FUNCTIONALIZED FLUOROALKYL SILANE, AND SYNTHETIC METHOD THEREFOR AND APPLICATION THEREOF
20230257402 · 2023-08-17
Assignee
Inventors
Cpc classification
C07D215/12
CHEMISTRY; METALLURGY
Y02P20/55
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
C07F7/081
CHEMISTRY; METALLURGY
C07F7/18
CHEMISTRY; METALLURGY
C07C33/18
CHEMISTRY; METALLURGY
C07F7/14
CHEMISTRY; METALLURGY
C07D453/04
CHEMISTRY; METALLURGY
International classification
C07F7/18
CHEMISTRY; METALLURGY
C07D453/04
CHEMISTRY; METALLURGY
C07C33/18
CHEMISTRY; METALLURGY
Abstract
Disclosed in the present invention are a functionalized fluoroalkyl silane compound and a synthetic method therefor. The method comprises: dissolving a halosilane and a fluoroalkyl source in an organic solvent; and synthesizing functionalized fluoroalkyl silane under the effect of an alkali or a tertiary phosphine compound. The functionalized fluoroalkyl silane can not only be used for constructing a series of high added-value compounds such as fluoroalkyl substituted alcohols, ketones and amines that can be constructed by conventional TMSR.sub.f, but also can transfer, by means of appropriate conversion, a functional group on a silicon protecting group to the obtained addition product in an addition reaction, for synthesizing some fluorine-containing compounds that cannot be synthesized by using a conventional TMSR.sub.f reagent, thereby greatly improving the synthesis efficiency and the atom economy of reactions. Also disclosed in the present invention are more excellent reaction efficiency and enantioselectivity, compared with conventional TMSCF.sub.3, exhibited by trifluoromethyl chloromethylsilane in synthesis of a 2-trifluoromethylquinoline compound and in an asymmetric trifluoromethylation reaction with α,β-unsaturated ketones.
Claims
1. A functionalized fluoroalkyl silane compound, wherein, the structure of the compound is shown in formula (1): ##STR00030## Wherein, FG is halogen, OMs, OTs, NO.sub.2, CF.sub.3, CN, CO.sub.2R, CONR.sub.2, —CH═CR.sub.2, —C≡CR, wherein, R is H, C.sub.1-10 alkyl, C.sub.1-15 aromatic ring, thiophene, furan, pyrrole, pyridine; R.sub.f is a C.sub.1-10 alkyl group containing fluorine atoms; R.sup.1 is C.sub.1-10 alkyl, aryl, the aryl is the electron donating group substituted benzene ring, the electron withdrawing group substituted benzene ring, naphthyl, thiophene, furan, pyrrole, pyridine, ester group; wherein, the electron donating group includes C.sub.1-10 alkyl, C.sub.1-10 alkoxy, the electron withdrawing group includes trifluoromethyl, ester group, nitro, cyano, halogen; n=1-10.
2. The functionalized fluoroalkyl silane compound according to claim 1, wherein, FG is F, Cl, Br, I, OMs, OTs, NO.sub.2, CF.sub.3, CN, CO.sub.2R, CONR.sub.2, —CH═CR.sub.2, —C≡CR, wherein, the R is H, C.sub.1-10 alkyl, C.sub.1-15 aromatic ring, thiophene, furan, pyrrole, pyridine; R.sub.f is CF.sub.3, CF.sub.2H, CFH.sub.2, C.sub.2F.sub.5, CF.sub.2CF.sub.2H, CF.sub.2CF.sub.2Cl, CF.sub.2CF.sub.2Br, CF.sub.2CH.sub.3, C.sub.3F.sub.7, CF.sub.2CF.sub.2CF.sub.2H, CF.sub.2CF.sub.2CH.sub.3, CF.sub.2CH.sub.2CH.sub.3, C.sub.4F.sub.9, CF.sub.2CF.sub.2CF.sub.2CF.sub.2H, CF.sub.2CF.sub.2CF.sub.2CH.sub.3, CF.sub.2CF.sub.2CH.sub.2CH.sub.3, CF.sub.2CH.sub.2CH.sub.2CH.sub.3; R.sup.1 is C.sub.1-10 alkyl, electron donating group substituted benzene ring, electron withdrawing group substituted benzene ring, naphthyl, thiophene, furan, pyrrole, pyridine, ester group; wherein, the electron donating group includes methyl, methoxy, the electron withdrawing group includes trifluoromethyl, ester group, nitro, cyano, fluorine, chlorine, bromine, iodine; n=1-10.
3. A synthesis method of functionalized fluoroalkyl silane compound, wherein, the fluoroalkyl source R.sub.fX reacts with halosilane compound in solvent under the effect of alkali or tertiary phosphine compound PR.sup.2.sub.3 to obtain functionalized fluoroalkyl silane compound; the reaction scheme is shown in formula (I): ##STR00031## Wherein, FG is halogen, OMs, OTs, NO.sub.2, CF.sub.3, CN, CO.sub.2R, CONR.sub.2, —CH═CR.sub.2, —C≡CR, R is H, C.sub.1-10 alkyl, C.sub.1-15 aromatic ring, thiophene, furan, pyrrole, pyridine; R.sub.f is a C.sub.1-10 alkyl group containing fluorine atoms; R.sup.1 is C.sub.1-10 alkyl, aryl, the aryl is the electron donating group substituted benzene ring, the electron withdrawing group substituted benzene ring, naphthyl, thiophene, furan, pyrrole, pyridine, ester group; wherein, the electron donating group includes C.sub.1-10 alkyl, C.sub.1-10 alkoxy, the electron withdrawing group includes trifluoromethyl, ester group, nitro, cyano, halogen; Y is halogen, OTf; n=1-10; X is H, halogen.
4. The method according to claim 3, wherein, FG is F, Cl, Br, I, OMs, OTs, NO.sub.2, CF.sub.3, CN, CO.sub.2R, CONR.sub.2, —CH═CR.sub.2, —C≡CR, wherein, the R is H, C.sub.1-10 alkyl, C.sub.1-15 aromatic ring, thiophene, furan, pyrrole, pyridine; R.sub.f is CF.sub.3, CF.sub.2H, CFH.sub.2, C.sub.2F.sub.5, CF.sub.2CF.sub.2H, CF.sub.2CF.sub.2Cl, CF.sub.2CF.sub.2Br, CF.sub.2CH.sub.3, C.sub.3F.sub.7, CF.sub.2CF.sub.2CF.sub.2H, CF.sub.2CF.sub.2CH.sub.3, CF.sub.2CH.sub.2CH.sub.3, C.sub.4F.sub.9, CF.sub.2CF.sub.2CF.sub.2CF.sub.2H, CF.sub.2CF.sub.2CF.sub.2CH.sub.3, CF.sub.2CF.sub.2CH.sub.2CH.sub.3, CF.sub.2CH.sub.2CH.sub.2CH.sub.3; R.sup.1 is C.sub.1-10 alkyl, electron donating group substituted benzene ring, electron withdrawing group substituted benzene ring, naphthyl, thiophene, furan, pyrrole, pyridine, ester group; wherein, the electron donating group includes methyl, methoxy, the electron withdrawing group includes trifluoromethyl, ester group, nitro, cyano, fluorine, chlorine, bromine, iodine; Y is Cl, Br, I, OTf; n=1-10; X is H, Br, I.
5. The method according to claim 3, wherein, the alkali is one or more of the following: lithium bis(trimethylsilyl) amide LiHMDS, potassium bis(trimethyl silyl) amide KHMDS, sodium bis(trimethylsilyl) amide NaHMDS, sodium amide NaNH.sub.2, sodium hydride NaH; and/or, R.sup.2 is C.sub.1-10 alkyl group, C.sub.1-10 alkoxy group, C.sub.1-10 alkylamine group, aryl, and the aryl is electron donating group substituted benzene ring, electron withdrawing group substituted benzene ring, naphthyl, thiophene, furan, pyrrole, pyridine, ester group; wherein, the electron donating group includes C.sub.1-10 alkyl group, C.sub.1-10 alkoxy group, the electron withdrawing group includes trifluoromethyl, ester group, nitro, cyano, halogen.
6. The method according to claim 3, wherein, the reaction temperature is −78˜100° C.; and/or the reaction time is 2˜36 hours.
7. The method according to claim 3, wherein, the molar ratio of the fluoroalkyl source R.sub.fX, the halosilane compound, the alkali or the tertiary phosphine compound PR.sup.2.sub.3 is R.sub.fX: halosilane compound: alkali or tertiary phosphine compound PR.sup.2.sub.3=(1-20):(1-3):(1-3).
8. The method according to claim 3, wherein, the solvent is any one or more of the following: benzonitrile, phenylacetonitrile, acetonitrile, dichloromethane, toluene, tetrahydrofuran THF, diethyl ether, dimethylformamide DMF, dimethylacetamide, dimethyl sulfoxide DMSO, N-methylpyrrolidone NMP, hexamethylphosphoric triamide HMPA.
9. The functionalized fluoroalkyl silane compound synthesized by the method according to claim 3.
10. The application of the functionalized fluoroalkyl silane compound according to claim 1 in silylation reaction and functional group transfer reaction.
11. The functionalized fluoroalkyl silane compound synthesized by the method according to claim 4.
12. The functionalized fluoroalkyl silane compound synthesized by the method according to claim 5.
13. The functionalized fluoroalkyl silane compound synthesized by the method according to claim 6.
14. The functionalized fluoroalkyl silane compound synthesized by the method according to claim 7.
15. The functionalized fluoroalkyl silane compound synthesized by the method according to claim 8.
16. The application of the functionalized fluoroalkyl silane compound according to claim 2 in silylation reaction and functional group transfer reaction.
17. The application of the functionalized fluoroalkyl silane compound according to claim 9 in silylation reaction and functional group transfer reaction.
Description
EXAMPLES
Synthesis of Functionalized Fluoroalkyl Silane Compounds
1) Conversion from Compound 1aa-1ad to Compound 2a
[0054] ##STR00005##
[0055] General operation procedure 1: CF.sub.3X (150-300 mmol) was condensated into a dry 250 mL three-necked flask at −78° C., and the organic solvent (80 mL), freshly distilled of halosilane 1aa-1ad (50-300 mmol) and tertiary phosphine (PR.sup.2.sub.3) (50-300 mmol) were slowly added to the reaction flask at this temperature; the resulting mixed solution was slowly raised to the temperature shown in Table 1 and stirred for reaction. The reaction process was monitored by .sup.1H NMR. After the raw materials 1aa-1ad were consumed, 2a as shown in Formula (III) was obtained by distillation under reduced pressure.
[0056] The specific experimental operations of Examples 1-15 are shown in general operation procedure 1, and the specific reaction condition and yield of each example are shown in Table 1.
TABLE-US-00001 TABLE 1 Specific reaction conditions and yields of specific Examples 1-15 1 (X) (mmol)/CF.sub.3X (mmoL)/PR.sup.2.sub.3 Temperature Time Yield Example (mmol) Solvent (° C.) (h) (%) 1 1aa Cl (150)/CF.sub.3Br (300)/P(NEt.sub.2).sub.3 PhCN −30° C. 12 78 (150) 2 1aa Cl (100)/CF.sub.3Br (200)/P(NEt.sub.2).sub.3 PhCN −50° C. 12 75 (100) 3 1aa Cl (100)/CF.sub.3Br (150)/P(NEt.sub.2).sub.3 (80) PhCN −60° C. 12 56 4 1aa Cl (150)/CF.sub.3Br (300)/P(OEt.sub.2).sub.3 Toluene −78° C. 12 42 (150) 5 1aa Cl (150)/CF.sub.3Br (300)/P(OMe).sub.3 THF −78° C. 12 46 (150) 6 1aa Cl (150)/CF.sub.3Br (300)/P(C.sub.3H.sub.7).sub.3 PhCN −78° C. 6 36 (150) 7 1aa Cl (150)/CF.sub.3Br (300)/P(C.sub.2H.sub.5).sub.3 PhCN −60° C. 12 34 (150) 8 1aa Cl (100)/CF.sub.3I (200)/P(NEt.sub.2).sub.3 (100) PhCN −78° C. 12 60 9 1aa Cl (100)/CF.sub.3I (200)/P(NEt.sub.2).sub.3 (100) PhCN −50° C. 12 63 10 1aa Cl (100)/CF.sub.3I (200)/P(NEt.sub.2).sub.3 (100) PhCN −50° C. 6 59 11 1aa Cl (100)/CF.sub.3Br (200)/P(NMe.sub.2).sub.3 PhCN −78° C. 12 40 (100) 12 1aa Cl (150)/CF.sub.3Br (300)/P(NMe.sub.2).sub.3 PhCN −78° C. 12 35 (150) 13 1ab Br (150)/CF.sub.3Br (300)/P(NEt.sub.2).sub.3 PhCN −78° C. 12 54 (150) 14 1ac I (150)/CF.sub.3Br (300)/P(NEt.sub.2).sub.3 (150) PhCN −78° C. 12 45 15 1ad I (150)/CF.sub.3Br (300)/P(NEt.sub.2).sub.3 (150) PhCN −50° C. 8 53
The NMR characterization data for compound 2a are as follows:
##STR00006##
[0057] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 2.97 (s, 2H), 0.42 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 130.4 (q, J=319 Hz), 25.3, −7.8; .sup.19F NMR (376 MHz, CDCl.sub.3): δ −64.31 (s, 3F).
2) Conversion from Compound 1b-1c to Compound 2b-2e
##STR00007##
[0058] General operation procedure 2: CF.sub.3Br (300 mmol) was condensated into a dry 250 mL three-necked flask at −78° C., and the organic solvent (80 mL), freshly distilled of halosilane 1b-1e (150 mmol) and PR.sup.2.sub.3 (150 mmol) were slowly added to the reaction flask at this temperature: the resulting mixed solution was slowly raised to the temperature shown in Table 2 and stirred for reaction. The reaction process was monitored by .sup.1H NMR. After the raw materials 1b-1e were consumed, 2b-2e as shown in Formula (IV) were obtained by distillation under reduced pressure.
[0059] The specific experimental operations of Examples 16-34 are shown in general operation procedure 2, and the specific reaction condition and yield of each example are shown in Table 2.
TABLE-US-00002 TABLE 2 Specific reaction conditions and yields of specific Examples 16-34 Temperature Time Product/Yield Example 1b-1e PR.sup.2.sub.3 Solvent (° C.) (h) (%) 16
The NMR characterization data for compound 2b-2e are as follows:
##STR00012##
[0060] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 2.75 (s, 2H), 0.39 (s, 6H): .sup.13C NMR (100 MHz, CDCl.sub.3): δ 130.8 (q, J=315 Hz), 27.0, −6.4; .sup.19F NMR (376 MHz, CDCl.sub.3): δ −64.73 (s, 3F).
##STR00013##
[0061] .sup.1H NMR (400 MHz, CDCl.sub.3): 5.72 (m, 1H), 5.03-5.10 (m, 2H), 1.67 (d, J=8.0 Hz, 2H), 0.28 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 135.2, 132.1 (q, J=311 Hz), 119.4, 11.2, −5.6; .sup.19F NMR (376 MHz, CDCl.sub.3): δ −65.56 (s, 3F).
##STR00014##
[0062] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 3.85 (t, J=8.0 Hz, 2H), 1.49-1.63 (m, 2H), 1.17 (t, J=8.0 Hz, 2H), 0.43 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 132.0 (q, J=322 Hz), 47.2, 27.6, 1.4, −5.4; .sup.19F NMR (376 MHz, CDCl.sub.3): δ −66.78 (s, 3F).
##STR00015##
[0063] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 5.28 (s, 1H), 0.59 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 141.3 (q, J=325 Hz), 31.2, −3.5; .sup.19F NMR (376 MHz, CDCl.sub.3): δ −62.54 (s, 3F).
3) Conversion from Compound 1Aa to Compound 2f-2i
##STR00016##
[0064] General operation procedure 3: R.sub.fBr (300 mmol) was condensated into a dry 250 mL three-necked flask at −78° C., and the organic solvent (80 mL), freshly distilled of halosilane 1aa (150 mmol) and PR.sup.2.sub.3 (150 mmol) were slowly added to the reaction flask at this temperature; the resulting mixed solution was slowly raised to the temperature shown in Table 3 and stirred for reaction. The reaction process was monitored by .sup.1H NMR. After the raw material 1aa was consumed, 2f-2i as shown in Formula (V) were obtained by distillation under reduced pressure.
[0065] The specific experimental operations of Examples 35-45 are shown in general operation procedure 3, and the specific reaction condition and yield of each example are shown in Table 3.
TABLE-US-00003 TABLE 3 Specific reaction conditions and yields of specific Examples 35-45 Prod- Temper- uct/ Exam- ature Time Yield ple R.sub.fBr PR.sup.2.sub.3 Solvent (° C.) (h) (%) 35 BrCF.sub.2H P(NEt.sub.2).sub.3 PhCN −50 8 2f/68 36 BrCF.sub.2H P(OEt.sub.2).sub.3 Et.sub.2O −100 8 2f/43 37 BrCF.sub.2H P(C.sub.2H.sub.5).sub.3 MeCN −78 10 2f/44 38 BrCF.sub.2CF.sub.3 P(NEt.sub.2).sub.3 PhCN −50 13 2g/70 39 BrCF.sub.2CF.sub.3 P(OEt.sub.2).sub.3 Et.sub.2O −78 12 2g/67 40 BrCF.sub.2CF.sub.3 P(C.sub.2H.sub.5).sub.3 THF −78 12 2g/43 41 BrCF.sub.2CF.sub.2CF.sub.3 P(NEt.sub.2).sub.3 PhCN −50 5 2h/45 42 BrCF.sub.2CF.sub.2CF.sub.3 P(OEt.sub.2).sub.3 Et.sub.2O −50 12 2h/56 43 BrCF.sub.2CF.sub.2CF.sub.3 P(C.sub.2H.sub.5).sub.3 THF −78 12 2h/59 44 BrCF.sub.2CF.sub.2H P(NEt.sub.2).sub.3 PhCN −50 7 2i/43 45 BrCF.sub.2CF.sub.2H P(OEt.sub.2).sub.3 Et.sub.2O −78 10 2i/39
The NMR characterization data for compound 2f-2i are as follows:
##STR00017##
[0066] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 5.27 (t, J=58.5 Hz, 1H), 2.89 (s, 2H), 0.35 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 110.4 (t, J=285 Hz), 20.4, −5.3; .sup.19F NMR (376 MHz, CDCl.sub.3): δ −140.33 (s, 2F).
##STR00018##
[0067] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 3.39 (s, 2H), 0.68 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 145.1 (q, J=327.2 Hz), 113.5 (t, J=265.8 Hz), 28.4, −4.1; .sup.19F NMR (376 MHz, CDCl.sub.3): δ −129.35 (s, 2F): −80.45 (s, 3F).
##STR00019##
[0068] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 3.41 (s, 2H), 0.75 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 145.8 (q, J=322.5 Hz), 117.6 (t, J=262.8 Hz), 113.5 (t, J=255.8 Hz), 28.4, −4.1; .sup.19F NMR (376 MHz, CDCl.sub.3): δ −129.06 (s, 2F), −125.33 (s, 2F), −79.45 (s, 3F).
##STR00020##
[0069] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 5.47 (t, J 56.5 Hz, 1H), 2.91 (s, 2H), 0.35 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 111.4 (t, J 280 Hz), 109.3 (t, J=256 Hz), 20.4, −5.3; .sup.19F NMR (376 MHz, CDCl.sub.3): δ −130.12 (s, 2F), −138.42 (s, 2F).
3) Conversion from Compound 1a-1c to Compound 2a-2c, 2f
##STR00021##
[0070] General operation procedure 4: alkali (100-300 mmol) was added into a dry 250 mL three-necked flask, freshly distilled of halosilane 1a-1c (100-300 mmol) was added at −78 C, then R.sub.fH (100-300 mmol) gas was added into the low-temperature reaction system (bubbling for 2 h), the resulting mixed solution was stirred for reaction at the temperature shown in Table 4. The reaction process was monitored by .sup.1H NMR. After the raw materials 1a-1c were consumed, 2a-2c or 2f as shown in Formula (VI) were obtained by distillation under reduced pressure.
[0071] The specific experimental operations of Examples 46-61 are shown in general operation procedure 4, and the specific reaction condition and yield of each example are shown in Table 4.
TABLE-US-00004 TABLE 4 Specific reaction conditions and yields of specific examples 46-61 Product/ 1a-1c (FG) (mmol) /R.sub.fH (mmol)/alkali Temperature Time T Yield Example (mmol) Solvent (° C.) (h) (%) 46 1a (Cl) (280)/CF.sub.3H (225)/KHMDS Toluene −78 7 2a/70 (225) 47 1a (Cl) (280)/CF.sub.3H (280)/LiHMDS THF −50 5 2a/68 (280) 48 1a (Cl) (280)/CF.sub.3H (300)/NaHMDS Toluene −78 8 2a/54 (280) 49 1a (Cl) (100)/CF.sub.3H (225)/NaH (100) DMF −78 10 2a/23 50 1b (Br) (280)/CF.sub.3H (300)/KHMDS Toluene −78 7 2b/59 (225) 51 1b (Br) (280)/CF.sub.3H (280)/LiHMDS THF −50 5 2b/67 (280) 52 1b (Br) (280)/CF.sub.3H (300)/NaHMDS Toluene −78 8 2b/44 (280) 53 1b (Br) (100)/CF.sub.3H (225)/NaH (100) DMF −78 10 2b/31 54 1c (CH═CH.sub.2) (280)/CF.sub.3H (225)/ Toluene −78 12 2c/77 KHMDS (225) 55 1c (CH═CH.sub.2) (280)/CF.sub.3H (300)/ THE −50 12 2c/73 LiHMDS (280) 56 1c (CH═CH.sub.2) (280)/CF.sub.3H (300)/ Toluene −78 15 2c/45 NaHMDS (280) 57 1c (CH═CH.sub.2) (100)/CF.sub.3H (225)/NaH DMF −78 15 2c/38 (100) 58 1a (Cl) (100)/CF.sub.2H.sub.2 (225)/KHMDS Toluene −100 8 2f/70 (100) 59 1a (Cl) (280)/CF.sub.2H.sub.2 (280)/LiHMDS THF −100 12 2f/56 (150) 60 1a (Cl) (280)/CF.sub.2H.sub.2 (300)/NaHMDS Toluene −81 6 2f/45 (150) 61 1a (Cl) (100)/CF.sub.2H.sub.2 (225)/NaH (100) DMF −50 7 2f/28
Application of Functionalized Fluoroalkyl Silane
Application Example 1: Asymmetric Trifluoromethylation Reaction Involving the Functionalized Trifluoromethyl Silane 2a Synthesized in Example 2 of the Present Invention, Follows the Reaction Path of Formula (VII)
[0072] ##STR00022##
[0073] In a dry 25 mL Schlenk tube, under the protection of nitrogen were added raw material 3a (29 mg, 0.2 mmol), Cat 1 (12 mg, 0.02 mmol), TMAF (2 mg, 0.02 mmol), followed by a mixed solution of anhydrous toluene and anhydrous dichloromethane (2.0 mL) with a volume ratio of 2:1, the resulting mixed solution was stirred at −78° C. for 10 min, and then 2a (70 μL, 0.4 mmol) was added to react. The reaction process was monitored by thin-layer chromatography. After the raw material 3a was consumed, 4a as shown in Formula (VII) was obtained by direct column chromatography with a yield of 94%.
The relevant characterization data for compound 4a are as follows:
##STR00023##
[0074] HPLC analysis: Chiralcel OJ-H, isopropanol/n-hexane=0.5/99.5, 10 mL/min, 230 nm; t.sub.r (major)=6.62 min, t.sub.r (minor)=8.03 min, 96% ee;
[0075] Optical rotation: [α].sub.D.sup.25=+38.6 (c=1.0, CHCl.sub.3);
[0076] .sup.1H NMR (300 MHz, CDCl.sub.3): 7.44-7.31 (m, 5H), 6.90 (d, J=8.0 Hz, 1H), 6.35 (d, J=8.0 Hz, 1H), 3.96 (s, 3H), 2.96 (s, 2H), 0.40 (d, J=2.0 Hz, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 137.3, 134.5, 130.8, 129.5, 128.8, 127.7 (q, J=287 Hz), 126.28, 75.8 (q, J=29 Hz), 29.8, 22.34, 3.3; .sup.19F NMR (376 MHz, CDCl.sub.3): δ −78.34 (s, 3F).
Application Example 2: Asymmetric Trifluoromethylation Reaction Involving the Functionalized Trifluoromethyl Silane 2a Synthesized in Example 2 of the Present Invention, Follows the Reaction Path of Formula (VIII)
[0077] ##STR00024##
[0078] In a dry 25 mL Schlenk tube, under the protection of nitrogen were added raw material 5a (34 mg, 0.2 mmol), Cat 2 (17 mg, 0.02 mmol), TMAF (4 mg, 0.04 mmol), followed by a mixed solution of anhydrous toluene and anhydrous dichloromethane (2.0 mL) with a volume ratio of 2:1, the resulting mixed solution was stirred at −78° C. for 10 min, and then 2a (70 μL, 0.4 mmol) was added to react. The reaction process was monitored by thin-layer chromatography. After the raw material 5a was consumed, 6a as shown in Formula (VIII) was obtained by direct column chromatography with a yield of 93%.
[0079] The relevant characterization data for compound 6a are as follows:
##STR00025##
[0080] HPLC analysis: Chiralcel OJ-H, isopropanol/n-hexane=0.5/99.5, 1.0 mL/min, 205 nm; t.sub.r (major)=5.12 min, t.sub.r (minor)=5.95 min, 90% ee;
[0081] Optical rotation: [α].sub.D.sup.25=+8.3 (c=1.0, CHCl.sub.3);
[0082] .sup.1H NMR (400 MHz, CDCl.sub.3): 7.99 (s, 1H), 7.87-7.82 (m, 3H), 7.65 (d, J=8.0 Hz, 1H), 7.52-7.48 (m, 2H), 2.80 (s, 2H), 1.94 (s, 3H), 0.28 (d, J=3.6 Hz, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 128.6, 128.0, 127.6, 126.8, 126.5, 126.4, 125.3 (q, J=284 Hz), 124.4, 77.8 (q, J=29 Hz); .sup.19F NMR (376 MHz, CDCl.sub.3): δ −80.98 (s, 3F).
Application Example 3: Trifluoromethylation Reaction of Quinoline Involving the Functionalized Trifluoromethyl Silane 2a Synthesized in Example 2 of the Present Invention, Follows the Reaction Path of Formula (IX)
[0083] ##STR00026##
[0084] In a plastic reaction tube that can be sealed with a stopcock, raw material 3b (82 mg, 0.5 mmol), KHF.sub.2 (117 mg, 1.5 mmol), DMPU (189 mg, 1.5 mmol), 1,4-dioxane (5 mL) were added, followed by trifluoroacetic acid (170 mg, 1.5 mmol), the resulting mixed solution was stirred at 25° C. for 24 h, and 2a (528 μL, 3.0 mmol) was added to react, stirred at 25° C. for 24 h, then PhI(OAc).sub.2 (240 mg, 0.75 mmol) was added and stirred for 2 h. The reaction was quenched by addition of saturated sodium carbonate solution, extracted with ethyl acetate (10 ml x 6 times), the organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. After purification by column chromatography, 7a of Formula (IX) can be obtained with a yield of 80%.
The relevant characterization data for compound 7a are as follows:
##STR00027##
[0085] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 7.75 (d, J=8.5 Hz, 2H), 7.90 (s, 1H), 8.16 (d, J=9.0 Hz, 1H), 8.28 (d, J=8.5 Hz, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 117.9 (q, J=2.2 Hz), 121.5 (q, J=275 Hz), 126.4, 129.5, 131.9, 132.1, 134.9, 137.4, 145.7, 148.4 (q, J=35.1 Hz); .sup.19F NMR (376 MHz, CDCl.sub.3): δ −69.5 (s, 3F).
Application Example 4: The Functional Group Transfer Reaction Involving the Functionalized Trifluoromethyl Silane 4a Synthesized in Application Example 1 of the Present Invention, Follows the Reaction Path of Formula (X)
[0086] ##STR00028##
[0087] In a dry 25 mL round-bottomed flask, 4a (322 mg, 1.0 mmol), NaI (900 mg, 6.0 mmol) anhydrous acetone (10 mL) were added, the resulting solution was heated and stirred under reflux for 6 h, then a large amount of white solid (NaCl) was produced, the white solid was filtered off through silica gel and the solvent was removed from the filtrate under reduced pressure to afford 8a. In a dry 25 mL Schlenk tube, crude 8a and acetonitrile (10 mL) were added, followed by a mixed solution of diisopropylethylamine (1.30 g, 10 mmol) and formic acid (460 mg, 10 mmol), deoxygenated by nitrogen bubbling, followed by adding [Ir(dtbbpy)[dF(CF.sub.3)ppy].sub.2]PF.sub.6 (28 mg, 0.025 mmol), and then the reaction system was placed under blue light irradiation and stirred at room temperature for 10 h. After column chromatography, 9a as shown in Formula (X) can be obtained with a yield of 68% and dr value of 20:1.
[0088] The relevant characterization data for compound 9a are as follows:
##STR00029##
[0089] HPLC analysis: Chiralcel OD-H, isopropanol/n-hexane=0.2/99.8, 1.0 mL/min, 205 nm; t.sub.r (major)=7.86 min, t.sub.r (minor)=8.58 min, 96% ee;
[0090] Optical rotation: [α].sub.D.sup.25=+32.5 (c=1.0, CHCl.sub.3);
[0091] .sup.1H NMR (400 MHz, CDCl.sub.3): 7.32-7.24 (m, 2H), 7.24-7.16 (m, 2H), 3.12-3.08 (m, 1H), 2.50-2.44 (m, 1H), 2.28 (t, J=12.0 Hz, 1H), 1.33 (s, 3H), 0.94-0.88 (m, 1H), 0.60-0.54 (m, 1H), 0.28 (s, 3H), 0.13 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3): δ 140.6, 129.1, 128.5, 126.9 (q, J=283 Hz), 126.3, 82.36 (q, J=28 Hz), 43.6, 39.8, 17.6, 16.8, 0.6, 0.4; .sup.19F NMR (376 MHz, CDCl.sub.3): δ−81.12 (s, 3F).
[0092] The protection content of the present invention is not limited to the above embodiments. Variations and advantages that can occur to those skilled in the art without departing from the spirit and scope of the inventive concept are included in the present invention, and the appended claims are the scope of protection.