Hydrogen and Water Splitting by Frustrated Lewis Pairs and Reactions thereof

The principle of combining a Lewis acid (LA) and a Lewis base (LB), prevented from the formation of classical Lewis adduct and thus possessing reactive potential, is known as frustrated Lewis pair (FLP). This powerful, yet simple concept allowed for a wide range of reactivities unprecedented for main group chemistry and is perceived as an alternative to transition metal catalysis. Among such reactivities, hydrogen activation and catalytic hydrogenations of unsaturated organic substrates, perhaps remain the most remarkable ones. In the literature review, our focus is limited to hydrogen activation and reactions thereof, and furthermore, FLPs comprising boron-centered LAs. First, mechanistic aspects of the process are discussed, including principles of assessment and modulation of Lewis acidity. Further, the review covers hydrogenation catalysis with FLPs, including hydrogenation of polar and non-polar substrates, functional group- and moisture- tolerant catalysts, and enantioselective hydrogenations. A separate section is devoted to intramolecular FLPs as a distinct subclass of FLPs. The results and discussion part summarizes the key findings reported in the attached original publications and can be divided into two subtopics. First is devoted to the development of linked FLPs aimed for generation of parahydrogen-induced hyperpolarization (PHIP). The phenomenon occurs upon parahydrogen (p-H2) pairwise splitting and causes substantial amplification of NMR signals of p-H2 originating fragments and neighboring nuclei. Therefore, the method can be promising for sensitivity enhancement in, e.g., NMR (MRI) signal imaging. In this work, the series of phenylene bridged ansa-aminoboranes (AABs) varied in the chemical environment around B were synthesised, and their ability to generate PHIP upon addition of p-H2 at ambient conditions was demonstrated. Kinetic, thermodynamic, and NMR parameters favorable for the efficient production of PHIP with such FLPs were formulated. Replacement of quadrupolar 14N nucleus of the amine site with 15N in the series led to spontaneous polarization transfer to nitrogen and strong signal enhancements. Further efforts were dedicated to overcoming the incompatibility of ansa-FLPs with water, bringing closer their realization as PHIP contrast agents in biologically relevant media. In this regard, thorough design of LA-LB active sites resulted in ansa-phosphinoborane capable of both H2 and H2O splitting in a reversible manner. Quite unexpectedly, this compound featured stoichiometric reduction of H2O to H2 via a proton “umpolung” mechanism. The second part is devoted to synthesizing (+)-camphor-based chiral boranes for asymmetric hydrogenation of imines. This study resulted in a highly enantioselective catalyst easily accessible from the synthetic point of view and shed light on the origin of the enantioselectivity.Lewis-hapon (LH) ja Lewis-emäksen (LE) yhdistelmä, jossa klassisen Lewis-adduktin muodostuminen on estynyt, tunnetaan turhautuneena Lewis -parina (Frustrated Lewis Pair, FLP). Tämä yksinkertainen konsepti mahdollistaa laajan kemiallisen reaktiivisuuden, joista monet ovat aikaisemmin tuntemattomia pääryhmän alkuaineiden kemiassa. Reaktiivisuuksista molekulaarisen vedyn aktivoiminen ja tyydyttymättömien orgaanisten substraattien katalyyttiset vedytykset ovat ehkä kaikkein merkittävimpiä, ja aikaisemmin tunnettu vain siirtymämetallikatalyyteille. Kirjallisuuskatsauksen painopiste on vedyn aktivoinnissa ja jatkoreaktioissa, ja turhautuneissa Lewis -pareissa, joiden LH:t sisältävät booria. Kirjallisuuskatsauksen aluksi käsitellään reaktiivisuuden perusteita, mukaan lukien Lewisin happamuuden arvioinnin ja moduloinnin periaatteet. Tämän lisäksi katsauksessa käsitellään vedytyskatalyysiä mukaan lukien polaaristen ja poolittomien substraattien vedytys, enantioselektiivinen vedytus ja katalyyttien kykyä sietää funktionaalisia ryhmiä ja kosteutta. Kirjallisuuskatsauksessa on myös erillinen osio omistettuna molekyylinsisäisille FLP:ille. Tulokset ja keskustelut –osio tiivistää alkuperäisissä julkaisuissa raportoidut keskeiset havainnot, jotka voidaan jakaa kahteen osaan. Ensimmäinen osa on omistettu molekyylinsisäisten FLP:iden kehittämiseen, joiden tarkoituksena on muodostaa hyperpolarisaatio paravedyn indusoimana (PHIP). Hyperpolarisaatio tapahtuu paravedyn (p-H2) aktivoinnilla aiheuttaen p-H2:sta peräisin olevien fragmenttien ja vierekkäisten ytimien NMR-signaalien huomattavan vahvistumisen. Siksi menetelmä voi olla lupaava herkkyyden parantamiseksi esim. NMR (MRI) -signaalikuvauksessa. Väitöskirjatyössä valmistettiin sarja fenyylisillallisia ansa-aminoboraaneja (AAB), joiden LH:n kemiallista rakennetta muokattiin. Näillä ABB:la tutkittiin PHIP:n muodostumista eri reaktio-olosuhteissa ja määritettiin optimaaliset kineettiset, termodynaamiset sekä NMR-parametrit. Huomionarvoista on myös, että amiinin (LE) 14N ytimen korvaaminen 15N:llä johti spontaaniin polarisaation siirtymiseen typelle ja siten voimakkaaseen signaalin kasvamiseen. Työssä tutkittiin myös mahdollisuutta valmistaa molekyylinsisäisiä FLP rakenteita, jotka kykenesivät H2:n aktivoimiseen veden läsnä ollessa. Tämä mahdollistaisi FLP:n hyödyntämisen PHIP-varjoaineina biologisesti merkityksellisissä liuoksissa. Tältä osin on huomionarvoista on, että LA-LB:n aktiivisten kohtien perusteellinen suunnittelu johti ansa-fosfinoboraaniin, joka pystyy sekä H2:n että H2O:n reversiibeliin aktivoimiseen. Yllättäen tämä yhdiste mahdollisti myös stoikiometrisen H2O:n pelkistyksen H2:ksi protonien "umpolung"-mekanismin kautta. Tulokset ja keskustelut –osion toisessa osassa käsitellään(+)-kamferipohjaisten kiraalisten boraanien valmistamista ja käyttöä imiinien asymmetrisessä vedytyksessä. Tämä tutkimus johti erittäin enantioselektiiviseen katalyyttiin, joka on synteettisestä näkökulmasta helposti saatavilla. Tutkimus myös valaisi enantioselektiivisyyden alkuperää FLP katalysoiduissa reaktioissa

Water Reduction and Dihydrogen Addition in Aqueous Conditions With ansa-Phosphinoborane

Ortho -phenylene-bridged phosphinoborane (2,6-Cl 2 Ph) 2 B-C 6 H 4 -PCy 2 1 was synthesized in three steps from commercially available starting materials. 1 reacts with H 2 or H 2 O under mild conditions to form corresponding zwitterionic phosphonium borates 1-H 2 or 1-H 2 O . NMR studies revealed both reactions to be remarkably reversible. Thus, when exposed to H 2 , 1-H 2 O partially converts to 1-H 2 even in the presence of multiple equivalents of water in the solution. The addition of parahydrogen to 1 leads to nuclear spin hyperpolarization both in dry and hydrous solvents, confirming the dissociation of 1-H 2 O to free 1 . These observations were supported by computational studies indicating that the formation of 1-H 2 and 1-H 2 O from 1 are thermodynamically favored. Unexpectedly, 1-H 2 O can release molecular hydrogen to form phosphine oxide 1-O . Kinetic, mechanistic, and computational (DFT) studies were used to elucidate the unique ?umpolung? water reduction mechanism.Peer reviewe

Parahydrogen-induced polarization study of imine hydrogenations mediated by a metal-free catalyst

Parahydrogen-induced polarization is a nuclear spin hyperpolarization technique that can provide strongly enhanced NMR signals for catalytic hydrogenation reaction products and intermediates. Among other matters, this can be employed to study the mechanisms of the corresponding chemical transformations. Commonly, noble metal complexes are used for reactions with parahydrogen. Herein, we present a PHIP study of metal-free imine hydrogenations catalyzed by the ansa-aminoborane catalyst QCAT. We discuss the reaction mechanism by showing the pairwise nature of the initial hydrogen activation step that leads to the formation of the negative net nuclear spin polarization of N-H hydrogen in the QCAT-H-2 intermediate, enabling the further transfer of parahydrogen-originating protons to the imine substrate with the accumulation of hyperpolarized amine products. Parahydrogen-induced polarization also demonstrates the reversibility of the catalytic cycle.Peer reviewe

Parahydrogen-induced polarization study of imine hydrogenations mediated by a metal-free catalyst

Parahydrogen-induced polarization is a nuclear spin hyperpolarization technique that can provide strongly enhanced NMR signals for catalytic hydrogenation reaction products and intermediates. Among other matters, this can be employed to study the mechanisms of the corresponding chemical transformations. Commonly, noble metal complexes are used for reactions with parahydrogen. Herein, we present a PHIP study of metal-free imine hydrogenations catalyzed by the ansa-aminoborane catalyst QCAT. We discuss the reaction mechanism by showing the pairwise nature of the initial hydrogen activation step that leads to the formation of the negative net nuclear spin polarization of N-H hydrogen in the QCAT-H-2 intermediate, enabling the further transfer of parahydrogen-originating protons to the imine substrate with the accumulation of hyperpolarized amine products. Parahydrogen-induced polarization also demonstrates the reversibility of the catalytic cycle.Peer reviewe

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

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 H-1, B-11 and N-15 signal enhancement and allowed advanced characterization of the catalytic process.Peer reviewe

Origin of Stereoselectivity in FLP-Catalyzed Asymmetric Hydrogenation of Imines

Development of metal-free strategies for stereoselective hydrogenation of unsaturated substrates is of particular interest in asymmetric synthesis. The emerging chemistry of frustrated Lewis pairs offers a promising approach along this line as demonstrated by recent achievements. However, the stereocontrol elements in these reactions are not clearly recognized thus far. Herein, we analyze the origin of stereoinduction in direct hydrogenation of imines catalyzed by a set of chiral boranes. We use the tools of computational chemistry to describe the elementary steps of the catalytic cycle, and we pay special attention to the stereoselectivity-determining hydride transfer process. The enantioselectivities predicted by the applied computational approach are in very good agreement with previous experimental observations. We find that the stereoselectivity is governed by a thermodynamically less favored conformer of the borohydride intermediate and not by the experimentally observed form. The most favored hydride transfer transition states are stabilized by specific aryl-aryl and alkyl-aryl noncovalent interactions, which play an important role in stereoinduction. This computational insight is exploited in proposing additional borane variants to improve the enantioselectivity, which could be demonstrated experimentallyPeer reviewe

Spontaneous N-15 Nuclear Spin Hyperpolarization in Metal-Free Activation of Parahydrogen by Molecular Tweezers

The ability of frustrated Lewis pairs (FLPs) to activate H-2 is of significant interest for metal-free catalysis. The activation of H-2 is also the key element of parahydrogen-induced polarization (PHIP), one of the nuclear spin hyper polarization techniques. It is demonstrated that o-phenylene-based ansa-aminoboranes (AABs) can produce H-1 nuclear spin hyperpolarization through a reversible interaction with parahydrogen at ambient temperatures. Heteronuclei are useful in NMR and MRI as well because they have a broad chemical shift range and long relaxation times and may act as background-free labels. We report spontaneous formation of N-15 hyperpolarization of the N-H site for a family of AABs. The process is efficient at the high magnetic field of an NMR magnet (7 T), and it provides up to 350-fold N-15 signal enhancements. Different hyperpolarization effects are observed with various AAB structures and in a broad temperature range. Spontaneous hyperpolarization, albeit an order of magnitude weaker than that for N-15, was also observed for B-11 nuclei.Peer reviewe

Nuclear spin hyperpolarization with ansa-aminoboranes : a metal-free perspective for parahydrogen-induced polarization

The parahydrogen-induced polarization (PHIP) phenomenon, observed when parahydrogen is used in H-2 addition processes, provides a means for substantial NMR signal enhancements and mechanistic studies of chemical reactions. Commonly, noble metal complexes are used for parahydrogen activation, whereas metal-free activation is rare. Herein, we report a series of unimolecular metal-free frustrated Lewis pairs based on an ansa-aminoborane (AAB) moiety in the context of PHIP. These molecules, which have a "molecular tweezers'' structure, differ in their substituents at the boryl site (-H, -Ph, -o-iPr-Ph, and -Mes). PHIP effects were observed for all the AABs after exposing their solutions to parahydrogen in a wide temperature range, and experimental measurements of their kinetic and thermodynamic parameters were performed. A theoretical analysis of their nuclear spin polarization effects is presented, and the roles of chemical exchange, chemical equilibrium and spin dynamics are discussed in terms of the key dimensionless parameters. The analysis allowed us to formulate the prerequisites for achieving strong polarization effects with AAB molecules, which can be applied for further design of efficient metal-free tweezers-like molecules for PHIP. Mechanistic (chemical and physical) aspects of the observed effects are discussed in detail. In addition, we performed quantum chemical calculations, which confirmed that the J-coupling between the parahydrogen-originated protons in AAB-H-2 molecules is mediated through dihydrogen bonding.Peer reviewe

Metal-Free sp²‑C–H Borylation as a Common Reactivity Pattern of Frustrated 2‑Aminophenylboranes

C–H borylation is a powerful and atom-efficient method for converting affordable and abundant chemicals into versatile organic reagents used in the production of fine chemicals and functional materials. Herein we report a facile C–H borylation of aromatic and olefinic C–H bonds with 2-aminophenylboranes. Computational and experimental studies reveal that the metal-free C–H insertion proceeds via a frustrated Lewis pair mechanism involving heterolytic splitting of the C–H bond by cooperative action of the amine and boryl groups. The adapted geometry of the reactive B and N centers results in an unprecedentently low kinetic barrier for both insertion into the sp²-C–H bond and intramolecular protonation of the sp²-C–B bond in 2-ammoniophenyl­(aryl)- or -(alkenyl)­borates. This common reactivity pattern serves as a platform for various catalytic reactions such as C–H borylation and hydrogenation of alkynes. In particular, we demonstrate that simple 2-aminopyridinium salts efficiently catalyze the C–H borylation of hetarenes with catecholborane. This reaction is presumably mediated by a borenium species isoelectronic to 2-aminophenylboranes

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 H₂ 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-H₂ intermediates through substantial ¹H, ¹¹B and ¹⁵N signal enhancement and allowed advanced characterization of the catalytic process