COSY NMR experiments

Tetraphenylsulfurane is the simplest but most unstable among the tetraaryl-sulfurane species. Although only tetraphenyltellurane has been isolated, and its crystal structure has been determined, tetraphenylsulfurane and -selenurane have neither been detected directly nor isolated in the earlier studies. Furukawa and Sato reinvestigated the reactions of triphenyl sulfonium salt 99 and diphenyl sulfoxide 100 with phenyllithium (PhLi) in tetrahydrofuran (THF) in order to attempt detection of tetraphenylsulfurane [10—S—4(C4)] 101 directly by 13C, and CH-COSY NMR experiments at low temperature, as shown in Scheme 40 [91]. As results, the detection of tetraphenyl sulfurane has been achieved by low temperature NMR studies while tetraphenyl tellurane has been isolated [92]. 

The 2,2 -biphenylylene diphenyl sulfurane [10-S-4(C4)] has already been postulated by Trost et al. [38] and Hori et al. as an intermediate in the reaction of 2,2 -biphenylylene phenyl sulfonium salt with phenyl lithium. However, they could not directly prove the existence of the corresponding sulfurane as an intermediate. Sato and Furukawa tried to obtain the first crucial evidence for formation of 2,2 -biphenylylene diphenyl sulfurane 105 in the reactions of 2,2 -biphenylylene phenyl sulfonium salt 104 with PhLi in a THF solution by low temperature 1H, 13C and CH-COSY NMR experiments [95]. By elevating the temperature of a THF solution to room temperature, each solution became colorless, to give phenyl o-terphenyl sulfide 106 quantitatively, after work up, as shown in Scheme 41. 

FIGURE 20.11. Schematic repesentation of a two-dimensional (2D) correlated (COSY) NMR experiment and spectrum after Jeiinski [30]. 

The NMR experiments 55 are obtained from actinomycin D in order to check the amino acid sequence, to assign proton-proton and some carbon-proton connectivities, and to deduce informations concerning proton distances and the spatial structure of both cyclopentapeptide lactone rings. Conditions CDCI3, 10 mg per 0.3 ml, 25 °C, 500 MHz H), 125 MHz ( C). (a) HH COSY plot ... 

Figure 1. Pulse sequences of some typical 2D-NMR experiments. COSY = correlation SpectroscopY, DQFCOSY = Double Quantum Filtered COSY, RELAY = RELAYed Magnetization Spectroscopy, and NOESY = Nuclear Overhauser Effect SpectroscopY.

Figure 1.45 Coherence transfer pathways in 2D NMR experiments. (A) Pathways in homonuclear 2D correlation spectroscopy. The first 90° pulse excites singlequantum coherence of order p= . The second mixing pulse of angle /3 converts the coherence into detectable magnetization (p= —1). (Bra) Coherence transfer pathways in NOESY/2D exchange spectroscopy (B b) relayed COSY (B c) doublequantum spectroscopy (B d) 2D COSY with double-quantum filter (t = 0). The pathways shown in (B a,b, and d) involve a fixed mixing interval (t ). (Reprinted from G. Bodenhausen et al, J. Magn. Resonance, 58, 370, copyright 1984, Rights and Permission Department, Academic Press Inc., 6277 Sea Harbor Drive, Orlando, Florida 32887.)...

There are basically three main types of 2D NMR experiments J-resolved, shift correlation through bonds (e.g., COSY), and shift correlations through space e.g., NOESY). These spectra may be of homonuclear or heteronuclear type involving interactions between similar nuclei (e.g., protons) or between different nuclear species (e.g., H with C). 

The NMR techniques discussed so far provide information about proton-proton interactions (e.g., COSY, NOESY, SECSY, 2D y-resolved), or they allow the correlation of protons with carbons or other hetero atoms (e.g., hetero COSY, COLOC, hetero /resolved). The resulting information is very useful for structure elucidation, but it does not reveal the carbon framework of the organic molecule directly. One interesting 2D NMR experiment, INADEQUATE (Incredible Natural Abundance Double Quantum Transfer Experiment), allows the entire carbon skeleton to be deduced directly via the measurement of C- C couplings. 

The oligomers as produced from saponified MHR were isolated using Sephadex G50 and preparative HPAEC. ID and 2D NMR experiments (COSY and ROESY) were used to determine the structure of the smallest oligosaccharide, eluting at 23 min upon HPAEC. The chemical shifts of the assigned peaks in the H NMR spectrum are summarised in Table II. 

Applications Useful 2D NMR experiments for identification of surfactants are homonuclear proton correlation (COSY, TOCSY) and heteronuclear proton-carbon correlation (HETCOR, HMQC) spectroscopy [200,201]. 2D NMR experiments employing proton detection can be performed in 5 to 20 min for surfactant solutions of more than 50 mM. Van Gorkum and Jensen [238] have described several 2D NMR techniques that are often used for identification and quantification of anionic surfactants. The resonance frequencies of spin-coupled nuclei are correlated and hence give detailed information on the structure of organic molecules. 

This problem cannot be solved by the usual NMR experiments (COSY, NOESY, HSQC, HMBC,...). It turns out that the selective HOESY experiment (Figure 9, bottom) applied to proton H5 provides an unambiguous... 

In 2006, Milosavljevic and co-workers64 reported a study of the complete 4H and 13C NMR assignment of a new triterpenoid saponin, leucantho-side-A (13), from Cephalaria leucantha L. In the course of determining the structure and assigning the spectra, the authors made extensive use of the normal ensemble of 2D NMR experiments in use for the characterization of natural product structures HSQC, HMBC, DQF-COSY, TOCSY, and NOESY. The authors supplemented the aforementioned list of experiments with 2D /-resolved, DINE-(Double INEPT-Edited)-HSQC, and INADEQUATE spectra. The authors made no mention of the use of the connectivity information derived from the 1,1-ADEQUATE spectrum in the assembly of the triterpene nucleus of the molecule but reported extensive tabulations of the 1,1-ADEQUATE correlations that were used to sequence and assign the saccharide resonances of the tri- and di-saccharide sub-units, 14 and 15, respectively, linked to the triterpene nucleus. 

LC-NMR plays a central role in the on-line identification of the constituents of crude plant extracts (Wolfender and others 2003). This technique alone, however, will not provide sufficient spectroscopic information for a complete identification of natural products, and other hyphenated methods, such as LC-UV-DAD and LC-MS/MS, are needed for providing complementary information. Added to this, LC-NMR experiments are time-consuming and have to be performed on the LC peak of interest, identified by prescreening with LC-UV-MS. NMR applied to phenolic compounds includes H NMR,13 C NMR, correlation spectroscopy (COSY), heteronuclear chemical shift correlation NMR (C-H HECTOR), nuclear Overhauser effect in the... 

One example of the use of 2D-NMR experiments in conformational analysis is the study of molecular interactions between cinchonidine and acetic acid [26]. These alkaloids are used as chiral auxiliaries in enantioselective hydrogenations, and the enantiomeric excess is dependent on solvent polarity, acetic acid being a good solvent This suggests that protonation and a preferred conformation play a role in achieving high enantioselectivities. With a combination of COSY-experiments, 3J coupling constants and NOESY experiments, it was shown that one conformer is preferred in acidic solutions. 

The dipole A-a-diphenylnitrone, upon reaction with enone 288 in refluxing toluene for 24 h, gave the diastereomeric products 289a and 289b in a ratio of 1 4.5. The regiochemistry of the addition was given by H and 13C NMR experiments (NOESY and COSY) (Equation 47) <1997T11731>. 

Fig. 8. Pulse schemes for 2H 2D NMR spectroscopy of weakly ordered, deuterated solutes (a) 2H Q-COSY, (b) 2H-13C HETCOR experiment with 13C decoupling, (c) 2H-2H COSY 2D experiment. (Reproduced by permission of American Chemical Society.)...

Hirota and coworkers41 reported a planar structure of new polyene macrolide antibiotic YS-822A (65), which they isolated. XH and 13C NMR spectra of 65 showed a number of broad and overlapping signals, but the 1H-1H and 13C- H COSY spectra implied the existence of a mycosamine moiety and several other partial structures. The connectivity of these partial structures was established by extensive 2D NMR experiments, including homonuclear Hartmann-Hahn and heteronuclear multiple-bond connectivity measurements, which led to the determination of the gross planar structure of 65. 

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