Dialkoxyphosphinyl-substituted enols of carboxamides.
Reactions of isocyanates XNCO (e.g., X = p-An, Ph, i-Pr) with (MeO)2P(=O)CH2CO2R [R = Me, CF3CH2, (CF3)2CH] gave 15 formal "amides" (MeO)2P(=O)CH(CO2R)CONHX (6/7), and with (CF3CH2O)2P(=O)CH2CO2R [R = Me, CF3CH2] they gave eight analogous amide/enols 17/18. X-ray crystallography of two 6/7, R = (CF3)2CH systems revealed Z-enols of amides structures (MeO)2P(=O)C(CO2CH(CF3)2)=C(OH)NHX 7 where the OH is cis and hydrogen bonded to the O=P(OMe)2 group. The solid phosphonates with R = Me, CF3CH2 have the amide 6 structure. The structures in solution were investigated by 1H, 13C, 19F, and 31P NMR spectra. They depend strongly on the substituent R and the solvent and slightly on the N-substituent X. All systems displayed signals for the amide and the E- and Z-isomers. The low-field two delta(OH) and two delta(NH) values served as a probe for the stereochemistry of the enols. The lower field delta(OH) is not always that for the more abundant enol. The % enol, presented as K(enol), was determined by 1H, 19F, and 31P NMR spectra, increases according to the order for R, Me < CF3CH2 < (CF3)2CH, and decreases according to the order of solvents, CCl4 > CDCl3 approximately THF-d8 > CD3CN >DMSO-d6. In DMSO-d6, the product is mostly only the amide, but a few enols with fluorinated ester groups were observed. The Z-isomers are more stable for all the enols 7 with E/Z ratios of 0.31-0.75, 0.15-0.33, and 0.047-0.16 when R = Me, CF3CH2, and (CF3)2CH, respectively, and for compounds 18, R = Me, whereas the E-isomers are more stable than the Z-isomers. Comparison with systems where the O=P(OMe)2 is replaced by a CO2R shows mostly higher K(enol) values for the O=P(OMe)2-substituted systems. A linear correlation exists between delta(OH)[Z-enols] activated by two ester groups and delta(OH)[E-enols] activated by phosphonate and ester groups. Compounds (MeO)2P(=O)CH(CN)CONHX show <or=7.3% enol in CDCl3 solution. For [(MeO)2P(=O)]2CHCONHX, activated by two O=P(OMe)2 groups, only the amides were observed in solution and in the solid. DFT calculations reproduce the general effect of R on Kenol, but the correlation between observed and calculated Kenol values is not linear. The roles of electron withdrawal by the activating phosphonate and ester groups, and the importance of N-H and O-H hydrogen bonding to them in stabilizing the enols are discussed.
Song
Jinhua
J
Department of Organic Chemistry and the Lise Meitner Minerva Center for Computational Quantum Chemistry, The Hebrew University, Jerusalem 91904, Israel.
Yamataka
Hiroshi
H
Rappoport
Zvi
Z