Preparation method of chiral fluoroalkyl ternary carbocyclic compound
A technology of fluoroalkyl ternary and fluoroalkyl cyclopropene, which is applied in the field of preparation of chiral fluoroalkyl ternary carbocyclic compounds, and can solve the problems of high explosiveness, limited preparation, purification, storage and use, and inapplicability to industrial applications, etc. question
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[0042] The invention provides a preparation method of a chiral fluoroalkyl three-membered carbocyclic compound, comprising the following steps:
[0043] When the chiral fluoroalkyl three-membered carbocyclic compound is a chiral fluoroalkyl cyclopropene compound:
[0044] The fluoroalkylsulfonylhydrazone derivative of the structure shown in formula I, the alkyne derivative of the structure shown in formula II, the first chiral metal catalyst, the first alkali compound and the first organic solvent are mixed, and the first [2 +1] cycloaddition reaction to obtain a chiral fluoroalkyl cyclopropene compound having a structure shown in formula III;
[0045] When the chiral fluoroalkyl three-membered carbocyclic compound is a chiral fluoroalkyl cyclopropane compound:
[0046] Mix the fluoroalkylsulfonylhydrazone derivative of the structure shown in formula I, the alkene derivative of the structure shown in formula IV, the second chiral metal catalyst, the second alkali compound and...
Embodiment 1
[0096]
[0097] Under nitrogen condition, o-trifluoromethylbenzenesulfonyl hydrazide (30mmol) and ketone compound trifluoromethylacetophenone (30mmol) were dissolved in 40mL ethyl acetate (EA), then boron trifluoride diethyl ether ( 45mmol), the resulting material was reacted overnight in an oil bath at 40°C, after the reaction, 40mL of saturated aqueous sodium chloride solution (mass concentration of 1.33g / mL) was added to the resulting product, extracted with EA, and the resulting extract was treated with sulfuric acid After drying over magnesium and concentrating under reduced pressure, the resulting product was subjected to silica gel column chromatography to obtain trifluoromethylbenzenesulfonylhydrazone 1a;
[0098] Under nitrogen conditions, the trifluoromethylbenzenesulfonylhydrazone 1a (39.6mg, 0.1mmol), phenylacetylene 2a (20mg, 0.2mmol) and the commercially available chiral metal catalyst Rh 2 (R-BTPCP) 4 (2mg, relative to 1a, 1mol%), DIPEA (33μl, 0.2mmol) and 3...
Embodiment 2
[0104]
[0105] Under nitrogen, trifluoromethylbenzenesulfonylhydrazone 1a (39.6mg, 0.1mmol), styrene 2b (21mg, 0.2mmol), chiral metal catalyst Rh 2 (R-PTAD) 4 (2mg, 1mol%), DIPEA (33μl, 0.2mmol), and 3mL of toluene were added to a 10mL reaction flask, and stirred at room temperature for 12h. After the reaction, the resulting product was filtered with diatomaceous earth, and the resulting filtrate was concentrated under reduced pressure. After separation by analysis, compound 3b (25.4 mg, yield 97%) was obtained as a colorless oily substance.
[0106] characterize
[0107] The compound 3b prepared in embodiment 2 is carried out NMR characterization, and the obtained spectrograms are respectively shown in Figure 4~6 ; The resulting characterization data are:
[0108] 1 H-NMR (600MHz, CDCl 3 )δ7.21-7.18(m,1H),7.16-7.12(m,4H),7.10-7.06(m,3H),6.79-6.76(m,2H),2.84(dd,J=7.0Hz,J= 9.6Hz,1H),1.87(dd,J=6.0Hz,J=9.6Hz,1H),1.69-1.66(m,1H). 13 C-NMR (150MHz, CDCl 3 )δ135.6, 132....
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