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Heteronuclear long‐range scalar coupling constants (nJCH) are a valuable tool for solving problems in organic chemistry and are especially suited for stereochemical and configurational analyses of small molecules and natural products. This tutorial will focus on the step‐by‐step implementation of several 2D 1H frequency selective HSQMBC experiments for the easy and accurate measurement of either the magnitude or both the magnitude and the sign of long‐range nJCH couplings. The performance of these experiments will be showcased with several scenarios in a range of different experimental conditions. [ABSTRACT FROM AUTHOR]

The development of new tools to improve the quality of nuclear magnetic resonance (NMR) spectra is a challenging task. The concept of "perfect NMR" includes the design of robust pulse sequences that allow an investigator to obtain undistorted pure in‐phase signals, with pure absorption lineshapes that are free of phase anomalies derived from undesired J modulations. Here, alternative NMR building blocks to the spin‐echo that are based on a general double SE module, known as a perfect‐echo, are reviewed. Several implementations to minimize/remove unwanted dispersive contributions in homonuclear and heteronuclear NMR experiments are described and illustrated with some examples of broad interest for small molecules. The concept of "perfect NMR" includes the design of robust pulse sequences that allow obtaining undistorted pure in‐phase signals, with pure absorption lineshapes and free of phase anomalies derived from undesired J modulations. Here, alternative NMR building blocks to spin‐echo which are based on a general double SE module, known as perfect‐echo, are reviewed. Several implementations to minimize/remove unwanted dispersive contributions in homonuclear and heteronuclear NMR experiments are described and illustrated with some examples of broad interest for small molecules. [ABSTRACT FROM AUTHOR]

A 1H‐1H total correlation spectroscopy (TOCSY) experiment incorporating 13C multiplicity information is proposed. In addition, broadband 1H homodecoupling in the indirect dimension can be implemented using a perfect BIRD module that affords exclusive 1H chemical shift evolution with full decoupling of all heteronuclear and homonuclear (including 2JHH) coupling constants. As a complement to the normal TOCSY and the recent PSYCHE‐TOCSY experiments, this novel multiplicity‐edited TOCSY experiment distinguishes between CH/CH3 (phased up) and CH2 (phased down) cross‐peaks, which facilitates resonance analysis and assignment. [ABSTRACT FROM AUTHOR]

1,n‐ADEQUATE is a powerful NMR technique for elucidating the structure of proton‐deficient small molecules that can help establish the carbon skeleton of a given molecule by providing long‐range three‐bond 13C─13C correlations. Care must be taken when using the experiment to identify the simultaneous presence of one‐bond 13C─13C correlations that are not filtered out, unlike the HMBC experiment that has a low‐pass J‐filter to filter 1JCH responses out. Dual‐optimized, inverted 1JCC 1,n‐ADEQUATE is an improved variant of the experiment that affords broadband inversion of direct responses, obviating the need to take additional steps to identify these correlations. Even though ADEQUATE experiments can now be acquired in a reasonable amount of experimental time if a cryogenic probe is available, low sensitivity is still the main impediment limiting the application of this elegant experiment. Here, we wish to report a further refinement that incorporates real‐time bilinear rotation decoupling‐based homodecoupling methodology into the dual‐optimized, inverted 1JCC 1,n‐ADEQUATE pulse sequence. Improved sensitivity and resolution are achieved by collapsing homonuclear proton–proton couplings from the observed multiplets for most spin systems. The application of the method is illustrated with several model compounds. [ABSTRACT FROM AUTHOR]

Two‐dimensional J‐resolved (Jres) NMR experiments offer a simple, user‐friendly spectral representation where the information of coupling constants and chemical shifts are separated into two orthogonal frequency axis. Since its initial proposal 40 years ago, Jres has been the focus of considerable interest both in improving the basic pulse sequence and in its successful application to a wide range of studies. Here, the latest developments in the design of novel Jres pulse schemes are reviewed, mainly focusing on obtaining pure absorption lineshapes, minimizing strong coupling artifacts, and also optimizing sensitivity and experimental measurements. A discussion of several Jres versions for the accurate measurement of a different number of homonuclear (JHH) and heteronuclear (JCH) coupling constants is presented, accompanied by some illustrative examples. [ABSTRACT FROM AUTHOR]

Selective refocusing (GSERF or the recent PSYCHEDELIC) experiments were originally designed to determine all proton-proton coupling constants ( JHH) for a selected proton resonance. They work for isolated signals on which selective excitation can be successfully applied but, as it happens in other selective experiments, fail for overlapped signals. To circumvent this limitation, a doubly-selective TOCSY-GSERF scheme is presented for the measurement of JHH in protons resonating in crowded regions. This new experiment takes advantage of the editing features of an initial TOCSY transfer to uncover hidden resonances that become accessible to perform the subsequent frequency-selective refocusing. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A fast residual dipolar coupling constant-assisted strategy involving the simultaneous determination of scalar and total coupling constants from a single 1 JCH/2 JHH-resolved NMR spectrum is reported. It is shown that the concerted use of the directly measured 1 DCH (for all CHn multiplicities) and 2 DHH residual dipolar couplings allows an on-the-fly assignment of diastereotopic CH2 protons, as well as of an efficient discrimination between diastereoisomeric structures of strychnine which contains six stereocenters. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Homonuclear 13C-13C couplings at natural abundance can be measured using the J-modulated Adequate DoublE QUAntumTransfer Experiment (ADEQUATE) experiment. To somewhat ameliorate F1 digitization requirements, a scaling factor was incorporated into the original pulse sequence. Non-uniform sampling provides an obvious avenue to further facilitate the acquisition of 1 JCC and n JCC homonuclear coupling constant data. We introduce homonuclear decoupling (HD) analogous to that described for the 1,1-HD-ADEQUATE and 1,n-HD-ADEQUATE experiments and evaluate the combination of non-uniform sampling and HD on the acquisition of both 1 JCC and n JCC homonuclear 13C-13C coupling constants using ibuprofen as a model compound. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In recent years, a great interest in the development of new broadband 1H homonuclear decoupled techniques providing simplified JHH multiplet patterns has emerged again in the field of small molecule NMR. The resulting highly resolved 1H NMR spectra display resonances as collapsed singlets, therefore minimizing signal overlap and expediting spectral analysis. This review aims at presenting the most recent advances in pure shift NMR spectroscopy, with a particular emphasis to the Zangger-Sterk experiment. A detailed discussion about the most relevant practical aspects in terms of pulse sequence design, selectivity, sensitivity, spectral resolution and performance is provided. Finally, the implementation of the different reported strategies into traditional 1D and 2D NMR experiments is described while several practical applications are also reviewed. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The presence of a highly abundant passive nucleus (Z = 19 F or 31P) allows the simultaneous determination of the magnitude and the sign of up to three different heteronuclear coupling constants from each individual cross-peak observed in a 2D 1H-X selHSQMBC spectrum. Whereas J(HZ) and J(XZ) coupling constants are measured from E.COSY multiplet patterns, J(XH) is independently extracted from the complementary IPAP pattern generated along the detected F2 dimension. The incorporation of an extended TOCSY transfer allows the extraction of a complete set of all these heteronuclear coupling constants and their signs for an entire 1H subspin system. 1H-X/1H-Y time-shared versions are also proposed for the simultaneous measurement of five different couplings ( J(XH), J(YH), J(XZ), J(YZ), and J(ZH)) for multiple signals in a single NMR experiment. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The amplitude and the phase of cross peaks in conventional 2D HSQC experiments are modulated by both proton-proton, J(HH), and proton-carbon, 1J(CH), coupling constants. It is shown by spectral simulation and experimentally that J(HH) interferences are suppressed in a novel perfect-HSQC pulse scheme that incorporates perfect-echo INEPT periods. The improved 2D spectra afford pure in-phase cross peaks with respect to 1J(CH) and J(HH), irrespective of the experiment delay optimization. In addition, peak volumes are not attenuated by the influence of J(HH), rendering practical issues such as phase correction, multiplet analysis, and signal integration more appropriate. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The effects of phase modulation due to homonuclear proton-proton coupling constants in HSQMBC-IPAP and HMBC-IPAP experiments are experimentally evaluated. We show that accurate values of small proton-carbon coupling constants, nJCH, can be extracted even for phase-distorted cross-peaks obtained from a selHSQMBC experiment applied simultaneously on two mutually J-coupled protons. On the other hand, an assessment of the reliability of nJCH measurement from distorted cross-peaks obtained in broadband IPAP versions of equivalent HMBC and HSQMBC experiments is also presented. Finally, we show that HMBC-COSY experiments could be an excellent complement to HMBC for the measurement of small nJCH values. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]