CN109897069A - 3,3- of one kind disubstituted indole quinoline ketone and its derivative and its synthetic method and application - Google Patents
3,3- of one kind disubstituted indole quinoline ketone and its derivative and its synthetic method and application Download PDFInfo
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Abstract
The invention discloses one kind 3,3- disubstituted indole quinoline ketone and its derivative and its synthetic method, using diazonium compound, substituted benzyl alcohol and two cobalt of (propilolic alcohol) six carbonyl as raw material, rhodium acetate and silver tetrafluoroborate are catalyst, in organic solvent, highly selective by three component reaction of a step, obtain product in high yield.The method of the present invention has many advantages, such as the mild good, reaction condition of selectivity, high income, easy to operate safe.Proposed by the present invention 3,3- disubstituted indole quinoline ketone and its derivative, not only contained indolinone skeleton itself is that much the important feature segment of biologically active complicated natural products and drug molecule has many bioactivity, and the enyne structure in such compound is also the important intermediate and reaction building block in many drug molecule synthesis, such compound can be used as the intermediate of important medicine and chemical industry, have wide application prospect in medicinal applications.
Description
Technical field
The invention belongs to synthesize field of medicine and chemical technology, and in particular to 3,3- of one kind disubstituted indole quinoline ketone and its derivative
Synthetic method and application.
Background technique
3,3- disubstituted indole quinoline ketone compounds are widely present in natural products and drug molecule, based on its high life
Object activity, the synthesis to such compound are one of the key areas of organic chemistry research.3,3- disubstituted indole quinoline ketones spread out
Biology has preferable antibacterial activity, is the important skeleton structure of a kind of building natural products and drug, is important organic conjunction
At and drug synthesis intermediate.3,3- disubstituted indole quinoline ketones derivant can also be used for synthesizing numerous anti-tumor drugs simultaneously,
Anti-leukocythemia and antibacterials etc..But since there is domain of the existence in such as reaction process to select for classical synthetic method
Property, or using the Heavy Metal Reagent of severe toxicity, the post-processing of reaction and the purification process of product are complicated, are not suitable for industry metaplasia
The problem of production, environmental pollution is serious.
Summary of the invention
The present invention overcomes the bottoms in the presence of 3,3- disubstituted indole quinoline ketone compounds preparation method in the prior art
The defects of object scope of application is wide, poor selectivity, proposes and utilizes propargyl n ion pair reactive intermediate --- and hydroxyl leaf is vertical
Moral captures the method that a tactful step efficiently synthesizes 3,3- disubstituted indole quinoline ketone and its derivative.Method of the invention has high
Atom economy and step economy, regioselectivity, substrate applicability are wide, reaction condition is mild, high income, peace easy to operate
Congruent beneficial effect.3,3- disubstituted indole quinoline ketone and its derivative prepared by the present invention can be used as important medicine and chemical industry
Intermediate, be with a wide range of applications in medicinal applications.
The invention proposes 3,3- of one kind disubstituted indole quinoline ketone and its derivative, structural formula is expressed as formula (I):
Wherein, the benzene that Ar is phenyl, the phenyl of halogen substitution, the alkyl-substituted phenyl of C1-C5, C1-C5 alkoxy replace
Phenyl, the naphthalene of phenyl, nitro substitution that base, trifluoromethyl replace.
Preferably, Ar be phenyl, p-bromophenyl, p-fluorophenyl, rubigan, p-methylphenyl, p-methoxyphenyl,
Bromophenyl, 3,4- Dimethoxyphenyl, 3,4,5- trimethoxyphenyls, 4- trifluoromethyl, 4- nitrobenzophenone, 2- bromobenzene
Base, 2- aminomethyl phenyl or 1- naphthalene.
It is further preferred that Ar is phenyl, p-methoxyphenyl, 2- bromophenyl, 2- methoxyphenyl or 1- naphthalene.
Wherein, R1For the alkyl of C4-C7, the alkoxy of C4-C7, halogen, Ethyl formate, nitro.
Preferably, R1For 5- methyl, 6- bromine, 6- chlorine, 6- nitro, 5- bromine, 5- methoxyl group, 6- methyl, 7- bromine, 6- formic acid second
Ester, 6- nitro.
It is further preferred that R1For 5- methyl, 6- bromine, 6- chlorine, 6- nitro, 5- bromine, 5- methoxyl group.
Wherein, R2Phenyl, the alkyl-substituted benzene of C1-C5 replaced for C1-C5 alkyl, trimethyl silicon substrate, phenyl, halogen
One of phenyl that phenyl, the nitro of phenyl, trifluoromethyl substitution that base, C1-C5 alkoxy replace replace is a variety of.
Preferably, R2Phenyl, p-bromophenyl, p-fluorophenyl, p-methylphenyl, p-methoxyphenyl, m-bromophenyl, 3,4-
Dimethoxyphenyl, 3,4,5- trimethoxyphenyls, 4- trifluoromethyl, 4- nitrobenzophenone, 2- bromophenyl, 2- methylbenzene
Base, 2- methoxyphenyl, trimethyl silicon substrate, methyl, ethyl, n-propyl, normal-butyl.
It is further preferred that R2For phenyl, normal-butyl, trimethyl silicon substrate.
Wherein n is 1-3；It preferably, is n=1.
The invention also provides a kind of formula (I) 3,3- disubstituted indole quinoline ketone and its chemical synthesis process of derivative, with
3- diazonium indolone shown in substituted benzyl alcohol shown in two cobalt of (propargyl alcohol) six carbonyl, formula (2) shown in formula (1) and formula (3) is
Raw material, with AgBF4And Rh2(OAc)4(Ni Gula is reacted by three component Nicholas of a step in organic solvent for catalyst
This reaction), the product 3 as shown in formula (I), 3- disubstituted indole quinoline ketone and its derivative are obtained with high selectivity.The present invention closes
At the reaction process of method as shown in reaction formula (II):
Wherein, the benzene that Ar is phenyl, the phenyl of halogen substitution, the alkyl-substituted phenyl of C1-C5, C1-C5 alkoxy replace
Phenyl, the naphthalene of phenyl, nitro substitution that base, trifluoromethyl replace.
Preferably, Ar be phenyl, p-bromophenyl, p-fluorophenyl, p-methylphenyl, p-methoxyphenyl, m-bromophenyl, 3,
4- Dimethoxyphenyl, 3,4,5- trimethoxyphenyls, 4- trifluoromethyl, 4- nitrobenzophenone, 2- bromophenyl, 2- methylbenzene
Base or 1- naphthalene.
It is further preferred that Ar is phenyl, p-methoxyphenyl, 2- bromophenyl, 2- methoxyphenyl or 1- naphthalene.
Wherein, R1For the alkyl of C4-C7, C4-C7 alkoxy, halogen, Ethyl formate, nitro.
Preferably, R1For 5- methyl, 6- bromine, 6- chlorine, 6- nitro, 5- bromine, 5- methoxyl group, 6- methyl, 7- bromine, 6- formic acid second
Ester, 6- nitro.
It is further preferred that R1For 5- methyl, 6- bromine, 6- chlorine, 6- nitro, 5- bromine, 5- methoxyl group.
Wherein, R2Phenyl, the alkyl-substituted benzene of C1-C5 replaced for C1-C5 alkyl, trimethyl silicon substrate, phenyl, halogen
One of phenyl that phenyl, the nitro of phenyl, trifluoromethyl substitution that base, C1-C5 alkoxy replace replace is a variety of.
Preferably, R2For phenyl, p-bromophenyl, p-fluorophenyl, p-methylphenyl, p-methoxyphenyl, m-bromophenyl, 3,
4- Dimethoxyphenyl, 3,4,5- trimethoxyphenyls, 4- trifluoromethyl, 4- nitrobenzophenone, 2- bromophenyl, 2- methylbenzene
Base, 2- methoxyphenyl, trimethyl silicon substrate, methyl, ethyl, n-propyl, normal-butyl.
It is further preferred that R2For phenyl, normal-butyl, trimethyl silicon substrate.
Wherein n is 1-3；Preferably, n n=1.
Wherein, substituted benzyl alcohol shown in the formula (2) be to bromobenzyl alcohol, to fluoro benzyl alcohol, to xylyl alcohol, to methoxybenzyl
Alcohol, bromobenzyl alcohol, 4- trifluoromethyl-benzyl-alcohol, 4- nitrobenzyl alcohol, 2- bromobenzyl alcohol, 2- xylyl alcohol, 2- methoxyl group benzylalcohol or 1- naphthalene
Methanol.
Wherein, two cobalt of (propargyl alcohol) six carbonyl shown in the formula (1) is (1- trimethyl silicane ethyl-acetylene base -2- cyclopentene -
1- alcohol) six carbonyls, two cobalt, two cobalt of (1- phenylene-ethynylene -2- cyclopentene -1- alcohol) six carbonyl, (1- hexin base -2- cyclopentene -1-
Alcohol) six carbonyls, two cobalt, two cobalt of (1- trimethyl silicane ethyl-acetylene base -2- cyclohexene -1- alcohol) six carbonyl, (1- trimethyl silicane ethyl-acetylene
Base -2- cycloheptene -1- alcohol) six carbonyls, two cobalt, (1- trimethyl silicane ethyl-acetylene base -2- methyl -2- cyclopentene -1- alcohol) six carbonyls two
Cobalt.
Wherein, shown in substituted benzyl alcohol and formula (3) shown in two cobalt of (propargyl alcohol) six carbonyl, formula (2) shown in the formula (1)
3- diazonium indolone molar ratio be (1.0~2.0): (1.0~2.0): (1.0~2.0)；Preferably, shown in the formula (1)
Two cobalt of (propargyl alcohol) six carbonyl, 3- diazonium indolone shown in substituted benzyl alcohol and formula (3) shown in formula (2) molar ratio be
1.0∶1.5∶1.5。
Wherein, obtained 3, the 3- disubstituted indole quinoline ketone of reaction and its derivative are chromatographed through column and carries out separating-purifying.
Wherein, the organic solvent is selected from DCM, DCE, CHCl3, toluene, one of chlorobenzene etc. or a variety of；Preferably
DCM。
Wherein, the temperature of the reaction is 0 DEG C -60 DEG C；It preferably, is 0 DEG C -40 DEG C；It is further preferred that being 40 DEG C.
Wherein, the time of the reaction is 1-12h；It preferably, is 2h.
Wherein, shown in formula (1) on the basis of two cobalt of (propargyl alcohol) six carbonyl, catalyst AgBF4Mole dosage be (third
Alkynol) six carbonyls two cobalt 5.0-10%, it is preferable that be 10%.
Wherein, shown in formula (1) on the basis of two cobalt of (propargyl alcohol) six carbonyl, catalyst Rh2(OAc)4Mole dosage be
The 0.5-2% of two cobalt of (propilolic alcohol) six carbonyl, it is preferable that be 1.0%.
It is as follows that the present invention innovates chemism involved in the above-mentioned synthetic method of proposition for the first time:
Formula (3) diazonium compound first is in metal Rh2(OAc)4Catalysis under be decomposed to form metal carbene and release nitrogen,
Nucleopilic reagent formula (2) substituted benzyl alcohol and metal carbene interaction generate reactive intermediate hydroxyl ylide (I, II), then formula
(1) propargyl alcohol is in lewis acid AgBF4Effect is lower to generate carbonium ion (III), and carbonium ion (III) is as electrophilic reagent to work
It sprinkles intermediate hydroxyl ylide (I, II) to capture, Nicholas reaction generation three component products, that is, formula (I) 3,3- bis- occurs and replaces
Indolinone and its derivative.
The invention also provides 3,3- disubstituted indole quinolines shown in the obtained formula of preparation method (I) according to the present invention
Ketone and its derivative.
The present invention relates to 3,3- of one kind disubstituted indole quinoline ketone and its derivative is synthesized, with diazonium compound, substituted benzyl alcohol
And two cobalt of (propargyl alcohol) six carbonyl is raw material, AgBF4And Rh2(OAc)4It is in a solvent, anti-by three component of a step for catalyst
It answers and highly selective obtains formula new in the present invention (I) compound 3,3- disubstituted indole quinoline ketone and its derivative.
In a specific embodiment, the synthetic method of 3,3- of present invention disubstituted indole quinoline ketone and its derivative are as follows: with
Two cobalt of formula (1) (propargyl alcohol) six carbonyl, formula (2) substituted benzyl alcohol and formula (3) 3- diazonium indolone are raw material, AgBF4And Rh2
(OAc)4It, by three component reaction of a step, removes organic solvent using organic solvent as solvent for catalyst and obtains crude product, through column
Chromatography purifies to obtain product.Specific steps are as follows: under the conditions of nitrogen protection, drying is added in silver tetrafluoroborate and rhodium acetate
10ml test tube in.40 DEG C are warming up to after the methylene chloride of 1.5ml is added, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzyl
Alcohol 2 (0.15mmol), 3- diazonium indolone 3 (0.15mmol) are mixed and are dissolved in 1ml methylene chloride, mixed solution is made
It is squeezed into test tube in 2 hours with peristaltic pump, continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution,
It samples and is dissolved in deuterated chloroform and use1H NMR measures d.r. value, uses column chromatographic isolation and purification after all solution are mixed
(petroleum ether: ethyl acetate=70: 1~20: 1), obtain pure product i.e. formula (I) 3,3- disubstituted indole quinoline ketone and its derivative
Object.
The present invention is using diazonium compound, substituted benzyl alcohol and two cobalt of (propargyl alcohol) six carbonyl as raw material, AgBF4And Rh2(OAc)4
, by three component reaction of a step, 3,3- disubstituted indole quinoline ketone and its derivative are obtained using organic solvent as solvent for catalyst
Object.
Beneficial effect of the present invention includes: to propose using carbonium ion in (1) present invention to reactive intermediate --- hydroxyl
Ylide captures strategy to synthesize the method and application of 3,3- disubstituted indole quinoline ketone compounds.(2) present invention passes through a step
The method that three component reactions synthesize 3,3- disubstituted indole quinoline ketone and its derivative, has high flexibility, and high regioselectivity is former
Subeconomy is high, substrate applicability is wide, product is easy to purify, and reaction condition is mild, high income (highest yield up to 90%), operation
Simple and safe advantage.(3) the 3 of the skeleton of the invention containing alkynyl, 3- disubstituted indole quinoline ketone and its derivative can be used as important
Medicine and chemical industry intermediate, be with a wide range of applications in medicinal applications.The method is with atom economy in recent years
Property concept it is increasingly developed, which will also will receive more and more concerns, and this kind of approach application is led in pharmaceutical synthesis
Domain also has broad prospects.(4) 3,3- disubstituted indole quinoline ketone and its derivative according to the present invention, in such compound
Contained indolinone skeleton is the important feature segment of many biologically active complicated natural products, while such is changed
The alkynyl moieties contained by object are closed to be widely present in the precursor and intermediate of many natural products and drug molecule.Therefore such
Compound can be used as the intermediate of important medicine and chemical industry, be with a wide range of applications in medicinal applications.
Detailed description of the invention
Fig. 1 is 1 products therefrom syn-4a's of embodiment1H NMR schematic diagram.
Fig. 2 is 1 products therefrom syn-4a's of embodiment13C NMR schematic diagram.
Fig. 3 is 1 products therefrom anti-4a's of embodiment1H NMR schematic diagram.
Fig. 4 is 1 products therefrom anti-4a's of embodiment13C NMR schematic diagram.
Fig. 5 is 2 products therefrom syn-4b's of embodiment1H NMR schematic diagram.
Fig. 6 is 2 products therefrom syn-4b's of embodiment13C NMR schematic diagram.
Fig. 7 is 2 products therefrom anti-4b's of embodiment1H NMR schematic diagram.
Fig. 8 is 2 products therefrom anti-4b's of embodiment13C NMR schematic diagram.
Fig. 9 is 3 products therefrom syn-4c's of embodiment1H NMR schematic diagram.
Figure 10 is 3 products therefrom syn-4c's of embodiment13C NMR schematic diagram.
Figure 11 is 3 products therefrom anti-4c's of embodiment1H NMR schematic diagram.
Figure 12 is 3 products therefrom anti-4c's of embodiment13C NMR schematic diagram.
Figure 13 is 4 products therefrom syn-4d's of embodiment1H NMR schematic diagram.
Figure 14 is 4 products therefrom syn-4d's of embodiment13C NMR schematic diagram.
Figure 15 is 4 products therefrom anti-4d's of embodiment1H NMR schematic diagram.
Figure 16 is 4 products therefrom anti-4d's of embodiment13C NMR schematic diagram.
Figure 17 is 5 products therefrom syn-4e's of embodiment1H NMR schematic diagram.
Figure 18 is 5 products therefrom syn-4e's of embodiment13C NMR schematic diagram.
Figure 19 is 5 products therefrom anti-4e's of embodiment1H NMR schematic diagram.
Figure 20 is 5 products therefrom anti-4e's of embodiment13C NMR schematic diagram.
Figure 21 is 6 products therefrom syn-4f's of embodiment1H NMR schematic diagram.
Figure 22 is 6 products therefrom syn-4f's of embodiment13C NMR schematic diagram.
Figure 23 is 6 products therefrom ami-4f's of embodiment1H NMR schematic diagram.
Figure 24 is 6 products therefrom ami-4f's of embodiment13C NMR schematic diagram.
Figure 25 is 7 products therefrom syn-4g's of embodiment1H NMR schematic diagram.
Figure 26 is the 1 of 7 products therefrom syn-4g of embodiment3CNMR schematic diagram.
Figure 27 is 7 products therefrom anti-4g's of embodiment1H NMR schematic diagram.
Figure 28 is 7 products therefrom anti-4g's of embodiment13C NMR schematic diagram.
Figure 29 is 8 products therefrom syn-4h's of embodiment1H NMR schematic diagram.
Figure 30 is 8 products therefrom syn-4h's of embodiment13C NMR schematic diagram.
Figure 31 is 8 products therefrom anti-4h's of embodiment1H NMR schematic diagram.
Figure 32 is 8 products therefrom anti-4h's of embodiment13C NMR schematic diagram.
Figure 33 is 9 products therefrom syn-4i's of embodiment1H NMR schematic diagram.
Figure 34 is 9 products therefrom syn-4i's of embodiment13C NMR schematic diagram.
Figure 35 is 9 products therefrom anti-4i's of embodiment1H NMR schematic diagram.
Figure 36 is 9 products therefrom anti-4i's of embodiment13C NMR schematic diagram.
Figure 37 is 10 products therefrom syn-4j's of embodiment1H NMR schematic diagram.
Figure 38 is 10 products therefrom syn-4j's of embodiment13C NMR schematic diagram.
Figure 39 is 10 products therefrom anti-4j's of embodiment1H NMR schematic diagram.
Figure 40 is 10 products therefrom anti-4j's of embodiment13C NMR schematic diagram.
Figure 41 is 11 products therefrom syn-4k's of embodiment1H NMR schematic diagram.
Figure 42 is 11 products therefrom syn-4k's of embodiment13C NMR schematic diagram.
Figure 43 is 11 products therefrom anti-4k's of embodiment1H NMR schematic diagram.
Figure 44 is 11 products therefrom anti-4k's of embodiment13C NMR schematic diagram.
Figure 45 is 12 products therefrom syn-41's of embodiment1H NMR schematic diagram.
Figure 46 is 12 products therefrom syn-4l's of embodiment13C NMR schematic diagram.
Figure 47 is 12 products therefrom anti-41's of embodiment1H NMR schematic diagram.
Figure 48 is 12 products therefrom anti-41's of embodiment13C NMR schematic diagram.
Figure 49 is 13 products therefrom syn-4m's of embodiment1H NMR schematic diagram.
Figure 50 is 13 products therefrom syn-4m's of embodiment13C NMR schematic diagram.
Figure 52 is 13 products therefrom anti-4m's of embodiment1H NMR schematic diagram.
Figure 51 is 13 products therefrom anti-4m's of embodiment13C NMR schematic diagram.
Figure 53 is 14 products therefrom syn-4n's of embodiment1H NMR schematic diagram.
Figure 54 is 14 products therefrom syn-4n's of embodiment13C NMR schematic diagram.
Figure 55 is 14 products therefrom anti-4n's of embodiment1H NMR schematic diagram.
Figure 56 is 14 products therefrom anti-4n's of embodiment13C NMR schematic diagram.
Figure 57 is 15 products therefrom syn-4o's of embodiment1H NMR schematic diagram.
Figure 58 is 15 products therefrom syn-4o's of embodiment13C NMR schematic diagram.
Figure 59 is 15 products therefrom anti-4o's of embodiment1H NMR schematic diagram.
Figure 60 is 15 products therefrom anti-4o's of embodiment13C NMR schematic diagram.
Figure 61 is 16 products therefrom syn-4p's of embodiment1H NMR schematic diagram.
Figure 62 is 16 products therefrom syn-4p's of embodiment13C NMR schematic diagram.
Figure 63 is 16 products therefrom anti-4p's of embodiment1H NMR schematic diagram.
Figure 64 is 16 products therefrom anti-4p's of embodiment13C NMR schematic diagram.
Specific embodiment
In conjunction with following specific embodiments and attached drawing, the present invention is described in further detail.Implement process of the invention,
Condition, experimental method etc., are among the general principles and common general knowledge in the art, and there are no special restrictions to content by the present invention.
Embodiment 1:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4a.Yield: 90%, anti: syn=43: 57.
Compound syn-4a:1H NMR (400MHz, CDCl3) δ 7.36 (t, J=7.7Hz, 1H), 7.31-7.21 (m, 6H),
7.02 (t, J=7.5Hz, 1H), 6.86 (d, J=7.7Hz, 1H), 6.12 (s, 1H), 4.14 (dd, J=63.1,10.7Hz,
2H), 3.63 (s, 1H), 3.21 (s, 3H), 2.45-2.32 (m, 1H), 2.21-2.10 (m, 1H), 2.10-1.95 (m, 1H),
1.50-1.38 (m, 1H), 0.30 (s, 9H)；13C NMR (101MHz, CDCl3) δ 200.15,175.47,144.38,144.14,
137.81,131.07,129.96,128.19,127.70,127.61,125.56,125.11,122.88,108.09,99.67,
84.47,80.87,67.69,53.80,37.02,26.10,24.15,0.73.
Compound a nti-4a:1H NMR (400MHz, CDCl3) δ 7.47 (d, J=7.3Hz, 1H), 7.38-7.27 (m,
6H), 7.07 (t, J=7.5Hz, 1H), 6.81 (d, J=7.8Hz, 1H), 5.63 (s, 1H), 4.18 (dd, J=55.6,
10.7Hz, 2H), 3.55 (d, J=8.1Hz, 1H), 3.22 (s, 3H), 2.67-2.57 (m, 1H), 2.56-2.44 (m, 2H),
2.36-2.25 (m, 1H), 0.23 (s, 9H)；13C NMR (101MHz, CDCl3) δ 199.99,176.12,144.29,143.73,
137.76,129.91,129.41,128.19,127.75,127.61,126.29,124.27,122.74,108.57,99.37,
84.64,80.56,67.80,54.48,37.41,25.96,24.75,0.66.
Embodiment 2:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4b.Yield: 66%, anti: syn=47: 53.
Compound syn-4b:1H NMR (400MHz, CDCl3) δ 7.36 (t, J=7.7Hz, 1H), 7.24 (s, 1H), 7.17
(d, J=8.4Hz, 2H), 7.03 (t, J=7.5Hz, 1H), 6.85 (d, J=7.8Hz, 1H), 6.81 (d, J=8.5Hz, 2H),
6.08 (s, 1H), 4.07 (dd, J=53.1,10.3Hz, 2H), 3.78 (s, 3H), 3.64-3.58 (m, 1H), 3.20 (s, 3H),
2.44-2.36 (m, 1H), 2.22-2.12 (m, 1H), 2.07-1.97 (m, 1H), 1.50-1.41 (m, 1H), 0.30 (s, 9H)；13C
NMR (101MHz, CDCl3) δ 200.12,175.57,159.20,144.36,144.07,131.15,129.94,129.89,
129.43,125.72,125.09,122.84,113.61,108.06,99.75,84.35,80.89,67.46,55.26,
53.82,37.03,26.07,24.13,0.73.
Compound a mi-4b:1H NMR (400MHz, CDCl3) δ 7.45 (d, J=7.3Hz, 1H), 7.30 (t, J=7.7Hz,
1H), 7.19 (d, J=8.2Hz, 2H), 7.05 (t, J=7.5Hz, 1H), 6.82 (d, J=8.3Hz, 2H), 6.78 (d, J=
7.8Hz, 1H), 5.59 (s, 1H), 4.09 (dd, J=49.4,10.3Hz, 2H), 3.78 (s, 3H), 3.51 (d, J=8.0Hz,
1H), 3.18 (s, 3H), 2.59-2.52 (m, 1H), 2.51-2.39 (m, 2H), 2.33-2.21 (m, 1H), 0.20 (s, 9H)；13C
NMR (101MHz, CDCl3) δ 199.98,176.20,159.17,144.20,143.70,129.87,129.83,129.48,
129.44,126.38,124.23,122.69,113.59,108.54,99.37,84.53,80.52,69.04,67.55,
55.24,54.47,37.37,25.90,24.74,0.62.
Embodiment 3:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4c.Yield: 77%, anti: syn=43: 57.
Compound syn-4c:1H NMR (400MHz, CDCl3) δ 7.38 (dd, J=16.8,8.0Hz, 3H), 7.22 (d, J=
7.2Hz, 1H), 7.13 (d, J=8.1Hz, 2H), 7.02 (t, J=7.5Hz, 1H), 6.86 (d, J=7.8Hz, 1H), 6.09 (s,
1H), 4.08 (dd, J=62.6,11.0Hz, 2H), 3.61 (s, 1H), 3.21 (s, 3H), 2.46-2.33 (m, 1H), 2.23-
2.11 (m, 1H), 2.09-1.98 (m, 1H), 1.45 (ddd, J=13.8,9.5,4.8Hz, 1H), 0.30 (s, 9H)；13C NMR
(101MHz, CDCl3) δ 200.12,175.31,144.34,144.32,136.78,131.26,130.77,130.06,
129.34,125.32,125.02,122.92,121.50,108.15,99.51,84.49,80.89,66.98,53.69,
36.97,26.09,24.12,0.70.
Compound a nti-4c:1H NMR (400MHz, CDCl3) δ 7.26-7.15 (m, 3H), 7.10-7.04 (m, 1H),
6.94 (d, J=7.9Hz, 2H), 6.84 (t, J=7.0Hz, 1H), 6.58 (d, J=7.5Hz, 1H), 5.40 (s, 1H), 3.89
(dd, J=49.7,10.9Hz, 2H), 3.30 (d, J=4.6Hz, 1H), 2.98 (s, 3H), 2.40-2.22 (m, 3H), 2.07 (s,
1H), 0.01 (d, J=5.1Hz, 9H)；13C NMR (101MHz, CDCl3) δ 200.01,175.96,144.42,143.70,
136.76,131.29,130.01,129.41,129.22,126.10,124.20,122.78,121.52,108.63,99.28,
84.65,80.58,67.11,54.39,37.37,25.95,24.69,0.63.
Embodiment 4:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in lml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4d.Yield: 55%, anti: syn=49: 51.
Compound syn-4d:1H NMR (400MHz, CDCl3) δ 7.43 (d, J=7.4Hz, 1H), 7.34 (s, 1H), 7.22
(d, J=7.2Hz, 2H), 6.98 (s, 1H), 6.92 (s, 1H), 6.84 (d, J=7.8Hz, 1H), 6.76 (d, J=8.2Hz,
1H), 6.18 (s, 1H), 4.20 (dd, J=59.0,11.5Hz, 2H), 3.70 (s, 3H), 3.64 (s, 1H), 3.22 (s, 3H),
2.44-2.34 (m, 1H), 2.18-2.09 (m, 1H), 2.06-1.95 (m, 1H), 1.46-1.37 (m, 1H), 0.30 (s, 9H)；13C
NMR (101MHz, CDCl3) δ 200.15,175.52,156.69,144.37,143.87,131.41,129.73,128.77,
128.47,126.38,125.60,125.29,122.64,120.32,109.89,107.89,99.72,84.37,80.79,
62.42,55.11,53.93,36.97,26.08,24.13,0.71.
Compound a nti-4d:1H NMR (400MHz, CDCl3) δ 7.44 (dd, J=17.8,7.2Hz, 2H), 7.29 (d, J
=7.6Hz, 1H), 7.21 (t, J=7.6Hz, 1H), 6.97 (dt, J=29.9,7.3Hz, 2H), 6.83-6.72 (m, 2H),
5.60 (s, 1H), 4.22 (dd, J=40.8,11.6Hz, 2H), 3.71 (s, 3H), 3.54 (d, J=6.9Hz, 1H), 3.20 (s,
3H), 2.70-2.59 (m, 1H), 2.55-2.40 (m, 2H), 2.35-2.24 (m, 1H), 0.21 (s, 9H)；13C NMR (101MHz,
CDCl3) δ 199.99,176.21,156.58,144.15,143.68,129.71,129.53,128.58,128.39,126.39,
124.37,122.53,120.33,109.84,108.43,99.42,84.49,80.50,62.46,55.11,54.65,37.41,
25.93,24.72,0.63.
Embodiment 5:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4e.Yield: 81%, anti: syn=48: 52.
Compound syn-4e1H NMR (400MHz, CDCl3) δ 7.53 (d, J=7.3Hz, 1H), 7.45 (d, J=7.9Hz,
1H), 7.35 (t, J=7.8Hz, 1H), 7.25 (dd, J=12.7,7.0Hz, 2H), 7.11 (t, J=7.6Hz, 1H), 6.98 (t,
J=7.5Hz, 1H), 6.87 (d, J=7.8Hz, 1H), 6.20 (s, 1H), 4.21 (dd, J=34.8,11.7Hz, 2H), 3.65
(s, 1H), 3.25 (s, 3H), 2.45-2.34 (m, 1H), 2.16 (d, J=8.2Hz, 1H), 2.07-1.97 (m, 1H), 1.47-
1.37 (m, 1H), 0.31 (s, 9H)；13C NMR (101MHz, CDCl3) δ 200.14,175.25,144.28,144.17,
137.17,132.29,131.02,130.03,129.73,128.98,127.31,125.32,125.04,122.84,122.61,
108.12,99.54,84.53,80.81,67.05,53.81,36.96,26.16,24.14,0.73.
Compound a nti-4e1H NMR (400MHz, CDCl3) δ 7.58 (d, J=7.6Hz, 1H), 7.48-7.41 (m, 2H),
7.30 (t, J=7.6Hz, 2H), 7.12 (t, J=7.6Hz, 1H), 7.03 (t, J=7.5Hz, 1H), 6.81 (d, J=7.8Hz,
1H), 5.61 (s, 1H), 4.23 (q, J=11.8Hz, 2H), 3.54 (d, J=8.1Hz, 1H), 3.22 (s, 3H), 2.69-2.59
(m, 1H), 2.55-2.44 (m, 2H), 2.37-2.26 (m, 1H), 0.21 (s, 9H)；13C NMR (101MHz, CDCl3)δ
199.96,175.87,144.37,143.60,137.18,132.22,129.99,129.56,129.27,128.91,127.33,
125.89,124.35,122.75,122.43,108.62,99.29,84.61,80.54,66.99,54.53,37.41,26.02,
24.70 0.64.
Embodiment 6:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20；1) pure product 4f, is obtained.Yield: 80%, anti: syn=41: 59.
Compound syn-4f:1H NMR (400MHz, CDCl3) δ 8.13 (d, J=8.3Hz, 1H), 7.82 (d, J=7.8Hz,
1H), 7.76 (dd, J=6.7,2.0Hz, 1H), 7.49 (dd, J=15.3,7.7Hz, 2H), 7.36 (t, J=8.2Hz, 3H),
7.28 (d, J=7.3Hz, 1H), 7.03 (t, J=7.5Hz, 1H), 6.88 (d, J=7.8Hz, 1H), 6.02 (s, 1H), 4.57
(dd, J=81.3,10.4Hz, 2H), 3.64 (d, J=2.3Hz, 1H), 3.25 (s, 3H), 2.46-2.35 (m, 1H), 2.25-
2.14 (m, 1H), 2.08-1.96 (m, 1H), 1.60-1.51 (m, 1H), 0.27 (s, 9H)；13C NMR (101MHz, CDCl3)δ
200.11,175.43,144.33,144.15,133.59,133.28,131.85,130.88,129.95,128.72,128.33,
126.80,126.19,125.65,125.60,125.11,125.07,124.19,122.86,108.13,99.64,84.58,
80.84,66.23,54.04,37.04,26.10,24.07.0.69.
Compound a nti-4f:1H NMR (400MHz, CDCl3) δ 8.18 (d, J=8.4Hz, 1H), 7.82 (d, J=
8.0Hz, 1H), 7.77 (d, J=7.3Hz, 1H), 7.54 (s, 1H), 7.46 (dd, J=10.6,7.8Hz, 2H), 7.35 (dd, J
=14.6,7.4Hz, 3H), 7.05 (s, 1H), 6.82 (d, J=7.8Hz, 1H), 5.67 (s, 1H), 4.59 (dd, J=114.7,
10.4Hz, 2H), 3.55 (d, J=8.5Hz, 1H), 3.24 (s, 3H), 2.47 (t, J=13.8Hz, 3H), 2.25-2.16 (m,
1H), 0.20 (s, 9H)；13C NMR (101MHz, CDCl3) δ 199.97,175.96,144.12,143.76,133.59,
133.34,131.83,129.90,129.56,128.67,128.30,126.63,126.33,126.18,125.67,125.11,
124.31 124.23,122.75,108.58,99.43,84.79,80.51,66.17,54.65,37.32,25.97,24.79,
0.61.
Embodiment 7:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4g.Yield: 57%, anti: syn=49: 51.
Compound syn-4g:1H NMR (400MHz, CDCl3) δ 7.33-7.20 (m, 6H), 6.89 (s, 1H), 6.86 (d, J
=8.4Hz, 1H), 6.75 (d, J=8.4Hz, 1H), 5.94 (s, 1H), 4.15 (dd, J=60.5,10.7Hz, 2H), 3.75 (s,
3H), 3.59 (s, 1H), 3.16 (s, 3H), 2.49-2.41 (m, 1H), 2.39-2.30 (m, 1H), 2.10-2.00 (m, 1H),
1.77 (dt, J=13.6,7.1Hz, 1H), 0.29 (s, 9H)；13C NMR (101MHz, CDCl3) δ 200.12,175.06,
156.25,144.30,137.82,137.64,130.48,128.17,127.71,127.58,113.05,108.26,99.67,
84.56,80.81,67.76,55.64,54.22,37.18,26.09,24.16,0.67.
Compound a mi-4g:1H NMR (400MHz, CDCl3) δ 7.31-7.23 (m, 5H), 7.06 (d, J=2.1Hz, 1H),
6.81 (dd, J=8.5,2.3Hz, 1H), 6.70 (d, J=8.5Hz, 1H), 5.61 (s, 1H), 4.17 (dd, J=58.2,
10.7Hz, 2H), 3.75 (s, 3H), 3.53 (d, J=7.3Hz, 1H), 3.18 (s, 3H), 2.60-2.44 (m, 3H), 2.35-
2.22 (m, 1H), 0.21 (s, 9H)；13C NMR (101MHz, CDCl3) δ 199.95,175.70,155.97,144.18,
137.75,137.05,129.47,128.17,127.73,127.58,113.60,111.84,108.81,99.36,84.86,
80.54,67.83,55.54,54.46,37.46,26.00,24.61,0.60.
Embodiment 8:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4h.Yield: 51%, anti: syn=42: 58.
Compound syn-4h:1H NMR (400MHz, CDCl3) δ 7.31-7.24 (m, 5H), 7.15 (d, J=7.9Hz, 1H),
7.04 (s, 1H), 6.74 (d, J=7.9Hz, 1H), 6.07 (s, 1H), 4.14 (dd, J=59.5,10.9Hz, 2H), 3.62 (s,
1H), 3.17 (s, 3H), 2.53-2.44 (m, 1H), 2.33 (d, J=11.4Hz, 1H), 2.29 (d, J=13.4Hz, 3H), 2.03
(ddd, J=18.1,11.5,7.1Hz, 1H), 1.61-1.52 (m, 1H), 0.31 (s, 9H)；13C NMR (101MHz, CDCl3)δ
200.16,175.40,143.74,142.01,137.97,132.47,131.06,130.22,128.14,127.59,127.51,
125.77,125.65,107.81,99.83,84.39,80.81,67.58,53.99,37.03,26.07,24.22,20.96,
0.70.
Compound a mi-4h:1H NMR (400MHz, CDCl3) δ 7.30-7.23 (m, 6H), 7.09 (d, J=7.9Hz, 1H),
6.68 (d, J=7.9Hz, 1H), 5.61 (s, 1H), 4.16 (dd, J=52.7,10.8Hz, 2H), 3.50 (d, J=7.5Hz,
1H), 3.18 (s, 3H), 2.70-2.57 (m, 1H), 2.56-2.42 (m, 2H), 2.34-2.22 (m, 4H), 0.21 (s, 9H)；13C
NMR (101MHz, CDCl3) δ 199.99,176.06,144.15,141.29,137.90,132.19,130.12,129.62,
128.15,127.64,127.52,126.29,125.07,108.28,99.44,84.67,80.50,67.68,54.4l,
37.47,25.95,24.71,21.00,0.60.
Embodiment 9:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4i.Yield: 75%, anti: syn=47: 53.
Compound syn-4i:1H NMR (400MHz, CDCl3) δ 7.39-7.22 (m, 7H), 6.77 (d, J=8.3Hz, 1H),
5.97 (s, 1H), 4.16 (dd, J=62.1,10.7Hz, 2H), 3.61 (s, 1H), 3.17 (s, 3H), 2.53-2.43 (m, 1H),
2.38 (d, J=7.2Hz, 1H), 2.13-2.01 (m, 1H), 1.69-1.59 (m, 1H), 0.30 (s, 9H)；13C NMR (101MHz,
CDCl3) δ 200.05,174.97,144.78,142.79,137.43,129.96,129.92,128.48,128.22,127.84,
127.75,127.69,125.14,109.05,99.22,84.22,80.88,67.95,54.00,37.10,26.14,24.07,
0.71.
Compound a nti-4i:1H NMR (400MHz, CDCl3) δ 7.40 (d, J=1.6Hz, 1H), 7.34-7.19 (m,
6H), 6.71 (d, J=8.3Hz, 1H), 5.56 (s, 1H), 4.18 (dd, J=55.3,10.6Hz, 2H), 3.52 (d, J=
8.8Hz, 1H), 3.18 (s, 3H), 2.52 (t, J=11.2Hz, 3H), 2.40-2.25 (m, 1H), 0.22 (s, 9H)；13C NMR
(101MHz, CDCl3) δ 199.93,175.60,144.85,142.21,137.36,129.79,128.75,128.31,
128.24,127.77,124.61,109.44,99.13,84.59,80.86,68.06,54.37,37.37,26.04,24.68,
0.61.
Embodiment 10:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4j.Yield: 67%, anti: syn=49: 51.
Compound syn-4j:1H NMR (400MHz, CDCl3) δ 7.29-7.19 (m, 5H), 7.15 (d, J=7.9Hz, 1H),
6.99 (d, J=7.9Hz, 1H), 6.86 (s, 1H), 6.09 (s, 1H), 4.13 (dd, J=65.4,10.7Hz, 2H), 3.63 (s,
1H), 3.19 (s, 3H), 2.50-2.36 (m, 1H), 2.27-2.15 (m, 1H), 2.11-1.95 (m, 1H), 1.43 (qd, J=
9.8,5.0Hz, 1H), 0.31 (s, 9H)；13C NMR (101MHz, CDCl3) δ 200.10,175.38,145.57,144.55,
137.48,135.89,130.46,128.21,127.72,127.66,126.01,123.94,122.67,108.92,99.35,
84.03,80.96,67.78,53.65,36.98,26.18,24.06,0.70.
Compound a nti-4j:1H NMR (400MHz, CDCl3) δ 7.36 (d, J=7.8Hz, 1H), 7.29 (dd, J=
12.3,5.7Hz, 5H), 7.02 (d, J=7.8Hz, 1H), 6.79 (s, 1H), 5.56 (s, 1H), 4.15 (dd, J=59.0,
10.6Hz, 2H), 3.52 (d, J=7.8Hz, 1H), 3.17 (s, 3H), 2.52 (dd, J=21.3,6.2Hz, 3H), 2.37-2.23
(m, 1H), 0.22 (s, 9H)；13C NMR (101MHz, CDCl3) δ 199.91,176.04,144.96,144.78,137.44,
135.86,128.79,128.23,127.75,125.13,124.72,122.59,109.35,99.12,84.29,80.74,
67.93,54.40,37.37,26.04,24.71,0.59.
Embodiment 11:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4k.Yield: 75%, anti: syn=45: 55.
Compound syn-4k:1H NMR (400MHz, CDCl3) δ 7.31-7.22 (m, 5H), 7.12 (dd, J=25.9,
7.8Hz, 2H), 7.01 (s, 1H), 6.08 (s, 1H), 4.13 (dd, J=65.5,10.7Hz, 2H), 3.62 (s, 1H), 3.18 (s,
3H), 2.42 (dd, J=9.6,5.4Hz, 1H), 2.22 (d, J=7.5Hz, 1H), 2.10-1.96 (m, 1H), 1.48-1.39 (m,
1H), 0.30 (s, 9H)；13C NMR (101MHz, CDCl3) δ 200.10,175.26,145.68,144.57,137.47,
130.44,128.22,127.73,127.67,126.34,125.64,124.53,123.77,111.69,99.36,84.09,
80.99,67.81,53.62,36.99,26.18,24.07,0.71.
Compound a nti-4k:1H NMR (400MHz, CDCl3) δ 7.32-7.24 (m, 6H), 7.19 (d, J=7.8Hz,
1H), 6.94 (s, 1H), 5.56 (s, 1H), 4.15 (dd, J=59.1,10.6Hz, 2H), 3.52 (d, J=8.8Hz, 1H), 3.17
(s, 3H), 2.57-2.42 (m, 3H), 2.35-2.24 (m, 1H), 0.22 (s, 9H)；13C NMR (101MHz, CDCl3)δ
199.95,175.92,145.05,144.81,137.41,128.74,128.23,127.74,125.55,125.45,125.28,
123.72,112.12,99.09,84.35,80.73,67.93,54.35,37.37,26.04,24.70,0.60.
Embodiment 12:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 41.Yield: 46%, anti: syn=40: 60.
Compound syn-4l:1H NMR (400MHz, CDCl3) δ 7.37 (t, J=7.7Hz, 1H), 7.31-7.21 (m, 5H),
7.09 (d, J=7.3Hz, 1H), 7.00 (t, J=7.5Hz, 1H), 6.88 (d, J=7.8Hz, 1H), 4.09 (dd, J=52.4,
10.7Hz, 2H), 3.51 (d, J=8.7Hz, 1H), 3.24 (s, 3H), 2.32-2.18 (m, 1H), 2.11 (s, 3H), 1.98-
1.85 (m, 2H), 1.24-1.13 (m, 1H), 0.36 (s, 9H)；13C NMR (101MHz, CDCl3) δ 200.41,175.48,
144.47,139.91,137.68,136.36,130.05,128.13,127.63,127.49,125.19,123.00,108.18,
97.90,85.46,80.94,67.49,57.32,38.72,26.06,23.67,17.85,1.49.
Compound a mi-41:1H NMR (400MHz, CDCl3) δ 7.46 (d, J=7.3Hz, 1H), 7.29 (dd, J=15.3,
7.8Hz, 6H), 7.04 (t, J=7.5Hz, 1H), 6.78 (d, J=7.8Hz, 1H), 4.14 (dd, J=71.1,10.6Hz, 2H),
3.55 (d, J=9.2Hz, 1H), 3.18 (s, 3H), 2.65-2.55 (m, 1H), 2.52-2.43 (m, 1H), 2.39-2.28 (m,
1H), 2.21-2.10 (m, 1H), 1.69 (s, 3H), 0.26 (s, 9H)；13C NMR (101MHz, CDCl3) δ 200.30,175.67,
143.88,137.80,137.50,135.63,129.94,128.18,127.79,127.57,126.42,124.06,123.06,
108.26,98.13,84.31,80.36,67.07,59.30,39.08,26.09,23.91,15.82,1.35.
Embodiment 13:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4m.Yield: 75%, anti: syn=37: 67.
Compound syn-4m:1H NMR (400MHz, CDCl3) δ 7.34 (t, J=7.4Hz, 1H), 7.28-7.21 (m, 6H),
6.98 (t, J=7.5Hz, 1H), 6.86 (d, J=7.8Hz, 1H), 6.63 (s, 1H), 4.16 (dd, J=75.9,10.5Hz,
2H), 3.22 (s, 3H), 3.11 (d, J=2.5Hz, 1H), 2.24-2.07 (m, 2H), 1.71-1.55 (m, 3H), 0.83-0.70
(m, 1H), 0.30 (s, 9H)；13C NMR (101MHz, CDCl3) δ 200.36,175.29,144.36,137.66,137.58,
129.89,128.18,128.11,127.79,127.54,125.71,124.94,122.86,108.66,108.11,84.30,
79.63,67.33,44.23,30.78,26.03,22.61,21.85,0.73.
Compound a mi-4m:1H NMR (400MHz, CDCl3) δ 7.37 (d, J=7.3Hz, 1H), 7.34-7.21 (m, 6H),
7.06 (t, J=7.5Hz, 1H), 6.83 (d, J=7.8Hz, 1H), 6.10 (s, 1H), 4.11 (dd, J=69.1,10.5Hz,
2H), 3.22 (s, 3H), 3.07 (dd, J=6.0,2.5Hz, 1H), 2.28-2.17 (m, 2H), 1.99-1.86 (m, 2H), 1.67-
1.57 (m, 1H), 1.50-1.39 (m, 1H), 0.26 (s, 9H)；13C NMR (101MHz, CDCl3) δ 200.22,175.16,
144.11,137.73,136.29,129.82,128.68,128.13,127.75,127.55,126.32,124.62,122.81,
108.44 108.40,84.37,79.31,67.35,44.96,31.16,26.03,22.84,22.44,0.70.
Embodiment 14:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4n.Yield: 70%, anti: syn=47: 53.
Compound syn-4n:1H NMR (400MHz, CDCl3) δ 7.41 (d, J=7.4Hz, 1H), 7.34 (d, J=7.7Hz,
1H), 7.23 (d, J=7.7Hz, 5H), 7.06 (t, J=7.5Hz, 1H), 6.87 (d, J=7.8Hz, 1H), 6.56 (d, J=
3.5Hz, 1H), 4.15 (dd, J=53.7,10.5Hz, 2H), 3.26-3.17 (m, 4H), 2.62-2.51 (m, 1H), 2.36-
2.25 (m, 1H), 1.93-1.85 (m, 1H), 1.78 (s, 1H), 1.63-1.49 (m, 2H), 1.26 (dd, J=22.6,12.5Hz,
2H), 0.99 (dd, J=24.0,11.4Hz, 1H), 0.26 (s, 9H)；13C NMR (101MHz, CDCl3) δ 200.30,175.61,
144.30,140.45,137.47,133.78,129.98,128.07,127.83,127.51,126.34,124.61,123.12,
111.88,108.40,83.81,80.29,67.29,47.44,35.41,30.22,26.82,26.16,26.11,0.74.
Compound a nti-4n:1H NMR (400MHz, CDCl3) δ 7.37 (t, J=7.4Hz, 2H), 7.24 (s, 5H), 7.09
(t, J=7.4Hz, 1H), 6.88 (d, J=7.8Hz, 1H), 5.90 (s, 1H), 4.13 (dd, J=69.4,10.6Hz, 2H),
3.26-3.12 (m, 4H), 2.69 (t, J=13.2Hz, 1H), 2.27-2.13 (m, 2H), 2.07 (d, J=13.9Hz, 1H),
1.85-1.76 (m, 1H), 1.68 (d, J=13.0Hz, 1H), 1.31-1.17 (m, 2H), 0.21 (s, 9H)；13C NMR
(101MHz, CDCl3) δ 200.19,175.60,144.53,140.76,137.67,133.63,130.02,128.10,
127.76,127.54,126.13,124.99,122.98,110.93,108.36,83.42,80.23,67.34,47.45,
35.29,31.70,26.55,26.13,26.03,0.55.
Embodiment 15:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4o.Yield: 64%, anti: syn=50: 50.
Compound syn-4o:1H NMR (400MHz, CDCl3) δ 7.48 (d, J=6.4Hz, 2H), 7.42-7.24 (m,
10H), 7.05 (t, J=7.5Hz, 1H), 6.87 (d, J=7.8Hz, 1H), 6.16 (s, 1H), 4.15 (dd, J=59.1,
10.7Hz, 2H), 3.68 (s, 1H), 3.20 (d, J=9.7Hz, 3H), 2.59-2.43 (m, 1H), 2.34-2.21 (m, 1H),
2.18-2.01 (m, 1H), 1.66-1.57 (m, 1H)；13C NMR (101MHz, CDCl3) δ 199.33,175.55,144.74,
144.40,138.14,137.77,130.51,129.97,129.32,128.87,128.22,127.87,127.82,127.67,
125.77,125.16,122.91,108.13,93.30,87.88,84.54,67.81,54.04,36.72,26.08,24.38.
Compound a mi-4o:1H NMR (400MHz, CDCl3) δ 7.51 (d, J=7.2Hz, 1H), 7.36 (t, J=7.7Hz,
1H), 7.32-7.21 (m, 10H), 7.12 (t, J=7.4Hz, 1H), 6.81 (d, J=7.7Hz, 1H), 5.69 (s, 1H), 4.18
(dd, J=54.5,10.6Hz, 2H), 3.60 (d, J=7.5Hz, 1H), 3.19 (s, 3H), 2.69-2.47 (m, 3H), 2.34 (d,
J=6.6Hz, 1H)；13C NMR (101MHz, CDCl3) δ 199.37,175.56,144.74,144.40,138.14,137.76,
130.51,129.97,129.32,128.87,128.22,127.87,127.82,127.67,125.76,125.17,122.91,
108.13,93.28,87.87,84.55,67.81,54.04,36.72,26.08,24.38.
Embodiment 16:
Under the conditions of nitrogen protection, silver tetrafluoroborate and rhodium acetate are added in dry 10ml test tube.It is added 1.5ml's
40 DEG C are warming up to after methylene chloride, by six carbonyl of propilolic alcohol, two cobalt 1 (0.1mmol), benzylalcohol 2 (0.15mmol), 3- diazonium indoles
Ketone 3 (0.15mmol) is mixed and is dissolved in 1ml methylene chloride, and mixed solution is squeezed into examination using peristaltic pump in 2 hours
Guan Zhong continues stirring 0.5 hour after being added dropwise.After solvent is removed under reduced pressure in reaction solution, sampling and being dissolved in deuterated chloroform makes
With1H NMR measure d.r. value, will all solution mix after using column chromatographic isolation and purification (petroleum ether: ethyl acetate=70: 1~
20: 1), obtaining pure product 4p.Yield: 67%, anti: syn=47: 53.
Compound syn-4p:1H NMR (400MHz, CDCl3) δ 7.35 (dd, J=11.1,4.3Hz, 1H), 7.32-7.23
(m, 6H), 7.03 (t, J=7.4Hz, 1H), 6.86 (d, J=7.8Hz, 1H), 6.07 (d, J=1.8Hz, 1H), 4.14 (dd, J
=58.1,10.7Hz, 2H), 3.63 (dd, J=6.8,4.2Hz, 1H), 3.21 (s, 3H), 2.90-2.79 (m, 2H), 2.45-
2.34 (m, 1H), 2.20-2.10 (m, 1H), 2.07-1.96 (m, 1H), 1.65-1.58 (m, 2H), 1.50-1.40 (m, 3H),
0.96 (t, J=7.3Hz, 3H)；13C NMR (101MHz, CDCl3) δ 199.92,175.55,144.40,144.21,137.81,
130.10,129.93,128.20,127.79,127.64,125.60,125.23,122.83,108.05,101.73,87.30,
84.53,67.76,53.82,36.22,34.03,26.06,24.19,22.70,13.87.
Compound a nti-4p:1H NMR (400MHz, CDCl3) δ 7.45 (d, J=7.3Hz, 1H), 7.36-7.24 (m,
6H), 7.05 (t, J=7.5Hz, 1H), 6.79 (d, J=7.8Hz, 1H), 5.55 (s, 1H), 4.16 (dd, J=55.1,
10.7Hz, 2H), 3.53 (d, J=8.5Hz, 1H), 3.19 (s, 3H), 2.75-2.66 (m, 2H), 2.62-2.53 (m, 1H),
2.51-2.37 (m, 2H), 2.33-2.22 (m, 1H), 1.52-1.37 (m, 4H), 0.95 (t, J=7.0Hz, 3H)；13C NMR
(101MHz, CDCl3) δ 199.80,176.13,144.38,143.80,137.81,129.81,128.55,128.18,
127.75,127.60,126.41,124.28,122.69,108.50,101.54,87.18,84.68,67.79,54.49,
36.56,33.87,33.80,25.94,24.80,22.66,13.83.
Protection content of the invention is not limited to above embodiments.Without departing from the spirit and scope of the invention, originally
Field technical staff it is conceivable that variation and advantage be all included in the present invention, and with appended claims be protect
Protect range.
Claims (10)
1. one kind 3,3- disubstituted indole quinoline ketone and its derivative, which is characterized in that shown in its structure such as formula (I):
Wherein, Ar is phenyl, the phenyl of halogen substitution, the alkyl-substituted phenyl of C1-C5, the phenyl of C1-C5 alkoxy substitution, three
Phenyl, the naphthalene of phenyl, nitro substitution that methyl fluoride replaces；
R1For the alkyl of C4-C7, the alkoxy of C4-C7, halogen, Ethyl formate, nitro；
R2Phenyl, the alkyl-substituted phenyl of C1-C5, C1-C5 alcoxyl replaced for C1-C5 alkyl, trimethyl silicon substrate, phenyl, halogen
The phenyl that phenyl, the nitro of phenyl, trifluoromethyl substitution that base replaces replace；
N is 1-3.
2. 3,3- disubstituted indole quinoline ketone as described in claim 1 and its derivative, which is characterized in that
In the formula (I),
The Ar be phenyl, p-bromophenyl, p-fluorophenyl, rubigan, p-methylphenyl, p-methoxyphenyl, m-bromophenyl,
3,4- Dimethoxyphenyls, 3,4,5- trimethoxyphenyls, 4- trifluoromethyl, 4- nitrobenzophenone, 2- bromophenyl, 2- methyl
Phenyl or 1- naphthalene；
The R1For 5- methyl, 6- bromine, 6- chlorine, 6- nitro, 5- bromine, 5- methoxyl group, 6- methyl, 7- bromine, 6- Ethyl formate, 6- nitre
Base；
The R2For phenyl, p-bromophenyl, p-fluorophenyl, p-methylphenyl, p-methoxyphenyl, m-bromophenyl, 3,4- dimethoxy
Base phenyl, 3,4,5- trimethoxyphenyls, 4- trifluoromethyl, 4- nitrobenzophenone, 2- bromophenyl, 2- aminomethyl phenyl, 2- first
Phenyl, trimethyl silicon substrate, methyl, ethyl, n-propyl, normal-butyl；
The n is 1.
3. one kind 3, the synthetic method of 3- disubstituted indole quinoline ketone and its derivative, which is characterized in that in the method, with formula
(1) diazonium compound shown in substituted benzyl alcohol shown in two cobalt of (propilolic alcohol) six carbonyl, formula (2) shown in and formula (3) is raw material,
With Rh2(OAc)4And AgBF4Formula as described in claim 1 (I) is obtained by single step reaction in organic solvent for catalyst
3,3- disubstituted indole quinoline ketone and its derivative；
Shown in the reaction process of the synthetic reaction such as following formulas (II):
Wherein, Ar is phenyl, the phenyl of halogen substitution, the alkyl-substituted phenyl of C1-C5, the phenyl of C1-C5 alkoxy substitution, three
Phenyl, the naphthalene of phenyl, nitro substitution that methyl fluoride replaces；
R1For the alkyl of C4-C7, the alkoxy of C4-C7, halogen, Ethyl formate, nitro；
R2Phenyl, the alkyl-substituted phenyl of C1-C5, trifluoromethyl replaced for C1-C5 alkyl, trimethyl silicon substrate, phenyl, halogen
The phenyl that phenyl, the nitro of substituted phenyl, the substitution of C1-C5 alkoxy replace；
N is 1-3.
4. synthetic method as claimed in claim 3, which is characterized in that in the formula (I),
The Ar be phenyl, p-bromophenyl, p-fluorophenyl, rubigan, p-methylphenyl, p-methoxyphenyl, m-bromophenyl,
3,4- Dimethoxyphenyls, 3,4,5- trimethoxyphenyls, 4- trifluoromethyl, 4- nitrobenzophenone, 2- bromophenyl, 2- methyl
Phenyl or 1- naphthalene；
The R1For 5- methyl, 6- bromine, 6- chlorine, 6- nitro, 5- bromine, 5- methoxyl group, 6- methyl, 7- bromine, 6- Ethyl formate, 6- nitre
Base；
The R2For phenyl, p-bromophenyl, p-fluorophenyl, p-methylphenyl, p-methoxyphenyl, m-bromophenyl, 3,4- dimethoxy
Base phenyl, 3,4,5- trimethoxyphenyls, 4- trifluoromethyl, 4- nitrobenzophenone, 2- bromophenyl, 2- aminomethyl phenyl, 2- first
Phenyl, trimethyl silicon substrate, methyl, ethyl, n-propyl, normal-butyl；
The n is 1.
5. synthetic method as claimed in claim 3, which is characterized in that the temperature of the reaction is 0 DEG C -60 DEG C.
6. synthetic method as claimed in claim 3, which is characterized in that the time of the reaction is 1-12h.
7. synthetic method as claimed in claim 3, which is characterized in that two cobalt of (propilolic alcohol) six carbonyl shown in the formula (1),
The molar ratio of diazonium compound shown in substituted benzyl alcohol shown in formula (2) and formula (3) is (1.0~2.0): (1.0~2.0):
(1.0~2.0).
8. synthetic method as claimed in claim 3, which is characterized in that in the reaction, with (propilolic alcohol) six shown in formula (1)
On the basis of two cobalt of carbonyl, the catalyst Rh2(OAc)4Mole dosage be two cobalt of (propilolic alcohol) six carbonyl 0.5-2%, it is described
Catalyst AgBF4Mole dosage be two cobalt of (propilolic alcohol) six carbonyl 5.0-10%.
9. synthetic method as claimed in claim 8, which is characterized in that in the reaction, with (propilolic alcohol) six shown in formula (1)
On the basis of two cobalt of carbonyl, the catalyst Rh2(OAc)4Mole dosage be two cobalt of (propilolic alcohol) six carbonyl 1.0%, it is described to urge
Agent AgBF4Mole dosage be two cobalt of (propilolic alcohol) six carbonyl 10%.
10. synthetic method as claimed in claim 3, which is characterized in that the organic solvent is selected from DCM, DCE, CHCl3, first
Benzene, chlorobenzene any one or a few.
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