The efficient copolymerization of
acrylates with ethylene using
Ni catalysts remains a challenge. Herein, we report two neutral Ni(II)
catalysts (POP-Ni-py (1) and PONap-Ni-py (2)) that exhibit high thermal stability and significantly higher incorporation
of polar monomer (for 1) or improved resistance to tert-butylacrylate (tBA)-induced chain transfer (for 2), in comparison to previously reported catalysts. Nickel
alkyl complexes generated after tBA insertion, POP-Ni-CCO(py) (3) and PONap-Ni-CCO(py) (4), were isolated and,
for the first time, characterized by crystallography. Weakened lutidine
vs pyridine coordination in 2-lut facilitated the isolation
of a N-donor-free adduct after acrylate insertion PONap-Ni-CCO (5) which represents a novel example of a four-membered chelate
relevant to acrylate polymerization catalysis. Experimental kinetic
studies of six cases of monomer insertion with aforementioned nickel
complexes indicate that pyridine dissociation and monomer coordination
are fast relative to monomer migratory insertion and that monomer
enchainment after tBA insertion is the rate limiting step of copolymerization.
Further evaluation of monomer insertion using density functional theory
studies identified a cis–trans isomerization via Berry-pseudorotation
involving one of the pendant ether groups as the rate-limiting step
for propagation, in the absence of a polar group at the chain end.
The energy profiles for ethylene and tBA enchainments are in qualitative
agreement with experimental measurements.
Palladium(II)‐catalyzed meta‐selective C−H allylation of arenes has been developed utilizing synthetically inert unactivated acyclic internal olefins as allylic surrogates. The strong σ‐donating and π‐accepting ability of pyrimidine‐based directing group facilitates the olefin insertion by overcoming inertness of the typical unactivated internal olefins. Exclusive allyl over styrenyl product selectivity as well as E stereoselectivity were achieved with broad substrate scope, wide functional‐group tolerance, and good to excellent yields. Late‐stage functionalisations of pharmaceuticals were demonstrated. Experimental and computational studies shed light on the mechanism and point to key steric control in the palladacycle, thus determining product selectivities.
General consideration S3 Experimental section S3 2.1 Preparation of starting materials S3 -S11 2.2 Optimization details for meta-CH alkynylation with (bromoethynyl)triisopropylsilane Screening of scaffolds S12 -S19 S20 2.3 2.3.1.a 2.3.1.b 2.3.1.c 2.3.1.d General procedure for palladium catalyzed meta-selective CH alkynylation of arene General procedure for palladium catalyzed meta-selective sequential hetero difunctionalization of arene General procedure for gram scale synthesis of meta-alkynylated protocol General procedure for directing group removal of meta-alkynylated protocol General procedure for different application of meta-alkynylated product S20 S21-S22 S23 S23 S24-S25 2.4 Characterization data of meta-alkynylated products S25 -S60 2.5 Mechanistic studies S60 -S66 2.6 Computational methods S67 -S115 References S115 -S122 NMR spectra S123 -S205S10 TBDMSO Br Ph ((1-(bromoethynyl)-4-phenylcyclohexyl)oxy)(tert-butyl)dimethylsilane: 1 H NMR (400 MHz, CDCl 3 ) δ 7.33 (t,
Directed C−H functionalization has been realized as a complementary tool to the traditional approaches for a straightforward access of non‐proteinogenic amino acids; albeit such a process is restricted mostly up to the γ‐position. In the present work, we demonstrate the diverse (hetero)arylation of amino acids and analogous aliphatic amines selectively at the remote δ‐position by tuning the reactivity controlled by ligands. An organopalladium δ‐C(sp3)−H activated intermediate has been isolated and crystallographically characterized. Mechanistic investigations carried out experimentally in conjunction with computational studies shed light on the difference in the mechanistic picture depending on the substrate structure.
While the icosahedral closo-[B 12 H 12 ] 2cluster does not display reversible electrochemical behavior, perfunctionalization of this species via substitution of all twelve B-H vertices with alkoxy or benzyloxy (OR) substituents engenders reversible redox chemistry, providing access to clusters in the dianionic, monoanionic, and neutral forms. Here, we evaluated the electrochemical behavior of the electron-rich B 12 (O-3-methylbutyl) 12 (1) cluster and discovered that a new reversible redox event that gives rise to a fourth electronic state is accessible through one-electron oxidation of the neutral species. Chemical oxidation of 1 with [N(2,4-Br 2 C 6 H 3) 3 ] •+ afforded the isolable [1] •+ cluster, which is the first example of an open-shell cationic B 12 cluster in which the unpaired electron is proposed to be delocalized throughout the boron cluster core. The oxidation of 1 is also chemically reversible, where treatment of [1] •+ with ferrocene resulted in its reduction back to 1. The identity of [1] •+ is supported by EPR, UV-vis, multinuclear NMR (1 H, 11 B), and X-ray photoelectron spectroscopic characterization. and characterization data for all new compounds is available free of charge via the Internet at http://pubs.acs.org.
The action of fluoroacetate as a broad-spectrum mammalian pesticide depends on the ‘lethal synthesis’ of fluorocitrate by citrate synthase, through a subtle enantioselective enolization of fluoroacetyl-coenzyme A. In this work, we demonstrate how a projection-based embedding method can be applied to calculate coupled cluster (CCSD(T)) reaction profiles from quantum mechanics/molecular mechanics optimized pathways for this enzyme reaction. Comparison of pro-R and pro-S proton abstraction in citrate synthase at the CCSD(T)-in-DFT//MM level yields the correct enantioselectivity. We thus demonstrate the potential of projection-based embedding for determining stereoselectivity in enzymatic systems. We further show that the method is simple to apply, eliminates variability due to the choice of density functional theory functional and allows the efficient calculation of CCSD(T) quality enzyme reaction barriers.
The applications of axially chiral benzonitriles and their derivatives remain mostly unexplored due to their synthetic difficulties. Here we disclose an unusual strategy for atroposelective access to benzonitriles via formation of the nitrile unit on biaryl scaffolds pre-installed with stereogenic axes in racemic forms. Our method starts with racemic 2-arylbenzaldehydes and sulfonamides as the substrates and N-heterocyclic carbenes as the organocatalysts to afford axially chiral benzonitriles in good to excellent yields and enantioselectivities. DFT calculations suggest that the loss of p-toluenesulfinate group is both the rate-determining and stereo-determining step. The axial chirality is controlled during the bond dissociation and CN group formation. The reaction features a dynamic kinetic resolution process modulated by both covalent and non-covalent catalytic interactions. The axially chiral benzonitriles from our method can be easily converted to a large set of functional molecules that show promising catalytic activities for chemical syntheses and anti-bacterial activities for plant protections.
Isotopic replacement has long-proven applications in small molecules. However, applications in proteins are largely limited to biosynthetic strategies or exchangeable (for example, N-H/D) labile sites only. The development of postbiosynthetic, C-H → C-H/D replacement in proteins could enable probing of mechanisms, among other uses. Here we describe a chemical method for selective protein α-carbon deuteration (proceeding from Cys to dehydroalanine (Dha) to deutero-Cys) allowing overall H→H/D exchange at a nonexchangeable backbone site. It is used here to probe mechanisms of reactions used in protein bioconjugation. This analysis suggests, together with quantum mechanical calculations, stepwise deprotonations via on-protein carbanions and unexpected sulfonium ylides in the conversion of Cys to Dha, consistent with a 'carba-Swern' mechanism. The ready application on existing, intact protein constructs (without specialized culture or genetic methods) suggests this C-D labeling strategy as a possible tool in protein mechanism, structure, biotechnology and medicine.
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