Investigating Hydrogen-Bonded Phosphonic Acids with Proton Ultrafast MAS NMR and DFT Calculations

Hydrogen-bonding plays a key role in the structure and dynamics of a wide range of materials from small molecules to complex biomolecules. ¹H NMR has emerged as a powerful tool for studying hydrogen-bonding because the proton isotropic chemical shift exhibits a dependence on the interatomic distances associated with the hydrogen bond. In the present work, we illustrate the use of ultrafast magic angle spinning at high magnetic field (800 MHz) for resolving multiple hydrogen-bonding sites in a set of crystalline phosphonic acids that contain various functional groups (−COOH, −PO₃H₂, and −NH₃⁺). Trends are observed between the proton chemical shift of the hydrogen-bonded proton and the associated hydrogen-bonding distances (O–H···X) from X-ray crystallography. Density functional theory calculations conducted on the phosphonic acid structures illustrate that the experimental proton chemical shift dependence on hydrogen-bond distance agrees with the expected theoretical trends. Further, it is shown that the chemical shift trend varies considerably depending on the functional group participating in the hydrogen bonding, albeit a −COOH, −PO₃H₂, or −NH₃⁺ moiety. An improved understanding of these trends for various functional groups should be useful for determining accurate hydrogen-bond strengths from the proton chemical shift in an array of systems

A Highly Active Manganese Precatalyst for the Hydrosilylation of Ketones and Esters

The reduction of (^Ph₂PPrPDI)­MnCl₂ allowed the preparation of the formally zerovalent complex, (^Ph₂PPrPDI)­Mn, which features a pentadentate bis­(imino)­pyridine chelate. This complex is a highly active precatalyst for the hydrosilylation of ketones, exhibiting TOFs of up to 76,800 h^–1 in the absence of solvent. Loadings as low as 0.01 mol % were employed, and (^Ph₂PPrPDI)Mn was found to mediate the atom-efficient utilization of Si–H bonds to form quaternary silane products. (^Ph₂PPrPDI)Mn was also shown to catalyze the dihydrosilylation of esters following cleavage of the substrate acyl C–O bond. Electronic structure investigation of (^Ph₂PPrPDI)Mn revealed that this complex possesses an unpaired electron on the metal center, rendering it likely that catalysis takes place following electron transfer to the incoming carbonyl substituent

Preparation and Hydrosilylation Activity of a Molybdenum Carbonyl Complex That Features a Pentadentate Bis(imino)pyridine Ligand

Attempts to prepare low-valent molybdenum complexes that feature a pentadentate 2,6-bis­(imino)­pyridine (or pyridine diimine, PDI) chelate allowed for the isolation of two different products. Refluxing Mo­(CO)₆ with the pyridine-substituted PDI ligand, ^PyEtPDI, resulted in carbonyl ligand substitution and formation of the respective bis­(ligand) compound (^PyEtPDI)₂Mo (<b>1</b>). This complex was investigated by single-crystal X-ray diffraction, and density functional theory calculations indicated that <b>1</b> possesses a Mo(0) center that back-bonds into the π*-orbitals of the unreduced PDI ligands. Heating an equimolar solution of Mo­(CO)₆ and the phosphine-substituted PDI ligand, ^Ph2PPrPDI, to 120 °C allowed for the preparation of (^Ph2PPrPDI)­Mo­(CO) (<b>2</b>), which is supported by a κ⁵-<i>N</i>,<i>N</i>,<i>N</i>,<i>P</i>,<i>P</i>-^Ph2PPrPDI chelate. Notably, <b>1</b> and <b>2</b> have been found to catalyze the hydrosilylation of benzaldehyde at 90 °C, and the optimization of <b>2</b>-catalyzed aldehyde hydrosilylation at this temperature afforded turnover frequencies of up to 330 h^–1. Considering additional experimental observations, the potential mechanism of <b>2</b>-mediated carbonyl hydrosilylation is discussed

A Pentacoordinate Mn(II) Precatalyst That Exhibits Notable Aldehyde and Ketone Hydrosilylation Turnover Frequencies

Heating (THF)₂MnCl₂ in the presence of the pyridine-substituted bis­(imino)­pyridine ligand, ^PyEtPDI, allowed preparation of the respective dihalide complex, (^PyEtPDI)­MnCl₂. Reduction of this precursor using excess Na/Hg resulted in deprotonation of the chelate methyl groups to yield the bis­(enamide)­tris­(pyridine)-supported product, (κ⁵-<i>N</i>,<i>N</i>,<i>N</i>,<i>N</i>,<i>N</i>-^PyEtPDEA)­Mn. This complex was characterized by single-crystal X-ray diffraction and found to possess an intermediate-spin (<i>S</i> = ³/₂) Mn­(II) center by the Evans method and electron paramagnetic resonance spectroscopy. Furthermore, (κ⁵-<i>N</i>,<i>N</i>,<i>N</i>,<i>N</i>,<i>N</i>-^PyEtPDEA)Mn was determined to be an effective precatalyst for the hydrosilylation of aldehydes and ketones, exhibiting turnover frequencies of up to 2475 min^–1 when employed under solvent-free conditions. This optimization allowed for isolation of the respective alcohols and, in two cases, the partially reacted silyl ethers, PhSiH­(OR)₂ [R = Cy and CH­(Me)­(ⁿBu)]. The aldehyde hydrosilylation activity observed for (κ⁵-<i>N</i>,<i>N</i>,<i>N</i>,<i>N</i>,<i>N</i>-^PyEtPDEA)Mn renders it one of the most efficient first-row transition metal catalysts for this transformation reported to date

Hydrosilylation of Aldehydes and Formates Using a Dimeric Manganese Precatalyst

The formally zero-valent Mn dimer [(^Ph2PEtPDI)­Mn]₂ has been synthesized upon reducing (^Ph2PEtPDI)­MnCl₂ with excess Na/Hg. Single crystal X-ray diffraction analysis has revealed that [(^Ph2PEtPDI)­Mn]₂ possesses a κ⁴-PDI chelate about each Mn center, as well as η²-imine coordination across the dimer. The chelate metrical parameters suggest single electron PDI reduction and EPR spectroscopic analysis afforded a signal consistent with two weakly interacting <i>S</i> = ¹/₂ Mn centers. At ambient temperature in the absence of solvent, [(^Ph2PEtPDI)­Mn]₂ has been found to catalyze the hydrosilylation of aldehydes at loadings as low as 0.005 mol % (0.01 mol % relative to Mn) with a maximum turnover frequency of 9,900 min^–1 (4,950 min^–1 per Mn). Moreover, the [(^Ph2PEtPDI)­Mn]₂-catalyzed dihydrosilylation of formates has been found to proceed with turnover frequencies of up to 330 min^–1 (165 min^–1 relative to Mn). These metrics are comparable to those described for the leading Mn catalyst for this transformation, the propylene-bridged variant (^Ph2PPrPDI)­Mn; however, [(^Ph2PEtPDI)­Mn]₂ is more easily inhibited by donor functionalities. Carbonyl and carboxylate hydrosilylation is believed to proceed through a modified Ojima mechanism following dimer dissociation

Reactivity of (Triphos)FeBr₂(CO) towards sodium borohydrides

<p>The addition of CO to (Triphos)FeBr₂ (Triphos = PhP(CH₂CH₂PPh₂)₂) resulted in formation of six-coordinate (Triphos)FeBr₂(CO). This coordination compound was found to have <i>cis</i>-bromide ligands and a <i>mer</i>-Triphos ligand by single crystal X-ray diffraction. Once characterized, the reactivity of this compound toward NaEt₃BH and NaBH₄ was investigated. Adding 1 eq. of NaEt₃BH to (Triphos)FeBr₂(CO) resulted in formation of (Triphos)FeH(Br)(CO), while the addition of 2.2 eq. afforded previously described (Triphos)Fe(CO)₂. In contrast, adding 2.2 eq. of NaBH₄ to (Triphos)FeBr₂(CO) resulted in carbonyl dissociation and formation of diamagnetic (Triphos)FeH(<i>η</i>²-BH₄), which has been structurally characterized. Notably, efforts to prepare (Triphos)FeH(<i>η</i>²-BH₄) following 2.2 eq. NaBH₄ addition to (Triphos)FeBr₂ were unsuccessful. The importance of these observations as they relate to previously reported (Triphos)Fe reactivity and recent developments in Fe catalysis are discussed.</p

Antineoplastic Agents. 595. Structural Modifications of Betulin and the X‑ray Crystal Structure of an Unusual Betulin Amine Dimer

The lupane-type triterpene betulin (<b>1</b>) has been subjected to a series of structural modifications for the purpose of evaluating resultant cancer cell growth inhibitory activity. The reaction sequence <b>7</b> → <b>11</b> → <b>12</b> was especially noteworthy in providing a betulin-derived amine dimer. Other unexpected synthetic results included the <b>11</b> and <b>13</b>/<b>14</b> → <b>17</b> conversions, which yielded an imidazo derivative. X-ray crystal structures of dimer <b>12</b> and intermediate <b>25</b> are reported. All of the betulin modifications were examined for anticancer activity against the P388 murine and human cell lines. Significant cancer cell growth inhibition was found for <b>4</b>, <b>8</b>, <b>9</b>, <b>15</b>/<b>16</b>, <b>19</b>, <b>20</b>, <b>24</b>, and <b>26</b>, which further defines the utility of the betulin scaffold

Mechanistic Investigation of Bis(imino)pyridine Manganese Catalyzed Carbonyl and Carboxylate Hydrosilylation

We recently reported a bis­(imino)­pyridine (or pyridine diimine, PDI) manganese precatalyst, (^Ph2PPrPDI)Mn (<b>1</b>), that is active for the hydrosilylation of ketones and dihydrosilylation of esters. In this contribution, we reveal an expanded scope for <b>1</b>-mediated hydrosilylation and propose two different mechanisms through which catalysis is achieved. Aldehyde hydrosilylation turnover frequencies (TOFs) of up to 4900 min^–1 have been realized, the highest reported for first row metal-catalyzed carbonyl hydrosilylation. Additionally, <b>1</b> has been shown to mediate formate dihydrosilylation with leading TOFs of up to 330 min^–1. Under stoichiometric and catalytic conditions, addition of PhSiH₃ to (^Ph2PPrPDI)Mn was found to result in partial conversion to a new diamagnetic hydride compound. Independent preparation of (^Ph2PPrPDI)­MnH (<b>2</b>) was achieved upon adding NaEt₃BH to (^Ph2PPrPDI)­MnCl₂ and single-crystal X-ray diffraction analysis revealed this complex to possess a capped trigonal bipyramidal solid-state geometry. When 2,2,2-trifluoroacetophenone was added to <b>1</b>, radical transfer yielded (^Ph2PPrPDI<b>·</b>)­Mn­(OC<b>·</b>(Ph)­(CF₃)) (<b>3</b>), which undergoes intermolecular C–C bond formation to produce the respective Mn­(II) dimer, [(μ-<i>O</i>,<i>N</i>_py-4-OC­(CF₃)­(Ph)-4-H-^Ph2PPrPDI)­Mn]₂ (<b>4</b>). Upon finding <b>3</b> to be inefficient and <b>4</b> to be inactive, kinetic trials were conducted to elucidate the mechanisms of <b>1</b>- and <b>2</b>-mediated hydrosilylation. Varying the concentration of <b>1</b>, substrate, and PhSiH₃ revealed a first order dependence on each reagent. Furthermore, a kinetic isotope effect (KIE) of 2.2 ± 0.1 was observed for <b>1</b>-catalyzed hydrosilylation of diisopropyl ketone, while a KIE of 4.2 ± 0.6 was determined using <b>2</b>, suggesting <b>1</b> and <b>2</b> operate through different mechanisms. Although kinetic trials reveal <b>1</b> to be the more active precatalyst for carbonyl hydrosilylation, a concurrent <b>2</b>-mediated pathway is more efficient for carboxylate hydrosilylation. Considering these observations, <b>1</b>-catalyzed hydrosilylation is believed to proceed through a modified Ojima mechanism, while <b>2-</b>mediated hydrosilylation occurs via insertion

Catalytic Hydrogen Evolution by Fe(II) Carbonyls Featuring a Dithiolate and a Chelating Phosphine

Two pentacoordinate mononuclear iron carbonyls of the form (bdt)­Fe­(CO)­P₂ [bdt = benzene-1,2-dithiolate; P₂ = 1,1′-diphenylphosphinoferrocene (<b>1</b>) or methyl-2-{bis­(diphenylphosphinomethyl)­amino}­acetate (<b>2</b>)] were prepared as functional, biomimetic models for the distal iron (Fe_d) of the active site of [FeFe]-hydrogenase. X-ray crystal structures of the complexes reveal that, despite similar ν­(CO) stretching band frequencies, the two complexes have different coordination geometries. In X-ray crystal structures, the iron center of <b>1</b> is in a distorted trigonal bipyramidal arrangement, and that of <b>2</b> is in a distorted square pyramidal geometry. Electrochemical investigation shows that both complexes catalyze electrochemical proton reduction from acetic acid at mild overpotential, 0.17 and 0.38 V for <b>1</b> and <b>2</b>, respectively. Although coordinatively unsaturated, the complexes display only weak, reversible binding affinity toward CO (1 bar). However, ligand centered protonation by the strong acid, HBF₄·OEt₂, triggers quantitative CO uptake by <b>1</b> to form a dicarbonyl analogue <b>[1­(H)-CO]⁺</b> that can be reversibly converted back to <b>1</b> by deprotonation using NEt₃. Both crystallographically determined distances within the bdt ligand and density functional theory calculations suggest that the iron centers in both <b>1</b> and <b>2</b> are partially reduced at the expense of partial oxidation of the bdt ligand. Ligand protonation interrupts this extensive electronic delocalization between the Fe and bdt making <b>1­(H)⁺</b> susceptible to external CO binding

Carbon Dioxide Promoted H⁺ Reduction Using a Bis(imino)pyridine Manganese Electrocatalyst

Heating a 1:1 mixture of (CO)₅MnBr and the phosphine-substituted pyridine diimine ligand, ^Ph2PPrPDI, in THF at 65 °C for 24 h afforded the diamagnetic complex [(^Ph2PPrPDI)­Mn­(CO)]­[Br] (<b>1</b>). Higher temperatures and longer reaction times resulted in bromide displacement of the remaining carbonyl ligand and the formation of paramagnetic (^Ph2PPrPDI)­MnBr (<b>2</b>). The molecular structure of <b>1</b> was determined by single crystal X-ray diffraction, and density functional theory (DFT) calculations indicate that this complex is best described as low-spin Mn­(I) bound to a neutral ^Ph2PPrPDI chelating ligand. The redox properties of <b>1</b> and <b>2</b> were investigated by cyclic voltammetry (CV), and each complex was tested for electrocatalytic activity in the presence of both CO₂ and Brønsted acids. Although electrocatalytic response was not observed when CO₂, H₂O, or MeOH was added to <b>1</b> individually, the addition of H₂O or MeOH to CO₂-saturated acetonitrile solutions of <b>1</b> afforded voltammetric responses featuring increased current density as a function of proton source concentration (<i>i</i>_cat/<i>i</i>_p up to 2.4 for H₂O or 4.2 for MeOH at scan rates of 0.1 V/s). Bulk electrolysis using 5 mM <b>1</b> and 1.05 M MeOH in acetonitrile at −2.2 V vs Fc^+/0 over the course of 47 min gave H₂ as the only detectable product with a Faradaic efficiency of 96.7%. Electrochemical experiments indicate that CO₂ promotes <b>1</b>-mediated H₂ production by lowering apparent pH. While evaluating <b>2</b> for electrocatalytic activity, this complex was found to decompose rapidly in the presence of acid. Although modest H⁺ reduction activity was realized, the experiments described herein indicate that care must be taken when evaluating Mn complexes for electrocatalytic CO₂ reduction