CN107056795B - A kind of loop coil hydroxyindole pentamethylene and β-lactones compound synthesis method - Google Patents
A kind of loop coil hydroxyindole pentamethylene and β-lactones compound synthesis method Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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Abstract
The invention discloses a kind of synthetic methods of compound in loop coil hydroxyindole pentamethylene and β, and specially with phenyl unsaturated aldehyde, beta-unsaturated ketone acid esters is reactant, and using N-heterocyclic carbine as catalyst, reaction obtains loop coil hydroxyindole pentamethylene and β‑Interior compound.Method raw material disclosed by the invention is simple and easy to get, and reaction condition is mild, and post-processing is simple and convenient, and applicable substrate spectrum is wide, high income, and cis-selectivity and enantioselectivity are high；Thus the product synthesized can be used to the intermediate of synthetic drug and insecticide.
Description
Technical field
The present invention relates to the synthesis of loop coil producing oxindoles compound, and in particular to a kind of loop coil hydroxyindole pentamethylene and β-is interior
The process for catalytic synthesis of compound.
Background technique
Loop coil producing oxindoles compound widely exists in natural products, have antiviral, sterilization, inhibitory enzyme activity,
The significant physiology such as anti-oxidant and radiation protection, antitumor and pharmacological activity.It is simultaneously also indispensable in many drug molecules
Important structural unit, therefore the concern by many scientists.And simultaneously the interior lipoid substance of β-also has good life to pentamethylene
Object activity and medical value, but leave away a molecule carbon dioxide since decarboxylation easily occurs for the product and be difficult to obtain.Therefore develop
Efficient method all comes together to synthesis of chiral loop coil hydroxyl Yin with bioactivity and the structure of pharmacological action for these two types of
Diindyl pentamethylene and the interior compound of β-have attracted the great interest of many chemists, but its synthetic method is not reported.
In organic synthesis field, the synthetic method by organic catalysis is a kind of synthesis hand that is efficient, having economic value
The method of property compound.It is widely used in the synthesis of various Complex Chiral Compounds nearly ten years.Loop coil oxindole compounds
Synthesis is exactly the hydroxyindole of nitro compds and three substitutions under the hot spot of a research, such as the catalysis of the thiocarbamide derived from golden pheasant soda
The Michael-Henry tandem reaction of derivative, this method can obtain hydroxyindole with good yield, outstanding enantioselectivity
Derivative cyclopentane derivatives.The synthetic method of loop coil oxindole derivatives is relatively common in the prior art, but loop coil hydroxyindole
Simultaneously β-lactones compound synthesis method is reported pentamethylene not yet, because simultaneously β-lactones product is difficult stable pentamethylene
It arrives, quaternary cyclic lactone is easy to open loop, the cyclopentene product after obtaining decarboxylation.In fact, beta-propiolactone be not only it is exceedingly useful
Building block, such as synthesize carboxylic acid, polyester, Oxygenic heterocyclic compounds (H. Nguyen, the G. Ma, T. of various straight chains
Gladysheva, T. Fremgen, D. Romo, J. Org. Chem. 2011,76,2-12.)；Beta-propiolactone itself
The intermediate that may be used as drug, resin and fibre modifier is also used as the disinfection sanitizer of blood plasma, vaccine, derives
ObjectβMercaptopropionic acid is the raw material of PVC stabilizer and medicine.
Therefore it is necessary to find a kind of simple, efficient synthesizing spiro hydroxyindole pentamethylene and the interior compound of β-
Synthetic method, this method enantioselectivity and cis-selectivity are outstanding, while required substrate is easily-synthesized, cheap and easy to get, catalysis
Agent high catalytic efficiency, reaction condition is mild, easy to operate.
Summary of the invention
The object of the present invention is to provide loop coil hydroxyindole pentamethylene and the process for catalytic synthesis of the interior compound of β-；Lead to for the first time
The efficient synthesizing spiro hydroxyindole pentamethylene of N-heterocyclic carbine and β-lactones structural compounds are crossed, structure novel avoids existing
The defect that technology ester bond is detached from form of carbon dioxide.
To achieve the above object of the invention, the technical solution adopted by the present invention is that: a kind of loop coil hydroxyindole pentamethylene and β-is interior
The synthetic method of compound, with phenyl unsaturated aldehyde, beta-unsaturated ketone acid esters is reactant, using N-heterocyclic carbine as catalyst,
Reaction obtains loop coil hydroxyindole pentamethylene and β-Interior compound；
The chemical structural formula of the phenyl unsaturated aldehyde is, wherein R1It is selected from: 2- methoxyl group, 3- nitre
One of base, 4- methoxyl group, chlorine, nitro, bromine, cyano, bis- chlorine substituent of 2,4-；
The chemical structural formula of the beta-unsaturated ketone acid esters is, wherein R2For 5- methyl, methoxyl group, fluorine, 7-
Methyl or 5,6- difluoro；R3For methyl, allyl, benzyl；
The loop coil hydroxyindole pentamethylene and β-The structural formula of interior compound are as follows:
。
In the present invention, the catalyst is N-heterocyclic carbine, and chemical structural formula is as follows:
In above-mentioned technical proposal, reaction process is included in 0 DEG C, and it is unsaturated that catalyst, phenyl are sequentially added into reaction flask
Aldehyde, beta-unsaturated ketone acid esters, 4 molecular sieves, solvent, magnetic agitation are reacted, and after reaction, crude product passes through simple column
Target product can be obtained in chromatography (eluant, eluent is preferably ethyl acetate: petroleum ether=1:5~1:10)；Product prepared by the present invention
For the first time retain quaternary lactonic ring, thus become many antibacterials, antitumor, resisting HIV, antivirotic and
The analog of enzyme inhibitor has huge potential using value.
The reaction carries out in ethers, benzene class or alcohols solvent；Such as methylene chloride, ether, tetrahydrofuran, first
In benzene, 1,2- dichloroethanes, paraxylene, mesitylene, meta-xylene, ortho-xylene, 1,4- dioxane or methanol into
Row, wherein cooperation N-heterocyclic carbine is that catalyst reaction effect is best when using mesitylene as solvent.
With molar amount, the dosage of the catalyst is the 5-20% of beta-unsaturated ketone acid esters；The dosage of phenyl unsaturated aldehyde is
1.5 times of beta-unsaturated ketone acid esters；In preferred scheme, the dosage of the catalyst is the 10% of beta-unsaturated ketone acid esters dosage.
In the present invention, the reaction temperature is 0 DEG C, and the time is 24 hours.
Preferably, the reaction carries out in the presence of 4 molecular sieve.
The invention also discloses according to above-mentioned loop coil hydroxyindole pentamethylene and β-The synthetic method synthesis of interior compound
Loop coil hydroxyindole pentamethylene and β-Interior compound, avoid prior art ester bond all with form of carbon dioxide be detached from defect,
Success is closed CC key and achieves unexpected technical effect to form four-membered ring lactonic ring.
The efficient synthesizing spiro hydroxyindole pentamethylene of first passage N-heterocyclic carbine of the present invention and β-lactones structural compounds,
It thus discloses N-heterocyclic carbine and is preparing loop coil hydroxyindole pentamethylene and β-Application in interior compound.It also discloses simultaneously
N-heterocyclic carbine in catalysis phenyl unsaturated aldehyde is reacted with beta-unsaturated ketone acid esters using and phenyl unsaturated aldehyde and/or not
Saturation keto ester is preparing loop coil hydroxyindole pentamethylene and β-Application in interior compound；The loop coil hydroxyindole pentamethylene is simultaneously
β-The structural formula of interior compound are as follows:
。
Above-mentioned reaction process is as follows:
Due to the above technical solutions, the present invention has the following advantages over the prior art:
1. it is to urge that the present invention, which is realized for the first time using phenyl unsaturated aldehyde and beta-unsaturated ketone acid esters as reactant, N-heterocyclic carbine,
The method of agent synthesizing spiro hydroxyindole pentamethylene and the interior compound of β-, this method is easy to operate, high income, enantioselectivity
It is good with cis-selectivity；
2. simultaneously β-lactones post-reaction treatment is simple for synthesizing spiro hydroxyindole pentamethylene disclosed in this invention, reaction belongs to
Aldol-Lactonizationization is reacted, and does not have by-product generation in system；Prior art ester bond is avoided all with carbon dioxide
The defect that form is detached from successfully is closed CC key to form four-membered ring lactonic ring and achieves unexpected technical effect；
3. the method suitable substrates range of synthesizing spiro hydroxyindole pentamethylene disclosed by the invention and the interior compound of β-is very
Extensively, raw material be industrialization, product cheap and easy to get, it is pollution-free；And functional group compatibility is high, and cis-selectivity is outstanding,
High income.
Specific embodiment
The present invention will be further described below with reference to examples:
Embodiment one
The chemical structural formula of N-heterocyclic carbine is as follows:
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1a (19.8mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of condition in 2a (26 mg, 0.1 mmol), 4 molecular sieves (10 mg)
Lower reaction 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:5) by simple column, can be obtained mesh
It marks product 3a (21.1 mg), white solid, yield 54%, > 99/1 dr, 91% ee；Antibacterials can be prepared.
N-heterocyclic carbine (1.85 mg, 0.005 mmol) is sequentially added in reaction flask as catalyst and 1a
0.5 mL mesitylene is added, 0 in (19.8mg, 0.15 mmol), 2a (26 mg, 0.1 mmol), 4 molecular sieves (5mg)
It is reacted 24 hours under the conditions of DEG C, reaction system chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:5) by simple column
Obtain target product 3a (15.2 mg), white solid, yield 39%, > 99/1 dr, 90% ee.
Sequentially added in reaction flask N-heterocyclic carbine (7.4 mg, 0.02 mmol) as catalyst and 1a (19.8mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of condition in 2a (26 mg, 0.1 mmol), 4 molecular sieves (20 mg)
Lower reaction 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:5) by simple column, can be obtained mesh
It marks product 3a (20.3 mg), white solid, yield 52%, > 99/1 dr, 90% ee.
Product 3a is analyzed, it is as a result as follows: to measure [Daicel Chiralcel OJ-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 11.70, t
(minor) = 13.29]; [α]20 D = –38.9 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 7.44 (dd, J = 7.2, 1.2 Hz, 1H), 7.23 (dd, J = 7.6, 1.2 Hz, 1H), 7.20 – 7.06
(m, 4H), 6.91 – 6.89 (m, 2H), 6.57 (d, J = 7.6 Hz, 1H), 4.97 (d, J = 8.0 Hz,
1H), 4.43 (q, J = 7.2 Hz, 2H), 4.00 (d, J = 8.4 Hz, 1H), 3.26 (d, J = 14.8
Hz, 1H), 2.81 (s, 3H), 2.72 (d, J = 14.8 Hz, 1H), 1.41 (t, J = 7.2 Hz, 3H).13C NMR (101 MHz, CDCl3) δ 176.7, 169.0, 166.9, 143.2, 133.3, 128.7, 127.6,
127.5, 127.1, 126.7, 122.5, 122.2, 107.8, 83.6, 65.4, 63.6, 62.3, 54.1, 39.4,
25.2, 13.6. IR (neat, cm-1): 3056,2965,2323,1982,1836,1748,1733,1699,
1469,1298,1093,1066,1056,808. HRMS (ESI): calcd. for C23H21NO5H+ [M + H] +
392.1492; found: 392.1498。
Embodiment two
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1b (24.3mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of condition in 2a (26 mg, 0.1 mmol), 4 molecular sieves (10 mg)
Lower reaction 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:5) by simple column, can be obtained mesh
It marks product 3b (23.9 mg), white solid, yield 57%, > 99/1 dr, 91% ee can prepare anti-tumor drug.
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1b (24.3mg,
0.15 mmol), 2a (26 mg, 0.1 mmol) is added 0.5 mL mesitylene, reacts 24 hours under the conditions of 0 DEG C, reacts
System, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:5) by simple column, can be obtained target product 3b (20.8mg),
White solid, yield 51%, > 99/1 dr, 88% ee.
Product 3b is analyzed, it is as a result as follows: to measure [Daicel Chiralcel AD-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 11.51, t
(minor) = 17.35]; [α]20 D = –51.7 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 7.48 (d, J = 7.6 Hz, 1H), 7.24 – 7.19 (m, 1H), 7.15 – 7.06 (m, 3H), 6.80
(t, J = 7.6 Hz, 1H), 6.64 (t, J = 7.2 Hz, 2H), 4.73 (d, J = 6.0 Hz, 1H), 4.54
(d, J = 6.4 Hz, 1H), 4.42 (q, J = 7.2 Hz, 2H), 3.51 (s, 3H), 3.31 (d, J =
15.2 Hz, 1H), 2.90 (s, 3H), 2.66 (d, J = 15.2 Hz, 1H), 1.40 (t, J = 7.2 Hz,
3H). 13C NMR (101 MHz, CDCl3) δ 176.5, 169.3, 167.2, 156.8, 142.7, 129.3,
128.5, 128.1, 127.7, 123.9, 123.5, 122.1, 119.8, 109.9, 107.3, 85.2, 65.1,
63.8, 62.2, 54.5, 47.9, 39.9, 25.4, 13.6. IR (neat, cm-1): 2924,1830,1716,
1601,1491,1483,1286,1102,902,750. HRMS (ESI): calcd. for C24H23NO6H+ [M +
H] + 422.1598; found: 422.1612。
Embodiment three
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1b (26.5mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of condition in 2a (26 mg, 0.1 mmol), 4 molecular sieves (10 mg)
Lower reaction 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column, can be obtained mesh
It marks product 3c (28.3 mg), white solid, yield 65%, > 99/1 dr, 86% ee can prepare enzyme inhibitor.
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1b (26.5mg,
0.15 mmol), 0.5 mL tetrahydrofuran is added, in 0 DEG C of condition in 2a (26 mg, 0.1 mmol), 4 molecular sieves (10 mg)
Lower reaction 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column, can be obtained mesh
It marks product 3c (20.6mg), white solid, yield 47%, > 99/1 dr, 81% ee.
Product 3c is analyzed, it is as a result as follows: to measure [Daicel Chiralcel OD-H, hexane/ with HPLC
iPrOH (80:20), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 15.64, t
(minor) = 12.77]; [α]20 D = 88.1 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 8.03 (dt, J = 7.2, 2.4 Hz, 1H), 7.72 (s, 1H), 7.49 (dd, J = 7.6, 1.2 Hz,
1H), 7.39 – 7.34 (m, 2H), 7.31 – 7.29 (m, 1H), 7.19 (td, J = 7.6, 1.2 Hz,
1H), 6.64 (d, J = 7.6 Hz, 1H), 4.95 (d, J = 8.0 Hz, 1H), 4.45 (q, J = 7.2 Hz,
2H), 4.10 (d, J = 8.0 Hz, 1H), 3.31 (d, J = 15.2 Hz, 1H), 2.87 (s, 3H), 2.75
(d, J = 15.2 Hz, 1H), 1.43 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
176.1, 168.2, 166.6, 147.4, 142.9, 136.0, 133.2, 129.3, 128.8, 126.1, 123.1,
122.6, 122.3, 122.3, 108.2, 83.5, 65.0, 63.7, 62.6, 53.2, 39.8, 25.4, 13.6.
IR (neat, cm-1): 3095,1830,1711,1605,1455,1434,1267,1124,901,741.
HRMS (ESI): calcd. for C23H20N2O7H+ [M + H] + 437.1343; found: 437.1355。
Example IV
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1d (24.3mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of condition in 2a (26 mg, 0.1 mmol), 4 molecular sieves (10 mg)
Lower reaction 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column, can be obtained mesh
It marks product 3d (26.5 mg), white solid, yield 63%, > 99/1 dr, 86% ee.
Product 3d is analyzed, it is as a result as follows: to measure [Daicel Chiralcel AD-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 13.35, t
(minor) = 17.93]; [α]20 D = –73.9 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 7.42 (dd, J = 7.6, 1.2 Hz, 1H), 7.23 (dd, J = 7.6, 1.2 Hz, 1H), 7.13 (td, J
= 7.6, 1.2 Hz, 1H), 6.84 – 6.82 (m, 2H), 6.62 – 6.58 (m, 3H), 4.90 (d, J =
8.4 Hz, 1H), 4.43 (q, J = 7.2 Hz, 2H), 3.95 (d, J = 8.4 Hz, 1H), 3.69 (s,
3H), 3.24 (d, J = 14.8 Hz, 1H), 2.84 (s, 3H), 2.69 (d, J = 14.8 Hz, 1H), 1.41
(t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 176.9, 169.0, 167.0, 158.7,
143.2, 128.7, 128.3, 126.9, 125.3, 122.5, 122.1, 113.0, 107.8, 83.5, 65.4,
63.8, 62.3, 54.7, 53.6, 39.4, 25.2, 13.6. IR (neat, cm-1): 2981,1834,1750,
1607,1375,1264,1071,905,761,674. HRMS (ESI): calcd. for C24H23NO6H+ [M +
H] + 422.1598; found: 422.1604。
Embodiment five
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1e (26.5mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of condition in 2a (26 mg, 0.1 mmol), 4 molecular sieves (10 mg)
Lower reaction 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column, can be obtained mesh
It marks product 3e (30.9 mg), white solid, yield 71%, > 99/1 dr, 91% ee.
Product 3e is analyzed, it is as a result as follows: to measure [Daicel Chiralcel OD-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 26.35, t
(minor) = 42.06]; [α]20 D = 68.2 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 7.97 (d, J = 8.8, 1H), 7.49 – 7.46 (m, 1H), 7.30 (td, J = 7.6, 1.2 Hz, 1H),
7.18 (td, J = 7.6, 0.8 Hz, 1H), 7.12 – 7.10 (m, 1H), 6.63 (d, J = 7.6 Hz,
1H), 4.97 (d, J = 8.4 Hz, 1H), 4.45 (q, J = 7.2 Hz, 2H), 4.09 (d, J = 8.0 Hz,
1H), 3.30 (d, J = 15.2 Hz, 1H), 2.85 (s, 3H), 2.75 (d, J = 14.8 Hz, 1H), 1.42
(t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 176.1, 168.2, 166.5, 147.1,
142.9, 140.9, 129.3, 128.3, 125.9, 123.0, 122.8, 122.2, 108.2, 83.5, 65.3,
63.5, 62.5, 53.3, 39.8, 25.4, 13.6. IR (neat, cm-1): 2987,2922,1792,1740,
1616,1541,1319,1123,668. HRMS (ESI): calcd. for C23H20N2O7H+ [M + H] +
437.1343; found: 437.1357。
Embodiment six
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1f (24.9mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of condition in 2a (26 mg, 0.1 mmol), 4 molecular sieves (10 mg)
Lower reaction 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column, can be obtained mesh
It marks product 3f (26.7 mg), white solid, yield 63%, > 99/1 dr, 91% ee.
Product 3f is analyzed, it is as a result as follows: to measure [Daicel Chiralcel AD-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 11.52, t
(minor) = 13.30]; [α]20 D = –27.4 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 7.43 (dd, J = 7.2, 1.2 Hz, 1H), 7.28 – 7.24 (m, 1H), 7.14 (td, J = 7.6, 0.8
Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.85 (d, J = 8.8 Hz, 2H), 6.61 (d, J = 7.6
Hz, 1H), 4.91 (d, J = 8.4 Hz, 1H), 4.43 (q, J = 7.2 Hz, 2H), 3.96 (d, J = 8.0
Hz, 1H), 3.25 (d, J = 15.2 Hz, 1H), 2.85 (s, 3H), 2.70 (d, J = 15.0 Hz, 1H),
1.41 (t, J = 6.8 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 176.5, 168.7, 166.8,
143.1, 133.46, 131.9, 128.9, 128.6, 127.8, 126.4, 122.7, 122.1, 108.0, 83.5,
65.3, 63.6, 62.4, 53.3, 39.5, 25.3, 13.6. IR (neat, cm-1): 2933, 1772, 1613,
1576, 1471, 1329, 1141, 1013, 720, 631. HRMS (ESI): calcd. for C23H20ClNO5H+ [M
+ H] + 426.1103; found: 426.1120。
Embodiment seven
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1g (31.3mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of condition in 2a (26 mg, 0.1 mmol), 4 molecular sieves (10 mg)
Lower reaction 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column, can be obtained mesh
It marks product 3g (28.1 mg), white solid, yield 60%, > 99/1 dr, 90% ee.
Product 3g is analyzed, it is as a result as follows: to measure [Daicel Chiralcel AD-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 14.50, t
(minor) = 12.17]; [α]20 D = 14.9 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 7.42 (dd, J = 7.2 Hz, 0.8 Hz, 1H), 7.25 – 7.21 (m, 3H), 7.15 (td, J = 7.6
Hz, 0.8 Hz, 1H), 6.79 (d, J = 8.4 Hz, 2H), 6.62 (d, J = 8.0 Hz, 1H), 4.90 (d,J = 8.4 Hz, 1H), 4.43 (q, J = 7.2 Hz, 2H), 3.95 (d, J = 8.4 Hz, 1H), 3.25 (d,J = 14.8 Hz, 1H), 2.86 (s, 3H), 2.70 (d, J = 15.2 Hz, 1H), 1.41 (t, J = 6.8
Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 176.5, 168.6, 166.7, 143.1, 132.5, 130.8,
129.0, 128.9, 126.4, 122.7, 122.1, 121.7, 108.0, 83.4, 65.2, 63.6, 62.4,
53.4, 39.6, 25.3, 13.6. IR (neat, cm-1): 3037, 2992, 1756, 1630, 1546, 1341,
1210, 1014, 765. HRMS (ESI): calcd. for C23H20BrNO5H+ [M + H] +470.0598; found:
470.0608。
Embodiment eight
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1h (23.5mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of condition in 2a (26 mg, 0.1 mmol), 4 molecular sieves (10 mg)
Lower reaction 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column, can be obtained mesh
It marks product 3h (28.7 mg), white solid, yield 69%, > 99/1 dr, 93% ee.
Product 3h is analyzed, it is as a result as follows: to measure [Daicel Chiralcel AD-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 29.59, t
(minor) = 38.27]; [α]20 D = 1246.7 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d) δ 7.47 (dd, J = 7.6, 1.2 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.31 – 7.27
(m, 1H), 7.17 (td, J = 7.6, 1.2 Hz, 1H), 7.04 (d, J = 8.4 Hz, 2H), 6.63 (d, J
= 7.6 Hz, 1H), 4.95 (d, J = 8.0 Hz, 1H), 4.43 (q, J = 7.2 Hz, 2H), 4.06 (d, J
= 8.0 Hz, 1H), 3.28 (d, J = 15.2 Hz, 1H), 2.84 (s, 3H), 2.75 (d, J = 15.2 Hz,
1H), 1.41 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 176.2, 168.3, 166.6,
142.9, 138.9, 131.4, 129.2, 128.1, 126.0, 122.9, 122.3, 117.8, 111.5, 108.1,
83.5, 65.3, 63.3, 62.5, 53.4, 39.6, 25., 13.6. IR (neat, cm-1): 2961, 2922,
1843, 1736, 1670, 1521, 1419, 1321, 1206, 990, 790. HRMS (ESI): calcd. for
C24H20N2O5H+ [M + H] + 417.1445; found: 417.1465。
Embodiment nine
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1i (30.0mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of condition in 2a (26 mg, 0.1 mmol), 4 molecular sieves (10 mg)
Lower reaction 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column, can be obtained mesh
It marks product 3i (31.2 mg), white solid, yield 68%, > 99/1 dr, 97% ee.
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1i (30.0mg,
0.15 mmol), 0.5 mL methanol is added in 2a (26 mg, 0.1 mmol), 4 molecular sieves (10 mg), anti-under the conditions of 0 DEG C
It answers 24 hours, reaction system, which chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column, can be obtained target production
Object 3i (25.8 mg), white solid, yield 56%, > 99/1 dr, 91% ee.
Product 3i is analyzed, it is as a result as follows: to measure [Daicel Chiralcel AD-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 9.06, t
(minor) = 18.54]; [α]20 D = 11.4 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 7.51 (d, J = 7.6 Hz, 1H), 7.40 (d, J = 8.4 Hz, 1H), 7.29 – 7.16 (m, 3H),
7.11 (t, J = 7.6 Hz, 1H), 6.68 (d, J = 8.0 Hz, 1H), 4.69 (d, J = 11.2 Hz,
1H), 4.43 (d, J = 7.6 Hz, 2H), 3.24 (d, J = 14.8 Hz, 1H), 2.99 (s, 3H), 2.71
(d, J = 15.2 Hz, 1H), 1.41 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
176.1, 167.9, 166.8, 142.7, 134.5, 133.8, 131.8, 129.3, 128.9, 128.8, 127.2,
126.8, 123.9, 122.6, 107.7, 84.23 65.5, 64.1, 62.5, 48.5, 40.5, 25.6, 13.6.
IR (neat, cm-1): 2972, 2918, 1800, 1715, 1636, 1507, 1457, 1338, 762, 669.
HRMS (ESI): calcd. for C23H19Cl2NO5H+ [M + H] + 460.0713; found: 460.0718。
Embodiment ten
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1i (30.0mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of item in 2b (28.5 mg, 0.1 mmol), 4 molecular sieves (10 mg)
It is reacted 24 hours under part, reaction system chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column and can be obtained
Target product 3j (30.5 mg), white solid, yield 63%, > 99/1 dr, 83% ee.
Product 3j is analyzed, it is as a result as follows: to measure [Daicel Chiralcel AD-H, hexane/ with HPLC
iPrOH (90:10), flow rate:1.0 mL·min-1 , λ = 254 nm, t (major) = 6.74, t
(minor) = 13.48]; [α]20 D = 68.6 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 7.52 (dd, J = 7.6, 1.2 Hz, 1H), 7.41 (d, J = 8.8 Hz, 1H), 7.23 (td, J =
8.0, 1.2 Hz, 1H), 7.19 (d, J = 2.4 Hz, 1H), 7.14 (dd, J = 8.4, 2.0 Hz, 1H),
7.10 (td, J = 7.6, 1.2 Hz, 1H), 6.65 (d, J = 8.0 Hz, 1H), 5.56 – 5.47 (m,
1H), 5.03 (dd, J = 14.4, 1.2 Hz, 1H), 4.78 (d, J = 7.2 Hz, 1H), 4.73 – 4.68
(m, 2H), 4.49 – 4.38 (m, 2H), 4.36 – 4.30 (m, 1H), 3.91 (dd, J = 16.4, 5.6
Hz, 1H), 3.26 (d, J = 15.2 Hz, 1H), 2.74 (d, J = 15.2 Hz, 1H), 1.40 (t, J =
7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 176.0, 167.9, 166.7, 142.0, 134.6,
133.8, 131.3, 129.9, 129.7, 128.9, 128.8, 126.9, 126.5, 124.1, 122.5, 117.0,
108.7, 83.9, 65.4, 64.5, 62.5, 47.9, 41.6, 40.8, 13.6. IR (neat, cm-1): 2921,
2850, 1832, 1738, 1703 1641, 1541, 1467, 1325, 1218, 1101, 967, 826, 755,
689. HRMS (ESI): calcd. for C25H21Cl2NO5H+ [M + H] + 486.0870; found: 486.0880。
Embodiment 11
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1i (30.0mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of item in 2c (33.5 mg, 0.1 mmol), 4 molecular sieves (10 mg)
It is reacted 24 hours under part, reaction system chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column and can be obtained
Target product 3k (29.4 mg), white solid, yield 55%, > 99/1 dr, 73% ee.
Product 3k is analyzed, it is as a result as follows: to measure [Daicel Chiralcel AD-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 8.32, t
(minor) = 27.46]; [α]20 D = –159.0 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d) δ 7.53 (dd, J = 7.2, 1.2 Hz, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.23 – 7.17
(m, 4H), 7.15 (dd, J = 8.0, 1.2 Hz, 1H), 7.08 (td, J = 7.6, 1.2 Hz, 1H), 7.03
(dd, J = 8.8, 2.4 Hz, 1H), 6.81 – 6.76 (d, J = 6.0 Hz, 2H), 6.54 (d, J = 7.6
Hz, 1H), 4.95 (d, J = 15.6 Hz, 1H), 4.83 (d, J = 7.6 Hz, 1H), 4.77 (d, J =
7.2 Hz, 1H), 4.48 – 4.39 (m, 3H), 3.31 (d, J = 15.2 Hz, 1H), 2.78 (d, J =
15.2 Hz, 1H), 1.41 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 176.5,
168.0, 166.7, 142.1, 134.7, 134.3, 133.8, 131.1, 129.8, 129.0, 128.9, 128.2,
127.1, 127.1, 126.4, 126.2, 124.2, 122.5, 108.8, 83.6, 65.5, 64.8, 62.5,
47.4, 43.1, 41.2, 13.6. IR (neat, cm-1): 2920, 2849, 1843, 1736, 1609, 1488,
1363, 1175, 1024, 857, 721. HRMS (ESI): calcd. for C29H23Cl2NO5H+ [M + H] +
536.1026; found: 536.1031。
Embodiment 12
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1i (30.0mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of item in 2d (27.3 mg, 0.1 mmol), 4 molecular sieves (10 mg)
It is reacted 24 hours under part, reaction system chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column and can be obtained
Target product 3l (30.3 mg), white solid, yield 62%, > 99/1 dr, 99% ee.
Product 3l is analyzed, it is as a result as follows: to measure [Daicel Chiralcel OD-H, hexane/ with HPLC
iPrOH (95:5), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 13.95, t
(minor) = 20.37]; [α]20 D = 138 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d) δ
7.40 (d, J = 8.4 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 7.17 (dd, J = 8.8, 2.4
Hz, 1H), 7.14 (d, J = 2.4 Hz, 1H), 6.79 (dd, J = 8.4, 2.4 Hz, 1H), 6.59 (d, J
= 8.4 Hz, 1H), 4.67 (q, J = 7.2 Hz, 2H), 4.47 – 4.39 (m, 2H), 3.82 (s, 3H),
3.25 (d, J = 15.2 Hz, 1H), 2.97 (s, 3H), 2.68 (d, J = 15.2 Hz, 1H), 1.41 (t,J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 175.6, 167.9, 166.8, 155.8, 136.0,
134.4, 133.8, 131.9, 129.4, 128.9, 128.3, 126.8, 113.8, 110.8, 108.2, 84.3,
65.6, 64.4, 62.5, 55.4, 48.6, 40.5, 25.7, 13.6. IR (neat, cm-1): 2924, 1830,
1743, 1601, 1558, 1435, 1234, 902. HRMS (ESI): calcd. for C24H21Cl2NO6H+ [M +
H] + 490.0819; found: 490.0822。
Embodiment 13
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1i (30.0mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of item in 2e (28.9 mg, 0.1 mmol), 4 molecular sieves (10 mg)
It is reacted 24 hours under part, reaction system chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column and can be obtained
Target product 3m (29.8 mg), white solid, yield 63%, > 99/1 dr, 89% ee.
Product 3m is analyzed, it is as a result as follows: to measure [Daicel Chiralcel AD-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 7.11, t
(minor) = 11.03]; [α]20 D = –50.4 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 7.40 (d, J = 8.4 Hz, 1H), 7.33 (d, J = 1.6 Hz, 1H), 7.19 – 7.15 (m, 2H),
7.05 (d, J = 8.8 Hz, 1H), 6.56 (d, J = 7.6 Hz, 1H), 4.68 (q, J = 9.2 Hz, 2H),
4.67 – 4.39 (m, 2H), 3.23 (d, J = 15.2 Hz, 1H), 2.96 (s, 3H), 2.69 (d, J =
15.2 Hz, 1H), 2.35 (s, 3H), 1.41 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3)
δ 176.0, 167.9, 166.9, 140.3, 134.4, 133.7, 132.2, 131.8, 129.3, 129.0,
128.9, 127.0, 126.7, 124.8, 107.4, 84.2, 65.5, 64.3, 62.4, 48.4, 40.4, 25.6,
20.7, 13.6. IR (neat, cm-1): 2924, 1831, 1716, 1653, 1541, 1506, 1419, 1334,
1220, 1151, 970, 701. HRMS (ESI): calcd. for C24H21Cl2NO5H+ [M + H] + 474.0870;
found: 474.0875。
Embodiment 14
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1a (19.8mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of item in 2e (28.9 mg, 0.1 mmol), 4 molecular sieves (10 mg)
It is reacted 24 hours under part, reaction system chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column and can be obtained
Target product 3n (21.8 mg), white solid, yield 52%, > 99/1 dr, 79% ee.
Product 3n is analyzed, it is as a result as follows: to measure [Daicel Chiralcel AD-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 26.29, t
(minor) = 42.68]; [α]20 D = –86.3 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 7.52 (d, J = 7.6 Hz, 1H), 7.41 (d, J = 8.8 Hz, 1H), 7.23 (t, J = 7.6 Hz,
1H), 7.18 (s, 1H), 7.15 (d, J = 8.8 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 6.65
(d, J = 8.0 Hz, 1H), 5.56 – 5.47 (m, 1H), 5.02 (d, J = 10.0 Hz, 1H), 4.78 (d,J = 7.2 Hz, 1H), 4.72 (d, J = 6.8 Hz, 1H), 4.72 (t, J = 6.8 Hz, 2H), 4.47 –
4.38 (m, 4H), 4.34 (d, J = 16.8 Hz, 1H), 3.91 (d, J = 17.2 Hz, 1H), 3.26 (d,J = 14.8 Hz, 1H), 2.75 (d, J = 15.2 Hz, 1H), 1.40 (t, J = 7.2 Hz, 3H). 13C NMR
(101 MHz, CDCl3) δ 176.4, 169.0, 166.9, 155.8, 136.6, 133.4, 128.0, 127.6,
127.5, 127.2, 113.0, 109.5, 108.2, 83.6, 65.7, 63.7, 62.3, 55.4, 54.1, 39.6,
25.3, 13.6. IR (neat, cm-1): 2924, 1840, 1747, 1614, 1471, 1352, 1206, 1177,
1145, 1047, 789. HRMS (ESI): calcd. for C24H23NO6H+ [M + H] + 422.1598; found:
422.1608。
Embodiment 15
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1i (30.0mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of item in 2f (27.7 mg, 0.1 mmol), 4 molecular sieves (10 mg)
It is reacted 24 hours under part, reaction system chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column and can be obtained
Target product 3o (26.7 mg), white solid, yield 56%, > 99/1 dr, 96% ee.
Product 3o is analyzed, it is as a result as follows: to measure [Daicel Chiralcel AD-H, hexane/ with HPLC
iPrOH (90:10), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 10.42, t
(minor) = 16.22]; [α]20 D = –20.8 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d)
δ 7.38 (d, J = 8.4 Hz, 1H), 7.29 (dd, J = 8.0, 2.4 Hz, 1H), 7.21 (d, J = 2.0
Hz, 1H), 7.18 (dd, J = 8.4, 2.4 Hz, 1H), 6.98 (td, J = 8.8, 2.8 Hz, 1H), 6.62
(dd, J = 8.8, 4.4 Hz, 1H), 4.68 (q, J = 4.0 Hz 1H), 4.47 – 4.40 (m, 2H), 3.26
(d, J = 15.2 Hz, 1H), 2.98 (s, 3H), 2.69 (d, J = 15.2 Hz, 1H), 1.41 (t, J =
7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 175.7, 167.5, 166.7, 160.0, 157.6,
138.6, 134.4, 133.9, 131.5, 129.3, 129.0, 128.8, 128.7, 126.8, 115.3, 115.0,
112.5, 112.2, 108.4, 108.3, 84.2, 65.5, 64.2, 64.2, 62.6, 48.5, 40.4, 25.7,
13.6. IR (neat, cm-1): 2980, 1840, 1740, 1613, 1493, 1303, 1179, 1023, 982.
HRMS (ESI): calcd. for C323H18Cl2FNO5H+ [M + H] + 478.0619; found: 478.0619。
Embodiment 16
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1i (30.0mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of item in 2g (29.5 mg, 0.1 mmol), 4 molecular sieves (10 mg)
It is reacted 24 hours under part, reaction system chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column and can be obtained
Target product 3p (28.7 mg), white solid, yield 58%, > 99/1 dr, 94% ee.
Product 3p is analyzed, it is as a result as follows: to measure [Daicel Chiralcel OD-H, hexane/ with HPLC
iPrOH (80:20), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 7.94, t
(minor) = 9.69]; [α]20 D = 22.6 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d) δ
7.40 (t, J = 7.6 Hz,1H), 7.35 (d, J = 8.4 Hz, 1H), 7.24 (d, J = 2.0 Hz, 1H),
7.20 (dd, J = 8.8, 2.4 Hz, 1H), 6.54 (dd, J = 9.6, 6.4 Hz, 1H), 4.64 (s, 2H),
4.47 – 4.41 (m, 2H), 3.24 (d, J = 15.2 Hz, 1H), 2.96 (s, 3H), 2.66 (d, J =
15.6 Hz, 1H), 1.42 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 175.7,
167.4, 166.7, 134.3, 134.1, 131.5, 130.1, 129.3, 129.0, 126.9, 122.8, 114.2,
114.0, 98.3, 98.0, 84.2, 65.4, 63.6, 62.6, 48.8, 40.4, 25.9, 13.6. IR (neat,
cm-1): 2923,2851,2361,1842,1714,1623,1507,1412,1351,1260,1220,1189,
1061,903. HRMS (ESI): calcd. for C23H17Cl2F2NO5H+ [M + H] + 496.0525; found:
496.0533。
Embodiment 17
Sequentially added in reaction flask N-heterocyclic carbine (3.7 mg, 0.01 mmol) as catalyst and 1i (30.0mg,
0.15 mmol), 0.5 mL mesitylene is added, in 0 DEG C of item in 2h (27.3 mg, 0.1 mmol), 4 molecular sieves (10 mg)
It is reacted 24 hours under part, reaction system chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column and can be obtained
Target product 3q (28.1 mg), white solid, yield 60%, > 99/1 dr, 94% ee.
Product 3q is analyzed, it is as a result as follows: to measure [Daicel Chiralcel OD-H, hexane/ with HPLC
iPrOH (80:20), flow rate: 1.0 mL·min-1 , λ = 254 nm, t (major) = 7.94, t
(minor) = 9.69]; [α]20 D = 22.6 (c 1, CHCl3); 1H NMR (400 MHz, Chloroform-d) δ
7.40 (t, J = 7.6 Hz,1H), 7.35 (d, J = 8.4 Hz, 1H), 7.24 (d, J = 2.0 Hz, 1H),
7.20 (dd, J = 8.8, 2.4 Hz, 1H), 6.54 (dd, J = 9.6, 6.4 Hz, 1H), 4.64 (s, 2H),
4.47 – 4.41 (m, 2H), 3.24 (d, J = 15.2 Hz, 1H), 2.96 (s, 3H), 2.66 (d, J =
15.6 Hz, 1H), 1.42 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 175.7,
167.4, 166.7, 134.3, 134.1, 131.5, 130.1, 129.3, 129.0, 126.9, 122.8, 114.2,
114.0, 98.3, 98.0, 84.2, 65.4, 63.6, 62.6, 48.8, 40.4, 25.9, 13.6. IR (neat,
cm-1): 2923,2851,2361,1842,1714,1623,1507,1412,1351,1260,1220,1189,
1061,903. HRMS (ESI): calcd. for C23H17Cl2F2NO5H+ [M + H] + 496.0525; found:
496.0533。
Claims (1)
1. a kind of loop coil hydroxyindole pentamethylene and β-The synthetic method of interior compound, which comprises the following steps: with
Phenyl unsaturated aldehyde, beta-unsaturated ketone acid esters is reactant, and using N-heterocyclic carbine as catalyst, reaction obtains loop coil hydroxyindole ring penta
Alkane and β-Interior compound；
The chemical structural formula of the phenyl unsaturated aldehyde is, wherein R1Selected from 2- methoxyl group, 3- nitro, 4-
One of methoxyl group, chlorine, nitro, bromine, cyano, bis- chlorine substituent of 2,4-；
The chemical structural formula of the beta-unsaturated ketone acid esters is, wherein R2For 5- methyl, methoxyl group, fluorine, 7- methyl
Or 5,6- difluoro；R3For methyl, allyl or benzyl；
The loop coil hydroxyindole pentamethylene and β-The structural formula of interior compound are as follows:
；
The reaction is in methylene chloride, ether, tetrahydrofuran, toluene, 1,2- dichloroethanes, paraxylene, mesitylene, two
It is carried out in toluene, ortho-xylene, 1,4- dioxane or methanol；
With molar amount, the dosage of the catalyst is the 5-20% of beta-unsaturated ketone acid esters；The dosage of phenyl unsaturated aldehyde is insatiable hunger
With 1.5 times of keto ester；
The reaction temperature is 0 DEG C, and the time is 24 hours；
The reaction carries out in the presence of 4 molecular sieve.
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