CN103214412B - Polycyclic derivative with chiral spiral oxoindole structure segment and synthetic method of polycyclic derivative - Google Patents
Polycyclic derivative with chiral spiral oxoindole structure segment and synthetic method of polycyclic derivative Download PDFInfo
- Publication number
- CN103214412B CN103214412B CN201310166069.7A CN201310166069A CN103214412B CN 103214412 B CN103214412 B CN 103214412B CN 201310166069 A CN201310166069 A CN 201310166069A CN 103214412 B CN103214412 B CN 103214412B
- Authority
- CN
- China
- Prior art keywords
- phenyl
- alkyl phenyl
- naphthyl
- halobenzene base
- adjacent
- 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.)
- Expired - Fee Related
Links
- 0 CC=C(C[C@@](CC(CC1)=O)[C@]11C(*2*)=O)[C@@]3C1=C2C=C(*)C3 Chemical compound CC=C(C[C@@](CC(CC1)=O)[C@]11C(*2*)=O)[C@@]3C1=C2C=C(*)C3 0.000 description 6
- FNAGKEKZTLQGPD-VWNXMTODSA-N CN(C([C@@]1([C@@H](C2)Sc3cc4ccccc4cc3)C=CC2=O)=O)c2c1cccc2 Chemical compound CN(C([C@@]1([C@@H](C2)Sc3cc4ccccc4cc3)C=CC2=O)=O)c2c1cccc2 FNAGKEKZTLQGPD-VWNXMTODSA-N 0.000 description 1
- SVYKKECYCPFKGB-UHFFFAOYSA-N CN(C)C1CCCCC1 Chemical compound CN(C)C1CCCCC1 SVYKKECYCPFKGB-UHFFFAOYSA-N 0.000 description 1
- NDULREHDYPTLHC-YUMQZZPRSA-N CN(C)[C@@H](CCCC1)[C@H]1NC(N)=S Chemical compound CN(C)[C@@H](CCCC1)[C@H]1NC(N)=S NDULREHDYPTLHC-YUMQZZPRSA-N 0.000 description 1
- ZRDOOGDGPMAXLS-VIJSPRBVSA-N CN(C)[C@H](CCCC1)[C@@H]1NC(N[C@H]([C@H](c1ccccc1)NS(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)(=O)=O)c1ccccc1)=S Chemical compound CN(C)[C@H](CCCC1)[C@@H]1NC(N[C@H]([C@H](c1ccccc1)NS(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)(=O)=O)c1ccccc1)=S ZRDOOGDGPMAXLS-VIJSPRBVSA-N 0.000 description 1
- FZRVDJCEHALPNR-OAHLLOKOSA-N CNC(N[C@H](Cc1ccccc1)c1ccccc1)=S Chemical compound CNC(N[C@H](Cc1ccccc1)c1ccccc1)=S FZRVDJCEHALPNR-OAHLLOKOSA-N 0.000 description 1
- AUTDFDZMDRVGEZ-CTNGQTDRSA-N Cc1cccc(S[C@H](CC(C=C2)=O)[C@]2(c(cccc2)c2N2C)C2=O)c1 Chemical compound Cc1cccc(S[C@H](CC(C=C2)=O)[C@]2(c(cccc2)c2N2C)C2=O)c1 AUTDFDZMDRVGEZ-CTNGQTDRSA-N 0.000 description 1
- LEEHHPPLIOFGSC-UHFFFAOYSA-N NC(NC1CCCCC1)=S Chemical compound NC(NC1CCCCC1)=S LEEHHPPLIOFGSC-UHFFFAOYSA-N 0.000 description 1
- BBMBNRUBUYBBTF-FQEVSTJZSA-N O=S(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)(N[C@@H](Cc1ccccc1)c1ccccc1)=O Chemical compound O=S(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)(N[C@@H](Cc1ccccc1)c1ccccc1)=O BBMBNRUBUYBBTF-FQEVSTJZSA-N 0.000 description 1
- DDCQSZQIMAOLQF-CLJLJLNGSA-N O=S(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)(N[C@@H]([C@@H](c1ccccc1)NC(NC1CCCCC1)=S)c1ccccc1)=O Chemical compound O=S(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)(N[C@@H]([C@@H](c1ccccc1)NC(NC1CCCCC1)=S)c1ccccc1)=O DDCQSZQIMAOLQF-CLJLJLNGSA-N 0.000 description 1
Landscapes
- Indole Compounds (AREA)
Abstract
The invention discloses a polycyclic derivative with a chiral spiral oxoindole structure segment and a synthetic method of the polycyclic derivative. The synthetic method of the polycyclic derivative comprises the following steps of: reacting under -20 DEG C to 25 DEG C in organic solvent under the protection of inert gases by using oxoindole cyclohexadiene acetone and aryl thiophenol as materials and using multi-hydrogen bond thiourea as catalyst; and evaporating the solvent, thus obtaining a target compound by column chromatography. The target compound has bactericidal activity.
Description
Technical field
The invention belongs to Chiral polycyclic compou nd synthesis technical field, particularly relate to a kind of Polycyclic derivative and the synthetic method thereof with chiral spiro Oxoindole structure fragment.
Background technology
In recent years due to more and more discovery with biological functional activity polynuclear compound, make to increase the demand of the polynuclear compound with special construction thereupon, so it is important to synthesize various non-natural polynuclear compound meaning, and cause concern ((a) J.I.Halliday widely, M.Chebib, M.D.Mcleod, Aust.J.Chem.2010, 63, 808. (b) J.F.Huang, C.M.Orac, S.McKay, D.B.McKay, S.C.Bergmeier, Bioorg.Med.Chem.2008, 16, 3816. (c) D.Barker, D.H.-S.Lin, J.E.Carland, C.P.-Y.Chu, M.Chebib, M.A.Brimble, G.P.Savage, M.D.McLeod, Bioorg.Med.Chem.2005, 13, 4565.).
The Polycyclic derivative with chiral spiro Oxoindole structure fragment is the important compound of a class; be mainly used in medicine and bioactive compounds ((a) L.Hong and R.Wang; Adv.Synth.Catal., 2013, doi:10.1002/adsc.201200808; (b) R.Dalpozzo, G.Bartoli and G.Bencivenni, Chem.Soc.Rev., 2012,41,7247; (c) F.Zhou, Y.L.Liu and J.Zhou, Adv.Synth.Catal., 2010,352,1381; (d) Quaternary Stereocenters:Challenges and Solutions for OrganicSynthesis, J.Christoffers, A.Baro, Eds.Wiley-VCH:Weinheim, 2005).
Summary of the invention
The object of this invention is to provide the Polycyclic derivative that a class has chiral spiro Oxoindole structure fragment.
Another object of the present invention is to provide a kind of method that efficient synthesis has the Polycyclic derivative of chiral spiro Oxoindole structure fragment.
Another object of the present invention is to provide the application of the Polycyclic derivative with chiral spiro Oxoindole structure fragment.
The Polycyclic derivative with chiral spiro Oxoindole structure fragment provided by the invention, its structural formula is:
Wherein:
R
1for to halobenzene base, adjacent halobenzene base, a halobenzene base, phenyl, to alkyl phenyl, adjacent alkyl phenyl, an alkyl phenyl, 2-naphthyl, 1-naphthyl, 2-thienyl or 3-thienyl;
R
2for methyl or benzyl;
R
3for halogen, alkoxyl group, alkyl or hydrogen.
Above-mentioned R
1be preferably adjacent fluorophenyl, to fluorophenyl, a fluorophenyl, rubigan, p-methylphenyl, o-methyl-phenyl-, an aminomethyl phenyl, phenyl, 2-naphthyl, 1-naphthyl or 2-thienyl.
Above-mentioned R
2be preferably methyl or benzyl.
Above-mentioned R
3be preferably hydrogen, methoxyl group, chlorine or methyl.
Above-mentioned R
4be preferably rubigan or 2-how base.
Present invention also offers the above-mentioned synthetic method with the Polycyclic derivative of chiral spiro Oxoindole structure fragment, comprise step:
In organic solvent, under protection of inert gas, with Oxoindole cyclohexadienone and aryl thiophenol for raw material, with many hydrogen bonds thiocarbamide for catalyzer, react at-20 ~ 25 DEG C of temperature, boil off solvent, obtain target compound through column chromatography
For above-mentioned synthetic method, can carry out preferably following:
1) above-mentioned organic solvent is trichloromethane.
2) mol ratio of above-mentioned Oxoindole cyclohexadienone and aryl thiophenol is 1:1.1.
3) above-mentioned column chromatography take silica gel as stopping composition, with the mixed solvent of sherwood oil and ethyl acetate for eluent, and: the volume ratio of sherwood oil and ethyl acetate is 5:1.
4) structural formula of above-mentioned many hydrogen bonds thiourea catalyst is
or
described many hydrogen bonds thiourea catalyst publication number be CN101225065, denomination of invention is be disclosed in the Chinese patent with many hydrogen bonds bifunctional chiral compound and preparation method and use thereof.
The target compound (I-1) of above-mentioned synthesis or (I-2) are placed in methanol solvate, with NaBH
4for catalyzer, through the first kind derivative that hydrogenation obtains
(II-2), wherein, R
1, R
2, R
3the same target compound of definition (I-1) and (I-2).
The target compound (I-1) of above-mentioned synthesis or (I-2) are placed in methanol solvate, with Pd (OH)
2/ C is catalyzer, through the Equations of The Second Kind derivative that hydrogenation obtains
(III-2), wherein, R
1, R
2, R
3the same target compound of definition (I-1) and (I-2).
The target compound (I-1) of above-mentioned synthesis or (I-2) are placed in dichloromethane solvent, with K
2cO
3for catalyzer, then add the 3rd analog derivative that phenyl thiophenol is obtained by reacting
(IV-1) or
(IV-2), the target compound adopted (I-1) or (I-2) and the mol ratio of phenyl thiophenol adopted are 1:1.2, wherein, R
1, R
2, R
3the same target compound of definition (I-1) and (I-2); R
4for to halobenzene base, adjacent halobenzene base, a halobenzene base, phenyl, to alkyl phenyl, adjacent alkyl phenyl, an alkyl phenyl, 2-naphthyl, 1-naphthyl, 2-thienyl or 3-thienyl, R
1and R
4identical or not identical.
The target compound (I-1) of above-mentioned synthesis or (I-2) are placed in alcohol solvent, add oxammonium hydrochloride and Na
2cO
3the 4th analog derivative be obtained by reacting
(V-2), wherein, R
2, R
3the same target compound of definition (I-1) and (I-2); R
4for to halobenzene base, adjacent halobenzene base, a halobenzene base, phenyl, to alkyl phenyl, adjacent alkyl phenyl, an alkyl phenyl, 2-naphthyl, 1-naphthyl, 2-thienyl or 3-thienyl.
Fungicidal activity detection is carried out to the first ~ tetra-analog derivative of target compound and target compound, finds that above-mentioned series has the equal tool fungicidal activity of Polycyclic derivative of chiral spiro Oxoindole structure fragment, can be used as the effective constituent of sterilant.
Compared with prior art, the present invention has following characteristics:
1) the inventive method synthesis is simple, and cost is low, and productive rate is high, and gained target compound corresponding selection is good, productive rate 77-95%, the excessive 82-95% of corresponding selection.
2) adopt the Polycyclic derivative with chiral spiro Oxoindole structure fragment of the series of new of the inventive method synthesis to have fungicidal activity, can be used as the effective constituent of sterilant;
3) many hydrogen bonds thiourea catalyst of the inventive method employing, shows the advantage that catalytic is fast and catalyst levels is low in the reaction.
Embodiment
For a better understanding of the present invention, below in conjunction with embodiment, the present invention is described further.
The structural formula of the chirality many hydrogen bonds thiourea catalyst adopted in the following example is
Synthesize target compound of the present invention
the concrete implementation step of one as follows:
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol aryl thiophenol; after stirring 18-60h; boil off solvent, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtain target compound (I-1) or (I-2).
Structural formula is all adopted to be in embodiment 1 ~ 15
many hydrogen bonds thiourea catalyst.
Embodiment 1
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol thiophenol; stir 18h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains yellow solid.
Productive rate 90%, fusing point 47 ° of C, [α]
25 d=+86 (c0.23, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.44 (t, J=7.8Hz, 1H); 7.29-7.21 (m, 6H), 7.11 (t, J=7.5Hz; 1H), 6.98 (d, J=7.5Hz, 1H); 6.58 (d, J=10.2Hz, 1H), 6.25 (d; J=10.2Hz, 1H), 4.22-4.15 (m, 1H); 3.28 (s, 3H), 3.02-2.98 (m, 2H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 196.6,176.1,146.3,144.3,133.3,132.3,130.1,129.0,128.1,125.3,125.0,123.0,108.9,54.8,49.9,42.0,26.7; IR (KBr) ν 3068,3017,1675,1568,1315,1128,819765,696; HRMS Calcd. calculated value C
20h
17nO
2s+H
+: 336.1061, observed value: the excessive 84%ee of enantioselectivity (Chiralpak AS-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=230nm) of 336.1053. product; t
r=9.97and13.20min.
Embodiment 2
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol o-methyl-benzene thiophenol; after stirring 60h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains faint yellow solid.
Productive rate 75%, fusing point 53 ° of C; [α]
25 d=+105.7 (c0.49, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.44 (t, J=7.5Hz, 1H), 7.34 (d, J=7.5Hz, 1H), 7.28 (d, J=7.5Hz, 1H), 7.16-7.11 (m, 4H), 6.96 (d, J=7.8Hz, 1H), 6.55 (d, J=9.9Hz, 1H), 6.23 (d, J=9.9Hz, 1H), 4.11 (dd, J
1=4.8Hz and J
2=13.2Hz, 1H), 3.23 (s, 3H), 3.10-2.90 (m, 2H), 2.30 (s, 3H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 196.5,175.9,146.4,144.1,141.1,130.4,130.0,128.5,126.4,125.3,125.0,123.0,108.9,54.6,48.9,41.8,26.5,20.8; IR (KBr) ν 3030,2945,1608,1473,1428,1337,1129,818,756,699; HRMS Calcd. calculated value C
21h
19nO
2s+H
+: 350.1218, observed value: the excessive 83%ee of enantioselectivity (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm) of 350.1209. product; t
r=9.48and14.13min.
Embodiment 3
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol to methylbenzene phenyl-sulfhydrate; after stirring 36h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains faint yellow solid.
Productive rate 85%, fusing point 72 ° of C; [α]
25 d=+113.4 (c0.52, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.43 (t; J=7.8Hz, 1H), 7.22-7.16 (m; 3H), 7.11 (d, J=7.5Hz; 1H), 7.04 (d, J=7.8Hz; 2H), 6.97 (d, J=7.8Hz; 1H), 6.56 (d, J=10.2Hz; 1H), 6.23 (d, J=10.2Hz; 1H), 4.14-4.10 (m, 1H); 3.28 (s, 3H), 2.99-2.95 (m; 2H), 2.29 (s, 3H);
13cNMR (CDCl
3, TMS, 75MHz) and δ 196.5,176.0,146.2,144.1,138.2,133.7,130.0,129.9,129.6,128.4,125.2,124.9,122.8,108.8,54.7,50.0,41.7,26.5,21.0; IR (KBr) ν 3068,3013,1702,1601,1319,1120,825,778,712; HRMS Calcd. calculated value C
21h
19nO
2s+H
+: 350.1218, observed value: the excessive 82%ee of enantioselectivity (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm) of 350.1209. product; t
r=10.81and17.16min.
Embodiment 4
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add methylbenzene phenyl-sulfhydrate between 0.22mmol; after stirring 36h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains white solid.
Productive rate 79%, fusing point 126 ° of C; [α]
25 d=+109.7 (c0.55, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.43 (t, J=7.2Hz, 1H); 7.21-7.10 (m, 6H), 6.97 (d, J=7.8Hz; 1H), 6.56 (d, J=9.9Hz, 1H); 6.23 (d, J=9.9Hz, 1H), 4.17 (t; J=8.1Hz, 1H), 3.27 (s, 3H); 2.99-2.96 (m, 2H), 2.27 (s, 3H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 196.6,176.0,146.2,144.2,138.7,133.8,131.6,130.0,129.9,128.9,128.7,125.2,125.0,122.9,108.8,107.1,54.7,49.5,41.8,26.6,21.1; IR (KBr) ν 3072,3031,1698,1574,1332,1173,809,747,687; HRMS Calcd. calculated value C
21h
19nO
2s+H
+: 350.1219, observed value: the enantioselectivity of 350.1209. product is excessive: 82%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=10.17and14.56min.
Embodiment 5
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add the adjacent fluoro thiophenol of 0.22mmol; after stirring 60h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains white solid.
Productive rate 60%, fusing point 51 ° of C; [α]
25 d=+132.4 (c0.54, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.44 (t, J=7.8Hz; 1H), 7.27-7.21 (m, 3H), 7.14-6.96 (m; 4H), 6.56 (d, J=9.9Hz, 1H); 6.24 (d, J=9.9Hz, 1H), 4.21 (t; J=9.3Hz, 1H), 3.25 (s, 3H); 3.03 (d, J=9.6Hz, 2H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 196.3,175.7,162.3 (d; J=24.6Hz), 146.3,144.2,135.8,132.4; 130.6 (d, J=8.0Hz), 127.8,125.0,124.5 (d; J=3.9Hz), 123.2,123.0,119.4; 119.2,160.0 (d, J=22.9Hz), 108.9; 54.8,49.1,41.8,26.6; IR (KBr) ν 3032,3013,1701,1568,1437,1255,1214,1108,818,754,699; HRMSCalcd. calculated value C
20h
16nO
2fS+H
+: 354.0970, observed value: the enantioselectivity of 354.0958. product is excessive: 88%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=10.54and21.55min.
Embodiment 6
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol to fluoro thiophenol; after stirring 40h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains white solid.
Productive rate 85%, fusing point 42 ° of C; [α]
25 d=+115.5 (c0.54, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.44 (t, J=7.5Hz, 1H), 7.27-7.19 (m, 3H), 7.13-7.08 (m, 1H), 7.00-6.91 (m, 3H), 6.57 (d, J=9.9Hz, 1H), 6.24 (d, J=9.9Hz, 1H), 4.09 (dd, J
1=6.9Hz andJ
2=11.7Hz, 1H), 3.30 (m, 3H), 3.00-2.95 (m, 2H);
13c NMR (CDCl
3, TMS, 125MHz) and δ 196.3,176.1; 162.8 (d, J=247.6Hz), 146.2,144.2; 136.0 (d, J=8.5Hz), 130.1,127.2 (d; J=2.6Hz), 125.2,125.0,116.1 (d; J=21.9Hz), 109.0,54.8; 50.4,41.8,26.6; IR (KBr) ν 3057,3007,1687,1591,1487,1136,1074,827,765,694; HRMS Calcd. calculated value C
20h
16nO
2fS+H
+: 354.0968, observed value: the enantioselectivity of 354.0958. product is excessive: 88%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=9.04and12.45min.
Embodiment 7
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add fluoro thiophenol between 0.22mmol; after stirring 40h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains yellow solid.
Productive rate 80%, fusing point 46 ° of C; [α]
25 d=+112 (c0.21, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.45 (t, J=7.8Hz; 1H), 7.23-7.20 (m, 2H), 7.14-7.09 (m; 2H), 7.00-6.92 (m, 3H), 6.59 (d; J=9.9Hz, 1H), 6.26 (d, J=10.2Hz; 1H), 4.25-4.19 (m, 1H), 3.28 (s; 3H), 3.03-2.99 (m, 2H);
13c NMR (CDCl
3, TMS, 125MHz) and δ 196.2,176.0; 162.4 (d, J=248.1Hz), 146.2,144.3; 134.5,134.4,130.2,128.5; 125.1,125.0,123.1,119.7 (d; J=21.9Hz), 115.2 (d, J=20.6Hz), 109.0; 54.7,49.7,41.9,26.7; IR (KBr) ν 3046,2981,1693,1582,1502,1227,1216,1113,830,767,685; HRMS Calcd. calculated value C
20h
16nO
2fS+H
+: 354.0966, observed value: the enantioselectivity of 354.0958. product is excessive: 85%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=9.82and11.53min.
Embodiment 8
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol to chlorothio-phenol; after stirring 20h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains white solid.
Productive rate 84%, fusing point 51 ° of C; [α]
25 d=+140.3 (c0.80, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.45 (t, J=7.8Hz, 1H), 7.22 (m, 5H), 7.11 (t, J=7.5Hz, 1H), 6.98 (d, J=8.7Hz, 1H), 6.58 (d, J=9.9Hz, 1H), 6.25 (d, J=9.9Hz, 1H), 4.14 (dd, J
1=6.6Hzand J
2=12.3Hz, 1H), 3.28 (s, 3H), 3.00-2.96 (m, 2H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 196.2,176.0,146.2,144.2,134.7,134.4,130.7,130.1,129.2,125.2,125.1,123.1,109.0,54.8,50.0,41.8,26.7; IR (KBr) ν 3048,2940,1617,1484,1472,1254,1103,1054,823,751,695; HRMS Calcd. calculated value C
20h
16nO
2sCl+H
+: 370.0670, observed value: the enantioselectivity of 370.0670. product is excessive: 89%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=10.78and14.50min.
Embodiment 9
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol1-thionaphthol; after stirring 18h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains white solid.
Productive rate 85%, fusing point 70 ° of C; [α]
25 d=+87.1 (c0.77, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 8.23 (d, J=8.1Hz, 1H), 7.81-7.79 (m, 2H), 7.63 (d, J=6.9Hz, 1H), 7.55-7.25 (m, 6H), 7.18-7.13 (m, 1H), 6.93 (d, J=7.8Hz, 1H), 6.55 (d, J=9.9Hz, 1H), 6.21 (d, J=9.9Hz, 1H), 4.26 (dd, J
1=4.8Hz and J
2=13.5Hz, 1H), 3.16 (s, 3H), 3.06-2.85 (m, 2H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 196.3,175.8,146.4,144.1,134.2134.1,133.9,129.9,129.6,129.0,128.4,126.8,126.2,125.5,125.4,125.3,125.0,122.9,109.0,54.6,49.5,41.6,26.4; IR (KBr) ν 3057,3016,1698,1591,1482,1351,1137,817,750,685; HRMS Calcd. calculated value C
24h
19nO
2s+H
+: 386.1218, observed value: the enantioselectivity of 386.1209. product is excessive: 93%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=11.73and17.38min.
Embodiment 10
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol2-thionaphthol; after stirring 18h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains white solid.
Productive rate 85%, fusing point 61 ° of C; [α]
25 d=+152.9 (c0.77, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.79-7.72 (m; 4H), 7.49-7.47 (m, 3H); 7.38 (d, J=8.4Hz, 1H); 7.26-7.22 (m, 1H), 7.15-7.10 (m; 1H), 6.99 (d, J=6.9Hz; 1H), 6.59 (d, J=9.9Hz; 1H), 6.25 (d, J=9.9Hz; 1H), 4.32 (t, J=9.6Hz; 1H) 3.25 (s; 3H), 3.04-3.01 (m, 2H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 196.4,176.1,146.3,144.2,133.2,132.6,130.2,130.1,130.0,129.2,128.7,127.6,127.5,126.6,125.3,125.1,123.0,109.0,54.8,49.3,41.8,26.6; IR (KBr) ν 3054,3018,1710,1580,1472,1352,1140,823,756,691; HRMSCalcd. calculated value C
24h
19nO
2s+H
+: 386.1217, observed value: the enantioselectivity of 386.1209. product is excessive: 91%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=13.66and18.92min.
Embodiment 11
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol2-thiophene thiophenol; after stirring 48h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains yellow solid.
Productive rate 52%, fusing point 53 ° of C; [α]
25 d=+99 (c0.18, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.44 (t, J=7.5Hz, 1H), 7.33 (d, J=4.5Hz, 1H), 7.18-7.06 (m, 2H), 6.99 (d, J=7.8Hz, 1H), 6.90-6.86 (m, 2H), 6.56 (d, J=9.9Hz, 1H), 6.24 (d, J=9.9Hz, 1H), 4.02 (dd, J
1=5.7Hz and J
2=12.6Hz, 1H), 3.34 (s, 3H), 3.10-2.92 (m, 2H);
13cNMR (CDCl
3, TMS, 75MHz) and δ 196.4,175.9,146.1,144.3,136.1,131.1,130.1,129.6,127.6,125.2,124.9,123.0,109.0,54.6,51.6,41.3,26.7; IR (KBr) ν 3034,3087,1614,1527,1432,1325,1134,864,826,743,690; HRMS Calcd. calculated value C
18h
15nO
2s
2+ H
+: 342.0624, observed value: the enantioselectivity of 342.0617. product is excessive: 95%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=12.98and18.15min.
Embodiment 12
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 5'-methoxyl group-1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol2-thionaphthol; after stirring 24h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains white solid.
Productive rate 82%, fusing point 86 ° of C; [α]
25 d=+201.9 (c0.84, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.79-7.72 (m, 4H), 7.49-7.46 (m; 2H), 7.39-7.36 (m, 1H), 6.97-6.88 (m, 2H); 6.79 (s, 1H), 6.59 (d, J=9.6Hz, 1H); 6.25 (d, J=9.9Hz, 1H), 4.30 (t, J=9.3Hz; 1H), 3.75 (s, 3H), 3.22 (s; 3H), 3.01 (d, J=10.2Hz, 2H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 196.3,175.5,155.9,146.3,137.5,133.1,132.5,130.2,129.9,129.1,128.5,127.5,127.4,126.4,113.8,112.6,109.1,55.6,55.1,49.0,41.6,26.6; IR (KBr) ν 3064,3012,1702,1611,1452,1375,1127,1070,820,743,690; HRMS Calcd. calculated value C
25h
21nO
3s+H
+: 416.1325, observed value: the enantioselectivity of 416.1315. product is excessive: 84%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=17.12and25.34min.
Embodiment 13
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 5'-chloro-1'-methyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol2-thionaphthol; after stirring 15h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains white solid.
. productive rate 70%, fusing point 98 ° of C; [α]
25 d=+223.7 (c0.66, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.81-7.71 (m, 4H), 7.50-7.47 (m; 2H), 7.44-7.41 (m, 1H), 7.38-7.35 (m, 1H); 7.19-7.18 (m, 1H), 6.91 (d, J=8.1Hz, 1H); 6.55 (d, J=9.9Hz, 1H), 6.27 (d; J=9.9Hz, 1H), 4.32-4.26 (m, 1H); 3.21 (s, 3H), 3.02-2.98 (m, 2H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 195.9,175.6,145.3,142.8,133.2,132.6,130.5,130.1,129.9,128.7,128.3,127.6,127.4,127.0,126.6,125.5,109.8,54.9,49.0,41.6,26.7; IR (KBr) ν 3030,3014,1698,1589,1491,1472,1324,1132,1084,817,745,696; HRMSCalcd. calculated value C
24h
18nO
2sCl+Na
+: 442.0647, observed value: the enantioselectivity of 442.0639. product is excessive: 84%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=12.54and17.21min.
Embodiment 14
preparation
Add in 25mL reaction tubes many hydrogen bonds thiourea catalyst of 0.02mmol and 0.2mmol 5'-methyl isophthalic acid '-methyl volution [[2; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol2-thionaphthol; after stirring 24h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains white solid.
White solid, productive rate 72%, fusing point 72 ° of C; [α]
25 d=+191.6 (c0.43, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.79-7.71 (m; 4H), 7.48-7.47 (m, 2H); 7.37 (d, J=8.1Hz, 1H); 7.26-7.23 (m, 1H), 6.99 (s; 1H), 6.88 (d, J=7.8Hz; 1H), 6.58 (d, J=9.9Hz; 1H), 6.24 (d, J=9.9Hz; 1H), 4.33-4.27 (m, 1H); 3.24 (s, 3H), 3.05-3.01 (m; 2H), 2.30 (s, 3H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 196.6,176.0,146.6,141.8,133.2,132.6,130.3,130.0,129.1,128.5,127.5,127.4,126.5,125.8,125.1,108.7,54.9,49.1,41.7,26.6,21.0; IR (KBr) ν 3043,1702,1596,1483,1459,1231,1145,821,752,689; HRMS Calcd. calculated value C
25h
21nO
2s+H
+: 400.1373, observed value: the enantioselectivity of 400.1366. product is excessive: 82%ee (Chiralpak IC, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=254nm); t
r=14.25and21.62min.
Embodiment 15
preparation
Many hydrogen bonds thiourea catalyst of 0.02mmol and the 1'-benzyl volution [[2 of 0.2mmol is added in 25mL reaction tubes; 5] cyclohexadiene-1,3'-indoles]-2', 4-diketone; under nitrogen protection; add 1mL trichloromethane, then at-20 DEG C, add 0.22mmol2-thionaphthol; after stirring 17h; boil off solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains white solid.
Productive rate 82%, fusing point 75 ° of C; [α]
25 d=+177.2 (c0.89, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.79-7.72 (m, 4H), 7.49-7.38 (m, 5H), 7.30-7.23 (m, 3H), 7.06 (t, J=7.2Hz, 1H), 6.86 (d, J=7.2Hz, 1H), 6.64 (d, J=9.9Hz, 1H), 6.27 (d, J=10.2Hz, 1H), 5.15 (d, J=15.9Hz, 1H), 4.85 (d, J=15.9Hz, 1H), 4.36 (dd, J
1=5.4Hz, J
2=12.6Hz1H), 3.16-3.07 (m, 2H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 196.4,176.4,146.2,143.3,135.0,133.3,132.5,130.1,130.0,129.3,128.7,127.7,127.6,127.5,127.3,126.5,125.3,125.1,123.0,110.1,54.8,49.3,44.3,42.1; IR (KBr) ν 3074,3021,1715,1587,1485,1457,1252,1234,814,748,685; HRMS Calcd. calculated value C
30h
23nO
2s+H
+: 462.1527, observed value: the enantioselectivity of 462.1522. product is excessive: 93%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=11.16and14.19min.
Embodiment 16
In 25mL reaction cup, add the compound 3aj of 0.2mmol, the Pd (OH) of 5mol%
2/ C, uses 1mL dissolve with methanol, then in autoclave, reacts 24h, pressure reducing and steaming solvent, and product, through silica gel column chromatography (petrol ether/ethyl acetate=5/1), obtains white solid.
Productive rate 92%; Fusing point 61 ° of C; [α]
25 d=+43.7 (c0.35, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.79-7.69 (m, 4H), 7.49-7.43 (m, 4H), 7.37 (d, J=8.7Hz, 1H), 7.13 (t, J=7.8Hz, 1H), 7.02 (d, J=7.8Hz, 1H), 3.97 (dd, J
1=6.9Hz, J
2=11.4Hz1H), 3.27 (s, 3H), 3.01-2.97 (m, 2H); 2.85-2.74 (m, 1H), 2.61-2.56 (m, 1H); 2.43-2.32 (m, 1H), 2.01-1.95 (m, 1H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 206.9,177.7,144.0,133.3,132.6,130.3,129.6,129.2,128.9,128.6,127.6,127.5,126.5,124.6,122.5,108.9,51.5,51.3,45.7,36.8,32.8,26.6; IR (KBr) ν 3057,1721,1603,1583,1317,1115,819,736,678; HRMS Calcd. calculated value C
24h
21nO
2s+H
+: 388.1379, observed value: the enantioselectivity of 388.1366. product is excessive: 88%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=13.93and21.18min.
Embodiment 17
In 25mL reaction tubes, add the compound 3aj of 0.2mmol, add 1mL dissolve with methanol, then add the NaBH of 0.24mmol
4, after reaction 1h, pressure reducing and steaming solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate=2/1), obtains white solid.
Productive rate 99%, fusing point 78 ° of C; [α]
25 d=+95.1 (c0.84, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.74-7.71 (m, 4H); 7.48-7.39 (m, 5H), 7.14 (t, J=7.5Hz; 1H), 6.90 (d, J=7.2Hz; 1H), 6.05 (d, J=9.9Hz; 1H), 5.37 (d, J=9.9Hz; 1H), 4.49 (s, 1H); (3.93 d, J=12.6Hz, 1H); 3.17 (s, 3H), 2.58-2.53 (m; 1H), 2.16 (q, J=13.2Hz; 1H), 1.93 (s, 1H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 177.9,143.5,134.4,133.1,132.2,131.4,130.6,129.9,128.9,128.8,128.3,127.4,127.2,126.3,126.1,125.9,125.3,122.6,108.2,66.2,54.3,48.8,36.3,26.3; IR (KBr) ν 3407,3052,2930,1695,1609,1491,1469,1351,1132,816,747,695; HRMS Calcd. calculated value C
24h
21nO
2s+Na
+: 410.1192, observed value: the enantioselectivity of 410.11852. product is excessive: 88%ee (Chiralpak IC, i-propanol/hexane=10/90, flow rate1.0mL/min, λ=254nm); t
r=32.63and42.00min.
Embodiment 18
In 25mL reaction tubes, add the compound 3aj of 0.2mmol, by the K of 10mol%
2cO
3add reaction tubes again after dissolving with methylene dichloride, then add the 2-thionaphthol of 0.24mmol, after reaction is spent the night, pressure reducing and steaming solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate 5/1), obtains white solid.
Productive rate 70%, fusing point 79 ° of C; [α]
25 d=+10 (c0.27, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.76-7.64 (m, 6H), 7.46-7.27 (m; 9H), 7.17 (d, J=8.1Hz, 1H), 6.95 (d; J=6.6Hz, 1H), 6.80 (t, J=7.2Hz, 1H); 4.15-4.11 (m, 1H), 3.89 (m, 1H); 3.61-3.44 (m, 2H), 3.32 (s, 3H); 2.97-2.92 (m, 1H), 2.67-2.61 (m, 1H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 206.3,175.5,144.0,133.1,132.7,132.5,130.3,130.0,129.3,129.1,128.8,128.5,127.6,126.6,126.4,122.1,108.2,54.8,51.1,50.0,44.6,42.1,26.4; IR (KBr) ν 3057,1696,1607,1484,1312,1023,857,762,662; HRMS Calcd. calculated value C
34h
27nO
2s
2+ Na
+: 568.1370, observed value: the enantioselectivity of 568.1375. product is excessive: 87%ee (Chiralpak IC, i-propanol/hexane=30/70, flow rate1.0mL/min, λ=254nm); t
r=22.00and38.87min.
Embodiment 19
In 25mL reaction tubes, add the compound 3aj of 0.2mmol, by the K of 10mol%
2cO
3with methylene dichloride dissolve after add reaction tubes, then add 0.24mmol to chlorothio-phenol, reaction spend the night after, pressure reducing and steaming solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate 5/1), obtains white solid.
Productive rate 81%, fusing point 83 ° of C; [α]
25 d=+10.5 (c0.44, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.76-7.69 (m, 4H), 7.48-7.34 (m, 4H), 7.26-7.24 (m, 1H), 7.11 (d, J=8.4Hz, 2H), 6.96-6.91 (m, 4H), 4.02 (dd, J
1=5.1Hz and J
2=12.6Hz, 1H), 3.85 (t, J=5.1Hz, 1H), 3.57 (dd, J
1=4.2Hz and J
2=15.6Hz, 1H), 3.46-3.36 (m, 1H), 3.28 (s, 3H), 2.88 (dd, J
1=4.5Hz and J
2=15.9Hz, 1H), 2.63 (dd, J
1=5.1Hz and J
2=15.9Hz, 1H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 205.9,175.3,143.9,134.8,134.3,133.4,132.8,132.6; 131.7,130.0,129.2,129.0,128.9,128.5,127.6,127.5,126.7; 126.5,122.2,108.2,54.8,51.1,50.5,44.3,42.1,26.4; IR (KBr) ν 3046,1711,1618,1482,1347,1123,827,745,697; HRMS Calcd. calculated value C
30h
24nO
2s
2cl+Na
+: 552.0842, observed value: the enantioselectivity of 552.0829. product is excessive: 86%ee (Chiralpak IC, i-propanol/hexane=30/70, flow rate1.0mL/min, λ=254nm); t
r=17.50and25.10min.
Embodiment 20
In 25mL reaction tubes, add the compound 3ah of 0.2mmol, by the K of 10mol%
2cO
3add reaction tubes after dissolving with methylene dichloride, then add the 2-thionaphthol of 0.24mmol, after reaction is spent the night, pressure reducing and steaming solvent, product, through silica gel column chromatography (petrol ether/ethyl acetate 5/1), obtains white solid.
Productive rate 85%, fusing point 81 ° of C; [α]
25 d=+11.2 (c0.37, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.77-7.75 (m; 1H), 7.65-7.62 (m, 2H); 7.48-7.43 (m, 3H), 7.32-7.26 (m; 2H), 7.20-7.14 (m, 5H); (6.94 d, J=7.5Hz, 1H); 6.79-6.75 (m, 1H), 4.08-4.04 (m; 1H), 3.74 (m, 1H); 3.59-3.40 (m, 2H), 3.34 (s; 3H), 2.95-2.90 (m, 1H); 2.60-2.54 (m, 1H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 206.1,134.8,133.2,132.6,130.3,129.4,128.6,127.6,126.6,126.4,122.1,108.3,51.5,50.0,44.5,42.1,26.5,14.2; IR (KBr) ν 3061,2935,1715,1514,1472,1341,1126,817,750,691; The enantioselectivity of product is excessive :-86%ee (Chiralpak IC, i-propanol/hexane=30/70, flow rate1.0mL/min, λ=254nm); t
r=19.78and32.49min.
Embodiment 21
In 25mL reaction tubes, add reaction tubes by after the compound 3aj 1mL dissolve with ethanol of 0.2mmol, then add oxammonium hydrochloride and the 0.24mmol sodium carbonate of 0.24mmol, after reaction backflow 0.5h, pressure reducing and steaming solvent, product, after methyl alcohol and methylene dichloride recrystallization, obtains white solid.
Productive rate 37%, fusing point 193 ° of C; [α]
25 d=+103.1 (c0.37, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.78-7.72 (m, 4H), 7.45-7.42 (m; 4H), 7.18-7.10 (m, 2H), 6.97-6.94 (m; 1H), 6.41 (d, J=9.6Hz, 1H); 5.92 (d, J=9.Hz, 1H), 4.06-4.02 (m; 1H), 3.68-3.62 (m, 1H), 3.24 (s; 3H), 2.79 (t, J=16.5Hz, 1H);
13c NMR (DMSO-d
6, TMS, 75MHz) and δ 176.4,151.6,144.0,133.1,131.9,131.7,130.7,130.0,129.3,129.0,128.6,127.6,127.5,127.3,126.8,126.4,126.1,124.7,122.6,109.0,54.1,48.2,27.1,26.4; IR (KBr) ν 3407,3034,2935,1701,1684,1611,1482,1452,1341,1129,813,742,685; The enantioselectivity of product is excessive: 85%ee (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=254nm); t
r=17.50and25.10min.
The productive rate of embodiment 1-21 gained compound and corresponding selection is excessive is shown in Table 1.
The productive rate of table 1 embodiment gained compound and enantiomeric excess
Embodiment 22
Fungicidal activity detects
Liquor strength 50ppm, made agar block is got with the 5mm device that fans the air, dividing chooses into each culture dish, if blank, it is cultivated 48-72 hour constant incubator 27 DEG C, check bacterial plaque diameter, inhibiting rate=(contrast bacterial plaque diameter-sample bacterial plaque diameter)/contrast bacterial plaque diameter × 100%, does a repetition simultaneously.Measurement result is in table 2.
Solubility promoter: dimethyl methyl phthalein amine; Emulsifying agent: tween-80; Obtain solution: sterilized water.Wherein, dimethyl methyl phthalein amine/H
2o=1/1000; Emulsifying agent/H
2o=5/1000 (weight percent).
The bacteriostasis rate of table 2 the compounds of this invention
Claims (9)
1. have the Polycyclic derivative of chiral spiro Oxoindole structure fragment, it is characterized in that, its structural formula is
or
wherein:
R
1for to halobenzene base, adjacent halobenzene base, a halobenzene base, phenyl, to alkyl phenyl, adjacent alkyl phenyl, an alkyl phenyl, 2-naphthyl, 1-naphthyl, 2-thienyl or 3-thienyl;
R
2for methyl or benzyl;
R
3for halogen, alkoxyl group, alkyl or hydrogen.
2. there is the synthetic method of the Polycyclic derivative of chiral spiro Oxoindole structure fragment as claimed in claim 1, it is characterized in that, comprise step:
In organic solvent, under protection of inert gas, with Oxoindole cyclohexadienone and aryl thiophenol for raw material, with many hydrogen bonds thiocarbamide for catalyzer, react at-20 ~ 25 DEG C of temperature, boil off solvent, obtain target compound through column chromatography
or
3. synthetic method as claimed in claim 2, is characterized in that:
Described Oxoindole cyclohexadienone and the mol ratio of aryl thiophenol are 1:1.1.
4. synthetic method as claimed in claim 2, is characterized in that:
The structural formula of described many hydrogen bonds thiourea catalyst is
or
5. the Polycyclic derivative with chiral spiro Oxoindole structure fragment according to claim 1 is placed in methanol solvate, with NaBH
4for catalyzer, through the first kind derivative that hydrogenation obtains
or
wherein:
R
1for to halobenzene base, adjacent halobenzene base, a halobenzene base, phenyl, to alkyl phenyl, adjacent alkyl phenyl, an alkyl phenyl, 2-naphthyl, 1-naphthyl, 2-thienyl or 3-thienyl;
R
2for methyl or benzyl;
R
3for halogen, alkoxyl group, alkyl or hydrogen.
6. the Polycyclic derivative with chiral spiro Oxoindole structure fragment according to claim 1 is placed in methanol solvate, with Pd (OH)
2/ C is catalyzer, through the Equations of The Second Kind derivative that hydrogenation obtains
or
wherein:
R
1for to halobenzene base, adjacent halobenzene base, a halobenzene base, phenyl, to alkyl phenyl, adjacent alkyl phenyl, an alkyl phenyl, 2-naphthyl, 1-naphthyl, 2-thienyl or 3-thienyl;
R
2for methyl or benzyl;
R
3for halogen, alkoxyl group, alkyl or hydrogen.
7. the 3rd analog derivative with the Polycyclic derivative of chiral spiro Oxoindole structure fragment according to claim 1
or
wherein:
R
1for to halobenzene base, adjacent halobenzene base, a halobenzene base, phenyl, to alkyl phenyl, adjacent alkyl phenyl, an alkyl phenyl, 2-naphthyl, 1-naphthyl, 2-thienyl or 3-thienyl;
R
2for methyl or benzyl;
R
3for halogen, alkoxyl group, alkyl or hydrogen;
R
4for to halobenzene base, adjacent halobenzene base, a halobenzene base, phenyl, to alkyl phenyl, adjacent alkyl phenyl, an alkyl phenyl, 2-naphthyl or 1-naphthyl, R
1and R
4identical or not identical.
8. the 4th analog derivative with the Polycyclic derivative of chiral spiro Oxoindole structure fragment according to claim 1
or
wherein:
R
1for to halobenzene base, adjacent halobenzene base, a halobenzene base, phenyl, to alkyl phenyl, adjacent alkyl phenyl, an alkyl phenyl, 2-naphthyl, 1-naphthyl, 2-thienyl or 3-thienyl;
R
2for methyl or benzyl;
R
3for halogen, alkoxyl group, alkyl or hydrogen.
9. the compound as described in claim 1,5,6,7 or 8 is as the application of the effective constituent of sterilant.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310166069.7A CN103214412B (en) | 2013-05-08 | 2013-05-08 | Polycyclic derivative with chiral spiral oxoindole structure segment and synthetic method of polycyclic derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310166069.7A CN103214412B (en) | 2013-05-08 | 2013-05-08 | Polycyclic derivative with chiral spiral oxoindole structure segment and synthetic method of polycyclic derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103214412A CN103214412A (en) | 2013-07-24 |
| CN103214412B true CN103214412B (en) | 2015-05-13 |
Family
ID=48812631
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310166069.7A Expired - Fee Related CN103214412B (en) | 2013-05-08 | 2013-05-08 | Polycyclic derivative with chiral spiral oxoindole structure segment and synthetic method of polycyclic derivative |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103214412B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104961670B (en) * | 2015-07-01 | 2018-01-23 | 中国计量学院 | A kind of preparation method of the disubstituted ketimide derivative of N, O |
| CN106866670A (en) * | 2017-04-28 | 2017-06-20 | 遵义医学院 | A kind of spiral shell [3,5` pyrroles [2,1 a] isoquinolin Oxoindole] class compound and preparation method thereof |
| CN115109020A (en) * | 2022-05-18 | 2022-09-27 | 南方科技大学 | Spirolactone substituted cyclohexadienone oxime compound and synthesis method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101225065A (en) * | 2008-01-29 | 2008-07-23 | 武汉大学 | Chiral compound having multi-hydrogen bonds dual-function as well as synthetic method and use thereof |
| CN102659494A (en) * | 2012-03-31 | 2012-09-12 | 华东师范大学 | Method for asymmetric synthesis of 3,3-disubstituted-2-oxindole compound |
| CN102675339A (en) * | 2012-04-27 | 2012-09-19 | 华南理工大学 | Screw epoxidation indole heterocyclic compound as well as synthetic method and purpose thereof |
-
2013
- 2013-05-08 CN CN201310166069.7A patent/CN103214412B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101225065A (en) * | 2008-01-29 | 2008-07-23 | 武汉大学 | Chiral compound having multi-hydrogen bonds dual-function as well as synthetic method and use thereof |
| CN102659494A (en) * | 2012-03-31 | 2012-09-12 | 华东师范大学 | Method for asymmetric synthesis of 3,3-disubstituted-2-oxindole compound |
| CN102675339A (en) * | 2012-04-27 | 2012-09-19 | 华南理工大学 | Screw epoxidation indole heterocyclic compound as well as synthetic method and purpose thereof |
Non-Patent Citations (7)
| Title |
|---|
| Catalysis》.2010,第352卷(第9期),第1381-1407页. * |
| Catalysis》.2013,第355卷(第6期),第1023-1052页. * |
| Feng Zhou 等.Catalytic Asymmetric Synthesis of Oxindoles Bearing a Tetrasubstituted Stereocenter at the C-3 Position.《Advanced Synthesis & * |
| Highly diastereoselective and enantioselective Michael addition of 5H-oxazol-4-ones to α,β-unsaturated ketones catalyzed by a new bifunctional organocatalyst with broad substrate scope and applicability;Huicai Huang 等;《Chem.Commun.》;20111111;第48卷(第3期);第461-463页 * |
| Liang Hong 等.Recent Advances in Asymmetric Organocatalytic Construction of 3,3′-Spirocyclic Oxindoles.《Advanced Synthesis & * |
| Organocatalytic asymmetric Michael addition of α-aryl cyclopentanones to nitroolefins for construction of adjacent quaternary and tertiary stereocenters;Xiu-Qin Dong 等;《Chem.Commun.》;20080123;第46卷(第36期);第6840-6842页 * |
| 含多氢键给体的氨基-硫脲类有机小分子催化剂的设计、合成及应用;张志海 等;《科学通报》;20091130;第54卷(第22期);第3407-3419页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103214412A (en) | 2013-07-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2014107545A (en) | METHOD FOR PRODUCING BENZO [b] THIOPHENE COMPOUND | |
| JP7234259B2 (en) | Photoreactors Useful for Conducting Photoreactions and Methods for Forming Aryl Carbon-Nitrogen Bonds Using Light | |
| Sakai et al. | Facile and efficient synthesis of polyfunctionalized benzofurans: three-component coupling reactions from an alkynylsilane, an o-hydroxybenzaldehyde derivative, and a secondary amine by a Cu (I)–Cu (II) cooperative catalytic system | |
| Lv et al. | Asymmetric Dimerization of Disubstituted Ketenes Catalyzed by N‐Heterocyclic Carbenes | |
| CN103214412B (en) | Polycyclic derivative with chiral spiral oxoindole structure segment and synthetic method of polycyclic derivative | |
| DK1678119T3 (en) | Process for the preparation of 2-dihalogenacyl-3-amino-acrylic acid esters and 3-dihalogenmethyl-pyrazole-4-carboxylic acid esters | |
| JP7021640B2 (en) | Glycol, method for producing diol, method for producing di (meth) acrylate and di (meth) acrylate | |
| ES2665093T3 (en) | New procedure for preparing 4-substituted imidazoles | |
| Yang et al. | Cycloaddition of 1, 4-diaryl-1, 3-butadiynes with nitriles: An atom-economic one-pot approach to benzo [f] quinazolines | |
| Huang et al. | A facile synthesis of β-amino carbonyl compounds through an aza-Michael addition reaction under solvent-free conditions | |
| CN105481867B (en) | Three step relays catalysis structure chiral spiro Oxoindole and its synthetic method and application | |
| Xu et al. | Copper‐Chiral Camphor β‐Amino Alcohol Complex Catalyzed Asymmetric Henry Reaction | |
| Zhao et al. | N‐Heterocyclic Carbene/Brønsted Base Cascade Catalysis: Base‐Controlled Selective Synthesis of Multifunctional Benzofuran‐3‐ones or Flavone Derivatives from the Reaction of 3‐(2‐Formylphenoxy) propenoates with Imines | |
| CN105085458A (en) | Synthesis method of coumarin derivatives | |
| CN103664821A (en) | Preparation method of benzothiazole compound based on aminothiophenol cyclization | |
| JP7331992B2 (en) | Fluorine-containing silane compound | |
| CN108727200B (en) | Method for synthesizing nonane diamine | |
| Monier et al. | Five-membered ring systems with one heteroatom: Synthetic routes, chemical reactivity, and biological properties of furan-carboxamide analogues | |
| CN105254530B (en) | A kind of synthetic method containing amphene base Schiff class compound | |
| CN104892485A (en) | 2-perfluoroalkyl indole derivative and synthesis method thereof | |
| KR101856537B1 (en) | Synthetic method of tetrahydroisoquinoline derivatives | |
| JP6429105B2 (en) | Diaryliodonium salt | |
| KR101275984B1 (en) | Chroman Derivatives Having Optical Avtivity and Their Preparation Methods | |
| CN107459530A (en) | A kind of 1,3 isoquinolin derovatives of novel silicon base substitution and preparation method thereof | |
| CN108299303A (en) | A kind of new synthetic method of four arylpyrazoles compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150513 Termination date: 20210508 |