Architectural Editing of Polyesters and Polyurethanes via Palladium(II)-Catalyzed [3,3]-Sigmatropic Oxo-Rearrangements.

Architecture underlies the thermomechanical properties of polymers. Yet, few strategies are available to tune a polymer's architecture after it is prepared without altering its chemical composition. The ability to edit the architecture of a polymer would dramatically expand the accessible architecture-property space of polymeric materials. Herein, we disclose a backbone rearrangement approach to tune the short-chain branching of polymers. Specifically, we demonstrate that palladium(II)-catalyzed [3,3]-sigmatropic oxo-rearrangements can transform branched polyesters and polyurethanes to their linear counterparts. While the effects on materials properties are generally subtle in the case of polyesters, more dramatic changes are observed in the case of polyurethanes: two polyurethanes undergo a soluble-to-insoluble transition, and one exhibits a dramatic increase in both strain at break and toughness after rearrangement. Additionally, the incorporation of alkenes in the polymer backbone through the rearrangement enables facile deconstruction via ethenolysis. In all, we disclose a powerful and broad-scope strategy to edit the architecture of polymer backbones and thereby tune their physical and chemical properties.

Mechanochemical Formation, Solution Rearrangements, and Catalytic Behavior of a Polymorphic Ca/K Allyl Complex.

Without solvents present, the often far-from-equilibrium environment in a mechanochemically driven synthesis can generate high-energy, non-stoichiometric products not observed from the same ratio of reagents used in solution. Ball milling 2 equiv. K[A'] (A'=[1,3-(SiMe3 )2 C3 H3 ]- ) with CaI2 yields a non-stoichiometric calciate, K[CaA'3 ], which initially forms a structure (1) likely containing a mixture of pi- and sigma-bound allyl ligands. Dissolved in arenes, the compound rearranges over the course of several days to a structure (2) with only η3 -bound allyl ligands, and that can be crystallized as a coordination polymer. If dissolved in alkanes, however, the rearrangement of 1 to 2 occurs within minutes. The structures of 1 and 2 have been modeled with DFT calculations, and 2 initiates the anionic polymerization of methyl methacrylate and isoprene; for the latter, under the mildest conditions yet reported for a heavy Group 2 species (one-atm pressure and room temperature).

Di(indenyl)beryllium.

The bonding in beryllocene, [BeCp2 ], took decades to establish, owing to its unexpected mixed hapticity structure (i.e., [Be(η5 -Cp)(η1 -Cp)]). Beryllium complexes containing the indenyl ligand, which is a close relative of the cyclopentadienyl anion, but which is also known to exhibit its own bonding peculiarities (e.g., facile η5 ⇄ η3 shifts), have remained unknown. Standard metathetical approaches to their synthesis (e.g., with K[Ind'] + BeX2 in an ether solvent) give rise to intractable oils from which nothing identifiable can be isolated. In contrast, mechanochemical preparation, involving the solvent-free grinding of BeBr2 and potassium indenides, leads to the production of discrete (indenyl)beryllium complexes, including [Be(C9 H7 )2 ] (1) and [Be{1,3-(SiMe3 )2 C9 H5 }Br] (2). The former displays η5 /η1 -coordinated ligands in the solid state, but DFT calculations indicate that an η5 /η5 -conformation is less than 5 kcal mol-1 higher in energy.

An η3 -Bound Allyl Ligand on Magnesium in a Mechanochemically Generated Mg/K Allyl Complex.

Milling two equivalents of K[1,3-(SiMe3 )2 C3 H3 ] (=K[A']) with MgX2 (X=Cl, Br) produces the allyl complex [K2 MgA'4 ] (1). Crystals grown from toluene are of the solvated species [((η6 -tol)K)2 MgA'4 ] ([1⋅2(tol)]), a trimetallic monomer with both bridging and terminal (η1 ) allyl ligands. When recrystallized from hexanes, the unsolvated 1 forms a 2D coordination polymer, in which the Mg is surrounded by three allyl ligands. The C-C bond lengths differ by only 0.028 Å, indicating virtually complete electron delocalization. This is an unprecedented coordination mode for an allyl ligand bound to Mg. DFT calculations indicate that in isolation, an η3 -allyl configuration on Mg is energetically preferred over the η1 - (σ-bonded) arrangement, but the Mg must be in a low coordination environment for it to be experimentally realized. Methyl methacrylate is effectively polymerized by 1, with activities that are comparable to K[A'] and greater than the homometallic magnesium complex [{MgA'2 }2 ].

Halide metathesis in overdrive: mechanochemical synthesis of a heterometallic group 1 allyl complex.

As a synthesis technique, halide metathesis (n RM + M'X n → R n M' + n MX) normally relies for its effectiveness on the favorable formation of a metal halide byproduct (MX), often aided by solubility equilibria in solution. Owing to the lack of significant thermodynamic driving forces, intra-alkali metal exchange is one of the most challenging metathetical exchanges to attempt, especially when conducted without solvent. Nevertheless, grinding together the bulky potassium allyl [KA']∞ (A' = [1,3-(SiMe3)2C3H3]-) and CsI produces the heterometallic complex [CsKA'2]∞ in low yield, which was crystallographically characterized as a coordination polymer that displays site disorder of the K+ and Cs+ ions. The entropic benefits of mixed Cs/K metal centers, but more importantly, the generation of multiple intermolecular K…CH3 and Cs…CH3 interactions in [CsKA'2]∞, enable an otherwise unfavorable halide metathesis to proceed with mechanochemical assistance. From this result, we demonstrate that ball milling and unexpected solid-state effects can permit seemingly unfavored reactions to occur.

Mechanochemically Driven Transformations in Organotin Chemistry: Stereochemical Rearrangement, Redox Behavior, and Dispersion-Stabilized Complexes.

Ball milling a mixture of the bulky allyl K[A'] {[A'] = [1,3-(SiMe3)2C3H3]-} and SnCl2 in a 2:1 ratio for 5 min leads to the tris(allyl) stannate [SnA'3K]∞, which forms a coordination polymer in the solid state. Longer grinding of the 2:1 mixture (15 min), or the use of a 3:1 ratio of reagents, initiates a disproportionation reaction and the chiral tetra(allyl)tin species [SnA'4] is produced. A small amount of a diastereomeric [SnA'4] complex with meso symmetry can also be isolated with extended grinding. These products have been structurally authenticated with single-crystal X-ray crystallography. The tetra(allyl) species [SnA'4] are sterically crowded and decompose relatively quickly (<1 h) in hydrocarbon solvents. In the solid state, they are much more persistent (several months) and evidently owe their stability to internal London dispersion interactions, as evidenced by multiple close H···H' interligand contacts. Dispersion-corrected DFT calculations have been used to confirm the critical contribution of dispersion interactions to their stability. None of these products are available in their isolated forms from solution-based reactions, demonstrating the ability of mechanochemical activation to access otherwise unobtainable transformations in organotin chemistry.

Lecithin:Cholesterol Acyltransferase Activation by Sulfhydryl-Reactive Small Molecules: Role of Cysteine-31.

Lecithin:cholesterol acyltransferase (LCAT) catalyzes plasma cholesteryl ester formation and is defective in familial lecithin:cholesterol acyltransferase deficiency (FLD), an autosomal recessive disorder characterized by low high-density lipoprotein, anemia, and renal disease. This study aimed to investigate the mechanism by which compound A [3-(5-(ethylthio)-1,3,4-thiadiazol-2-ylthio)pyrazine-2-carbonitrile], a small heterocyclic amine, activates LCAT. The effect of compound A on LCAT was tested in human plasma and with recombinant LCAT. Mass spectrometry and nuclear magnetic resonance were used to determine compound A adduct formation with LCAT. Molecular modeling was performed to gain insight into the effects of compound A on LCAT structure and activity. Compound A increased LCAT activity in a subset (three of nine) of LCAT mutations to levels comparable to FLD heterozygotes. The site-directed mutation LCAT-Cys31Gly prevented activation by compound A. Substitution of Cys31 with charged residues (Glu, Arg, and Lys) decreased LCAT activity, whereas bulky hydrophobic groups (Trp, Leu, Phe, and Met) increased activity up to 3-fold (P < 0.005). Mass spectrometry of a tryptic digestion of LCAT incubated with compound A revealed a +103.017 m/z adduct on Cys31, consistent with the addition of a single hydrophobic cyanopyrazine ring. Molecular modeling identified potential interactions of compound A near Cys31 and structural changes correlating with enhanced activity. Functional groups important for LCAT activation by compound A were identified by testing compound A derivatives. Finally, sulfhydryl-reactive ß-lactams were developed as a new class of LCAT activators. In conclusion, compound A activates LCAT, including some FLD mutations, by forming a hydrophobic adduct with Cys31, thus providing a mechanistic rationale for the design of future LCAT activators.

Reassessment of N2 activation by low-valent Ti-amide complexes: a remarkable side-on bridged bis-N2 adduct is actually an arene adduct.

The complex {(TMEDA)2Li}{[Ti(N(TMS)2)2]2(µ-η2:η2-N2)2} (5-Li) is the only transition metal N2 complex ever reported with two side-on N2 adducts. In this report, the similarity of 5-Li to a new inverse sandwich toluene adduct {(PhMe)K}{[Ti(N(TMS)2)2]2(µ-PhMe)} (6-K) necessitated a re-examination of the structure of 5-Li. Through a reassessment of the original disordered crystal data of 5-Li and new independent syntheses brought about through revisitation of the original reaction conditions, 5-Li has been re-assigned as an inverse sandwich toluene adduct, {(TMEDA)2Li}{[Ti(N(TMS)2)2]2(µ-PhMe)} (6-Li). The original crystal data could be fitted almost equally well to structural solutions as either 5-Li or 6-Li, and this study highlights the importance of a holistic examination of modeled data and the need for secondary/complementary analytical methods in paramagnetic inorganic syntheses, especially when presenting unique and unexpected results. In addition, further examination of reduction reactions of Ti[N(TMS)2]3 and [(TMS)2N]2TiCl(THF) in the presence of KC8 revealed rich solvent- and counterion-dependent chemistry, including several degrees of N2 activation (bridging nitride complexes, terminal bridging N2 complexes) as well as ligand C-H activation.