CN109293484A - From carboxylic acid using complex of iridium as catalyst blue light illumination under prepare the method for deuterated aldehyde - Google Patents

From carboxylic acid using complex of iridium as catalyst blue light illumination under prepare the method for deuterated aldehyde Download PDF

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CN109293484A
CN109293484A CN201811227050.8A CN201811227050A CN109293484A CN 109293484 A CN109293484 A CN 109293484A CN 201811227050 A CN201811227050 A CN 201811227050A CN 109293484 A CN109293484 A CN 109293484A
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carboxylic acid
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dtbbpy
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CN109293484B (en
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谢劲
朱成建
张目亮
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Nanjing University
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Abstract

A method of from carboxylic acid using complex of iridium as catalyst blue light illumination under prepare deuterated aldehyde, it is with aromatic carboxylic acids (ArCOOH) for raw material, triphenylphosphine is as deoxidier, under blue light light irradiation, in the solution of methylene chloride and heavy water, under argon atmosphere, under conditions of dipotassium hydrogen phosphate is alkali, with [Ir (dF (CF3)ppy)2(dtbbpy)]PF6For photochemical catalyst, benzenethiol 2,4,6-triisopropylbenzenethiol is organic micromolecule catalyst, obtains deuterated Aromatic aldehyde compound.Or it is with aliphatic carboxylic acid (Alk-COOD) for raw material, hexichol base oxethyl phosphine is as deoxidier, with [Ir (dF (Me) ppy)2(dtbbpy)]PF6For photochemical catalyst, benzenethiol 2,4,6-triisopropylbenzenethiol is organic micromolecule catalyst, under blue light light irradiation, in the solution of toluene, under argon atmosphere, under conditions of 2,6- lutidines does alkali, obtains deuterated aliphatic aldehyde compound.

Description

From carboxylic acid using complex of iridium as catalyst blue light illumination under prepare the method for deuterated aldehyde
Technical field
The present invention relates to a kind of methods for preparing deuterated aldehyde from acid.
Background technique
Deuterium (deuterium) is a kind of stable isotope of hydrogen, the symbol of element be D or2H, in organic synthesis and drug Chemical field has a wide range of applications.Deuterium is introduced in the non-metabolism site of drug molecule and non-active site, can not influenced The absorption of drug molecule, distribution, metabolism and excretion etc. are studied in the case where drug effect.Specifically many drugs exist The intracorporal metabolism of people can all be related to c h bond fracture, so introducing D-atom in the metabolism site of drug, can slow down well Or prevent C-D key from being broken, and then achieve the purpose that change drug metabolic rate or metabolic pathway (Mullard, A.Nat.Rev.Drug Discov.2016,15,219).It is a kind of simple and effective that current deuterated drug technique, which is also generally believed that, Mold of drug development (Loh et al., Science 2017,358,1182-1187).
Aldehyde is widely used as synthesizing organic fine chemicals, and such as drug, agricultural chemicals or fragrance, various aldehydes are just small Scale or medium-scale production.A kind of most practical approach of production aldehyde is exactly the direct-reduction by carboxylic acid, currently, usual two kinds Strategy is employed to prepare aldehyde: carboxylic acid hydro-reduction to alcohol is oxidized to aldehyde relatively mildly later；Activity is converted more for carboxylic acid High carboxylic acid derivates such as acyl chlorides, acid anhydrides, amide or Acibenzolar, catalytic hydrogenation or hydro-reduction are aldehyde later.These tactful nothings It doubts and all shows very poor chemo-selective and functional group's tolerance, and severe reaction conditions, need using sensitive agents etc., It is even more a kind of challenge (Angew.Chem.Int.Ed.2017,56,7808-that deuterated aldehyde is especially prepared with the above strategy 7812).Using a kind of photocatalysis approach of mild condition, it is raw material from the carboxylic acid being easy to get is stablized, can efficiently realizes all kinds of deuteriums For the preparation of aldehyde compound, there is preferable application in fine chemistry industry, material science and pharmaceutical field.
Summary of the invention
Deuterated aldehyde side is prepared from acid cheap and easy to get the technical problem to be solved in the present invention is to provide a kind of mild condition Method.
Synthetic route of the invention is as follows:
A method of from aromatic carboxylic acids using complex of iridium as catalyst, blue light illumination under prepare deuterated aldehyde, it is with virtue Fragrant carboxylic acid (ArCOOH) is raw material, and triphenylphosphine is as deoxidier, under blue light light irradiation, in methylene chloride and heavy water
In solution, wherein the volume ratio of methylene chloride and heavy water is 1:1, quickly stirs (1500 turns/min), argon gas gas Under atmosphere, under conditions of dipotassium hydrogen phosphate is alkali, with [Ir (dF (CF3)ppy)2(dtbbpy)]PF6For photochemical catalyst, 2,4,6- Triisopropyl benzenethiol (2,4,6-triisopropylbenzenethiol) is organic micromolecule catalyst, obtains deuterated fragrance Aldehyde compound.
Photochemical catalyst [Ir (dF (the CF3)ppy)2(dtbbpy)]PF6And 2,4,6- triisopropyl benzenethiols (2,4, 6-triisopropylbenzenethiol) just like flowering structure:
Above-mentioned preparation method, it is characterized in that: the Ar group in the aromatic carboxylic acids can be various substituted aryl Or heteroaryl.
Above-mentioned preparation method, it is characterized in that: the ratio between the amount of substance of the aromatic carboxylic acids and triphenylphosphine is 1:1- 2。
Above-mentioned preparation method, it is characterized in that: the ratio between the amount of substance of the dipotassium hydrogen phosphate and aromatic carboxylic acids is 1: 1-2。
Above-mentioned preparation method the, it is characterized in that: photochemical catalyst [Ir (dF (CF3)ppy)2(dtbbpy)]PF6Dosage It is 1% mole of aromatic carboxylic acids molal quantity；Described 2,4,6- triisopropyl benzenethiol catalyst amounts are aromatic carboxylic acids 15% mole of molal quantity.
A method of from aliphatic carboxylic acid using complex of iridium as catalyst, blue light illumination under prepare deuterated aldehyde,
It is with deuterated aliphatic carboxylic acid (Alk-COOD) for raw material, and hexichol base oxethyl phosphine is as deoxidier, with [Ir (dF(Me)ppy)2(dtbbpy)]PF6For photochemical catalyst, 2,4,6- triisopropyl benzenethiols (2,4,6- It triisopropylbenzenethiol is) organic micromolecule catalyst, under blue light light irradiation, in toluene solution, argon gas Under atmosphere, under the conditions of 2,6- lutidines is existing, deuterated aliphatic aldehyde compound is obtained.
Photochemical catalyst [the Ir (dF (Me) ppy)2(dtbbpy)]PF6With 2,4,6- triisopropyl benzenethiol catalyst Respectively just like flowering structure:
Above-mentioned preparation method, it is characterized in that: the aliphatic carboxylic acid can be the aliphatic carboxylic acid of various different alkyl.
Above-mentioned preparation method, it is characterized in that: the ratio between the amount of substance of the aliphatic carboxylic acid and hexichol base oxethyl phosphine It is 1:1-2.
Above-mentioned preparation method, it is characterized in that: the ratio between 2, the 6- lutidines and the amount of substance of aliphatic carboxylic acid It is 1:1-2.
Above-mentioned preparation method the, it is characterized in that: photochemical catalyst [Ir (dF (Me) ppy)2(dtbbpy)]PF6Dosage It is 2.5% mole of aliphatic carboxylic acid molal quantity；Described 2, the dosage of 4,6- triisopropyl benzenethiol catalyst are fat 40% mole of carboxylic acid molal quantity.
This method is easy to operate in mild condition using phosphine free-radical chemistry by light and small organic molecule concerted catalysis The step of under, directly from it is cheap, be easy to get, type carboxylic acid abundant is raw material, can efficient reality using cheap deuterium-oxide as deuterium source The preparation of existing all kinds of deuterated aldehyde compounds, shows good chemo-selective and functional group's tolerance.It simultaneously can be easily The modification that the later period is carried out to complicated drug molecule and compound, is of great importance to the research and development of deuterated drug.
Specific embodiment
It will be helpful to understand the present invention using following embodiments, but be not intended to limit the contents of the present invention.
Deuterated aromatic aldehyde preparating example:
Embodiment 1
First weigh(39.6mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue Under LEDs lamp (brand: Ai Delang, model: LED lamp band, similarly hereinafter) irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water Quenching, and (3x 10mL) is extracted with DCM.Organic phase is through anhydrous Na2SO4Solvent, dry method loading, column chromatography is evaporated off in dry back spin (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, volume ratio: 30-15:1) obtains product31.5mg, yield 86%, D incorporation by1H NMR:96%.1H NMR(400MHz, Chloroform-d) δ 10.06 (s, 0.04H), 7.96 (d, J=8.2Hz, 2H), 7.76 (d, J=8.2Hz, 2H), 7.69- 7.61(m,2H),7.52–7.40(m,3H)。13C NMR (100MHz, Chloroform-d) δ 191.5 (t, J=26.6Hz), (147.2,139.7,135.1 t, J=3.6Hz), 130.3,129.0,128.5,127.7,127.4.2H NMR(92MHz, Chloroform-d)δ10.08(s,1D).HRMS(ESI)Calculated for C13H10DO+([M+H]+):184.0867, found:184.0869。
Embodiment 2
First weigh(35.6mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy) PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 100-50:1) obtain product28.7mg, yield 88%, D incorporation by 1H NMR:97%.1H NMR(400MHz,Chloroform-d)δ9.98(s,0.03H),7.82(d, J=8.6Hz, 2H), 7.56 (d, J=8.6Hz, 2H), 1.36 (s, 9H)13C NMR(100MHz,Chloroform-d)δ191.6 (t, J=26.6Hz), 158.5,134.0 (t, J=3.5Hz), 129.7,126.0,35.4,31.1.2H NMR(92MHz, Chloroform-d)δ10.04(s,1D).HRMS(ESI)Calculated for C11H14DO+([M+H]+):164.1180, found:164.1183。
Embodiment 3
First weigh(33mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy)PF6 (2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P (0.22mmol, 57.6mg, 1.1equiv.) adds Enter reaction tube, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O (2.0mL, 1:1v/v) is then small 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are added in the heart, and then tube sealing is placed under 5W blue led s light irradiation, room Temperature is lower to react 36h.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase is through anhydrous Na2SO4It is dry Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, body Product ratio: 30-10:1) obtain product20.4mg, yield 68%, D incorporation by1H NMR: 96%.1H NMR (400MHz, Chloroform-d) δ 9.73 (s, 0.04H), 7.74 (d, J=8.9Hz, 2H), 6.70 (d, J= 8.9Hz,2H),3.08(s,6H).13C NMR (100MHz, Chloroform-d) δ 190.2 (t, J=25.9Hz), 154.4, 132.0,125.0 (t, J=3.3Hz), 111.0,40.1.HRMS (ESI) Calculated for C9H11DNO+([M+H]+): 151.0976,found:151.0978。
Embodiment 4 first weighs(45.6mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x10mL) with DCM.Organic phase is through nothing Water Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-second Acetoacetic ester, volume ratio: 30-10:1) obtain product30.7mg, yield 72%, Dincorporation by1H NMR:95%.1H NMR (400MHz, Chloroform-d) δ 9.89 (s, 0.05H), 7.85 (d, J=8.8Hz, 2H), 7.55-7.31 (m, 5H), 7.08 (d, J=8.8Hz, 2H), 5.15 (s, 2H)13C NMR(100MHz,Chloroform-d)δ 190.4 (t, J=26.4Hz), 163.8,136.0,132.0,130.0 (t, J=3.4Hz), 128.8,128.4,127.5, 115.2,70.3.HRMS(ESI)Calculated for C14H12DO2 +([M+H]+):214.0973,found:214.0976。
Embodiment 5
First weigh(33.6mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy) PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x10mL) with DCM.Organic phase is through nothing Water Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-second Acetoacetic ester, volume ratio: 40-10:1) obtain product24.8mg, yield 81%, D incorporation by 1H NMR:95%.1H NMR (400MHz, Chloroform-d) δ 9.89 (s, 0.05H), 7.85 (d, J=8.8Hz, 2H), 7.55-7.31 (m, 5H), 7.08 (d, J=8.8Hz, 2H), 5.15 (s, 2H)13C NMR(100MHz,Chloroform-d)δ 190.4 (t, J=26.4Hz), 163.8,136.0,132.0,130.0 (t, J=3.4Hz), 128.8,128.4,127.5, 115.2,70.3.HRMS(ESI)Calculated for C14H12DO2 +([M+H]+):214.0973,found:214.0976。
Embodiment 6
First weigh(47.4mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 30-10:1) obtain product40.0mg, yield 90%, D incorporation by 1H NMR:96%.1H NMR(400MHz,Chloroform-d)δ9.96(s,0.04H),7.93(s, 1H), 7.63 (d, J=7.5Hz, 1H), 7.55 (d, J=8.8Hz, 1H), 7.44 (t, J=7.5Hz, 1H), 6.83 (br s, 1H),1.52(s,9H)。13C NMR (100MHz, Chloroform-d) δ 191.8 (t, J=26.8Hz), 152.7,139.4, 137.0 (t, J=3.2Hz), 129.7,124.2,124.1,119.3,81.1,28.3.HRMS (ESI) Calculated for C12H15DNO3 +([M+H]+):223.1187,found:223.1190。
Embodiment 7
First weigh(33.2mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy) PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 30-10:1) obtain product23.0mg, yield 76%, D incorporation by 1H NMR:95%.1H NMR(400MHz,Chloroform-d)δ9.81(s,0.05H),7.55–7.38(m,1H),7.34 (d, J=1.5Hz, 1H), 6.93 (d, J=7.9Hz, 1H), 6.08 (s, 2H)13C NMR(100MHz,Chloroform-d)δ 189.9 (t, J=26.7Hz), 153.1,148.7,131.8 (t, J=3.5Hz), 128.7,108.4,106.9,102.1.HRMS (ESI)Calculated for C8H6DO3 +([M+H]+):152.0452,found:152.0454。
Embodiment 8
First weigh(31.1mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy) PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 100-50:1) obtain product23.1mg, yield 82%, D incorporation by 1H NMR:95%.1H NMR (400MHz, Chloroform-d) δ 9.97 (s, 0.05H), 7.75 (d, J=8.5Hz, 2H), 7.68 (d, J=8.5Hz, 2H)13C NMR (100MHz, Chloroform-d) δ 190.5 (t, J=26.9Hz), 141.0, 134.6 (t, J=3.7Hz), 130.9,129.5.HRMS (ESI) Calculated for C7H5DClO+([M+H]+): 142.0164,found:142.0166。
Embodiment 9
First weigh(39.9mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy) PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 100-50:1) obtain product32.0mg, yield 87%, D incorporation by 1H NMR:95%.1H NMR (400MHz, Chloroform-d) δ 9.97 (s, 0.05H), 7.75 (d, J=8.5Hz, 2H), 7.68 (d, J=8.5Hz, 2H)13C NMR (100MHz, Chloroform-d) δ 190.7 (t, J=26.9Hz), 135.0 (t, J =3.7Hz), 132.5,131.0,129.8.HRMS (ESI) Calculated for C7H5DBrO+([M+H]+):185.9659, found:185.9660。
Embodiment 10
First weigh(49.5mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy)PF6 (2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P (0.22mmol, 57.6mg, 1.1equiv.) adds Enter reaction tube, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O (2.0mL, 1:1v/v) is then small 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are added in the heart, and then tube sealing is placed under 5W blue led s light irradiation, room Temperature is lower to react 36h.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase is through anhydrous Na2SO4It is dry Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, body Product ratio: 100-50:1) obtain product23.7mg, yield 51%, D incorporation by1H NMR: 95%.1H NMR (400MHz, Chloroform-d) δ 9.95 (s, 0.05H), 7.91 (d, J=8.4Hz, 2H), 7.59 (d, J= 8.4Hz,2H).13C NMR (100MHz, Chloroform-d) δ 191.0 (t, J=27.0Hz), 138.4,135.5 (t, J= 3.6Hz),130.8,102.9.HRMS(ESI)Calculated for C7H5DIO+([M+H]+):233.9521,found: 233.9525。
Embodiment 11
First weigh(36.0mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent is evaporated off in dry back spin, column chromatography (300-400 mesh chromatographic silica gel): dry method loading obtains product24.1mg, yield 73%, D incorporation by1H NMR:94%.1H NMR(400MHz, Chloroform-d) δ 10.08 (s, 0.06H), 8.53 (s, 1H), 8.30 (d, J=7.8Hz, 1H), 8.09 (d, J=9.1Hz, 1H), 7.63 (t, J=7.8Hz, 1H), 3.96 (s, 3H)13C NMR (100MHz, Chloroform-d) δ 190.9 (t, J= 27.0Hz), 166.0,136.5 (t, J=3.6Hz), 135.2,133.1,131.3,131.2,129.3,52.5.HRMS (ESI) Calculated for C9H8DO3 +([M+H]+):166.0609,found:166.0610。
Embodiment 12
First weigh(32.8mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 40-10:1) obtain product22.1mg, yield 74%, D incorporation by 1H NMR:96%.1H NMR(400MHz,Chloroform-d)δ10.09(s,0.04H),8.44 (s, 1H), 8.22 (d, J=9.0Hz, 1H), 8.09 (d, J=9.0Hz, 1H), 7.66 (t, J=7.7Hz, 1H), 2.67 (s, 3H).13C NMR (100MHz, Chloroform-d) δ 197.0,191.1 (t, J=26.9Hz), 137.8,136.5 (t, J= 3.6Hz),133.8,133.6,129.6,129.5,26.7.HRMS(ESI)Calculated for C9H8DO2 +([M+H]+): 150.0660,found:150.0663。
Embodiment 13
First weigh(39.8mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 15-4:1) obtain product19.5mg, yield 53%, D incorporation by1H NMR:94%.1H NMR(400MHz,CDCl3) δ 10.11 (s, 0.06H), 8.90 (d, J= 1.8Hz, 1H), 8.66 (d, J=4.8Hz, 1H), 8.11 (s, 1H), 8.00-7.92 (m, 2H), 7.90-7.84 (m, 1H), 7.68 (t, J=7.7Hz, 1H), 7.42 (dd, J=7.6,5.1Hz, 1H)13C NMR(100MHz,Chloroform-d)δ191.5(t, ), J=26.9Hz 149.2,148.2,138.9,137.0 (t, J=3.5Hz), 135.3,134.5,133.0,129.9,129.6, 128.0,123.8.2H NMR(92MHz,Chloroform-d)δ10.14(s,1D).HRMS(ESI)Calculated for C12H9DNO+([M+H]+):185.0820,found:185.0822。
Embodiment 14
First weigh(35.2mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy) PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), being then carefully added into 2,4,6- triisopropyl benzenethiols, (0.03mmol, 7.1mg, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 40-10:1) obtain product20.3mg, yield 63%, D incorporation by 1H NMR:92%.1H NMR(400MHz,CDCl3) δ 10.07 (s, 0.08H), 8.22 (s, 1H), 8.14 (d, J=7.9, 1H), 7.66 (d, J=7.9Hz, 1H), 3.91-3.15 (m, 2H), 2.97-2.36 (m, 2H)13C NMR(100MHz, Chloroform-d) δ 205.7,190.8 (t, J=26.8Hz), 161.1,137.8,135.9 (t, J=3.5Hz), 133.9, 127.6,126.4,36.4,26.4.HRMS(ESI)Calculated for C10H8DO2 +([M+H]+):162.0660,found: 162.0663。
Embodiment 15
First weigh(34.4mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy) PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 100-50:1) obtain product26.7mg, yield 85%, D incorporation by 1H NMR:97%.1H NMR(400MHz,Chloroform-d)δ10.16(s,0.03H),8.34 (s,1H),8.08–7.80(m,4H),7.72–7.50(m,2H).13C NMR(100MHz,Chloroform-d)δ191.9(t,J =26.7Hz), 136.5,134.6,134.0 (t, J=3.5Hz), 132.6,129.5,129.2,129.1,128.1,127.1, 122.8.2H NMR(92MHz,Chloroform-d)δ10.19(s,1D).HRMS(ESI)Calculated for C11H8DO+ ([M+H]+):158.0711,found:158.0714。
Embodiment 16
First weigh(34.4mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy)PF6 (2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P (0.22mmol, 57.6mg, 1.1equiv.) adds Enter reaction tube, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O (2.0mL, 1:1v/v) is then small 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are added in the heart, and then tube sealing is placed under 5W blue led s light irradiation, room Temperature is lower to react 36h.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase is through anhydrous Na2SO4It is dry Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, body Product ratio: 100-50:1) obtain product28.9mg, yield 92%, D incorporation by1H NMR: 95%.1H NMR (400MHz, Chloroform-d) δ 10.39 (s, 0.05H), 9.25 (d, J=8.4Hz, 1H), 8.09 (d, J =8.2Hz, 1H), 7.98 (dd, J=7.0,1.2Hz, 1H), 7.92 (d, J=8.2Hz, 1H), 7.75-7.54 (m, 3H)13C NMR (100MHz, Chloroform-d) δ 193.2 (t, J=26.7Hz), 136.7,135.3,133.7,131.3 (t, J= 3.5Hz),130.6,129.1,128.5,127.0,124.9.HRMS(ESI)Calculated forC11H8DO+([M+H]+): 158.0711,found:158.0713。
Embodiment 17
First weigh(39.6mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy)PF6 (2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P (0.22mmol, 57.6mg, 1.1equiv.) adds Enter reaction tube, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O (2.0mL, 1:1v/v) is then small 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are added in the heart, and then tube sealing is placed under 5W blue led s light irradiation, room Temperature is lower to react 36h.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase is through anhydrous Na2SO4It is dry Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, body Product ratio: 20-10:1) obtain product28.2mg, yield 77%, D incorporation by1H NMR:94% .1H NMR (400MHz, Chloroform-d) δ 9.98 (s, 0.06H), 8.04 (dd, J=7.8,1.4Hz, 1H), 7.64 (td, J =7.5,1.4Hz, 1H), 7.55-7.42 (m, 5H), 7.42-7.34 (m, 2H)13C NMR(100MHz,Chloroform-d)δ 192.0 (t, J=27.1Hz), 146.0,137.8,133.6,130.8,130.1,128.5,128.1,127.8,127.6.HR MS (ESI)Calculated for C13H10DO+([M+H]+):184.0867,found:184.0869。
Embodiment 18
First weigh(58.4mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent is evaporated off in dry back spin, column chromatography (300-400 mesh chromatographic silica gel): dry method loading obtains product42.1mg, yield 76%, D incorporation by1H NMR:97%.1H NMR (400MHz, Chloroform-d) δ 10.00 (s, 0.03H), 7.90-7.84 (m, 1H), 7.71 (d, J=8.3Hz, 2H), 7.63-7.55 (m, 1H), 7.40 (t, J=8.0Hz, 1H), 7.34 (d, J=8.1Hz, 2H), 7.20 (d, J=8.2Hz, 1H), 2.46(s,3H).13C NMR (100MHz, Chloroform-d) δ 186.9 (t, J=28.2Hz), 151.2,146.3,135.3, 131.3,130.2,129.2 (t, J=3.3Hz), 128.6,128.5,127.6,123.7,21.8.HRMS (ESI) Calculated for C14H12DO4S+([M+H]+):278.0592,found:278.0593。
Embodiment 19
First weigh(35.6mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy) PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), being then carefully added into 2,4,6- triisopropyl benzenethiols, (0.03mmol, 7.1mg, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 30-10:1) obtain product24.8mg, yield 76%, D incorporation by 1H NMR:95%.1H NMR(400MHz,Chloroform-d)δ9.97(s,0.05H),7.65–7.36(m,3H),7.24– 7.19 (m, 1H), 6.21-5.98 (m, 1H), 5.44 (dq, J=17.3,1.6Hz, 1H), 5.32 (dq, J=10.5,1.5Hz, 1H), 4.61 (dt, J=5.3,1.5Hz, 2H)13C NMR (100MHz, Chloroform-d) δ 191.9 (t, J=26.5Hz), 159.1,137.7 (t, J=3.4Hz), 132.6,130.1,123.6,122.1,118.1,113.1,69.0.HRMS (ESI) Calculated for C10H10DO2 +([M+H]+):164.0816,found:164.0818。
Embodiment 20
First weigh(35.2mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 20-10:1) obtain product21.3mg, yield 66%, D incorporation by 1H NMR:94%.1H NMR(400MHz,Chloroform-d)δ9.99(s,0.06H),7.56– 7.44 (m, 3H), 7.28-7.24 (m, 1H), 4.76 (s, 2H), 2.55 (t, J=2.4Hz, 0.5H, 50%D)13C NMR (100MHz, Chloroform-d) δ 191.7 (t, J=26.7Hz), 158.1,137.7 (t, J=3.6Hz), 130.2,124.1, 122.2,113.5,77.9,76.1,56.0.2H NMR(92MHz,Chloroform-d)δ10.03(s,1D),2.55(s,1D) .HRMS(ESI)Calculated for C10H8DO2 +([M+H]+):162.0660,found:162.0664。
Embodiment 21
First weigh(35.2mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 20-4:1) obtain product19.2mg, yield 70%, D incorporation by 1H NMR:95%.1H NMR (400MHz, Chloroform-d) δ 10.00 (s, 0.05H), 7.88 (d, J=8.2Hz, 2H), 7.53 (d, J=8.2Hz, 2H), 4.81 (s, 2H)13C NMR (100MHz, Chloroform-d) δ 191.6 (t, J= 26.4Hz), 147.8,135.6 (t, J=3.6Hz), 130.0,127.0,64.6.2H NMR(92MHz,Chloroform-d)δ 10.06(s,1D).HRMS(ESI)Calculated for C8H8DO2 +([M+H]+):138.0660,found:138.0662。
Embodiment 22
First weigh(46.8mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio 10-5:1) obtain product26.3mg, yield 60%, D incorporation by 1H NMR:96%.1H NMR(400MHz,Chloroform-d)δ10.03(s,0.04H),8.30 (s, 1H), 8.05 (d, J=6.2Hz, 1H), 7.94 (d, J=6.1Hz, 1H), 7.50 (t, J=7.5Hz, 1H), 3.79 (s, 4H),1.03(s,6H).13C NMR (100MHz, Chloroform-d) δ 192.5 (t, J=26.5Hz), 139.9,136.4, 135.6 (t, J=3.1Hz), 130.8,128.3,72.4,32.0,21.9.HRMS (ESI) Calculated for C12H15DBO3 +([M+H]+):220.1250,found:220.1253。
Embodiment 23
First weigh(49.6mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 15-5:1) obtain product37.7mg, yield 81%, D incorporation by 1H NMR:96%.1H NMR(400MHz,Chloroform-d)δ10.05(s,0.04H),7.96 (d, J=8.1Hz, 2H), 7.87 (d, J=8.2Hz, 2H), 1.37 (s, 12H)13C NMR(100MHz,Chloroform-d)δ 192.5 (t, J=26.7Hz), 138.03 (t, J=3.4Hz), 135.2,128.7,84.3,24.9.HRMS (ESI) Calculated for C13H17DBO3 +([M+H]+):234.1406,found:234.1409。
Embodiment 24
First weigh(37.2mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy)PF6 (2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P (0.22mmol, 57.6mg, 1.1equiv.) adds Enter reaction tube, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O (2.0mL, 1:1v/v) is then small 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are added in the heart, and then tube sealing is placed under 5W blue led s light irradiation, room Temperature is lower to react 36h.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase is through anhydrous Na2SO4It is dry Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, body Product ratio: 40-10:1) obtain product26.7mg, yield 78%, D incorporation by1H NMR: 95%.1H NMR(400MHz,Chloroform-d)δ9.92(s,0.05H),7.44(s,1H),7.29(s,1H),7.16(s, 1H),3.87(s,3H).13C NMR (100MHz, Chloroform-d) δ 190.3 (t, J=27.2Hz), 160.8,138.4 (t, J =3.6Hz), 135.9,122.8,120.9,111.7,55.9.HRMS (ESI) Calculated forC8H7DClO2 +([M+H]+): 172.0270,found:172.0272。
Embodiment 25
First weigh(33.2mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy) PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 15-4:1) obtain product15.1mg, yield 50%, D incorporation by 1H NMR:94%.1H NMR(400MHz,Chloroform-d)δ11.59(br s,1H),10.01(s,0.06H),9.95 (s, 1H), 8.15 (d, J=2.0Hz, 1H), 8.08 (dd, J=8.7,2.1Hz, 1H), 7.14 (d, J=8.7Hz, 1H)13C NMR (100MHz, Chloroform-d) δ 195.7 (t, J=27.5Hz), 189.4,166.3,137.2,136.5,129.2, 120.2 (t, J=3.1Hz), 118.9.HRMS (ESI) Calculated for C8H6DO3 +([M+H]+):152.0452, found:152.0454。
Embodiment 26
First weigh(42.9mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy) PF6(2.3mg,0.002mol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg,1.1equiv.) Reaction tube is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O (2.0mL, 1:1v/v), then 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are carefully added into, then tube sealing is placed under 5W blue led s light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase is through anhydrous Na2SO4 Dry back spin is evaporated off solvent, dry method loading, column chromatograph (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, Volume ratio: 20-10:1) obtain product34.0mg, yield 85%, D incorporation by1H NMR: 93%.1H NMR(400MHz,CDCl3) δ 9.81 (s, 0.07H), 7.32 (d, J=8.2Hz, 1H), 6.93-6.79 (m, 2H), 6.20(br s,2H).13C NMR (100MHz, Chloroform-d) δ 192.8 (t, J=26.5Hz), 150.5,136.9, (130.5,119.8,118.6,117.6 t, J=3.2Hz)2H NMR(92MHz,Chloroform-d)δ9.85(s,1D) .HRMS(ESI)Calculated for C7H6DBrNO+([M+H]+):200.9768,found:200.9769。
Embodiment 27
First weigh(34.6mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy) PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P(0.22mmol,57.6mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), being then carefully added into 2,4,6- triisopropyl benzenethiols, (0.03mmol, 7.1mg, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 10-3:1) obtain product14.2mg, yield 45%, D incorporation by 1H NMR:95%.1H NMR(400MHz,CDCl3) δ 10.21 (s, 0.05H), 9.06 (dd, J=4.2,1.7Hz, 1H), 8.44-8.27 (m, 2H), 8.22 (d, J=1.6Hz, 2H), 7.54 (dd, J=8.3,4.3Hz, 1H)13C NMR(100MHz, Chloroform-d) δ 191.1 (t, J=27.2Hz), 153.1,150.9,137.5,134.2 (t, J=3.4Hz), 133.6, 130.8,127.7,126.8,122.2.HRMS(ESI)Calculated for C10H7DNO+([M+H]+):159.0663, found:159.0665。
Embodiment 28
First weigh(35.0mg, 0.2mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy)PF6 (2.3mg,0.002mmol),K2HPO4(34.8mg, 1.0equiv.), and Ph3P (0.22mmol, 57.6mg, 1.1equiv.) adds Enter reaction tube, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O (2.0mL, 1:1v/v) is then small 2,4,6- triisopropyl benzenethiols (0.03mmol, 7.1mg) are added in the heart, and then tube sealing is placed under 5W blue led s light irradiation, room Temperature is lower to react 36h.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase is through anhydrous Na2SO4It is dry Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, body Product ratio: 20-10:1) obtain product29.4mg, yield 92%, D incorporation by1H NMR: 96%.1H NMR (400MHz, Chloroform-d) δ 9.89 (s, 0.04H), 7.74 (d, J=8.1Hz, 1H), 7.53-7.33 (m,2H),7.25(s,1H),7.22–7.15(m,1H),4.10(s,3H).13C NMR(100MHz,Chloroform-d)δ 182.5 (t, J=27.0Hz), 140.9,135.6 (t, J=4.3Hz), 126.9,126.3,123.4,120.9,117.5, 110.4,31.6.2H NMR(92MHz,Chloroform-d)δ9.91(s,1D).HRMS(ESI)Calculatedfor C10H9DNO+([M+H]+):161.0820,found:161.0822。
Embodiment 29
First weigh(29.8mg, 0.1mmol), photochemical catalyst Ir [dF (CF3)ppy]2 (dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 2.0equiv.), and Ph3P(0.11mmol,28.8mg, Reaction tube 1.1equiv.) is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O(2.0mL,1: 1v/v), 2,4,6- triisopropyl benzenethiols (0.02mmol, 4.7mg) are then carefully added into, then tube sealing is placed in 5W blue led s Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x 10mL) with DCM.Organic phase warp Anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether- Ethyl acetate, volume ratio: 20-5:1) obtain product26.0mg, yield 92%, Dincorporation by 1H NMR:97%.1H NMR(400MHz,Chloroform-d)δ9.94(s,0.03H),7.64 (d, J=8.0Hz, 1H), 7.60 (s, 1H), 7.45 (d, J=8.0Hz, 1H), 3.04-2.97 (m, 2H), 2.54-2.41 (m, 2H), 2.36 (td, J=10.8,3.9Hz, 1H), 2.22-2.02 (m, 3H), 2.03-1.96 (m, 1H), 1.76-1.40 (m, 6H),0.92(s,3H).13C NMR (100MHz, Chloroform-d) δ 220.5,191.9 (t, J=26.3Hz), 147.1, 137.5,134.2 (t, J=3.1Hz), 130.2,127.2,126.1,50.5,47.9,44.9,37.7,35.8,31.5,29.2, 26.2,25.6,21.6,13.8.HRMS(ESI)Calculated for C19H22DO2 +([M+H]+):284.1755,found: 284.1757。
Embodiment 30
First weigh(51.4mg, 0.1mmol), photochemical catalyst Ir [dF (CF3)ppy]2(dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 2.0equiv.), and Ph3P Reaction tube is added in (0.11mmol, 28.8mg, 1.1equiv.), substitutes gas three times by vacuum pipeline, under argon atmosphere, adds Enter DCM/D2O (2.0mL, 1:1v/v) is then carefully added into 2,4,6- triisopropyl benzenethiols (0.02mmol, 4.7mg), then Tube sealing is placed under 5W blue led s light irradiation, reacts 36h at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x with DCM 10mL).Organic phase is through anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatography (300-400 mesh chromatographic silica gel) (is washed De- agent: petroleum ether-ethyl acetate, volume ratio: 4-1:1) obtain product 33.4mg, yield 67%, D incorporation by1H NMR:95%.1HNMR(400MHz,Chloroform-d)δ9.91 (s, 0.05H), 7.99 (d, J=7.8Hz, 1H), 7.80-7.76 (m, 1H), 7.63-7.56 (m, 1H), 7.53-7.46 (m, 2H), 7.41 (s, 1H), 7.39-7.33 (m, 2H), 7.32 (s, 1H), 7.31-7.25 (m, 3H), 7.14 (d, J=8.2Hz, 2H), 5.47 (s, 2H), 3.81 (s, 3H), 2.93 (t, J=7.8Hz, 2H), 2.77 (s, 3H), 1.92-1.67 (m, 2H), 1.05 (t, J=7.4Hz, 3H)13C NMR (100MHz, Chloroform-d) δ 191.8 (t, J=26.2Hz), 156.4,154.6, 145.0,143.2,142.8,137.5,136.7,136.0,135.1,133.7,132.0 (t, J=3.4Hz), 130.7, 129.5,128.0,127.8,126.2,124.1,123.9,122.6,122.4,119.5,109.6,108.9,46.8,31.8, 29.8,21.9,16.9,14.1.HRMS(ESI)Calculated for C33H30DN4O+([M+H]+):500.2555,found: 500.2557。
Embodiment 31
First weigh(41.2mg, 0.1mmol), photochemical catalyst Ir [dF (CF3) ppy]2(dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 2.0equiv.), and Ph3P(0.11mmol, 28.8mg, 1.1equiv.) reaction tube is added, gas is substituted three times by vacuum pipeline, under argon atmosphere, DCM/D is added2O (2.0mL, 1:1v/v) is then carefully added into 2,4,6- triisopropyl benzenethiols (0.02mmol, 4.7mg), and then tube sealing is placed in Under 5W blue led s light irradiation, 36h is reacted at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x with DCM 10mL).Organic phase is through anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, volume ratio: 20-5:1) obtains product 29.0mg, yield 73%, D incorporation by1H NMR:96%.1H NMR(400MHz,Chloroform-d)δ 10.15 (s, 0.04H), 8.34 (s, 1H), 8.09-8.01 (m, 2H), 7.97 (s, 2H), 7.84 (dd, J=8.4,1.7Hz, 1H), 7.61 (d, J=2.3Hz, 1H), 7.56 (dd, J=8.4,2.3Hz, 1H), 7.01 (d, J=8.4Hz, 1H), 3.91 (s, 3H),2.18(s,6H),2.11(s,3H),1.81(s,6H).13C NMR (100MHz, Chloroform-d) δ 192.1 (t, J= 27.0Hz), 159.1,142.3,139.1,137.0,134.4,133.7 (t, J=3.1Hz), 132.3,131.4,129.9, 129.2,126.9,126.0,125.8,125.0,123.2,112.1,55.2,40.6,37.2,37.1,29.1.HRMS(ESI) Calculated for C28H28DO2 +([M+H]+):398.2225,found:398.2227。
Embodiment 32
First weigh(46.4mg, 0.1mmol), photochemical catalyst Ir [dF(CF3)ppy]2(dtbbpy)PF6(2.3mg,0.002mmol),K2HPO4(34.8mg, 2.0equiv.), and Ph3P Reaction tube is added in (0.11mmol, 28.8mg, 1.1equiv.), substitutes gas three times by vacuum pipeline, under argon atmosphere, adds Enter DCM/D2O (2.0mL, 1:1v/v) is then carefully added into 2,4,6- triisopropyl benzenethiols (0.02mmol, 4.7mg), then Tube sealing is placed under 5W blue led s light irradiation, reacts 36h at room temperature.Reaction terminates, and mixture adds water to quench, and extracts (3x with DCM 10mL).Organic phase is through anhydrous Na2SO4Solvent, dry method loading is evaporated off in dry back spin, and column chromatography (300-400 mesh chromatographic silica gel) (is washed De- agent: petroleum ether-ethyl acetate, volume ratio: 30-10:1) obtain product 28.7mg, yield 64%, D incorporation by1H NMR:94%.1H NMR(400MHz,Chloroform-d)δ 10.07 (s, 0.06H), 8.52 (s, 1H), 8.29 (d, J=10.7Hz, 1H), 8.07 (d, J=10.5Hz, 1H), 7.62 (t, J =7.7Hz, 1H), 5.42 (d, J=4.7,1H), 4.94-4.83 (m, 1H), 2.55-2.40 (m, 3H), 2.20 (d, J= 10.8Hz, 1H), 2.12 (s, 3H), 2.05-1.99 (m, 3H), 1.93 (dt, J=13.3,3.4Hz, 1H), 1.77-1.43 (m, 9H),1.27–1.18(m,3H),1.07(s,3H),0.63(s,3H).13C NMR(100MHz,Chloroform-d)δ209.6, 191.1 (t, J=27.8Hz), 164.9,139.4,136.4 (t, J=3.5Hz), 135.2,133.1,131.9,131.1, 129.2,122.7,75.1,63.7,56.8,49.9,44.0,38.8,38.1,37.0,36.7,31.8,31.8,31.6,27.8, 24.5,22.8,21.1,19.4,13.2.2H NMR(92MHz,Chloroform-d)δ10.13(s,1D).HRMS(ESI) Calculated for C29H36DO4 +([M+H]+):450.2749,found:450.2752。
Deuterated fatty aldehyde preparating example:
Embodiment 33
First weigh(15.1mg, 0.1mmol), photochemical catalyst Ir [dF (Me) ppy]2(dtbbpy) PF6Reaction tube is added in (2.5mg, 0.0025mmol), substitutes gas three times by vacuum pipeline, and under argon atmosphere, toluene is added (5.0mL) is then carefully added into 2,4,6- triisopropyl benzenethiols (0.04mmol, 9.4mg), hexichol base oxethyl phosphine (0.12mmol, 27.6mg), then tube sealing is placed in 45W blue led s lamp photograph to 2,6- lutidines (0.12mmol, 12.8mg) It penetrates down, reacts 36h at room temperature.Reaction terminates, and solvent, dry method loading is removed under reduced pressure, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, volume ratio: 100-50:1) obtains product7.6mg, yield 56%, D incorporation by 1H NMR:63%.1H NMR(400MHz,Chloroform-d)δ9.82(s,0.37H),7.29 (t, J=7.3Hz, 2H), 7.23-7.16 (m, 3H), 2.96 (t, J=7.5Hz, 2H), 2.78 (t, J=7.5Hz, 2H)13C NMR (100MHz, Chloroform-d) δ 201.1 (t, J=26.2Hz), 140.3,128.6,128.3,126.3,45.3, 28.1.HRMS(ESI)Calculated for C9H10DO+([M+H]+):136.0867,found:136.0870。
Embodiment 34
First weigh(19.7mg, 0.1mmol), photochemical catalyst Ir [dF (Me) ppy]2 (dtbbpy)PF6Reaction tube is added in (2.5mg, 0.0025mmol), substitutes gas three times by vacuum pipeline, under argon atmosphere, It is added toluene (5.0mL), is then carefully added into 2,4,6- triisopropyl benzenethiols (0.04mmol, 9.4mg), diphenyl ethoxy Base phosphine (0.12mmol, 27.6mg), then tube sealing is placed in 45W blue led s to 2,6- lutidines (0.12mmol, 12.8mg) Under light irradiation, 36h is reacted at room temperature.Reaction terminates, and solvent is removed under reduced pressure, dry method loading, (300-400 mesh chromatographs silicon to column chromatography Glue) (eluant, eluent: petroleum ether-ethyl acetate, volume ratio: 100-50:1) obtain product7.4mg is produced Rate 41%, dr=5:1, D incorporation by1H NMR:58%.1HNMR(400MHz,CDCl3) δ 9.34 (d, J= 4.5Hz, 0.42H), 7.26 (d, J=8.4,2H), 7.04 (d, J=8.4Hz, 2H), 2.63-2.57 (m, 1H), 2.18-2.12 (m,1H),1.77–1.68(m,1H),1.54–1.44(m,1H).13C NMR(100MHz,Chloroform-d)δ199.1(t,J =23.2Hz), 137.5,132.6,128.7,127.7,33.7,26.0,16.5.HRMS (ESI) Calculated for C10H9DClO+([M+H]+):182.0477,found:182.0479。
Embodiment 35
First weigh(16.3mg, 0.1mmol), photochemical catalyst Ir [dF (Me) ppy]2(dtbbpy)PF6 Reaction tube is added in (2.5mg, 0.0025mmol), substitutes gas three times by vacuum pipeline, and under argon atmosphere, toluene is added (5.0mL) is then carefully added into 2,4,6- triisopropyl benzenethiols (0.04mmol, 9.4mg), hexichol base oxethyl phosphine (0.12mmol, 27.6mg), then tube sealing is placed in 45W blue led s lamp photograph to 2,6- lutidines (0.12mmol, 12.8mg) It penetrates down, reacts 36h at room temperature.Reaction terminates, and solvent, dry method loading is removed under reduced pressure, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, volume ratio: 100-50:1) obtains product8.8mg, yield 60%, D incorporation by 1H NMR:75%.1H NMR (400MHz, Chloroform-d) δ 9.77 (d, J=1.3Hz, 0.24H),7.29–7.20(m,2H),7.17–7.11(m,2H),3.37–3.24(m,3H),3.22–3.12(m,2H).13C NMR (100MHz, Chloroform-d) δ 202.6 (t, J=23.2Hz), 141.1,126.8,124.6,50.7,32.9.HRMS (ESI)Calculated for C10H10DO+([M+H]+):148.0867,found:148.0868。
Embodiment 36
First weigh(35.2mg, 0.1mmol), photochemical catalyst Ir [dF (Me) ppy]2(dtbbpy) PF6Reaction tube is added in (2.5mg, 0.0025mmol), substitutes gas three times by vacuum pipeline, and under argon atmosphere, toluene is added (5.0mL) is then carefully added into 2,4,6- triisopropyl benzenethiols (0.04mmol, 9.4mg), hexichol base oxethyl phosphine (0.12mmol, 27.6mg), then tube sealing is placed in 45W blue led s lamp photograph to 2,6- lutidines (0.12mmol, 12.8mg) It penetrates down, reacts 36h at room temperature.Reaction terminates, and solvent, dry method loading is removed under reduced pressure, and column chromatographs (300-400 mesh chromatographic silica gel) (eluant, eluent: petroleum ether-ethyl acetate, volume ratio: 10-2:1) obtains product19.2mg, yield 57%, D incorporation by 1H NMR:72%.1H NMR (400MHz, CDCl3) δ 9.64 (s, 0.28H), 7.76 (d, J= 7.5Hz, 2H), 7.57 (d, J=7.5Hz, 2H), 7.40 (t, J=7.4Hz, 2H), 7.31 (t, J=7.9Hz, 2H), 4.45 (s, 2H), 4.24 (t, J=6.6Hz, 1H), 4.02-3.91 (m, 2H), 2.99 (t, J=12.1Hz, 2H), 2.66-2.26 (m, 1H), 1.87 (s, 2H), 1.50 (s, 2H) .13C NMR (100MHz, Chloroform-d) δ 202.3 (t, J=26.2Hz), 155.1, 144.0,141.4,127.7,127.1,124.9,120.0,67.2,47.7,47.4,43.0,25.0.HRMS(ESI) Calculated for C21H21DNO3 +([M+H]+):337.1657,found:337.1658。

Claims (10)

1. it is a kind of from aromatic carboxylic acids using complex of iridium as catalyst, blue light illumination under prepare the method for deuterated aldehyde, it is characterized in that: it It is using aromatic carboxylic acids as raw material, triphenylphosphine is as deoxidier, under blue light light irradiation, in the solution of methylene chloride and heavy water In, wherein the volume ratio of methylene chloride and heavy water is 1:1, is quickly stirred, under argon atmosphere, in the item that dipotassium hydrogen phosphate is alkali Under part, with [Ir (dF (CF3)ppy)2(dtbbpy)]PF6For photochemical catalyst, 2,4,6- triisopropyl benzenethiols are small organic molecule Catalyst obtains deuterated Aromatic aldehyde compound.
2. preparation method according to claim 1, it is characterized in that: the Ar group in the aromatic carboxylic acids is various substitutions Aryl or heteroaryl.
3. preparation method according to claim 1, it is characterized in that: the amount of the substance of the aromatic carboxylic acids and triphenylphosphine The ratio between be 1:1-2.
4. preparation method according to claim 1, it is characterized in that: the substance of the dipotassium hydrogen phosphate and aromatic carboxylic acids The ratio between amount is 1:1-2.
5. according to the above-mentioned preparation method of right 1, it is characterized in that: the photochemical catalyst [Ir (dF (CF3)ppy)2(dtbbpy)] PF6Dosage is 1% mole of aromatic carboxylic acids molal quantity；Described 2,4,6- triisopropyl benzenethiol catalyst amounts are virtues 15% mole of fragrant carboxylic acid molal quantity.
6. it is a kind of from aliphatic carboxylic acid using complex of iridium as catalyst, blue light illumination under prepare the method for deuterated aldehyde, it is characterized in that: It is using deuterated aliphatic carboxylic acid as raw material, and hexichol base oxethyl phosphine is as deoxidier, with [Ir (dF (Me) ppy)2 (dtbbpy)]PF6For photochemical catalyst, 2,4,6- triisopropyl benzenethiols are organic micromolecule catalyst, under blue light light irradiation, In toluene solution, under argon atmosphere, under the conditions of 2,6- lutidines is existing, deuterated aliphatic aldehyde compound is obtained.
7. preparation method according to claim 6, it is characterized in that: the aliphatic carboxylic acid is the fat of various different alkyl Carboxylic acid.
8. preparation method according to claim 6, it is characterized in that: the object of the aliphatic carboxylic acid and hexichol base oxethyl phosphine The ratio between amount of matter is 1:1-2.
9. preparation method according to claim 6, it is characterized in that: the object of 2, the 6- lutidines and aliphatic carboxylic acid The ratio between amount of matter is 1:1-2.
10. preparation method according to claim 6 the, it is characterized in that: photochemical catalyst [Ir (dF (Me) ppy)2 (dtbbpy)]PF6Dosage is 2.5% mole of aliphatic carboxylic acid molal quantity；Described 2,4,6- triisopropyl benzenethiols are urged The dosage of agent is 40% mole of aliphatic carboxylic acid molal quantity.
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WO2021118827A1 (en) * 2019-12-11 2021-06-17 Arizona Board Of Regents On Behalf Of The University Of Arizona Visible-light mediated organophotoredox catalytic deuteration of aromatic and aliphatic aldehydes
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Publication number Priority date Publication date Assignee Title
CN109824530A (en) * 2019-04-04 2019-05-31 南京大学 A method of adjacent amino aromatic ketone is synthesized by aromatic carboxylic acids
CN109824530B (en) * 2019-04-04 2021-09-28 南京大学 Method for synthesizing o-amino aromatic ketone from aromatic carboxylic acid
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CN111943826A (en) * 2020-08-19 2020-11-17 河南师范大学 Preparation method of novel deuterated aromatic aldehyde compound
CN114075108A (en) * 2020-08-19 2022-02-22 南开大学 Deuteration of aldehyde and application in preparing deuteration aldehyde

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