Executing and Rationalizing the Synthesis of a Difluorinated Analogue of a Ring-Expanded Calystegine B₂

A difluorinated analogue of a ring-expanded calystegine B₂ and some <i>N</i>-protected species were prepared via microwave-mediated transannular ring-opening of an epoxyketone. The diastereofacial selectivity of the epoxidation reaction, which delivers the key intermediate, and the regioselectivity of the transannular reactions were analyzed by density functional theory (DFT) methods. The epoxidation stereoselectivity arises from simple steric control, whereas the ring-closure reactions are subject to thermodynamic control

Executing and Rationalizing the Synthesis of a Difluorinated Analogue of a Ring-Expanded Calystegine B₂

A difluorinated analogue of a ring-expanded calystegine B₂ and some <i>N</i>-protected species were prepared via microwave-mediated transannular ring-opening of an epoxyketone. The diastereofacial selectivity of the epoxidation reaction, which delivers the key intermediate, and the regioselectivity of the transannular reactions were analyzed by density functional theory (DFT) methods. The epoxidation stereoselectivity arises from simple steric control, whereas the ring-closure reactions are subject to thermodynamic control

Toward a Simulation Approach for Alkene Ring-closing Metathesis: Scope and Limitations of a Model for RCM

A published model for revealing solvent effects on the ring-closing metathesis (RCM) reaction of diethyl diallylmalonate <b>7</b> has been evaluated over a wider range of conditions, to assess its suitability for new applications. Unfortunately, the model is too flexible and the published rate constants do not agree with experimental studies in the literature. However, by fixing the values of important rate constants and restricting the concentration ranges studied, useful conclusions can be drawn about the relative rates of RCM of different substrates, precatalyst concentration can be simulated accurately and the effect of precatalyst loading can be anticipated. Progress has also been made toward applying the model to precatalyst evaluation, but further modifications to the model are necessary to achieve much broader aims

Suzuki–Miyaura Coupling Reactions of Iodo(difluoroenol) Derivatives, Fluorinated Building Blocks Accessible at Near-Ambient Temperatures

A recently developed method for the near-ambient generation of difluorovinylzinc reagents has facilitated the preparation of 1-(<i>N</i>,<i>N</i>-diethylcarbamoyloxy)-2,2-difluoro-1-iodoethene and 2,2-difluoro-1-iodo-1-(2′-methoxyethoxymethoxy)­ethene. The utility of these reagents has been investigated in Suzuki–Miyaura couplings with a range of potassium trifluoroborate coupling partners, with the scope of successful couplings proving wide. Deiodinated species appeared as significant side products, but a solvent change from <i>i</i>-PrOH to <i>t</i>-BuOH suppressed the pathway to these species and improved coupling yields

Olefin Metathesis by Grubbs–Hoveyda Complexes: Computational and Experimental Studies of the Mechanism and Substrate-Dependent Kinetics

The potential energy surfaces for the activation of Grubbs–Hoveyda-type precatalysts with the substrates ethene, propene, 1-hexene, and ethyl vinyl ether (EVE) have been probed at the density functional theory (DFT) (M06-L) level. The energetically favored pathway of the reaction leading to a 14e Fischer carbene and styrene starts with an initiation step in which the incoming substrate and outgoing alkene ligand are both clearly associated with the ruthenium center. For these substrates, with the exception of ethene, the rate determining step is predicted to be the formation of the metallocyclobutane (MCB). We have taken the initial reactant to be a weak van der Waals complex between substrate and precatalyst. This model yields good agreement between the computed activation parameters for both the parent Grubbs–Hoveyda and Grela complex with EVE substrate, and the experimental values, reported here. The alternative model which takes the initial reactant to be two isolated molecules requires an estimate of the entropy loss on formation of the initial complex in solution which is difficult to evaluate. Our estimate of this quantity yields a barrier for the rate determining step for the interchange mechanism which is close to the value we find for the alternative mechanism in which the rate determining step is the initial dissociation of the precatalyst. The relative energetics of these two mechanisms involving different initiation steps but with similar activation barriers, could well be dependent upon the precatalyst and substrate in line with the recent experimental findings of Plenio and co-workers

Synergic Effects Between N‑Heterocyclic Carbene and Chelating Benzylidene–Ether Ligands Toward the Initiation Step of Hoveyda–Grubbs Type Ru Complexes

Synergic effects between ancillary N-heterocyclic carbenes [(1,3-bis­(2,4,6-trimethylphenyl)-1,3-imidazoline-2-ylidene or 1,3-bis­(2,6-di<i>iso</i>propylphenyl)-1,3-imidazoline-2-ylidene] and chelating benzylidene–ether ligands were investigated by studying initiation rates and kinetic profiles of Hoveyda–Grubbs (HG) type Ru complexes. A newly designed Ru-benzylidene-oxazinone precatalyst <b>4</b> was compared with Grela and Blechert complexes bearing modified <i>iso</i>propyloxy chelating leaving groups and with the standard HG complex to understand how the ancillary and the leaving ligands interact and influence the catalytic activity