CN112824384B - Propargylated 3, 3-disubstituted indoline-2-ketone compound containing continuous chiral center and synthesis method thereof - Google Patents

Propargylated 3, 3-disubstituted indoline-2-ketone compound containing continuous chiral center and synthesis method thereof Download PDF

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CN112824384B
CN112824384B CN201911147238.6A CN201911147238A CN112824384B CN 112824384 B CN112824384 B CN 112824384B CN 201911147238 A CN201911147238 A CN 201911147238A CN 112824384 B CN112824384 B CN 112824384B
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propargylated
indoline
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胡向平
夏金涛
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Dalian Institute of Chemical Physics of CAS
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Abstract

The invention relates to a propargylated 3, 3-disubstituted indoline-2-ketone compound containing a continuous chiral center and a synthesis method thereof. The chiral copper catalyst is prepared from copper salt and chiral tridentate P, N, N-ligand (L2 or L3) or chiral tridentate N, N, N-ligand (L1) in situ in various polar and nonpolar solvents. The invention can conveniently prepare various propargylated 3, 3-disubstituted indoline-2-ketone compounds containing continuous chiral centers, the diastereomer excess ratio is up to 99:1, and the enantiomeric excess percentage is up to 99%. The method has the characteristics of simple operation steps, easy preparation of raw materials, wide application range of the substrate, excellent yield, high diastereo-selectivity and enantioselectivity and the like.

Description

Propargylated 3, 3-disubstituted indoline-2-ketone compound containing continuous chiral center and synthesis method thereof
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a propargylated 3, 3-disubstituted indoline-2-ketone compound containing a continuous chiral center and a synthesis method thereof.
Background
Chiral 3, 3-disubstituted indoline-2-ketone compounds are widely used as an important structural unit in various natural products with biological activity and a series of active drug molecules. [ (a) Canas-Rodriguez, a.; leeming, p.r.j.med.chem.1972,15,762; (b) tam, s.w.; zaczek, r.adv.exp.med.biol.1995,363, 47; (c) marti, c.; carreira, e.m.eur.j.org.chem.2003, 2209; (d) neel, d.a.; brown, m.l.; lander, p.a.; grese, t.a.; defauw, j.m.; doti, r.a.; fields, t.; kelley, s.a.; smith, s.; zimmerman, k.m.; steinberg, m.i.; jadhav, p.k.bioorg.med.chem.lett.2005,15,2553; (e) may, j.a.; stoltz, b.tetrahedron.2006,62,5262；(f)Galliford,C.V.；Scheidt,K.A.Angew.Chem.,Int.Ed.2007,46,8748；(g)Uddin,M.K.；Reignier,S.G.；Coulter,T.；Montalbetti,C.；Granas,C.；Butcher,S.；Krog-Jensen,C.；Felding,J.Bioorg.Med.Chem.Lett.2007,17,2854；(h)Volk,B.；
Figure BDA0002282546270000011
J.；Hegedus,E.；Udvari,S.；Gacsályi,I.；Mezei,T.；Pallagi,K.；Kompagne,H.；Lévay,G.；Egyed,A.；L.Hársing,G.；Spedding,M.；Simig,G.J.Med.Chem.2008,51,2522；(i)Siengalewicz,P.；Gaich,T.；Mulzer,J.Angew.Chem.,Int.Ed.2008,47,8170；(j)Ruck,R.T.；Huffman,M.A.；Kim,M.M.；Shevlin,M.；Kandur,W.V.；Davies,I.W.Angew.Chem.2008,120,4789；Angew.Chem.Int.Ed.2008,47,4711；(k)Klein,J.E.M.N.；Perry,A.；Pugh,D.S.；Taylor,R.J.K.Org.Lett.2010,12,3446；(l)Volk,B.；Gacsályi,I.；Pallagi,K.；Poszávácz,L.；
Figure BDA0002282546270000012
I.；Szabó,
Figure BDA0002282546270000013
；Bakó,T.；Spedding,M.；Simig,G.Szénási,G.J.Med.Chem.2011,54,6657；(m)T.Wang,W.Yao,F.Zhong,G.H.Pang,Y.Lu,Angew.Chem.2014,126,3008；Angew.Chem.Int.Ed.2014,53,2964；(n)Herth,M.M.；Andersen,V.L.；Hansen,H.D.；Stroth,N.；Volk,B.；Lehel,S.；Dyssegaard,A.；Ettrup,A.；Svenningsson,P.；Knudsen,G.M.；Kristensen,J.L.J.Med.Chem.2015,58,3631.]therefore, the efficient synthesis of chiral 3, 3-disubstituted indolin-2-one compounds has been the interest of research by researchers, and is one of the hot spots in the field of organic synthesis. At present, the synthesis method of chiral 3, 3-disubstituted indoline-2-ketone compounds mainly comprises the steps of [ (a) Trost, B.M ]; frederiksen, m.u.angelw.chem., int.ed.2005,44,308 (b) Luan, x.; wu, l.; drinkel, e.; mariz, r.; gatti, m.; dorta, r.org.lett.2010,12,1912.(c)
Figure BDA0002282546270000021
V.；Cuthbertson,J.D.；Pickworth,M.；Pugh,D.S.；Taylor,R.J.K.Org.Lett.2011,13,4264.(d)Trost,B.M.；Masters,J.T.；Burns,A.C.Angew.Chem.,Int.Ed.2013,52,2260.(e)Ren,L.；Lian,X.-L.；Gong,L.-Z.Chem.-Eur.J.2013,19,3315.(f)Shimizu,S.；Tsubogo,T.；Xu,P.；Kobayashi,S.Org.Lett.2015,17,2006.(g)Cao,Z.-Y.；Wang,Y.-H.；Zeng,X.-P.；Zhou,J.Tetrahedron Lett.2014,55,2571.(h)Trost,B.M.；Chan,W.H.；Malhotra,S.Chem.-Eur.J.2017,23,4405.(i)Yamamoto,K.；Qureshi,Z.；Tsoung,J.；Pisella,G.；Lautens,M.Org.Lett.2016,18,4954.(j)Li,Y.；Wang,K.；Ping,Y.；Wang,Y.；Kong,W.Org.Lett 2018,20,921.(k)Wang,K.；Ding,Z.；Zhou,Z.；Kong,W.J.Am.Chem.Soc.2018,140,12364.(l)Ma,T.；Chen,Y.；Li,Y.；Ping,Y.；Kong,W.ACS.Catal.2019,9,9127.(m)Ping,Y.；Li,Y.；Zhu,J.；Kong,W.Angew.Chem.,Int.Ed.2019,58,1562.；(n)Xu,S.；Wang,K.；Kong,W.Org.Lett.2019,21,7498.(o)Che,J.；Reddy,A.G.K.；Niu,L.；Xing,D.；Hu,W.Org.Lett.2019,21,4571.]And organocatalysis [ (a) You, y; wu, z. -j.; wang, z. -h.; xu, x. -y.; zhang, x. -m.; yuan, w. — c.j.org.chem.2015,80,8470.(b) Zhu, l.; chen, q.; shen, d.; zhang, w.; shen, c.; zeng, x.; zhong, g.org.lett.2016,18,2387.(c) Dalpozzo, r.; bartoli, g.; bendevinni, g.chem.soc.rev.2012,41,7247, (d) Cheng, d.; ishihara, y.; tan, b.; barbas, c.f.; ACS cata.2014, 4,743 (e) Xia, x.; zhu, q.; wang, j.; chen, j.; cao, w.; zhu, Bo.; wu, x.j.org.chem.2018,83,14617.(f) Zhao, j.; li, Ya.; chen L. -Y; ren, x.j.org.chem.2019,84,5099.]And (4) carrying out two aspects. These methods include the nucleophilic addition to isatin [ (a) g.luppi, Cozzi, p.g.; monari, m.; kaptein, b.; broxterman, q.b.; tomasini, c.j.org.chem.2005,70,7418.; (b) shintani, r.; inoue, m.; hayaashi, t.angelw.chem.2006, 118, 3431; angew chem int ed 2006 45,3353; (c) toulec, p.y.r.b.; c.; de Vries, J.G.; fernga, b.l.; minnaard, a.j.org.lett.2006,8,2715; (d) nakamura, s.; hara, n.; nakashima, h.; kubo, k.; shibata, n.; toru, t.chem.eur.j.2008,14,8079; (e) alcamide, b.; almondros, p.angelw.chem.2008, 120, 4710; angew.chem.int.ed.2008,47,4632; (f) cheng, x.; velalath, s.; goddard, r.;List,B.J.Am.Chem.Soc.2008,130,15786.；(g)Itoh,T.；Ishikawa,H.；Hayashi,Y.Org.Lett.2009,11,3854.；(h)Tomita,D.；Yamatsugu,K.；Kanai,M.；Shibasaki,M.J.Am.Chem.Soc.2009,131,6946.；(i)Itoh,J.；Han,S.B.；Krische,M.J.Angew.Chem.2009,121,6431.；Angew.Chem.Int.Ed.2009,48,6313.；(j)Hanhan,V.；Sahin,A.H.；Chang,T.W.；Fettinger,J.C.；Franz,A.K.Angew.Chem.2010,122,756.；Angew.Chem.Int.Ed.2010,49,744.]by alkylation or arylation [ (a) Trost, b.m.; frederiksen, M.U.Angew.chem.2005,117, 312; angew.chem.int.ed.2005,44,308; (b) trost, b.m.; zhang, y.j.am.chem.soc.2006,128, 4590; (c) trost, b.m.; zhang, y.j.am.chem.soc.2007,129, 14548; (d) trost, b.m.; zhang, y.chem.eur.j.2010,16,296; (e) xiao, z. -k.; yin, h. -y.; shao, l. -x.org.lett.2013,15,1254.]Fluorinated [ (a) Hamashima, y.; suzuki, t.; takano, h.; shimura, y.; sodeoka, m.j.am.chem.soc.2005,127, 10164; (b) shibata, n.; kohno, j.; takai, k.; ishimaru, t.; nakamura, s.; toru, t.; kanemasa, s.angelw.chem.2005, 117, 4276; angew.chem.int.ed.2005,44,4204; (c) ishimaru, t.; shibata, n.; horikawa, t.; yasuda, n.; nakamura, s.; toru, t.; shiro, m.angelw.chem.2008, 120, 4225; angew. chem.int.ed.2008,47,4157.]Hydroxylated [ (a) Ishimaru, t.; shibata, n.; nagai, j.; nakamura, s.; toru, t.; kanemasa, s.j.am.chem.soc.2006,128, 16488; (b) sano, d.; nagata, k.; itoh, t.org.lett.2008,10,1593.]And aldol condensation reaction [ (a) Ogawa, s.; shibata, n.; inagaki, j.; nakamura, s.; toru, t.; shiro, m.angelw.chem.2007, 119, 8820; angew.chem.int.ed.2007,46,8666; (b) shen, k.; liu, x.; zheng, k.; li, W.; hu, x.; lin, l.; feng, x.chem.eur.j.2010,16,3736.]Mannich reaction [ (a) Tian, X; jiang, k.; peng, j.; du, w.; chen, y. -c.org.lett.2008,10,3583.; (b) he, r.; ding, c.; maruoka, k.angelw.chem.2009, 121, 4629.; angew.chem.int.ed.2009,48,4559.]Michael addition reaction [ (a) galzeano, p.; benivenni, g.; pesciaioli, f.; mazzani, a.; giannichi, b.; sambri, l.; bartoli, g.; melchiorre, p.; chem.eur.j.2009,15,7846; (b) bui, t.; syed, s.; barbas III, c.f.j.am.chem.soc.2009,131, 8758.; (c) kato, y.; furutachi, m.; chen, z.; mitsunuma,H.；Matsunaga,S.；Shibasaki,M.J.Am.Chem.Soc.2009,131,9168.；(d)He,R.；Shirakawa,S.；Maruoka,K.J.Am.Chem.Soc.2009,131,16620.]Amination [ (a) Cheng, l.; liu, l.; wang, d.; chen, y. -j.org.lett.2009,11,3874.; (b) qian, z. -q.; zhou, f.; du, t. -p.; wang, B. -L.; ding, m.; zhao, x. -l.; zhou, j.chem.commun.2009, 6753; (c) mouri, s.; chen, z.; mitsunuma, h.; furutachi, m.; matsunaga, s.; shibasaki, m.j.am.chem.soc.2010,132,1255.]And arylation reactions [ Taylor, a.m.; altman, r.a.; buchwald, s.l.j.am.chem.soc.2009,131,9900.]Direct functionalization of 3-substituted indole 2-ones. However, according to our knowledge, the direct asymmetric propargyl substitution of 3-substituted indole 2-ones in these processes has hardly been reported correspondingly. The propargyl-substituted molecule is used as a multifunctional unit, so that subsequent diversity derivatization of the molecule can be realized, such as various reactions including click reaction, Sonogashira coupling, hydrogenation and the like, and a plurality of convenient ways are provided for the construction of some drug molecules. The invention realizes a synthetic method of propargylated 3, 3-disubstituted indoline-2-ketone compounds containing continuous chiral centers through copper-catalyzed asymmetric propargyl substitution reaction, and has important research significance for further enriching the synthesis and application of chiral 3, 3-disubstituted indoline-2-ketone compounds.
Disclosure of Invention
The invention aims to provide a propargylated 3, 3-disubstituted indoline-2-ketone compound containing a continuous chiral center and a synthesis method thereof, and the synthesis method is used for preparing the propargylated 3, 3-disubstituted indoline-2-ketone compound containing the continuous chiral center through a nucleophilic substitution reaction between a copper-catalyzed 3-substituted indoline-2-ketone compound and propargyl acetate. The method has the characteristics of simple operation steps, easy preparation of raw materials, mild reaction conditions, wide substrate application range, excellent reaction yield, high diastereoselectivity and enantioselectivity and the like.
A propargylated 3, 3-disubstituted indolin-2-one compound containing a continuous chiral center, the propargylated 3, 3-disubstituted indolin-2-one compound containing a continuous chiral center having one of the following structures:
Figure BDA0002282546270000051
i and II are enantiomers, III and IV are enantiomers, I and III or IV are diastereomers, and II and III or IV are diastereomers;
in the formula: r 1 ,R 2 ，R 3 ，R 4 Is C1-C40 alkyl, C3-C12 cycloalkyl or C3-C12 cycloalkyl with substituent, phenyl and substituted phenyl, benzyl and substituted benzyl, five-membered or six-membered heterocyclic aromatic group containing one or more than two oxygen, sulfur and nitrogen atoms, ester group;
the substituent on the C3-C12 naphthenic base, the substituent on the phenyl and the substituent on the benzyl are respectively one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituents is 1-5.
The invention provides a method for synthesizing propargylated 3, 3-disubstituted indoline-2-ketone compounds containing continuous chiral centers, which synthesizes propargylated 3, 3-disubstituted indoline-2-ketone compounds containing continuous chiral centers by catalyzing nucleophilic substitution reaction between 3-substituted indoline-2-ketone compounds and propargyl acetate by using a chiral copper catalyst in the presence of an alkaline additive.
The method comprises the following specific steps:
(1) preparation of chiral copper catalyst: under the protection of nitrogen, copper salt and chiral P, N, N-ligand are stirred in a reaction medium for 1-2 hours according to the molar ratio of 1: 0.1-10 to prepare a chiral copper catalyst; the chiral tridentate ligand is a chiral tridentate P, N, N-ligand (L-2 or L-3) or a chiral tridentate N, N, N-ligand (L-1);
(2) preparation of propargylated 3, 3-disubstituted indoline-2-ones containing a continuous chiral center: dissolving a 3-substituted indoline-2-ketone compound, propargyl acetate and an alkaline additive in a reaction medium, and then adding the solution into the stirred solution of the chiral copper catalyst under the protection of nitrogen, and stirring and reacting at-40-0 ℃ for not less than 10 hours; after the reaction is finished, concentrating under reduced pressure until no solvent exists basically, separating by silica gel column chromatography, concentrating under reduced pressure, and drying in vacuum to obtain a target product;
the molar ratio of the chiral copper catalyst to the 3-substituted indoline-2-ketone compound is 0.01-100% to 1;
the molar ratio of the alkaline additive to the propargyl acetate compound is 0.5-10: 1;
the molar ratio of the 3-substituted indoline-2-ketone compound to the propargyl acetate compound is 1: 1 to 4.
The reaction medium is at least one of methanol, ethanol, isopropanol, isobutanol, toluene, dichloromethane, diethyl ether, tetrahydrofuran, dimethyl sulfoxide or N, N-dimethylformamide.
The propargylated 3, 3-disubstituted indoline-2-ketone compound containing a continuous chiral center has one of the following structures:
Figure BDA0002282546270000071
i and II are enantiomers of each other, III and IV are enantiomers of each other, I and III or IV are diastereomers of each other, and II and III or IV are diastereomers of each other. In the formula: r 1 ,R 2 ，R 3 ，R 4 Is C1-C40 alkyl, C3-C12 cycloalkyl or C3-C12 cycloalkyl with substituent, phenyl and substituted phenyl, benzyl and substituted benzyl, five-membered or six-membered heterocyclic aromatic group containing one or more than two oxygen, sulfur and nitrogen atoms and ester group. The substituents on the C3-C12 naphthenic base, the substituents on the phenyl and the substituents on the benzyl are respectively one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituents is 1-5.
The 3-substituted indoline-2-ketone compound has the following structure:
Figure BDA0002282546270000072
in the formula: r 2 ，R 3 ，R 4 Is one or more than two of C1-C40 alkyl, C3-C12 cycloalkyl or C3-C12 cycloalkyl with substituent, phenyl and substituted phenyl, benzyl and substituted benzyl, five-membered or six-membered heterocyclic aromatic group containing one or more than two oxygen, sulfur and nitrogen atoms and ester group; the substituents on the C3-C12 naphthenic base, the substituents on the phenyl and the substituents on the benzyl are respectively one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituents is 1-5.
The propargyl acetate compound has the following structure:
Figure BDA0002282546270000081
in the formula: r is 1 Is one or more than two of C1-C10 alkyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, C5-C10 sulfur-containing heterocycle and C5-C10 oxygen-containing heterocycle; the substituent on the substituted phenyl, the substituted naphthyl, the sulfur-containing heterocycle of C5-C10 and the oxygen-containing heterocycle of C5-C10 is one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituent is 1-5.
The copper salt is Cu (OAc) 2 ·H 2 O、Cu(OAc) 2 、Cu(OTf) 2 、CuCl 2 、CuOAc、CuCl、CuI、CuClO 4 、CuOTf·0.5C 6 H 6 、Cu(CH 3 CN) 4 BF 4 、Cu(CH 3 CN) 4 ClO 4 Or Cu (CH) 3 CN) 4 PF 6 One or more than two of them.
The chiral P, N, N-ligand or chiral tridentate N, N, N-ligand has one of the following structural features:
Figure BDA0002282546270000082
in the formula: r 4 ，R 5 H, alkyl in C1-C10, cycloalkyl in C3-C8, phenyl and substituted phenyl, benzyl and substituted benzyl; the substituent on the substituted phenyl or the substituted benzyl is one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituent is 1-5;
R 6 ，R 7 is H, halogen, alkyl and cycloalkyl, phenyl and substituted phenyl, alkoxy, phenoxy, acyl or nitro;
R 8 is C1-C40 alkyl, C3-C12 cycloalkyl, phenyl and substituted phenyl, naphthyl and substituted naphthyl, and contains one or more than two five-membered or six-membered heterocyclic aromatic groups of oxygen, sulfur and nitrogen atoms; the substituent on the substituted phenyl or the substituted naphthyl is one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituent is 1-5.
The alkaline additive is various inorganic bases or organic bases: i Pr 2 NEt、NEt 3 、 i PrNMe 2 、 i Bu 3 N、CyNMe 2 、Cy 2 NMe、 t BuOK、KOH、K 2 CO 3 、K 3 PO 4 、NaOH、Na 2 CO 3 、NaHCO 3 or Cs 2 CO 3 One or more than two of them. Preference is given to i Pr 2 NEt、Et 3 N、Cs 2 CO 3 Or K 2 CO 3 。
The catalytic reaction conditions are preferably as follows:
temperature: -40 ℃ -0 ℃;
reaction medium: protic solvents, preferably methanol;
pressure: normal pressure;
time: >0.5 hours, preferably 10 hours.
The molar ratio of the chiral copper catalyst to the 3-substituted indoline-2-ketone compound is 0.01-100% to 1;
the molar ratio of the alkaline additive to the propargyl acetate compound is 0.5-10: 1;
the molar ratio of the 3-substituted indoline-2-ketone compound to the propargyl acetate compound is 1: 1-4;
the reaction equation of the invention is as follows:
Figure BDA0002282546270000091
the invention has the following advantages:
1. high reaction yield, good stereoselectivity and mild reaction conditions.
2. The starting materials are easy to prepare.
3. The chiral ligand is simple and convenient to synthesize, the catalyst is easy to prepare, and the catalyst loading capacity is low.
4. Compared with the traditional method, the method can efficiently synthesize various propargylated 3, 3-disubstituted indoline-2-ketone compounds containing continuous chiral centers.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIG. 1 is a NMR spectrum of 1-methyl-3-phenyl-3- (1-phenylprop-2-yn-1-yl) indolin-2-one I-1 prepared in example 1;
FIG. 2 is a NMR carbon spectrum of 1-methyl-3-phenyl-3- (1-phenylprop-2-yn-1-yl) indolin-2-one I-1 prepared in example 1;
FIG. 3 is a NMR spectrum of 1-methyl-3-p-methylphenyl-3- (phenylprop-2-yn-1-yl) indolin-2-one I-2 prepared in example 11;
FIG. 4 is a NMR carbon spectrum of 1-methyl-3-p-methylphenyl-3- (phenylprop-2-yn-1-yl) indolin-2-one I-2 prepared in example 11;
FIG. 5 is a NMR spectrum of 1, 3-dimethyl-3- (1-phenylprop-2-yn-1-yl) indolin-2-one I-3 prepared in example 12;
FIG. 6 is a NMR carbon spectrum of 1, 3-dimethyl-3- (1-phenylprop-2-yn-1-yl) indolin-2-one I-3 prepared in example 12;
FIG. 7 is a NMR spectrum of 1-methyl-3-phenyl-3- (1-p-methylphenylprop-2-yn-1-yl) indolin-2-one I-4 prepared in example 13;
FIG. 8 is a NMR carbon spectrum of 1-methyl-3-phenyl-3- (1-p-methylphenylprop-2-yn-1-yl) indolin-2-one I-4 prepared in example 13;
FIG. 9 is a NMR spectrum of 1-phenyl-3- (1-phenylprop-2-yn-1-yl) indolin-2-one I-5 prepared in example 14;
FIG. 10 is a NMR carbon spectrum of 1-phenyl-3- (1-phenylprop-2-yn-1-yl) indolin-2-one I-5 prepared in example 14;
FIG. 11 is a NMR spectrum of 6-chloro-1-methyl-3-phenyl-3- (1-phenylprop-2-yn-1-yl) indolin-2-one I-6 prepared in example 15;
FIG. 12 is a NMR carbon spectrum of 6-chloro-1-methyl-3-phenyl-3- (1-phenylprop-2-yn-1-yl) indolin-2-one I-6 prepared in example 15;
Detailed Description
The following examples further illustrate the invention but are not intended to limit the invention thereto. Melting points were determined by a melting point apparatus, High Performance Liquid Chromatography (HPLC) by Agilent 1100 series HPLC, optical rotation by JASCO P-1020 polarimeter, nuclear magnetic resonance by Bruker nuclear magnetic resonance apparatus, and molecular weights by liquid chromatography High Resolution Mass Spectrometry (HRMS) MicroMass.
Example 1
Cu(CH 3 CN) 4 PF 6 And L-2-1 are complexed as a catalyst to perform catalytic reaction to generate propargylated 1-methyl-3-phenyl-3- (1-phenylpropyl-2-alkyne-1-yl) indoline-2-ketone I-1 containing two continuous chiral centers.
Before adding metal into the reaction bottleBulk Cu (CH) 3 CN) 4 PF 6 (0.015mmol, 5 mol%) and chiral ligand L-2-1(0.0165mmol, 5.5 mol%), adding 1.0mL of anhydrous methanol under the protection of nitrogen, and stirring at room temperature for 0.5 h. Then the reaction tube was transferred to a constant temperature reaction freezer at-40 ℃ to mix 1-methyl-3-phenylindolin-2-one V-1 (0.3mmol, 1.0equiv), 1-phenylpropargyl acetate VI-1 (0.36mmol, 1.2equiv) and Cs 2 CO 3 (0.36mmol, 1.2equiv) was dissolved in 2.0mL of anhydrous methanol, and the solution was added to the stirred solution of the catalyst under nitrogen protection and stirred at-40 ℃ for 10 h. After the reaction is finished, concentrating under reduced pressure until no solvent exists basically, separating by silica gel column chromatography, concentrating under reduced pressure, drying in vacuum to obtain white foamy solid with 99 percent yield,>20/1d.r.,>99% ee. The hydrogen and carbon nuclear magnetic resonance spectra of the product I-1 are shown in FIGS. 1 and 2: m.p. 150 ℃ and 152 ℃.>99％ee was determined by chiral HPLC(Daicel Chiralcel OD-H,0.46cm×25cm,n-hexane/i-PrOH＝98/2,1.0ml/min,254nm,40℃):t R (major enantiomer)＝11.2min,t R (minor enantiomer)＝19.0min.[α] D 25 ＝331(c 0.55,CH 2 Cl 2 ). 1 H NMR analysis of crude products indicated d.r.>20:1. 1 H NMR(400MHz,CDCl 3 )δ7.90(d,J＝7.1Hz,1H),7.60(d,J＝7.2Hz,2H),7.46–7.21(m,4H),7.16(t,J＝7.2Hz,1H),7.11–6.84(m,5H),6.51(d,J＝7.5Hz,1H),4.96(s,1H),2.74(s,3H),2.21(s,1H). 13 C NMR(101MHz,CDCl 3 )δ176.0,144.1,137.8,135.2,129.2,128.9,128.5,128.3,128.1,127.7,127.4,127.3,126.9,122.1,108.0,82.9,73.4,60.7,45.1,26.0.HRMS(ESI)calc.for C 24 H 20 NO[M+H] + :338.1539,found:338.1540.
The structural formula of V-1, VI-1, I-1, L-2-1 is as follows:
Figure BDA0002282546270000121
example 2
L-1-1 is used as ligand to react to generate a product I-1
The ligand L-2-1 in example 1 is replaced by the ligand L-1-1, the temperature is 0 ℃, the alkali additive is diisopropylethylamine, and the reaction is stirred for 10 hours, and the rest is the same as example 1. The reaction gave compound I-1 in 92% yield, 54/46dr, 90% ee.
The structural formula of L-1-1 is as follows:
Figure BDA0002282546270000122
example 3
L-3-1 is used as ligand to react to generate a product I-1
The ligand L-2-1 in example 1 was replaced with ligand L-3-1 at 0 deg.C and the base additive was diisopropylethylamine, and the reaction was stirred for 10h, the remainder being the same as in example 1. The reaction gave compound I-1 in 92% yield, 65/35dr, 95% ee.
The structural formula of L-3-1 is as follows:
Figure BDA0002282546270000131
example 4
Cu(OTf) 2 Catalytically reacting with L-2-1 to produce a product I-1
Cu (CH) in example 1 3 CN) 4 PF 6 With Cu (OTf) 2 Instead, the rest is the same as example 1. Compound I-1 was obtained in 36% yield, 94/6dr, 98% ee.
Example 5
Cu(CH 3 CN) 4 BF 4 And L-2-1 to generate a product I-1
Cu (CH) in example 1 3 CN) 4 PF 6 With Cu (CH) 3 CN) 4 BF 4 Instead, the rest is the same as example 1. Compound I-1 was obtained in 78% yield, 94/6dr, 99% ee.
Example 6
Cu(CH 3 CN) 4 ClO 4 Catalytically reacting with L-2-1 to produce a product I-1
Cu (CH) in example 1 3 CN) 4 PF 6 With Cu (CH) 3 CN) 4 ClO 4 Instead, the rest is the same as example 1. Compound i-1 was obtained in 82% yield, 98/2dr,>99％ee。
example 7
TEA as a base additive to give the product I-1
Cs in example 1 2 CO 3 The TEA was replaced, as in example 1. Compound i-1 was obtained in 43% yield, 73/27dr,>99％ee。
example 8
K 3 PO 4 As an alkali additive to produce the product I-1
Cs in example 1 2 CO 3 Is replaced by K 3 PO 4 Otherwise, the same procedure as in example 1 was repeated. Compound i-1 was obtained in 63% yield, 98/2dr,>99％ee。
example 9
KO t Bu is used as an alkali additive to react to generate a product I-1
Cs in example 1 2 CO 3 Replacement is with KO t Bu, otherwise as in example 1. Compound i-1 was obtained in 79% yield, 97/3dr,>99％ee。
example 10
K 2 CO 3 As an alkali additive to produce the product I-1
Cs in example 1 2 CO 3 Is replaced by K 2 CO 3 Otherwise, the same procedure as in example 1 was repeated. Compound i-1 was obtained in 79% yield, 97/3dr,>99％ee。
example 11
The V-2 is used as a substrate to react to generate 1-methyl-3-p-methylphenyl-3- (phenylpropane-2-alkyne-1-yl) indoline-2-ketone I-2
The procedure of example 1 was repeated except for replacing 1-methyl-3-phenylindolin-2-one V-1 in example 1 with 1-methyl-3-p-methylphenylindolin-2-one V-2 to give compound I-2 in 90% yield, 13.3/dr, 97% ee. The hydrogen and carbon nuclear magnetic resonance spectra of the product I-2 are shown in FIGS. 3 and 4: m.p. 162-.>99％ee was determined by chiral HPLC(Daicel Chiralcel OD-H,2×0.46cm×25cm,n-hexane/i-PrOH＝98/2,1.0ml/min,254nm,40℃):t R (major enantiomer)＝22.4min,t R (minor enantiomer)＝41.3min.[α] D 20 ＝+274.52(c 0.68,CH 2 Cl 2 ). 1 H NMR analysis of crude products indicated d.r.>20:1. 1 H NMR(400MHz,CDCl 3 )δ7.89(d,J＝7.4Hz,1H),7.47(d,J＝8.1Hz,2H),7.26(t,J＝7.7Hz,1H),7.16(d,J＝7.7Hz,3H),7.07–6.95(m,5H),6.50(d,J＝7.8Hz,1H),4.94(d,J＝2.4Hz,1H),2.72(s,3H),2.32(s,3H),2.22(d,J＝2.3Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ176.1,144.1,137.4,135.3,134.8,129.2,129.2,128.8,128.5,127.9,127.4,127.3,126.9,122.1,107.9,83.0,73.4,60.5,45.0,26.0,21.1.HRMS(ESI)calc.for C 25 H 22 NO[M+H] + :352.1696,found:352.1692.
The structural formula of V-2 and I-2 is as follows:
Figure BDA0002282546270000151
example 12
V-3 is used as a substrate to react to generate 1, 3-dimethyl-3- (1-phenylpropane-2-alkyne-1-yl) indoline-2-keto I-3
Example 1 was followed by substituting 1-methyl-3-phenylindolin-2-one V-1 in example 1 with 1, 3-dimethylindolin-2-one V-3. Compound i-3 was obtained in 76% yield, 99/1dr,>99% ee. The hydrogen and carbon nuclear magnetic resonance spectra of the product I-3 are shown in FIGS. 5 and 6:>99％ee was determined by chiral HPLC(Daicel Chiralcel AD-H,0.46cm×25cm,n-hexane/i-PrOH＝95/5,1.0ml/min,254nm,40℃):t R (major enantiomer)＝6.5min,t R (minor enantiomer)＝7.1min.[α] D 25 ＝54.4(c 0.40,CH 2 Cl 2 ). 1 H NMR analysis of crude products indicated d.r.>99:1. 1 H NMR(400MHz,CDCl 3 )δ7.74(d,J＝7.3Hz,1H),7.19(t,J＝7.7Hz,1H),7.08(t,J＝7.5Hz,1H),7.02(d,J＝7.1Hz,1H),6.97(t,J＝7.4Hz,2H),6.90(d,J＝7.5Hz,2H),6.47(d,J＝7.7Hz,1H),4.18(d,J＝2.2Hz,1H),2.77(s,3H),2.47(d,J＝2.4Hz,1H),1.69(s,3H). 13 C NMR(101MHz,CDCl 3 )δ178.3,143.1,135.7,130.6,128.5,128.3,127.3(overlapping),124.3,122.1,107.6,82.9,73.4,52.3,45.4,25.7,21.6.HRMS(ESI)calc.for C 19 H 18 NO[M+H] + :276.1383,found:276.1384.
the structural formula of V-3 and I-3 is as follows:
Figure BDA0002282546270000161
example 13
V-4 is used as a substrate to react to generate 1-methyl-3-phenyl-3- (1-p-methylphenyl prop-2-alkyne-1-yl) indoline-2-ketone I-4
The procedure of example 1 was repeated except that 1-phenylpropargyl acetate VI-1 in example 1 was replaced with 1-p-methylphenylpargyl acetate VI-2. Compound I-4 was obtained in 66% yield, 19/1dr, 99% ee. The hydrogen and carbon nuclear magnetic resonance spectra of the product I-4 are shown in FIGS. 7 and 8:>99％ee was determined by chiral HPLC(Daicel Chiralcel OJ-H,2×0.46cm×25cm,n-hexane/i-PrOH＝95/5,0.8ml/min,254nm,40℃):t R (major enantiomer)＝44.9min,t R (minor enantiomer)＝31.1min.[α] D 25 ＝260(c 0.86,CH 2 Cl 2 ). 1 H NMR analysis of crude products indicated d.r.＝19:1. 1 H NMR(400MHz,CDCl 3 )δ7.83(d,J＝6.9Hz,1H),7.57–7.47(m,2H),7.27(t,J＝7.3Hz,2H),7.24–7.17(m,2H),7.09(td,J＝7.6,0.8Hz,1H),6.84(d,J＝8.1Hz,2H),6.73(d,J＝8.0Hz,2H),6.46(d,J＝7.7Hz,1H),4.84(d,J＝2.5Hz,1H),2.69(s,3H),2.12(d,J＝2.6Hz,1H),2.10(s,3H). 13 C NMR(101MHz,CDCl 3 )δ176.1,144.2,137.9,137.0,132.2,129.4,129.0,128.8,128.4,128.0,127.7,126.9,126.6,122.1,108.0,83.2,73.2,60.7,44.7,26.0,21.0.HRMS(ESI)calc.for C 25 H 22 NO[M+H] + :352.1696,found:352.1692.
the structural formula of V-4 and I-4 is as follows:
Figure BDA0002282546270000171
example 14
V-5 is used as a substrate to react to generate 1-phenyl-3- (1-phenylpropane-2-alkyne-1-yl) indoline-2-ketone I-5
Example 1 was followed except that 1-methyl-3-phenylindolin-2-one V-1 in example 1 was replaced with 1-phenyl-3-phenylindolin-2-one V-5. Compound i-5 was obtained in 66% yield, 8/1dr,>99% ee. The hydrogen and carbon nuclear magnetic resonance spectra of the product I-5 are shown in FIGS. 9 and 10:>99％ee was determined by chiral HPLC(Daicel Chiralcel OD-H,0.46cm×25cm,n-hexane/i-PrOH＝95/5,1.0ml/min,254nm,40℃):t R (major enantiomer)＝10.4min,t R (minor enantiomer)＝9.3min.[α] D 25 ＝228(c 0.85,CH 2 Cl 2 ). 1 H NMR analysis of crude products indicated d.r.＝8:1.NMR for the major product: 1 H NMR(400MHz,CDCl 3 )δ8.07–7.93(m,1H),7.69(d,J＝7.9Hz,2H),7.40(t,J＝7.6Hz,2H),7.36–7.26(m,4H),7.21(dd,J＝5.6,3.4Hz,2H),7.18–7.12(m,1H),7.12–7.04(m,4H),6.72(d,J＝7.5Hz,2H),6.52–6.39(m,1H),5.02(d,J＝2.4Hz,1H),2.26(d,J＝2.3Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ175.4,144.4,137.8,135.5,134.1,129.9,129.6,129.4,128.8,128.6,128.4,128.2,128.1,127.8,127.7,127.3,126.8,126.7,122.6,109.3,82.9,73.5,60.6,45.5.HRMS(ESI)calc.for C 29 H 22 NO[M+H] + :400.1696,found:400.1700.
the structural formula of V-5 and I-5 is as follows:
Figure BDA0002282546270000181
example 15
V-6 is used as a substrate to react to generate 6-chloro-1-methyl-3-phenyl-3- (1-phenylpropane-2-alkyne-1-yl) indoline-2-keto I-6
The 1-methyl-3-phenylindolin-2-one V-1 in example 1 was replaced by 6-chloro-1-methyl3-phenylindolin-2-one V-6, the remainder of the same as in example 1. Compound i-6 was obtained in 77% yield, 19/1dr,>99% ee. The hydrogen and carbon nuclear magnetic resonance spectra of the product I-6 are shown in FIGS. 11 and 12:>99％ee was determined by chiral HPLC(Daicel Chiralcel OD-H,0.46cm×25cm,n-hexane/i-PrOH＝95/5,1.0ml/min,254nm,40℃):t R (major enantiomer)＝9.0min,t R (minor enantiomer)＝12.2min.[α] D 25 ＝248.4(c 0.37,CH 2 Cl 2 ). 1 H NMR analysis of crude products indicated d.r.＝19:1. 1 H NMR(400MHz,CDCl 3 )δ7.82(d,J＝8.0Hz,1H),7.60–7.53(m,2H),7.41–7.29(m,3H),7.16(dd,J＝8.0,1.9Hz,1H),7.10–7.03(m,4H),6.54(d,J＝1.9Hz,1H),4.94(d,J＝2.6Hz,1H),2.74(s,3H),2.24(d,J＝2.6Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ175.9,145.3,137.3,134.8,134.7,129.1,128.5,127.9,127.9,127.8,127.6,127.5,126.7,122.0,108.6,82.6,73.6,60.5,45.0,26.1.HRMS(ESI)calc.for C 24 H 19 ClNO[M+H] + :372.1150,found:372.1150.
the structural formula of V-6 and I-6 is as follows:
Figure BDA0002282546270000182
examples 16 to 43
Reaction substrate suitability
The invention has wide substrate applicability, a plurality of substrates can participate in the reaction, and the 3, 3-disubstituted oxindole compound can be obtained with high yield and high stereoselectivity. See table 1:
Figure BDA0002282546270000191
TABLE 1
entry Ⅴ(R 2 ,R 3 ,R 4 ) Ⅵ(R 1 ) yield(％) dr ee(％)
16 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Me R 1 ＝2-FC 6 H 4 54 >20:1 99
17 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Me R 1 ＝3-ClC 6 H 4 93 19:1 >99
18 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Me R 1 ＝4-ClC 6 H 4 93 19:1 >99
19 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Me R 1 ＝4-FC 6 H 4 62 19:1 >99
20 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Me R 1 ＝4-BrC 6 H 4 95 >20:1 98
21 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Me R 1 ＝4-OMeC 6 H 4 92 >20:1 >99
22 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Me R 1 ＝4-CF 3 C 6 H 4 70 >20:1 95
23 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Me R 1 ＝2-naphthyl 43 >20:1 >99
24 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Me R 1 ＝2-thienyl 89 >20:1 99
25 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Me R 1 ＝H - - -
26 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Me R 1 ＝Me - - -
27 R 2 ＝4-OMeC 6 H 4 ,R 3 ＝H,R 4 ＝Me R 1 ＝C 6 H 5 84 >20:1 >99
28 R 2 ＝3-MeC 6 H 4 ,R 3 ＝H,R 4 ＝Me R 1 ＝C 6 H 5 79 13:1 >99
29 R 2 ＝3-OMeC 6 H 4 ,R 3 ＝H,R 4 ＝Me R 1 ＝C 6 H 5 91 >20:1 >99
30 R 2 ＝3-CF 3 C 6 H 4 ,R 3 ＝H,R 4 ＝Me R 1 ＝C 6 H 5 93 7:1 >99
31 R 2 ＝2-MeC 6 H 4 ,R 3 ＝H,R 4 ＝Me R 1 ＝C 6 H 5 66 >20:1 >99
32 R 2 ＝2-OHC 6 H 4 ,R 3 ＝H,R 4 ＝Me R 1 ＝C 6 H 5 88 >20:1 >99
33 R 2 ＝2-naphthyl,R 3 ＝H,R 4 ＝Me R 1 ＝C 6 H 5 89 12:1 >99
34 R 2 ＝2-thienyl,R 3 ＝H,R 4 ＝Me R 1 ＝C 6 H 5 75 >20:1 99
35 R 2 ＝3-methyl-2-thienyl,R 3 ＝H,R 4 ＝Me R 1 ＝C 6 H 5 89 >20:1 >99
36 R 2 ＝1-pyrrolyl,R 3 ＝H,R 4 ＝Me R 1 ＝C 6 H 5 81 >20:1 >99
37 R 2 ＝C 6 H 5 ,R 3 ＝4-Cl,R 4 ＝Me R 1 ＝C 6 H 5 - - -
38 R 2 ＝C 6 H 5 ,R 3 ＝5-F,R 4 ＝Me R 1 ＝C 6 H 5 95 12:1 >99
39 R 2 ＝C 6 H 5 ,R 3 ＝5-OMe,R 4 ＝Me R 1 ＝C 6 H 5 90 5:1 >99
40 R 2 ＝C 6 H 5 ,R 3 ＝7-CF 3 ,R 4 ＝Me R 1 ＝C 6 H 5 39 >20:1 95
41 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Bn R 1 ＝C 6 H 5 78 9:1 99
42 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝Boc R 1 ＝C 6 H 5 79 19:1 >99
43 R 2 ＝C 6 H 5 ,R 3 ＝H,R 4 ＝H R 1 ＝C 6 H 5 - - -

Claims (6)

1. A synthetic method for preparing propargylated 3, 3-disubstituted indoline-2-ketone compounds containing continuous chiral centers is characterized by comprising the following steps: in the presence of an alkaline additive, a chiral copper catalyst catalyzes a nucleophilic substitution reaction between a 3-substituted indoline-2-ketone compound and a propargyl acetate compound in a reaction medium to prepare a propargylated 3, 3-disubstituted indoline-2-ketone compound containing a continuous chiral center; the chiral copper catalyst is prepared from copper salt and chiral tridentate P, N, N-ligand or chiral tridentate N, N, N-ligand; the 3-substituted indoline-2-ketone compound has the following structure:
Figure FDA0003704330860000011
in the formula R 2 Is one of phenyl, 2-naphthyl, substituted phenyl, methyl, and five-membered or six-membered heterocyclic aromatic group containing one or more than two sulfur and nitrogen atoms; the substituent of the substituted phenyl is one of methyl, methoxy, hydroxyl and trifluoromethyl; r 3 Is one of hydrogen, fluorine, chlorine, methoxyl and trifluoromethyl; r 4 Is one of methyl, phenyl, benzyl and Boc;
the propargyl acetate compound has the following structure:
Figure FDA0003704330860000012
in the formula: r 1 Is one of methyl, phenyl, substituted phenyl, 2-naphthyl and 2-thienyl; the substituent on the substituted phenyl is one of fluorine, chlorine, bromine, methoxy and trifluoromethyl;
the chiral tridentate P, N, N-ligand or the chiral tridentate N, N, N-ligand has the following structural characteristics:
Figure FDA0003704330860000021
the propargylated 3, 3-disubstituted indoline-2-ketone compound containing a continuous chiral center has one of the following structures:
Figure FDA0003704330860000022
2. the method for synthesizing propargylated 3, 3-disubstituted indolin-2-ones containing a continuous chiral center according to claim 1, wherein the method comprises the following steps: the method comprises the following specific steps:
(1) preparation of chiral copper catalyst: under the protection of nitrogen, copper salt and chiral tridentate ligand are stirred in a reaction medium for 30 minutes according to the molar ratio of 1: 0.1-10 to prepare a chiral copper catalyst;
the chiral tridentate ligand is a chiral tridentate P, N, N-ligand or a chiral tridentate N, N, N-ligand;
(2) preparation of propargylated 3, 3-disubstituted indoline-2-ones containing a continuous chiral center: dissolving 3-substituted indoline-2-ketone, propargyl acetate and an alkaline additive in a reaction medium, then adding the solution into the solution of the chiral copper catalyst stirred in the step (1) under the protection of nitrogen for catalytic reaction, and stirring for reaction at a certain temperature for not less than 10 hours; after the reaction is finished, concentrating under reduced pressure until no solvent exists basically, separating by silica gel column chromatography, concentrating under reduced pressure, and drying in vacuum to obtain a target product;
the molar ratio of the chiral copper catalyst to the 3-substituted indoline-2-ketone compound is 0.01-100% to 1;
the molar ratio of the alkaline additive to the propargyl acetate compound is 0.5-10: 1;
the molar ratio of the 3-substituted indoline-2-ketone compound to the propargyl acetate compound is 1: 1 to 4.
3. The method for synthesizing propargylated 3, 3-disubstituted indolin-2-ones containing a continuous chiral center according to claim 1 or 2, wherein the method comprises the following steps: the reaction medium is at least one of methanol, ethanol, isopropanol, isobutanol, toluene, dichloromethane, diethyl ether, tetrahydrofuran, dimethyl sulfoxide or N, N-dimethylformamide.
4. The method for synthesizing propargylated 3, 3-disubstituted indoline-2-one compounds containing continuous chiral centers according to claim 2, wherein the method comprises the following steps: the copper salt is Cu (OAc) 2 ·H 2 O、Cu(OAc) 2 、Cu(OTf) 2 、CuCl 2 、CuOAc、CuCl、CuI、CuClO 4 、CuOTf·0.5C 6 H 6 、Cu(CH 3 CN) 4 BF 4 、Cu(CH 3 CN) 4 ClO 4 Or Cu (CH) 3 CN) 4 PF 6 One or more than two of them.
5. The method for synthesizing propargylated 3, 3-disubstituted indoline-2-one compounds containing continuous chiral centers according to claim 1, wherein the method comprises the following steps: the alkaline additive is i Pr 2 NEt、NEt 3 、 i PrNMe 2 、 i Bu 3 N、CyNMe 2 、Cy 2 NMe、 t BuOK、KOH、K 2 CO 3 、K 3 PO 4 、NaOH、Na 2 CO 3 、NaHCO 3 Or Cs 2 CO 3 One or more than two of them.
6. The method for synthesizing propargylated 3, 3-disubstituted indolin-2-ones containing a continuous chiral center according to claim 1 or 2, wherein the method comprises the following steps: the catalytic reaction conditions are as follows:
temperature: -40 ℃ to 0 ℃;
reaction medium: a protic solvent;
pressure: and (4) normal pressure.
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* Cited by examiner, † Cited by third party
Title
Catalytic Asymmetric Synthesis of Oxindoles Bearing a Tetrasubstituted Stereocenter at the C-3 Position;Feng Zhou等;《Advanced Synthesis & Catalysis》;20100528;第352卷(第9期);第1381-1407页 *
Copper-Catalyzed Asymmetric Propargylic Alkylation with Oxindoles: Diastereo- and Enantioselective Construction of Vicinal Tertiary and All-Carbon Quaternary Stereocenters;Jin-Tao Xia等;《Organic Letters》;20200124;第1102-1107页 *
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Enantioselective synthesis of chiral phosphonylated 2,3‐dihydrofurans by copper catalyzed asymmetric formal [3+2] cycloaddition of propargylic esters with β‐keto phosphonates;Xiushuai Chen等;《Chinese Journal of Catalysis》;20161231;第37卷(第8期);第1389-1384页 *

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