CN106188078A - A kind of chiral spiro hydroxyindole benzopyrone the synthetic method of 3,4 dihydropyrane compounds - Google Patents

A kind of chiral spiro hydroxyindole benzopyrone the synthetic method of 3,4 dihydropyrane compounds Download PDF

Info

Publication number
CN106188078A
CN106188078A CN201610558105.8A CN201610558105A CN106188078A CN 106188078 A CN106188078 A CN 106188078A CN 201610558105 A CN201610558105 A CN 201610558105A CN 106188078 A CN106188078 A CN 106188078A
Authority
CN
China
Prior art keywords
alpha
compound
benzopyran
dihydro
mmol
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201610558105.8A
Other languages
Chinese (zh)
Other versions
CN106188078B (en
Inventor
王兴旺
殷少杰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Suzhou University
Original Assignee
Suzhou University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Suzhou University filed Critical Suzhou University
Priority to CN201610558105.8A priority Critical patent/CN106188078B/en
Priority to CN201810027686.1A priority patent/CN108358941B/en
Publication of CN106188078A publication Critical patent/CN106188078A/en
Application granted granted Critical
Publication of CN106188078B publication Critical patent/CN106188078B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • 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
    • C07D491/12—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 three hetero rings
    • C07D491/20—Spiro-condensed systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/32—Addition reactions to C=C or C-C triple bonds
    • B01J2231/324—Cyclisations via conversion of C-C multiple to single or less multiple bonds, e.g. cycloadditions

Abstract

The invention discloses a kind of chiral spiro hydroxyindole benzopyrone the synthetic method of 3,4 dihydropyrane compounds, be specially and derive with isatinβ,γUnsaturatedαKeto ester and 3 hydroxyl 4 hydrogen chromene 4 ketone are reactant, and under chirality Multifunctional chiral quinine thiourea is catalyzed, synthesis obtains product in a solvent.Method raw material disclosed by the invention is simple and easy to get, and reaction condition is gentle, and post processing is simple and convenient, and the substrate spectrum being suitable for is wide, and yield is high, and enantioselectivity is high, thus synthesizes the product obtained and may be used to the intermediate of synthetic drug, insecticide and photoelectric material.

Description

A kind of chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound Synthetic method
Technical field
The present invention relates to the synthesis of chiral spiro compound, be specifically related to a kind of chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one And the process for catalytic synthesis of-3,4-dihydro-pyran compound.
Background technology
Chirality oxa-volution producing oxindoles compound is widely present in natural product and drug molecule, have antitumor, Antiphytoviral, plant growth regulating, weeding, sterilization, inhibitory enzyme activity, antioxidation and radioprotective, destruction biological cell membrane etc. Biological activity widely, and paid close attention to by a lot of scientists.Chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro- Pyrylium compound, has similar potential using value equally, therefore selects the oxa-volution hydroxyl of efficient method synthesis of chiral Indole hemiketal compound has attracted the great interest of many chemists, has recently emerged many synthetic methods.The oxygen of chirality Miscellaneous volution hydroxyindole hemiketal compound has continuous print conjugated structure, and this continuous conjugated structure makes it be susceptible to electronics to turn Move and transition, therefore oxa-volution hydroxyindole hemiketal compound also has potential application in terms of electron transfer, photoelectric material It is worth.In organic synthesis field, by the reaction of asymmetric little Journal of Molecular Catalysis owing to only just can obtain with a small amount of chiral catalyst The method obtaining the newest active substance and become most effective, have the synthesizing chiral compound of economic worth.
In prior art, the method report of synthesis of chiral oxa-volution producing oxindoles compound is fewer.β , γ-no Saturatedα-one acid esters has many reaction site, electron deficiency as oneβ , γ-unsaturated system and activationα-carbonyl The application of skeleton is of great interest and report, and isatin derivesβ , γ-unsaturatedα-one acid esters skeleton participates in The report of chemical reaction fewer.Shi Min seminar reported in 2014 with (DHQ)2AQN is catalyst, and isatin derivesβ , γ-unsaturatedα-one acid esters and asymmetric [3+2] cycloaddition reaction of connection alkene ester, can be with the yield and 76% of 56% 99% The enantioselectivity of 98% obtains chirality oxa-volution producing oxindoles compound.(H.-B. Yang, Y.-Z. Zhao, R. Sang, Y. Wei, M. Shi, Asymmetric Synthesis of Bioxindole-Substituted Hexahydro-furo[2,3-b ] furans via Hydroquinine Anthraquinone-1,4-diyl Di- ether-Catalyzed Domino Annulation of Acylidenoxindoles/Isatins, Acylidenoxindoles and Allenoates. Adv.Synth.Catal.,2014,356, 3799-380), But the catalyst amount of this reaction is relatively big, and the cis-selectivity of reaction is not the highest, thus limits the further of this reaction Using value.
A kind of new synthesis of chiral volution hydroxyindole of the most necessary searching-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyrrole Muttering the method for compound, the method not only yield is high, enantioselectivity is outstanding, the most also needs substrate to be easily-synthesized, low cost, reaction Mild condition, simple to operate.
Summary of the invention
It is an object of the invention to provide a kind of chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran chemical combination The process for catalytic synthesis of thing and the chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound thus prepared.
To achieve the above object of the invention, the technical solution used in the present invention is: a kind of oxa-volution hydroxyindole hemiketal The synthetic method of compound, particularly as follows: derive beta, gamma-unsaturation alpha-keto ester compound and 3-hydroxyl-4 hydrogen-chromene-4-with isatin Ketone is reactant, and with chirality quinine thiourea as catalyst, in halogenated hydrocarbon solvent, reaction obtains product chiral spiro hydroxyl Yin Diindyl-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound；
Described isatin derives the chemical structural formula of β, γ-unsaturation alpha-keto ester compound, wherein R1 It is selected from: the one in methyl, methoxy, benzyl, pi-allyl, benzyloxycarbonyl group；R2It is selected from: hydrogen, 5-fluorine, 5-chlorine, 5-bromine, 5- One in methyl, 5-methoxyl group, 6-chlorine, 6-bromine, 6-methoxyl group, 7-fluorine, 7-methyl, 5,6-difluoro, 5,7-dimethyl；R3Choosing From: the one in methyl, ethyl；
The chemical structural formula of described 3-hydroxyl-4 hydrogen-chromene-4-ketonic compound is, wherein R is hydrogen, 6- One in fluorine, 6-bromine, 6-methyl, 7-methoxyl group；
The structural formula of described chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound is:
。
Preferably in technical scheme, with molar amount, the consumption of described catalyst is that isatin derives beta, gamma-unsaturation α-one The 2-10% of ester compound；More preferably 5%.
Preferably in technical scheme, with molar amount, the consumption of 3-hydroxyl-4 hydrogen-chromene-4-ketonic compound is that isatin spreads out 1-2 times of raw β, γ-unsaturation alpha-keto ester compound；More preferably 1.5 times.
Preferably in technical scheme, reaction temperature is less than room temperature, and such as-30 DEG C to room temperature；Response time is that 36-41 is little Time.Preferably-20 DEG C are reacted 40 hours.
Preferably in technical scheme, described catalyst is chirality quinine thiourea；Its chemical structural formula is as follows:
In technique scheme, course of reaction includes at low temperatures, is sequentially added into catalyst, isatin derives β in reaction bulb, γ-unsaturation alpha-keto ester compound, solvent, add 3-hydroxyl-4 hydrogen-chromene-4-ketonic compound and enter after stirring 15-35 minute Row reaction, after reaction terminates, crude product by simple column chromatography (eluant is preferably petroleum ether: ethyl acetate=2:1～1: 1) i.e. can get target product；This compounds is the analog of a lot of antibacterials, antiviral agent and enzyme inhibitor, has huge Potential using value.The oxa-volution hydroxyindole hemiketal compound of chirality has continuous print conjugated structure, this most common Yoke structure makes it be susceptible to electron transfer and transition, therefore oxa-volution hydroxyindole hemiketal compound can be used as electronics and turn Shifting, photoelectric material.
The present invention discloses above-mentioned chirality quinine thiourea further and derives β, γ-unsaturation alpha-keto ester chemical combination at catalysis isatin Application in thing and 3-hydroxyl-4 hydrogen-chromene-4-reactive ketone.
Above-mentioned course of reaction is as follows:
Owing to technique scheme is used, the present invention compared with prior art has the advantage that
1. the present invention achieves first and derives β, γ-unsaturation 2-ketoacid with 3-hydroxyl-4 hydrogen-chromene-4-ketonic compound and isatin Ester compounds be reactant, chirality multi-functional quinine thiourea be catalyst synthesis of chiral volution hydroxyindole-.alpha.-5:6-benzopyran-one also- The method of 3,4-dihydro-pyran compounds, the method is easy and simple to handle, and yield is high, and stereo selectivity is good；
The post-reaction treatment of synthesis oxa-volution hydroxyindole hemiketal compound the most disclosed in this invention is simple, and reaction does not exists Dynamic Resolution process, belongs to Michael addition-cyclisation cascade reaction, does not has by-product to generate in system；
The method suitable substrates wide range of synthesis oxa-volution hydroxyindole hemiketal compound the most disclosed by the invention, raw material is equal For industrialization, product cheap and easy to get, pollution-free；And functional group compatibility is high, and corresponding selection is outstanding, yield is high.
Detailed description of the invention
Below in conjunction with embodiment, the invention will be further described:
Embodiment one:
Reaction bulb is sequentially added into quinine thiourea (5.9 mg, 0.01 mmol), and 1a (25.9mg, 0.1 mmol), 2a (16.2 mg, 0.1 mmol), adds 1 mL dichloromethane, at ambient temperature reaction 12 hours, and reaction system is by simple Column chromatography (eluant is petroleum ether: ethyl acetate=1.8:1) i.e. can get target product 3a (36.6mg), yellow solid, Mp:198-201 DEG C, yield is 87%, > 20/1 dr, 87% ee.
Reaction bulb is sequentially added into quinine thiourea (5.9 mg, 0.01 mmol), and 1a (25.9mg, 0.1 mmol), 2a (16.2 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 12 hours under the conditions of zero degrees celsius, and reaction system is passed through (eluant is petroleum ether to simple column chromatography: ethyl acetate=1.8:1) i.e. can get target product 3a (33.3mg), yellow is solid Body, mp:198-201 DEG C, yield is 79%, > 20/1 dr, 96% ee.
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1a (25.9mg, 0.1 mmol), Add 1 mL dichloromethane, stir 20 minutes under subzero 20 degrees celsius, add 2a (24.3 mg, 0.15 mmol), Continuing reaction 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.8:1) To target product 3a (40.8 mg), yellow solid, mp:198-201 DEG C, yield is 97%, > 20/1 dr, 98% ee.
Being analyzed product 3a, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (70:30), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 13.936, t (minor) = 24.650]; [α]D 25 = + 63.0 (c = 0.51, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 0.5H), 8.21 (ddd, J = 13.2, 8.0, 1.2 Hz, 1H), 7.89 (d, J = 7.6 Hz, 1H), 7.54 – 7.49 (m, 1H), 7.45 (td, J = 8.0, 1.2 Hz, 0.5H), 7.38 (td, J =8.0, 1.2 Hz, 1H), 7.33 – 7.29 (m, 1H), 7.23 – 7.18 (m, 1H), 7.15 – 7.03 (m, 2H), 6.98 (d, J = 7.8 Hz, 0.5H), 5.05 (s, 0.5H), 4.42 – 4.32 ((dq, J = 7.2, 6.8 Hz, 2H)), 3.38 (d, J = 8.0 Hz, 3H), 3.31 (d, J = 14.0 Hz, 0.5H), 3.07 (d, J = 14.8 Hz, 0.5H), 2.69 (d, J = 14.8 Hz, 0.5H), 2.33 (d, J = 14.0 Hz, 0.5H), 1.38 (dt, J = 15.8, 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.71, 175.47, 171.97, 171.84, 168.43, 167.33, 155.05, 154.99, 147.63, 145.48, 143.87, 143.78, 137.11, 136.67, 133.58, 133.44, 130.23, 129.86, 129.54, 128.80, 127.69, 126.32, 126.08, 124.78, 124.77, 124.60, 123.76, 123.74, 123.71, 123.41, 118.07, 117.87, 109.66, 108.61, 94.90, 93.63, 63.71, 62.80, 50.16, 49.56, 37.60, 37.51, 27.41, 27.25, 14.15, 14.08; IR: 3276.4, 2961.7, 1740.5, 1714.4, 1627.4, 1611.0, 1468.6, 1260.0, 1192.0, 1034.8, 1020.7, 796.4, 758.9, 692.5 cm-1; HRMS calcd. for C23H19NNaO7 [M+Na]+444.1054, found: 444.1065；More than count It is demonstrated that the success of purpose Product formation.
Embodiment two:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1b (28.9mg, 0.1 mmol), adds 1 ML dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues anti- Answering 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.6:1) i.e. can get target Product 3b (42.8 mg), yellow solid, mp:141-144 DEG C, yield is 95%, > 20/1 dr, 98% ee.
Being analyzed product 3b, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (70:30), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 12.362, t (minor) = 17.090]; [α]D 25 = + 98.0 (c = 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 0.3H), 8.22 (d, J = 7.2 Hz, 0.4H), 8.18 (d, J = 7.6 Hz, 0.6H), 7.93 (d, J = 7.6 Hz, 0.6H), 7.51 – 7.49 (m, 1H), 7.42 (t, J = 7.2 Hz, 0.3H), 7.36 (t, J = 7.6 Hz, 0.7H), 7.33 – 7.28 (m, 1H), 7.23 (d, J = 2.9 Hz, 0.3H), 7.21 – 7.15 (m, 1H), 7.11 – 7.04 (m, 1.7H), 5.29 (s, 0.7H), 5.29 (t, J = 10.1 Hz, 1H), 5.21 (dd, J = 10.8, 5.2 Hz, 1H), 4.36 (dq, J = 12.7, 5.7 Hz, 2H), 3.42 (d, J = 7.6 Hz, 3H), 3.30 (d, J = 13.6 Hz, 0.7H), 3.11 (d, J = 14.8 Hz, 0.3H), 2.72 (d, J = 14.8 Hz, 0.3H), 2.39 (d, J = 14.0 Hz, 0.35H), 1.37 (dt, J = 14.2, 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 178.59, 176.28, 171.92, 171.75, 168.29, 167.22, 155.00, 154.96, 147.42, 145.43, 142.10, 141.90, 136.94, 136.49,133.73, 133.58, 130.34, 129.65, 129.37, 128.27, 127.82, 126.40, 126.18, 125.12, 124.86, 124.67, 123.90, 123.84, 123.74, 123.70, 117.73, 117.61, 110.10, 110.06, 94.80, 93.64, 72.17, 71.95, 63.68, 62.88, 56.61, 56.37, 50.50, 49.96, 37.78, 37.62, 14.14, 14.07; IR: 3514.9, 3282.1, 2961.4, 2928.7, 1738.7, 1720.6, 1631.9, 1620.9, 1484.3, 1467.9, 1368.6, 1341.2, 1217.1, 1194.4, 1147.4, 1103.9, 1039.2, 977.2, 923.7, 860.6, 775.0, 758.9, 701.2, 660.5, 613.3 cm-1; HRMS calcd. for C24H22NO8 [M+H]+ 452.1340, found:452.1348。
Embodiment three:
Reaction bulb is sequentially added into quinine thiourea (0.002 mmol), and 1c (33.5mg, 0.1 mmol), adds 1 mL dichloro Methane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues reaction 38 little Time, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.8:1) i.e. can get target product 3c (48.3mg), white solid, mp:141-144 ° of C, yield is 91%, > 20/1 dr, 96% ee.
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1c (33.5mg, 0.1 mmol), Add 1 mL dichloromethane, react 20 minutes under subzero 20 degrees celsius, add 2a (24.3 mg, 0.15 mmol), Continuing reaction 36 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.8:1) To target product 3c (48.7 mg), white solid, mp:141-144 DEG C, yield is 98%, > 20/1 dr, 99% ee.
Being analyzed product 3c, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (70:30), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 17.371, t (minor) = 25.698]; [α]D 25 = + 114.0 (c = 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 0.4H), 8.23 (d, J = 8.0 Hz, 0.45H), 8.18 (d, J = 8.0 Hz, 0.55H), 7.94 (d, J = 7.6 Hz, 0.55H), 7.55 – 7.50 (m, 1H), 7.42 – 7.33 (m, 5H), 7.32 – 7.30 (m, 1H), 7.23 (d, J = 8.4 Hz, 1H), 7.12 (t, J = 7.6 Hz, 0.5H), 7.06 (d,J = 7.6 Hz, 0.7H), 7.02 (d, J = 3.2 Hz, 0.5H), 7.00 (d, J = 4.4 Hz, 0.3H), 6.92 (d, J = 8.0 Hz, 0.4H), 6.85 (d, J = 7.6 Hz, 0.55H), 5.33 (s, 0.6H), 5.26 (t, J = 15.6 Hz, 1H), 4.81 (t, J = 15.2 Hz, 1H), 4.37 (dq, J = 7.2, 5.2 Hz, 2H), 3.38 (dd, J = 14.0, 2.0 Hz, 0.6H), 3.13 (d, J = 15.2 Hz, 0.4H), 2.76 (d,J = 14.8 Hz, 0.4H), 2.42 (d, J = 14.0 Hz, 0.6H), 1.38 (dt, J = 7.2, 5.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.95, 175.64, 171.97, 171.81, 168.39, 167.31, 154.00, 154.96, 147.84, 145.80, 136.90, 136.45, 135.44, 134.53, 133.66, 133.48, 130.15, 129.87, 129.44, 129.13, 128.94, 128.71, 128.32, 127.99, 127.78, 127.32, 127.30, 126.37, 126.13, 124.80, 124.70, 124.60, 123.79, 123.75, 123.69, 123.43, 117.76, 117.60, 110.65, 109.59, 94.90, 93.66, 63.64, 62.83, 50.17, 49.55, 44.63, 44.46, 37.42, 37.37, 14.13, 14.07; IR: 3484.2, 3281.4, 2959.1, 2923.7, 1739.1, 1714.4, 1632.2, 1610.4, 1485.9, 1466.6, 1364.0, 1346.3, 1284.3, 1263.4, 1216.9, 1197.6, 1182.2, 1145.9, 1081.0, 1038.4, 974.7, 947.8, 883.8, 808.3, 753.4, 734.7, 698.6, 630.1 cm-1; HRMS calcd. for C29H24NO7 [M+H]+498.1547, found:498.1545, data above proves purpose product Synthesize successfully.
Embodiment four:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1d (28.5mg, 0.1 mmol), adds 1 ML dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues anti- Answering 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.8:1) i.e. can get target Product 3d (46.0 mg), white solid, mp:158-160 DEG C, yield is 97%, > 20/1 dr, 99% ee.
Being analyzed product 3d, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (70:30), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 15.593, t (minor) = 19.550]; [α]D 25 = + 97.3 (c = 0.52, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.79 (s, 0.45H), 8.21 (dd, J = 17.2, 7.6 Hz, 1H), 7.93 (d, J = 7.6 Hz, 0.50H), 7.54 – 7.50 (m, 1H), 7.41 (t, J = 7.6 Hz, 0.6H), 7.36 – 7.29 (m, 1.4H), 7.25 (d, J = 7.2 Hz, 0.5H), 7.17 (t, J = 7.6 Hz, 0.5H), 7.11 – 7.01 (m, 2H), 6.94 (d, J = 7.6 Hz, 0.5H), 5.99 – 5.88 (m, 1H), 5.34 (dd, J = 16.8, 10.6 Hz, 2H), 5.21 (s, 0.55H), 4.60 (dd, J = 16.8, 3.6 Hz, 1H), 4.36 (dt, J = 7.6, 5.6 Hz, 3H), 3.33 (d, J = 14.0 Hz, 0.55H), 3.11 (d, J = 14.8 Hz, 0.45H), 2.72 (d, J = 14.8 Hz, 0.45H), 2.38 (d, J = 14.0 Hz, 0.55H), 1.38 (dt, J = 14.4, 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.59, 175.22, 171.98, 171.82, 168.42, 167.32, 155.02, 149.97, 147.72, 145.61, 143.07, 142.90, 136.98, 136.52, 133.66, 133.50, 130.76, 130.16, 129.96, 129.83, 129.45, 128.72, 127.78, 126.37, 126.12, 124.80, 124.70,124.61, 123.82, 123.74, 123.70, 123.37, 118.00, 117.85, 117.68, 117.44, 110.51, 109.49, 94.88, 93.64, 63.69, 62.83, 50.16, 49.53, 43.05, 42.92, 37.50, 37.47, 14.15,14.08; IR: 3544.6, 3259.4, 2963.1, 2854.3, 1740.2, 1710.8, 1625.9, 1609.6, 1487.0, 1467.4, 1432.8, 1280.3, 1260.9, 1238.1, 1198.6, 1186.3, 1107.0, 1039.8, 1004.7, 977.5, 943.9, 884.7, 855.7, 797.5, 761.9, 702.3, 668.9, 655.5, 636.0, 619.9 cm-1; HRMS calcd. for C25H22NO7 [M+H]+448.1391, found:448.1393；Data above proves purpose Product formation success.
Embodiment five:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1e (37.9mg, 0.1 mmol), adds 1 ML dichloromethane, reacts 30 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues anti- Answering 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.8:1) i.e. can get target Product 3e (39.4 mg), yellow solid, mp:196-198 DEG C, yield is 73%, > 20/1 dr, 99% ee.
Being analyzed product 3e, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (70:30), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 28.027, t (minor) = 41.336]; [α]D 25 = + 98.4 (c = 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.82 (s, 0.45H), 8.23 (dd, J = 14.8, 7.6 Hz, 1H), 7.93 (d, J = 7.6 Hz, 0.55H), 7.54 (t, J = 7.6 Hz, 1H), 7.40 – 7.29 (m, 6.45H), 7.23 – 7.01 (m, 3H), 6.92 (d, J = 7.6 Hz, 0.5H), 6.85 (d, J = 7.6 Hz, 0.5H), 5.27 (t, J = 15.6 Hz, 1H), 5.11 (s, 0.55H), 4.82 (t, J = 14.0 Hz, 1H), 4.39 (dq, J = 12.4, 7.2 Hz, 2H), 3.39 (d, J = 14.0 Hz, 0.55H), 3.14 (d, J = 14.8 Hz, 0.45H), 2.75 (d, J = 15.2 Hz, 0.45H), 2.41 (d, J = 14.0 Hz, 0.55H), 1.40 (dt, J = 12.4, 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 178.00, 175.66, 171.99, 171.85, 168.45, 167.34, 155.07, 155.02, 147.80, 143.05, 142.86, 136.95, 136.50, 135.47, 134.56, 133.69, 133.54, 130.18, 129.89, 129.50, 129.18, 128.99, 128.78, 128.38, 128.04, 127.80, 127.37, 127.36, 126.46, 126.22, 124.86, 124.75, 124.67, 123.84, 123.78, 123.47, 117.81, 117.64, 110.66, 109.64, 94.93, 93.64, 63.78, 62.90, 50.21, 49.56, 44.69, 44.52, 37.46, 14.18, 14.12; IR: 3482.3, 3279.6, 2960.8, 2922.9, 1743.1, 1715.8, 1640.6, 1609.8, 1488.3, 1467.7, 1432.2, 1369.4, 1282.4, 1262.1, 1196.7, 1184.7, 1146.1, 1109.0, 1040.2,1013.5, 972.1, 860.0, 772.8, 753.5, 728.6, 696.9, 630.7 cm-1; HRMS calcd. for C30H24NO9 [M+H]+542.1146, found:542.1153；Data above proves that purpose Product formation becomes Merit.
Embodiment six:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1f (28.7mg, 0.1 mmol), adds 1 ML dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues anti- Answering 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.8:1) i.e. can get target Product 3f (24.2 mg), yellow solid, mp:150-153 DEG C, yield is 54%, > 20/1 dr, 98% ee.
Being analyzed product 3f, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (70:30), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 15.747, t (minor) = 20.035]; [α]D 25 = + 113.3 (c = 0.30, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 8.0 Hz, 0.8H), 8.31 (d, J = 6.4 Hz, 0.2H), 8.23 – 8.21 (m, 1H), 7.95 (d, J = 7.6 Hz, 0.7H), 7.56 (dd, J = 7.2, 1.2 Hz, 1H), 7.95 (d, J = 2.8 Hz, 0.3H), 7.47 – 7.40 (m, 1H), 7.34 – 7.29 (m, 1H), 7.23 (d, J = 8.0 Hz, 0.7H), 7.18 (d, J = 8.4 Hz, 0.7H), 7.14 (d, J = 8.4 Hz, 0.3H), 5.10 (s, 0.7H), 4.38 (dq, J = 15.6, 7.2 Hz, 2H), 3.32 (d, J = 14.0 Hz, 0.8H), 3.08 (d,J = 15.2 Hz, 0.2H), 2.81 (d, J = 15.2 Hz, 0.3H), 2.74 (d, J = 5.7 Hz, 3H), 2.47 (d, J = 14.0 Hz, 0.7H), 1.38 (dt, J = 15.2, 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.06, 171.94, 170.71, 168.06, 155.10, 147.08, 140.19, 136.56, 133.94, 133.82, 129.91, 128.76, 127.90, 127.28, 126.85, 126.41, 126.22, 125.96, 125.62, 125.08, 124.91, 123.69, 123.42, 118.05, 117.96, 117.37, 116.65, 94.46, 93.56 , 63.93, 63.21, 50.70, 50.51, 38.87, 38.56, 27.35, 27.01, 14.17, 14.13; IR: 3350.2, 2926.9, 2924.5, 1760.2, 1741.5, 1724.4, 1640.9, 1613.6, 1465.6, 1434.8, 1370.1, 1339.0, 1306.9, 1268.1, 1198.3, 1147.9, 1107.9, 1063.4, 973.7, 802.7, 763.4 cm-1; HRMS calcd. for C24H20NO8 [M+ H]+450.1183, found:450.1188；Data above proves the success of purpose Product formation.
Embodiment seven:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1g (27.7mg, 0.1 mmol), adds 1 ML dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues anti- Answering 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.8:1) i.e. can get target Product 3g (35.9 mg), reddish Solid, mp:114-116 DEG C, yield is 82%, > 20/1 dr, 99% ee.
Being analyzed product 3g, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (85:15), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 30.576]; [α]D 25 = + 135.8 (c = 0.46, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.75 (s, 0.3H), 8.22 (dd, J = 8.0, 1.6 Hz, 0.3H), 8.18 (dd, J = 8.0, 1.6 Hz, 0.7H), 7.69 (dd, J = 8.4, 2.4 Hz, 0.7H), 7.55 – 7.50 (m, 1H), 7.34 – 7.27 (m, 1H), 7.13 (dd, J = 8.8, 2.4 Hz, 1H), 7.10 – 7.05 (m, 1H), 7.00 – 6.96 (m, 0.7H), 6.89 (dd, J = 8.4, 4.0 Hz, 0.7H), 5.28 (d, J = 2.2 Hz, 0.7H), 4.36 (m, 2H), 3.35 (dt, J = 14.4, 7.1 Hz, 2H), 3.31 (d, J = 2.4 Hz, 0.3H), 3.27 (d, J = 2.4 Hz, 0.3H), 3.02 (d, J = 14.8 Hz, 0.3H), 2.70 (d, J = 14.8 Hz, 0.3H), 2.34 (d, J = 14.0 Hz, 0.7H), 2.09 (s, 0.6H), 1.37 (dt, J = 14.4, 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.40, 175.14, 171.96, 171.75, 168.21, 167.19, 160.22 (J = 243.2 Hz), 154.50 (J = 239.6 Hz), 155.02, 154.09, 147.07, 144.79, 139.79, 139.77, 137.16, 136.60, 133.72, 133.57, 131.23, 131.14, 130.71 (J = 6.4 Hz) 130.66 (J = 6.9 Hz), 128.94, 126.36, 126.12, 124.90, 124.72, 123.71, 123.68, 118.00, 117.84, 116.75 (J = 23.6 Hz), 116.08 ( J = 26.1 Hz), 115.93 ( J = 23.6 Hz), 112.15 ( J = 25.4 Hz), 110.44 ( J = 8.1 Hz), 109.03 (J = 8.1 Hz), 94.79, 93.59, 63.73, 62.89, 50.41(J = 1.7 Hz), 49.86 (J = 1.6 Hz), 37.43, 27.58, 27.41, 14.14, 14.07; IR: 3298.6, 2927.8, 1747.9, 1722.8, 1636.2, 1613.7, 1492.8, 1469.3, 1352.8, 1258.6, 1198.5, 1151.0, 1105.5, 1030.8, 972.2, 866.1, 797.3, 734.3, 683.5 cm-1; HRMS calcd. for C23H19FNO7 [M+H]+ 440.1140, found: 440.1146；Data above proves the success of purpose Product formation.
Embodiment eight:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1h (29.3 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.6:1) i.e. can get mesh Mark product 3h (42.7 mg), yellow solid, mp:128-131 DEG C, yield is 77%, > 20/1 dr, 94% ee.
Being analyzed product 3h, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (85:15), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 30.714, t (minor) = 28.046]; [α]D 25 = + 188.8 (c = 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.63 (s, 0.3H), 8.21 (dd, J = 14.0, 8.0 Hz, 1H), 7.90 (d, J = 1.6 Hz, 0.7H), 7.55 – 7.51 (m, 1H), 7.42 (dd, J = 8.0, 1.6 Hz, 0.3H), 7.35 (dd, J = 8.4, 2.0 Hz, 0.77H), 7.32 – 7.28 (m, 1H), 7.21 (d, J = 1.6 Hz, 0.3H), 7.14 (d, J = 8.4 Hz, 0.7H), 7.10 (d, J = 8.8 Hz, 0.3H), 6.97 (d, J = 8.4 Hz, 0.3H), 6.90 (d, J = 8.4 Hz, 0.7H), 5.18 (s, 0.7H), 4.37 (dq, J = 14.8, 7.2 Hz, 2H), 3.35 (d, J = 9.5 Hz, 3H), 3.28 (d, J = 14.0 Hz, 0.7H), 3.03 (d, J = 14.8 Hz, 0.3H), 2.69 (d, J = 14.8 Hz, 0.3H), 2.33 (d, J = 14.0 Hz, 0.7H), 1.37 (dt, J = 14.8, 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.30, 175.04, 171.93, 171.73, 168.17, 167.16, 155.02, 154.96, 146.91, 144.69, 142.39, 137.18, 136.63, 133.73, 133.59, 131.22, 131.04, 130.38, 130.30, 130.25, 129.57, 128.84, 128.26, 126.39, 126.15, 124.92, 124.75, 124.39, 123.71, 118.03, 117.90, 110.64, 109.52, 94.77, 93.55, 63.78, 62.93, 50.18, 49.64, 37.44, 27.57, 27.39, 14.16, 14.09; IR: 3474.2, 2932.3, 1746.1, 1728.2, 1632.8, 1611.2, 1489.4, 1468.1, 1429.9, 1345.7, 1189.4, 1148.1, 1104.3, 1030.5, 977.3, 834.7, 808.9, 762.2, 703.7, 676.4 cm-1; HRMS calcd. for C23H19ClNO7 [M+H]+456.0845, found:456.0832；Data above proves the success of purpose Product formation.
Embodiment nine:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1i (36.5 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.8:1) i.e. can get mesh Mark product 3i (46.9 mg), white solid, mp:124-127 DEG C, yield is 89%, > 20/1 dr, 93% ee.
Being analyzed product 3i, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (80:20), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 22.013, t (minor) =19.790]; [α]D 25 = + 78.6 (c = 0.60, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.61 (s, 0.3H), 8.22 (dd, J = 8.0, 1.6 Hz, 0.3H), 8.18 (dd, J = 8.0, 1.2 Hz, 0.7H), 8.03 (d, J = 1.6 Hz, 0.7H), 7.57 – 7.48 (m, 2H), 7.34 (d, J = 2.0 Hz, 0.3H), 7.31 (d, J = 8.0 Hz, 0.7H), 7.13 (d, J = 8.4 Hz, 0.7H), 7.10 (d, J = 8.4 Hz, 0.3H), 6.92 (d, J = 8.4 Hz, 0.3H), 6.85 (d, J = 8.0 Hz, 0.7H), 5.22 (s, 0.7H), 4.36 (dq, J = 14.4, 7.2 Hz, 2H), 3.35 (d, J = 9.7 Hz, 3H), 3.29 (d, J = 2.0 Hz, 0.3H), 3.26 (d, J = 2.4 Hz, 0.3H), 3.03 (d, J = 14.8 Hz, 0.3H), 2.68 (d, J = 14.8 Hz, 0.3H), 2.33 (d, J = 14.0 Hz, 0.7H), 1.36 (dt, J = 14.4, 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.18, 174.93, 171.91, 171.70, 168.14, 167.15, 154.99, 154.94, 146.89, 144.69, 142.90, 142.87, 137.17, 136.62, 133.72, 133.57, 133.20, 132.46, 131.54, 130.94, 130.66, 127.09, 126.35, 126.12, 124.90, 124.73, 123.72, 123.69, , 118.02, 117.91, 117.38, 116.15, 111.09, 110.03, 94.76, 93.55, 63.75, 62.91, 50.10, 49.56, 37.46, 37.44, 27.54, 27.36, 14.15, 14.08; IR: 3494.2, 3280.2, 2961.3, 1723.3, 1364.5, 1610.4, 1480.4, 1467.2, 1339.7, 1282.0, 1218.4, 1173.6, 1146.4, 1106.2, 1040.3, 977.1, 961.1, 813.5, 797.2, 764.6, 747.7, 669.0, 643.9 cm-1; HRMS calcd. for C23H19ClNO7 [M+H]+500.0339, found:500.0339；Data above proves that purpose is produced Thing synthesizes successfully.
Embodiment ten:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1j (27.3 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 38 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.8:1) i.e. can get mesh Mark product 3j (41.7 mg), white solid, mp:226-228 DEG C, yield is 99%, > 20/1 dr, 96% ee.
Being analyzed product 3j, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (80:20), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 17.666, t (minor) = 15.895]; [α]D 25 = + 24.2 (c = 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.89 (s, 0.5H), 8.22 (dd, J = 8.0, 1.6 Hz, 0.5H), 8.18 (dd, J = 8.0, 1.6 Hz, 0.5H), 7.69 (s, 0.5H), 7.53 – 7.48 (m, 1H), 7.32 – 7.28 (m, 1H), 7.22 (d, J = 8.0 Hz, 0.5H), 7.17 – 7.13 (m, 1H), 7.09 (d, J = 8.4 Hz, 0.5H), 7.02 (s, 0.5H), 6.91 (d, J = 7.6 Hz, 0.5H), 6.85 (d, J = 8.0 Hz, 0.5H), 5.08 (d, J = 2.2 Hz, 0.5H), 4.35 (dt, J = 7.2, 5.0 Hz, 2H), 3.34 (d, J = 8.0 Hz, 3H), 3.29 (dd, J = 14.0, 2.4 Hz, 0.5H), 3.04 (d, J = 14.8 Hz, 0.5H), 2.66 (d, J = 14.8 Hz, 0.5H), 2.31 (d, J = 14.0 Hz, 0.5H), 2.30 (d, J = 8.8 Hz, 3H), 1.37 (dt, J = 16.6, 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.59, 175.37, 171.98, 171.84, 168.48, 167.37, 155.04, 154.99, 147.87, 145.70, 141.43, 141.36, 137.05, 136.59, 134.65, 133.52, 133.38, 132.99, 130.47, 129.86, 128.74, 128.73, 128.38, 126.28, 126.03, 124.71, 124.55, 124.47, 123.74, 123.71, 118.11, 117.94, 109.39, 108.30, 94.91, 93.64, 63.66, 62.76, 50.18, 49.61, 37.59, 27.41, 27.25, 21.32, 21.23, 14.14, 14.07; IR: 3494.7, 3282.8, 2961.6, 1745.8, 1718.6, 1636.8, 1611.3, 1499.5, 1359.2, 1282.1, 1260.8, 1196.1, 1103.7, 1037.9, 977.5, 964.8, 811.7, 796.6, 760.2, 699.6, 669.8, 647.7 cm-1; HRMS calcd. for C24H22NO7 [M+H]+436.1391, found:436.1396；Data above proves purpose product Synthesize successfully.
Embodiment 11:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1k (28.9 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.8:1) i.e. can get mesh Mark product 3k (44.2 mg), white solid, mp:191-193 DEG C, yield is 98%, > 20/1 dr, 98% ee.
Being analyzed product 3k, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (80:20), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 22.303, t (minor) = 27.639]; [α]D 25 = + 141.6 (c = 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.95 (s, 0.5H), 8.20 – 8.16 (m, 1H), 7.55 (d, J = 2.0 Hz, 0.5H), 7.53 – 7.49 (m, 1H), 7.29 (t,J = 1.2 Hz, 1H), 7.11 (dd, J = 19.6, 8.4 Hz, 1H), 6.93 (s, 1H), 6.89 (d, J = 2.4 Hz, 0.5H), 6.84 (d, J = 18.8 Hz, 1H), 5.07 (d, J = 1.6 Hz, 0.5H), 4.34 (dq, J = 15.6, 7.2 Hz, 2H), 3.74 (d, J = 8.0 Hz, 3H), 3.33 (d, J = 7.6 Hz, 3H), 3.28 (d, J = 2.0 Hz, 0.5H), 3.04 (d, J = 14.8 Hz, 0.5H), 2.67 (d, J = 14.8 Hz, 0.5H), 2.32 (d, J = 14.0 Hz, 0.5H), 1.36 (dt, J = 15.6, 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.27, 175.05, 171.92, 171.81, 168.41, 167.37, 157.49, 156.38, 155.02, 154.97, 147.62, 145.52, 137.15, 137.06, 136.99, 136.59, 136.59, 133.54, 133.42, 130.97, 129.96, 126.24, 126.02, 124.73, 124.57, 123.71, 123.69, 118.08, 117.92, 114.82, 114.58, 114.29, 110.57, 110.22, 108.92, 94.91, 93.60, 63.69 , 62.77, 55.95, 55.82, 50.51, 49.89, 37.63, 37.45, 27.47, 27.31, 14.14, 14.06; IR: 3350.6, 2963.2, 2922.7, 1748.1, 1714.7, 1652.5, 1637.1, 1611.6, 1497.2, 147.0, 1363.4, 1339.6, 1260.9, 1236.3, 1202.1, 1160.5, 1144.2, 1108.8, 1039.5, 1025.3, 977.0, 806.5, 758.1, 694.3, 679.9, 646.6 cm-1; HRMS calcd. for C24H22NO8 [M+H]+452.1340, found: 452.1352；Data above proves the success of purpose Product formation.
Embodiment 12:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1l (29.3 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.5:1) i.e. can get mesh Mark product 3l (39.1 mg), yellow solid, mp:111-113 DEG C, yield is 86%, > 20/1 dr, 97% ee.
Being analyzed product 3l, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (80:20), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 22.883, t (minor) = 30.794]; [α]D 25 = + 57.2 (c = 0.65, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.58 (s, 0.3H), 8.22 (dd, J = 8.0, 1.2 Hz, 0.3H), 8.18 (dd, J = 8.0, 1.6 Hz, 0.7H), 7.82 (d, J = 8.0 Hz, 0.7H), 7.55 – 7.51 (m, 1H), 7.34 – 7.28 (m, 1H), 7.15 (d, J = 7.4 Hz, 1H), 7.10 (d, J = 8.4 Hz, 0.3H), 7.05 – 7.03 (m, 1H), 6.97 (d, J = 2.0 Hz, 0.7H), 5.19 (s, 0.7H), 4.36 (dq, J = 11.1, 5.6 Hz, 2H), 3.35 (d, J = 9.2 Hz, 3H), 3.27 (d, J = 14.4 Hz, 0.7H), 3.03 (d, J = 14.8 Hz, 0.3H), 2.67 (d, J = 14.8 Hz, 0.3H), 2.31 (d, J = 14.0 Hz, 0.7H), 1.36 (dt, J = 11.1, 5.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.76, 175.49, 171.96, 171.77, 168.28, 167.21, 155.03, 154.97, 147.06, 145.02, 144.88, 137.15, 136.64, 136.18, 135.45, 133.74, 133.61, 128.85, 128.11, 127.09, 126.39, 126.13, 124.92, 124.81, 123.74, 124.67, 123.73, 123.69, 123.29, 118.03, 117.85, 110.51, 109.38, 94.80, 93.58, 63.79, 62.93, 49.84, 49.25, 37.57, 37.40, 27.56, 27.38, 14.16, 14.09; IR: 3348.8, 3277.2, 2961.0, 2923.4, 1722.4, 1365.8, 1607.2, 1468.0, 1365.6, 1281.9, 1260.5, 1188.7, 1147.4, 1103.4, 1078.4, 1025.5, 971.2, 798.4, 759.1,645.0, 621.5 cm-1; HRMS calcd. for C23H19ClNO7 [M+H]+456.0845, found:456.0833；Data above proves the success of purpose Product formation.
Embodiment 13:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1m (33.7 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.5:1) i.e. can get mesh Mark product 3m (42.9 mg), yellow solid, mp:105-107 DEG C, yield is 86%, > 20/1 dr, 97% ee.
Being analyzed product 3m, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (80:20), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 22.846, t (minor) = 31.330]; [α]D 25 = + 245.2 (c = 0.25, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.57 (s, 0.3H), 8.22 (dd, J = 8.0, 1.6 Hz, 0.3H), 8.18 (dd, J = 8.0, 1.6 Hz, 0.7H), 7.76 (d, J = 8.4 Hz, 0.7H), 7.55 – 7.51 (m, 1H), 7.32 – 7.28 (m, 1.3H), 7.21 (d, J = 2.0 Hz, 0.3H), 7.19 (d, J = 1.6 Hz, 0.7H), 7.15 (d, J = 8.4 Hz, 0.7H), 7.12 (d, J = 1.6 Hz, 0.7H), 7.09 (d, J = 1.6 Hz, 0.3H), 5.13 (d, J = 2.0 Hz, 0.7H), 4.36 (dt, J = 14.4, 7.1 Hz, 2H), 3.35 (d, J = 9.3 Hz, 3H), 3.28 (dd, J = 14.4, 1.6 Hz, 0.7H), 3.02 (d, J = 14.8 Hz, 0.3H), 2.67 (d,J = 15.2 Hz, 0.3H), 2.30 (d, J = 14.0 Hz, 0.7H), 1.37 (dt, J = 14.4, 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.63, 175.35, 171.89, 171.72, 168.25, 167.19, 155.01, 154.96, 146.91, 145.14, 144.77, 137.16, 136.67, 133.73, 133.60, 129.17, 128.66, 127.69, 1127.61, 126.37, 126.23, 126.13, 125.12, 124.90, 124.73, 123.86, 123.70, 123.30, 118.02, 117.85, 113.27, 112.16, 94.79, 93.55, 63.80, 62.91, 49.89, 49.29, 37.49, 37.34, 27.55, 27.37, 14.15, 14.09; IR: 3396.7, 3280.6, 2961.7, 2924.1, 1723.6, 1636.6, 1602.5, 1468.6, 1365.5, 1282.9,1260.5, 1188.9, 1149.5, 1101.7, 1025.4, 970.9, 798.9, 759.3, 707.0, 643.9, 620.5 cm-1; HRMS calcd. for C23H19BrNO7 [M+H]+ 500.0339, found: 500.0346；Data above proves the success of purpose Product formation.
Embodiment 14:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1n (28.9 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.5:1) i.e. can get mesh Mark product 3n (33.4 mg), reddish Solid, mp:210-211 DEG C, yield is 74%, > 20/1 dr, > 99% ee.
Being analyzed product 3n, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (80:20), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 26.010]; [α]D 25 = + 186.0 (c = 0.20, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.77 (s, 0.4H), 8.24 – 8.19 (m, 1H), 7.76 (d, J = 8.0 Hz, 0.5H), 7.52 (t, J = 7.6 Hz, 1H), 7.30 (dd,J = 14.4, 7.2 Hz, 1H), 7.15 (d, J = 8.4 Hz, 0.5H), 7.10 (d, J = 8.4 Hz, 1H), 6.66 – 6.59 (m, 1H), 6.56 – 6.54 (m, 1H), 4.94 (d, J = 1.8 Hz, 0.6H), 4.36 (dd, J = 14.9, 7.3 Hz, 2H), 3.86 (d, J = 7.6 Hz, 3H), 3.34 (d, J = 6.0 Hz, 3H), 3.28 (dd, J = 14.0, 2.0 Hz, 0.6H), 3.02 (d, J = 15.2 Hz, 0.4H), 2.65 (d,J = 15.2 Hz, 0.4H), 2.29 (d, J = 14.0 Hz, 0.6H), 1.38 (dd, J = 14.9, 7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 178.34, 176.05, 171.99, 171.89, 168.52, 167.41, 161.64, 161.11, 155.07, 155.03, 147.89, 145.81, 145.16, 136.54, 133.43, 128.53, 126.36, 126.11, 124.75, 124.60, 124.56, 123.76, 121.88, 120.28, 118.11, 117.91, 108.28, 106.82, 97.87, 96.71, 94.98, 93.67, 63.75, 62.82, 55.88, 55.72, 49.74, 49.13, 37.77, 37.68, 27.42, 27.28, 14.18, 14.11; IR: 3334.4, 2962.9, 2938.6, 1740.2, 1707.5, 1629.4, 1612.5, 1470.9, 1456.4, 1373.9, 1288.0, 1262.2, 1194.5, 1149.8, 1101.2, 1062.6, 969.3, 927.7, 877.8, 804.3, 758.7, 691.5, 649.3, 639.4, 617.3 cm-1; HRMS calcd. for C24H22NO8 [M+H]+ 452.1340, found:452.1353；Data above proves the success of purpose Product formation.
Embodiment 15:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1o (27.7 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.5:1) i.e. can get mesh Mark product 3o (43.5 mg), yellow solid, mp:190-192 DEG C, yield is 99%, > 20/1 dr, 99% ee.
Being analyzed product 3o, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (80:20), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 19.841, t (minor) = 40.459]; [α]D 25 = + 132.9 (c = 0.54, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 0.4H), 8.21 (dd, J = 8.0, 1.2 Hz, 0.4H), 8.17 (dd, J = 8.0, 1.2 Hz, 0.6H), 7.71 (d, J = 7.2 Hz, 0.6H), 7.55 – 7.50 (m, 1H), 7.33 – 7.28 (m, 1H), 7.18 – 7.16 (m, 1H), 7.16 (d, J = 8.4 Hz, 1H), 7.14 (d, J = 2.4 Hz, 0.4H), 7.12 – 7.07 (m, 1H), 7.02 – 6.97 (m, 1H), 5.20 (s, 0.6H), 4.35 (dq, J = 14.6, 7.2 Hz, 3H), 3.56 (d, J = 2.8 Hz, 3H), 3.28 (dd, J = 14.4, 1.6 Hz, 0.6H), 3.03 (d, J = 14.8 Hz, 0.4H), 2.70 (d, J = 14.8 Hz, 0.4H), 2.34 (d, J = 14.0 Hz, 0.6H), 1.36 (dt, J = 14.6, 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.34, 175.14, 171.93, 171.75, 168.27, 167.19, 155.02, 154.97, 148.02 (d, J = 244.8 Hz), 147.84 (d, J = 242.0 Hz), 147.11, 137.02, 136.57, 133.71, 136.57, 132.35 (d, J = 2.5 Hz), 131.41 (d, J = 2.7 Hz), 130.56 (d, J = 8.4 Hz), 130.53(d, J = 8.8 Hz), 126.33, 126.08, 125.45 (d, J = 6.5 Hz), 124.86, 124.67, 123.84 (d, J = 8.6 Hz), 123.68 (d, J = 4.2 Hz), 123.58 (d, J = 3.2 Hz), 119.65 (d, J = 3.3 Hz), 118.28 (d, J = 19.0 Hz), 118.03, 117.85, 117.47 (d, J = 18.8 Hz), 94.81, 93.54, 63.72, 62.86, 50.33 (d, J = 1.9 Hz), 49.69 (d, J = 2.1 Hz), 37.76, 37.59, 30.02 (d, J = 5.8 Hz), 29.84 (d, J = 6.2 Hz), 14.13, 14.06; IR: 3516.5, 3277.3, 2961.2, 2922.7, 1736.5, 1715.6, 1624.6, 1610.9, 1477.8, 1466.6, 1364.9, 1336.3, 1284.1, 1260.1, 1245.1, 1196.8, 1108.1, 1080.2, 1048.3, 1023.4, 988.0, 963.4, 800.7, 758.6, 702.5, 642.4, 628.9 cm-1; HRMS calcd. for C23H19FNO7 [M+H]+440.1140, found:440.1151；Data above Prove the success of purpose Product formation.
Embodiment 16:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1p (27.3 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.5:1) i.e. can get mesh Mark product 3p (43.0 mg), yellow solid, mp:191-194 DEG C, yield is 99%, > 20/1 dr, > 99% ee.
Being analyzed product 3p, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (80:20), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 31.735]; [α]D 25 = + 92.0 (c = 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.92 (s, 0.65H), 8.21 (dd, J = 8.0, 1.2 Hz, 0.65H), 8.17 (dd, J = 8.0, 1.6 Hz, 0.35H), 7.73 (d, J = 7.2 Hz, 0.35H), 7.53 – 7.49 (m, 1H), 7.29 (t, J =7.2 Hz, 1H), 7.18 – 7.12 (m, 1H), 7.10 – 7.07 (m, 0.35H), 7.05 – 7.02 (m, 1H), 6.93 (t, J = 7.6 Hz, 0.35H), 5.07 (s, 0.35H), 4.34 (dt, J = 16.0, 7.2 Hz, 2H), 3.62 (s, 3H), 3.28 (d, J = 14.0 Hz, 0.35H), 2.99 (d, J = 14.8 Hz, 0.35H), 2.66 (d, J = 3.2 Hz, 3H), 2.62 (d, J = 14.4 Hz, 0.65H), 2.30 (d, J = 14.4 Hz, 0.35H), 1.36 (dt, J = 16.0, 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 178.28, 176.32, 171.95, 171.83, 168.44, 167.33, 155.06, 155.00, 147.92, 145.78, 141.50, 141.46, 137.04, 137.64, 133.93, 133.53, 133.38, 133.31, 130.50, 129.38, 126.25, 126.01, 125.51, 124.71, 124.59, 124.55, 123.70, 123.18, 121.64, 121.33, 120.03, 118.10, 117.90, 94.91, 93.63, 63.63, 62.73, 49.61, 49.04, 38.10, 37.95, 30.79, 30.75, 19.40, 19.01, 14.14.05; IR: 3503.2, 3277.8, 2960.2, 2924.9, 1736.6, 1694.9, 1667.7, 1648.6, 1634.0, 1612.0, 1466.3, 1377.1, 1361.1, 1287.1, 1260.5, 1195.2, 1145.4, 1111.1, 1071.5, 1021.2, 965.3, 909.4, 795.5, 763.3, 749.9, 699.7, 643.2, 623.9 cm-1; HRMS calcd. for C23H19FNO7 [M+H]+ 436.1391, found:436.1400；Data above proves the success of purpose Product formation.
Embodiment 17:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1q (28.7 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.7:1) i.e. can get mesh Mark product 3q (35.9 mg), yellow solid, mp:200-202 DEG C, yield is 80%, > 20/1 dr, 98% ee.
Being analyzed product 3q, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (80:20), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 21.379, t (minor) = 19.769]; [α]D 25 = + 45.0 (c = 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.98 (s, 0.7H), 8.22 (dd, J = 8.0, 1.6 Hz, 0.7H), 8.18 (dd, J = 8.0, 1.6 Hz, 0.3H), 7.54 – 7.50 (m, 1.3H), 7.32 (d, J = 0.8 Hz, 0.2H), 7.29 (d, J = 8.0 Hz, 0.8H), 7.18 (d, J = 8.4 Hz, 0.3H), 7.14 (d, J = 8.4 Hz, 0.7H), 6.94 (s, 0.7H), 6.89 (s, 0.3H), 6.82 (s, 0.7H), 5.03 (d, J = 2.0 Hz, 0.3H), 4.35 (dq,J = 16.8, 7.2 Hz, 3H), 3.59 (s, 3H), 3.27 (dd, J = 14.0, 2.4 Hz, 1H), 2.98 (d, J = 14.8 Hz, 0.7H), 2.63 (d, J = 11.2 Hz, 0.6H), 2.62 (s, 3H), 2.29 (d, J = 14.4 Hz, 0.4H), 2.23 (d, J = 7.2 Hz, 3H), 1.36 (dt, J = 16.8, 7.2 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 178.16, 176.23, 171.99, 171.87, 168.52, 167.41, 155.08, 155.03, 148.16, 146.01, 139.04, 139.00, 137.00, 136.59, 134.37, 133.76, 133.48, 133.35, 132.69, 130.61, 129.42, 126.26, 126.11, 126.01, 124.68, 124.53,123.74, 122.28, 120.99, 118.17, 117.99, 94.94, 93.64, 63.64, 62.73, 49.67, 49.12, 38.10, 38.06, 30.72, 20.97, 20.88, 19.23, 18.84, 14.14, 14.07; IR: 3151.5, 2961.7, 2921.9, 1757.4, 1710.4, 1660.6, 1632.5, 1612.4, 1485.3, 1468.8, 1442.9, 1371.2, 1287.2, 1260.4, 1200.4, 1139.1, 1099.0, 1077.0, 1025.7, 961.6, 870.6, 800.3, 761.7, 695.9, 648.9 cm-1; HRMS calcd. for C25H24NO7 [M+H]+450.1547, found:450.1558；Data above proves the success of purpose Product formation.
Embodiment 18:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1r (29.5 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.7:1) i.e. can get mesh Mark product 3r (42.5 mg), yellow solid, mp:113-115 DEG C, yield is 96%, > 20/1 dr, 93% ee.
Being analyzed product 3r, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (80:20), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 22.295, t (minor) = 27.049]; [α]D 25 = + 98.2 (c = 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 0.2H), 8.20 (dd, J = 8.0, 1.2 Hz, 0.2H), 8.16 (dd, J = 8.0, 1.6 Hz, 0.8H), 7.82 (dd, J = 10.0, 8.0 Hz, 0.8H), 7.55 – 7.51 (m, 1H), 7.29 (t, J = 8.0 Hz, 1H), 7.14 (d, J = 8.4 Hz, 0.8H), 7.10 (t, J = 8.0 Hz, 0.2H), 6.90 (dd, J = 9.2, 6.0 Hz, 2H), 6.80 (dd, J = 9.6, 6.4 Hz, 0.8H), 5.51 (s, 0.8H), 4.36 (dq, J = 13.6, 6.4 Hz, 2H), 3.34 (d, J = 10.2 Hz, 3H), 3.25 (dd, J = 14.0, 1.6 Hz, 0.8H), 3.00 (d, J = 14.8 Hz, 0.2H), 2.69 (d, J = 15.2 Hz, 0.2H), 2.33 (d, J = 14.4 Hz, 0.8H), 1.36 (dt, J = 13.6, 6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 17.54, 175.30, 171.96, 171.70, 168.10, 167.14, 154.98, 154.93, 151.39, (d, J = 248.2 Hz), 151.25 (d, J = 248.1 Hz), 146.83 (d, J = 241.4 Hz), 146.76, 146.71 (d, J = 244.3 Hz), 140.26 (d, J = 11.6 Hz), 137.19, 136.55, 136.55, 133.82, 133.68, 126.38 (s), 126.13, 124.99 (d, J = 2.9 Hz), 124.92 (d, J = 4.0 Hz), 124.80, 123.68, 123.62, 118.01 (d, J = 11.7 Hz), 117.95, 117.83 (d, J = 42.0 Hz), 98.90, 98.67, 94.76, 93.61, 63.73, 62.96, 50.06, 49.52, 37.53, 37.41, 27.69, 27.51, 14.12, 14.06; IR: 3279.2, 3070.6, 2961.2, 2161.1, 2031.0, 1979.4, 1626.2, 1613.7, 1506.3, 1428.2, 1391.7, 1368.7, 1283.9, 1252.0, 1185.7, 1152.3, 1096.7, 1024.9, 1007.6, 960.4, 873.5, 786.3, 758.8,688.3, 645.2, 618.4 cm-1; HRMS calcd. for C23H18F2NO7 [M+H]+ 458.1046, found:458.1048；Data above proves the success of purpose Product formation.
Embodiment 19:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1s (24.5 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2a (24.3 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.5:1) i.e. can get mesh Mark product 3s (35.8 mg), reddish Solid, mp:205-207 DEG C, yield is 98%, > 20/1 dr, 98% ee.
Being analyzed product 3s, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (70:30), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 20.279, t (minor) = 32.183]; [α]D 25 = + 71.5 (c = 0.52, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.88 (s, 0.55H), 8.22 (dd, J = 8.0, 1.2 Hz, 0.6H), 8.19 (dd, J = 8.4, 1.6 Hz, 0.4H), 7.87 (d, J = 7.6 Hz, 0.4H), 7.53 – 7.49 (m, 1H), 7.44 (td, J = 7.6, 1.2 Hz, 0.6H), 7.38 (dt, J = 8.0, 1.2 Hz, 0.45H), 7.33 – 7.29 (m, 1H), 7.20 (dd, J = 12.0, 6.4 Hz, 1H), 7.15 – 7.12 (m, 0.55H), 7.09 – 7.06 (m, 1H), 7.04 (d, J = 8.0 Hz, 0.6H), 6.97 (d, J = 7.6 Hz, 0.4H), 5.01 (d, J = 2.0 Hz, 0.45H), 3.91 (s, 3H), 3.37 (d, J = 10.8 Hz, 3H), 3.30 (dd, J = 14.0, 2.4 Hz, 0.45H), 3.07 (d, J = 14.8 Hz, 0.55H), 2.69 (d, J = 15.2 Hz, 1H), 2.33 (d, J = 14.0 Hz, 0.45H); 13C NMR (101 MHz, CDCl3) δ 177.71, 175.38, 171.94, 171.84, 168.87, 167.82, 155.06, 155.00, 147.64, 145.48, 143.86, 143.00, 137.03, 136.56, 133.62, 133.47, 130.27, 129.82, 129.57, 128.71, 127.64, 126.33, 126.08, 124.81, 124.79, 124.63, 123.75, 123.72, 123.69, 123.43, 118.08, 117.88, 109.69, 108.62, 94.97, 93.72, 54.07, 53.52, 50.15, 49.49, 37.64, 37.48, 27.43, 27.25; IR: 3316.0, 2961.4, 2922.7, 1752.1, 1725.6, 1637.8, 1610.0, 1468.3, 1432.1, 1366.3, 1351.3, 1280.3, 1270.1, 1260.5, 1219.0, 1188.0, 1146.9, 1124.0, 1070.1, 979.7, 966.8, 945.6, 811.9, 801.2, 760.7, 746.8, 660.7, 640.5, 616.8 cm-1; HRMS calcd. for C30H24NO9 [M+H]+ 408.1078, found:408.1084；Data above proves the success of purpose Product formation.
Embodiment 20:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1a (25.9 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2b (27.0 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.5:1) i.e. can get mesh Mark product 3t (37.4 mg), reddish Solid, mp:170-173 DEG C, yield is 88%, > 20/1 dr, 93% ee.
Being analyzed product 3t, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (70:30), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 12.258, t (minor) = 22.094]; [α]D 25 = + 80.2 (c = 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.81 (s, 0.5H), 7.88 (dd, J = 7.6, 0.8 Hz, 0.5H), 7.84 (dd, J = 8.0, 2.8 Hz, 0.5H), 7.80 (dd, J = 8.0, 2.8 Hz, 0.5H), 7.45 (td, J = 7.6, 1.2 Hz, 0.5H), 7.38 (td, J = 7.6, 1.2 Hz, 0.5H), 7.24 – 7.21 (m, 1H), 7.20 – 7.13 (m, 1H), 7.04 (d, J = 7.6 Hz, 0.5H), 6.97 (d, J = 7.6 Hz, 0.5H), 5.17 (s, 0.5H), 4.35 (tq, J =14.4, 7.2 Hz, 2H), 3.36 (d, J = 9.6 Hz, 3H), 3.28 (d, J = 14.0 Hz, 0.5H), 3.05 (d, J = 15.2 Hz, 0.5H), 2.68 (d, J = 15.2 Hz, 1H), 2.33 (d, J = 14.4 Hz, 0.5H), 1.37 (dt, J = 14.4, 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 177.58, 175.35, 171.24, 171.11, 168.33, 167.22, 159.24 (J = 245.3 Hz), 159.17 (J = 245.1 Hz), 151.33, 151.25, 148.05, 145.86, 143.82, 143.73, 136.77, 136.35, 130.33, 129.73, 129.63, 128.63, 127.70, 124.86, 124.84 (J = 6.3 Hz), 124.75 (J = 4.6 Hz), 123.78, 123.48, 120.06 (J = 14.6 Hz), 121.75 (J = 14.5 Hz), 120.26 (J = 8.1 Hz), 120.06 (J = 8.0 Hz), 110.94 (J = 27.1 Hz), 10.70 (J = 26.9 Hz), 109.72, 108.67, 100.09, 94.97, 93.70, 63.75, 62.86, 50.16, 49.57, 37.64, 37.48, 27.44, 27.27, 14.14, 14.08; IR: 3430.1, 2987.5, 1755.6, 1711.6, 1610.3, 1483.3, 1469.4, 1369.7, 1259.8, 1186.1, 1163.3, 1100.0, 1022.9, 994.4, 852.4, 831.0, 799.5, 757.7, 691.1, 642.2 cm-1; HRMS calcd. for C23H19FNO7 [M+H]+440.1140, found:440.1143；Data above proves the success of purpose Product formation.
Embodiment 21:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1a (25.9 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2c (35.8 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.5:1) i.e. can get mesh Mark product 3u (37.4 mg), reddish Solid, mp:136-138 DEG C, yield is 65%, > 20/1 dr, 92% ee.
Being analyzed product 3u, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (70:30), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 15.695, t (minor) = 31.396]; [α]D 25 = + 355.0 (c = 0.61, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.82 (s, 0.5H), 8.32 (d, J = 2.4 Hz, 0.5H), 8.27 (d, J = 2.0 Hz, 0.5H), 7.88 (d, J = 7.6 Hz, 0.5H), 7.58 (dt, J = 8.8, 2.4 Hz, 1H), 7.47 – 7.36 (m, 1H), 7.24 – 7.18 (m, 1H), 7.10 – 7.04 (m, 1H), 7.03 (d, J = 4.8 Hz, 0.5H), 6.99 – 6.96 (m, 1H), 5.22 (s, 0.5H), 4.35 (dq, J = 7.2, 4.4 Hz, 3H), 3.36 (d,J = 10.0 Hz, 3H), 3.27 (d, J = 14.0 Hz, 0.5H), 3.05 (d, J = 15.2 Hz, 0.5H), 2.68 (d, J = 15.2 Hz, 0.5H), 2.34 (d, J = 14.4 Hz, 0.5H), 1.36 (dt, J = 14.6, 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.52, 175.27, 170.73, 170.59, 168.29, 167.18, 153.81, 153.75, 148.11,145.88, 143.81, 143.71, 137.27, 136.81, 136.58, 136.42, 130.36, 129.65, 128.70, 128.53, 128.46, 127.73, 125.00, 124.98, 124.88, 123.80, 123.51, 120.07, 119.87, 118.24, 118.06, 109.73, 108.67, 95.01, 93.73, 63.75, 62.88, 50.15, 49.57, 37.66, 37.46, 27.45, 27.28, 14.15, 14.08; IR: 3331.6, 2926.6, 1741.1, 1723.1, 1626.8, 1606.3, 1467.2, 1418.4, 1352.2, 1242.0, 1227.8, 1098.5, 1074.8, 987.5, 963.1, 835.7, 754.6, 660.7 cm-1; HRMS calcd. for C23H19BrNO7 [M+H]+ 500.0339, found: 500.0337；Data above proves the success of purpose Product formation.
Embodiment 22:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1a (25.9 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2d (26.4 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.4:1) i.e. can get mesh Mark product 3v (42.2 mg), yellow solid, mp:106-108 DEG C, yield is 97%, > 20/1 dr, 98% ee.
Being analyzed product 3v, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (70:30), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 19.812, t (minor) = 41.106]; [α]D 25 = + 52.8 (c = 0.60, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.81 (s, 0.5H), 7.97 (dd, J = 18.8, 1.2 Hz, 0.5H), 7.88 (d, J = 7.6 Hz, 0.5H), 7.43 (td, J = 8.0, 1.2 Hz, 0.5H), 7.36 (td, J = 8.0, 1.2 Hz, 0.5H), 7.32 – 7.29 (m, 1H), 7.21 – 7.14 (m, 1H), 7.07 (dd, J = 7.6, 0.8 Hz, 0.5H), 7.02 (d, J = 8.4 Hz, 0.5H), 6.97 (d, J = 3.2 Hz, 0.5H), 6.95 (d, J = 2.4 Hz, 0.5H), 5.15 (s, 0.5H), 4.39 (dq, J = 16.8, 7.2 Hz, 2H), 3.35 (d, J = 8.4 Hz, 3H), 3.28 (d, J = 14.0 Hz, 0.5H), 3.04 (d, J = 14.8 Hz, 0.5H), 2.66 (d, J = 14.8 Hz, 0.5H), 2.36 (d, J = 5.6 Hz, 3H), 2.32 (d, J = 14.0 Hz, 0.5H), 1.36 (dt, J = 16.8, 7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 177.74, 175.52, 172.02, 171.88, 168.45, 167.35, 153.37, 153.30, 147.52, 145.35, 143.84, 143.75, 136.96, 136.51, 134.90, 134.77, 134.74, 134.52, 130.17, 129.93, 129.47, 128.85, 127.68, 125.43, 125.18, 124.73, 123.72, 123.37, 117.79, 117.60, 109.62, 108.56, 94.85, 93.63, 63.62, 62.76, 50.15, 49.56, 37.62, 37.51, 27.38, 27.21, 20.86, 14.13, 14.06; IR: 3283.4, 2936.0, 1717.8, 1611.6, 1488.4, 1471.8, 1368.8, 1278.3, 1191.7, 1161.4, 1129.7, 1031.4, 961.7, 692.2, 662.7 cm-1; HRMS calcd. for C24H22NO7 [M+H]+436.1391, found:436.1381；Data above is demonstrate,proved The Product formation success of improving eyesight.
Embodiment 23:
Reaction bulb is sequentially added into quinine thiourea (3.0 mg, 0.005 mmol), and 1a (25.9 mg, 0.1 mmol), adds 1 mL dichloromethane, reacts 20 minutes under subzero 20 degrees celsius, adds 2e (28.8 mg, 0.15 mmol), continues Reacting 40 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.4:1) i.e. can get mesh Mark product 3w (44.6 mg), yellow solid, mp:218-220 DEG C, yield is 99%, > 20/1 dr, 99% ee.
Reaction bulb is sequentially added into quinine thiourea (90.65 mg, 0.005 mmol), and 1a (906.5 mg, 3.5 Mmol), add 5 mL dichloromethane, react 20 minutes under subzero 20 degrees celsius, add 2e (1.51g 5.25 Mmol), continuing reaction 41 hours, by simple column chromatography, (eluant is petroleum ether to reaction system: ethyl acetate=1.4:1) I.e. can get target product 3w (1.76 g), yellow solid, mp:218-220 DEG C, yield is 92%, > 20/1 dr, 99% ee。
Being analyzed product 3w, result is as follows: measure [Daicel Chiralpak IA, hexane/ with HPLCi - PrOH (70:30), flow rate: 1.0 mL·min-1, λ = 254 nm, t (major) = 16.022, t (minor) = 23.611]; [α]D 25 = + 43.6 (c = 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.80 (s, 0.5H), 8.11 (d, J = 9.2 Hz, 0.5H), 8.05 (d, J = 8.8 Hz, 0.5H), 7.92 (d, J = 7.2 Hz, 0.5H), 7.45 (t, J = 8.4 Hz, 0.5H), 7.39 (t, J = 7.2 Hz, 0.5H), 7.24 – 7.17 (m, 1H), 7.11 – 7.04 (m, 1H), 6.98 (d, J = 8.0 Hz, 0.5H), 6.85 (ddd, J = 15.6, 8.8, 2.0 Hz, 1H), 6.49 (d, J = 2.4 Hz, 0.5H), 6.44 (d, J = 2.0 Hz, 0.5H), 5.41 (s, 0.5H), 4.36 (q, J = 7.2 Hz, 2H), 3.77 (s, 3H), 3.37 (d, J = 8.0 Hz, 3H), 3.25 (d, J = 14.0 Hz, 0.5H), 3.04 (d, J = 14.8 Hz, 0.5H), 2.67 (d, J = 14.8 Hz, 0.5H), 2.34 (d, J = 14.0 Hz, 0.5H), 1.37 (dt, J = 16.9, 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 177.74, 175.61, 171.50, 171.27, 168.44, 167.36, 164.14, 164.03, , 156.86, 156.77, 147.09, 144.90, 143.83, 143.73, 137.00, 136.50, 130.16, 129.94, 129.44, 128.86, 127.77, 127.58, 127.27, 124.75, 123.76, 123.40, 117.60, 117.49, 114.60, 114.49, 109.65, 108.65, 99.92, 94.86, 93.72, 63.52, 62.76, 55.89, 55.85, 50.07 (, 49.53, 37.76, 37.60, 27.40, 27.24, 14.12, 14.05; IR: 3287.6, 2962.2, 1733.3, 1609.8, 1446.5, 1422.9, 1368.4, 1265.9, 1167.8, 1153.7, 1100.4, 1028.0, 973.5, 833.4, 748.5, 694.1, 635.9 cm-1; HRMS calcd. for C24H22NO8 [M+H]+ 452.1340, found:452.1343；Data above proves the success of purpose Product formation.

Claims (10)

1. chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3, the synthetic method of 4-dihydro-pyran compound, its feature exists In, comprise the following steps: derive beta, gamma-unsaturation alpha-keto ester compound with isatin and 3-hydroxyl-4 hydrogen-chromene-4-assimilation is closed Thing is reactant, and with chirality quinine thiourea as catalyst, in halogenated hydrocarbon solvent, reaction obtains oxa-volution hydroxyindole half contracting Ketonic compound；
Described isatin derives the chemical structural formula of β, γ-unsaturation alpha-keto ester compound, wherein R1Choosing From: the one in methyl, methoxy, benzyl, pi-allyl, benzyloxycarbonyl group；R2It is selected from: hydrogen, 5-fluorine, 5-chlorine, 5-bromine, 5-first One in base, 5-methoxyl group, 6-chlorine, 6-bromine, 6-methoxyl group, 7-fluorine, 7-methyl, 5,6-difluoro, 5,7-dimethyl；R3Choosing From: the one in methyl, ethyl；
The chemical structural formula of described 3-hydroxyl-4 hydrogen-chromene-4-ketonic compound is, wherein R is hydrogen, 6- One in fluorine, 6-bromine, 6-methyl, 7-methoxyl group；
The structural formula of described chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound is:
。
The conjunction of chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound the most according to claim 1 One-tenth method, it is characterised in that: described halogenated hydrocarbon solvent is dichloromethane.
The conjunction of chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound the most according to claim 1 One-tenth method, it is characterised in that: with molar amount, the consumption of described catalyst is that isatin derives beta, gamma-unsaturation 2-ketoacid esterification The 2-10% of compound.
The synthesis of chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound the most according to claim 1 Method, it is characterised in that: with molar amount, the consumption of described 3-hydroxyl-4 hydrogen-chromene-4-ketone is that isatin derives beta, gamma-insatiable hunger With alpha-keto ester compound 1-2 times.
The conjunction of chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound the most according to claim 1 One-tenth method, it is characterised in that: the described response time is 36-41 hour.
The conjunction of chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound the most according to claim 1 One-tenth method, it is characterised in that: described reaction temperature be-30 DEG C to room temperature.
The conjunction of chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound the most according to claim 1 One-tenth method, it is characterised in that: in reactor, it is sequentially added into catalyst, isatin derives beta, gamma-unsaturation alpha-keto ester chemical combination Thing, halogenated hydrocarbon solvent, add 3-hydroxyl-4 hydrogen-chromene-4-ketonic compound, react after stirring 15-35 minute, reaction knot Shu Hou, crude product i.e. can get chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran chemical combination by column chromatography Thing.
The synthesis of chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound the most according to claim 1 Method, it is characterised in that: the chemical structural formula of described chirality quinine thiourea is:
。
9. chirality quinine thiourea catalysis isatin derive β, γ-unsaturation alpha-keto ester compound and 3-hydroxyl-4 hydrogen-chromene- Application in the reaction of 4-ketonic compound, it is characterised in that: with molar amount, the consumption of described chirality quinine thiourea is that isatin spreads out The 2-10% of raw β, γ-unsaturation alpha-keto ester compound；
Described isatin derives the chemical structural formula of β, γ-unsaturation alpha-keto ester compound, wherein R1Choosing From: the one in methyl, methoxy, benzyl, pi-allyl, benzyloxycarbonyl group；R2It is selected from: hydrogen, 5-fluorine, 5-chlorine, 5-bromine, 5-first One in base, 5-methoxyl group, 6-chlorine, 6-bromine, 6-methoxyl group, 7-fluorine, 7-methyl, 5,6-difluoro, 5,7-dimethyl；R3Choosing From: the one in methyl, ethyl；
The chemical structural formula of described 3-hydroxyl-4 hydrogen-chromene-4-ketonic compound is, wherein R is hydrogen, 6- One in fluorine, 6-bromine, 6-methyl, 7-methoxyl group.
10. according to any one chiral spiro hydroxyindole described in claim 1-8-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran Chiral spiro hydroxyindole-.alpha.-5:6-benzopyran-one also-3,4-dihydro-pyran compound prepared by the synthetic method of compound.
CN201610558105.8A 2016-07-15 2016-07-15 A kind of synthetic method of chiral spiro hydroxyindole benzopyrone and 3,4 dihydropyrane compounds Active CN106188078B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201610558105.8A CN106188078B (en) 2016-07-15 2016-07-15 A kind of synthetic method of chiral spiro hydroxyindole benzopyrone and 3,4 dihydropyrane compounds
CN201810027686.1A CN108358941B (en) 2016-07-15 2016-07-15 The application of chiral quinine thiocarbamide

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610558105.8A CN106188078B (en) 2016-07-15 2016-07-15 A kind of synthetic method of chiral spiro hydroxyindole benzopyrone and 3,4 dihydropyrane compounds

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN201810027686.1A Division CN108358941B (en) 2016-07-15 2016-07-15 The application of chiral quinine thiocarbamide

Publications (2)

Publication Number Publication Date
CN106188078A true CN106188078A (en) 2016-12-07
CN106188078B CN106188078B (en) 2018-04-03

Family

ID=57476045

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201610558105.8A Active CN106188078B (en) 2016-07-15 2016-07-15 A kind of synthetic method of chiral spiro hydroxyindole benzopyrone and 3,4 dihydropyrane compounds
CN201810027686.1A Active CN108358941B (en) 2016-07-15 2016-07-15 The application of chiral quinine thiocarbamide

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN201810027686.1A Active CN108358941B (en) 2016-07-15 2016-07-15 The application of chiral quinine thiocarbamide

Country Status (1)

Country Link
CN (2) CN106188078B (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107056784A (en) * 2017-06-26 2017-08-18 苏州大学 A kind of chiral double hydroxyindole spiro-compounds and its synthetic method
CN107176959A (en) * 2017-06-26 2017-09-19 苏州大学 A kind of chiral spiro hydroxyindole dihydropyran derivatives and its synthetic method
CN108912123A (en) * 2018-08-17 2018-11-30 河南师范大学 A method of passing through asymmetric [3+3] cyclization synthesis of chiral six-membered carbon ring purine nucleosides
CN113004296A (en) * 2021-03-22 2021-06-22 重庆大学 General synthetic method for preparing chiral oxygen heterocyclic compound by novel [4+1] and [5+1] cyclization strategies
CN113248480A (en) * 2021-05-12 2021-08-13 常州大学 Method for inserting 2-pyridone or 3-pyridazinone N-H bond in furan carbene chemoselectivity and enantioselectivity
CN114516881A (en) * 2022-03-08 2022-05-20 贵州大学 Azacyclocarbene-catalyzed chiral compound containing pyrazolopyran skeleton and preparation method thereof
CN115124450A (en) * 2022-07-15 2022-09-30 苏州大学 Synthetic method of indolone derivative containing crotonamide structure

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102153477A (en) * 2011-02-25 2011-08-17 苏州大学 Novel method for synthesizing chiral 4-nitryl-3, 5-diaryl cyclohexanone
CN102432526A (en) * 2011-09-06 2012-05-02 苏州大学 Chiral 2',5-dicarbonyl-3-aryl spiro[cyclohexane-1,3'-indole]-2,2-dinitrile derivative and preparation method thereof
CN102964304A (en) * 2012-09-28 2013-03-13 苏州大学 Preparation method of chiral amino cyanide containing pyrazolidone structure
CN103554117A (en) * 2013-10-16 2014-02-05 苏州大学张家港工业技术研究院 Preparation method of chiral spiro naphthoquinone benzopyran hydroxyindole compound

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104447604B (en) * 2014-11-27 2016-08-24 苏州大学 A kind of synthetic method of chirality quaternary carbon oxazoline ketonic compound
CN104860911B (en) * 2015-05-25 2017-03-22 苏州大学 Synthesis method of chiral 3,4-dihydrocoumarin derivative compound

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102153477A (en) * 2011-02-25 2011-08-17 苏州大学 Novel method for synthesizing chiral 4-nitryl-3, 5-diaryl cyclohexanone
CN102432526A (en) * 2011-09-06 2012-05-02 苏州大学 Chiral 2',5-dicarbonyl-3-aryl spiro[cyclohexane-1,3'-indole]-2,2-dinitrile derivative and preparation method thereof
CN102964304A (en) * 2012-09-28 2013-03-13 苏州大学 Preparation method of chiral amino cyanide containing pyrazolidone structure
CN103554117A (en) * 2013-10-16 2014-02-05 苏州大学张家港工业技术研究院 Preparation method of chiral spiro naphthoquinone benzopyran hydroxyindole compound

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HAI-BIN YANG ET AL.: ""Asymmetric Synthesis of Bioxindole-Substituted Hexahydrofuro[2,3-b]furans via Hydroquinine Anthraquinone-1,4-diyl Diether-Catalyzed Domino Annulation of Acylidenoxindoles/Isatins, Acylidenoxindoles and Allenoates"", 《ADV. SYNTH. CATAL.》 *
V. PRATAP REDDY GAJULAPALLI ET AL.: ""Organocatalytic construction of spirooxindole naphthoquinones through Michael/hemiketalization using L-proline derived bifunctional thiourea"", 《RSC ADVANCES》 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107056784A (en) * 2017-06-26 2017-08-18 苏州大学 A kind of chiral double hydroxyindole spiro-compounds and its synthetic method
CN107176959A (en) * 2017-06-26 2017-09-19 苏州大学 A kind of chiral spiro hydroxyindole dihydropyran derivatives and its synthetic method
CN108912123A (en) * 2018-08-17 2018-11-30 河南师范大学 A method of passing through asymmetric [3+3] cyclization synthesis of chiral six-membered carbon ring purine nucleosides
CN113004296A (en) * 2021-03-22 2021-06-22 重庆大学 General synthetic method for preparing chiral oxygen heterocyclic compound by novel [4+1] and [5+1] cyclization strategies
CN113248480A (en) * 2021-05-12 2021-08-13 常州大学 Method for inserting 2-pyridone or 3-pyridazinone N-H bond in furan carbene chemoselectivity and enantioselectivity
CN113248480B (en) * 2021-05-12 2023-08-22 常州大学 Method for chemically and enantioselectively inserting N-H bond of 2-pyridone or 3-pyridazinone into furan carbene
CN114516881A (en) * 2022-03-08 2022-05-20 贵州大学 Azacyclocarbene-catalyzed chiral compound containing pyrazolopyran skeleton and preparation method thereof
CN115124450A (en) * 2022-07-15 2022-09-30 苏州大学 Synthetic method of indolone derivative containing crotonamide structure
CN115124450B (en) * 2022-07-15 2024-03-19 苏州大学 Synthesis method of indolone derivative containing butenamine structure

Also Published As

Publication number Publication date
CN108358941A (en) 2018-08-03
CN108358941B (en) 2019-10-29
CN106188078B (en) 2018-04-03

Similar Documents

Publication Publication Date Title
CN106188078B (en) A kind of synthetic method of chiral spiro hydroxyindole benzopyrone and 3,4 dihydropyrane compounds
Li et al. Recent advances in the total synthesis of cyclobutane-containing natural products
CN107056795B (en) A kind of loop coil hydroxyindole pentamethylene and β-lactones compound synthesis method
Zhang et al. Highly efficient enantioselective synthesis of bispiro [benzofuran-oxindole/benzofuran-chromanone] s through organocatalytic inter-/intramolecular Michael cycloaddition
Zhu et al. Stereoselective construction of Bi-spirooxindole frameworks via a Michael addition/cyclization and an unexpected redox/oxidative coupling/cyclization
Iwamoto et al. Preparation of new chiral building blocks via asymmetric catalysis
Sunazuka et al. Absolute stereochemistries and total synthesis of (+)-arisugacins A and B, potent, orally bioactive and selective inhibitors of acetylcholinesterase
Schweighauser et al. Bidentate Lewis Acid catalyzed inverse-electron-demand Diels–Alder reaction for the selective functionalization of aldehydes
AIMI et al. Studies on plants containing indole alkaloids. VII. Isolation of several Aspidosperma-and Vincamine-type alkaloids from the seeds of Amsonia elliptica Roem. et Schult.
Takayama Total Syntheses of Lycopodium and Monoterpenoid Indole Alkaloids Based on Biosynthesis-Inspired Strategies
Konopelski et al. Enantiomerically pure vinyl ketene acetals as dienes in the Diels-Alder reaction
CN105131014B (en) A kind of loop coil hydroxyindole imidazoline and oxygen azatropylidene compound and its synthetic method
Yaji et al. Construction of a fully substituted cyclopentenone as the core skeleton of stemonamide via a Nazarov cyclization
Pawar et al. Intramolecular reductive cyclization strategy to the synthesis of (−)-6-methyl-3-hydroxy-piperidine-2-carboxylic acid,(+)-6-methyl-(2-hydroxymethyl)-piperidine-3-ol and their glycosidase inhibitory activity
Kawasaki et al. Silyl-enolization-asymmetric Claisen rearrangement of 2-allyloxyindolin-3-one: enantioselective total synthesis of 3a-hydroxypyrrolo [2, 3-b] indoline alkaloid alline
Ihara Syntheses of biologically active natural products and leading compounds for new pharmaceuticals employing effective construction of a polycyclic skeleton
Rahman et al. The C-19 methyl substituted sarpagine-macroline-ajmaline alkaloids: Diversity, occurrence, bioactivity, and synthesis
CN107176959B (en) A kind of chiral spiro hydroxyindole dihydropyran derivatives and its synthetic method
CN108530510A (en) A kind of C19- is acylated the preparation method of triptolide
Suh et al. A formal synthesis of (+)-brefeldin A
CN107056796B (en) A kind of chiral spiro hydroxyindole dihydropyrane compound and its synthetic method containing phenol structure
Yamano et al. Versatile amine-promoted mild methanolysis of 3, 5-dinitrobenzoates and its application to the synthesis of colorado potato beetle pheromone
Matsushima et al. Novel concise synthesis of (±)-Noviose and L-(+)-Noviose by palladium-catalyzed epoxide opening
Banwell et al. Competitive Intramolecular Diels–Alder Reactions of bis-α, β-Unsaturated Ester Derivatives of Enzymatically Derived and Enantiopure cis-1, 2-Dihydrocatechols. Enantiodivergent Synthesis of Monochiral Bicyclo [2.2. 2] oct-2-enes
Rahman Part I Shorter and Improved Access to the Key Tetracyclic Core of C-19 Methyl Substituted Bioactive Sarpagine-Macroline-Ajmaline Indole Alkaloids via a New Ambidextrous Asymmetric Pictet-Spengler Reaction Beginning from Either D-(+)-or L-(-)-Tryptophan Part II the Total Synthesis of a Number of Bioactive C-19 Methyl Substituted Macroline-Sarpagine Indole Alkaloids Including Macrocarpines Ag, Talcarpine, N (4)-Methyl-N (4), 21-Secotalpinine, Deoxyperaksine, Dihydroperaksine, Talpinine, O-Acetyltalpinine, as Well as N (4)-Methyltalpinine

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant