Josep Saurí

Nuclear Magnetic Resonance (NMR) spectroscopy has long been a cornerstone in the structural elucidation of molecules, offering unique insights into atomic-level connectivity, conformation, and dynamics. Over the past decades, methodological and technological advances have significantly expanded its capabilities and applications. This manuscript charts the evolution of NMR from classical 1D/2D experiments to modern methods empowered by ultrahigh magnetic fields, cryogenic probes, non-uniform sampling, new methodologies, and hyperpolarization. We emphasize the growing synergy between experiment and computation, where automated analysis, quantum chemical calculations, and machine learning are dramatically enhancing the accuracy and efficiency of structure determination. We also highlight NMR’s broadening scope in areas ranging from complex mixtures and natural products to biomolecular and materials science.

Flat aromatic compounds containing a boron–nitrogen (BN) fragment have gained significant attention in the field of organic optoelectronics. Unsurprisingly, therefore, an increasing number of synthetic methodology groups have devoted efforts and creativity to developing new strategies for accessing diverse structures incorporating a BN unit, which is isosteric with the olefinic CC bond. In contrast, the potential of BN isosterism to expand the structural diversity of three-dimensional architectures based on sp³-hybridized atoms remains largely underexplored. In this study, we introduce a strategy to construct an alkane-type quaternary–quaternary Bsp³–Nsp³ molecular axis via double addition of a carbon-based nucleophile/electrophile pair to a readily accessible olefin-type BN moiety. The approach is showcased through the synthesis of a BN-[4.4.4]-propellane, in which the rapidly assembled tetrahydro-BN-naphthalene intermediate undergoes a polar double allylation of its BN bond. Despite the unfavorable trans preference in this addition step, efficient [4.4.4]-propellane formation was achieved through a tandem metathesis-based trans-to-cis isomerization and ring-closing reaction. The resulting BN-propellane exhibits a C₃-symmetric helical arrangement in the solid state and shows fluxional behavior in the ¹H NMR spectrum at room temperature due to a helicity flip, for which variable-temperature NMR measurements yielded an activation barrier (ΔG^‡) of approximately 14.6 kcal mol⁻¹.

The discorhabdin natural products are a large subset of pyrroloiminoquinone alkaloids with a myriad of biological activities. Despite garnering much synthetic attention, few members have thus far been completed, particularly those featuring a bridging carbon‐nitrogen bond that is found in numerous discorhabdins, including discorhabdin V. Herein we report the first total synthesis and full stereochemical assignment of (+)‐discorhabdin V. To access the pyrroloiminoquinone we developed a convergent N‐alkylation/oxidative aminocyclization/bromination cascade that joins two key components, which are both made on multigram scale. An intramolecular Heck reaction then forms the quaternary carbon center in an intermediate containing the carbon‐nitrogen bridge, and a reductive N,O‐acetal cyclization sequence introduces the final piperidine ring. Furthermore, we have established the relative configuration of (+)‐discorhabdin V through experimental NOESY data and DP4 NMR probability calculations. The absolute configuration of the natural product has also been determined by circular dichroism and the use of an amino acid derived chiral starting material. Our work represents one of only two reports of a total synthesis of a nitrogen‐bridged discorhabdin and paves the way for future biological evaluation of such compounds.

The discorhabdin natural products are a large subset of pyrroloiminoquinone alkaloids with a myriad of biological activities. Despite garnering much synthetic attention, few members have thus far been completed, particularly those featuring a bridging carbon‐nitrogen bond that is found in numerous discorhabdins, including discorhabdin V. Herein we report the first total synthesis and full stereochemical assignment of (+)‐discorhabdin V. To access the pyrroloiminoquinone we developed a convergent N‐alkylation/oxidative aminocyclization/bromination cascade that joins two key components, which are both made on multigram scale. An intramolecular Heck reaction then forms the quaternary carbon center in an intermediate containing the carbon‐nitrogen bridge, and a reductive N,O‐acetal cyclization sequence introduces the final piperidine ring. Furthermore, we have established the relative configuration of (+)‐discorhabdin V through experimental NOESY data and DP4 NMR probability calculations. The absolute configuration of the natural product has also been determined by circular dichroism and the use of an amino acid derived chiral starting material. Our work represents one of only two reports of a total synthesis of a nitrogen‐bridged discorhabdin and paves the way for future biological evaluation of such compounds.

A novel, convergent synthesis of aminotriazoloquinazolines is reported. These heterocycles are reliably prepared via a "click-like" reaction between readily available aryl carbodiimides and acyl or aryl hydrazides. Such products are of particular interest with respect to their inhibitory activity against the A_2A and A_2B adenosine receptors, and the title two-component coupling reaction has greatly accelerated the discovery of potent/selective chemical matter in this space.

Three new aryl alkaloids named suberitamides A–C (1–3), were isolated from an extract of the marine sponge Pseudosuberites sp. collected along the coast of North Carolina. Their planar structures were established by extensive nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis. To assign the challenging relative configuration of the saturated five-membered ring in suberitamide A (1), a simple and efficient NMR protocol was applied that is based on the analysis of 2- and 3-bond ¹H-¹³C spin-spin coupling constants using a PIP (pure in-phase) HSQMBC (heteronuclear single quantum multiple bond correlation) IPAP (in-phase and anti-phase) experiment. Suberitamides A (1) and B (2) inhibited Cbl-b, an E3 ubiquitin ligase that is an important modulator of immune cell function, with IC₅₀ values of approximately 11 μM.

The optimum detection and accurate measurement of longer‐range (⁴J and higher) heteronuclear NMR correlations is described. The magnitude and/or the sign of a wide range of large and small long‐range couplings can be simultaneously determined for protonated and non‐protonated ¹³C and ¹⁵N nuclei using the LR‐selHSQMBC experiment.

Heteronuclear long‐range scalar coupling constants (ⁿJ_CH) 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 ⁿJ_CH couplings. The performance of these experiments will be showcased with several scenarios in a range of different experimental conditions.

High accuracy for DFT-predicted ¹J_CH-couplings can be achieved without ad hoc corrections or empirical scaling by careful selection of the DFT method utilized for geometry optimization and J-coupling calculations.