CN102153557B - Chiral center nitrogen heterocyclic carbine precursor salt with quadrol skeleton, synthetic method and application - Google Patents
Chiral center nitrogen heterocyclic carbine precursor salt with quadrol skeleton, synthetic method and application Download PDFInfo
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- 0 *[C@](*1C(C2)=**(c3ccc(*)cc3)=C1)[C@@](*)*2I Chemical compound *[C@](*1C(C2)=**(c3ccc(*)cc3)=C1)[C@@](*)*2I 0.000 description 5
- DLJPMMLGLJNPGO-SNVBAGLBSA-N CCOC(C[C@H](COc1c2cccc1C)C2=O)=O Chemical compound CCOC(C[C@H](COc1c2cccc1C)C2=O)=O DLJPMMLGLJNPGO-SNVBAGLBSA-N 0.000 description 1
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Abstract
The invention provides a chiral center nitrogen heterocyclic carbine precursor salt with a quadrol skeleton, a synthetic method and application. The precursor salt has a structural formula shown in the specifications, and can be prepared from cheap and readily-available chiral substituted diamine as an initial raw material by three-step synthesis, well applied to a polarity inversion reaction of catalytic aldehyde compounds, and used for preparing chiral benzopyrone compounds.
Description
Technical field
The present invention relates to a class chirality aza ring carbene precursor salt, synthetic method and purposes, i.e. a kind of multichiral center aza ring carbene precursor salt, synthetic method and purposes with quadrol skeleton.
Background technology
Recent two decades comes, N-heterocyclic carbine has obtained chemists' extensive concern [(a) D.Enders and T.Balensiefer as organic micromolecule catalyst, Acc.Chem.Res.2004,37,534. (b) D.Enders, O.Niemeier and A.Henseler, Chem.Rev.2007,107,5606. (c) V.Nair, S.Vellalath, B.P.Babu Chem.Soc.Rev.2008,37,2691. (d) E.M.Phillips, A.Chan, K.A.Scheidt, AldrichimicaActa 2009,42, and 55.].In this field, our latest developments a kind of multichiral center aza ring carbene precursor salt, synthetic method and purposes with quadrol skeleton.Set out take the commercial optical purity substituted ethylene diamine that cheaply is easy to get as raw material, can synthesizing series have the multichiral center aza ring carbene precursor salt of quadrol skeleton.Such precursor salt has in the pole reversal reaction of catalysis aldehyde compound preferably to be used.
Along with people to the reaching its maturity of chirality carbone catalyst research, N-heterocyclic carbine is obtained very large development as the organic micromolecule catalyst catalytic asymmetric reaction, some outstanding chirality carbone catalysts occurred successively, wherein, have and the triazole carbone catalyst of ring structure has been obtained huge success [(a) D.Enders, O.Niemeier, T.Balensiefer, Angew.Chem., Int.Ed.2006,45,1463. (b) M.He, J.R.Struble, J.W.Bode, J.Am.Chem.Soc.2006,128,8418. (c) Q.Liu, S.Perreault, and T.Rovis, J.Am.Chem.Soc.2008,130,14066. (d) D.A.DiRocco, K.M.Oberg, D.M.Dalton, and T.Rovis, J.Am.Chem.Soc.2009,131,10872.].But in general, the skeleton structure of N-heterocyclic carbine catalyzer is limited, and seeking the chirality N-heterocyclic carbine catalyzer of Novel framework and making it to be applicable to some reactions or more reactions and can have catalytic activity and the enantioselectivity of getting well is one of focus of chemist research always.
Chirality substituted ethylene diamine skeleton such as cyclohexanediamine, 1,2-diphenyl ethylene diamine skeleton etc. can provide outstanding chiral environment, chiral ligand, prothetic group with substituted ethylene diamine skeleton are deeply systematically studied [(a) E.J.Corey, C.M.Yu, S.S.Kim, J.Am.Chem.Soc.1989,111,5495; (b) H.Doucet, T.Ohkuma, K.Murata, T.Yokozawa, E.Kozawa, A.F.England, T.Ikariya, R.Noyori, Angew.Chem., Int.Ed.1998,37,1703. (c) M.S.Sigman, E.N.Jacobsen, J.Am.Chem.Soc.1998,120,4901.].In view of the substituted ethylene diamine compounds can provide outstanding chiral environment, and two kinds of equal wide material sources of enantiomorph, cheaply be easy to get, the inventor has been developed this type of and has been had multichiral center aza ring carbene precursor salt, synthetic method and the purposes of quadrol skeleton.
Summary of the invention
One of purpose of the present invention provides a kind of multichiral center aza ring carbene precursor salt with quadrol skeleton.
Two of purpose of the present invention provides the synthetic method of this kind aza ring carbene precursor salt.
Three of purpose of the present invention provides the purposes of this kind aza ring carbene precursor salt.
The invention provides a kind of multichiral center aza ring carbene precursor salt with quadrol skeleton, its structural formula is
Wherein, * represents chiral centre; R wherein
1Be aryl sulfonyl, substituted aryl alkylsulfonyl, C
1～C
16Alkyl sulphonyl, C
1～C
16Fluoro-alkyl alkylsulfonyl, aryl-acyl, substituted aryl acyl group, C
1～C
16Alkyl acyl or C
1～C
16The fluoro-alkyl acyl group; R
2, R
3Be selected from arbitrarily C
1～C
16The aryl of alkyl, aryl or replacement, perhaps R
2With R
2Between can connect into five to octatomic ring; Above-mentioned aryl is phenyl, naphthyl, pyridyl, furyl, thienyl, 9-anthryl or 9-phenanthryl; Substituting group on the described substituted aryl is selected from arbitrarily H, F, Cl, Br, I, C
1～C
16-oxyl, C
1～C
16Alkyl or C
1～C
16Fluoro-alkyl, nitro or amino; X is selected from arbitrarily Cl, Br, I, OTf, BF
4Or ClO
4Described Tf is trifyl.
The synthetic method of compound provided by the invention is to be set out to synthesize by the replacement diamines to make.Its reaction formula is as follows:
Solvent refers to organic solvent in the top reaction formula.
Further describing of this reaction is: in organic solvent, temperature is 0 ℃～150 ℃, has lactan and the general molecular formula H of chirality substituted ethylene diamine skeleton
2NNHR
3Hydrazine and Mel external cause reagent, orthoformate alkyl ester be raw material, reacted 10 minutes～5 days.
Described lactan and general molecular formula H with quadrol skeleton
2The mol ratio of the hydrazine of NNHR and Mel external cause reagent, orthoformate alkyl ester is followed successively by 1: 0.8～and 5: 1～5: 1～20.The mol ratio of recommendation response is: lactan: general molecular formula H
2The hydrazine of NNHR: Mel external cause reagent: orthoformate alkyl ester=1: 1～2: 1～2: 5～10.
Temperature of reaction is relevant with the time, and when temperature of reaction was relatively lower, the reaction times was just relatively long, and the recommendation response temperature is: 110～140 ℃.
R in the formula
1Be aryl sulfonyl, substituted aryl alkylsulfonyl, C
1～C
16Alkyl sulphonyl, C
1～C
16Fluoro-alkyl alkylsulfonyl, aryl-acyl, substituted aryl acyl group, C
1～C
16Alkyl acyl or C
1～C
16The fluoro-alkyl acyl group; R
2, R
3Can be selected from arbitrarily C as previously mentioned
1～C
16The aryl of alkyl, aryl or replacement, R
2With R
2Between can connect into five to octatomic ring; Above-mentioned aryl is phenyl, naphthyl, pyridyl, furyl, thienyl, 9-anthryl or 9-phenanthryl; Substituting group on the described substituted aryl is selected from arbitrarily H, F, Cl, Br, I, C
1～C
16-oxyl, C
1～C
16Alkyl or C
1～C
16Fluoro-alkyl, nitro or amino; X is selected from arbitrarily Cl, Br, I, OTf, BF
4Or ClO
4Described Tf is trifyl.
Described organic solvent can be chlorobenzene, benzene, tetracol phenixin, tetrahydrofuran (THF) (THF), ether, methylene dichloride, toluene, hexanaphthene, sherwood oil, acetone, pyridine, dioxane or acetonitrile.
The by product that reaction produces can separate smoothly with the method for column chromatography or recrystallization usually.Reaction product is a kind of multichiral center aza ring carbene precursor salt with quadrol skeleton of the present invention.Adopt the inventive method products therefrom-aza ring carbene precursor salt with the process recrystallization, thin-layer chromatography, the methods such as column chromatography are separated.Such as the method with recrystallization, recommending solvent is the mixed solvent of polar solvent and non-polar solvent.Recommend solvent to can be methanol-acetone, methyl alcohol-ethyl acetate, methylene dichloride-normal hexane, Virahol-sherwood oil, ethyl acetate-sherwood oil, ethyl acetate-normal hexane or Virahol-ethyl acetate-mixed solvents such as sherwood oil.With thin-layer chromatography and column chromatography method, used developping agent is the mixed solvent of polar solvent and non-polar solvent.Recommend solvent to can be Virahol-sherwood oil, ethyl acetate-sherwood oil, ethyl acetate-normal hexane or Virahol-ethyl acetate-mixed solvents such as sherwood oil, its volume ratio can be respectively: polar solvent: non-polar solvent=1: 0.1～500.For example: ethyl acetate: sherwood oil=1: 0.1～50, Virahol: sherwood oil=1: 0.1～500.
Multichiral center aza ring carbene precursor salt with quadrol skeleton of the present invention can be applied in the pole reversal reaction of carbene catalyzed aldehyde compound, can effectively prepare the Benzofurantone compound with chirality.
The invention provides a kind of brand-new N-heterocyclic carbine catalyst precursor salt, the simple synthetic method of this compound, mild condition, starting raw material cheaply are easy to get, and are suitable for industrialization.This part is compared with existing N-heterocyclic carbine catalyst precursor salt for the preparation of the Benzofurantone compound with chirality, and speed of reaction, productive rate, enantioselectivity are all good, have higher actual application value, are suitable for a large amount of productions.
Embodiment
To help to understand the present invention by following embodiment, but not limit content of the present invention.
Embodiment 1
(1) (5R, 6R)-5,6-phenylbenzene piperazine-2-ketone synthetic
Wherein, rt represents room temperature; Reflux represents to reflux.
The ethanol solution of the 20mL of ethyl bromoacetate 1.65g (1.1mL, 10mmol) slowly is added drop-wise to (1R, 2R)-1,2-phenylbenzene-1, the 30mL ethanol solution of 2-quadrol (2.12g, 10mmol) and NaOH 0.4g (10mmol) needs three hours approximately.Room temperature reaction two days, 80 degree reflux and spend the night.Removal of solvent under reduced pressure, column chromatography are separated (ethyl acetate/methanol=20/1) and are got product white solid 1.4 grams (5.55mmol, productive rate 54%).
P1 (5R, 6R)-5,6-phenylbenzene piperazine-2-ketone
1H?NMR(300MHz，CDCl
3)δ7.11-6.86(m，10H)，6.51(s，1H)，4.40(d，J＝9.0Hz，2H)，3.63(m，3H)，2.19(brs，1H).
13C?NMR(75MHz，CDCl
3)δ169.7，138.5，138.4，128.26，128.23，128.17，128.09，127.7，127.4，65.8，64.4，50.0.
(2) (5R, 6R)-5,6-phenylbenzene-4-p-toluenesulfonyl piperazine-2-ketone synthetic
Lactan 1.0g (4mmol) is dissolved in the 20mL pyridine (pyridine) minute three slow Tosyl chloride 0.99g (5.2mmol), reaction solution room temperature reactions 24 hours of adding.The reaction solution extracted with diethyl ether, the hydrochloric acid soln of a mol/L is washed, the organic phase anhydrous sodium sulfate drying.Removal of solvent under reduced pressure, column chromatography are separated (ethyl acetate/petroleum ether=1/1) and are got white solid 1.4g (3.44mmol, productive rate 87%).
P2 (5R, 6R)-5,6-phenylbenzene-4-p-toluenesulfonyl piperazine-2-ketone
[α]
D 20=+22.4 (c=1.0, CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 7.03-7.42 (m, 14H), 5.40 (s, 1H), 4.97 (s, 1H), 3.89 (dd, J=5.6,1.8Hz, 2H), 2.27 (s, 3H).
13C NMR (75MHz, CDCl
3) δ 167.5,143.5,139.8,137.3,135.3,129.4,128.9,128.3,128.1,127.3,127.1,61.3,59.2,45.0,21.5.IR (thin film): v
Max(cm
-1)=3431,3423,2914,1685,1344,1162,1096,1056,807,762,695,668,572; MS (ESI, m/z, rel.intensity) 407.2 (M+H); HRMS (MALDI) calculated value C
23H
22N
2O
3S (M+H): 407.1429; Measured value: 407.1424.m.p.178-179 ℃.
(3) N-heterocyclic carbine catalyst precursor salt is synthetic:
In the single neck bottle of 50mL, add lactan (0.81g, 2.0mmol), CH
2Cl
2(15mL), trimethoxy tetrafluoride boron salt (0.36g, 2.4mmol), stirring at room one day, TLC follows the tracks of reaction until raw material consumes substantially.Add hydrazine (2.4-12mmol), stirring at room two days, TLC follows the tracks of reaction until upper step raw material consumes substantially.CH is removed in decompression
2Cl
2, add chlorobenzene (20mL), triethyl orthoformate (2.5mL/day, 15mmol), 120 ℃ were refluxed three days.NMR tracks to reaction system without considerable change.Recover room temperature, removal of solvent under reduced pressure, behind the simple column chromatography (ethyl acetate), recrystallization (petrol ether/ethyl acetate) is purified.
P3(R
1＝Ts，R
2＝R
3＝Ph，X＝BF
4)
White solid.[α]
D 20=+121.3 ° of (c=0.20, CHCl
3).
1H NMR (300MHz, CDCl
3) δ 10.05 (s, 1H), 7.79 (d, J=17.7Hz, 2H), (7.47-7.24 m, 13H), 7.15 (d, J=8.1Hz, 2H), (7.02 d, J=7.5Hz, 2H), 6.78 (s, 1H), 5.79 (d, J=1.8Hz, 1H), (5.13 d, J=17.4Hz, 1H), 4.48 (d, J=17.7Hz, 1H), 2.38 (s, 3H);
19F NMR (282MHz, CDCl
3): δ-150,2 ,-150.3;
13C NMR (75MHz, CDCl
3) δ 149.3,144.7,139.7,135.2,134.3,133.0,131.4,130.2,130.0,129.7,129.3,127.22,127.17,126.4,120.7,62.1,61.6,38.0,21.5; IR (thin film): v
Max(cm
-1)=3064,2918,1595,1455,1353,1162,1055,760,689; MS (ESI, m/z, rel.intensity) 507.1 (M-BF
4); HRMS (ESI) calculated value C
30H
27N
4O
2S (M-BF
4): 507.1849; Measured value: 507.1851.m.p.213-216 ℃.
P4(R
1＝Ts，R
2＝Ph，R
3＝4-OMePh，X＝BF
4)
Light yellow solid.[α]
D 20=+24.3 ° of (c=0.20, CHCl
3).
1H NMR (300MHz, CDCl
3) δ 10.00 (s, 1H), 7.72 (d, J=8.7Hz, 2H), 7.36-6.93 (m, 16H), 6.77 (s, 1H), 5.80 (s, 1H), 5.09 (d, J=17.4Hz, 1H), 4.46 (d, J=17.4Hz, 1H), 3.80 (s, 3H), 2.40 (s, 3H);
19FNMR (282MHz, CDCl
3): δ-150,2 ,-150.3;
13C NMR (75MHz, CDCl
3) δ 161.6,148.9,144.6,138.9,135.4,135.2,133.0,130.0,129.61,129.58,129.3,127.4,127.2,126.3,122.3,115.2,61.9,61.65,55.7,37.9,21.5; IR (thin film): v
Max(cm
-1)=3059,2918,2842,1597,1520,1454,1352,1260,1162,1057,835,729,699; MS (ESI, m/z, rel.intensity) 537.5 (M-BF
4); HRMS (ESI) calculated value C
31H
29N
4O
3S (M-BF
4): 537.1955; Measured value: 537.1957.m.p.124-126 ℃.
P5(R
1＝Ts，R
2＝Ph，R
3＝2，4，6-(Me)
3Ph，X＝BF
4)
White solid.[α]
D 20=+68.4 ° of (c=0.20, CHCl
3).
1H NMR (300MHz, CDCl
3) δ 9.77 (s, 1H), 7.42-7.31 (m, 10H), 7.19 (d, J=6.3Hz, 2H), 7.04 (d, J=5.7Hz, 2H), (6.98 s, 3H), 5.86 (s, 1H), (5.10 d, J=17.4Hz, 1H), 4.53 (d, J=17.4Hz, 1H), 2.43 (s, 3H), (2.33 s, 3H), 1.96 (s, 6H);
19F NMR (282MHz, CDCl
3): δ-150,1 ,-150.2;
13C NMR (75MHz, CDCl
3) δ 149.7,144.7,144.4,142.6,135.4,135.2,133.2,130.0,129.8,129.69,129.65,129.3,127.2,127.1,126.1,62.3,61.7,38.1,21.6,21.2,17.0; IR (thin film): v
Max(cm
-1)=3065,2924,2854,1651,1597,1579,1500,1450,1354,1267,1162,1059,930,815,757,730,699; MS (ESI, m/z, rel.intensity) 549.4 (M-BF
4); HRMS (ESI) calculated value C
33H
33N
4O
2S (M-BF
4): 549.2319; Measured value: 549.2315.m.p.221-223 ℃.
P6(R
1＝Ts，R
2＝Ph，R
3＝3，5-(CF
3)
2Ph，X＝BF
4)
(and enantiomorph)
White solid.[α]
D 20=+31.7 ° of (c=0.20, CHCl
3).
1H NMR (300MHz, CDCl
3) δ 10.15 (s, 1H), 8.41 (s, 2H), (8.00 s, 1H), 7.39-7.10 (m, 14H), (6.59 d, J=3.3Hz, 1H), 5.79 (d, J=3.3Hz, 1H), 5.13 (d, J=17.7Hz, 1H), 4.53 (d, J=17.7Hz, 1H), 2.39 (s, 3H);
19F NMR (282MHz, CDCl
3): δ-63.5 ,-150,1 ,-150.1;
13C NMR (75MHz, CDCl
3) δ 150.4,144.8,141.5,135.8,135.3,134.3,134.1,133.8,133.1,130.1,130.0,129.8,129.5,129.4,127.5,127.2,126.9,121.95,121.92,62.9,61.6,38.1,21.5; IR (thin film): v
Max(cm
-1)=3068,2922,1596,1538,1455,1367,1281,1144,1074,898,814,756,698; MS (ESI, m/z, rel.intensity) 643.2 (M-BF
4); HRMS (ESI) calculated value C
32H
25F
6N
4O
2S (M-BF
4): 643.1597; Measured value: 643.1597.m.p.162-163 ℃.
P7 (R
1=Ts, R
2=Ph, R
3=9-anthryl, X=BF
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.01 (s, 1H), 7.75 (d, J=17.7Hz, 2H), (7.43-7.21 m, 17H), 7.12 (d, J=8.1Hz, 2H), (7.00 d, J=7.5Hz, 2H), 6.74 (s, 1H), 5.75 (d, J=1.8Hz, 1H), (5.10 d, J=17.4Hz, 1H), 4.45 (d, J=17.7Hz, 1H), 2.34 (s, 3H); MS (ESI, m/z, rel.intensity) 607.5 (M-BF
4); HRMS (ESI) calculated value C
38H
32N
4O
2S (M-BF
4): 607.2162; Measured value: 607.2160.
P8 (R
1=Ts, R
2=Ph, R
3=9-phenanthryl, X=BF
4)
(and enantiomorph)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.09 (s, 1H), 7.78 (d, J=17.7Hz, 2H), (7.47-7.23 m, 17H), 7.16 (d, J=8.1Hz, 2H), (7.04 d, J=7.5Hz, 2H), 6.78 (s, 1H), 5.79 (d, J=1.8Hz, 1H), (5.13 d, J=17.4Hz, 1H), 4.48 (d, J=17.7Hz, 1H), 2.36 (s, 3H); MS (ESI, m/z, rel.intensity) 607.6 (M-BF
4); HRMS (ESI) calculated value C
38H
31N
4O
2S (M-BF
4): 607.2162; Measured value: 607.2163.
P9(R
1＝Ts，R
2＝Ph，R
3＝4-MePh，X＝BF
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.79 (s, 1H), 7.43-7.30 (m, 10H), (7.17 d, J=6.3Hz, 2H), 7.02 (d, J=5.7Hz, 2H), 6.97 (s, 3H), (5.84 s, 1H), 5.11 (d, J=17.4Hz, 1H), 4.52 (d, J=17.4Hz, 1H), (2.43 s, 3H), 2.31 (s, 3H); MS (ESI, m/z, rel.intensity) 521.6 (M-BF
4); HRMS (ESI) calculated value C
31H
29N
4O
2S (M-BF
4): 521.2006; Measured value: 521.2004.
P10(R
1＝Ts，R
2＝Ph，R
3＝4-NO
2Ph，X＝BF
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.05 (s, 1H), 8.24 (d, J=8.7Hz, 2H), 8.10 (d, J=8.5Hz, 2H), (7.76-7.33 m, 14H), 6.87 (s, 1H), (5.89 s, 1H), 5.19 (d, J=17.4Hz, 1H), 4.48 (d, J=17.4Hz, 1H), 2.40 (s, 3H); MS (ESI, m/z, rel.intensity) 552.6 (M-BF
4); HRMS (ESI) calculated value C
30H
26N
5O
4S (M-BF
4): 552.1700; Measured value: 521.1702.
P11 (R
1=Ts, R
2=Ph, R
3=cyclohexyl, X=BF
4)
(and enantiomorph)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.65 (s, 1H), 7.43 (d, J=17.1Hz, 2H), 7.23-7.01 (m, 13H), 6.85 (d, J=8.1Hz, 2H), 6.72 (d, J=7.5Hz, 2H), 6.58 (s, 1H), 5.70 (d, J=1.8Hz, 1H), 5.03 (d, J=17.4Hz, 1H), 4.31 (d, J=17.7Hz, 1H), 2.31 (s, 3H), 1.49-1.58 (m, 5H), (1.42-1.45 m, 2H), 1.31-1.34 (m, 2H), 1.23-1.25 (m, 2H); MS (ESI, m/z, rel.intensity) 513.6 (M-BF
4); HRMS (ESI) calculated value C
30H
33N
4O
2S (M-BF
4): 513.2319; Measured value: 513.2318.
P12(R
1＝Ts，R
2-R
2＝(CH
2)
4，R
3＝Ph，X＝BF
4)
White solid.
1HNMR (300MHz, CDCl
3) δ 10.01 (s, 1H), 7.69 (d, J=17.7Hz, 2H), 7.38-7.23 (m, 5H), 7.13 (d, J=8.1Hz, 2H), 6.76 (s, 1H), (5.72 d, J=1.8Hz, 1H), 5.11 (d, J=17.4Hz, 1H), 4.41 (d, J=17.7Hz, 1H), 2.68-2.74 (m, 1H), (2.56-2.62 m, 2H), 2.41 (s, 3H), 2.26-2.24 (m, 1H), (1.84-1.77 m, 2H), 1.30-1.24 (m, 2H), 1.22-1.14 (m, 2H); MS (ESI, m/z, rel.intensity) 409.2 (M-BF
4); HRMS (ESI) calculated value C
22H
25N
4O
2S (M-BF
4): 406.1693; Measured value: 406.1692.
P13(R
1＝Ac，R
2＝R
3＝Ph，X＝BF
4)
(and enantiomorph)
White solid.
1H NMR (300MHz, CDCL
3) δ 10.01 (s, 1H), 7.69 (d, J=17.7Hz, 2H), 7.42-7.21 (m, 11H), 7.13 (d, J=8.1Hz, 2H), 6.75 (s, 1H), (5.74 d, J=1.8Hz, 1H), 5.10 (d, J=17.4Hz, 1H), 4.43 (d, J=17.7Hz, 1H), 2.24 (s, 3H); MS (ESI, m/z, rel.intensity) 395.2 (M-BF
4); HRMS (ESI) calculated value C
25H
23N
4O (M-BF
4): 395.1866; Measured value: 395.1868.
P14(R
1＝Ac，R
2＝Ph，R
3＝4-OMePh，X＝BF
4)
Light yellow solid.
1H NMR (300MHz, CDCl
3) δ 9.95 (s, 1H), 7.65 (d, J=8.7Hz, 2H), 7.31-6.91 (m, 12H), 6.72 (s, 1H), 5.74 (s, 1H), 5.13 (d, J=17.4Hz, 1H), 4.35 (d, J=17.4Hz, 1H), 3.76 (s, 3H), 2.19 (s, 3H); MS (ESI, m/z, rel.intensity) 425.2 (M-BF
4); HRMS (ESI) calculated value C
25H
23N
4O (M-BF
4): 425.1972; Measured value: 425.1973.
P15(R
1＝Ac，R
2＝Ph，R
3＝2，4，6-(Me)
3Ph，X＝BF
4)
(and enantiomorph)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.73 (s, 1H), 7.40-7.30 (m, 8H), 7.16 (d, J=6.3Hz, 2H), 7.02 (d, J=5.7Hz, 2H), (6.95 s, 1H), 5.83 (s, 1H), (5.10 d, J=17.4Hz, 1H), 4.53 (d, J=17.4Hz, 1H), 2.38 (s, 3H), (2.27 s, 3H), 1.96 (s, 6H); MS (ESI, m/z, rel.intensity) 437.5 (M-BF
4); HRMS (ESI) calculated value C
28H
29N
4O (M-BF
4): 437.2336; Measured value: 437.2335.
P16(R
1＝Ac，R
2＝Ph，R
3＝3，5-(CF
3)
2Ph，X＝BF
4)
(and enantiomorph)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.13 (s, 1H), 8.41 (s, 2H), (8.01 s, 1H), 7.36-7.09 (m, 14H), (6.57 d, J=3.3Hz, 1H), 5.75 (d, J=3.3Hz, 1H), 5.11 (d, J=17.7Hz, 1H), 4.51 (d, J=17.7Hz, 1H), 2.24 (s, 3H); MS (ESI, m/z, rel.intensity) 531.5 (M-BF
4); HRMS (ESI) calculated value C
27H
21F
6N
4O (M-BF
4): 531.1614; Measured value: 531.1615.
P17(R
1＝Boc，R
2＝Ph，R
3＝2，4，6-(Me)
3Ph，X＝BF
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.74 (s, 1H), 7.41-7.31 (m, 8H), 7.16 (d, J=6.3Hz, 2H), 7.03 (d, J=5.7Hz, 2H), (6.96 s, 1H), 5.81 (s, 1H), (5.12 d, J=17.4Hz, 1H), 4.54 (d, J=17.4Hz, 1H), 2.37 (s, 3H), (1.98 s, 6H), 1.56 (s, 9H); MS (ESI, m/z, rel.intensity) 495.5M-BF
4); HRMS (ESI) calculated value C
31H
35N
4O
2(M-BF
4): 495.2755; Measured value: 495.2754.
P18 (R
1=trifluoroacetyl group, R
2=Ph, R
3=2,4,6-(Me)
3Ph, X=BF
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.93 (s, 1H), 7.45-7.34 (m, 8H), (7.19 d, J=6.3Hz, 2H), 7.05 (d, J=5.7Hz, 2H), 6.95 (s, 1H), (5.89 s, 1H), 5.15 (d, J=17.4Hz, 1H), 4.57 (d, J=17.4Hz, 1H), (2.38 s, 3H), 1.96 (s, 6H); MS (ESI, m/z, rel.intensity) 491.5 (M-BF
4); HRMS (ESI) calculated value C
28H
29N
4O (M-BF
4): 491.2053; Measured value: 491.2054.
P19 (R
1=trifyl, R
2=Ph, R
3=2,4,6-(Me)
3Ph, X=BF
4)
(and enantiomorph)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.85 (s, 1H), 7.44-7.31 (m, 8H), (7.19 d, J=6.3Hz, 2H), 7.08 (d, J=5.7Hz, 2H), 6.99 (s, 1H), (5.86 s, 1H), 5.14 (d, J=17.4Hz, 1H), 4.55 (d, J=17.4Hz, 1H), (2.38 s, 3H), 1.98 (s, 6H); MS (ESI, m/z, rel.intensity) 527.5 (M-BF
4); HRMS (ESI) calculated value C
28H
29N
4O (M-BF
4): 527.1723; Measured value: 527.1724.
P20 (R
1=ten seven fluoro-octane alkylsulfonyls, R
2=Ph, R
3=2,4,6-(Me)
3Ph, X=BF
4)
White solid.
1HNMR (300MHz, CDCl
3) δ 9.83 (s, 1H), 7.44-7.31 (m, 8H), (7.18 d, J=6.3Hz, 2H), 7.05 (d, J=5.7Hz, 2H), 6.97 (s, 1H), (5.83 s, 1H), 5.12 (d, J=17.4Hz, 1H), 4.54 (d, J=17.4Hz, 1H), (2.38 s, 3H), 1.98 (s, 6H); MS (ESI, m/z, rel.intensity) 877.5 (M-BF
4); HRMS (ESI) calculated value C
28H
29N
4O (M-BF
4): 877.1500; Measured value: 877.1501.
P21(R
1＝Ts，R
2＝R
3＝Ph，X＝Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.05 (s, 1H), 7.79 (d, J=17.7Hz, 2H), (7.47-7.24 m, 13H), 7.15 (d, J=8.1Hz, 2H), (7.02 d, J=7.5Hz, 2H), 6.78 (s, 1H), 5.79 (d, J=1.8Hz, 1H), (5.13 d, J=17.4Hz, 1H), 4.48 (d, J=17.7Hz, 1H), 2.38 (s, 3H);
19F NMR (282MHz, CDCl
3): δ-150,2 ,-150.3; MS (ESI, m/z, rel.intensity) 507.1 (M-Cl); HRMS (ESI) calculated value C
30H
27N
4O
2S (M-Cl): 507.1849; Measured value: 507.1850.
P22(R
1＝Ts，R
2＝Ph，R
3＝4-OMePh，X＝Cl)
Light yellow solid.
1H NMR (300MHz, CDCl
3) δ 10.00 (s, 1H), 7.72 (d, J=8.7Hz, 2H), 7.36-6.93 (m, 16H), 6.77 (s, 1H), 5.80 (s, 1H), 5.09 (d, J=17.4Hz, 1H), 4.46 (d, J=17.4Hz, 1H), 3.80 (s, 3H), 2.40 (s, 3H); MS (ESI, m/z, rel.intensity) 537.5 (M-Cl); HRMS (ESI) calculated value C
31H
29N
4O
3S (M-Cl): 537.1955; Measured value: 537.1957.
P23(R
1＝Ts，R
2＝Ph，R
3＝2，4，6-(Me)
3Ph，X＝Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.77 (s, 1H), 7.42-7.31 (m, 10H), 7.19 (d, J=6.3Hz, 2H), 7.04 (d, J=5.7Hz, 2H), (6.98 s, 3H), 5.86 (s, 1H), (5.10 d, J=17.4Hz, 1H), 4.53 (d, J=17.4Hz, 1H), 2.43 (s, 3H), (2.33 s, 3H), 1.96 (s, 6H); MS (ESI, m/z, rel.intensity) 549.4 (M-Cl); HRMS (ESI) calculated value C
33H
33N
4O
2S (M-Cl): 549.2319; Measured value: 549.2315.
P24(R
1＝Ts，R
2＝Ph，R
3＝3，5-(CF
3)
2Ph，X＝Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.15 (s, 1H), 8.41 (s, 2H), (8.00 s, 1H), 7.39-7.10 (m, 14H), (6.59 d, J=3.3Hz, 1H), 5.79 (d, J=3.3Hz, 1H), 5.13 (d, J=17.7Hz, 1H), 4.53 (d, J=17.7Hz, 1H), 2.39 (s, 3H); MS (ESI, m/z, rel.intensity) 643.2 (M-Cl); HRMS (ESI) calculated value C
32H
25F
6N
4O
2S (M-Cl): 643.1597; Measured value: 643.1597.
P25 (R
1=Ts, R
2=Ph, R
3=9-anthryl, X=Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.01 (s, 1H), 7.75 (d, J=17.7Hz, 2H), (7.43-7.21 m, 17H), 7.12 (d, J=8.1Hz, 2H), (7.00 d, J=7.5Hz, 2H), 6.74 (s, 1H), 5.75 (d, J=1.8Hz, 1H), (5.10 d, J=17.4Hz, 1H), 4.45 (d, J=17.7Hz, 1H), 2.34 (s, 3H); MS (ESI, m/z, rel.intensity) 607.5 (M-Cl); HRMS (ESI) calculated value C
38H
32N
4O
2S (M-Cl): 607.2162; Measured value: 607.2160.
P26 (R=Ph, R
1=Ts, R
2=9-phenanthryl, X=Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.09 (s, 1H), 7.78 (d, J=17.7Hz, 2H), (7.47-7.23 m, 17H), 7.16 (d, J=8.1Hz, 2H), (7.04 d, J=7.5Hz, 2H), 6.78 (s, 1H), 5.79 (d, J=1.8Hz, 1H), (5.13 d, J=17.4Hz, 1H), 4.48 (d, J=17.7Hz, 1H), 2.36 (s, 3H); MS (ESI, m/z, rel.intensity) 607.6 (M-Cl); HRMS (ESI) calculated value C
38H
31N
4O
2S (M-Cl): 607.2162; Measured value: 607.2163.
P27(R
1＝Ts，R
2＝Ph，R
3＝4-MePh，X＝Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.79 (s, 1H), 7.43-7.30 (m, 10H), (7.17 d, J=6.3Hz, 2H), 7.02 (d, J=5.7Hz, 2H), 6.97 (s, 3H), (5.84 s, 1H), 5.11 (d, J=17.4Hz, 1H), 4.52 (d, J=17.4Hz, 1H), (2.43 s, 3H), 2.31 (s, 3H); MS (ESI, m/z, rel.intensity) 521.6 (M-Cl); HRMS (ESI) calculated value C
31H
29N
4O
2S M-Cl): 521.2006; Measured value: 521.2004.
P28(R
1＝Ts，R
2＝Ph，R
3＝4-NO
2Ph，X＝Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.05 (s, 1H), 8.24 (d, J=8.7Hz, 2H), 8.10 (d, J=8.5Hz, 2H), (7.76-7.33 m, 14H), 6.87 (s, 1H), (5.89 s, 1H), 5.19 (d, J=17.4Hz, 1H), 4.48 (d, J=17.4Hz, 1H), 2.40 (s, 3H); MS (ESI, m/z, rel.intensity) 552.6 (M-Cl); HRMS (ESI) calculated value C
30H
26N
5O
4S (M-Cl): 552.1700; Measured value: 521.1702.
P29 (R
1=Ts, R
2=Ph, R
3=cyclohexyl, X=Cl)
White solid.
1HNMR (300MHz, CDCl
3) δ 9.65 (s, 1H), 7.43 (d, J=17.1Hz, 2H), 7.23-7.01 (m, 13H), 6.85 (d, J=8.1Hz, 2H), 6.72 (d, J=7.5Hz, 2H), 6.58 (s, 1H), 5.70 (d, J=1.8Hz, 1H), 5.03 (d, J=17.4Hz, 1H), 4.31 (d, J=17.7Hz, 1H), 2.31 (s, 3H), 1.49-1.58 (m, 5H), (1.42-1.45 m, 2H), 1.31-1.34 (m, 2H), 1.23-1.25 (m, 2H); MS (ESI, m/z, rel.intensity) 513.6 (M-Cl); HRMS (ESI) calculated value C
30H
33N
4O
2S (M-Cl): 513.2319; Measured value: 513.2318.
P30(R
1＝Ts，R
2-R
2＝(CH
2)
4，R
3＝Ph，X＝Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.01 (s, 1H), 7.69 (d, J=17.7Hz, 2H), 7.38-7.23 (m, 5H), 7.13 (d, J=8.1Hz, 2H), 6.76 (s, 1H), (5.72 d, J=1.8Hz, 1H), 5.11 (d, J=17.4Hz, 1H), 4.41 (d, J=17.7Hz, 1H), 2.68-2.74 (m, 1H), (2.56-2.62 m, 2H), 2.41 (s, 3H), 2.26-2.24 (m, 1H), (1.84-1.77 m, 2H), 1.30-1.24 (m, 2H), 1.22-1.14 (m, 2H); MS (ESI, m/z, rel.intensity) 409.2 (M-Cl); HRMS (ESI) calculated value C
22H
25N
4O
2S (M-Cl): 409.1693; Measured value: 409.1692.
P31(R
1＝Ac，R
2＝R
3＝Ph，X＝Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.01 (s, 1H), 7.69 (d, J=17.7Hz, 2H), 7.42-7.21 (m, 11H), 7.13 (d, J=8.1Hz, 2H), 6.75 (s, 1H), (5.74 d, J=1.8Hz, 1H), 5.10 (d, J=17.4Hz, 1H), 4.43 (d, J=17.7Hz, 1H), 2.24 (s, 3H); MS (ESI, m/z, rel.intensity) 395.2 (M-Cl); HRMS (ESI) calculated value C
25H
23N
4O (M-Cl): 395.1866; Measured value: 395.1868.
P32(R
1＝Ac，R
2＝Ph，R
3＝4-OMePh，X＝Cl)
Light yellow solid.
1H NMR (300MHz, CDCl
3) δ 9.95 (s, 1H), 7.65 (d, J=8.7Hz, 2H), 7.31-6.91 (m, 12H), 6.72 (s, 1H), 5.74 (s, 1H), 5.13 (d, J=17.4Hz, 1H), 4.35 (d, J=17.4Hz, 1H), 3.76 (s, 3H), 2.19 (s, 3H); MS (ESI, m/z, rel.intensity) 425.2 (M-Cl); HRMS (ESI) calculated value C
25H
23N
4O (M-Cl): 425.1972; Measured value: 425.1973.
P33(R
1＝Ac，R
2＝Ph，R
3＝2，4，6-(Me)
3Ph，X＝Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.73 (s, 1H), 7.40-7.30 (m, 8H), 7.16 (d, J=6.3Hz, 2H), 7.02 (d, J=5.7Hz, 2H), (6.95 s, 1H), 5.83 (s, 1H), (5.10 d, J=17.4Hz, 1H), 4.53 (d, J=17.4Hz, 1H), 2.38 (s, 3H), (2.27 s, 3H), 1.96 (s, 6H); MS (ESI, m/z, rel.intensity) 437.5 (M-Cl); HRMS (ESI) calculated value C
28H
29N
4O (M-Cl): 437.2336; Measured value: 437.2335.
P34(R
1＝Ac，R
2＝Ph，R
3＝3，5-(CF
3)
2Ph，X＝Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.13 (s, 1H), 8.41 (s, 2H), (8.01 s, 1H), 7.36-7.09 (m, 14H), (6.57 d, J=3.3Hz, 1H), 5.75 (d, J=3.3Hz, 1H), 5.11 (d, J=17.7Hz, 1H), 4.51 (d, J=17.7Hz, 1H), 2.24 (s, 3H); MS (ESI, m/z, rel.intensity) 531.5 (M-Cl); HRMS (ESI) calculated value C
27H
21F
6N
4O (M-Cl): 531.1614; Measured value: 531.1615.
P35(R
1＝Boc，R
2＝Ph，R
3＝2，4，6-(Me)
3Ph，X＝Cl)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.74 (s, 1H), 7.41-7.31 (m, 8H), 7.16 (d, J=6.3Hz, 2H), 7.03 (d, J=5.7Hz, 2H), (6.96 s, 1H), 5.81 (s, 1H), (5.12 d, J=17.4Hz, 1H), 4.54 (d, J=17.4Hz, 1H), 2.37 (s, 3H), (1.98 s, 6H), 1.56 (s, 9H); MS (ESI, m/z, rel.intensity) 495.5 (M-Cl); HRMS (ESI) calculated value C
31H
35N
4O
2(M-Cl): 495.2755; Measured value: 495.2754.
P36(R
1＝Ts，R
2＝R
3＝Ph，X＝ClO
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.05 (s, 1H), 7.79 (d, J=17.7Hz, 2H), (7.47-7.24 m, 13H), 7.15 (d, J=8.1Hz, 2H), (7.02 d, J=7.5Hz, 2H), 6.78 (s, 1H), 5.79 (d, J=1.8Hz, 1H), (5.13 d, J=17.4Hz, 1H), 4.48 (d, J=17.7Hz, 1H), 2.38 (s, 3H);
19F NMR (282MHz, CDCl3): δ-150,2 ,-150.3; MS (ESI, m/z, rel.intensity) 507.1 (M-ClO
4); HRMS (ESI) calculated value C
30H
27N
4O
2S (M-ClO
4): 507.1849; Measured value: 507.1850.
P37(R
1＝Ts，R
2＝Ph，R
3＝4-OMePh，X＝ClO
4)
Light yellow solid.
1H NMR (300MHz, CDCl
3) δ 10.00 (s, 1H), 7.72 (d, J=8.7Hz, 2H), 7.36-6.93 (m, 16H), 6.77 (s, 1H), 5.80 (s, 1H), 5.09 (d, J=17.4Hz, 1H), 4.46 (d, J=17.4Hz, 1H), 3.80 (s, 3H), 2.40 (s, 3H); MS (ESI, m/z, rel.intensity) 537.5 (M-ClO
4); HRMS (ESI) calculated value C
31H
29N
4O
3S (M-ClO
4): 537.1955; Measured value: 537.1957.
P38(R
1＝Ts，R
2＝Ph，R
3＝2，4，6-(Me)
3Ph，X＝ClO
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.77 (s, 1H), 7.42-7.31 (m, 10H), 7.19 (d, J=6.3Hz, 2H), 7.04 (d, J=5.7Hz, 2H), (6.98 s, 3H), 5.86 (s, 1H), (5.10 d, J=17.4Hz, 1H), 4.53 (d, J=17.4Hz, 1H), 2.43 (s, 3H), (2.33 s, 3H), 1.96 (s, 6H); MS (ESI, m/z, rel.intensity) 549.4 (M-ClO
4); HRMS (ESI) calculated value C
33H
33N
4O
2S (M-ClO
4): 549.2319; Measured value: 549.2315.
P39(R
1＝Ts，R
2＝Ph，R
3＝3，5-(CF
3)
2Ph，X＝ClO
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.15 (s, 1H), 8.41 (s, 2H), (8.00 s, 1H), 7.39-7.10 (m, 14H), (6.59 d, J=3.3Hz, 1H), 5.79 (d, J=3.3Hz, 1H), 5.13 (d, J=17.7Hz, 1H), 4.53 (d, J=17.7Hz, 1H), 2.39 (s, 3H); MS (ESI, m/z, rel.intensity) 643.2 (M-ClO
4); HRMS (ESI) calculated value C
32H
25F
6N
4O
2S (M-ClO
4): 643.1597; Measured value: 643.1597.
P40 (R
1=Ts, R
2=Ph, R
3=9-anthryl, X=ClO
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.01 (s, 1H), 7.75 (d, J=17.7Hz, 2H), (7.43-7.21 m, 17H), 7.12 (d, J=8.1Hz, 2H), (7.00 d, J=7.5Hz, 2H), 6.74 (s, 1H), 5.75 (d, J=1.8Hz, 1H), (5.10 d, J=17.4Hz, 1H), 4.45 (d, J=17.7Hz, 1H), 2.34 (s, 3H); MS (ESI, m/z, rel.intensity) 607.5 (M-ClO
4); HRMS (ESI) calculated value C
38H
32N
4O
2S (M-ClO
4): 607.2162; Measured value: 607.2160.
P41 (R
1=Ts, R
2=Ph, R
3=9-phenanthryl, X=ClO
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.09 (s, 1H), 7.78 (d, J=17.7Hz, 2H), (7.47-7.23 m, 17H), 7.16 (d, J=8.1Hz, 2H), (7.04 d, J=7.5Hz, 2H), 6.78 (s, 1H), 5.79 (d, J=1.8Hz, 1H), (5.13 d, J=17.4Hz, 1H), 4.48 (d, J=17.7Hz, 1H), 2.36 (s, 3H); MS (ESI, m/z, rel.intensity) 607.6 (M-ClO
4); HRMS (ESI) calculated value C
38H
31N
4O
2S (M-ClO
4): 607.2162; Measured value: 607.2163.
P42(R
1＝Ts，R
2＝Ph，R
3＝4-MePh，X＝ClO
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.79 (s, 1H), 7.43-7.30 (m, 10H), (7.17 d, J=6.3Hz, 2H), 7.02 (d, J=5.7Hz, 2H), 6.97 (s, 3H), (5.84 s, 1H), 5.11 (d, J=17.4Hz, 1H), 4.52 (d, J=17.4Hz, 1H), (2.43 s, 3H), 2.31 (s, 3H); MS (ESI, m/z, rel.intensity) 521.6 (M-ClO
4); HRMS (ESI) calculated value C
31H
29N
4O
2S (M-ClO
4): 521.2006; Measured value: 521.2004.
P43(R
1＝Ts，R
2＝Ph，R
3＝4-NO
2Ph，X＝ClO
4)
White solid.
1H NMR (300MHz, CDCL
3) δ 10.05 (s, 1H), 8.24 (d, J=8.7Hz, 2H), 8.10 (d, J=8.5Hz, 2H), (7.76-7.33 m, 14H), 6.87 (s, 1H), (5.89 s, 1H), 5.19 (d, J=17.4Hz, 1H), 4.48 (d, J=17.4Hz, 1H), 2.40 (s, 3H); MS (ESI, m/z, rel.intensity) 552.6 (M-ClO
4); HRMS (ESI) calculated value C
30H
26N
5O
4S (M-ClO4): 552.1700; Measured value: 521.1702.
P44 (R
1=Ts, R
2=Ph, R
3=cyclohexyl, X=ClO
4)
(and enantiomorph)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.65 (s, 1H), 7.43 (d, J=17.1Hz, 2H), 7.23-7.01 (m, 13H), 6.85 (d, J=8.1Hz, 2H), 6.72 (d, J=7.5Hz, 2H), 6.58 (s, 1H), 5.70 (d, J=1.8Hz, 1H), 5.03 (d, J=17.4Hz, 1H), 4.31 (d, J=17.7Hz, 1H), 2.31 (s, 3H), 1.49-1.58 (m, 5H), (1.42-1.45 m, 2H), 1.31-1.34 (m, 2H), 1.23-1.25 (m, 2H); MS (ESI, m/z, rel.intensity) 513.6 (M-ClO
4); HRMS (ESI) calculated value C
30H
33N
4O
2S (M-ClO
4): 513.2319; Measured value: 513.2318.
P45(R
1＝Ts，R
2-R
2＝(CH
2)
4，R
3＝Ph，X＝ClO
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.01 (s, 1H), 7.69 (d, J=17.7Hz, 2H), 7.38-7.23 (m, 5H), 7.13 (d, J=8.1Hz, 2H), 6.76 (s, 1H), (5.72 d, J=1.8Hz, 1H), 5.11 (d, J=17.4Hz, 1H), 4.41 (d, J=17.7Hz, 1H), 2.68-2.74 (m, 1H), (2.56-2.62 m, 2H), 2.41 (s, 3H), 2.26-2.24 (m, 1H), (1.84-1.77 m, 2H), 1.30-1.24 (m, 2H), 1.22-1.14 (m, 2H); MS (ESI, m/z, rel.intensity) 409.2 (M-ClO
4); HRMS (ESI) calculated value C
22H
25N
4O
2S (M-ClO
4): 406.1693; Measured value: 406.1692.
P46(R
1＝Ac，R
2＝R
3＝Ph，X＝ClO
4)
(and enantiomorph)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.01 (s, 1H), 7.69 (d, J=17.7Hz, 2H), 7.42-7.21 (m, 11H), 7.13 (d, J=8.1Hz, 2H), 6.75 (s, 1H), (5.74 d, J=1.8Hz, 1H), 5.10 (d, J=17.4Hz, 1H), 4.43 (d, J=17.7Hz, 1H), 2.24 (s, 3H); MS (ESI, m/z, rel.intensity) 395.2 (M-ClO
4); HRMS (ESI) calculated value C
25H
23N
4O (M-ClO
4): 395.1866; Measured value: 395.1868.
P47(R
1＝Ac，R
2＝Ph，R
3＝4-OMePh，X＝ClO
4)
Light yellow solid.
1H NMR (300MHz, CDCl
3) δ 9.95 (s, 1H), 7.65 (d, J=8.7Hz, 2H), 7.31-6.91 (m, 12H), 6.72 (s, 1H), 5.74 (s, 1H), 5.13 (d, J=17.4Hz, 1H), 4.35 (d, J=17.4Hz, 1H), 3.76 (s, 3H), 2.19 (s, 3H); MS (ESI, m/z, rel.intensity) 425.2 (M-ClO
4); HRMS (ESI) calculated value C
25H
23N
4O (M-ClO
4): 425.1972; Measured value: 425.1973.
P48(R
1＝Ac，R
2＝Ph，R
3＝2，4，6-(Me)
3Ph，X＝ClO
4)
White solid.
1H NMR (300MHz, CDCl
3) δ 9.73 (s, 1H), 7.40-7.30 (m, 8H), 7.16 (d, J=6.3Hz, 2H), 7.02 (d, J=5.7Hz, 2H), (6.95 s, 1H), 5.83 (s, 1H), (5.10 d, J=17.4Hz, 1H), 4.53 (d, J=17.4Hz, 1H), 2.38 (s, 3H), (2.27 s, 3H), 1.96 (s, 6H); MS (ESI, m/z, rel.intensity) 437.5 (M-ClO
4); HRMS (ESI) calculated value C
28H
29N
4O (M-ClO
4): 437.2336; Measured value: 437.2335.
P49(R
1＝Ac，R
2＝Ph，R
3＝3，5-(CF
3)
2Ph，X＝ClO
4)
(and enantiomorph)
White solid.
1H NMR (300MHz, CDCl
3) δ 10.13 (s, 1H), 8.41 (s, 2H), (8.01 s, 1H), 7.36-7.09 (m, 14H), (6.57 d, J=3.3Hz, 1H), 5.75 (d, J=3.3Hz, 1H), 5.11 (d, J=17.7Hz, 1H), 4.51 (d, J=17.7Hz, 1H), 2.24 (s, 3H); MS (ESI, m/z, rel.intensity) 531.5 (M-ClO
4); HRMS (ESI) calculated value C
27H
21F
6N
4O (M-ClO
4): 531.1614; Measured value: 531.1615.
P50(R
1＝Boc，R
2＝Ph，R
3＝2，4，6-(Me)
3Ph，X＝ClO
4)
White solid.
1HNMR (300MHz, CDCl
3) δ 9.74 (s, 1H), 7.41-7.31 (m, 8H), 7.16 (d, J=6.3Hz, 2H), 7.03 (d, J=5.7Hz, 2H), (6.96 s, 1H), 5.81 (s, 1H), (5.12 d, J=17.4Hz, 1H), 4.54 (d, J=17.4Hz, 1H), 2.37 (s, 3H), (1.98 s, 6H), 1.56 (s, 9H); MS (ESI, m/z, rel.intensity) 495.5 (M-ClO
4); HRMS (ESI) calculated value C
31H
35N
4O
2(M-ClO
4): 495.2755; Measured value: 495.2754.
Embodiment 2
The application of N-heterocyclic carbine in the synthesis of chiral chromone compound
Wherein, base represents alkali, and solvent refers to organic solvent.
General experimental implementation: catalyst precursor is dissolved in the dimethylbenzene, adds alkali, stirring at room 0.5 hour.Add substrate 0.1mmol, room temperature reaction.After TLC followed the tracks of and reacts completely, 0 ℃ added the distilled water cancellation, and ethyl acetate extraction merges organic phase, anhydrous sodium sulfate drying, and removal of solvent under reduced pressure, column chromatography is purified, and (sherwood oil: ethyl acetate) get product, the ee value is measured by chirality HPLC.
Colorless oil, 95%yield (productive rate), 93%ee[chiral column AD-H, normal hexane/Virahol=97/3, v=0.7mLmin
-1, λ=254nm, t (major)=23.1min, t (minor)=34.9min]; [α]
D 20=-6.8 (c=1.0, CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 7.89 (dd, J=1.8,7.8Hz, 1H), 7.51-7.45 (m, 1H), (7.05-6.96 m, 2H), 4.60 (dd, J=5.4,11.1Hz, 1H), 4.30 (t, J=11.7Hz, 1H), 4.19 (q, J=7.2Hz, 2H), 3.39-3.29 (m, 1H), 2.94 (dd, J=4.8,17.1Hz, 1H), 2.42 (dd, J=8.1,17.1Hz, 1H), 1.28 (t, J=7.2Hz, 3H).
Colorless oil, 98%yield, 95%ee[chiral column AD-H, normal hexane/Virahol=95/5, v=1.0mLmin
-1, λ=254nm, t (major)=13.4min, t (minor)=20.8min]; [α]
D 20=-20.5 (c=1.0, CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 7.67 (s, J=1H), 7.28 (d, J=8.1Hz, 1H), (6.87 d, J=8.4Hz, 1H), 4.57 (dd, J=5.1,11.1Hz, 1H), 4.17-4.26 (m, 3H), 3.35-3.25 (m, 1H), 2.92 (dd, J=4.8,16.8Hz, 1H), (2.41 dd, J=8.7,17.1Hz, 1H), 2.30 (s, 3H), 1.28 (t, J=7.2Hz, 3H).
Yellow oil, 95%yield, 88%ee[chiral column AD-H, normal hexane/Virahol=95/5, v=1.0mLmin
-1, λ=254nm, t (major)=19.9min, t (minor)=28.6min]; [α]
D 20=-24.2 (c=1.0, CHCl
3).
1H NMR (300MHz, CDCl
3) δ 7.31 (d, J=3.0Hz, 1H), 7.08 (dd, 3.3,9.0Hz, 1H), 6.91 (d, J=9.0Hz, 1H), 4.56 (dd, J=5.1,11.1Hz, 1H), 4.30-4.16 (m, 3H), (3.77 s, 3H), 3.36-3.26 (m, 1H), 2.90 (dd, J=4.5,16.8Hz, 1H), 2.43 (dd, J=8.1,17.1Hz, 1H), 1.27 (t, J=7.2Hz, 3H).
Yellow oil, 87%yield, 97%ee[chiral column AD-H, normal hexane/Virahol=95/5, v=1.0mLmin
-1, λ=254nm, t (major)=21.4min, t (minor)=27.5min]; [α]
D 20=-10.8 (c=1.0, CHCl
3).
1H NMR (300MHz, CDCl
3) δ 7.82 (d, J=8.7Hz, 1H), 6.59 (dd, J=2.4,8.7Hz, 1H), 6.41 (d, J=2.4Hz, 1H), 4.59 (dd, J=5.4,11.1Hz, 1H), 4.28 (t, J=11.4Hz, 1H), 4.19 (q, J=7.2Hz, 2H), 3.83 (s, 3H), 3.31-3.24 (m, 1H), (2.94 dd, J=4.8,17.1Hz, 1H), 2.39 (dd, J=8.4,16.8Hz, 1H), 1.29 (t, J=7.2Hz, 3H).
Yellow oil, 56%yield, 95%ee[chiral column AD-H, normal hexane/Virahol=90/10, v=1.0mLmin
-1, λ=254nm, t (major)=18.9min, t (minor)=20.7min]; [α]
D 20=+9.5 (c=1.0, CHCl
3).
1H NMR (300MHz, CDCl
3) δ 7.74 (d, J=9.0Hz, 1H), 6.34 (dd, J=2.4,9.0Hz, 1H), 6.04 (d, J=2.4Hz, 1H), 4.52 (dd, J=5.1,11.1Hz, 1H), 4.26-4.14 (m, 3H), 3.38 (q, J=7.2Hz, 4H), 3.23-3.15 (m, 1H), 2.95 (dd, J=4.8,17.1Hz, 1H), 2.35 (dd, J=8.7,16.8Hz, 1H), 1.28 (t, J=7.2Hz, 3H), 1.20 (t, J=7.2Hz, 6H).
Yellow oil, 98%yield, 80%ee[chiral column AD-H, normal hexane/Virahol=97/3, v=0.7mLmin
-1, λ=254nm, t (major)=17.9min, t (minor)=24.0min]; [α]
D 20=-11.2 (c=1.0, CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 7.74 (d, J=7.5Hz, 1H), 7.34 (d, J=7.2Hz, 1H), (6.92 t, J=7.5Hz, 1H), 4.64 (dd, J=5.4,10.8Hz, 1H), 4.29 (t, J=12.0Hz, 1H), 4.19 (q, J=7.2Hz, 2H), 3.35-3.28 (m, 1H), 2.94 (dd, J=4.5,17.1Hz, 1H), 2.40 (dd, J=8.1,16.8Hz, 1H), (2.24 s, 3H), 1.29 (t, J=7.2Hz, 3H).
Yellow oil, 98%yield, 81%ee[chiral column AD-H, normal hexane/Virahol=90/10, v=1.0mLmin
-1, λ=254nm, t (major)=16.2min, t (minor)=22.1min]; [α]
D 20=-26.1 (c=1.0, CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 7.47 (dd, J=1.5,7.8Hz, 1H), 7.04 (dd, J=1.5,7.8Hz, 1H), 6.95 (t, J=8.1Hz, 1H), 4.69 (dd, J=5.4,11.4Hz, 1H), 4.35 (t, J=11.1Hz, 1H), (4.16 q, J=7.2Hz, 2H), 3.89 (s, 3H), 3.38-3.28 (m, 1H), 2.91 (dd, J=4.8,17.1Hz, 1H), 2.45 (dd, J=8.7,16.8Hz, 1H), 1.28 (t, J=7.2Hz, 3H).
Yellow oil, 98%yield, 78%ee[chiral column AD-H, normal hexane/Virahol=95/5, v=1.0mLmin
-1, λ=254nm, t (major)=14.8min, t (minor)=21.6min]; [α]
D 20=-13.7 (c=1.1, CHCl
3).
1H NMR (300MHz, CDCl
3) δ 7.83 (d, J=2.7Hz, 1H), 7.39-7.43 (m, 1H), 6.94 (d, J=9.0Hz, 1H), 4.61 (dd, J=5.4,11.4Hz, 1H), 4.30 (t, J=11.7Hz, 1H), 4.19 (q, J=7.2Hz, 2H), 3.36-3.26 (m, 1H), 2.92 (dd, J=4.8,17.1Hz, 1H), 2.43 (dd, J=8.1,17.4Hz, 1H), 1.28 (t, J=7.2Hz, 3H).
Yellow oil, 93%yield, 78%ee[chiral column OD-H, normal hexane/Virahol=97/3, v=0.5mLmin
-1, λ=254nm, t (minor)=29.1min, t (major)=32.1min]; [α]
D 20=-12.9 (c=1.0, CHCl
3).
1H NMR (400MHz, CDCl
3) δ 7.98 (d, J=2.1Hz, 1H), 7.54 (dd, J=2.7,9.0Hz, 1H), 6.88 (d, J=8.7Hz, 1H), 4.60 (dd, J=5.4,11.1Hz, 1H), 4.29 (t, J=11.4Hz, 1H), 4.18 (q, J=7.2Hz, 2H), 3.36-3.26 (m, 1H), 2.91 (dd, J=4.5,17.1Hz, 1H), 2.43 (dd, J=8.1,17.1Hz, 1H), 1.26 (t, J=7.2Hz, 3H).
Yellow oil, 70%yield, 89%ee[chiral column AD-H, normal hexane/Virahol=97/3, v=0.7mLmin
-1, λ=254nm, t (major)=21.0min, t (minor)=25.6min]; [α]
D 20=-62.2 (c=1.0, CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 8.09 (d, J=8.1Hz, 1H), 7.37 (t, J=7.2Hz, 1H), 7.26 (d, J=6.6Hz, 1H), 7.20 (t, J=7.5Hz, 1H), 4.19 (q, J=7.2Hz, 2H), (3.37-3.34 m, 2H), 3.13-3.10 (m, 1H), 2.98 (dd, J=5.1,16.8Hz, 1H), 2.60 (dd, J=6.9,16.8Hz, 1H), 1.29 (t, J=7.2Hz, 3H).
13C NMR (75MHz, CDCl
3) δ 194.5,171.6,141.7,133.2,130.3,129.6,127.3,124.9,60.8,44.4,34.3,30.8,14.1.IR (thin film): v
Max(cm
-1)=2980,1732,1681,1588,1437,1177,1028,765,737; MS (EI, m/z, rel.intensity) 250 (M
+, 5), 163 (100); HRMS (EI) calculated value C
13H
14O
3S (M
+): 250.0664. measured value: 250.0662.
White solid, 90%yield, 0%ee[chiral column AD-H, normal hexane/Virahol=70/30, v=1.0mLmin
-1, λ=254nnm, t (major)=12.7min, t (minor)=20.3min].
1H NMR (300MHz, CDCl
3) δ 8.78 (d, J=2.7Hz, 1H), 8.34 (dd, J=2.7,9.0Hz, 1H), 7.13 (d, J=9.0Hz, 1H), 4.76 (dd, J=5.4,11.4Hz, 1H), 4.44 (t, J=11.7Hz, 1H), 4.20 (q, J=7.2Hz, 1H), 3.45-3.35 (m, 1H), 2.96 (dd, J=4.8,17.1Hz, 1H), 2.51 (dd, J=7.5,17.1Hz, 1H), 1.30 (t, J=7.2Hz, 1H).
13C NMR (75MHz, CDCl
3) δ 190.6,170.8,165.6,142.1,130.3,123.9,120.0,119.2,70.6,61.2,42.1,29.8,14.1.IR (thin film): v
Max(cm
-1)=2986,1731,1692,1439,1339,1012,856,750,622; MS (EI, m/z, rel.intensity) 279 (M
+, 1), 192 (100); HRMS (EI) calculated value C
13H
13NO
6(M
+): 279.0743. measured value: 279.0745; M.p.86-88 ℃.
Yellow oil, 59%yield, 0%ee[chiral column OB-H, normal hexane/Virahol=90/10, v=1.0mLmin
-1, λ=254nmm, t (minor)=21.3min, t (major)=37.9min].
1H NMR (300MHz, CDCl
3) δ 7.69 (d, J=7.5Hz, 1H), 7.62 (t, J=7.5Hz, 1H), 7.15-7.08 (m, 2H), 4.89 (dd, J=3.9,7.5Hz, 1H), 4.18-4.11 (m, 2H), 3.09 (dd, J=3.6,17.1Hz, 1H), 2.83 (dd, J=7.5,16.8Hz, 1H), 1.20 (t, J=7.2Hz, 3H).
13C NMR (75MHz, CDCl
3) δ 200.4,172.4,169.3,138.0,124.2,122.1,120.9,113.5,81.0,61.2,36.0,13.9.IR (thin film): v
Max(cm
-1)=2983,2935,1724,1615,1464,1327,1191,1026,891,760; MS (EI, m/z, rel.intensity) 220 (M
+, 28), 147 (100); HRMS (EI) calculated value C
12H
12O
4(M
+): 220.0736. measured value: 220.0739.
Claims (8)
1. multichiral center aza ring carbene precursor salt with quadrol skeleton, its general structure is:
* represent chiral centre;
Wherein, R
1Be aryl sulfonyl, substituted aryl alkylsulfonyl, C
1～C
16Alkyl sulphonyl, C
1～C
16Fluoro-alkyl alkylsulfonyl, aryl-acyl, substituted aryl acyl group, C
1～C
16Alkyl acyl or C
1～C
16The fluoro-alkyl acyl group;
R
2Be selected from arbitrarily phenyl or R
2With R
2Between can connect into five to octatomic ring;
R
3Be selected from arbitrarily the aryl of aryl or replacement;
Above-mentioned aryl is phenyl, naphthyl, 9-anthryl, 9-phenanthryl; Substituting group on the described substituted aryl is selected from arbitrarily F, Cl, Br, I, C
1～C
16-oxyl, C
1～C
16Alkyl or C
1～C
16Fluoro-alkyl, nitro or amino;
X is selected from arbitrarily Cl, Br, I, OTf, BF
4Or ClO
4Described Tf is trifyl.
2. multichiral center aza ring carbene precursor salt with quadrol skeleton, its general structure is:
3. a kind of multichiral center aza ring carbene precursor salt with quadrol skeleton as claimed in claim 1, its structural molecule general formula is:
R wherein
1, R
2, R
3, X and * as claimed in claim 1.
4. synthetic method that has as claimed in claim 1 the multichiral center aza ring carbene precursor salt of quadrol skeleton is characterized in that in organic solvent and 0 ℃ to 150 ℃ that lactan, molecular formula with quadrol skeleton are H
2NNHR
3Hydrazine, Mel external cause reagent and orthoformate alkyl ester reaction 10 minutes～5 days, described lactan, molecular formula H with quadrol skeleton
2NNHR
3The mol ratio of hydrazine, Mel external cause reagent and orthoformate alkyl ester be followed successively by 1: 0.8～5: 1～5: 1～20;
Described Mel external cause reagent is trimethoxy tetrafluoride boron salt
Described lactan with quadrol skeleton has following structural formula:
5. a kind of synthetic method with multichiral center aza ring carbene precursor salt of quadrol skeleton as claimed in claim 4 is characterized in that described lactan with quadrol skeleton: molecular formula H
2NNHR
3Hydrazine: Mel external cause reagent: the mol ratio of orthoformate alkyl ester is followed successively by 1: 1～2: 1～2: 5～10;
Described Mel external cause reagent is trimethoxy tetrafluoride boron salt.
6. a kind of synthetic method with multichiral center aza ring carbene precursor salt of quadrol skeleton as claimed in claim 4 is characterized in that described organic solvent is chlorobenzene, benzene, tetracol phenixin, sherwood oil, tetrahydrofuran (THF), dimethyl formamide, ether, methylene dichloride, trichloromethane, toluene, dimethylbenzene, hexanaphthene, normal hexane, normal heptane, dioxane or acetonitrile.
7. a kind of synthetic method with multichiral center aza ring carbene precursor salt of quadrol skeleton as claimed in claim 4 is characterized in that products therefrom is through the Methods For Purification of recrystallization or column chromatography.
8. the purposes with multichiral center aza ring carbene precursor salt of quadrol skeleton as claimed in claim 1 or 2 is characterized in that the Benzofurantone compound that has chirality as preparation.
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