Rapid and Modular Access to Quaternary Carbons from Tertiary Alcohols via Bimolecular Homolytic Substitution.

Quaternary carbons are ubiquitous in bioactive molecules; however, synthetic methods for the construction of this motif remain underdeveloped. Here, we report the synthesis of quaternary carbons from tertiary alcohols, a class of structurally diverse, bench-stable feedstocks, via the merger of photoredox catalysis and iron-mediated SH2 bond formation. This alcohol-bromide cross-coupling is enabled by a novel halogen-atom transfer (XAT) reagent, which is the first reductively activated XAT reagent to be reported. A wide variety of sterically congested quaternary products can be accessed through this mild and practical protocol including products derived from both alkylation and benzylation of tertiary fragments. We further demonstrate the synthetic utility of this method through the expedited synthesis of a liver receptor agonist and through a two-step conversion of ketones and esters to quaternary products, which enables the modular control of up to three of the four substituents on a quaternary center.

Synthesis and Crystallographic Characterization of a Reduced Bimetallic Yttrium ansa-Metallocene Hydride Complex, [K(crypt)][(µ-CpAn)Y(µ-H)]2 (CpAn = Me2Si[C5H3(SiMe3)-3]2), with a 3.4 Å Yttrium-Yttrium Distance.

The reduction of a bimetallic yttrium ansa-metallocene hydride was examined to explore the possible formation of Y-Y bonds with 4d1 Y(II) ions. The precursor [CpAnY(µ-H)(THF)]2 (CpAn = Me2Si[C5H3(SiMe3)-3]2) was synthesized by hydrogenolysis of the allyl complex CpAnY(η3-C3H5)(THF), which was prepared from (C3H5)MgCl and [CpAnY(µ-Cl)]2. Treatment of [CpAnY(µ-H)(THF)]2 with excess KC8 in the presence of one equivalent of 2.2.2-cryptand (crypt) generates an intensely colored red-brown product crystallographically identified as [K(crypt)][(µ-CpAn)Y(µ-H)]2. The two rings of each CpAn ligand in the reduced anion [(µ-CpAn)Y(µ-H)]21- are attached to two yttrium centers in a "flyover" configuration. The 3.3992(6) and 3.4022(7) Å Y···Y distances between the equivalent metal centers within two crystallographically independent complexes are the shortest Y···Y distances observed to date. Ultraviolet-visible (UV-visible)/near infrared (IR) and electron paramagnetic resonance (EPR) spectroscopy support the presence of Y(II), and theoretical analysis describes the singly occupied molecular orbital (SOMO) as an Y-Y bonding orbital composed of metal 4d orbitals mixed with metallocene ligand orbitals. A dysprosium analogue, [K(18-crown-6)(THF)2][(µ-CpAn)Dy(µ-H)]2, was also synthesized, crystallographically characterized, and studied by variable temperature magnetic susceptibility. The magnetic data are best modeled with the presence of one 4f9 Dy(III) center and one 4f9(5dz2)1 Dy(II) center with no coupling between them. CASSCF calculations are consistent with magnetic measurements supporting the absence of coupling between the Dy centers.

Divalent Lanthanide Metallocene Complexes with a Linear Coordination Geometry and Pronounced 6s-5d Orbital Mixing.

A small but growing number of molecular compounds have been isolated featuring divalent lanthanides with 4fn5dz21 electron configurations. While the majority of these possess trigonal coordination geometries, we previously reported the first examples of linear divalent metallocenes Ln(CpiPr5)2 (Ln = Tb, Dy; CpiPr5 = pentaisopropylcyclopentadienyl). Here, we report the synthesis and characterization of the remainder of the Ln(CpiPr5)2 (1-Ln) series (including Y and excluding Pm). The compounds can be synthesized through salt metathesis of LnI3 and NaCpiPr5 followed by potassium graphite reduction for Ln = Y, La, Ce, Pr, Nd, Gd, Ho, and Er, by in situ reduction during salt metathesis of LnI3 and NaCpiPr5 for Ln = Tm and Lu, or through salt metathesis from LnI2 and NaCpiPr5 for Ln = Sm, Eu, and Yb. Single crystal X-ray diffraction analyses of 1-Ln confirm a linear coordination geometry with pseudo-D5d symmetry for the entire series. Structural and ultraviolet-visible spectroscopy data support a 4fn+1 electron configuration for Ln2+ = Sm, Eu, Tm, and Yb and a 4fn5dz21 configuration for the other lanthanides ([Kr]4dz21 for Y2+). Characterization of 1-Ln (Ln = Y, La) using electron paramagnetic resonance spectroscopy reveals significant s-d orbital mixing in the highest occupied molecular orbital and hyperfine coupling constants that are the largest reported to date for divalent compounds of yttrium and lanthanum. Evaluation of the room temperature magnetic susceptibilities of 1-Ln and comparison with values previously reported for trigonal Ln2+ compounds suggests that the more pronounced 6s-5d mixing may be associated with weaker 4f-5d spin coupling.

A Uranium(II) Arene Complex That Acts as a Uranium(I) Synthon.

Two-electron reduction of the amidate-supported U(III) mono(arene) complex U(TDA)3 (2) with KC8 yields the anionic bis(arene) complex [K[2.2.2]cryptand][U(TDA)2] (3) (TDA = N-(2,6-di-isopropylphenyl)pivalamido). EPR spectroscopy, magnetic susceptibility measurements, and calculations using DFT as well as multireference CASSCF methods all provide strong evidence that the electronic structure of 3 is best represented as a 5f4 U(II) metal center bound to a monoreduced arene ligand. Reactivity studies show 3 reacts as a U(I) synthon by behaving as a two-electron reductant toward I2 to form the dinuclear U(III)-U(III) triiodide species [K[2.2.2]cryptand][(UI(TDA)2)2(µ-I)] (6) and as a three-electron reductant toward cycloheptatriene (CHT) to form the U(IV) complex [K[2.2.2]cryptand][U(η7-C7H7)(TDA)2(THF)] (7). The reaction of 3 with cyclooctatetraene (COT) generates a mixture of the U(III) anion [K[2.2.2]cryptand][U(TDA)4] (1-crypt) and U(COT)2, while the addition of COT to complex 2 instead yields the dinuclear U(IV)-U(IV) inverse sandwich complex [U(TDA)3]2(µ-η8:η3-C8H8) (8). Two-electron reduction of the homoleptic Th(IV) amidate complex Th(TDA)4 (4) with KC8 gives the mono(arene) complex [K[2.2.2]cryptand][Th(TDA)3(THF)] (5). The C-C bond lengths and torsion angles in the bound arene of 5 suggest a direduced arene bound to a Th(IV) metal center; this conclusion is supported by DFT calculations.

Substituent Effects on Exchange Coupling and Magnetic Relaxation in 2,2'-Bipyrimidine Radical-Bridged Dilanthanide Complexes.

Systematic analysis of related compounds is crucial to the design of single-molecule magnets with improved properties, yet such studies on multinuclear lanthanide complexes with strong magnetic coupling remain rare. Herein, we present the synthesis and magnetic characterization of the series of radical-bridged dilanthanide complex salts [(Cp*2Ln)2(µ-5,5'-R2bpym)](BPh4) (Ln = Gd, Dy; R = NMe2 (1), OEt (2), Me (3), F (4); bpym = 2,2'-bipyrimidine). Modification of the substituent on the bridging 5,5'-R2bpym radical anion allows the magnetic exchange coupling constant, JGd-rad, for the gadolinium compounds in this series to be tuned over a range from -2.7 cm-1 (1) to -11.1 cm-1 (4), with electron-withdrawing or -donating substituents increasing or decreasing the strength of exchange coupling, respectively. Modulation of the exchange coupling interaction has a significant impact on the magnetic relaxation dynamics of the single-molecule magnets 1-Dy through 4-Dy, where stronger JGd-rad for the corresponding Gd3+ compounds is associated with larger thermal barriers to magnetic relaxation (Ueff), open magnetic hysteresis at higher temperatures, and slower magnetic relaxation rates for through-barrier processes. Further, we derive an empirical linear correlation between the experimental Ueff values for 1-Dy through 4-Dy and the magnitude of JGd-rad for the corresponding gadolinium derivatives that provides insight into the electronic structure of these complexes. This simple model applies to other organic radical-bridged dysprosium complexes in the literature, and it establishes clear design criteria for increasing magnetic operating temperatures in radical-bridged molecules.

Synthesis and Magnetism of Neutral, Linear Metallocene Complexes of Terbium(II) and Dysprosium(II).

The divalent metallocene complexes Ln(CpiPr5)2 (Ln = Tb, Dy) were synthesized through the KC8 reduction of Ln(CpiPr5)2I intermediates and represent the first examples of neutral, linear metallocenes for these elements. X-ray diffraction analysis, density functional theory calculations, and magnetic susceptibility measurements indicate a 4fn5d1 electron configuration with strong s/d mixing that supports the linear coordination geometry. A comparison of the magnetic relaxation behavior of the two divalent metallocenes relative to salts of their trivalent counterparts, [Ln(CpiPr5)2][B(C6F5)4], reveals that lanthanide reduction has opposing effects for dysprosium and terbium, with magnetic relaxation times increasing from TbIII to TbII and decreasing from DyIII to DyII. The impact of this effect is most notably evident for Tb(CpiPr5)2, which displays an effective thermal barrier to magnetic relaxation of 1205 cm-1 and a 100-s blocking temperature of 52 K, the highest values yet observed for any nondysprosium single-molecule magnet.

Isolation of a TMTAA-Based Radical in Uranium bis-TMTAA Complexes.

We report the synthesis, characterization, and electronic structure studies of a series of thorium(IV) and uranium(IV) bis-tetramethyltetraazaannulene complexes. These sandwich complexes show remarkable stability towards air and moisture, even at elevated temperatures. Electrochemical studies show the uranium complex to be stable in three different oxidation states; isolation of the oxidized species reveals a rare case of a non-innocent tetramethyltetraazaannulene (TMTAA) ligand.

A Trinuclear Radical-Bridged Lanthanide Single-Molecule Magnet.

Assembly of the triangular, organic radical-bridged complexes Cp*6 Ln3 (µ3 -HAN) (Cp*=pentamethylcyclopentadienyl; Ln=Gd, Tb, Dy; HAN=hexaazatrinaphthylene) proceeds through the reaction of Cp*2 Ln(BPh4 ) with HAN under strongly reducing conditions. Significantly, magnetic susceptibility measurements of these complexes support effective magnetic coupling of all three LnIII centers through the HAN3-. radical ligand. Thorough investigation of the DyIII congener through both ac susceptibility and dc magnetic relaxation measurements reveals slow relaxation of the magnetization, with an effective thermal relaxation barrier of Ueff =51 cm-1 . Magnetic coupling in the DyIII complex enables a large remnant magnetization at temperatures up to 3.0 K in the magnetic hysteresis measurements and hysteresis loops that are open at zero-field up to 3.5 K.

High-yield lithiation of azobenzenes by tin-lithium exchange.

The lithiation of halogenated azobenzenes by halogen-lithium exchange commonly leads to substantial degradation of the azo group to give hydrazine derivatives besides the desired aryl lithium species. Yields of quenching reactions with electrophiles are therefore low. This work shows that a transmetalation reaction of easily accessible stannylated azobenzenes with methyllithium leads to a near-quantitative lithiation of azobenzenes in para, meta, and ortho positions. To investigate the scope of the reaction, various lithiated azobenzenes were quenched with a variety of electrophiles. Furthermore, mechanistic (119) Sn NMR spectroscopic studies on the formation of lithiated azobenzenes are presented. A tin ate complex of the azobenzene was detected and characterized at low temperature.

Alcohol-alcohol cross-coupling enabled by SH2 radical sorting.

Alcohols represent a functional group class with unparalleled abundance and structural diversity. In an era of chemical synthesis that prioritizes reducing time to target and maximizing exploration of chemical space, harnessing these building blocks for carbon-carbon bond-forming reactions is a key goal in organic chemistry. In particular, leveraging a single activation mode to form a new C(sp3)-C(sp3) bond from two alcohol subunits would enable access to an extraordinary level of structural diversity. In this work, we report a nickel radical sorting-mediated cross-alcohol coupling wherein two alcohol fragments are deoxygenated and coupled in one reaction vessel, open to air.

Ultrahard magnetism from mixed-valence dilanthanide complexes with metal-metal bonding.

Magnetic effects of lanthanide bonding Lanthanide coordination compounds have attracted attention for their persistent magnetic properties near liquid nitrogen temperature, well above alternative molecular magnets. Gould et al. report that introducing metal-metal bonding can enhance coercivity. Reduction of iodide-bridged terbium or dysprosium dimers resulted in a single electron bond between the metals, which enforced alignment of the other valence electrons. The resultant coercive fields exceeded 14 tesla below 50 and 60 kelvin for the terbium and dysprosium compounds, respectively. ­JSY

A biomimetic SH2 cross-coupling mechanism for quaternary sp3-carbon formation.

Bimolecular homolytic substitution (SH2) is an open-shell mechanism that is implicated across a host of biochemical alkylation pathways. Surprisingly, however, this radical substitution manifold has not been generally deployed as a design element in synthetic C­C bond formation. We found that the SH2 mechanism can be leveraged to enable a biomimetic sp3-sp3 cross-coupling platform that furnishes quaternary sp3-carbon centers, a long-standing challenge in organic molecule construction. This heteroselective radical-radical coupling uses the capacity of iron porphyrin to readily distinguish between the SH2 bond-forming roles of open-shell primary and tertiary carbons, combined with photocatalysis to generate both radical classes simultaneously from widely abundant functional groups. Mechanistic studies confirm the intermediacy of a primary alkyl­Fe(III) species prior to coupling and provide evidence for the SH2 displacement pathway in the critical quaternary sp3-carbon bond formation step.

Isolation of a triplet benzene dianion.

Baird's rule predicts that molecules with 4n π electrons should be aromatic in the triplet state, but the realization of simple ring systems with such an electronic ground state has been stymied by these molecules' tendency to distort into structures bearing a large singlet-triplet gap. Here, we show that the elusive benzene diradical dianion can be stabilized through creation of a binucleating ligand that enforces a tightly constrained inverse sandwich structure and direct magnetic exchange coupling. Specifically, we report the compounds [K(18-crown-6)(THF)2]2[M2(BzN6-Mes)] (M = Y, Gd; BzN6-Mes = 1,3,5-tris[2',6'-(N-mesityl)dimethanamino-4'-tert-butylphenyl]benzene), which feature a trigonal ligand that binds one trivalent metal ion on each face of a central benzene dianion. Antiferromagnetic exchange in the Gd3+ compound preferentially stabilizes the triplet state such that it becomes the molecular ground state. Single-crystal X-ray diffraction data and nucleus-independent chemical shift calculations support aromaticity, in agreement with Baird's rule.

Structure and magnetism of a tetrahedral uranium(iii) ß-diketiminate complex.

We describe the functionalisation of the previously reported uranium(iii) ß-diketiminate complex (BDI)UI2(THF)2 (1) with one and two equivalents of a sterically demanding 2,6-diisopropylphenolate ligand (ODipp) leading to the formation of two heteroleptic complexes: [(BDI)UI(ODipp)]2 (2) and (BDI)U(ODipp)2 (3). The latter is a rare example of a tetrahedral uranium(iii) complex, and it shows single-molecule magnet behaviour.

High-temperature magnetic blocking and magneto-structural correlations in a series of dysprosium(iii) metallocenium single-molecule magnets.

A series of dysprosium(iii) metallocenium salts, [Dy(CpiPr4R)2][B(C6F5)4] (R = H (1), Me (2), Et (3), iPr (4)), was synthesized by reaction of DyI3 with the corresponding known NaCpiPr4R (R = H, iPr) and novel NaCpiPr4R (R = Me, Et) salts at high temperature, followed by iodide abstraction with [H(SiEt3)2][B(C6F5)4]. Variation of the substituents in this series results in substantial changes in molecular structure, with more sterically-encumbering cyclopentadienyl ligands promoting longer Dy-C distances and larger Cp-Dy-Cp angles. Dc and ac magnetic susceptibility data reveal that these structural changes have a considerable impact on the magnetic relaxation behavior and operating temperature of each compound. In particular, the magnetic relaxation barrier increases as the Dy-C distance decreases and the Cp-Dy-Cp angle increases. An overall 45 K increase in the magnetic blocking temperature is observed across the series, with compounds 2-4 exhibiting the highest 100 s blocking temperatures yet reported for a single-molecule magnet. Compound 2 possesses the highest operating temperature of the series with a 100 s blocking temperature of 62 K. Concomitant increases in the effective relaxation barrier and the maximum magnetic hysteresis temperature are observed, with 2 displaying a barrier of 1468 cm-1 and open magnetic hysteresis as high as 72 K at a sweep rate of 3.1 mT s-1. Magneto-structural correlations are discussed with the goal of guiding the synthesis of future high operating temperature DyIII metallocenium single-molecule magnets.

Incubation of 2-methylisoborneol synthase with the intermediate analog 2-methylneryl diphosphate.

Incubation of synthetic 2-methylneryl diphosphate (2-MeNPP, 10) with 2-methylisoborneol synthase (MIBS) gave a mixture of products that differed significantly from that derived from the natural substrate (E)-2-methylgeranyl diphosphate (3, 2-MeGPP). The proportion of (-)-2-methylisoborneol (1) decreased from 89 to 17% while that of 2-methylenebornane (4) increased from 10 to 26%, with the relative yields of the isomeric homo-monoterpenes 2-methyl-2-bornene (5) and 1-methylcamphene (6) remaining essentially unchanged (<1% each), as determined by chiral GC-MS analysis. The majority of the product mixture resulting from the MIBS-catalyzed cyclization of 2-MeNPP (10) consisted of the anomalous monocyclic homo-monoterpenes (±)-2-methylllimonene (15, 39%) and 2-methyl-α-terpineol (13, 10%), as well as the acylic derivatives 2-methylnerol (11, 7%) and 2-methyllinalool (14, <1%). The steady-state kinetic parameters of the MIBS-catalyzed reaction, determined using [1-3H]-2-methylneryl diphosphate (2-MeNPP), were kcat 0.0046±0.0003 s-1, Km 18±6 µm and kcat/Km 2.55 × 102 M-1 s-1. In comparison, the natural substrate 2-MeGPP had a kcat 0.105±0.007 s-1, Km 95±49 µm and kcat/Km 1.11 × 103 M-1 s-1. Taken together with earlier X-ray crystallographic studies of MIBS, as well as previous investigations of the mechanistically related plant monoterpene cyclase, bornyl diphosphate synthase, these results provide important insights into the binding and cyclization of both native substrates and intermediates and their analogs.