CN110655451A - Method for preparing hydroxyl and trifluoromethyl substituted compound by reaction of olefin and trifluorobromomethane - Google Patents

Method for preparing hydroxyl and trifluoromethyl substituted compound by reaction of olefin and trifluorobromomethane Download PDF

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CN110655451A
CN110655451A CN201910884188.3A CN201910884188A CN110655451A CN 110655451 A CN110655451 A CN 110655451A CN 201910884188 A CN201910884188 A CN 201910884188A CN 110655451 A CN110655451 A CN 110655451A
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trifluorobromomethane
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李苏华
李乾坤
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Sun Yat Sen University
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Abstract

The invention discloses a method for preparing hydroxyl and trifluoromethyl substituted compounds by olefin addition reaction. The method takes a compound containing carbon-carbon double bonds and trifluorobromomethane as raw materials, takes a metal salt-tertiary amine system as a catalyst, takes air as an oxidant, and can carry out addition reaction on the carbon-carbon double bonds to prepare a compound substituted by hydroxyl and trifluoromethyl at the same time; the metal salt is one or more of cobalt salt, silver salt, bismuth salt, nickel salt, ferric salt or copper salt; the tertiary amine is N-isopropyl-N-methyl tert-butylamine or N, N-diisopropylethylamine. The method takes the metal salt-tertiary amine as a catalytic system for the first time, realizes the hydroxyl substitution and trifluoromethyl substitution of the olefin, and only needs one-step reaction, the reaction process conditions are mild, the reaction raw materials are cheap and easy to obtain, and the cost is low; the substrate applicability of the reaction is strong, the reaction can be participated in as long as carbon-carbon double bonds exist in the structure, the influence of the types of substituents on double-bond carbon atoms is avoided, and the yield of the product is good.

Description

Method for preparing hydroxyl and trifluoromethyl substituted compound by reaction of olefin and trifluorobromomethane
Technical Field
The invention relates to the technical field of olefin addition reaction, in particular to a preparation method for preparing hydroxyl and trifluoromethyl substituted compounds by reacting olefin with trifluorobromomethane.
Background
The method has important significance for preparing a plurality of functional groups from one simple functional group in one step, can efficiently construct a large number of compounds with rich structures, and has great application value in the fields of drug research and development and the like. The alkene is a compound existing in chemical engineering, medicines or intermediates thereof in a large amount, and has important significance in directly carrying out bifunctional on the alkene under very mild conditions. Hydroxyl is a very important functional group, can regulate and control the polarity of molecules, provides hydrogen bonds, and simultaneously has a large number of methods for converting the hydroxyl into other diversified functional groups in organic synthesis, such as fluoro, chloro, ammoniation, deoxidation and reduction, oxidation to ketone, esterification, cyano substitution, etherification, deoxidation coupling and the like. Therefore, if the trifluoromethyl and the hydroxyl can be simultaneously introduced into the olefin in one step, on one hand, the compound has potential physiological activity, and on the other hand, the compound with diversified trifluoromethyl substitutions can be constructed through one-step conversion. The method has great application value in the aspects of rapid late modification of the drugs, construction of small molecule compound libraries and the like.
However, at present, many methods for introducing trifluoromethyl into an olefin compound through an addition reaction are available, but few reports are available on methods for simultaneously introducing trifluoromethyl and hydroxyl, so that a preparation method which can simultaneously introduce trifluoromethyl and hydroxyl into an olefin compound by one step is necessary to have important application value.
Disclosure of Invention
The invention aims to provide a preparation method for preparing hydroxyl and trifluoromethyl substituted compounds by reacting olefin with trifluorobromomethane. The method uses cheap and easily-obtained trifluorobromomethane as a raw material, adopts metal salt-tertiary amine as a catalytic system, uses oxygen as an oxidant, and can simultaneously substitute hydroxyl and trifluoromethyl in a product compound structure through one-step reaction; the reaction condition is mild, and the product is easy to separate and purify; the substrate of the reaction has good applicability, and can be reacted by adopting the method provided by the invention as long as the structure has carbon-carbon double bonds, and the method is not influenced by the types of substituents on double-bond carbon atoms.
The above object of the present invention is achieved by the following scheme:
a preparation method for preparing hydroxyl and trifluoromethyl substituted compound by the reaction of olefin and trifluorobromomethane, wherein a compound containing carbon-carbon double bonds and the trifluorobromomethane are used as raw materials, a metal salt-tertiary amine system is used as a catalyst, air is used as an oxidant, and the carbon-carbon double bonds can undergo addition reaction to prepare a compound substituted by the hydroxyl and substituted by the trifluoromethyl simultaneously;
the metal salt is one or more of cobalt salt, silver salt, bismuth salt, nickel salt, ferric salt or copper salt; the tertiary amine is N-isopropyl-N-methyl tert-butylamine or N, N-diisopropylethylamine.
The trifluorobromomethane adopted by the invention is a supply raw material of trifluoromethyl, and is cheap and easy to obtain; meanwhile, the adopted catalyst is low in cost, and the metal salt and the tertiary amine act together to achieve a good catalytic effect; the adopted oxidant is also easy to obtain; the whole reaction condition is mild, the yield of the reaction product is high, and the product is easy to separate and purify.
By addition of the radical scavenger TEMPO and radical clock experiments [ as shown in the examples, formulae (1) and (2)]The radical mechanism of this reaction was confirmed. Using isotopes18O-labeled water or oxygen experiments prove that the oxygen on the hydroxyl group in the product is completely from oxygen in the air, but not from water; it is shown that in this catalytic system, the reduction of the peroxyalcohol requires the co-participation of metal salts such as cobalt and tertiary amines.
Based on the experimental results of the above mechanism research, the metal is exemplified by cobalt, and the mechanism of the above reaction is: first, cobalt and amine are coordinated to form a complex which gives an electron donor CF3Br to CF3The free radical, followed by addition with an olefin, gives a substituted trifluoropropyl radical. The free radicals capture oxygen in the air and then capture a hydrogen to produce peroxyalcohol. The peroxyalcohol is reduced by the cobalt amine complex to give the alcoholic hydroxyl group (as shown in figure 1).
Preferably, the compound shown in the formula I and the trifluorobromomethane are used as raw materials, a metal salt-tertiary amine system is used as a catalyst, and air is used as an oxidant to react to prepare the compound shown in the formula II;
Figure RE-GDA0002291413580000021
wherein R is1、R2、R3And R4Each independently is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkane, substituted or unsubstituted heterocycloalkane, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl. The above alkyl, cycloalkane, heterocycloalkane, aryl and heteroaryl groups are substituents commonly used in the art, such as halogen and C1～12Alkyl radical, C1～12Haloalkyl, C1～12Hydroxy-substituted alkyl, C1～12Amino-substituted alkyl, C1～12Nitro-substituted alkyl, C1～12Cyano-substituted alkyl, C3～12Cycloalkyl radical, C3～12Halogenocycloalkyl, C3～12Cycloalkyl substituted by hydroxy, C3～12Amino-substituted cycloalkyl, pyridine, pyrimidine, thiophene, furan, phenyl, benzyl, naphthalene, C8～18Fused rings and the like, wherein the heteroatom is one or more, one or more of N, S, O or P; the substituents in the substituted alkyl, substituted cycloalkane, substituted heterocycloalkane, substituted aryl and substituted heteroaryl are all the substituents commonly used in the art, such as halogen and C1～12Alkyl radical, C1～12Haloalkyl, C1～12Hydroxy-substituted alkyl, C1～12Amino-substituted alkyl, C1～12Nitro-substituted alkyl, C1～12Cyano-substituted alkyl, C3～12Cycloalkyl radical, C3～12Halogenocycloalkyl, C3～12Cycloalkyl substituted by hydroxy, C3～12Amino-substituted cycloalkyl, pyridine, pyrimidine, thiophene, furan, phenyl, benzyl, naphthalene, and the like.
As is clear from the above reaction mechanism, R is not particularly limited1、R2、R3And R4Whether or not it is hydrogen, orOther substituents do not participate in the reaction, and the addition reaction does not have any influence, so that the reaction can be carried out only by the presence of a carbon-carbon double bond in the compound shown in the formula I in the system.
Preferably, the metal salt is typically a divalent cobalt salt, a trivalent bismuth salt, an iridium salt, a rhodium salt, a chromium salt, or a silver salt; the tertiary amine is tertiary amine with larger steric hindrance, such as N-isopropyl-N-methyl tert-butylamine or Diisopropylethylamine (DIPEA) and the like.
Preferably, the metal salt is Co (BF)4)2·6H2O、CoCl2·6H2O、CoI2、CoBr2Or hydrated, Bi (OTf)3、 IrCl3、RhCl3、CrCl3·6H2O or AgOAc.
Preferably, the reaction is carried out in a sealed system, with evacuation followed by introduction of CF3Br, and then air is introduced for reaction.
Preferably, the reaction is carried out in one or more solvents of acetonitrile, DMF, toluene, tetrahydrofuran and water.
Preferably, the reaction molar ratio of the compound shown as the formula I, the trifluorobromomethane, the metal salt and the tertiary amine is as follows: 1: 1-10: 0.01-2: 1-10; the reaction temperature is 0-120 ℃.
Compared with the prior art, the invention has the following beneficial effects:
the method takes the metal salt-tertiary amine as a catalytic system for the first time, realizes the hydroxyl substitution and trifluoromethyl substitution of the olefin, and only needs one-step reaction, the reaction process conditions are mild, the reaction raw materials are cheap and easy to obtain, and the cost is low; the substrate applicability of the reaction is strong, the reaction can be participated in as long as carbon-carbon double bonds exist in the structure, the influence of the types of substituents on double-bond carbon atoms is avoided, and the yield of the product is good.
Drawings
FIG. 1 is a reaction scheme for preparing hydroxy and trifluoromethyl substituted compounds in example 1.
Detailed Description
The present invention is further described in detail below with reference to specific examples, which are provided for illustration only and are not intended to limit the scope of the present invention. The test methods used in the following examples are all conventional methods unless otherwise specified; the materials, reagents and the like used are, unless otherwise specified, commercially available reagents and materials. 1. Investigating the reactivity of different metal salts
The method takes 1-1 and trifluorobromomethane as raw materials, takes DIPEA (N, N-diisopropylethylamine) and different metal salts as catalytic systems, and carries out reaction, and the specific reaction formula is shown as follows:
the yields of the products obtained by the reaction are shown in table 1.
TABLE 1 yield results for different metal salts and reaction products thereof
entry Cat. yield of 2-1(％) rsm(％)
1 CoCl2·6H2O 57 20
2b Bi(OTf)3 42 30
3b RuCl3 0 71
4b RhCl3 13 30
5b PdCl2 0 71
6b IrCl3 19 25
7b PhF 3B 6 88
8b Ph3B 1 91
9b InCl3 0 76
10b GaCl3 0 61
11 CrCl3·6H2O 7 50
13 YCl3·H2O 0 90
14 SnCl4·5H2O 0 86
15 BF3·2H2O 0 100
16b Sc(OTf)3 0 85
17b Yb(OTf)3 0 89
18b ZnCl2 0 100
19b SnCl2 0 100
20 FeCl2·4H2O 0 88
21 Mn(OAc)2·4H2O 0 81
22 Ni(OAc)2·4H2O 1 84
23b AgOAc 28 20
24b Cu(OTf)2 0 90
aNMR yield;b H2the amount of O was 0.2mL.
The influence of the type of the metal salt on the reaction is obvious, when the metal salt is RuCl3、PdCl2、InCl3、GaCl3、 YCl3·H2O、SnCl4·5H2O、BF3·2H2O、Sc(OTf)3、Yb(OTf)3、ZnCl2、SnCl2、FeCl2·4H2O、 Mn(OAc)2·4H2O and Cu (OTf)2When no reaction occurs, when the metal salt is PhF 3B、Ph3B and Ni (OAc)2·4H2O, the yield of reaction products is extremely low and almost no reaction occurs; when the metal salt is Co (BF)4)2·6H2O、CoCl2·6H2O、CoI2、 CoBr2Or a hydrate thereof, Bi (OTf)3、IrCl3、RhCl3、CrCl3·6H2O or AgOAc, the yield of the reaction product is high.
2. Effect of Tertiary amines on the reaction
Figure RE-GDA0002291413580000051
aReaction conditions 1-1(1.0mmol,1.0equiv), CF3Br(1atm,balloon),CoCl2·6H2O(1.0equiv),amine(4.0 equiv),CH3CN (1.0mL),25mL Schlenk tube, rt. yield in parentheses as feed recovery;breaction conditions 1-1(1.0mmol,1.0equiv), CF3Br(1atm),CoCl2·6H2O(1.0equiv),amine(4.0equiv),CH3CN (4.0mL),50mL Schlenk flash, air balloon, rt;c5% (NMR)3,3, 3-trifluo-1-phenylpropan-1-one;dreaction conditions 1-1(1.0mmol,1.0equiv), CF3Br(1atm),Co(BF4)2·6H2O(0.3equiv),amine(4.0equiv),CH3CN(4.0mL),H2O (76. mu.L), 50mL schlenk flash, air balloon, rt.
The above results are for the compound of formula 1 and trifluorobromomethane in CoCl2·H2O and various tertiary amine systems, wherein "NR" indicates that no reaction has occurred, no product of formula 2 is produced, the percentage is the yield of product, and the percentage in parentheses after that is the recovery of the starting material. From the above results, it is understood that when the tertiary amine is a1, A3, a4, a5, A6, a7, A8, a10, a11, a13, a14, a15, and a16, the reaction does not occur; the reaction occurs only when the tertiary amine is a2, a9, and a12, and the yield of the product is low when the tertiary amine is a 9; when the tertiary amine is A2 or A12, the reaction is carried out more completely, and the yield of the product is higher.
3. Investigation of reaction mechanism
By addition of the radical scavenger TEMPO and radical clock experiments [ formulae (1), (2)]The radical mechanism of this reaction was confirmed. Using isotopes18O-labeled water or oxygen experiments prove that the oxygen on the hydroxyl group in the product is completely from oxygen in the air, but not from water; it is shown that in this catalytic system, the reduction of the peroxyalcohol requires the co-participation of metal salts such as cobalt and tertiary amines.
The reaction formula is shown as follows:
Figure RE-GDA0002291413580000061
based on the experimental results of the above mechanism research, the metal is exemplified by cobalt, and the mechanism of the above reaction is: first, cobalt and amine are coordinated to form a complex which gives an electron donor CF3Br to CF3The free radical, followed by addition with an olefin, gives a substituted trifluoropropyl radical. The free radicals capture oxygen in the air and then capture a hydrogen to produce peroxyalcohol. The peroxyalcohol is reduced by the cobalt amine complex to give the alcoholic hydroxyl group (as shown in figure 1).
4. Substrate application scope
In the compound shown in the formula 1, no matter mono-substitution, di-substitution or tri-substitution, addition reaction can be carried out according to the following formula, and after a carbon-carbon double bond is broken, hydroxyl and trifluoromethyl are simultaneously substituted to obtain a product.
Reaction of a monosubstituted compound represented by formula 1:
Figure RE-GDA0002291413580000071
reaction of a disubstituted compound of formula 1:
Figure RE-GDA0002291413580000072
reaction of a tri-or tetra-substituted compound of formula 1:
aconditions 1(1.0mmol), CF3Br(1atm),Co(BF4)2·6H2O(0.3mmol,30mol％),A12(4.0mmol),H2O(76μL), CH3CN (4.0mL), rt,24 h; the yield in parentheses is the nuclear magnetic yield of the raw material recovery.b65℃.c45℃.dConditions 1(1.0mmol), CF3Br(1atm),Co(BF4)2·6H2O(0.01mmol,1mol％),A12(4.0equiv),H2O(106μL),DMF(4.0mL),80 ℃,24h；eAfter the reaction is finished, NaBH is added4(1.0equiv)。
In the compound shown in the formula 1, the reaction can occur no matter the compound is mono-substituted or multi-substituted, only a carbon-carbon double bond exists in the compound shown in the formula 1, and the substrate of the reaction has very wide applicability and is not influenced by the number and the type of the substituent groups.
Example 1
Preparation of Compound 2-1:
Figure RE-GDA0002291413580000082
co (BF) is added into a reaction device4)2·6H2O (102.8mg,0.301mmol), sealing the system, vacuumizing, introducing trifluorobromomethane, and connecting with an air balloon; then adding other reagent, CH, into the reaction system3CN (4mL), water (76 μ L), alkene 1-1(115 μ L, d 0.906g/mL,1.00mmol) and N-isoproyl-N-methyl-tert-butyl amine (675 μ L, d 0.767g/mL,4.01mmol) reacted at room temperature for 24 hours, then filtered, concentrated, and column chromatographed to give 2-1(160.4mg, 84% yield) as a light yellow oil.
TLC:Rf＝0.28in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3):δ7.46-7.29(m,5H),5.08(dt,J＝8.8,2.8Hz,1H), 2.72-2.55(m,1H),2.54-2.37(m,1H),2.20(d,J＝2.7Hz,1H).
13C NMR(100MHz,CDCl3)δ142.46,128.92,128.48,125.99(q,J＝277.4Hz),125.79, 68.87(q,J＝3.1Hz),42.81(q,J＝26.9Hz).
19F NMR(376MHz,CDCl3):δ-64.26.
MS(EI):m/z(％)190(M+,10.78),107(100).
Example 2
Preparation of Compound 2-2:
Figure RE-GDA0002291413580000091
reference example 1, alkene 1-2(135 μ L, d ═ 1.01g/mL, 98% purity,0.997mmol), CF3Br, Co(BF4)2·6H2O (102.2mg,0.300mmol), N-isoproyl-N-methyl-tert-butyl amine (675 μ L, d ═ 0.767g/mL,4.01mmol), water (76 μ L), acetonitrile (4mL) and air gave 2-2(205.6mg, 94% yield) as a light yellow oil.
TLC:Rf＝0.24in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.27(d,J＝8.6Hz,2H),6.88(d,J＝8.7Hz,2H),4.99(d, J＝8.3Hz,1H),3.79(s,3H),2.70-2.51(m,1H),2.49-2.34(m,1H),2.33-2.18(m,1H).
13C NMR(100MHz,CDCl3)δ159.59,134.71,127.09,125.98(q,J＝277.4Hz),114.19, 68.39(q,J＝3.0Hz),55.32,42.68(q,J＝26.8Hz).
19F NMR(376MHz,CDCl3):δ-64.21.
MS(EI):m/z(％)220(M+,22.27),137(100).
Example 3
Preparation of Compounds 2-7:
Figure RE-GDA0002291413580000101
reference example 1, alkene 1-7(125 μ L, d ═ 1.02g/mL, 95% purity,0.993mmol), CF3Br, Co(BF4)2·6H2O (102.6mg,0.301mmol), N-Isopropyl-N-methyl-tert-butyl amine (675. mu.L, d 0.767g/mL,4.01mmol), water (76. mu.L), CH3CN (4mL) and air to give 2-7(170.4mg, 83% yield) as a light yellow oil.
TLC:Rf＝0.24in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.49-7.30(m,2H),7.07(t,J＝8.6Hz,2H),5.18-4.96(m, 1H),2.72-2.52(m,1H),2.52-2.32(m,1H),2.25(d,J＝2.9Hz,1H).
13C NMR(100MHz,CDCl3)δ162.68(d,J＝246.6Hz),138.23(d,J＝3.0Hz),127.57 (d,J＝8.2Hz),125.88(q,J＝277.4Hz),115.79(d,J＝21.6Hz),68.26(q,J＝3.1Hz),42.87(q,J＝27.0Hz).
19F NMR(376MHz,CDCl3):δ-64.23,-114.11.
MS(EI):m/z(％)208(M+,10.77),125(100).
Example 4
Preparation of Compounds 2-10:
reference example 1, alkene 1-10(150 μ L, d ═ 1.17g/mL, 98% purity,1.00mmol), CF3Br, Co(BF4)2·6H2O(103.6mg,0.304mmol),N-Isopropyl-N-methyl-tert-butyl amine (675 μ L, d 0.767g/mL,4.01mmol), water (76 μ L), CH3CN (4mL) and air. To 2-10(189.5mg, 73% yield), as a pale yellow oil.
TLC:Rf＝0.32in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.65(d,J＝8.3Hz,2H),7.52(d,J＝8.1Hz,2H), 5.26-5.05(m,1H),2.72-2.54(m,1H),2.54-2.38(m,1H),2.32-2.20(m,1H).
13C NMR(100MHz,CDCl3)δ146.19,130.77(q,J＝32.7Hz),126.18,125.96(q,J＝ 3.7Hz),125.83(q,J＝277.6Hz).124.07(q,J＝272.4Hz),68.40(q,J＝3.1Hz),43.10(q,J＝27.2Hz).
19F NMR(376MHz,CDCl3):δ-63.19,-64.20.
MS(EI):m/z(％)258(M+,4.41),175(100).
Example 5
Preparation of Compounds 2-17:
Figure RE-GDA0002291413580000111
reference example 1, alkene 1-17(144.9mg,1.01mmol), CF3Br,Co(BF4)2·6H2O (104.5mg, 0.306mmol), N-Isopropyl-N-methyl-tert-butyl amine (675. mu.L, d 0.767g/mL,4.01mmol), water (76. mu.L), CH3CN (4mL) and air. 2-17(145.1mg, 63% yield) was obtained as a pale yellow solid.
TLC:Rf＝0.41in 2:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ8.23(bs,1H),7.63(s,1H),7.38(d,J＝8.4Hz,1H),7.23 (t,J＝2.5Hz,1H),7.19(d,J＝8.4Hz,1H),6.60-6.50(m,1H),5.16(dd,J＝8.9,2.8Hz,1H), 2.80-2.60(m,1H),2.60-2.40(m,1H),2.13(s,1H).
13C NMR(100MHz,CDCl3)δ135.76,134.01,127.95,126.15(q,J＝277.4Hz),125.34, 119.82,118.13,111.63,102.74,69.57(q,J＝3.1Hz),42.96(q,J＝26.7Hz).
19F NMR(376MHz,CDCl3):δ-64.26.
IR(neat):3412,1343,1247,1096,729cm-1.
MS(EI):m/z(％)229(M+,44.02),118(100).
HRMS(ESI+):m/z calc’d for(M+H)+:230.0793,found 230.0795.
Example 6
Preparation of Compounds 2-20:
Figure RE-GDA0002291413580000112
reference example 1, alkene 1-20(281.3mg,1.00mmol), CF3Br,Co(BF4)2·6H2O(104.0mg, 0.305mmol),N-Isopropyl-N-methyl-tert-butylamine(675μL,d＝0.767g/mL,4.01mmol),water(76μL)，CH3CN (4mL) and air. 2-20(309.1mg, 84% yield) was obtained as a white foamy solid.
TLC:Rf＝0.19in 5:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.31(d,J＝8.0Hz,1H),7.15(d,J＝8.1Hz,1H),7.12(s, 1H),5.02(dt,J＝6.4,3.0Hz,1H),2.93(dd,J＝8.7,4.0Hz,2H),2.70-2.37(m,4H), 2.36-2.23(m,2H),2.22-1.92(m,4H),1.74-1.37(m,6H),0.91(s,3H).
13C NMR(100MHz,CDCl3)δ221.21,140.14,139.84,136.99,126.35,126.31,125.99 (q,J＝277.4Hz),125.77,123.12,68.39,50.46,47.99,44.36,42.71(q,J＝26.8Hz),38.09, 35.82,31.54,29.43,26.45,25.72,21.58,13.79.
19F NMR(376MHz,CDCl3):δ-64.23.
IR(neat):3445,2935,1735,1259,1116cm-1.
MS(EI):m/z(％)366(M+,53.14),283(100).
HRMS(ESI+):m/z calc’d for(M+H)+:367.1885,found 367.1884.
Example 7
Preparation of Compounds 2-21:
Figure RE-GDA0002291413580000121
reference example 1, alkene 1-21(235 μ L, d ═ 0.758g/mL, 95% purity,1.01mmol), CF3Br, Co(BF4)2·6H2O (3.4mg,0.00997mmol), N-isoproyl-N-methyl-tert-butyl amine (675 μ L, d ═ 0.767g/mL,4.01mmol), water (106 μ L), DMF (4mL) and air. 2-21(101.3mg, 40% yield) was obtained as a colorless oil.
TLC:Rf＝0.56in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ4.00(s,1H),2.37-2.13(m,2H),1.97(s,1H),1.60-1.20 (m,18H),0.88(t,J＝6.8Hz,3H).
13C NMR(100MHz,CDCl3)δ126.65(q,J＝277.0Hz),66.36(q,J＝2.7Hz),41.27(q, J＝26.4Hz),37.33,32.05,29.73,29.71,29.67,29.53,29.47,25.34,22.83,14.22.
19F NMR(376MHz,CDCl3):δ-64.04.
IR(neat):3379,2925,2857,1253,1147cm-1.
MS(EI):m/z(％)236((M-H2O)+,1.34),56(100).
HRMS(EI):m/z calc’d for(M-H2O)+:236.1746,found 236.1745.
Example 8
Preparation of Compounds 2-23:
reference example 1, alkene 1-23(130 μ L, d ═ 0.909g/mL, 99% pure, 0.991mmol), CF3Br, Co(BF4)2·6H2O(102.4mg,0.300mmol),N-Isopropyl-N-methyl-tert-butylamine(675μL,d＝ 0.767g/mL,4.01mmol),water(76μL)，CH3CN (4mL) and air. 2-23(180.3mg, 89% yield) was obtained as a pale yellow oil.
TLC:Rf＝0.27in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.50-7.42(m,2H),7.40-7.33(m,2H),7.32-7.25(m,1H), 2.74-2.55(m,2H),2.21(bs,1H),1.70(s,3H).
13C NMR(101MHz,CDCl3)δ146.32,128.53,127.48,125.91(q,J＝278.4Hz),124.53, 72.03(q,J＝2.1Hz),46.62(q,J＝25.7Hz),29.61.
19F NMR(376MHz,CDCl3):δ-60.58.
MS(EI):m/z(％)204(M+,5.38),121(100).
Example 9
Preparation of Compounds 2-29:
Figure RE-GDA0002291413580000132
reference example 1, alkene 1-29(203.5mg, 97% pure, 1.00mmol), CF3Br,Co(BF4)2·6H2O (100.6mg,0.295mmol),N-Isopropyl-N-methyl-tert-butylamine(675μL,d＝0.767g/mL, 4.01mmol),water(76μL)，CH3CN (4mL) with an air balloon and air. 2-29(260.7mg, 92% yield) was obtained as a white solid.
TLC:Rf＝0.22in 5:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ3.86(s,2H),3.18(t,J＝11.6Hz,2H),2.34(q,J＝11.4 Hz,2H),2.15-1.95(m,1H),1.85-1.55(m,4H),1.47(s,9H).
13C NMR(100MHz,CDCl3)δ154.86,126.21(q,J＝278.4Hz),79.83,67.61(q,J＝ 1.8Hz),45.73(q,J＝25.5Hz),39.49(bs),36.59,28.47.
19F NMR(376MHz,CDCl3):δ-60.02.
IR(neat):3421,1662,1247,1126,1083cm-1.
MS(EI):m/z(％)283(M+,1.06),57(100).
HRMS(EI):m/z calc’d for(M+,283.1390),found 283.1392.
Example 10
Preparation of Compounds 2-34a and 2-34 b:
Figure RE-GDA0002291413580000141
reference example 1, alkene 1-34(302.2mg, 98% purity,1.00mmol), CF3Br,Co(BF4)2·6H2O (100.6mg,0.295mmol),N-Isopropyl-N-methyl-tert-butylamine(675μL,d＝0.767g/mL,
4.01mmol),water(76μL)，DMF(2mL)，CH3CN (2mL) and air. 2-34a (115.6mg, 30% yield) and 2-34b (126.0mg, 33% yield) were obtained as white solids.
2-34a:
TLC:Rf＝0.58in 1:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.07(d,J＝10.1Hz,1H),6.16(d,J＝10.2Hz,1H),6.11 (s,1H),3.30(s,1H),2.90-2.72(m,1H),2.67-2.18(m,4H),2.14-1.92(m,2H),1.91-1.80(m, 2H),1.79-1.56(m,2H),1.45(s,3H),1.33-1.06(m,4H),0.94(s,3H).
13C NMR(100MHz,CDCl3)δ220.14,186.56,165.24,158.19,126.18(q,J＝278.5Hz), 125.76,124.04,71.84,51.27,50.34,47.77,44.44,43.20(q,J＝26.0Hz),42.11,35.75,31.22, 30.50,21.86,21.83,21.37,13.92.
19F NMR(376MHz,CDCl3):δ-58.25.
IR(neat):3423,1734,1659,1118,731cm-1.
MS(EI):m/z(％)382(M+,23.07),111(100).
HRMS(ESI+):m/z calc’d for(M+H)+:383.1834,found 383.1837.
2-34b:
TLC:Rf＝0.39in 1:1hexanes/EtOAc.
1H NMR(400MHz,DMSO)δ7.23(d,J＝10.1Hz,1H),6.54(d,J＝1.1Hz,1H),6.12 (dd,J＝9.9,1.0Hz,1H),5.39(s,1H),3.10-2.90(m,1H),2.80-2.60(m,1H),2.44(dd,J＝19.0,8.7Hz,1H),2.20-1.78(m,5H),1.69(d,J＝12.7Hz,1H),1.65-1.46(m,2H),1.36-1.14(m,6H),1.04(t,J＝9.7Hz,1H),0.91(s,3H).
13C NMR(100MHz,DMSO)δ219.10,185.37,168.71,157.27,126.26(q,J＝279.0 Hz),125.52,124.55,70.56,50.57,49.47,47.10,45.84,43.45,41.83(q,J＝25.0Hz),35.20, 31.36,30.90,21.48,21.06,20.74,13.67.
19F NMR(376MHz,DMSO):δ-57.04.
IR(neat):3384,2925,1738,1657,1264cm-1.
MS(EI):m/z(％)382(M+,13.80),79(100).
HRMS(ESI+):m/z calc’d for(M+H)+:383.1834,found 383.1837.
Example 11
Preparation of Compounds 2-38a and 2-38 b:
Figure RE-GDA0002291413580000151
reference example 1, alkene 1-38(455.7mg, 95% purity,1.01mmol), CF3Br,Co(BF4)2·6H2O (101.0mg,0.296mmol), N-isoproyl-N-methyl-tert-butyl amine (675 μ L, d ═ 0.767g/mL,4.01mmol), water (76 μ L), DMF (4mL) and air. 2-38(49.0mg, 9% yield, colorless oil) and 2-38b (226.3mg, 44% yield, white solid) were obtained.
2-38a:
TLC:Rf＝0.37in 10:1hexanes/EtOAc.
1H NMR(400MHz,Acetone)δ5.22-4.99(m,1H),3.61(s,1H),2.55-2.40(m,1H), 2.20-2.10(m,1H),2.09-2.00(m,2H),1.96(s,3H),1.93-1.10(m,25H),1.08(s,3H),0.95(d, J＝6.5Hz,3H),0.88(d,J＝6.6,3H),0.87(d,J＝6.6,3H),0.72(s,3H).
13C NMR(100MHz,Acetone)δ170.42,129.12(q,J＝281.8Hz),74.97,70.79,57.13, 56.47,45.69,45.65(q,J＝22.0Hz),43.62,40.95,40.25,37.52,36.95,36.63,34.79,31.33, 28.98,28.69,27.10,26.49(q,J＝2.9Hz),24.64,24.61,23.10,22.86,22.12,21.24,19.10, 16.58,12.53.
19F NMR(376MHz,CDCl3):δ-63.96.
IR(neat):3467,2937,1725,1269,1121cm-1.
HRMS(APCI):m/z calc’d for(M-H)-:513.3561,found 513.3565.
2-38b:
TLC:Rf＝0.29in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ5.22-5.01(m,1H),2.34-2.09(m,3H),2.06-1.94(m,4H), 1.92-1.78(m,3H),1.75-1.47(m,8H),1.45-1.23(m,8H),1.23-1.02(m,10H),0.90(d,J＝6.4 Hz,3H),0.86(d,J＝6.4Hz,6H),0.67(s,3H).
13C NMR(100MHz,CDCl3)δ171.26,127.19(q,J＝280.8Hz),76.16,71.11,56.54, 56.02,50.67(q,J＝24.8Hz),45.75,42.88,40.08,39.62,39.27,38.53,36.32,36.01,33.15, 31.88,28.38,28.14,26.86,26.46,24.23,24.17,22.92,22.69,21.55,21.26,18.74,16.28(q,J ＝3.5Hz),12.33.
19F NMR(376MHz,CDCl3):δ-60.88.
IR(neat):3413,2937,1735,1704,1246cm-1.
HRMS(APCI):m/z calc’d for(M-H)-:513.3561,found 513.3565.
Example 12
Preparation of Compounds 2-39:
Figure RE-GDA0002291413580000161
reference example 1, alkene 1-39(100 μ L, d ═ 0.857g/mL, 97% purity,0.990mmol), CF3Br, Co(BF4)2·6H2O(103.5mg,0.304mmol),N-Isopropyl-N-methyl-tert-butylamine(675μL,d＝ 0.767g/mL,4.01mmol),water(76μL)，CH3CN (4mL) and air. 2-39(39.3mg, 23% yield) was obtained as a white solid (lower boiling point, crude spectral yield 51% yield, purified by the19F NMR analysis of the crude mixture with PhCF3 as the internal standard)。
TLC:Rf＝0.43in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ1.61(s,1H),1.31(q,J＝1.1Hz,6H),1.17(q,J＝0.7Hz, 6H).
13C NMR(100MHz,CDCl3)δ129.75(q,J＝284.8Hz),73.40,47.55(q,J＝21.3Hz), 26.72(q,J＝2.2Hz),18.50(q,J＝2.7Hz).
19F NMR(376MHz,CDCl3)δ-70.85.
IR(neat):3365,2923,2852,1466,1101cm-1.
MS(EI):m/z(％)155((M-CH3)+,100).
HRMS(EI):m/z calc’d for:(M-CH3)+,155.0678,found 155.0675.
Example 13
Figure RE-GDA0002291413580000171
The preparation process is referred to example 1.
TLC:Rf＝0.26in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.73-7.57(m,4H),7.55-7.35(m,5H),5.13(d,J＝8.5Hz,1H),2.78-2.60 (m,1H),2.60-2.39(m,2H).
13C NMR(100MHz,CDCl3)δ141.43,141.38,140.57,128.96,127.63,127.19,126.25,126.01(q,J＝ 277.5Hz),68.66(q,J＝3.1Hz),42.86(q,J＝26.9Hz).
19F NMR(376MHz,CDCl3):δ-64.22.
MS(EI):m/z(％)266(M+,61.55),183(100).
Example 14
Figure RE-GDA0002291413580000172
The preparation process is referred to example 1.
TLC:Rf＝0.26in 5:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.37(d,J＝8.3Hz,2H),7.08(d,J＝8.3Hz,2H),5.05(dd,J＝8.9,2.8Hz, 1H),2.67-2.52(m,1H),2.50-2.35(m,2H),2.29(s,3H).
13C NMR(100MHz,CDCl3)δ169.74,150.48,140.18,126.90,125.90(q,J＝277.3Hz),121.95,68.17(q, J＝3.1Hz),42.81(q,J＝27.0Hz),21.06.
19F NMR(376MHz,CDCl3):δ-64.24.
MS(EI):m/z(％)248(M+,5.01),123(100).
Example 15
Figure RE-GDA0002291413580000173
The preparation process is referred to example 1.
TLC:Rf＝0.22in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.25(d,J＝8.1Hz,2H),7.18(d,J＝8.0Hz,2H),5.03(d,J＝8.7Hz,1H), 2.70-2.52(m,1H),2.51-2.38(m,1H),2.35(s,3H),2.18-2.08(m,1H).
13C NMR(100MHz,CDCl3)δ139.57,138.31,129.57,126.02(q,J＝277.4Hz),125.75,68.72(q,J＝3.1 Hz),42.79(q,J＝26.8Hz),21.17.
19F NMR(376MHz,CDCl3):δ-64.26.
MS(EI):m/z(％)204(M+,20.38),121(100).
Example 16
The preparation process is referred to example 1.
TLC:Rf＝0.17in 10:1hexanes/EtOAc.
1H NMR(400MHz,Acetone)δ9.18(bs,1H),7.62(d,J＝8.5Hz,2H),7.35(d,J＝8.5Hz,2H),5.00(app. dt,J＝8.7,4.4Hz,1H),4.75-4.57(m,1H),2.72-2.43(m,2H),2.07(s,3H).
13C NMR(100MHz,Acetone)δ169.17,139.74,139.67,127.28(q,J＝277.0Hz),127.06,119.97,68.39 (q,J＝3.2Hz),43.21(q,J＝26.2Hz),24.21.
19F NMR(376MHz,Acetone):δ-62.75.
IR(neat):3340,3265,1634,1598,1123cm-1.
MS(EI):m/z(％)247(M+,21.60),122(100).
HRMS(ESI+):m/z calc’d for(M+H)+:248.0898,found 248.0902.
Example 17
Figure RE-GDA0002291413580000182
The preparation process is referred to example 1.
TLC:Rf＝0.26in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.39-7.28(m,4H),5.14-5.00(m,1H),2.69-2.51(m,1H),2.51-2.33(m,1H), 2.28-2.15(m,1H).
13C NMR(100MHz,CDCl3)δ140.83,134.23,129.08,127.19,125.83(q,J＝277.4Hz),68.25(q,J＝3.1 Hz),42.84(q,J＝27.0Hz).
19F NMR(376MHz,CDCl3):δ-64.20.
MS(EI):m/z(％)224(M+(35Cl),18.15),141(100).
Example 18
Figure RE-GDA0002291413580000183
The preparation process is referred to example 1.
TLC:Rf＝0.27in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.50(d,J＝8.4Hz,2H),7.24(d,J＝8.4Hz,2H),5.02(d,J＝8.9Hz,1H), 2.66-2.49(m,1H),2.48-2.32(m,2H).
13C NMR(100MHz,CDCl3)δ141.30,132.00,127.49,125.77(q,J＝277.5Hz),122.29,68.23(q,J＝3.1 Hz),42.69(q,J＝27.0Hz).
19F NMR(376MHz,CDCl3):δ-64.17.
MS(EI):m/z(％)268(M+(79Br),18.52),77(100).
Example 19
Figure RE-GDA0002291413580000191
The preparation process is referred to example 1.
TLC:Rf＝0.29in 5:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ8.00(d,J＝8.4Hz,2H),7.43(d,J＝8.2Hz,2H),5.13(dt,J＝6.1,2.8Hz, 1H),3.90(s,3H),2.73-2.53(m,2H),2.52-2.36(m,1H).
13C NMR(100MHz,CDCl3)δ167.07,147.69,130.05,129.77,125.74,52.29,125.79(q,J＝277.5Hz), 68.26(q,J＝3.1Hz),42.67(q,J＝27.1Hz).
19F NMR(376MHz,CDCl3):δ-64.14.
IR(neat):3447,1704,1438,1246,1099cm-1.
MS(EI):m/z(％)248(M+,8.08),165(100).
HRMS(ESI+):m/z calc’d for(M+H)+:249.0739,found 249.0743.
Example 20
Figure RE-GDA0002291413580000192
The preparation process is referred to example 1.
TLC:Rf＝0.28in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.26(t,J＝7.4Hz,1H),7.21-7.10(m,3H),5.10-4.95(m,1H),2.70-2.51(m, 1H),2.51-2.38(m,1H),2.36(s,3H),2.16(bs,1H).
13C NMR(100MHz,CDCl3)δ142.46,138.70,129.21,128.82,126.46,126.03(q,J＝277.4Hz),122.81, 21.45,68.88(q,J＝3.1Hz),42.81(q,J＝26.9Hz).
19F NMR(376MHz,CDCl3):δ-64.28.
MS(EI):m/z(％)204(M+,33.69),121(100).
Example 21
Figure RE-GDA0002291413580000201
The preparation process is referred to example 1.
TLC:Rf＝0.30in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.55-7.42(m,1H),7.30-7.10(m,3H),5.32(dt,J＝9.1,2.7Hz,1H), 2.69-2.47(m,1H),2.46-2.28(m,1H),2.34(s,3H),2.10(bs,1H).
13C NMR(100MHz,CDCl3)δ140.61,134.19,130.80,128.11,126.69,126.16(q,J＝277.5Hz),125.18, 122.03,65.16(q,J＝3.1Hz),41.90(q,J＝26.9Hz),18.75.
19F NMR(376MHz,CDCl3):δ-64.64.
MS(EI):m/z(％)204(M+,10.42),121(100).
Example 22
Figure RE-GDA0002291413580000202
The preparation process is referred to example 1.
TLC:Rf＝0.24in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.63(dd,J＝7.8,1.3Hz,1H),7.55(dd,J＝8.0,0.7Hz,1H),7.38(t,J＝7.3 Hz,1H),7.19(td,J＝7.8,1.5Hz,1H),5.47(d,J＝9.6Hz,1H),2.66-2.36(m,2H),2.33(d,J＝3.6Hz,1H).
13C NMR(100MHz,CDCl3)δ141.22,133.02,129.73,128.16,127.29,125.96(q,J＝277.8Hz),121.35, 67.72(q,J＝3.1Hz),41.33(q,J＝27.2Hz).
19F NMR(376MHz,CDCl3):δ-64.30.
MS(EI):m/z(％)268(M+(79Br),15.01),77(100).
Example 23
Figure RE-GDA0002291413580000203
The preparation process is referred to example 1.
TLC:Rf＝0.26in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.94-7.79(m,4H),7.58-7.43(m,3H),5.24(d,J＝8.9Hz,1H),2.80-2.63 (m,1H),2.63-2.46(m,1H),2.34(bs,1H).
13C NMR(100MHz,CDCl3)δ139.67,133.28,133.27,128.86,128.12,127.83,126.58,126.43,126.01(q, J＝277.5Hz),124.78,123.41,68.95(q,J＝3.1Hz),42.69(q,J＝27.0Hz).
19F NMR(376MHz,CDCl3):δ-64.17.
MS(EI):m/z(％)240(M+,35.00),129(100).
Example 24
The preparation process is referred to example 1.
TLC:Rf＝0.36in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.89(d,J＝8.3Hz,1H),7.84(s,1H),7.50(d,J＝5.4Hz,1H),7.40-7.30(m, 2H),5.21(d,J＝8.8Hz,1H),2.81-2.61(m,1H),2.61-2.43(m,1H),2.25(s,1H).
13C NMR(100MHz,CDCl3)δ139.89,139.71,138.74,127.53,125.97(q,J＝277.5Hz),123.92,123.02, 121.96,120.80,68.97(q,J＝3.1Hz),43.05(q,J＝26.9Hz).
19F NMR(376MHz,CDCl3):δ-64.22.
IR(neat):3394,1427,1247,1109,701cm-1.
MS(EI):m/z(％)246(M+,55.18),135(100).
HRMS(EI):m/z calc’d for(M+,246.0321),found 246.0324.
Example 25
Figure RE-GDA0002291413580000212
The preparation process is referred to example 1.
TLC:Rf＝0.14in 2:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ8.77(d,J＝3.3Hz,1H),8.09(d,J＝8.2Hz,1H),7.98(d,J＝8.7Hz,1H), 7.78(s,1H),7.71-7.60(m,1H),7.36(dd,J＝8.2,4.2Hz,1H),5.27(dd,J＝8.6,3.3Hz,1H),4.19(bs,1H), 2.80-2.62(m,1H),2.62-2.44(m,1H).
13C NMR(100MHz,CDCl3)δ150.19,147.44,141.63,136.61,129.43,128.08,127.54,125.99(q,J＝ 277.5Hz),124.55,121.52,68.06(q,J＝3.0Hz),42.96(q,J＝26.9Hz).
19F NMR(376MHz,CDCl3):δ-64.04.
IR(neat):3188,1368,1247,1112,833cm-1.
MS(EI):m/z(％)241(M+,33.36),130(100).
HRMS(ESI+):m/z calc’d for(M+H)+:242.0793,found 242.0797.
Example 26
Figure RE-GDA0002291413580000221
The preparation process is referred to example 1.
TLC:Rf＝0.26in 1:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ8.60-8.40(m,2H),7.75(d,J＝7.9Hz,1H),7.32(dd,J＝7.7,4.9Hz,1H), 5.12(dd,J＝8.3,3.0Hz,1H),3.61(bs,1H),2.79-2.57(m,1H),2.57-2.34(m,1H).
13C NMR(101MHz,CDCl3)δ148.78,147.08,139.06,134.29,125.75(q,J＝277.4Hz),124.01,66.05(q, J＝3.1Hz),42.75(q,J＝27.0Hz).
19F NMR(376MHz,CDCl3):δ-64.05.
IR(neat):3178,1376,1251,1120,713cm-1.
MS(EI):m/z(％)191(M+,18.90),108(100).
HRMS(ESI+):m/z calc’d for(M+H)+:192.0636,found 192.0639.
Example 27
The preparation process is referred to example 1.
TLC:Rf＝0.24in 10:1hexanes/EtOAc.
2-22a:1H NMR(400MHz,CDCl3)δ7.55-7.20(m,5H),6.68(d,J＝15.8Hz,1H),6.21(dd,J＝15.8,6.6 Hz,1H),4.69(s,1H),2.59-2.28(m,2H),1.94(bs,1H).
2-22b:1H NMR(400MHz,CDCl3)δ7.55-7.20(m,5H),5.94(dd,J＝15.3,5.7Hz,1H),5.81-5.71(m,1H), 5.23(d,J＝4.7Hz,1H),2.94-2.76(m,2H),1.94(bs,1H).
2-22a and 2-22b:13C NMR(100MHz,CDCl3)δ142.25,139.49,136.08,131.86,129.58,128.80,128.30, 128.12,126.75,126.44,126.01(q,J＝277.3Hz),119.01(q,J＝3.3Hz),100.08,74.41,67.46(q,J＝3.1Hz), 41.26(q,J＝26.8Hz).
19F NMR(376MHz,CDCl3):δ-63.79(2-22a),-66.81(2-22b).
IR(neat):3377,1252,1145,1119,967cm-1 .
MS(EI):m/z(％)216(M+,66.61),105(100).
HRMS(EI):m/z calc’d for M+:216.0757,found 216.0758.
Example 28
Figure RE-GDA0002291413580000231
The preparation process is referred to example 1.
TLC:Rf＝0.50in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.48(d,J＝8.0Hz,2H),7.36(t,J＝7.6Hz,2H),7.28(t,J＝7.3Hz,1H), 2.89-2.65(m,2H),1.91(s,1H),1.46-1.35(m,1H),0.62-0.50(m,2H),0.48-0.38(m,1H),0.38-0.28(m,1H).
13C NMR(100MHz,CDCl3)δ144.78,128.32,127.50,126.00(q,J＝278.3Hz),125.26,72.34(q,J＝2.1 Hz),45.90(q,J＝25.5Hz),21.31,1.80,1.11.
19F NMR(376MHz,CDCl3):δ-59.72.
MS(EI):m/z(％)202((M-C2H4)+,100).
Example 29
Figure RE-GDA0002291413580000232
The preparation process is referred to example 1.
TLC:Rf＝0.60in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.69-7.59(m,2H),7.41-7.28(m,3H),3.38(s,3H),3.01(dq,J＝15.7,10.9 Hz,1H),2.89(s,1H),2.80(dq,J＝15.7,10.9Hz,1H),2.35-2.06(m,4H),1.55-1.41(m,1H),1.05-0.87(m,1H).
13C NMR(100MHz,CDCl3)δ140.09,127.62,127.46,126.98,126.85(q,J＝278.4Hz),84.63,76.92(q,J ＝1.9Hz),51.11,37.87(q,J＝25.3Hz),25.02,24.56,12.16.
19F NMR(376MHz,CDCl3)δ-58.36.
IR(neat):3547,1368,1265,1097,701cm-1.
MS(EI):m/z(％)246((M-C2H4)+,2.75),85(100).
HRMS(ESI+):m/z calc’d for(M+Na)+:297.1078,found 297.1083.
Example 30
Figure RE-GDA0002291413580000233
The preparation process is referred to example 1.
TLC:Rf＝0.18in 1:1hexanes/EtOAc.
1H NMR(400MHz,Acetone)δ8.54(d,J＝5.5Hz,2H),7.55(d,J＝6.0Hz,2H),4.92(s,1H),2.92-2.71 (m,2H),1.67(s,3H).
13C NMR(100MHz,Acetone)δ157.07,150.20,126.88(q,J＝277.9Hz),120.95,71.25(q,J＝2.0Hz), 46.20(q,J＝25.7Hz),30.56.
19F NMR(376MHz,Acetone):δ-59.27.
MS(EI):m/z(％)205(M+,28.42),106(100).
Example 31
Figure RE-GDA0002291413580000241
The preparation process is referred to example 1.
TLC:Rf＝0.34in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.41(d,J＝7.5Hz,4H),7.32(t,J＝7.4Hz,4H),7.28-7.22(m,2H),3.19(q, J＝10.3Hz,2H),2.65(s,1H).
13C NMR(100MHz,CDCl3)δ145.26,128.50,127.63,125.86(q,J＝278.8Hz),125.67,75.74(q,J＝2.1 Hz),44.99(q,J＝25.5Hz).
19F NMR(376MHz,CDCl3):δ-58.71.
MS(EI):m/z(％)266(M+,5.98),105(100).
Example 32
Figure RE-GDA0002291413580000242
The preparation process is referred to example 1.
TLC:Rf＝0.30in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.41-7.18(m,5H),2.89(d,J＝13.5Hz,1H),2.84(d,J＝13.5Hz,1H),2.32 (q,J＝11.4Hz,2H),1.74(s,1H),1.34(s,3H).
13C NMR(100MHz,CDCl3)δ136.15,130.79,128.55,127.11,126.31(q,J＝277.9Hz),70.31(q,J＝1.8 Hz),48.54,44.15(q,J＝26.1Hz),26.76.
19F NMR(376MHz,CDCl3):δ-60.28.
IR(neat):3455,1262,1138,1091,703cm-1.
MS(EI):m/z(％)203((M-CH3)+,1.03),92(100).
HRMS(EI):m/z calc’d for(M-CH3)+:203.0678,found 203.0676.
Example 33
Figure RE-GDA0002291413580000251
The preparation process is referred to example 1.
2-30a:1H NMR(400MHz,CDCl3)δ2.29(q,J＝11.6Hz,2H),1.85(s,1H),1.73-1.42(m,8H),1.36-1.16 (m,2H).
2-30b:1H NMR(400MHz,CDCl3)δ8.01(s,1H),2.44(q,J＝11.7Hz,2H),1.73-1.42(m,8H),1.36-1.16 (m,2H).
2-30a and 2-30b:13C NMR(100MHz,CDCl3)δ126.61(q,J＝278.3Hz),126.24(q,J＝277.7Hz),80.50, 69.69(q,J＝1.8Hz),45.15(q,J＝25.4Hz),39.75(q,J＝26.3Hz),37.47,32.83,29.83,25.40,21.86,21.52.
19F NMR(376MHz,CDCl3)δ-60.09(2-30a),-60.58(2-30b).
IR(neat):3377,2925,1376,1266,1113cm-1.
2-30a:MS(EI):m/z(％)182(M+,5.28),55(100).
2-30b:MS(EI):m/z(％)198(M+,0.07),165((M-OOH)+,74.36),55(100).
2-30a:HRMS(EI):m/z calc’d for(M+,182.0913),found 182.0912.
2-30b:HRMS(EI):m/z calc’d for(M-OOH)+:165.0886,found 165.0885.
Example 34
The preparation process is referred to example 1.
TLC:Rf＝0.31in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.43-7.31(m,5H),5.27(d,J＝12.1Hz,1H),5.19(d,J＝12.1Hz,1H),3.44 (s,1H),2.78-2.63(m,1H),2.63-2.48(m,1H),1.49(s,3H).
13C NMR(101MHz,CDCl3)δ174.91,134.81,128.86,128.81,128.53,125.34(q,J＝278.0Hz),71.31(q, J＝2.4Hz),68.49,42.97(q,J＝27.3Hz),27.05,
19F NMR(376MHz,CDCl3):δ-62.11.
MS(EI):m/z(％)262(M+,0.68),91(100).
Example 35
Figure RE-GDA0002291413580000261
The preparation process is referred to example 1.
TLC:Rf＝0.39in 1:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.05(bs,1H),3.95-3.60(m,1H),2.84-2.69(m,4H),2.59-2.43(m,1H), 1.51(s,3H).
13C NMR(101MHz,CDCl3)δ174.73,125.87(q,J＝278.0Hz),72.86,42.52(q,J＝26.7Hz),27.17, 26.25.
19F NMR(470MHz,CDCl3):δ-61.52.
IR(neat):3360,1655,1548,1264,1176cm-1.
MS(EI):m/z(％)185(M+,1.19),58(100).
HRMS(ESI+):m/z calc’d for(M+H)+:186.0742,found 186.0747.
Example 36
Figure RE-GDA0002291413580000262
The preparation process is referred to example 1.
2-33-ketone:
1H NMR(400MHz,CDCl3)δ7.94(d,J＝8.7Hz,2H),6.97(d,J＝8.7Hz,2H),4.27-4.11(m,1H),3.88(s, 3H),1.45(d,J＝7.1Hz,3H).
19F NMR(376MHz,CDCl3)δ-68.80.
2-33:
TLC:Rf＝0.24in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.28-7.18(m,2H),6.88(d,J＝8.6Hz,2H),5.10(d,J＝2.6Hz,0.46H), 4.72(d,J＝8.1Hz,0.54H),3.79(s,3H),2.68-2.15(m,2H),1.08(d,J＝7.1Hz,1.38H),0.84(d,J＝7.2Hz, 1.62H).
13C NMR(100MHz,CDCl3)δ159.77,159.26,133.81,133.29,128.26,127.85(q,J＝280.7Hz),126.98, 114.12,113.96,73.75-73.55(m),70.46(q,J＝2.6Hz),55.42,45.90-44.40(m),10.66(q,J＝3.0Hz),6.26(q,J ＝2.3Hz).
19F NMR(376MHz,CDCl3)δ-69.11,-70.48.
IR(neat):3447,1513,1247,1168,1114cm-1.
MS(EI):m/z(％)234(M+,7.24),137(100).
HRMS(EI):m/z calc’d for(M+,234.0862),found 234.0865.
Example 37
The preparation process is referred to example 1.
TLC:Rf＝0.35in 10:1hexanes/EtOAc.
1H NMR(400MHz,CD3CN)(trans isomer,major)δ7.62-7.56(m,2H),7.42-7.33(m,2H),7.33-7.23(m, 1H),3.22(s,1H),2.77-2.63(m,1H),2.52-2.40(m,1H),2.27-2.13(m,1H),2.03-1.70(m,4H),1.69-1.47(m, 2H).
(cis isomer,minor)δ7.55-7.48(m,2H),7.42-7.33(m,2H),7.33-7.23(m,1H),3.26(s,1H),2.88-2.77(m, 1H),2.52-2.40(m,1H),2.27-2.13(m,1H),2.03-1.70(m,4H),1.69-1.47(m,2H).
13C NMR(100MHz,CD3CN)δ149.24,147.85,128.84,128.74,128.15,128.13(q,J＝281.1Hz),127.03, 126.74,125.39,73.93,72.42,50.73(q,J＝22.5Hz),49.99(q,J＝22.5Hz),43.33,34.52,31.65,25.17,23.09(q, J＝2.7Hz),22.87(q,J＝2.7Hz),21.99,21.74.
19F NMR(376MHz,CD3CN)δ-59.89(trans),-63.60(cis).
MS(EI):m/z(％)244(M+,18.88),133(100).
Example 38
Figure RE-GDA0002291413580000272
The preparation process is referred to example 1.
TLC:Rf＝0.34,0.28in 10:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ7.50-7.22(m,5H),2.78-2.55(m,1H),2.18(s,0.28H),1.91(s,0.72H), 1.75-1.64(m,3H),1.07-0.93(m,3H).
13C NMR(100MHz,CDCl3)δ146.60,145.97,128.41,128.34,128.11(q,J＝281.8Hz),127.54,127.15, 125.42,124.78,74.74,74.34,48.50(q,J＝23.1Hz),47.85(q,J＝23.3Hz),29.25(q,J＝2.3Hz),25.58,10.70 (q,J＝2.9Hz),9.47(q,J＝3.1Hz).
19F NMR(376MHz,CDCl3):δ-65.23,-65.50.
IR(neat):3474,1264,1172,1121,1070cm-1.
MS(EI):m/z(％)218(M+,0.07),121(100).
HRMS(EI):m/z calc’d for(M-CH3)+:203.0678,found 203.0677.
Example 39
Figure RE-GDA0002291413580000281
The preparation process is referred to example 1.
2-37a:
TLC:Rf＝0.53in 2:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ5.17-5.05(m,1H),2.45(dd,J＝19.3,8.1Hz,1H),2.40-2.30(m,1H), 2.17-2.05(m,2H),2.03(s,3H),2.01-1.92(m,1H),1.91-1.20(m,16H),1.03(s,3H),0.87(s,3H).
13C NMR(100MHz,CDCl3)δ220.58,170.74,127.93(q,J＝282.1Hz),74.83,70.19,50.64,48.00,45.05, 44.81,40.25,37.24,35.90,33.82,31.59,30.68,26.36,24.67(q,J＝2.9Hz),21.75,21.52,20.71,16.43,14.00.
19F NMR(376MHz,CDCl3):δ-64.01.
IR(neat):3455,2942,1734,1267,1172cm-1.
MS(EI):m/z(％)416(M+,4.76),55(100).
HRMS(ESI+):m/z calc’d for(M+Na)+:439.2072,found 439.2073.
2-37b:
TLC:Rf＝0.44in 2:1hexanes/EtOAc.
1H NMR(400MHz,CDCl3)δ5.21-5.06(m,1H),2.45(dd,J＝19.3,8.6Hz,1H),2.35-2.05(m,4H),2.03 (s,3H),1.99-1.74(m,7H),1.71-1.40(m,6H),1.40-1.20(m,3H),1.06(s,3H),0.87(s,3H).
13C NMR(101MHz,CDCl3)δ220.97,171.25,127.04(q,J＝280.9Hz),75.93,70.90,51.02,50.41(q,J＝ 25.0Hz),47.92,45.84,39.19,38.69,35.84,33.10,31.57,31.51,26.76,25.43,21.73,21.53,20.44,16.22(q,J＝ 3.5Hz),14.03.
19F NMR(376MHz,CDCl3):δ-60.93.
IR(neat):3455,1730,1243,1096,1028cm-1.
MS(EI):m/z(％)416(M+,15.54),55(100).
HRMS(ESI+):m/z calc’d for(M+Na)+:439.2072,found 439.2072.
It should be finally noted that the above examples are only intended to illustrate the technical solutions of the present invention, and not to limit the scope of the present invention, and that other variations and modifications based on the above description and thought may be made by those skilled in the art, and that all embodiments need not be exhaustive. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.

Claims (7)

1. A preparation method for preparing hydroxyl and trifluoromethyl substituted compound by the reaction of olefin and trifluorobromomethane is characterized in that a compound containing carbon-carbon double bonds and the trifluorobromomethane are used as raw materials, a metal salt-tertiary amine system is used as a catalyst, air is used as an oxidant, and the carbon-carbon double bonds can undergo addition reaction to prepare the compound substituted by the hydroxyl and the trifluoromethyl simultaneously;
the metal salt is one or more of cobalt salt, silver salt, bismuth salt, nickel salt, ferric salt or copper salt; the tertiary amine is N-isopropyl-N-methyl tert-butylamine or N, N-diisopropylethylamine.
2. The method for preparing hydroxyl and trifluoromethyl substituted compound by the reaction of olefin and trifluorobromomethane according to claim 1, wherein the compound shown in formula II is prepared by taking the compound shown in formula I and the trifluorobromomethane as raw materials, taking a metal salt-tertiary amine system as a catalyst and taking air as an oxidant;
wherein R is1、R2、R3And R4Each independently is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkane, substituted or unsubstituted heterocycloalkane, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.
3. The process for the preparation of hydroxy and trifluoromethyl substituted compounds by reacting an olefin with trifluorobromomethane according to claim 1 or 2, wherein the metal salt is typically a divalent cobalt salt, a trivalent bismuth salt, an iridium salt, a rhodium salt, a chromium salt or a silver salt; the tertiary amine is N-isopropyl-N-methyl tert-butylamine or Diisopropylethylamine (DIPEA).
4. The process for preparing hydroxy and trifluoromethyl substituted compounds by reacting an olefin with trifluorobromomethane according to claim 3, wherein the metal salt is Co (BF)4)2·6H2O、CoCl2·6H2O、CoI2、CoBr2Or hydrated, Bi (OTf)3、IrCl3、RhCl3、CrCl3·6H2O or AgOAc.
5. The process for preparing hydroxy-and trifluoromethyl-substituted compounds by reacting an olefin with trifluorobromomethane according to claim 1 or 2, wherein the reaction is carried out in a sealed system by first evacuating and then introducing CF3Br, and then air is introduced for reaction.
6. The process for the preparation of hydroxy and trifluoromethyl substituted compounds by the reaction of an olefin with trifluorobromomethane according to claim 1 or 2, wherein the reaction is carried out in one or more solvents selected from acetonitrile, DMF, toluene, tetrahydrofuran and water.
7. The process for preparing hydroxy and trifluoromethyl substituted compounds by reacting an olefin with trifluorobromomethane according to claim 2, wherein the molar ratio of the compound of formula i to the trifluorobromomethane to the metal salt to the tertiary amine is: 1: 1-10: 0.01-2: 1-10; the reaction temperature is 0-120 ℃.
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CN113121295A (en) * 2021-03-30 2021-07-16 中山大学 Method for preparing fluoroalkane substituted compound by reducing halogenated fluoroalkane and olefin by using metal simple substance

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Publication number Priority date Publication date Assignee Title
CN112574056A (en) * 2020-12-28 2021-03-30 浙江工业大学 Synthetic method of alpha, alpha-difluoro-gamma-hydroxyacetamide derivative
CN113121295A (en) * 2021-03-30 2021-07-16 中山大学 Method for preparing fluoroalkane substituted compound by reducing halogenated fluoroalkane and olefin by using metal simple substance

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