<i>N,N</i>-bis-(dimethylfluorosilylmethyl)amides of <i>N</i>-organosulfonylproline and sarcosine: synthesis, structure, stereodynamic behaviour and <i>in silico</i> studies

(O→Si)-Chelate difluorides R3R2NCH(R1)C(O)N(CH2SiMe2F)2 (9a–c, R1R2 = (CH2)3, R3 = Ms (a), Ts (b); R1 = H, R2 = Me, R3 = Ms (c)), containing one penta- and one tetracoordinate silicon atoms were synthesized by silylmethylation of amides R3R2NCH(R1)C(O)NH2, subsequent hydrolysis of unstable intermediates R3R2NCH(R1)C(O)N(CH2SiMe2Cl)2 (7a–c) into 4-acyl-2,6-disilamorpholines R3R2NCH(R1)C(O)N(CH2SiMe2O)2 (8a–c) and the reaction of the latter compounds with BF3·Et2O. The structures of disilamorpholines 8a,c and difluoride 9a were confirmed by an X-ray diffraction study. According to the IR and NMR data, the O→Si coordination in solutions of these compounds was weaker than that in the solid state due to effective solvation of the Si–F bond. A permutational isomerisation involving an exchange of equatorial Me groups at the pentacoordinate Si atom in complexes 9a–c was detected, and its activational parameters were determined by 1H DNMR. In silico estimation of possible pharmacological effects and acute rat toxicity by PASS Online and GUSAR Online services showed a potential for their further pharmacological study

Stereochemical rearrangements of dibromides of hexacoordinated germanium containing amidomethyl and lactamomethyl chelate ligands

For the first time a slow (on the NMR time scale) dynamic exchange between two diastereomers of hexacoordinated dibromogermanes containing two amidomethyl and lactamomethyl C,O-chelate ligands has been observed at room temperature in solution. The influence of temperature and solvent on the ratio of diastereomers was studied. At higher temperatures only one set of signals of the products were detected in the NMR spectra. Based on the dynamic NMR and quantum-chemical calculations (ab initio FR 3-21G), as well as on the structures determined for these compounds in the solid state, a cis-configuration of monodentate ligands was proposed for one of the diastereomers and an all-trans-configuration for the other. At low temperatures interconversion of enantiomers in the cis-diastereomer was observed. In the case of bis[(N-methylacetamido)methyl]dibromogermane the activation and thermodynamic parameters of enantiomerization (DeltaG(298)(#) 12.0+/-0.1 kcal mol(-1), DeltaH(#) 10.7+/-0.3 kcal mol(-1), DeltaS(#) -4.6+/-2.5 cal mol(-1) K-1) and diastereomeric exchange OcCtBrcreversible arrowOtCtBrt (DeltaG(298)(#), 15.0+/-0.1 kcal mol(-1); DeltaH(#) 0.1+/-0.8 kcal mol(-1); DeltaS(#) -50.0+/-5.8 cal mol(-1) K-1; DeltaG(298)degrees -0.2+/-0.1 kcal mol(-1); DeltaHdegrees -0.8+/-0.8 kcal mol(-1); DeltaSdegrees -2.6+/-1.0 cal mol(-1) K-1) were determined. (C) 2003 Published by Elsevier Science B.V

Structures and stereochemical non-rigidity of Si-substituted N-(dimethylsilylmethyl)- and N-(methylphenylsilylmethyl)amides and -lactams

Eleven new silicon-substituted N-(dimethylsilylmethyl)- and N-(methylphenylsilylmethyl)amides and -lactams bearing a chiral carbon in the amide or lactam fragment, and containing the OSiC3X (X = Hal, OTf) coordination fragment have been synthesized and their structures determined in solution by spectroscopic means. These structures are consistent with the hypervalency model. Quantum chemical calculations adequately reflect correlations between the type of monodentate ligand X and the geometric parameters of the N–C�O–Si�X fragments. The activation parameters for enantiomerization and diastereomerization in these new compounds and the other related compounds were determined by the dynamic NMR (DNMR) method using full line-shape analysis. The free activation energy values in the absence of external nucleophiles vary from 9 to 27 kcal mol?1. The entropies of activation (?S#) are negative (?20 to ?50 cal mol?1 K?1) in all cases except for the chloride derivatives of 4-phenyl-2-pyrrolidone and 4-oxazolidinone that have weaker intramolecular O ? Si coordination. Irregular mechanisms of permutational isomerization were proposed on the basis of the DNMR data and the results of quantum-chemical calculations carried out by ab initio (HF) and DFT (PBE, B3PW91, 6-311++G(d,p)). Depending on the coordination environment at silicon, the mechanisms proposed involve either the dissociation of the Si–X bond followed by the Berry pseudorotation or similar in the intermediate or the cleavage of intramolecular O–Si bond with subsequent inversion at the silicon atom. The apparently simple pseudorotation mechanism involving only the pentacoordinate structures 1–21 does not appear to be favoured in any of the examples studied

Synthesis, structure and dynamic stereochemistry of (O→Si)-chelate <i>N</i>-(trifluorosilylmethyl)-[<i>N</i>-(S)-(1-phenylethyl)]acetamide and 1-(trifluorosilylmethyl)-2-oxoperhydroazepine: Retention of the O→Si coordination in the adduct with KF and 18-crown-6

The novel compounds, N-(trifluorosilylmethyl)-[N-(S)-(1-phenylethyl)]-acetamide (1a) and 1-(trifluorosilylmethyl)-2-oxoperhydroazepine (1b) have been prepared from the corresponding NH-compounds using ClCH2SiCl3/Et3N or ClCH2SiCl3/(Me3Si)2NH followed by methanolysis or hydrolysis of the reaction mixture in the presence of Lewis bases, and then BF3 etherate. Potassium-(18-crown-6)-(2-oxoperhydroazepinomethyl)tetrafluorosilicate (2) was synthesized by reaction of the trifluoride (1b) with KF in the presence of 18-crown-6. Using 19F, 29Si NMR and X-ray diffraction techniques it was established that the silicon atom is pentacoordinate in the trifluorides (1a, b) and hexacoordinate in the adduct 2. Thus the internal coordination of the O → Si bond present in the trifluoride (1b) is retained in the adduct 2. The stereochemical non-rigidity of the trifluorides (1a, b) and the N-(trifluorosilylmethyl)-N-methylacetamide (1c) was investigated using dynamic 19F NMR spectroscopy. The activation barriers for permutational isomerization are in the range 9.5–10 kcal mol−1. Lower values of ΔG# for permutation of trifluorides (1a–c) compared to the monofluorides with the coordination core OSiC3F together with small negative values for the activation entropy implies a non-dissociative mechanism. Quantum-chemical analysis suggests a mechanism involving a turnstile rotation

Synthesis, structures, and stereodynamic behavior of novel pentacoordinate fluorosilanes: fluorosilyl derivatives of proline

The (O→Si)-chelate N'-(dimethylfluorosilylmethyl))-N'-methyl-N-(organosulfonyl)prolinamides RSO2-Pro-N(Me)CH2SiMe2F (2a-f, R = Me (a), Ph (b), 4-MeC6H4 (c), 4-ClC6H4 (d), 4-BrC6H4 (e), 4-NO2C6H4 (f)) were synthesized from the corresponding disiloxanes 1a-f using Et2O•BF3. According to the NMR and IR data, the extent of dimerization of fluorosilanes 2a-f in solution is negligible, while the O→Si coordination in solution is weaker than that in the solid state. Comparative CP/MAS NMR and X-ray diffraction studies revealed that in solution the coordination Si-O bond length varies in a narrow range (2.22-2.24 angstrom) that is 0.02-0.11 angstrom longer than in the crystalline state. Dynamic NMR (DNMR) studies of the fluorides revealed a fine structure of the 19F signals in the 0-20°C temperature range, which was related to the structural features of the coordination set in these complexes. The temperature dependence of the SiMe2 signals in the 1H DNMR spectra was attributed to a permutational isomerization process involving a positional exchange of equatorial ligands. The narrow range of activational barriers of the process (23-24 kcal mol-1 and more) and high negative values of the entropy of activation are similar to those observed earlier for Si-substituted N-(dimethylsilylmethyl) and N-(methylphenylsilylmethyl) amides and lactams, which suggests similar permutational processes in all cases. Gas-phase quantum chemical studies demonstrate that the solvation of F- reduces the activation barrier

Synthesis, Structures, and Stereodynamic Behavior of Novel Pentacoordinate Fluorosilanes: Fluorosilyl Derivatives of Proline

The (O→Si)-chelate <i>N</i>′-(dimethylfluorosilylmethyl))-<i>N</i>′-methyl-<i>N</i>-(organosulfonyl)­prolinamides RSO₂-Pro-N­(Me)­CH₂SiMe₂F (<b>2a</b>–<b>f</b>, R = Me (<b>a</b>), Ph (<b>b</b>), 4-MeC₆H₄ (<b>c</b>), 4-ClC₆H₄ (<b>d</b>), 4-BrC₆H₄ (<b>e</b>), 4-NO₂C₆H₄ (<b>f</b>)) were synthesized from the corresponding disiloxanes <b>1a</b>–<b>f</b> using Et₂O·BF₃. According to the NMR and IR data, the extent of dimerization of fluorosilanes <b>2a</b>–<b>f</b> in solution is negligible, while the O→Si coordination in solution is weaker than that in the solid state. Comparative CP/MAS NMR and X-ray diffraction studies revealed that in solution the coordination Si–O bond length varies in a narrow range (2.22–2.24 Å) that is 0.02–0.11 Å longer than in the crystalline state. Dynamic NMR (DNMR) studies of the fluorides revealed a fine structure of the ¹⁹F signals in the 0–20 °C temperature range, which was related to the structural features of the coordination set in these complexes. The temperature dependence of the SiMe₂ signals in the ¹H DNMR spectra was attributed to a permutational isomerization process involving a positional exchange of equatorial ligands. The narrow range of activational barriers of the process (23–24 kcal mol^–1 and more) and high negative values of the entropy of activation are similar to those observed earlier for Si-substituted <i>N</i>-(dimethylsilylmethyl) and <i>N</i>-(methylphenylsilylmethyl) amides and lactams, which suggests similar permutational processes in all cases. Gas-phase quantum chemical studies demonstrate that the solvation of F^– reduces the activation barrier

Synthesis, Structures, and Stereodynamic Behavior of Novel Pentacoordinate Fluorosilanes: Fluorosilyl Derivatives of Proline

The (O→Si)-chelate <i>N</i>′-(dimethylfluorosilylmethyl))-<i>N</i>′-methyl-<i>N</i>-(organosulfonyl)­prolinamides RSO₂-Pro-N­(Me)­CH₂SiMe₂F (<b>2a</b>–<b>f</b>, R = Me (<b>a</b>), Ph (<b>b</b>), 4-MeC₆H₄ (<b>c</b>), 4-ClC₆H₄ (<b>d</b>), 4-BrC₆H₄ (<b>e</b>), 4-NO₂C₆H₄ (<b>f</b>)) were synthesized from the corresponding disiloxanes <b>1a</b>–<b>f</b> using Et₂O·BF₃. According to the NMR and IR data, the extent of dimerization of fluorosilanes <b>2a</b>–<b>f</b> in solution is negligible, while the O→Si coordination in solution is weaker than that in the solid state. Comparative CP/MAS NMR and X-ray diffraction studies revealed that in solution the coordination Si–O bond length varies in a narrow range (2.22–2.24 Å) that is 0.02–0.11 Å longer than in the crystalline state. Dynamic NMR (DNMR) studies of the fluorides revealed a fine structure of the ¹⁹F signals in the 0–20 °C temperature range, which was related to the structural features of the coordination set in these complexes. The temperature dependence of the SiMe₂ signals in the ¹H DNMR spectra was attributed to a permutational isomerization process involving a positional exchange of equatorial ligands. The narrow range of activational barriers of the process (23–24 kcal mol^–1 and more) and high negative values of the entropy of activation are similar to those observed earlier for Si-substituted <i>N</i>-(dimethylsilylmethyl) and <i>N</i>-(methylphenylsilylmethyl) amides and lactams, which suggests similar permutational processes in all cases. Gas-phase quantum chemical studies demonstrate that the solvation of F^– reduces the activation barrier

Synthesis, Structures, and Stereodynamic Behavior of Novel Pentacoordinate Fluorosilanes: Fluorosilyl Derivatives of Proline

The (O→Si)-chelate <i>N</i>′-(dimethylfluorosilylmethyl))-<i>N</i>′-methyl-<i>N</i>-(organosulfonyl)­prolinamides RSO₂-Pro-N­(Me)­CH₂SiMe₂F (<b>2a</b>–<b>f</b>, R = Me (<b>a</b>), Ph (<b>b</b>), 4-MeC₆H₄ (<b>c</b>), 4-ClC₆H₄ (<b>d</b>), 4-BrC₆H₄ (<b>e</b>), 4-NO₂C₆H₄ (<b>f</b>)) were synthesized from the corresponding disiloxanes <b>1a</b>–<b>f</b> using Et₂O·BF₃. According to the NMR and IR data, the extent of dimerization of fluorosilanes <b>2a</b>–<b>f</b> in solution is negligible, while the O→Si coordination in solution is weaker than that in the solid state. Comparative CP/MAS NMR and X-ray diffraction studies revealed that in solution the coordination Si–O bond length varies in a narrow range (2.22–2.24 Å) that is 0.02–0.11 Å longer than in the crystalline state. Dynamic NMR (DNMR) studies of the fluorides revealed a fine structure of the ¹⁹F signals in the 0–20 °C temperature range, which was related to the structural features of the coordination set in these complexes. The temperature dependence of the SiMe₂ signals in the ¹H DNMR spectra was attributed to a permutational isomerization process involving a positional exchange of equatorial ligands. The narrow range of activational barriers of the process (23–24 kcal mol^–1 and more) and high negative values of the entropy of activation are similar to those observed earlier for Si-substituted <i>N</i>-(dimethylsilylmethyl) and <i>N</i>-(methylphenylsilylmethyl) amides and lactams, which suggests similar permutational processes in all cases. Gas-phase quantum chemical studies demonstrate that the solvation of F^– reduces the activation barrier

Synthesis, Structures, and Stereodynamic Behavior of Novel Pentacoordinate Fluorosilanes: Fluorosilyl Derivatives of Proline

The (O→Si)-chelate <i>N</i>′-(dimethylfluorosilylmethyl))-<i>N</i>′-methyl-<i>N</i>-(organosulfonyl)­prolinamides RSO₂-Pro-N­(Me)­CH₂SiMe₂F (<b>2a</b>–<b>f</b>, R = Me (<b>a</b>), Ph (<b>b</b>), 4-MeC₆H₄ (<b>c</b>), 4-ClC₆H₄ (<b>d</b>), 4-BrC₆H₄ (<b>e</b>), 4-NO₂C₆H₄ (<b>f</b>)) were synthesized from the corresponding disiloxanes <b>1a</b>–<b>f</b> using Et₂O·BF₃. According to the NMR and IR data, the extent of dimerization of fluorosilanes <b>2a</b>–<b>f</b> in solution is negligible, while the O→Si coordination in solution is weaker than that in the solid state. Comparative CP/MAS NMR and X-ray diffraction studies revealed that in solution the coordination Si–O bond length varies in a narrow range (2.22–2.24 Å) that is 0.02–0.11 Å longer than in the crystalline state. Dynamic NMR (DNMR) studies of the fluorides revealed a fine structure of the ¹⁹F signals in the 0–20 °C temperature range, which was related to the structural features of the coordination set in these complexes. The temperature dependence of the SiMe₂ signals in the ¹H DNMR spectra was attributed to a permutational isomerization process involving a positional exchange of equatorial ligands. The narrow range of activational barriers of the process (23–24 kcal mol^–1 and more) and high negative values of the entropy of activation are similar to those observed earlier for Si-substituted <i>N</i>-(dimethylsilylmethyl) and <i>N</i>-(methylphenylsilylmethyl) amides and lactams, which suggests similar permutational processes in all cases. Gas-phase quantum chemical studies demonstrate that the solvation of F^– reduces the activation barrier

Synthesis, Structures, and Stereodynamic Behavior of Novel Pentacoordinate Fluorosilanes: Fluorosilyl Derivatives of Proline

The (O→Si)-chelate <i>N</i>′-(dimethylfluorosilylmethyl))-<i>N</i>′-methyl-<i>N</i>-(organosulfonyl)­prolinamides RSO₂-Pro-N­(Me)­CH₂SiMe₂F (<b>2a</b>–<b>f</b>, R = Me (<b>a</b>), Ph (<b>b</b>), 4-MeC₆H₄ (<b>c</b>), 4-ClC₆H₄ (<b>d</b>), 4-BrC₆H₄ (<b>e</b>), 4-NO₂C₆H₄ (<b>f</b>)) were synthesized from the corresponding disiloxanes <b>1a</b>–<b>f</b> using Et₂O·BF₃. According to the NMR and IR data, the extent of dimerization of fluorosilanes <b>2a</b>–<b>f</b> in solution is negligible, while the O→Si coordination in solution is weaker than that in the solid state. Comparative CP/MAS NMR and X-ray diffraction studies revealed that in solution the coordination Si–O bond length varies in a narrow range (2.22–2.24 Å) that is 0.02–0.11 Å longer than in the crystalline state. Dynamic NMR (DNMR) studies of the fluorides revealed a fine structure of the ¹⁹F signals in the 0–20 °C temperature range, which was related to the structural features of the coordination set in these complexes. The temperature dependence of the SiMe₂ signals in the ¹H DNMR spectra was attributed to a permutational isomerization process involving a positional exchange of equatorial ligands. The narrow range of activational barriers of the process (23–24 kcal mol^–1 and more) and high negative values of the entropy of activation are similar to those observed earlier for Si-substituted <i>N</i>-(dimethylsilylmethyl) and <i>N</i>-(methylphenylsilylmethyl) amides and lactams, which suggests similar permutational processes in all cases. Gas-phase quantum chemical studies demonstrate that the solvation of F^– reduces the activation barrier