CN109721564A - A kind of new method synthesizing the polysubstituted alkene of sulfur-bearing - Google Patents
A kind of new method synthesizing the polysubstituted alkene of sulfur-bearing Download PDFInfo
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Abstract
It is, using propyne derivative and thiazolone as reaction raw materials, using chiral phosphoric acid as catalyst, to react to obtain four substitution connection vinyl compounds in reaction dissolvent the invention discloses a kind of synthetic method for synthesizing the polysubstituted vinyl compound of sulfur-bearing.Reaction condition of the present invention is mild, and raw material is easy to get inexpensive, and operation is simple, and yield is higher, provides crucial skeleton structure for the synthesis of many natural products and drug, can be widely used in industrial-scale production.
Description
Technical field
Present invention relates particularly to a kind of new methods for preparing the polysubstituted alkene of sulfur-bearing, belong to organic compound technique application skill
Art field.
Background technique
Polysubstituted vinyl compound is a kind of extremely important pharmaceutical-chemical intermediate, has very high application value.
Polysubstituted alkene is alternatively arranged as chiral complex, chiral catalyst.It is as follows:
The conventional method of polysubstituted alkene is mainly the spontaneous preparation that is converted by using metal catalytic or chiral alkynes.But
It is that the use of the at high cost and heavy metal of spontaneous conversion can cause environment seriously to pollute, the application of the method is made to be restricted.
Summary of the invention
The present invention overcomes the disadvantages described above of the prior art, innovatively proposes for the first time a kind of environmentally protective, is simple and efficient system
The new method of the standby polysubstituted vinyl compound of sulfur-bearing, is catalyst by using chiral phosphoric acid, can efficiently realize reaction
Conversion.As shown in the above formula (I), the present invention is utilized using propyne derivative and thiazolone as reaction raw materials, is with chiral phosphoric acid
Catalyst is reacted in reaction dissolvent, and synthesis four replaces connection vinyl compound.
In the present invention, R is alkyl or aromatic radical or substituted aromatic ring and heterocycle, all kinds of side chains.
In the present invention, the usage ratio of the starting material propyne derivative and thiazolone is 1:1-1:5.Preferably, two
Person's usage ratio is 1:1.2.
In the present invention, the catalyst is chiral phosphoric acid；The dosage of the catalyst is 1-100%.The catalyst
Dosage is the 1-100mol% of raw material propyne derivative.Preferably, the catalyst amount is 1mol%.
In the present invention, the reaction dissolvent be methylene chloride, chloroform, tetrahydrofuran, methanol, 1,2- dichloroethanes,
Acetonitrile, toluene, 1,4- dioxane.The reaction dissolvent include but is not limited to more than, can also be ether, ethyl acetate,
Benzotrifluoride, xylene compound or methyl phenyl ethers anisole.
In the present invention, the synthetic reaction is carried out at a temperature of 0-80 DEG C.It preferably, is carried out anti-at a temperature of 25 DEG C
It answers.
Specifically, synthetic reaction of the present invention is in reaction flask A, by propyne derivative (substrate 1, X mmol) and thiazolone
(substrate 2, Y mmol) is dissolved in Z mL reaction dissolvent, at room temperature, is added chiral phosphoric acid (W mmol).Reaction is at 0-80 DEG C
React 48 hours.Reaction process is detected with TLC.After completion of the reaction, directly plus silica gel, dry chromatography, isolated target are revolved
Product 3.
The advantages of synthetic reaction of the present invention includes: that each raw material used in synthetic method of the present invention is very simple, is work
Industry commodity, it is simple and easy to get, it is from a wealth of sources, and performance is highly stable, does not need special preservation condition.It is each used in the present invention
Kind catalyst is also all common commercial reagents, highly stable.Synthesize traditional method one of polysubstituted vinyl compound
As be to be realized using reacting for the propyne derivative of metal catalytic and other substrates.But due to the adaptation of propyne derivative
Property is not extensive enough, and the use of heavy metal can cause environment seriously to pollute, and very big limitation is caused to industrialized production.The present invention
Using propyne derivative and thiazolone simple and easy to get as reaction raw materials, under chiral phosphoric acid effect, reaction obtains polysubstituted alkene
Class compound.Operation is fairly simple, and reaction condition is mild, and yield is higher, is suitble to large-scale industrial production.The present invention closes
At four replace connection vinyl compounds be many natural products and active drug molecule core skeleton, innovative design of the present invention
Reaction route provides a generally applicable preparation method to synthesize this kind of compound.
Specific embodiment
In conjunction with following specific embodiments, the present invention is described in further detail, and of the invention protects content not limit to
In following embodiment.Without departing from the spirit and scope of the invention, those skilled in the art it is conceivable that variation and excellent
Point is all included in the present invention, and using appended claims as protection scope.Implement process of the invention, condition,
Reagent, experimental method etc. are among the general principles and common general knowledge in the art, this hair in addition to what is specifically mentioned below
It is bright that there are no special restrictions to content.Data given by following embodiment include concrete operations and reaction condition and product.Product is pure
Degree is identified by nuclear magnetic resonance.
Embodiment 1
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1a (0.05mmol, 15.0mg), substrate
2a (0.06mmol, 15.2mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3aa (89%).1H NMR(DMSO-d6,500MHz):δ(ppm)9.77 (s,1H),8.12-
8.11(m,2H),7.76-7.75(m,1H),7.60-7.57(m,4H),7.37-7.17(m,15H), 6.89-6.87(m,2H)
.13C NMR(DMSO-d6,125MHz):δ(ppm)206.9,194.1,189.6, 158.2,136.8,136.3,135.4,
134.0,131.6,130.0,129.8,129.4,129.3,129.0,129.0, 128.9,128.4,128.3,128.2,
128.0,127.4,125.3,116.2,115.5,109.8,74.0.HRMS (ESI):exact mass calculated for
M+(C36H26NO2S)requires m/z 536.1679,found m/z 536.1679.
Embodiment 2
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1a (0.05mmol, 15.0mg), substrate
2b (0.06mmol, 19.8mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ab (81%).1H NMR(DMSO-d6,500MHz):δ(ppm)9.59 (s,1H),8.08-
8.06(m,1H),7.87-7.83(m,2H),7.55-7.50(m,2H),7.45-7.34(m,7H), 7.28-7.19(m,6H),
7.07-7.01(m,1H),6.94-6.93(m,1H),6.88-6.86(m,1H), 6.78-6.77(m,1H),6.63-6.60(m,
1H).13C NMR(DMSO-d6,125MHz):δ(ppm) 206.8,194.0,189.5,158.1,136.7,136.2,135.3,
133.9,131.5,129.9,129.7,129.3, 129.1,128.9,128.9,128.8,128.3,128.2,128.1,
127.8,127.3,125.2,116.1,115.4, 109.7,73.9.HRMS(ESI):exact mass calculated for
M+(C36H25BrNO2S)requires m/z 616.0769,found m/z 616.0764.
Embodiment 3
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1a (0.05mmol, 15.0mg), substrate
2c (0.06mmol, 16.0mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ac (89%).1H NMR(DMSO-d6,500MHz):δ(ppm) 9.71(s,1H),8.04-
8.03(m,2H),7.57-7.55(m,2H),7.44-7.42(m,2H),7.36-7.33(m, 3H),7.25-7.14(m,12H),
6.86-6.84(m,2H),2.41(s,3H).13C NMR(DMSO-d6,125 MHz):δ(ppm)206.9,193.6,189.5,
158.1,147.6,137.0,135.4,134.1,130.6,129.7, 129.4,129.3,129.1,129.0,128.9,
128.4,128.3,128.1,127.9,127.4,125.3,116.2, 115.4,109.8,73.8,21.9.HRMS(ESI):
exact mass calculated for M+(C37H28NO2S) requires m/z 550.1841,found m/z
550.1837.
Embodiment 4
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1a (0.05mmol, 15.0mg), substrate
2d (0.06mmol, 16.0mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ad (85%).1H NMR(CDCl3,500MHz):δ(ppm) 7.93-7.91(m,2H),
7.65-7.63(m,2H),7.49-7.47(m,1H),7.40-7.37(m,1H), 7.31-7.28(m,7H),7.25-7.15(m,
8H),6.81-6.80(m,2H),5.79(s,1H),2.42(s,3H). 13C NMR(CDCl3,125MHz):δ(ppm)207.3,
194.4,190.2,155.9,139.0,136.6,136.1, 135.4,134.3,131.9,130.0,129.4,128.9,
128.9,128.5,128.4,128.4,128.3,127.8, 127.6,127.5,127.5,127.3,126.1,115.7,
115.6,109.7,74.2,21.2.HRMS(ESI):exact mass calculated for M+(C37H28NO2S)
requires m/z 550.1841,found m/z 550.1835.
Embodiment 5
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1a (0.05mmol, 15.0mg), substrate
2e (0.06mmol, 17.0mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ae (85%).1H NMR(DMSO-d6,500MHz):δ(ppm)9.73 (s,1H),7.72-
7.71(m,1H),7.58-7.51(m,4H),7.37-7.32(m,4H),7.27-7.15(m,12H), 6.87-6.86(m,2H),
3.83(s,3H).13C NMR(DMSO-d6,125MHz):δ(ppm)207.0,194.0, 189.5,160.1,158.1,136.8,
135.4,134.0,132.9,131.2,129.7,129.4,129.3,129.1, 128.9,128.4,128.3,128.2,
127.9,127.4,125.3,122.8,121.6,116.2,115.5,112.7, 109.8,74.0,56.0.HRMS(ESI):
exact mass calculated for M+(C37H28NO3S)requires m/z 566.1790,found m/z
566.1787.
Embodiment 6
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1a (0.05mmol, 15.0mg), substrate
2f (0.06mmol, 16.3mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3af (81%).1H NMR(DMSO-d6,500MHz):δ(ppm)9.75 (s,1H),8.21-
8.18(m,1H),7.85-7.76(m,1H),7.61-7.59(m,2H),7.52-7.44(m,2H), 7.40-7.33(m,4H),
7.28-7.18(m,11H),6.89-6.88(m,2H).13C NMR(DMSO-d6,125 MHz):δ(ppm)207.0,189.5,
189.0,162.2 (d, J=1030.0Hz), 158.2,138.1 (d, J=40.0Hz), 136.6,135.4,133.9,131.2,
(129.7,129.4,129.3,129.05,128.9,128.3 d, J=120.0Hz), 128.2,128.0,127.4,126.4,
126.1 (d, J=10.0Hz), 125.3,119.7 (d, J=35.0Hz), 117.7 (d, J=85.0Hz), 116.2,115.6,
109.7,72.4.HRMS(ESI):exact mass calculated for M+(C36H25FNO2S)requires m/z
554.1590,found m/z 554.1587.
Embodiment 7
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1a (0.05mmol, 15.0mg), substrate
2g (0.06mmol, 17.2mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ag (83%).1H NMR(DMSO-d6,500MHz):δ(ppm)9.74 (s,1H),7.93-
7.92(m,1H),7.68-7.67(m,2H),7.60-7.52(m,3H),7.41-7.34(m,3H), 7.29-7.16(m,12H),
6.88-6.86(m,2H).13C NMR(DMSO-d6,125MHz):δ(ppm) 207.0,193.2,189.2,158.2,136.4,
135.4,133.9,132.8,131.9,131.7,130.9,129.8, 129.5,129.3,129.2,129.1,128.5,
128.5,128.3,128.2,127.9,127.3,125.2,116.2, 115.7,109.4,74.0.HRMS(ESI):exact
mass calculated for M+(C36H25ClNO2S) requires m/z 570.1295,found m/z 570.1295.
Embodiment 8
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1a (0.05mmol, 15.0mg), substrate
2h (0.06mmol, 19.8mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ah (76%).1H NMR(DMSO-d6,500MHz):δ(ppm)9.73 (s,1H),7.86-
7.84(m,1H),7.77-7.75(m,1H),7.61-7.56(m,4H),7.42-7.18(m,15H), 6.87-6.85(m,2H)
.13C NMR(DMSO-d6,125MHz):δ(ppm)207.1,194.8,189.3, 158.2,136.4,135.5,135.0,
133.9,133.3,131.4,129.8,129.6,129.3,129.2,129.1, 128.8,128.6,128.4,128.2,
127.9,127.3,125.2,121.0,116.2,115.7,109.3,74.6. HRMS(ESI):exact mass
calculated for M+(C36H25BrNO2S)requires m/z 616.0769, found m/z 616.0767.
Embodiment 9
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1a (0.05mmol, 15.0mg), substrate
2i (0.06mmol, 16.0mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ai (83%).1H NMR(CDCl3,500MHz):δ(ppm) 7.84-7.83(m,2H),
7.56-7.52(m,3H),7.39-7.28(m,10H),7.25-7.21(m,4H), 7.14-7.08(m,3H),6.92-6.90
(m, 2H), 3.81 (d, J=15.0Hz, 1H), 3.50 (d, J=15.0Hz, 1H)13C NMR(CDCl3,125MHz):δ(ppm)
206.2,195.4,192.9,155.9,135.5,134.9, 134.8,134.3,131.9,130.8,130.1,128.8,
128.6,128.5,128.3,128.2,128.0,127.9, 127.8,127.5,127.3,115.7,114.1,109.9,
71.9,43.6.HRMS(ESI):exact mass calculated for M+(C37H28NO2S)requires m/z
550.1841,found m/z 550.1838.
Embodiment 10
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1a (0.05mmol, 15.0mg), substrate
2j (0.06mmol, 13.1mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3aj (75%).1H NMR(CDCl3,500MHz):δ(ppm) 8.05-8.03(m,2H),
7.64-7.61(m,3H),7.47-7.44(m,2H),7.38-7.28(m,7H), 7.23-7.20(m,3H),6.89-6.87(m,
2H), 5.80 (s, 1H), 2.87-2.81 (m, 1H), 0.99-0.98 (d, J=5.0Hz, 1H), 0.96-0.94 (d, J=
10.0Hz,1H).13C NMR(CDCl3,125MHz):δ(ppm) 206.4,196.2,193.5,155.5,135.8,135.5,
134.9,132.1,130.2,129.7,128.9,128.7, 128.5,128.5,128.3,128.2,127.8,127.7,
115.5,113.1,109.0,78.5,35.2,20.7,17.7. HRMS(ESI):exact mass calculated for M+
(C33H28NO2S)requires m/z 502.1841, found m/z 502.1835.
Embodiment 11
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1b (0.05mmol, 16.7mg), substrate
2a (0.06mmol, 15.2mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ba (87%).1H NMR(DMSO-d6,500MHz):δ(ppm)9.75 (s,1H),8.13-
8.11(m,2H),7.80-7.77(m,1H),7.62-7.55(m,4H),7.38-7.32(m,5H), 7.20-7.14(m,9H),
6.87-6.85(m,2H).13C NMR(DMSO-d6,125MHz):δ(ppm) 207.3,194.0,189.0,156.0,141.9,
136.2,135.3,135.1,133.4,132.9,131.8,130.0, 129.1,128.9,128.9,128.8,128.7,
128.6,128.4,128.3,127.8,127.1,115.9,115.7, 109.1,74.1.HRMS(ESI):exact mass
calculated for M+(C36H25ClNO2S)requires m/z 570.1295,found m/z 570.1291.
Embodiment 12
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1c (0.05mmol, 18.9mg), substrate
2a (0.06mmol, 15.2mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ca (93%).1H NMR(CDCl3,500MHz):δ(ppm) 7.99-7.93(m,3H),
7.54-7.51(m,1H),7.45-7.40(m,5H),7.30-7.28(m,6H), 7.22-7.20(m,2H),7.14-7.13(m,
1H),7.06-7.05(m,2H),6.82-6.81(m,2H), 6.68-6.67(m,1H).13C NMR(CDCl3,125MHz):δ
(ppm)207.3,194.1,190.0,156.0, 136.2,135.4,135.1,133.4,131.6,129.9,129.1,
129.1,129.0,128.9,128.6,128.5, 128.3,127.8,126.9,126,0,121.6,116.1,115.7,
115.1,109.2,74.1.HRMS(ESI): exact mass calculated for M+(C36H25BrNO2S)requires
m/z 614.0789,found m/z 614.0791.
Embodiment 13
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1d (0.05mmol, 15.7mg), substrate
2a (0.06mmol, 15.2mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3da (83%).1H NMR(CDCl3,500MHz):δ(ppm) 8.12-8.10(m,2H),
7.67-7.63(m,3H),7.51-7.48(m,2H),7.30-7.29(m,5H), 7.25-7.14(m,7H),7.03-7.02(m,
2H),6.81-6.79(m,2H),2.27(s,3H).13C NMR (CDCl3,125MHz):δ(ppm)207.0,194.3,190.2,
155.9,137.4,136.6,135.5,135.2, 132.0,131.3,130.0,129.5,129.2,129.0,128.9,
128.8,128.8,128.5,128.4,128.3, 128.3,127.9,127.6,127.4,115.6,109.6,74.4,
21.1.HRMS(ESI):exact mass calculated for M+(C37H28NO2S)requires m/z 550.1841,
found m/z 550.1838.
Embodiment 14
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1e (0.05mmol, 15.9mg), substrate
2a (0.06mmol, 15.2mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ea (89%).1H NMR(DMSO-d6,500MHz):δ(ppm)9.77 (s,1H),8.14-
8.13(m,2H),7.80-7.77(m,1H),7.62-7.57(m,4H),7.39-7.30(m,4H), 7.22-7.15(m,7H),
7.05-7.03(m,2H),6.90-6.86(m,3H).13C NMR(DMSO-d6,125 MHz):δ(ppm)207.1,194.1,
189.4,162.5 (d, J=970.0Hz), 158.3,136.8 (d, J=30.0 Hz), 136.5 (d, J=20.0Hz), 135.0,
131.5,131.4 (d, J=30.0Hz), 130.0,129.8,129.5,129.1,129.1,128.6,128.4,127.9,
(124.9,123.6,116.3,116.0,115.1 d, J=85.0Hz), 113.9 (d, J=95.0Hz), 109.1,
73.8.HRMS(ESI):exact mass calculated for M+ (C36H25FNO2S)requires m/z 554.1590,
found m/z 554.1589.
Embodiment 15
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1f (0.05mmol, 18.9mg), substrate
2a (0.06mmol, 15.2mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3fa (75%).1H NMR(CDCl3,500MHz):δ(ppm) 7.95-7.89(m,3H),
7.50-7.46(m,2H),7.41-7.36(m,5H),7.25-7.22(m,5H), 7.18-7.16(m,2H),7.10-7.09(m,
1H),7.02-7.01(m,2H),6.78-6.76(m,2H), 6.64-6.63(m,1H).13C NMR(CDCl3,125MHz):δ
(ppm)207.4,194.1,190.0,156.1, 136.7,136.1,135.3,135.0,131.8,130.6,130.5,
130.0,129.9,129.1,129.0,128.9, 128.6,128.5,128.3,127.9,127.8,126.9,126.0,
122.6,116.1,115.7,109.0,74.1. HRMS(ESI):exact mass calculated for M+
(C36H25BrNO2S)requires m/z 616.0769, found m/z 616.0766.
Embodiment 16
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1g (0.05mmol, 15.7mg), substrate
2a (0.06mmol, 15.2mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ga (82%).1H NMR(CDCl3,500MHz):δ(ppm) 8.12-8.10(m,2H),
7.68-7.63(m,3H),7.52-7.48(m,2H),7.32-7.27(m,5H), 7.25-7.24(m,2H),7.17-7.00(m,
7H),6.82-6.80(m,2H),5.76(s,1H),2.23(s,3H). 13C NMR(CDCl3,125MHz):δ(ppm)207.2,
194.2,190.2,155.9,138.1,136.6,135.5, 135.2,134.3,132.0,130.0,129.0,128.9,
128.8,128.4,128.4,128.3,128.3,127.9, 127.6,127.4,124.6,115.6,115.5,109.8,
74.4,21.6.HRMS(ESI):exact mass calculated for M+(C37H28NO2S)requires m/z
550.1841,found m/z 550.1837.
Embodiment 17
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1h (0.05mmol, 15.3mg), substrate
2a (0.06 mmol, 15.2mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ha (81%).1H NMR(DMSO-d6,500MHz):δ(ppm)9.75(s, 1H),8.17-
8.15(m,2H),7.83-7.80(m,1H),7.65-7.59(m,4H),7.40-7.36(m,4H), 7.22-7.13(m,7H),
6.90-6.88(m,1H),6.86-6.85(m,2H),6.58-6.57(m,1H).13C NMR(DMSO-d6,125MHz):δ(ppm)
206.2,194.4,188.9,158.3,138.4,136.5,136.3, 135.3,131.6,130.1,129.9,129.4,
129.1,128.6,128.5,128.4,128.1,126.7,126.0, 125.2,116.2,115.7,110.0,106.0,
74.6.HRMS(ESI):exact mass calculated for M+ (C34H24NO2S2)requires m/z 542.1248,
found m/z 542.1248.
Embodiment 18
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1i (0.05mmol, 15.9mg), substrate
2a (0.06mmol, 15.2mg), CPA (0.0005mmol, 0.38mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ag (91%).1H NMR(CDCl3,500MHz):δ(ppm) 8.11-8.10(m,2H),
7.68-7.67(m,1H),7.64-7.62(m,2H),7.53-7.50(m,2H), 7.32-7.27(m,7H),7.24-7.19(m,
5H),6.85-6.81(m,4H),5.72(s,1H).13C NMR (CDCl3,125MHz):δ(ppm)207.2,194.3,190.2,
162.3 (d, J=985.0Hz), 156.0,136.4,135.3,134.1,131.9,131.4 (d, J=15.0Hz), 130.0,
129.9,129.9,129.1,128.8 (d, J=25.0Hz), 128.6,128.5,127.9,127.6,127.5,127.2,
115.7,115.3 (d, J=90.0 Hz), 114.8,110.0,74.3.HRMS (ESI): exact mass calculated
for M+(C36H25FNO2S) requires m/z 554.1590,found m/z 554.1589.
Embodiment 19
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times.By substrate 1j (0.05mmol, 16.7mg), substrate
2a (0.06mmol, 15.2mg), CPA (0.0005mmol, 0.37mg) are successively weighed into reaction tube, and nitrogen is changed in evacuation, and in nitrogen
Benzotrifluoride (0.3mL) is added under atmosphere, reacts 48 hours at room temperature.TCL is detected after reaction, directly plus silica gel, rotation
Dry chromatography obtains yellow solid 3ah (91%).1H NMR(DMSO-d6,500MHz):δ(ppm)9.81 (s,1H),8.09-
8.07(m,2H),7.74-7.71(m,1H),7.58-7.54(m,4H),7.36-7.16(m,14H), 6.92-6.90(m,2H)
.13C NMR(DMSO-d6,125MHz):δ(ppm)207.1,194.1,189.6, 158.3,136.7,136.3,134.4,
133.9,133.1,131.6,129.9,129.8,129.4,129.3,129.1, 129.0,128.3,128.0,127.5,
125.0,116.3,114.6,110.4,74.0.HRMS(ESI):exact mass calculated for M+
(C36H25ClNO2S)requires m/z 570.1295,found m/z 570.1293。
Claims (5)
1. a kind of new method for synthesizing the polysubstituted alkene of sulfur-bearing, which is characterized in that with compound 1 be reaction raw materials, with chiral phosphorus
Acid is catalyst, reacts in reaction dissolvent under certain temperature and obtains four substitutions connection vinyl compound；Wherein, the temperature is 0-
80℃；Shown in reaction process such as formula (I)；
Wherein R1, R2, R3And R4It is alkyl, aromatic radical or heterocycle.
2. as described in claim 1 four replace the synthetic method of connection vinyl compound, which is characterized in that the catalyst is hand
Property phosphoric acid；The dosage of the catalyst is 1-100%.
3. as described in claim 1 four replace the synthetic method of connection vinyl compound, which is characterized in that the reaction dissolvent is
Methylene chloride, chloroform, tetrahydrofuran, methanol, 1,2- dichloroethanes, acetonitrile, toluene, 1,4- dioxane, ether, acetic acid
Ethyl ester, benzotrifluoride, xylene compound or methyl phenyl ethers anisole.
4. as described in claim 1 four replace the synthetic method of connection vinyl compound, which is characterized in that 1 He of compound
The ratio of compound 2 is 1:1-1:5.
5. one kind four replaces the synthetic method of connection vinyl compound, reaction process is as shown in following formulas；
In the test tube reactor of 25mL, with nitrogen exchange of air 3 times；By 0.05 mmol substrate 1a, 0.06 mmol substrate 2a
It is successively weighed into reaction tube with 0.0005 mmol CPA, nitrogen is changed in evacuation, and 0.3 mL benzotrifluoride is added under nitrogen atmosphere；
Reaction system is reacted at room temperature 48 hours；TCL is detected after reaction, and directly plus silica gel, rotation dry chromatography obtain 3aa.
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