Application of unsymmetrical indirect covariance NMR methods to the computation of the (13)C <--> (15)N HSQC-IMPEACH and (13)C <--> (15)N HMBC-IMPEACH correlation spectra

Utilization of long-range (1)H--(15)N heteronuclear chemical shift correlation has continually grown in importance since the first applications were reported in 1995. More recently, indirect covariance NMR methods have been introduced followed by the development of unsymmetrical indirect covariance processing methods. The latter technique has been shown to allow the calculation of hyphenated 2D NMR data matrices from more readily acquired nonhyphenated 2D NMR spectra. We recently reported the use of unsymmetrical indirect covariance processing to combine (1)H--(13)C GHSQC and (1)H--(15)N GHMBC long-range spectra to yield a (13)C--(15)N HSQC-HMBC chemical shift correlation spectrum that could not be acquired in a reasonable period of time without resorting to (15)N-labeled molecules. We now report the unsymmetrical indirect covariance processing of (1)H--(13)C GHMBC and (1)H--(15)N IMPEACH spectra to afford a (13)C--(15)N HMBC-IMPEACH spectrum that has the potential to span as many as six to eight bonds. Correlations for carbon resonances long-range coupled to a protonated carbon in the (1)H--(13)C HMBC spectrum are transferred via the long-range (1)H--(15)N coupling pathway in the (1)H--(15)N IMPEACH spectrum to afford a much broader range of correlation possibilities in the (13)C--(15)N HMBC-IMPEACH correlation spectrum. The indole alkaloid vincamine is used as a model compound to illustrate the application of the method.     

Spin-spin coupling across intramolecular N-H(+)-N hydrogen bonds in models for proton sponges: an ab initio investigation

Ab initio calculations have been performed to obtain structures and coupling constants (1)J(N-H), (1h)J(H-N), and (2h)J(N-N) for models of proton sponges with symmetric and asymmetric N-H(+)-N intramolecular hydrogen bonds (IMHBs). For a given model, the asymmetric structure has a lower energy, a longer N-N distance, and a hydrogen bond which has a greater deviation from linearity. The computed values of (2h)J(N-N) for the models are significantly less than predicted values based on the distance dependence of (2h)J(N-N) for complexes with intermolecular N-H(+)-N hydrogen bonds. However, the reduced values of (2h)J(N-N) cannot be attributed solely to the distortion of the hydrogen bond in the models, but also reflect differences in s electron populations at the nitrogens in both the ground state and the excited states which couple to it through the Fermi-contact (FC) operator. Values of (2h)J(N-N) for IMHBs can be related quadratically to the N-N distances in the models, and demonstrate that there is no discrepancy between computed values of (2h)J(N-N) at the short N-N distances found in these systems and experimental data for proton sponges.     

Palladium-catalyzed sequential formation of C-C bonds: efficient assembly of 2-substituted and 2,3-disubstituted quinolines

A series of substituted quinolines was prepared from arylamines, aldehydes, and terminal olefins (see scheme). The palladium-catalyzed sequential formation of C-C bonds proceeds smoothly with both electron-deficient and electron-rich olefins. When acrylic acid is used as terminal olefin, decarboxylation occurs to provide 2-substituted quinolines.     

Utilizing unsymmetrical indirect covariance processing to define 15N- 13C connectivity networks

There has been considerable interest over the past decade in the utilization of direct and long-range 1H- 15N heteronuclear shift correlation methods at natural abundance to facilitate the elucidation of small molecule structures. Recently, there has also been a high level of interest in the exploration of indirect covariance NMR methods. Our initial explorations in this area led to the development of unsymmetrical indirect covariance methods, which allow the calculation of hyphenated 2D NMR spectra such as 2D GHSQC-COSY and GHSQC-NOESY from the discrete component 2D NMR experiments. We now wish to report the utilization of unsymmetrical indirect covariance NMR methods for the combination of 1H- 13C GHSQC and 1H- 15N long-range (GHMBC, IMPEACH-MBC, CIGAR-HMBC, etc.) heteronuclear chemical shift correlation spectra to determine 15N- 13C correlation pathways.     

C-C versus C-H activation and versus agostic C-C interaction controlled by electron density at the metal center

Based on the PCN ligand 2, a remarkable degree of control over C-C versus C-H bond activation and versus formation of an agostic C-C complex was demonstrated by choice of cationic [Rh(CO)(n)(C(2)H(4))(2-n)] (n=0, 1, 2) precursors. Whereas reaction of 2 with [Rh(C(2)H(4))(2)(solv)(n)]BF(4) results in exclusive C-C bond activation to yield product 5, reaction with the dicarbonyl precursor [Rh(CO)(2)(solv)(n)]BF(4) leads to formation of the C-H activated complex 9. The latter process is promoted by intramolecular deprotonation of the C-H bond by the hemilabile amine arm of the PCN ligand. The mixed monocarbonyl monoethylene Rh species [Rh(CO)(C(2)H(4))]BF(4) reacts with the PCN ligand 2 to give an agostic complex 7. The C-C activated complex 5 is easily converted to the C-H activated one (9) by reaction with CO; the reaction proceeds by a unique sequence of 1,2-metal-to-carbon methyl shift, agostic interaction, and C-H activation processes. Similarly, the C-C agostic complex 7 is converted to the same C-H activated product 9 by treatment with CO.     

Iron-catalyzed C2-C3 bond cleavage of phenylpyruvate with O2: insight into aliphatic C-C bond-cleaving dioxygenases

Iron(II)-phenylpyruvate complexes of tetradentate tris(6-methyl-2-pyridylmethyl)amine (6-Me3-TPA) and tridentate benzyl bis(2-quinolinylmethyl)amine (Bn-BQA) were prepared to gain insight into C-C bond cleavage catalyzed by dioxygenase enzymes. The complexes we have prepared and characterized are [Fe(6-Me3-tpa)(prv)][BPh4] (1), [Fe2(6-Me3-tpa)2(pp)][(BPh4)2] (2), and [Fe2(6-Me3-tpa)2(2'-NO2-pp)][(BPh4)2] (3), [Fe(6-Me3-tpa)(pp-Me)][BPh4] (4), [Fe(6-Me3-tpa)(CN-pp-Et)][BPh4] (5), and [Fe(Bn-bqa)(pp)] (8), in which PRV is pyruvate, PP is the enolate form of phenylpyruvate, 2'-NO2-PP is the enolate form of 2'-nitrophenylpyruvate, PP-Me is the enolate form of methyl phenylpyruvate, and CN-PP-Et is the enolate form of ethyl-3-cyanophenylpyruvate. The structures of mononuclear complexes 1 and 5 were determined by single-crystal X-ray diffraction. Both the PRV ligand in 1 and the CN-PP-Et ligand in 5 bind to the iron(II) center in a bidentate manner and form 5-membered chelate rings, but the alpha-keto moiety is in the enolate form in 5 with concomitant loss of a C-H(beta) proton. The PP ligands of 2, 3, 4, and 8 react with dioxygen to form benzaldehyde and oxalate products, which indicates that the C2-C3 PP bond is cleaved, in contrast to cleavage of the C1-C2 bond previously observed for complexes that do not contain alpha-ketocarboxylate ligands in the enolate form. These reactions serve as models for metal-containing dioxygenase enzymes that catalyze the cleavage of aliphatic C-C bonds.