CN102964390B - A kind of Planar chiral ferrocene compound, synthetic method and purposes - Google Patents
A kind of Planar chiral ferrocene compound, synthetic method and purposes Download PDFInfo
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Abstract
The present invention relates to a kind of Planar chiral ferrocene compound, synthetic method and application.This Planar chiral ferrocene compound has following structural formula:
Description
Technical field
The present invention relates to a kind of Planar chiral ferrocene compound, synthetic method and application.The method can with the methyl substituted ferrocene of amine, substituted aryl boric acid or heteroaryl-boronic acids or aryl ethylene ylboronic acid or alkylboronic acids are raw material, and chiral amino acid and palladium are this kind of Planar chiral ferrocene compound of synthesis of catalyzer high-level efficiency, high enantioselectivity.This kind of Planar chiral ferrocene compound conveniently can be converted into chiral ligand, and can be applied in the asymmetric reaction of some metal catalytics.
Background technology
Chiral ferrocene at asymmetry catalysis, Materials science and biomedical sector have extensive research [For books see:(a) Hayashi, T., Togni, A., Eds.In Ferrocenes; VCH:Weinheim, Germany, 1995. (b) Togni, A., Haltermann, R.L., Eds.In Metallocenes; VCH:Weinheim, Germany, 1998. (c) Stepnicka, P., Ed.In Ferrocenes; Wiley:Chichester, 2008. (d) Dai, L.-X.; Hou, X.-L., Eds.In Chiral Ferrocenes in Asymmetric Catalysis; Wiley:2010.]; especially for having for planar chiral ferrocene, in asymmetry catalysis, show catalytic activity [(a) Halterman, R.L.Chem.Rev.1992 very efficiently; 92; 965. (b) Togni, A.Angew.Chem.Int.Ed.1996,35; 1475. (c) Richards, C.J.; Locke, A.J.Tetrahedron:Asymmetry 1998,9,2377. (d) Dai, L.-X.; Tu, T.; You, S.-L.; Deng, W.-P.; Hou, X.-L.Acc.Chem.Res.2003,36,659. (e) Colacot, T.J.Chem.Rev.2003,103,3101. (f) Fu, G.C.Acc.Chem.Res.2004,37,542. (g) Array á s, R.G; Adrio, J.; Carretero, J.C.Angew.Chem., Int.Ed.2006,45,7674. (h) Fu, G.C.Acc.Chem.Res.2006,39,853. (i) Arae, S.; Ogasawara, M.J.Syn.Org.Chem.2012,70,593.].Therefore, chemists are devoted to the efficient method of development one class all the time planar chiral are introduced ferrocene frame having ferrocene frame.Up to the present, the most conventional strategy is that the diastereomeric utilizing all kinds of chiral auxiliary to induce is ortho-metalated.Obviously in the method, need to introduce in advance in ferrocene central chirality [Selected examples:(a) Battelle, L.F.; Bau, R.; Gokel, G.W.; Oyakawa, R.T.; Ugi, I.K.J.Am.Chem.Soc.1973,95,482. (b) Gokel, G.W.; Marquarding, D.; Ugi, I.K.J.Org.Chem.1972,37,305. (c) Riant, O.; Samuel, O.; Kagan, H.B.J.Am.Chem.Soc.1993,115,5835. (d) Riant, O.; Samuel, O.; Flessner, T.; Taudien, S.; Kagan, H.B.J.Org.Chem.1997,62,6733.].It is worth noting; Snieckus seminar utilizes external chiral base; as (-)-sparteine; develop asymmetric ortho-metalated reaction; the method directly can obtain the ferrocene-containing compound of planar chiral; but need the lithium reagent of equivalent, chiral base and comparatively harsh reaction conditions [Selected examples:(a) Tsukazaki, M.; Tinkl, M.; Roglans, A.; Chapell, B.J.; Taylor, N.J.; Snieckus, V.J.Am.Chem.Soc.1996,118,685. (b) Laufer, R.S.; Veith, U.; Taylor, N.J.; Snieckus, V.Org.Lett.2000,2,629.].Recently, Ogasawara seminar utilizes olefin metathesis ring closure reaction to synthesize planar chiral ferrocene, but expensive catalyst, be difficult to obtain, severe reaction conditions [Ogasawara, M.; Watanabe, S.; Nakajima, K.; Takahashi, T.J.Am.Chem.Soc.2010,130,2136.].But up to the present, utilize the synthesis Planar chiral ferrocene compound of the method efficient quick of asymmetry catalysis also to lack corresponding method.
In the past few decades, transition metal-catalyzed c h bond functionalization achieve significant achievement in research [Selected reviews:(a) Daugulis, O.; Zaitsev, V.G.; Shabashov, D.; Pham, Q.N.; Lazareva, A.Synlett 2006,3382. (b) Campeau, L.C.; Fagnou, K.Chem.Commun.2006,1253. (c) Li, B.-J.; Yang, S.-D.; Shi, Z.-J.Synlett 2008,949. (d) Chen, X.; Engle, K.M.; Wang, D.-H.; Yu, J.-Q.Angew.Chem., Int.Ed.2009,48,5094. (e) Yu, J.-Q.; Shi, Z.-J.Top.Curr.Chem.2010,292. (f) Sun, C.-L.; Li, B.-J.; Shi, Z.-J.Chem.Commun.2010,46,677. (g) Lyons, T.W.; Sanford, M.S.Chem.Rev.2010,110,1147. (h) Sehnal, P.; Taylor, R.J.K.; Fairlamb, I.J.S.Chem.Rev.2010,110,824.].However, the asymmetric c h bond functionalization reaction of catalysis is still very challenging problem [(a) Giri, R.; Shi, B.-F.; Engle, K.M.; Maugelc, N.; Yu, J.-Q.Chem.Soc.Rev.2009,38,3242. (b) Peng, H.M.; Dai, L.-X.; You, S.-L.Angew.Chem.Int.Ed.2010,49,5826. (c) Siegel, S.; Schmalz, H.-G.Angew.Chem.Int.Ed.1997,36,2456. (d) Mikami, K.; Hatano, M.; Terada, M.Chem.Lett.1999,28,55. (e) Kakiuchi, F.; Le Gendre, P.; Yamada, A.; Ohtaki, H.; Murai, S.Tetrahedron:Asymmetry 2000,11,2647. (f) Thalji, R.K.; Ellman, J.A.; Bergman, R.G.J.Am.Chem.Soc.2004,126,7192. (g) Albicker, M.R.; Cramer, N.Angew.Chem.Int.Ed.2009,48,9139. (h) Renaudat, A.; Jean-G é rard, L.; Jazzar, R.; Kefalidis, C.E.; Clot, E.; Baudoin, O.Angew.Chem.Int.Ed.2010,49,7261. (i) Nakanishi, M.; Katayev, D.; Besnard, C.; K ü ndig E.P.Angew.Chem.Int.Ed.2011,50,7438. (j) Anas, S.; Cordi, A.; Kagan, H.B.Chem.Commun.2011,47,11483. (k) Katayev, D.; Nakanishi, M.; B ü rgib, T.; K ü ndig, E.P.Chem.Sci.2012,3,1422. (l) Saget, T.; Lemouzy, S.J.; Cramer, N.Angew.Chem.Int.Ed.2012,51,2238. (m) Martin, N.; Pierre, C.; Davi, M.; Jazzar, R.; Baudoin, O.Chem.Eur.J.2012,18,4480. (n) Yamaguchi, K.; Yamaguchi, J.; Studer, A.; Itami, K.Chem.Sci.2012,3,2165. (o) Shintani, R.; Otomo, H.; Ota, K.; Hayashi, T.J.Am.Chem.Soc.2012,134,7305.].Recently, Yu Jinquan seminar finds that the amino acid of chirality list protection can realize asymmetric c h bond functionalization [(a) Shi, the B.-F. of prochiral substrate as part; Maugel, N.; Zhang, Y.-H.; Yu, J.-Q.Angew.Chem.Int.Ed.2008,47,4882. (b) Shi, B.-F.; Zhang, Y.-H.; Lam, J.K.; Wang, D.-H.; Yu, J.-Q.J.Am.Chem.Soc.2010,132,460. (c) Wasa, M.; Engle, K.M.; Lin, D.W.; Yoo, E.J.; Yu, J.-Q.J.Am.Chem.Soc.2011,133,19598. (d) Musaev, D.G.; Kaledin, A.; Shi, B.-F.; Yu, J.-Q.J.Am.Chem.Soc.2012,134,1690.].In view of Planar chiral ferrocene compound purposes widely, but lack efficient synthetic method.The invention provides a kind of method of efficient synthesis Planar chiral ferrocene compound, the chiral amino acid derivative utilizing business to be easy to get is as part, efficient synthesis has Planar chiral ferrocene compound, and has investigated its application of chiral ligand in the asymmetric reaction of some metal catalytics as Material synthesis.Such Planar chiral ferrocene compound also has potential using value in other asymmetric reaction.
Goal of the invention
The object of this invention is to provide the ferrocene-containing compound that a class has planar chiral;
Object of the present invention also provides a kind of efficient synthesis the above-mentioned method with Planar chiral ferrocene compound.
Another object of the present invention there is provided the application of the ferrocene-containing compound of above-mentioned planar chiral, the application of chiral ligand in the asymmetric allylic substitution of catalyzing by metal palladium of being synthesized by the ferrocene-containing compound of above-mentioned planar chiral.
Summary of the invention
The invention provides a class Planar chiral ferrocene compound;
The invention provides the method for the above-mentioned Planar chiral ferrocene compound of a kind of efficient synthesis;
The present invention also provides the application of the chiral ligand synthesized via above-mentioned Planar chiral ferrocene compound in asymmetric allylic substitution.
The structural formula of the Planar chiral ferrocene compound molecule synthesized by the present invention is:
wherein R
1be selected from H arbitrarily, the alkyl of C1-C16 or the cycloalkyl of C3-C16;
Wherein R
2for be selected from arbitrarily C1-C16 alkyl or replace aryl as:
or hetero-aromatic ring as
or replace aryl vinyl as
wherein R
4, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12, R
13and R
14be selected from H, F, Cl, Br, I, CF arbitrarily
3, the-oxyl of C1-C16, the alkyl of C1-C16, X is selected from N, O or S arbitrarily; R
3be selected from H, F, Cl, Br, I, CF arbitrarily
3, the-oxyl of C1-C16, the alkyl of C1-C16,
or two conjugation aryl phosphorus; Wherein R
17, R
18, R
19, R
20and R
21be selected from H, F, Cl, Br, I, CF arbitrarily
3, the alkoxyl group of COOEt, C1-C16, the alkyl of C1-C16, described conjugation aryl is naphthyl, anthryl or phenanthryl.
The ferrocene-containing compound with planar chiral of the present invention is with the ferrocene deriv of aminomethyl replacement and alkylboronic acids, or aryl boric acid, or heteroaryl-boronic acids, or aryl ethylene ylboronic acid is raw material, with chiral amino acid derivative and palladium for catalyzer, at alkali, under the existence of quaternary ammonium salt and oxygenant, reaction is obtained, and available following reaction formula represents:
In reaction formula, L* represents chiral ligand, and Base represents alkali, and [O] represents oxygenant, and Solvent represents organic solvent.
The mol ratio of the ferrocene deriv that described aminoalkyl group replaces, boric acid, chiral amino acid, palladium, alkali, quaternary ammonium salt and oxygenant is 1:1.0-3.0:0.01-0.2:0.005-0.1:1.0-5.0:0.1-1.0:1-100.The ferrocene deriv of the aminoalkyl group replacement of recommendation response, boric acid, chiral amino acid, palladium, alkali, quaternary ammonium salt mol ratio are 1:2:0.2:0.1:1.0:0.25, and air is as oxygenant.Temperature of reaction is 0 DEG C-100 DEG C, and recommendation response temperature is 60 DEG C of-80 ° of C.Reaction times is 6-24 hour.
Wherein the ferrocene deriv structural formula of aminomethyl replacement is as follows:
wherein R
1and R
3as previously mentioned;
Described boric acid is aryl boric acid, and structure is
heteroaryl-boronic acids, structure is
aryl alkenyl boric acid structure is
be R with alkylboronic acids
2b (OH)
2, wherein R
4, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12, R
13and R
14be selected from H, F, Cl, Br, I, CF arbitrarily
3, the alkoxyl group of C1_C16, the alkyl of C1_C16; Wherein X is selected from N arbitrarily, O and S; Wherein R
3be selected from H, F, Cl, Br, I, CF arbitrarily
3, the alkoxyl group of C1_C16, the alkyl of C1_C16,
or two conjugation aryl phosphorus, wherein R
17, R
18, R
19, R
20and R
21be selected from H, F, Cl, Br, I, CF arbitrarily
3, the alkoxyl group of COOEt, C1-C16, the alkyl of C1_C16, described conjugation aryl is naphthyl, anthryl or phenanthryl.
Described alkali is triethylamine, 1,8-diazabicylo [5,4,0] 11 carbon-7-alkene, 1,5-diazabicylo [4,3,0]-5-alkene in the ninth of the ten Heavenly Stems, cesium carbonate, salt of wormwood, sodium carbonate, saleratus, sodium bicarbonate, Potassium ethanoate and potassiumphosphate.
Described chiral amino acid derivative is the optical pure compound of R or the S configuration with following structure:
wherein R
15be selected from arbitrarily methoxycarbonyl, allyloxycarbonyl (Alloc), tertbutyloxycarbonyl (Boc), carbobenzoxy-(Cbz) (Cbz), ethanoyl (Ac), fluorenylmethyloxycarbonyl (Fmoc), benzyl, benzoyl; R
16be selected from arbitrarily the alkyl of C1-C16, sec.-propyl, isobutyl-, the tertiary butyl, benzyl, replacement aryl as:
wherein R
4, R
5, R
6, R
7, R
8described in the same.
Described palladium is palladium, trifluoracetic acid palladium, Palladous chloride and two (methyl ethyl diketone) palladium.
Described quaternary ammonium salt is Tetrabutyl amonium bromide, tetrabutylammonium chloride, tetrabutylammonium iodide, tetraethylammonium bromide, etamon chloride, benzyl triethyl ammonium bromide and benzyltriethylammoinium chloride.
Described oxygenant is air, oxygen, silver suboxide, Silver monoacetate, silver carbonate, Trisilver phosphate, neutralized verdigris, copper trifluoromethanesulfcomposite and benzoquinone.
The invention provides a kind of from simple substrate, the chiral amino acid utilizing business to be easy to get, as part, has succinctly synthesized the method with Planar chiral ferrocene compound efficiently.The method reaction conditions is gentle, and raw material is easy to get, simple to operate, obtains outstanding yield and enantioselectivity.
The chiral ferrocene compound of the present invention's synthesis, through Synthesis chiral ligand, can be applied in asymmetric allylic substitution and the asymmetric Isosorbide-5-Nitrae-conjugate addition reaction research of palladium chtalyst, obtain outstanding yield and enantioselectivity.
Embodiment
To contribute to understanding the present invention by following embodiment, but not limit content of the present invention.
Embodiment 1: partial amino-acid the selection result
In reaction formula, OAc represents acetate moiety, Boc-Val-OH represents (S)-2-(tert-butoxycarbonyl-amino)-3 Methylbutanoic acid, and mol describes mole, and TBAB represents Tetrabutyl amonium bromide, and DMA represents N,N-dimethylacetamide.
Corresponding boric acid 2a(0.4mmol is added in the Schlenk reaction flask of drying) and DMA (1.5mL), add amino acid (0.04mmol) successively again, palladium (4.5mg, 0.02mmol), salt of wormwood (27.6mg, 0.2mmol), Tetrabutyl amonium bromide (16.1mg, 0.05mmol) and ferrocene 1(0.2mmol).60 DEG C of reactions are heated under air atmosphere.After reaction terminates, with saturated sodium bicarbonate cancellation reaction, extraction into ethyl acetate.Merge organic phase, use water and saturated common salt water washing successively, anhydrous sodium sulfate drying, filter, removal of solvent under reduced pressure residue obtains target product 3a(ethyl acetate/petroleum ether=1/10 through column chromatography for separation, v/v, 2%Et
3n).
Embodiment 2: the asymmetric synthesis of Planar chiral ferrocene compound
In reaction formula, OAc represents acetate moiety, Boc-Val-OH represents (S)-2-(tert-butoxycarbonyl-amino)-3 Methylbutanoic acid, and mol describes mole, and TBAB represents Tetrabutyl amonium bromide, and DMA represents N,N-dimethylacetamide.
Corresponding boric acid 2(0.4mmol is added in the Schlenk reaction flask of drying) and DMA (15mL), add Boc-L-Val-OH (8.7mg more successively, 0.04mmol) or Boc-D-Val-OH (8.7mg, 0.04mmol), palladium (4.5mg, 0.02mmol), salt of wormwood (27.6mg, 0.2mmol), Tetrabutyl amonium bromide (16.1mg, 0.05mmol) and ferrocene 1(0.2mmol).60 DEG C of reactions are heated under air atmosphere.After reaction terminates, with saturated sodium bicarbonate cancellation reaction, extraction into ethyl acetate.Merge organic phase, use water and saturated common salt water washing successively, anhydrous sodium sulfate drying, filter.Removal of solvent under reduced pressure residue obtains target product 3(ethyl acetate/petroleum ether=1/10 through column chromatography for separation, v/v, 2%Et
3n).
(Sp)-1-dimethylaminomethylene-2-diphenylphosphino ferrocene
(Sp)-1-Dimethylaminomethyl-2-phenyl ferrocene
Yellow oil (50.7mg, productive rate 79%, 98%ee). analytical data [α]
d 20=+182.3 ° (c=0.25 acetone, 98%ee).
1h NMR (400MHz, CDCl
3) δ 2.17 (s, 6H), 3.15 (AB, J
aB=12.8Hz, 1H), 3.64 (BA, J
bA=12.8Hz, 1H), 4.05 (s; 5H), 4.23-4.24 (m, 1H); 4.30-4.31 (m, 1H), 4.46-4.47 (m; 1H), 7.23-7.30 (m, 1H); 7.31-7.34 (m; 2H), 7.70-7.73 (m, 2H);
13cNMR (100MHz, CDCl
3) δ 45.0,57.9,67.1,69.9,70.0,71.5,82.2,88.1,126.0,127.9,129.3,138.9; IR (film) 3070,2932,2762,1725,1600,1452,1357,1255,1171,1105,1014,816,761,697cm
-1; HRMS (ESI) calculated value (C
19h
21nFe) m/z 317.1065, measured value m/z 317.1073. chiral column phenomenex cellulose-4 (25cm), normal hexane/Virahol=29/1,0.3mL/min, determined wavelength=254nm, t (minor)=15.35min, t (major)=15.93min.
(Rp)-1-dimethylaminomethylene-2-diphenylphosphino ferrocene
(Rp)-1-Dimethylaminomethyl-2-phenyl ferrocene
Yellow oil (productive rate 81% productive rate, 98%ee). analytical data: [α]
d 20=-170.3 ° (c=0.25 acetone, 98%ee).
1h NMR (400MHz, CDCl
3) δ 2.17 (s, 6H), 3.15 (AB, J
ab=12.8Hz, 1H), 3.64 (BA, J
bA=12.8Hz, 1H), 4.05 (s; 5H), 4.23-4.24 (m, 1H); 4.30-4.31 (m, 1H), 4.46-4.47 (m; 1H), 7.23-7.30 (m, 1H); 7.31-7.34 (m; 2H), 7.70-7.73 (m, 2H);
13cNMR (100MHz, CDCl
3) δ 45.0,57.9,67.1,69.9,70.0,71.5,82.2,88.1,126.0,127.9,129.3,138.9; IR (film) 3070,2932,2762,1725,1600,1452,1357,1255,1171,1105,1014,816,761,697cm
-1; HRMS (ESI) calculated value (C
19h
21nFe) m/z317.1065, measured value m/z 317.1073.
(Sp)-1-dimethylaminomethylene-2-(4-aminomethyl phenyl) ferrocene
(Sp)-1-Dimethylaminomethyl-2-(4-methylphenyl)ferrocene
Yellow oil (47mg, 70% productive rate, 97%ee). analytical data [α]
d 20=+157.9 ° (c=0.25Acetone, 97%ee).
1h NMR (400MHz, CDCl
3) δ 2.16 (s, 6H), 2.34 (s, 3H), 3.15 (AB, J
aB=12.4Hz, 1H), 3.63 (BA, J
bA=12.4Hz, 1H), 4.03 (s, 5H), 4.19-4.21 (m, 1H); 4.27-4.28 (m, 1H), 4.42-4.43 (m, 1H), 7.12 (d; J=8.0Hz, 2H), 7.59 (d, J=8.0Hz, 2H);
13c NMR (100MHz, CDCl
3) δ 21.1,45.0,57.8,66.9,69.6,69.9,71.3,82.0,88.3,128.6,129.2,135.5,135.6; IR (film) 3092,2935,2811,2762,1726,1524,1454,1301,1258,1173,1105,1016,815,721cm
-1; HRMS (ESI) data calculated (C
20h
23nFe) m/z 331.1221, test data m/z331.1213. chiral column phenomenex cellulose-4 (25cm), normal hexane/Virahol=29/1,0.3mL/min, determined wavelength=254nm, t (minor)=14.36min, t (major)=15.40min.
(Sp)-1-dimethylaminomethylene-2-(3-aminomethyl phenyl) ferrocene
(Sp)-1-Dimethylaminomethyl-2-(3-methylphenyl)ferrocene
Yellow oil (54.3mg, 81% productive rate, 99%ee), analytical data: [α]
d 20=+168.1 ° (c=0.25Acetone, 99%ee).
1h NMR (400MHz, CDCl
3) δ 2.19 (s, 6H), 2.39 (s, 3H), 3.15 (AB, J
aB=12.4Hz, 1H), 3.65 (BA, J
bA=12.4Hz, 1H), 4.06 (s; 5H), 4.06-4.23 (m, 1H); 4.30-4.31 (m 1H), 4.46-4.47 (m, 1H); (7.05 d, J=7.6Hz, 1H); 7.21-7.24 (m; 1H), 7.52-7.54 (m, 2H);
13c NMR (100MHz, CDCl
3) δ 21.5,44.9,57.8,66.9,69.8,69.9,71.3,82.1,88.2,126.4,126.8,127.7,130.0,137.2,138.7; IR (film) 3093,2936,2811,2762,1727,1605,1499,1454,1354,1258,1173,1105,1020,1000,807,785,705cm
-1; HRMS (ESI) exact mass calcd for (C
20h
23nFe) requires m/z 331.1221, foundm/z 331.1214. chiral column Daicel Chiralcel OD-H (25cm), normal hexane/Virahol=29/1,0.3mL/min, determined wavelength=254nm, t (minor)=14.95min, t (major)=16.31min.
(Rp)-1-dimethylaminomethylene-2-(3-aminomethyl phenyl) ferrocene
(Rp)-1-Dimethylaminomethyl-2-(3-methylphenyl) ferrocene (3c) yellow oil (81% productive rate, 98%ee), analytical data [α]
d 20=-168.1 ° (c=0.25 acetone, 99%ee).
1h NMR (400MHz, CDCl
3) δ 2.19 (s, 6H), 2.39 (s, 3H), 3.15 (AB, J
aB=12.4Hz, 1H), 3.65 (BA, J
bA=12.4Hz, 1H), 4.06 (s; 5H), 4.06-4.23 (m, 1H); 4.30-4.31 (m 1H), 4.46-4.47 (m, 1H); (7.05 d, J=7.6Hz, 1H); 7.21-7.24 (m; 1H), 7.52-7.54 (m, 2H);
13c NMR (100MHz, CDCl
3) δ 21.5,44.9,57.8,66.9,69.8,69.9,71.3,82.1,88.2,126.4,126.8,127.7,130.0,137.2,138.7; IR (film) 3093,2936,2811,2762,1727,1605,1499,1454,1354,1258,1173,1105,1020,1000,807,785,705cm
-1; HRMS (ESI) data calculated (C
20h
23nFe) requires m/z 331.1221, detects data m/z 331.1214.
P3d:(Sp)-1-dimethylaminomethylene-2-(2-aminomethyl phenyl) ferrocene
(Sp)-1-Dimethylaminomethyl-2-(2-methylphenyl)ferrocene(3d)
Yellow oil (22.4mg, 33% productive rate, 94%ee). analytical data 3d:[α]
d 20=-128.1 ° (c=0.25Acetone, 94%ee).
1h NMR (400MHz, CDCl
3) δ 1.91 (s, 6H), 2.15 (s, 3H), 3.21 (AB, J
aB=12.8Hz, 1H), 3.47 (BA, J
bA=12.8Hz, 1H), 4.19 (s, 5H) 4.28-4.31 (m, 2H), 4.39-4.30 (m, 1H), 7.14-7.25 (m, 3H), 7.82-7.84 (m, 1H);
13c NMR (100MHz, CDCl
3) δ 20.7,44.3,56.1,66.5,69.2,69.6,69.7,83.7,90.0,124.9,126.7,129.8,132.9,136.0,137.7; IR (film) 3093,2926,2812,2763,2322,1676,1498,1454,1247,1175,1106,1018,1001,814,762,726cm
-1; HRMS (ESI) exact mass calcd for (C
20h
23nFe) requires m/z 331.1221, found m/z 331.1216. chiral column Daicel ChiralcelOD-H (25cm), normal hexane/Virahol=29/1,0.3mL/min, determined wavelength=254nm, t (major)=16.13min, t (minor)=17.49min.
(Sp)-1-dimethylaminomethylene-2-(4-p-methoxy-phenyl) ferrocene
(Sp)-1-Dimethylaminomethyl-2-(4-methoxyphenyl)ferrocene
Yellow oil (59% productive rate, 96%ee). analytical data: [α]
d 20=+173.5 ° (c=0.25 Acetone, 96%ee).
1h NMR (400MHz, CDCl
3) δ 2.15 (s, 6H), 3.12 (AB, J
aB=12.4Hz, 1H), 3.61 (BA, J
bA=12.4Hz, 1H), 3.82 (s; 3H), 4.03 (s, 5H); 4.18-4.19 (m, 1H), 4.25-4.26 (m; 1H), 4.39-4.40 (m, 1H); 6.85-6.88 (m; 2H), 7.62-7.65 (m, 2H);
13c NMR (100MHz, CDCl
3) δ 45.0,55.2,57.9,66.8,69.5,69.9,71.2,82.0,88.3,113.3,130.3,130.9,158.0; IR (film) 3092,2934,2812,2764,1610,1574,1521,1455,1364,1288,1244,1176,1105,1034,830cm
-1; HRMS (ESI) exact mass calcd for (C
20h
23nOFe) requires m/z 347.1170, found m/z 347.1162. chiral column phenomenex cellulose-4 (25cm), normal hexane/Virahol=29/1,0.3mL/min, determined wavelength=254nm, t (minor)=18.79min, t (major)=20.32min.
Sp)-1-dimethylaminomethylene-2-(how base) ferrocene
(Sp)-1-Dimethylaminomethyl-2-(2-naphthyl)ferrocene
Yellow oil (55.8mg, 75% productive rate, 96%ee). analytical data [α]
d 20=-42.6 ° (c=0.25Acetone, 96%ee).
1h NMR (400MHz, CDCl
3) δ 2.24 (s, 6H), 3.15 (AB, J
aB=12.4Hz, 1H), 3.73 (BA, J
bA=12.4Hz, 1H), 4.05 (s; 5H), 4.27-4.28 (m, 1H); 4.33-4.34 (m, 1H), 4.58-459 (m; 1H), 7.41-7.47 (m, 2H); 7.78-7.84 (m; 4H), 8.24 (s, 1H);
13c NMR (100MHz, CDCl
3) δ 45.1,58.2,67.4,70.0,70.1,71.9,82.3,87.8,125.4,126.0,127.2,127.3,127.6,127.9,128.0,132.0,133.5,136.4; IR (film) 3090,2934,2852,2811,2763,1724,1628,1599,1508,1454,1354,1253,1173,1104,1016,999,963,813,746cm
-1; HRMS (ESI) exact mass calcd for (C
23h
23nFe) requires m/z 367.1221, found m/z 367.1217. chiral column Daicel Chiralcel OD-H (25cm), normal hexane/Virahol=29/1,0.3mL/min, determined wavelength=254nm, t (minor)=16.88min, t (major)=18.28min.
P3g:(Sp)-1-dimethylaminomethylene-2-(4-chloro-phenyl-) ferrocene
(Sp)-1-Dimethylaminomethyl-2-(4-chlorophenyl)ferrocene(3g)
Yellow oil (50.9mg, 72% productive rate, 97%ee). analytical data 3g:[α]
d 20=+185.7 ° (c=0.25Acetone, 97%ee).
1h NMR (300MHz, CDCl
3) δ 2.19 (s, 6H), 3.09 (AB, J
aB=12.8Hz, 1H), 3.61 (BA, J
bA=12.8Hz, 1H), 4.04 (s, 5H), 4.04-4.25 (m; 1H), 4.30-4.31 (m, 1H), 4.46-4.47 (m, 1H); 7.27-7.30 (m, 2H), 7.68-7.71 (m, 2H);
13c NMR (100MHz, CDCl
3) δ 45.0,58.0,67.3,70.0,70.1,71.9,82.1,86.8,128.1,130.4,131.6,137.6; IR (film) 3092,2936,2812,2765,1725,1503,1454,1257,1174,1091,1014,971,817,726cm
-1; HRMS (ESI) exact mass calcd for (C
19h
20nClFe) requires m/z 351.0675, found m/z 351.0668. chiral column phenomenex cellulose-4 (25cm), normal hexane/Virahol=29/1,0.3mL/min, determined wavelength=254nm, t (minor)=13.94min, t (major)=14.70min.
(Sp)-1-dimethylaminomethylene-2-(4-fluorophenyl) ferrocene
(Sp)-1-Dimethylaminomethyl-2-(4-fluorophenyl)ferrocene
Yellow oil (37.5mg, 55% productive rate, 97%ee). analytical data: [α]
d 20=+153.1 ° (c=0.25Acetone, 97%ee).
1h NMR (400MHz, CDCl
3) δ 2.16 (s, 6H), 3.09 (AB, J
aB=12.8Hz, 1H), 3.68 (BA, J
bA=12.8Hz, 1H), 4.03 (s, 5H), 4.20-4.21 (m; 1H), 4.26-4.27 (m, 1H), 4.41-4.42 (m, 1H); 6.97-7.02 (m, 2H), 7.68-7.72 (m, 2H);
13c NMR (100MHz, CDCl
3) δ 45.0,57.9,67.0,69.9,70.0,71.6,82.1,87.3,114.7 (d, J=21.0Hz), 130.6 (d, J=7.2Hz), 134.7 (d, J=3.2Hz), 161.3 (d, J=243.6Hz);
19f NMR (376MHz, CDCl
3) δ-116.8; IR (film) 3093,2935,2813,2766,1604,1519,1455,1364,1301,1221,1159,1105,1016,811cm
-1; HRMS (ESI) exact mass calcd for (C
19h
20nFFe) requires m/z 335.0970, found m/z 335.0961. chiral column phenomenex cellulose-4 (25cm), normal hexane/Virahol=29/1,0.3mL/min, determined wavelength=254nm, t (minor)=14.23min, t (major)=15.06min.
P3i:(Sp)-1-dimethylaminomethylene-2-(4-trifluoromethyl) ferrocene
(Sp)-1-Dimethylaminometh yl-2-(4-trif1uoromethylphenyl)ferrocene(3i)
Yellow oil (47.0mg, 61% productive rate, 94%ee). analytical data: [α]
d 20=+198.1 ° (c=0.25Acetone, 94%ee).
1h NMR (400MHz, CDCl
3) δ 2.21 (s, 6H), 3.09 (AB, J
aB=12.8Hz, 1H), 3.63 (BA, J
bA=12.8Hz, 1H), 4.05 (s, 5H), 4.28-4.30 (m, 1H); 4.34-4.35 (m, 1H), 4.4-4.55 (m, 1H), 7.56 (d; J=8.0Hz, 2H), 7.88 (d, J=8.0Hz, 2H);
13c NMR (100MHz, CDCl
3) δ 45.0,58.0,67.6,70.2,70.6,72.4,82.2,85.9,124.4 (q, J=270.7Hz), 124.8 (q, J=3.8Hz), 127.7 (q, J=31.6Hz), 129.1,143.4 (q, J=1.3Hz).
19fNMR (376MHz, CDCl
3) δ-62.3; IR (film) 3094,2767,2330,1615,1529,1456,1409,1322,1258,1160,1117,1069,1016,973,819,689,655cm
-1; HRMS (ESI) exactmass calcd for (C
20h
20nF
3fe) requires m/z 385.0939, found m/z 385.0930. chiral column phenomenex cellulose-4 (25cm), normal hexane/Virahol=98/2,0.3mL/min, determined wavelength=254nm, t (minor)=13.08min, t (major)=13.74min.
(Sp)-1-dimethylaminomethylene-2-(4-carbethoxy phenyl) ferrocene
(Sp)-1-Dimethylaminomethyl-2-(4-ethoxycarbonylphenyl)ferrocene(3j)
Yellow oil (56.3mg, 72% productive rate, 95%ee). analytical data 3j:[α]
d 20=+207.9 ° (c=0.25Acetone, 95%ee).
1h NMR (400MHz, CDCl
3) δ 1.39 (t, J=7.2Hz, 3H), 2.17 (s, 6H), 3.08 (AB, J
aB=12.8Hz, 1H), 3.62 (BA, J
bA=12.8Hz, 1H), 4.01 (s, 5H); 4.26-4.28 (m, 1H), 4.32-4.33 (m; 1H), 4.37 (q, J=7.2Hz; 2H), 4.52-4.54 (m, 1H); (7.79 d, J=8.4Hz, 2H); (7.97 d, J=8.4Hz, 2H);
13c NMR (100MHz, CDCl
3) δ 14.4,45.0,58.1,60.8,67.8,70.3,70.6,72.5,82.3,86.2,127.8,128.8,129.2,144.8,166.7; IR (film) 2976,2935,2855,2813,1709,1606,1520,1456,1365,1269,1175,1098,1018,817,774,709cm
-1; HRMS (ESI) exact mass calcd for (C
22h
25nO
2fe) requires m/z 389.1276, found m/z 389.1265. chiral column Diacel Chiralcel OD-H (25cm), normal hexane/Virahol=29/1,0.3mL/min, determined wavelength=254nm, t (major)=19.35min, t (minor)=22.20min.
(Rp)-1-dimethylaminomethylene-2-(4-carbethoxy phenyl) ferrocene
(Rp)-1-Dimethylaminomethyl-2-(4-ethoxycarbonylphenyl) ferrocene yellow oil (56.3mg, 72% productive rate, 95%ee). analytical data: [α]
d 20=+207.9 ° (c=0.25Acetone, 95%ee).
1h NMR (400MHz, CDCl
3) δ 1.39 (t, J=7.2Hz, 3H), 2.17 (s, 6H), 3.08 (AB, J
aB=12.8Hz, 1H), 3.62 (BA, J
bA=12.8Hz, 1H), 4.01 (s, 5H); 4.26-4.28 (m, 1H), 4.32-4.33 (m; 1H), 4.37 (q, J=7.2Hz; 2H), 4.52-4.54 (m, 1H); (7.79 d, J=8.4Hz, 2H); (7.97 d, J=8.4Hz, 2H);
13c NMR (100MHz, CDCl
3) δ 14.4,45.0,58.1,60.8,67.8,70.3,70.6,72.5,82.3,86.2,127.8,128.8,129.2,144.8,166.7; IR (film) 2976,2935,2855,2813,1709,1606,1520,1456,1365,1269,1175,1098,1018,817,774,709cm
-1; HRMS (ESI) exact mass calcd for (C
22h
25nO
2fe) requires m/z 389.1276, found m/z 389.1265.
(Sp)-1-dimethylaminomethylene-2-(4-methyl) ferrocene
(Sp)-1-Dimethylaminomethyl-2-methyl ferrocene
Yellow oil (14% productive rate, 90%ee). analytical data: [α]
d 20=-40.0 ° (c=0.25Acetone).
1hNMR (400MHz, CDCl
3) δ 1.99 (s, 3H), 2.18 (s, 6H), 3.27 (AB, J
aB=12.8Hz, 1H), 3.36 (BA, J
bA=12.8Hz, 1H), 3.99 (t, J=2.8Hz, 1H), 4.01 (s, 5H), 4.06 (t, J=1.6Hz, 1H), 4.12 (q, J=1.2Hz, 1H);
13c NMR (100MHz, CDCl
3) δ 13.4,44.8,57.2,65.8,69.0,69.5,69.7,82.3,84.0; IR (film) 3402,3089,2922,2473,2324,1727,1633,1475,1383,1262,1104,1036927,810cm
-1; HRMS (ESI) exact mass calcd for (C
14h
19nFe) requires m/z 255.0908, found m/z 255.0906.
(Sp)-1-diethylin methylene radical-2-diphenylphosphino ferrocene
(Sp)-1-Diethylaminomethyl-2-phenyl ferrocene
Yellow oil (46.3mg, 67% productive rate, 90%ee). analytical data: [α]
d 20=+178.4 ° (c=0.25Acetone, 90%ee).
1h NMR (400MHz, CDCl
3) δ 0.94 (t, J=7.2Hz), 2.41 (q, J=7.2Hz, 2H), 2.53 (q, J=7.2Hz, 2H), 3.42 (AB, J
aB=13.2Hz, 1H), 3.72 (BA, J
bA=13.2Hz, 1H), 4.06 (s; 5H), 4.21-4.23 (m, 1H); 4.31-4.32 (m, 1H), 4.44-4.45 (m; 1H), 7.22-7.25 (m, 1H); 7.29-7.33 (m; 2H), 7.76-7.79 (m, 2H);
13c NMR (100MHz, CDCl
3) δ 11.5,46.0,51.4,66.9,69.7,70.0,71.6,83.0,88.4,126.0,127.8,129.6,138.9; IR (film) 3092,3057,2966,2931,2792,2349,2322,1601,1506,1456,1369,1286,1195,1167,1105,1033,1000,807,763,700,650cm
-1; HRMS (ESI) exactmass calcd for (C
21h
25nFe) requires m/z 345.1378, found m/z 345.1370. chiral column phenomenex cellulose-1 (25cm), CH
3oH/IPA=9/1,0.7mL/min, determined wavelength=214nm, t (minor)=5.51min, t (major)=5.85min.
(Sp)-1-(1-Pyrrolidine methylene radical-2-diphenylphosphino ferrocene
(Sp)-1-(Pyrrolidin-1-yl-methyl)-2-phenyl ferrocene
Yellow oil (49.0mg, 71% productive rate, 98%ee). analytical data: [α]
d 20=+162.4 ° (c=0.25Acetone, 98%ee).
1h NMR (400MHz, CDCl
3) δ 1.71 (t, J=6.4Hz, 4H), 2.44 (t, J=8.0Hz, 4H), 3.33 (AB, J
aB=12.8Hz, 1H), 3.83 (BA, J
bA=12.8Hz, 1H), 4.05 (s, 5H); 4.22 (t, J=2.4Hz, 1H); 4.33 (t, J=2.0Hz, 1H); 4.45 (t, J=2.0Hz, 1H); 7.23-7.25 (m, 1H), 7.30-7.34 (m; 2H), 7.70-7.72 (m, 2H);
13c NMR (100MHz, CDCl
3) δ 23.5,53.9,54.1,67.0,69.8,70.0,71.0,83.0,87.8,126.0,127.9,129.4,139.0; IR (film) 3091,3056,2959,2925,2777,1730,1601,1506,1459,1343,1317,1260,1105,1033,1000,933,877,808,764,701cm
-1; HRMS (ESI) exact mass calcd for (C
21h
23nFe) requires m/z 343.1221, found m/z 343.1216. chiral column phenomenex cellulose-1 (25cm), CH
3cN/IPA=95/5,0.5mL/min, determined wavelength=214nm, t (major)=10.12min, t (minor)=10.70min.
P3n:(Sp)-1-dimethylaminomethylene-2-phenyl-1 ,-bromine ferrocene
(Sp)-1-Dimethylaminomethyl-2-phenyl-1’-bromo ferrocene(3n)
Yellow oil (54.9mg, 69% productive rate, 97%ee). analytical data 3n:[α]
d 20=+173.6 ° (c=0.25Acetone, 97%ee).
1h NMR (400MHz, CDCl
3) δ 2.17 (s, 6H), 3.18 (AB, J
aB=12.8Hz, 1H), 3.60 (BA, J
bA=12.8Hz, 1H), 3.95-3.98 (m; 2H), 4.20-4.21 (m, 1H); 4.26-4.27 (m, 1H), 4.31-4.32 (m; 2H), 4.48-4.49 (m, 1H); 7.24-7.35 (m; 3H), 7.72-7.74 (m, 2H);
13c NMR (100MHz, CDCl
3) δ 45.0,56.9,69.3,69.7,70.0,71.6,72.2,72.3,74.5,78.4,83.4,89.4,126.3,128.0,129.4,137.8; IR (film) 3084,3056,2938,2812,2763,2322,1727,1601,1506,1456,1409,1351,1258,1174,1151,1017,871,804,764,700cm
-1; HRMS (ESI) exact mass calcd for (C
19h
20nBrFe) requiresm/z 395.0170, found m/z 395.0158. chiral column Daicel Chiralcel OD-H (25cm), normal hexane/Virahol=98/2,0.3mL/min, determined wavelength=210nm, t (minor)=17.10min, t (major)=19.41min.
(Rp)-1-dimethylaminomethylene-2-phenyl-1 ,-bromine ferrocene
(Rp)-1-Dimethylaminomethyl-2-phenyl-1’-bromo ferrocene
Yellow oil (54.9mg, 69% productive rate, 97%ee). analytical data: [α]
d 20=-170.6 ° (c=0.25 acetone, 97%ee).
1h NMR (400MHz, CDCl
3) δ 2.17 (s, 6H), 3.18 (AB, J
aB=12.8Hz, 1H), 3.60 (BA, J
bA=12.8Hz, 1H), 3.95-3.98 (m; 2H), 4.20-4.21 (m, 1H); 4.26-4.27 (m, 1H), 4.31-4.32 (m; 2H), 4.48-4.49 (m, 1H); 7.24-7.35 (m; 3H), 7.72-7.74 (m, 2H);
13c NMR (100MHz, CDCl
3) δ 45.0,56.9,69.3,69.7,70.0,71.6,72.2,72.3,74.5,78.4,83.4,89.4,126.3,128.0,129.4,137.8; IR (film) 3084,3056,2938,2812,2763,2322,1727,1601,1506,1456,1409,1351,1258,1174,1151,1017,871,804,764,700cm
-1; HRMS (ESI) exact mass calcd for (C
19h
20nBrFe) requires m/z 395.0170, found m/z 395.0158. chiral column Daicel Chiralcel OD-H (25cm), normal hexane/Virahol=98/2,0.3mL/min, determined wavelength=210nm, t (major)=17.10min, t (minor)=19.41min.
(Sp)-1-dimethylaminomethylene-2-vinyl base ferrocene yellow oil (50% productive rate, 78%ee).
1h NMR (400MHz, CDCl
3) δ 2.18 (s, 6H), 3.27 (AB, J
aB=12.8Hz, 1H), 3.36 (BA, J
bA=12.8Hz, 1H), 3.99 (t, J=2.8Hz; 1H), 4.01 (s, 5H); 4.06 (t, J=1.6Hz, 1H); 4.12 (q, J=1.2Hz, 1H); 5.18 (d, 1H), 5.61 (d; 1H), 6.63 (dd, 2H); HRMS (ESI) calculated value (C
15h
19nFe) m/z 269.1336, measured value m/z269.1350.
(Sp)-1-dimethylaminomethylene-2-(2-thienyl) ferrocene
Yellow oil (60% productive rate, 82%ee).
1h NMR (400MHz, CDCl
3) δ 2.19 (s, 6H), 3.16 (AB, J
aB=12.8Hz, 1H), 3.64 (BA, J
bA=12.8Hz, 1H), 4.05 (s; 5H), 4.23-4.24 (m, 1H); 4.30-4.31 (m, 1H), 4.46-4.47 (m; 1H), 7.16-7.25 (m, 1H); 7.31-7.42 (m; 1H), 7.70-7.73 (m, 1H); HRMS (ESI) calculated value (C
17h
19nFeS) m/z 325.3185, measured value m/z325.3222.
(Sp)-1-dimethylaminomethylene-2-octyl ferrocene
Yellow oil (66% productive rate, 83%ee).
1h NMR (400MHz, CDCl
3) δ 0.88 (t, 3H), 1.22-1.65 (m, 12H), 2.19 (s, 6H), 2.65 (t, 2H), 3.16 (AB, J
aB=12.8Hz, 1H), 3.64 (BA, J
bA=12.8Hz, 1H), 4.05 (s, 5H), 4.23-4.24 (m, 1H), 4.30-4.31 (m, 1H), 4.46-4.47 (m, 1H); HRMS (ESI) calculated value (C
22h
33nFe) m/z 355.4075, measured value m/z 355.4100
(Sp)-1-dimethylaminomethylene-2-cyclohexyl ferrocene
Yellow oil (70% productive rate, 88%ee).
1h NMR (400MHz, CDCl
3) δ 1.41-1.92 (m, 10H), 2.17 (s, 6H), 2.71 (m, 1H), 3.16 (AB, J
aB=12.8Hz, 1H), 3.62 (BA, J
bA=12.8Hz, 1H), 4.03 (s, 5H), 4.23-4.24 (m, 1H), 4.30-4.31 (m, 1H), 4.46-4.47 (m, 1H); HRMS (ESI) calculated value (C
19h
27nFe) m/z 325.4175, measured value m/z 325.4204
(Sp)-1-dimethylaminomethylene-2-cyclopropyl ferrocene
Yellow oil (84% productive rate, 90%ee).
1h NMR (400MHz, CDCl
3) δ 1.00-1.51 (m, 5H), 2.17 (s, 6H), 3.16 (AB, J
aB=12.8Hz, 1H), 3.62 (BA, J
bA=12.8Hz, 1H), 4.03 (s, 5H), 4.23-4.24 (m, 1H), 4.30-4.31 (m, 1H), 4.46-4.47 (m, 1H); HRMS (ESI) calculated value (C
16h
21nFe) m/z 283.3575, measured value m/z 283.3518
(Sp)-1-dimethylaminomethylene-2-(9-phenanthryl) ferrocene
Yellow oil (84% productive rate, 91%ee).
1h NMR (400MHz, CDCl
3) δ 2.17 (s, 6H), 3.16 (AB, J
aB=12.8Hz, 1H), 3.62 (BA, J
bA=12.8Hz, 1H), 4.03 (s, 5H), 4.23-4.24 (m, 1H), 4.30-4.31 (m, 1H), 4.46-4.47 (m, 1H), 7.71-8.93 (m, 9H); HRMS (ESI) calculated value (C
27h
25nFe) m/z 419.4081, measured value m/z 419.4028
(Sp)-1-dimethylaminomethylene-2-(9-anthryl) ferrocene
Yellow oil (80% productive rate, 86%ee).
1h NMR (400MHz, CDCl
3) δ 2.17 (s, 6H), 3.16 (AB, J
aB=12.8Hz, 1H), 3.62 (BA, J
bA=12.8Hz, 1H), 4.03 (s, 5H), 4.23-4.24 (m, 1H), 4.30-4.31 (m, 1H), 4.46-4.47 (m, 1H), 7.71-8.93 (m, 9H); HRMS (ESI) calculated value (C
27h
25nFe) m/z 419.4081, measured value m/z 419.4028
Embodiment 3: the application in the synthesis of ligand L 1 and the asymmetric allyl reaction of palladium chtalyst thereof
The synthesis of ligand L 1
In reaction formula, THF represents tetrahydrofuran (THF).
Under argon shield; compound (Sp)-3n (473mg; 1.1mmol) be dissolved in THF (8.8mL); be cooled to-78 ° of C, be added dropwise to n-BuLi (0.55mL, 1.3mmol; 2.4M normal hexane (in n-hexane). at such a temperature; reaction adds diphenyl phosphorus chloride (0.29mL, 1.5mmol) after stirring half an hour.Reaction is slowly warming up to 0 DEG C, stirs 1 hour.Add water cancellation in reaction system, extracted with diethyl ether.Merge organic phase, with brine It, anhydrous sodium sulfate drying, filter.Decompression is revolved and is desolventized, and resistates is through column chromatography (ethyl acetate/petroleum ether=1/15v/v, 2%Et
3n) separation and purification obtains 406mg ligand L 1 (68% productive rate, 92%ee).
Analytical data L1:[α]
d 20=+24.8 ° (c=0.25Acetone, 92%ee).
1h NMR (400MHz, CDCl
3) δ 2.13 (s, 6H), 2.88 (AB, J
aB=12.8Hz, 1H), 3.52 (BA, J
bA=12.8Hz, 1H), 4.05 (s, 2H), 4.11-4.13 (m, 2H); 4.20 (s, 1H), 4.24 (s, 1H), 4.41 (s; 1H), 7.19-7.41 (m, 13H), 7.63-7.65 (m, 2H);
31p NMR (CDCl
3161MHz) δ-16.91; IR (film) 3055,2930,2819,2772,2361,1598,1504,1455,1434,1303,1250,1158,1091,1065,1017,970,921,886,825,765,744cm
-1; HRMS (ESI) exact mass calcd for (C
31h
30nPFe) requires m/z 501.1507, found m/z 501.1523. chiral column Diacel Chiralcel OD-H (25cm), normal hexane/Virahol=98/2,0.3mL/min, determined wavelength=210nm, t (minor)=18.78min, t (major)=22.80min.
(Sp)-1-dimethylaminomethylene-2-p-trifluoromethyl phenyl-1 '-diphenylphosphine base ferrocene
1H NMR(400MHz,CDCl
3)δ2.13(s,6H),2.88(AB,J
AB=12.8Hz,1H),3.52(BA,J
BA=12.8Hz,1H),4.05(s,2H),4.11-4.13(m,2H),4.20(s,1H),4.24(s,1H),4.41(s,1H),7.19-7.41(m,12H),7.63-7.65(m,2H);
31P NMR(CDCl
3161MHz)δ-17.25
(Sp)-1-(1-Pyrrolidine methylene radical-2-phenyl-1 '-diphenylphosphine base ferrocene
1h NMR (400MHz, CDCl
3) δ 1.72 (t, J=6.4Hz, 4H), 2.44 (t, J=8.0Hz, 4H), 3.33 (AB, J
aB=12.8Hz, 1H), 3.83 (BA, J
bA=12.8Hz, 1H), 4.06 (s, 5H); 4.22 (t, J=2.4Hz, 1H); 4.33 (t, J=2.0Hz, 1H); 4.45 (t, J=2.0Hz, 1H); 7.23-7.25 (m, 1H), 7.30-7.34 (m; 12H), 7.70-7.72 (m, 2H);
31p NMR (CDCl
3application 161MHz) in δ-16.29 palladium chtalyst asymmetric allylation
Ligand L 1 (10.1mg, 0.02mmol) and [Pd (C
3h
5) Cl]
2(3.7mg, 0.01mmol) is dissolved in dry THF (2mL), stirring at room temperature half an hour.Add compound (100.9mg, 0.4mmol), then after stirring 10 minutes, add dimethyl malonate (0.08mL, 0.8mmol), alkali (0.8mmol) and CH
2cl
2solvent (2mL)], react at 20 DEG C and disappear to raw material, saturated ammonium chloride solution cancellation is reacted, extracted with diethyl ether.Merge organic phase, with brine It, anhydrous sodium sulfate drying, filter.Decompression is revolved and is desolventized, and resistates obtains 126mg compound 10 (98% productive rate, 85%ee) through column chromatography (ethyl acetate/petroleum ether=10/1) separation and purification.
Analytical data 10:
1h NMR (400MHz, CDCl
3) δ 3.51 (s, 3H), 3.70 (s, 3H); 3.96 (d, J=11.2Hz, 1H), 4.27 (dd; J=8.8,10.4Hz, 1H); 6.33 (dd, J=8.8,15.8Hz; 1H), 6.48 (d, J=16.0Hz; 1H), 7.17-7.33 (m, 10H); Chiral column Diacel Chiralcel OD-H (25cm), normal hexane/Virahol=90/10,0.7mL/min, determined wavelength=254nm, the absolute configuration of t (minor)=8.12min, t (major)=8.71min. product 10 is defined as S configuration.
The application of embodiment 3 in the asymmetric Isosorbide-5-Nitrae-conjugate addition reaction of palladium chtalyst
In reaction formula, OTf represents trifluoromethanesulfonic acid root.
Ligand L 1 (4.5mg, 9 μm of ol) and [Cu (OTf)]
2c
6h
5cH
3(3.7mg, 3.8 μm of ol) are dissolved in dry toluene (1.3mL), stirring at room temperature 1 hour.Be cooled to-70 DEG C, add compound 11 (31.4mg, 0.151mmol), Et
2zn [(226 μ L, 0.226mmol, 1.0N in hexane)].Rise to-0 DEG C, reaction 24h.Add 1N HCl quencher reaction, extracted with diethyl ether, merge organic phase, use saturated common salt water washing, anhydrous sodium sulfate drying, filter.Decompression is revolved and is desolventized, and resistates obtains 30.4mg compound 12 (86% productive rate, 90%ee) through column chromatography (ethyl acetate/petroleum ether=1/30) separation and purification.
Analytical data 12:
1h NMR (400MHz, CDCl
3) δ 0.88 (t, J=7.3Hz 3H), 1.61-1.83 (m, 2H), 3.21-3.31 (m, 3H), 7.14-7.31 (m, 5H), 7.39-7.55 (m, 3H), 7.88-7.91 (m, 2H); Chiral column Diacel Chiralcel OD-H (25cm), normal hexane/Virahol=99/1,1.0mL/min, determined wavelength=254nm, t (major)=7.94min, t (minor)=8.89min. is by compared with the specific rotation of bibliographical information, and the absolute configuration of product 12 is defined as S configuration.List concrete specific rotation and literature value [α]
d 20in=+ 8.0 ° of (c=1.52Ethanol, 90%ee) documents [α]
d 20=+7..3 ° (c=1.52Ethanol, 86%ee)
The partial amino-acid structure that the present invention is used
General formula can be prepared by method provided by the present invention
represented ferrocene compounds, below expressed portion divide compound structure:
Claims (6)
1. a Planar chiral ferrocene compound, is characterized in that the optical pure compound with following structural formula:
Wherein R
1be selected from arbitrarily the alkyl of H or C1_C16;
R
2for being selected from arbitrarily
wherein R
4, R
5, R
6, R
7, R
8be selected from H, F, Cl, Br, I, CF arbitrarily
3, the alkoxyl group of COOEt, C1_C16 or the alkyl of C1_C16; R
3be selected from arbitrarily
wherein R
17, R
18, R
19, R
20and R
21be selected from H, F, Cl, Br, I, CF arbitrarily
3, the alkoxyl group of COOEt, C1_C16, the alkyl of C1_C16.
2. a Planar chiral ferrocene compound, is characterized in that the optical pure compound with following structural formula:
3. the synthetic method of a planar chiral ferrocene heterocompound as claimed in claim 1, it is characterized in that in 0 DEG C to 100 DEG C and organic solvent, the ferrocene deriv replaced with aminomethyl and boric acid are for raw material, with chiral amino acid and palladium for catalyzer, under the existence of alkali, quaternary ammonium salt and oxygenant, there is asymmetric c h bond arylation reaction, obtain the ferrocene-containing compound with planar chiral; The mol ratio of the ferrocene deriv that described aminomethyl replaces, boric acid, chiral amino acid, palladium, alkali, quaternary ammonium salt and oxygenant is 1:1.0-3.0:0.01-0.2:0.005-0.1:1.0-5.0:0.1-1.0:1-100;
The ferrocene deriv structural formula that described aminomethyl replaces is
Described boric acid is
wherein R
1, R
2, R
3, R
4, R
5, R
6, R
7, R
8as claimed in claim 1;
Described alkali is triethylamine, 1,8-diazabicylo [5,4,0] 11 carbon-7-alkene, 1,5-diazabicylo [4,3,0]-5-alkene in the ninth of the ten Heavenly Stems, cesium carbonate, salt of wormwood, sodium carbonate, saleratus, sodium bicarbonate, Potassium ethanoate or potassiumphosphate;
Described chiral amino acid compound is the optical pure compound of R or the S configuration with following structure:
wherein R
15be selected from arbitrarily methoxycarbonyl, allyloxycarbonyl, tertbutyloxycarbonyl, carbobenzoxy-(Cbz), ethanoyl, fluorenylmethyloxycarbonyl, benzyl or benzoyl; R
16be selected from arbitrarily the alkyl of C1_C16, benzyl,
wherein R
4, R
5, R
6, R
7, R
8as described in the appended claim 1;
Described palladium is palladium, trifluoracetic acid palladium, Palladous chloride or two (methyl ethyl diketone) palladium;
Described quaternary ammonium salt is Tetrabutyl amonium bromide, tetrabutylammonium chloride, tetrabutylammonium iodide, tetraethylammonium bromide, etamon chloride, benzyl triethyl ammonium bromide or benzyltriethylammoinium chloride;
Described oxygenant is air, oxygen, silver suboxide, Silver monoacetate, silver carbonate, Trisilver phosphate, neutralized verdigris, copper trifluoromethanesulfcomposite or benzoquinone.
4. the synthetic method of synthesis Planar chiral ferrocene compound as claimed in claim 3, it is characterized in that described organic solvent is benzene, tetracol phenixin, sherwood oil, tetrahydrofuran (THF), N-Methyl pyrrolidone, dimethyl sulfoxide (DMSO), N, dinethylformamide, N,N-dimethylacetamide, ether, methylene dichloride, trichloromethane, toluene, dimethylbenzene, hexanaphthene, normal hexane, normal heptane, dioxane or acetonitrile.
5. the synthetic method of synthesis Planar chiral ferrocene compound as claimed in claim 3, is characterized in that products therefrom is through recrystallization, thin-layer chromatography, column chromatography or underpressure distillation separation and purification.
6. a purposes for Planar chiral ferrocene compound as claimed in claim 1 or 2, is characterized in that being used as chiral ligand and metal complex as the catalyzer in asymmetric allyl reaction and asymmetric Isosorbide-5-Nitrae-conjugate addition reaction.
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| Catalytic Asymmetric Synthesis with Trans-Chelating Chiral Diphosphine Ligand TRAP Rhodium-Catalyzed Asymmetric Michael Addition of a-Cyano Carboxylates;Masaya Sawamura et al.;《J. Am. Chem. Soc.》;19921031;第114卷(第21期);第8295-8296页 * |
| Tamio Hayashi et al..Asymmetric Synthesis Catalyzed by Chiral Ferrocenyl phosphine-Transition-Metal Complexes,Palladium-Catalyzed Asymmetric Allylic Amination.《J. Am. Chem. Soc.》.1989,第111卷(第16期),第6301-6311页. * |
| 二茂铁配体在不对称烯丙基取代反应中的应用;游书力;《中国博士学位论文全文数据库 工程科技Ⅰ辑》;20071015;第6-9页 * |
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