Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

The reactions of 2,4-di-tert-butyl-6-(diphenylphosphino)phenol and various Michael acceptors (acrylonitrile, acrylamide, methyl vinyl ketone, several acrylates, methyl vinyl sulfone) yield the respective phosphonium phenolate zwitterions at room temperature. Nine different zwitterions were synthesized and fully characterized. Zwitterions with the poor Michael acceptors methyl methacrylate and methyl crotonate formed, but could not be isolated in pure form. The solid-state structures of two phosphonium phenolate molecules were determined by single-crystal X-ray crystallography. The bonding situation in the solid state together with NMR data suggests an important contribution of an ylidic resonance structure in these molecules. The phosphonium phenolates are characterized by UV–vis absorptions peaking around 360 nm and exhibit a negative solvatochromism. An analysis of the kinetics of the zwitterion formation was performed for three Michael acceptors (acrylonitrile, methyl acrylate, and acrylamide) in two different solvents (chloroform and methanol). The results revealed the proton transfer step necessary to stabilize the initially formed carbanion as the rate-determining step. A preorganization of the carbonyl bearing Michael acceptors allowed for reasonable fast direct proton transfer from the phenol in aprotic solvents. In contrast, acrylonitrile, not capable of forming a similar preorganization, is hardly reactive in chloroform solution, while in methanol the corresponding phosphonium phenolate is formed.

Experimental procedures, plot of the solid-state structure of 2f, crystallographic data, NMR spectra, UV-vis spectra and experimental and simulated time conversion plots for the zwitterion formation Synthesis of zwitterions.In a standard procedure 1 (0.2 mmol, 78 mg, 1 equiv) was dissolved in 0.5 mL dichloromethane in a 4 mL screw-cap vial.The Michael acceptor (0.21 mmol, 1.05 equiv) was dissolved in 0.5 mL dichloromethane in a separate vial and then added to the solution of 1 dropwise.Zwitterion formation was indicated by a color change to yellow of the solution.The reaction mixture was stirred at room temperature for 24 h and the solvent evaporated.The compounds were purified via recrystallization.

Page S31
For stability tests, 20 mg of 2d (0.042 mmol) were dissolved in 600 µL of the respective solvent (CDCl3 or DMSO-d6) in an NMR tube.The tubes were sealed with caps and parafilm.The samples were either kept at room temperature or heated to 60 °C.All samples were subjected to 1 H and 31 P NMR spectroscopy after 24, 48, and 72 h.

Figure
Figure S2: 1 H NMR spectrum of 2a recorded from a solution in CDCl3 at 298 K.

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Figure S3: 13 C{ 1 H} NMR spectrum of 2a recorded from a solution in CDCl3 at 298 K.

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Figure S4: 1 H-1 H COSY NMR spectrum of 2a recorded from a solution in CDCl3 at 298 K.

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Figure S5: 1 H-13 C HSQC NMR spectrum of 2a recorded from a solution in CDCl3 at 298 K.

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Figure S7: 1 H NMR spectrum of 2b recorded from a solution in CDCl3 at 298 K.

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Figure S9: 1 H-1 H COSY NMR spectrum of 2b recorded from a solution in CDCl3 at 298 K.

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Figure S11: 31 P{ 1 H} NMR spectrum of 2b recorded from a solution in CDCl3 at 298 K.

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Figure S12: 1 H NMR spectrum of 2c recorded from a solution in CDCl3 at 298 K. Trace impurities are marked with an asterisk.

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Figure S13: 13 C{ 1 H} NMR spectrum of 2c recorded from a solution in CDCl3 at 298 K. Trace impurities are marked with an asterisk.

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Figure S14: 1 H-1 H COSY NMR spectrum of 2c recorded from a solution in CDCl3 at 298 K.

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Figure S15: 1 H-13 C HSQC NMR spectrum of 2c recorded from a solution in CDCl3 at 298 K.

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Figure S17: 1 H NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K.

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Figure S19: 1 H-1 H COSY NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K.

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Figure S21: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K.

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Figure S23: 13 C{ 1 H} NMR spectrum of 2e recorded from a solution in CDCl3 at 298 K.

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Figure S24: 1 H-1 H COSY NMR spectrum of 2e recorded from a solution in CDCl3 at 298 K.

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Figure S25: 1 H-13 C HSQC NMR spectrum of 2e recorded from a solution in CDCl3 at 298 K.

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Figure S27: 1 H NMR spectrum of 2f recorded from a solution in CDCl3 at 298 K.

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Figure S29: 1 H-1 H COSY NMR spectrum of 2f recorded from a solution in CDCl3 at 298 K.

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Figure S30: 1 H-13 C HSQC NMR spectrum of 2f recorded from a solution in CDCl3 at 298 K.

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Figure S31: 31 P{ 1 H} NMR spectrum of 2f recorded from a solution in CDCl3 at 298 K.

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Figure S32: 1 H NMR spectrum of 2g recorded from a solution in CDCl3 at 298 K.

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Figure S33: 13 C{ 1 H} NMR spectrum of 2g recorded from a solution in CDCl3 at 298 K.

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Figure S35: 1 H-13 C HSQC NMR spectrum of 2g recorded from a solution in CDCl3 at 298 K.

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Figure S37: 1 H NMR spectrum of 2h recorded from a solution in CDCl3 at 298 K. Trace impurities are marked with an asterisk.

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Figure S39: 1 H-1 H COSY NMR spectrum of 2h recorded from a solution in CDCl3 at 298 K.

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Figure S40: 1 H-13 C HSQC NMR spectrum of 2h recorded from a solution in CDCl3 at 298 K.

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Figure S41: 31 P{ 1 H} NMR spectrum of 2h recorded from a solution in CDCl3 at 298 K. Trace impurities are marked with an asterisk.

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Figure S42: 1 H NMR spectrum of 2i recorded from a solution in CDCl3 at 298 K. Trace impurities are marked with an asterisk.

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Figure S43: 13 C{ 1 H} NMR spectrum of 2i recorded from a solution in CDCl3 at 298 K.

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Figure S44: 1 H-1 H COSY NMR spectrum of 2i recorded from a solution in CDCl3 at 298 K.

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Figure S45: 1 H-13 C HSQC NMR spectrum of 2i recorded from a solution in CDCl3 at 298 K.

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Figure S46: 31 P{ 1 H} NMR spectrum of 2i recorded from a solution in CDCl3 at 298 K. Trace impurities are marked with an asterisk.

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Figure S47: 1 H NMR spectrum of the attempted zwitterion formation from 1 and methyl methacrylate recorded from a solution in CDCl3 at 298 K. Marked peaks indicate the presence of a zwitterionic species.

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Figure S48: 1 H NMR spectrum of the attempted zwitterion formation from 1 and methyl crotonate recorded from a solution in CDCl3 at 298 K. Marked peaks indicate the presence of a zwitterionic species.

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Figure S49: 1 H NMR spectrum of the deuteration experiment for the synthesis of 2a.

Figure 50
Figure 50: 1 H NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after storage as a solid for two months.

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Figure S51: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after storage as a solid for two months.

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Figure S52: 1 H NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at RT for 24 h.

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Figure S53: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at RT for 24 h.

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Figure S54: 1 H NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at 60 °C for 24 h.

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Figure S55: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at 60 °C for 24 h.

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Figure S56: 1 H NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at RT for 24 h.

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Figure S57: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at RT for 24 h.

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Figure S58: 1 H NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at 60 °C for 24 h.

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Figure S59: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at 60 °C for 24 h.

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Figure S60: 1 H NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at RT for 48 h.

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Figure S61: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at RT for 48 h.

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Figure S62: 1 H NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at 60 °C for 48 h.

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Figure S63: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at 60 °C for 48 h.

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Figure S64: 1 H NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at RT for 48 h.

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Figure S65: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at RT for 48 h.

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Figure S66: 1 H NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at 60 °C for 48 h.

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Figure S67: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at 60 °C for 48 h.

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Figure S68: 1 H NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at RT for 72 h.

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Figure S69: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at RT for 72 h.

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Figure S70: 1 H NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at 60 °C for 72 h.

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Figure S71: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in CDCl3 at 298 K after keeping in solution at 60 °C for 72 h.

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Figure S72: 1 H NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at RT for 72 h.

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Figure S73: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at RT for 72 h.

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Figure S74: 1 H NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at 60 °C for 72 h.

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Figure S75: 31 P{ 1 H} NMR spectrum of 2d recorded from a solution in DMSO-d6 at 298 K after keeping in solution at 60 °C for 72 h.

Figure S76 :
Figure S76: Experimental (left) and simulated (right) time conversion plots for the reaction of 1 and acrylonitrile in chloroform

Figure S77 :
Figure S77: Experimental (left) and simulated (right) time conversion plots for the reaction of 1 and acrylonitrile in methanol

Figure S78 :
Figure S78: Experimental (left) and simulated (right) time conversion plots for the reaction of 1 and acrylamide in chloroform

Figure S79 :
Figure S79: Experimental (left) and simulated (right) time conversion plots for the reaction of 1 and acrylamide in methanol

Figure S80 :
Figure S80: Experimental (left) and simulated (right) time conversion plots for the reaction of 1 and methyl acrylate in chloroform

Figure S81 :
Figure S81: Experimental (left) and simulated (right) time conversion plots for the reaction of 1 and methyl acrylate in methanol

Figure S82 :
Figure S82: UV-vis spectra of 2a-i in chloroform (straight lines) and 2a, 2b and 2d in methanol (dotted lines); the inset shows a photograph of a vial containing a solution of 2a in chloroform.

Table S1 :
Crystallographic data for compounds 2a and 2f