Parahydrogen‐Induced Polarization in Hydrogenation Reactions Mediated by a Metal‐Free Catalyst

Abstract

We report nuclear spin hyperpolarization of various alkenes achieved in alkyne hydrogenations with parahydrogen over a metal-free hydroborane catalyst (HCAT). Being an intramolecular frustrated Lewis pair aminoborane, HCAT utilizes a non-pairwise mechanism of H 2 transfer to alkynes that normally prevents parahydrogen-induced polarization (PHIP) from being observed. Nevertheless, the specific spin dynamics in catalytic intermediates leads to the hyperpolarization of predominantly one hydrogen in alkene. PHIP enabled the detection of important HCAT-alkyne-H 2 intermediates through substantial 1 H, 11 B and 15 N signal enhancement and allowed advanced characterization of the catalytic process.Nuclear magnetic resonance provides versatile tools for structure elucidation and understanding dynamics at the molecular level. [1] It is also at the heart of magnetic resonance imaging (MRI), a non-invasive and highly informative imaging method. However, the low intrinsic sensitivity of NMR dictated by low thermal spin polarization often leads to the insufficient signal strengths to perform reliable analysis. To date, several spin hyperpolarization techniques have been developed to boost the sensitivity. [2] Among them, parahydrogen-induced polarization (PHIP) is based on the chemical activation of parahydrogen, [3] the nuclear spin-0 isomer of H 2 . The hyperpolarization is produced upon chemical addition of parahydrogen to a substrate due to breaking the magnetic equivalence of protons originating from parahydrogen. [4] The pair of H atoms must not be separated completely to observe the hyperpolarization, that is, the atoms must end up in the same molecule. These prerequisites are fulfilled, for instance, if parahydrogen molecules are involved in the homogeneous catalytic hydrogenations mediated by metal complexes. [3b,5] However, toxicity issues require efficient methods of catalyst separation from hyperpolarized products [6] and can limit their applications, especially in in vivo studies. Heterogeneous catalysts based on immobilized metal complexes, metal nanoparticles and binary metal compounds have also been demonstrated to enable PHIP. [7] The separation is easier in this case as compared to homogeneous catalysts but achieved hyperpolarization levels are typically quite modest.Metal-free homogeneous catalytic systems may provide essentially new alternatives for PHIP. Naturally, substances made of main biogenic elements can be more environmentally and biologically friendly as compared to their metal-containing counterparts. The mechanisms of H 2 activation, however, are significantly different for the metal and nonmetal extremes. Pioneered by Stephan et al., [8] activation of H 2 by frustrated Lewis pairs (FLPs) attracts extraordinary attention. First observations of spin hyperpolarization effects with metal-free systems were reported for ansa-aminoboranes (AABs), the intramolecular N-B FLPs of 2-boryl-benzylamine core. [9] Later, aromatic triphosphabenzene [10] and several novel 2-aminophenylboranes [11] were dem...

Advancing homogeneous catalysis for parahydrogen-derived hyperpolarisation and its NMR applications

“…The use of para-H 2 to enhance NMR signal intensity is a versatile platform that allows the hyperpolarisation of a range of different functionalities including metal complexes, 14,30,36,38,45 alkenes, 14,30,57 alkanes, 14,30 esters, 88 aldehydes, [23][24][25][26][27]114 carboxylic acids, 126,192 N-heterocycles, 17,29 amines, 58,193 diazirines, 124,194,195 nitriles, 167 silanes, 132 sulfoxides, 147,172 a-ketoacids, 125,146,147,157,196 amino acids, 197 peptides 78,80,82,198 and many others. Enhanced NMR signals can be achieved most commonly for 1 H, 13 C and 15 N sites, although PHIP and SABRE-enhanced 2 H, 199,200 11 B, 28,64,66 19 F, 85,128,129,…”

“…213,214,217 It is expected that further catalyst development will be a large driving force behind further extension of substrate scope, increased efficiency, and enhanced biocompatibility. In particular, novel metal-free, 28,[64][65][66][67] trans hydrogenation, 106,109,181,182 sulfoxide-containing SABRE catalysts 125,146,147,157 and cobalt-based SABRE-like systems 59,179 are likely to lead to exciting new results in this area in the years ahead.…”

“…Very recently, ansa -aminoboranes have been shown to hydrogenate alkynes with para-H 2 leading to hyperpolarisation of alkene products. 28 In the reported examples, a frustrated Lewis pair (HCAT) reacts with an alkyne to form a HCAT-alkyne adduct ( Fig. 7a ).…”

“…At the same time, PHIP can be observed for catalytic intermediates if initial para-H 2 activation by the catalyst active centre is pairwise, although the full cycle can be non-pairwise. Based on this possibility, effects such as oneH-PHIP [23][24][25][26][27][28] can be observed wherein only one of the para-H 2 originating protons ends up in the hyperpolarised product. There are also reactions in which molecules can become hyperpolarised without chemical incorporation of para-H 2 into the target structures, as takes place in SABRE.…”

H-atom Abstraction Reactivity through the Lens of Asynchronicity and Frustration with their Counter-Acting Effects on Barriers

“…In contrast to canonical equation ( 12), all trained methods were parametrized using metal-oxo oxidants and their transferability to a purely organic chemical space would be paramount as the field of organocatalysis continues to bloom. 36,37,38 The predictions from the four models on the organic test set are condensed in Figure 7. Borovik's model, adapted to the prediction of relative HAA barriers, displays two parameters, (α,…”