.2，22.6，21.6，14.0；
19F?NMR(282MHz，CDCl
3)δ-106.9；
IR(neat)v(cm
-1)3473，3029，2958，2931，2870，1670，1607，1487，1464，1379，1341，1234，1210，1135，1078，1?057；
MS(70eV，EI)m/z(％)：250(M
+，6.23)，165(100)；
Elemental?analysis：Calcd?for?C
16H
23FO：C，76.76，H，9.26；Found：C，76.89，H，9.05。
Embodiment 8
Press embodiment 1 described method, different is that used substrate and reagent are: 3-m-trifluoromethylphenyl-1,2-heptadiene (120.0mg, 0.5mmol), 1-chloromethyl-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) (212.4mg, 0.60mmol), 5.0mL MeCN and 0.5mL H
2O gets product 54.8mg, and productive rate is 40%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.80(s，1H)，7.69(d，J＝7.8Hz，1H)，7.56(d，J＝7.5Hz，1H)，7.48(t，J＝7.8Hz，1H)，4.85(dd，J＝6.6?&?3.3Hz，1H)，4.74(dd，J＝25.8?&?3.3Hz，1H)，2.30(s，1H)，1.87-2.18(m，2H)，1.26-1.44(m，3H)，1.10-1.26(m，1H)，0.89(t，J＝6.9Hz，3H)；
13C?NMR(75MHz，CDCl
3)δ167.2(d，J＝260.4Hz)，143.9，130.7(q，J＝31.6Hz)，129.0，128.7，125.9，124.5(q，J＝4.1Hz)，122.4(q，J＝4.7Hz)，90.9(d，J＝18.6Hz)，76.2，38.8，25.2(d，J＝8.6Hz)，22.8，13.8(d，J＝9.6Hz)；
19F?NMR(288MHz，CDCl
3)δ-62.6，-107.6；
IR(neat)v(cm
-1)3475，2961，1672，1442，1330，1167，1129，1076；
MS(70eV，EI)m/z(％)：277(M
++H，90.0)，237(100)；
HRMS?Calcd?for?C
14H
16OF
4(M
+)：276.1137，Found：276.1134。
Embodiment 9
Press embodiment 1 described method, different is that used substrate and reagent are: 3-p-methylphenyl-1,2-heptadiene (93.5mg, 0.5mmol), 1-chloromethyl-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) (212.4mg, 0.60mmol), 5.0mL MeCN and 0.5mL H
2O gets product 98.7mg, and productive rate is 88%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.42(d，J＝8.1Hz，2H)，7.20(d，J＝8.1Hz，2H)，4.83(dd，J＝10.5?&?3.3Hz，1H)，4.69(dd，J＝21.9?&?3.3Hz，1H)，2.37(s，3H)，2.29(s，1H)，2.25-1.89(m，2H)，1.48-1.17(m，4H)，0.92(t，J＝7.2Hz，3H)；
13C?NMR(75MHz，CDCl
3)δ167.6(d，J＝260.0Hz)，139.8，137.3，128.9，125.4，90.2(d，J＝18.5Hz)，76.5(d，J＝28.7Hz)，38.5，25.4，22.9，21.0，13.9；
19F?NMR(288MHz，CDCl
3)δ-107.1；
IR(neat)v(cm
-1)3477，2958，1670，1464，1380，1235，1115；
MS(70eV，EI)m/z(％)：222(M
+，3.87)，165(100)；
HRMS?Calcd?for?C
14H
19OF(M
+)：222.1420，Found：222.1424。
Embodiment 10
Press embodiment 1 described method, different is that used substrate and reagent are: 3-is to fluorophenyl-1,2-nonadiene (109.0mg, 0.5mmol), 1-chloromethyl-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) (212.4mg, 0.60mmol), 5.0mL MeCN and 0.5mL H
2O gets product 98.5mg, and productive rate is 78%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.48(dd，J＝8.7?&?5.7Hz，2H)，7.04(t，J＝8.7Hz，2H)，4.81(dd，J＝6.9?&?3.3Hz，1H)，4.70(dd，J＝25.8?&?3.3Hz，1H)，2.26(s，1H)，2.11-1.85(m，2H)，1.48-1.17(m，8H)，0.87(t，J＝6.6Hz，3H)；
13C?NMR(75MHz，CDCl
3)δ167.8(d，J＝260.1Hz)，162.2(d，J＝244.6Hz)，138.5(d，J＝2.8Hz)，127.4(d，J＝8.0Hz)，115.0(d，J＝20.6Hz)，90.5(d，J＝18.9Hz)，76.3(d，J＝28.3Hz)，39.0，31.7，29.4，23.2，22.5，14.0；
19F?NMR(288MHz，CDCl
3)δ-107.3，-115.2；
IR(neat)v(cm
-1)3473，2967，1671，1509，1233，1162；
MS(70eV，EI)m/z(％)：254(M
+，2.03)，169(100)；
HRMS?Calcd?for?C
15H
20OF
2(M
+)：254.1482，Found：254.1483。
Embodiment 11
Press embodiment 1 described method, different is that used substrate and reagent are: 3-o-methyl-phenyl--1,2-heptadiene (93.1mg, 0.5mmol), 1-chloromethyl-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) (212.4mg, 0.60mmol), 5.0mL MeCN and 0.5mL H
2O gets product 49.8mg, and productive rate is 45%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.55-7.47(m，1H)，7.24-7.13(m，3H)，4.81(dd，J＝18.0?&?3.3Hz，1H)，4.66(dd，J＝20.4?&?3.3Hz，1H)，2.50(s，3H)，2.23(s，1H)，2.21-2.00(m，2H)，1.46-1.10(m，4H)，0.90(t，J＝7.2Hz，3H)；
13C?NMR(75MHz，CDCl
3)δ168.0(d，J＝260.0Hz)，139.4，136.4，132.5，127.7，127.0，125.6，91.1(d，J＝19.4Hz)，77.5(d，J＝28.2Hz)，37.3，25.6，22.9，21.6，14.0；
19F?NMR(288MHz，CDCl
3)δ-106.6；
IR(neat)v(cm
-1)3477，2959，1669，1458，1234，1124；
MS(70eV，EI)m/z(％)：222(M
+，2.19)，165(100)；
HRMS?Calcd?for?C
14H
19OF(M
+)：222.1420，Found：222.1415。
Embodiment 12
Press embodiment 1 described method, different is that used substrate and reagent are: 3-o-methyl-phenyl--1,2-nonadiene (106.8mg, 0.5mmol), 1-chloromethyl-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate (Selectfluor) (212.4mg, 0.60mmol), 5.0mL MeCN and 0.5mL H
2O gets product 49.9mg, and productive rate is 40%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.53-7.46(m，1H)，7.24-7.12(m，3H)，4.80(dd，J
1＝18.3Hz，J
2＝3.0Hz，1H)，4.65(dd，J
1＝20.4Hz，J
2＝3.0Hz，1H)，2.49(s，3H)，2.22(s，1H)，2.19-1.99(m，2H)，1.45-1.12(m，8H)，0.86(t，J＝6.3Hz，3H)；
13C?NMR(75MHz，CDCl
3)δ167.4(d，J＝260.3Hz)，139.4，136.4，132.5，127.7，127.0，125.6，91.0(d，J＝18.8Hz)，77.5(d，J＝39.8Hz)，37.6，31.7，29.5，23.4，22.6，21.6，14.0；
19F?NMR(282MHz，CDCl
3)δ-106.5；
IR(neat)v(cm
-1)3471，2930，2857，1669，1459，1374，1233，1125；
MS(70eV，EI)m/z(％)：250(M
+，3.92)，165(100)；
Elemental?analysis：Calcd?for?C
16H
23FO：C，76.76，H，9.26；Found：C，76.95，H，9.01。
Claims (2)
1. the method for a synthetic polysubstituted 2-fluorine allyl alcohol compound, by the hydroxyl fluoridation of connection alkene and fluorine-containing electrophilic reagent, Synthetic 2-fluorine allyl alcohol compound, reaction formula is as follows:
R is C
4H
9, Ar is o-methyl-phenyl-, an aminomethyl phenyl, p-methylphenyl or m-trifluoromethylphenyl; R is C
6H
13, Ar is o-methyl-phenyl-, an aminomethyl phenyl or to fluorophenyl, reactions steps is:
1), at room temperature will joining alkene 1, to join volume ratio be in 10: 1 the acetonitrile and water mixed solvent, stir and add 1-chloromethyl-4-fluoro-1 down, 4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate 2, described 1-chloromethyl-4-fluoro-1,4-diaza-bicyclo [2.2.2] octane a tetrafluoro borate is 1.2～1.5: 1 with the mol ratio of connection alkene, reaction is 2-20 hour under the room temperature, adds water;
2), use extracted with diethyl ether, anhydrous sodium sulfate drying filters, concentrate, rapid column chromatography, 2-fluorine allyl alcohol compound 3.
2. according to the method for the described synthetic polysubstituted 2-fluorine allyl alcohol compound of claim 1, it is characterized in that: it is 10 milliliters that the connection alkene of described 1 mmole needs the amount of solubilizing agent acetonitrile.
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Non-Patent Citations (5)
| Title |
|---|
| G. Sankar Lal.Site-Selective Fluorination of Organic Compounds Using 1-Alkyl-4-fluoro-1, 4-diazabicyclo[2.2.2]octane Salts(SelectfluorReagents).《Journal of Organic Chemistry》.1993,第58卷(第10期),表II、第2795页左栏倒数第17行-右栏第20行. * |
| Gaj Stavber et al..Selective and Effective Fluorination of Organic Compounds inWater Using Selectfluor F-TEDA-BF4.《Organic Letters》.2004,第6卷(第26期),4973-4976. * |
| M Carmen Pacheco et al..Electrophilic Fluorodesilylation of Allenylmethylsilanes:ANovelEntry to 2-Fluoro-1, 3-dienes.《Organic Letters》.2005,第7卷(第7期),1267-1270. * |
| MCarmenPachecoetal..ElectrophilicFluorodesilylationofAllenylmethylsilanes:ANovelEntryto2-Fluoro-1 3-dienes.《Organic Letters》.2005 |
| Shengming Ma.Some Typical Advances in the Synthetic Applications ofAllenes.《Chemical Reviews》.2005,第105卷(第7期),2829-2871. * |
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