CN110172015A - α-quaternary carbon trifluoromethyl ketone compound and preparation method thereof - Google Patents
α-quaternary carbon trifluoromethyl ketone compound and preparation method thereof Download PDFInfo
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Abstract
α-quaternary carbon trifluoromethyl ketone compound method and such compound are prepared the invention discloses a kind of.Trifluoromethyl ketone compound is alkylated effect under the action of catalyst, has fast and efficiently synthesized α shown in formula (I)-quaternary carbon trifluoromethyl ketone compound.The advantages of present invention has raw material cheap and easy to get, and reaction condition is mild, the compatible height of substrate functional group, energy Quick Extended product structure.Meanwhile the present invention also provides a kind of methods for preparing polyfunctional group trifluoromethyl synthon.
Description
Technical field
The invention belongs to technical field of organic synthetic chemistry, it is related to a kind of α-quaternary carbon trifluoromethyl ketone compound and its preparation
Method.
Background technique
Fluorine atom and hydrogen atom radius are close, but have very big electronegativity difference.With fluorine replace molecule in hydrogen it
Resulting fluorochemical has special physics, chemical property afterwards.For example, it is very high that there is the material of perfluoroalkyl often to have
Chemical stability and the characteristics such as thermal stability, ultralow interfacial tension, hydrophobic；Can significantly it change after introducing fluoro-containing group into molecule
The stability and pharmacological activity of kind drug, increase lipophilicity, metabolic stability and the bioavilability of drug.Therefore, fluorine-containing
Compound is played an important role in national economy, science and techniques of defence and medicine research and development industry, is widely used in material, space flight, energy
The various fields such as source, life science and agricultural, the synthesis of fluorochemical and performance study are always one of research hotspot (1, R.
D. Chambers FRS, Fluorine in Organic Chemistry, Wiley-Blackwell, 2004；2, minister in ancient times phoenix
Tail feather, Qiu little Long, organic fluorine chemistry, Science Press, 2007；3,I. Ojima, Fluorine in Medicinal
Chemistry and Chemical Biology, Wiley-Blackwell, 2009；4,P. Kirsch, Modern
Fluoroorganic Chemistry: Synthesis, Reactivity, Applications, Wiley-VCH
Verlag GmbH, 2013.).
As the smallest perfluoroalkyl unit, trifluoromethyl is common fluorine-containing functional group.Trifluoromethyl is also strongest
One of lipophilic group.Rationally introducing trifluoromethyl can be enhanced lipophilicity, metabolic stability and the bioavilability of molecule.?
Medicine, Material Field, the compound containing trifluoromethyl yield unusually brilliant results, and are widely used in fluorescence probe, anticancer, anti parasitic, resist
The exploitation of the drugs such as virus.Therefore, synthetic method is also concerned.In numerous molecules containing trifluoromethyl, trifluoro
Methyl ketone is a kind of important compound.As a variety of enzyme inhibitors, trifluoromethyl alkyl ketone has good bioactivity, together
When still synthesize other important intermediates containing trifluoromethyl compound.The synthesis and Transformation Application of trifluoromethyl ketone compound
Exploitation also in continuous update (1, J.-P. B é gu é, D. Bonnet-Delpon,Tetrahedron 1991, 47,
3207； 2,G. K. S. Prakash, A. K. Yudin,Chem. Rev. 1997, 97, 757; 3、C. B.
Kelly, M. A. Mercadante, N. E. Leadbeater, Chem. Commun. 2013, 49, 11133；4,D.
Yang, Y. Zhou, Q. Chang, Y. Zhao, J. Qu, Progress in Chemistry 2014, 26, 976；
5、D. Yang, Y. Zhou, Q. Chang, Y. Zhao, J. Qu, Progress in Chemistry 2014, 26,
976; 5、W. Wu, Z. Weng, Synthesis 2018, 50, 1958.).
Many natural products and pharmaceutical activity molecule all contain quaternary carbon center, and it is special that these molecules are often shown in vivo
Physicochemical property and bioactivity.However, due to being connected with four biggish groups of volume on quaternary carbon atom, steric hindrance compared with
Greatly, therefore, the building of quaternary carbon still face so far it is huge challenge (1, J. Christoffers, A, Baro,Quaternary Stereocenters: Challenges and Solutions for Organic Synthesis, Wiley,
Weinheim, 2005；2,E. J. Corey, A. Guzman-Perez,Angew. Chem. Int. Ed. 1998, 37, 388; 3、J. Christoffers, A. Mann, Angew. Chem. Int. Ed. 2001, 40, 4591；4,
C. J. Douglas, L. E. Overman, Proc. Natl. Acad. Sci. U. S. A. 2004, 101,
5363; 5、B. M. Trost, C. Jiang, Synthesis 2006, 369；6,Y. Liu, S.-J. Han, W.-B.
Liu, B. M. Stoltz, Acc. Chem. Res. 2015, 48, 740; 7、K. S. Petersen,Tetrahedron Lett.2015, 56, 6523；8, T. Ling, F. Rivas,Tetrahedron 2016, 72,
6729; 9、X.-P. Zeng, Z.-Y. Cao, Y.-H. Wang, F. Zhou, J. Zhou, Chem. Rev. 2016,116, 7330；10,Y. Zhu, J. Han, J. Wang, N. Shibata, M. Sodeoka, V. A.
Soloshonok, J. A. S. Coelho, F. D. Toste, Chem. Rev. 2018, 118, 3887.).
Quaternary carbon containing trifluoromethyl is the nuclear structure (such as following formula) of many drugs and bioactive molecule, by trifluoromethyl
Being introduced into quaternary carbon structure is the common strategy in one, drug research field, and still, existing method all haves the defects that very big.It is first
First, existing method is all based on greatly directly introduces trifluoromethyl into molecule, still, trifluoromethyl reagent, such as Umemoto reagent
(T. Umemoto, S. Ishihara, J. Am. Chem. Soc. 1993, 115, 2156), Togni reagent (I.
Kieltsch, P. Eisenberger, A. Togni, Angew. Chem. Int. Ed. 2007, 46, 754),
Ruppert-Prakash reagent (Me3SiCF3) (G. K. S. Prakash, R. Krishnamurti, G. A. Olah,J. Am. Chem. Soc. 1989, 111, 393) price it is all costly, moreover, requiring to be added in these schemes
The trifluoromethyl reagent of amount；Secondly, what existing method obtained is mostly the simple compound of some structures, synthesis is obtained
The compound of structure novel will be expected to be found to have the compound of new function.
In order to overcome drawbacks described above, it is an object of the invention to disclose it is a kind of utilize trifluoromethyl ketone carry out alpha-alkylization preparation α-
The method of quaternary carbon trifluoromethyl ketone compound.The present invention has raw material cheap and easy to get, and reaction condition is mild, substrate functional group is compatible
Property it is high, can Quick Extended product structure the advantages of.Meanwhile the synthesis of polyfunctional group trifluoromethyl is prepared the present invention also provides a kind of
The method of son.
Summary of the invention
The present invention can overcome the disadvantages that the shortcomings that existing synthetic method, and economy efficiently synthesizes α-quaternary carbon trifluoromethyl ketone compound.
The present invention is alkylated effect using trifluoromethyl ketone compound as raw material under the action of catalyst, quickly, efficiently
Ground synthesizes α-quaternary carbon trifluoromethyl ketone compound shown in formula (I).
Formula (I)
Wherein, R, R1、R2It can be hydrogen, alkyl, aryl.
Shown in the preparation method such as formula (II)
Formula (II)
Wherein, LG can be OH, OCOOR, OCOR, OPO (OR)2, halogen.
The following steps are included:
Step (1) weighs catalyst, and catalyst amount is 5 mol%, and solvent is added；
Step (2), weighs raw material, stirs 10 hours under certain temperature after addition；
Step (3), after fully reacting, gained crude product column Chromatographic purification and obtain product.
Specific implementation method
In conjunction with following specific embodiments, the present invention is described in further detail.Protection content of the invention be not limited to
Lower embodiment.Without departing from the spirit and scope of the invention, various changes and advantages that will be apparent to those skilled in the art are all
It is included in the present invention, and using appended claims as protection scope.Implement process of the invention, condition, reagent,
Experimental method etc. is among the general principles and common general knowledge in the art in addition to what is specifically mentioned below, and the present invention does not have
Especially limitation content.
The specific steps of preparation method of the present invention include: first to weigh catalyst to be added in reaction flask, and solvent usage, which is added, is
1.0 L/mol are added trifluoromethyl ketone and alkylating reagent, are stirred to react at -50 DEG C, with thin-layer chromatography detection reaction to raw material
Consumption is complete.Gained crude product is used column chromatography to obtain the α-quaternary carbon trifluoromethyl ketone pure compounds.
Example 1 prepares 2-(to methyl cinnamyl base) -2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (A)
Under protection of argon gas, Pd (PPh is added in 10 mL catalysis test tube3)4 (0.005 mmol), dried solvent (1
ML), 2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (0.11 mmol) is then added, to methyl cinnamyl base carbonic ester (1
Mmol), TLC is monitored, and column chromatographic purifying obtains target product, yield 98% after reaction.1H NMR (600 MHz,
CDCl3) δ 8.07 (dd, J = 7.8, 0.7 Hz, 1H), 7.55 (td, J = 7.5, 1.3 Hz, 1H), 7.36
(t, J = 7.6 Hz, 1H), 7.27 (d, J = 7.7 Hz, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.10
(d, J = 7.9 Hz, 2H), 6.48 (d, J = 15.8 Hz, 1H), 6.20 – 6.02 (m, 1H), 3.22 –
3.08 (m, 1H), 2.98 (ddd, J = 14.8, 11.5, 6.0 Hz, 2H), 2.74 (dd, J = 14.3, 8.6
Hz, 2H), 2.32 (s, 3H), 2.24 (dt, J = 13.6, 4.8 Hz, 1H).13C NMR (151 MHz,
CDCl3) δ 194.24, 190.48 (q, J = 33.8 Hz), 142.78, 137.85, 135.02, 134.73,
134.16, 130.70, 129.52, 129.16, 128.52, 127.58, 126.47, 122.59, 115.78 (q, J
= 294.0 Hz), 61.56, 35.37, 27.56, 24.78, 21.38。
Example 2 prepares (S) -2-(to methyl cinnamyl base) -2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (B)
Under protection of argon gas, Pd is added in 10 mL catalysis test tube2 (dba)3 (0.005 mmol), chiral ligand (0.012
Mmol) dried solvent (1 mL), 30oC stirs half an hour, and 2- trifluoroacetyl group -3,4- dihydro -1- naphthalene is then added
Ketone (0.11 mmol) monitors methyl cinnamyl base carbonic ester (1 mmol), TLC, and column chromatographic purifying obtains mesh after reaction
Mark product, yield 96%, enantiomeric excess value 94%.1H NMR (600 MHz, CDCl3) δ 8.07 (dd, J = 7.8,
0.7 Hz, 1H), 7.55 (td, J = 7.5, 1.3 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.27
(d, J = 7.7 Hz, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 6.48
(d, J = 15.8 Hz, 1H), 6.20 – 6.02 (m, 1H), 3.22 – 3.08 (m, 1H), 2.98 (ddd, J
= 14.8, 11.5, 6.0 Hz, 2H), 2.74 (dd, J = 14.3, 8.6 Hz, 2H), 2.32 (s, 3H),
2.24 (dt, J = 13.6, 4.8 Hz, 1H).13C NMR (151 MHz, CDCl3) δ 194.24, 190.48 (q,J = 33.8 Hz), 142.78, 137.85, 135.02, 134.73, 134.16, 130.70, 129.52, 129.16,
128.52, 127.58, 126.47, 122.59, 115.78 (q, J = 294.0 Hz), 61.56, 35.37,
27.56, 24.78, 21.38。
Example 3 prepares 2- to chlorine cinnamyl -2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (C)
Under protection of argon gas, Pd (PPh is added in 10 mL catalysis test tube3)4 (0.005 mmol), dried solvent (1
), mL 2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (0.11 mmol) is then added, to chlorine cinnamyl carbonic ester (1
Mmol), TLC is monitored, and column chromatographic purifying obtains target product, yield 95% after reaction.1H NMR (600 MHz,
CDCl3) δ 8.08 (d, J = 7.3 Hz, 1H), 7.56 (td, J = 7.6, 1.2 Hz, 1H), 7.46 (s,
1H), 7.39 (d, J = 7.6 Hz, 1H), 7.37 – 7.34 (m, 1H), 7.29 (s, 1H), 7.26 (s,
2H), 7.24 (d, J = 7.8 Hz, 1H), 7.16 (t, J = 7.8 Hz, 1H), 6.44 (d, J = 15.8
Hz, 1H), 6.25 – 6.11 (m, 1H), 3.22 – 3.09 (m, 1H), 3.01 (ddd, J = 15.1, 10.8,
5.7 Hz, 3H), 2.85 – 2.70 (m, 2H), 2.22 (dt, J = 13.6, 4.9 Hz, 2H).13C NMR (151
MHz, CDCl3) δ 194.01, 190.42 (q,J=33.8 Hz), 142.64, 139.07, 134.85, 133.76,
130.86, 130.71, 130.34, 129.5, 129.19, 128.60, 127.70, 125.46, 125.20,
123.06, 114.79, 61.50, 35.29, 27.80, 24.84。
Example 4 prepares (S) -2- to chlorine cinnamyl -2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (D)
Under protection of argon gas, Pd is added in 10 mL catalysis test tube2 (dba)3 (0.005 mmol), chiral ligand (0.012
Mmol) dried solvent (1 mL), 30oC stirs half an hour, and 2- trifluoroacetyl group -3,4- dihydro -1- naphthalene is then added
Ketone (0.11 mmol) monitors chlorine cinnamyl carbonic ester (1 mmol), TLC, and column chromatographic purifying obtains target after reaction
Product, yield 94%, enantiomeric excess value 93%.1H NMR (600 MHz, CDCl3) δ 8.08 (d, J = 7.3 Hz,
1H), 7.56 (td, J = 7.6, 1.2 Hz, 1H), 7.46 (s, 1H), 7.39 (d, J = 7.6 Hz, 1H),
7.37 – 7.34 (m, 1H), 7.29 (s, 1H), 7.26 (s, 2H), 7.24 (d, J = 7.8 Hz, 1H),
7.16 (t, J = 7.8 Hz, 1H), 6.44 (d, J = 15.8 Hz, 1H), 6.25 – 6.11 (m, 1H),
3.22 – 3.09 (m, 1H), 3.01 (ddd, J = 15.1, 10.8, 5.7 Hz, 3H), 2.85 – 2.70 (m,
2H), 2.22 (dt, J = 13.6, 4.9 Hz, 2H).13C NMR (151 MHz, CDCl3) δ 194.01, 190.42
(q,J=33.8 Hz), 142.64, 139.07, 134.85, 133.76, 130.86, 130.71, 130.34, 129.5,
129.19, 128.60, 127.70, 125.46, 125.20, 123.06, 114.79, 61.50, 35.29, 27.80,
24.84。
Example 5 prepares 2- to fluorine cinnamyl -2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (E)
Under protection of argon gas, Pd (PPh is added in 10 mL catalysis test tube3)4 (0.005 mmol), dried solvent (1
), mL 2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (0.11 mmol) is then added, to fluorine cinnamyl carbonic ester (1
Mmol), TLC is monitored, and column chromatographic purifying obtains target product, yield 98% after reaction.1H NMR (600 MHz,
CDCl3) δ 8.08 (dd, J = 7.9, 0.8 Hz, 1H), 7.56 (td, J = 7.5, 1.3 Hz, 1H), 7.37
(t, J = 7.6 Hz, 1H), 7.34 – 7.26 (m, 3H), 6.98 (t, J = 8.7 Hz, 2H), 6.47 (d,J = 15.8 Hz, 1H), 6.21 – 5.96 (m, 1H), 3.22 – 3.09 (m, 1H), 3.00 (ddd, J =
15.2, 10.6, 5.5 Hz, 2H), 2.76 (dd, J = 14.3, 8.5 Hz, 2H), 2.23 (dt, J = 13.6,
4.9 Hz, 1H).13C NMR (151 MHz, CDCl3) δ 194.14, 190.42 (q, J = 33.8 Hz), 162.65
(d, J = 247.1 Hz), 142.68, 134.81, 133.92, 133.11 (d, J = 3.3 Hz), 130.68,
129.18, 128.52, 128.08 (d, J = 8.0 Hz), 127.63, 123.46 (d, J = 2.1 Hz),
115.75 (q, J = 293.8 Hz), 115.71 (d, J = 21.7 Hz), 61.53 35.27, 27.71, 24.79。
Example 6 prepares (S) -2- to fluorine cinnamyl -2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (F)
Under protection of argon gas, Pd is added in 10 mL catalysis test tube2 (dba)3 (0.005 mmol), chiral ligand (0.012
Mmol) dried solvent (1 mL), 30oC stirs half an hour, and 2- trifluoroacetyl group -3,4- dihydro -1- naphthalene is then added
Ketone (0.11 mmol) monitors fluorine cinnamyl carbonic ester (1 mmol), TLC, and column chromatographic purifying obtains target after reaction
Product, yield 96%, enantiomeric excess value 94%.1H NMR (600 MHz, CDCl3) δ 8.08 (dd, J = 7.9, 0.8
Hz, 1H), 7.56 (td, J = 7.5, 1.3 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.34 –
7.26 (m, 3H), 6.98 (t, J = 8.7 Hz, 2H), 6.47 (d, J = 15.8 Hz, 1H), 6.21 –
5.96 (m, 1H), 3.22 – 3.09 (m, 1H), 3.00 (ddd, J = 15.2, 10.6, 5.5 Hz, 2H),
2.76 (dd, J = 14.3, 8.5 Hz, 2H), 2.23 (dt, J = 13.6, 4.9 Hz, 1H).13C NMR (151
MHz, CDCl3) δ 194.14, 190.42 (q, J = 33.8 Hz), 162.65 (d, J = 247.1 Hz),
142.68, 134.81, 133.92, 133.11 (d, J = 3.3 Hz), 130.68, 129.18, 128.52,
128.08 (d, J = 8.0 Hz), 127.63, 123.46 (d, J = 2.1 Hz), 115.75 (q, J = 293.8
Hz), 115.71 (d, J = 21.7 Hz), 61.53 35.27, 27.71, 24.79。
Example 7 prepares 2-(3,5- dibromo cinnamyl) -2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (G)
Under protection of argon gas, Pd (PPh is added in 10 mL catalysis test tube3)4 (0.005 mmol), dried solvent (1
ML), 2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (0.11 mmol), 3,5- dibromo cinnamyl carbonic ester (1 is then added
Mmol), TLC is monitored, and column chromatographic purifying obtains target product, yield 93% after reaction.1H NMR (600 MHz,
CDCl3) δ 8.08 (d, J = 7.8 Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H), 7.50 (s, 1H),
7.46 – 7.33 (m, 3H), 7.29 (d, J = 7.7 Hz, 1H), 6.36 (d, J = 15.8 Hz, 1H),
6.25 – 6.12 (m, 1H), 3.18 – 3.09 (m, 1H), 3.07 – 2.93 (m, 2H), 2.86 – 2.72
(m, 2H), 2.19 (dt, J = 13.6, 4.8 Hz, 1H).13C NMR (151 MHz, CDCl3) δ 193.85,
190.49 (q, J = 33.8 Hz), 142.52, 140.44, 134.92, 133.16, 132.42, 130.60,
129.20, 128.56, 128.25, 127.72, 127.10, 123.39, 115.71 (q, J = 293.8 Hz),
61.44, 35.14, 27.87, 24.80。
Example 8 prepares (S) -2-(3,5- dibromo cinnamyl) -2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (H)
Under protection of argon gas, Pd is added in 10 mL catalysis test tube2 (dba)3 (0.005 mmol), chiral ligand (0.012
Mmol) dried solvent (1 mL), 30oC stirs half an hour, and 2- trifluoroacetyl group -3,4- dihydro -1- naphthalene is then added
Ketone (0.11 mmol), 3,5- dibromo cinnamyl carbonic ester (1 mmol), TLC monitoring, column chromatographic purifying obtains after reaction
Target product, yield 85%, enantiomeric excess value 89%.1H NMR (600 MHz, CDCl3) δ 8.08 (d, J = 7.8
Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H), 7.50 (s, 1H), 7.46 – 7.33 (m, 3H), 7.29
(d, J = 7.7 Hz, 1H), 6.36 (d, J = 15.8 Hz, 1H), 6.25 – 6.12 (m, 1H), 3.18 –
3.09 (m, 1H), 3.07 – 2.93 (m, 2H), 2.86 – 2.72 (m, 2H), 2.19 (dt, J = 13.6,
4.8 Hz, 1H).13C NMR (151 MHz, CDCl3) δ 193.85, 190.49 (q, J = 33.8 Hz),
142.52, 140.44, 134.92, 133.16, 132.42, 130.60, 129.20, 128.56, 128.25,
127.72, 127.10, 123.39, 115.71 (q, J = 293.8 Hz), 61.44, 35.14, 27.87, 24.80。
Example 9 prepares the bromo- 3,4- dihydro -1- naphthalenone (I) of 2- cinnamyl -2- trifluoroacetyl group -7-
Under protection of argon gas, Pd (PPh is added in 10 mL catalysis test tube3)4 (0.005 mmol), dried solvent (1
), mL the bromo- 3,4- dihydro -1- naphthalenone of 2- trifluoroacetyl group -7- (0.11 mmol), cinnamyl carbonic ester (1 is then added
Mmol), TLC is monitored, and column chromatographic purifying obtains target product, yield 95% after reaction.1H NMR (600 MHz,
CDCl3) δ 8.20 (d, J = 2.0 Hz, 1H), 7.66 (dd, J = 8.2, 2.1 Hz, 1H), 7.31 (dt,J = 15.1, 7.5 Hz, 4H), 7.27 – 7.21 (m, 1H), 7.18 (t, J = 9.5 Hz, 1H), 6.51
(d, J = 15.8 Hz, 1H), 6.26 – 6.05 (m, 1H), 3.13 – 3.03 (m, 1H), 3.03 – 2.88
(m, 2H), 2.74 (ddd, J = 14.4, 12.5, 6.7 Hz, 2H), 2.24 (dt, J = 13.7, 5.0 Hz,
1H).13C NMR (151 MHz, CDCl3) δ 192.92, 190.06 (q, J = 34.0 Hz), 141.42,
137.56, 136.78, 135.45, 132.21, 131.22, 130.96, 128.85, 128.08, 126.59,
123.21, 121.64, 115.71 (q, J = 293.8 Hz), 61.32, 35.45, 27.59, 24.46。
Example 10 prepares the bromo- 3,4- dihydro -1- naphthalenone (J) of (S) -2- cinnamyl -2- trifluoroacetyl group -7-
Under protection of argon gas, Pd is added in 10 mL catalysis test tube2 (dba)3 (0.005 mmol), chiral ligand (0.012
Mmol) dried solvent (1 mL), 30oC stirs half an hour, and bromo- 3, the 4- dihydro-of 2- trifluoroacetyl group -7- is then added
1- naphthalenone (0.11 mmol), cinnamyl carbonic ester (1 mmol), TLC monitoring, column chromatographic purifying obtains target after reaction
Product, yield 94%, enantiomeric excess value 95%.1H NMR (600 MHz, CDCl3) δ 8.20 (d, J = 2.0 Hz,
1H), 7.66 (dd, J = 8.2, 2.1 Hz, 1H), 7.31 (dt, J = 15.1, 7.5 Hz, 4H), 7.27 –
7.21 (m, 1H), 7.18 (t, J = 9.5 Hz, 1H), 6.51 (d, J = 15.8 Hz, 1H), 6.26 –
6.05 (m, 1H), 3.13 – 3.03 (m, 1H), 3.03 – 2.88 (m, 2H), 2.74 (ddd, J = 14.4,
12.5, 6.7 Hz, 2H), 2.24 (dt, J = 13.7, 5.0 Hz, 1H).13C NMR (151 MHz, CDCl3) δ
192.92, 190.06 (q, J = 34.0 Hz), 141.42, 137.56, 136.78, 135.45, 132.21,
131.22, 130.96, 128.85, 128.08, 126.59, 123.21, 121.64, 115.71 (q, J = 293.8
Hz), 61.32, 35.45, 27.59, 24.46。
Example 11 prepares 2- (3- cyclohexyl -2- allyl) -2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (K)
Under protection of argon gas, Pd (PPh is added in 10 mL catalysis test tube3)4 (0.005 mmol), dried solvent (1
), mL 2- trifluoroacetyl group -3,4- dihydro -1- naphthalenone (0.11 mmol), 2- (3- cyclohexyl -2- allyl) carbon is then added
Acid esters (1 mmol), TLC monitoring, column chromatographic purifying obtains target product, yield 98% after reaction.1H NMR (600
MHz, CDCl3) δ 8.04 (d, J = 7.8 Hz, 1H), 7.53 (t, J = 7.4 Hz, 1H), 7.35 (t, J
= 7.6 Hz, 1H), 7.28 – 7.22 (m, 1H), 5.52 (dd, J = 15.4, 6.8 Hz, 1H), 5.39 –
5.29 (m, 1H), 3.14 – 3.04 (m, 1H), 2.96 (dt, J = 17.4, 4.8 Hz, 1H), 2.80 (dd,J = 14.3, 6.0 Hz, 1H), 2.75 – 2.63 (m, 1H), 2.51 (dd, J = 14.3, 8.3 Hz, 1H),
2.18 (dt, J = 13.5, 4.8 Hz, 1H), 1.98 – 1.86 (m, 1H), 1.66 (dd, J = 33.8,
16.1 Hz, 5H), 1.29 – 1.19 (m, 2H), 1.14 (t, J = 12.4 Hz, 1H), 1.07 – 0.97 (m,
2H).13C NMR (151 MHz, CDCl3) δ 193.46, 189.34 (q, J = 33.6 Hz), 141.80,
141.59, 133.57, 129.88, 128.11 , 127.43, 126.47, 119.98, 114.77 (q, J = 294.0
Hz), 60.46, 39.93, 34.04, 32.19, 32.10, 26.49, 25.36, 25.16 (d, J = 1.4 Hz),
23.71。
Example 12 prepares the bromo- 3,4- dihydro -1- naphthalenone (L) of (S) -2- cinnamyl -2- trifluoroacetyl group -7-
Under protection of argon gas, Pd is added in 10 mL catalysis test tube2 (dba)3 (0.005 mmol), chiral ligand (0.012
Mmol) dried solvent (1 mL), 30oC stirs half an hour, and 2- trifluoroacetyl group -3,4- dihydro -1- naphthalene is then added
Ketone (0.11 mmol), 2- (3- cyclohexyl -2- allyl) carbonic ester (1 mmol), TLC monitoring, column chromatography is pure after reaction
Change obtains target product, yield 95%, enantiomeric excess value 93%.1H NMR (600 MHz, CDCl3) δ 8.04 (d, J =
7.8 Hz, 1H), 7.53 (t, J = 7.4 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.28 – 7.22
(m, 1H), 5.52 (dd, J = 15.4, 6.8 Hz, 1H), 5.39 – 5.29 (m, 1H), 3.14 – 3.04
(m, 1H), 2.96 (dt, J = 17.4, 4.8 Hz, 1H), 2.80 (dd, J = 14.3, 6.0 Hz, 1H),
2.75 – 2.63 (m, 1H), 2.51 (dd, J = 14.3, 8.3 Hz, 1H), 2.18 (dt, J = 13.5, 4.8
Hz, 1H), 1.98 – 1.86 (m, 1H), 1.66 (dd, J = 33.8, 16.1 Hz, 5H), 1.29 – 1.19
(m, 2H), 1.14 (t, J = 12.4 Hz, 1H), 1.07 – 0.97 (m, 2H).13C NMR (151 MHz,
CDCl3) δ 193.46, 189.34 (q, J = 33.6 Hz), 141.80, 141.59, 133.57, 129.88,
128.11 , 127.43, 126.47, 119.98, 114.77 (q, J = 294.0 Hz), 60.46, 39.93,
34.04, 32.19, 32.10, 26.49, 25.36, 25.16 (d, J = 1.4 Hz), 23.71。
Finally, it is stated that preferred embodiment above is only used to illustrate the technical scheme of the present invention and not to limit it, although logical
It crosses above preferred embodiment the present invention is described in detail, however, those skilled in the art should understand that, can be
Various changes are made to it in form and in details, without departing from claims of the present invention limited range.
Claims (5)
1. the preparation of α-quaternary carbon trifluoromethyl ketone compound, which is characterized in that prepared using the alkylated reaction of trifluoromethyl ketone
α-quaternary carbon trifluoromethyl ketone compound；
Under the effect of the catalyst, trifluoromethyl ketone is reacted with allylation reagent, and α-quaternary carbon three as shown in formula (I) is prepared
Methyl fluoride ketone compound；
Formula (I)
Wherein, R, R1、R2It can be hydrogen, alkyl, aryl；
Shown in the preparation method such as formula (II)
Formula (II)
The following steps are included:
Step (1) weighs catalyst, and catalyst amount is 5 mol%, and solvent is added；
Step (2), weighs raw material, stirs 10 hours under certain temperature after addition；
Step (3), after fully reacting, gained crude product column Chromatographic purification and obtain product.
2. preparation method as described in claim 1, which is characterized in that in the compound, R, R1、R2It can be hydrogen, alkyl, virtue
Base.
3. preparation method as described in claim 1, which is characterized in that the α being prepared-quaternary carbon trifluoromethyl ketone chemical combination
Object is individual isomer either its enantiomeric mixture.
4. preparation method as described in claim 1, which is characterized in that the catalyst is Pd2(dba)3、Pd(PPh)4And
The complex compound of they and chiral ligand formation.
5. preparation method as described in claim 1, which is characterized in that chiral ligand used is imines, BINAP, oxazole
Quinoline.
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