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The authors thank the EPSRC for funding (EP/M003868/1). This paper reports experimental and computational studies on the mechanism of a rhodium-catalysed hydroformylation that is selective for branched aldehyde products from unbiased alkene substrates. This highly unusual selectivity relies on a phospholane-phosphite ligand prosaically called BOBPHOS. Kinetic studies using in situ high pressure IR (HPIR) and the reaction progress kinetic analysis methodology suggested two steps in the catalytic cycle were involved as turnover determining. Negative order in CO and positive orders in alkene and H2 were found and the effect of hydrogen and carbon monoxide partial pressures on selectivity were measured. Labeling studies found rhodium hydride addition to the alkene to be largely irreversible. Detailed spectroscopic HPIR and NMR characterization of activated rhodium-hydrido dicarbonyl species were carried out. In the absence of H2, reaction of the rhodium-hydrido dicarbonyl with allylbenzene allowed further detailed spectroscopic characterization of four- and five-coordinate rhodium-acyl species. Under single-turnover conditions the ratios of branched to linear acyl species were preserved in the final ratios of aldehyde products. Theoretical investigations uncovered unexpected stabilizing CH-π interactions between the ligand and substrate which influenced the high branched selectivity by causing potentially low energy pathways to become unproductive. Energy span and degree of TOF control analysis strongly support experimental observations and mechanistic rationale. A three-dimensional quadrant model was built to represent the structural origins of regio- and enantioselectivity. Postprint

The authors wish to thank EaStCHEM, the School of Chemistry and the EPSRC (grant code EP/J018139/1) for funding Redox potentials are computed for the active form (compound I) of lignin peroxidase (LiP) using a suitable QM/MM methodology (B3LYP/SDD/6-311G**//BP86/SVP:CHARMM). Allowing for dynamic conformational averaging, a potential of 0.67(33) V relative to ferrocenium/ferrocene is obtained for the active form with its oxoiron(IV) core. The computed redox potential is very sensitive to the charge distribution around the active site: protonation of titratable residues close to the metal center increases the redox potential, thereby rationalising the known pH dependence of LiP activity. A simple MM-charge deletion scheme is used to identify residues that are critical for the redox potential. Two mutant proteins are studied through homology modelling, E40Q and D183N, which are predicted to have an increased redox potential by 140 mV and 190 mV, respectively, relative to the wild type. These mutant proteins are thus promising targets for synthesis and further exploration toward a rational design of biocatalytic systems for oxidative degradation of lignin. Publisher PDF

The authors thank the EPSRC and the ERC (FUNCAT) for funding. S.P.N. is a Royal Society Wolfson Merit Award holder. A mechanistic study of the gold-catalysed protodecarboxylation is described. Each reaction step has been investigated experimentally and computationally. More specifically, the activation parameters for the decarboxylation step have been determined through kinetic studies. Further experimental studies on the hydrolysis of the arylgold intermediate have revealed that the protodeauration can become competitive with the decarboxylation process at high conversions. This switch in rate-limiting step has been shown to be pKa-dependent. These studies have been supported by DFT calculations and permit a better understanding of which prevalent features of the reaction mechanism account for the decarboxylation process. Postprint

The authors thank the School of Chemistry and EaStCHEM for support. A detailed mechanism for alkyne alkoxycarbonylation mediated by a palladium catalyst has been characterised at the B3PW91-D3/PCM level of density functional theory (including bulk solvation and dispersion corrections). This transformation, investigated via the methoxycarbonylation of propyne, involves a uniquely dual role for the P, N hemilabile ligand acting co-catalytically as both an in situ base and proton relay coupled with a Pd0 centre, allowing for surmountable barriers (highest ΔG≠ of 22.9 kcal mol-1 for alcoholysis). This proton-shuffle between methanol and coordinated propyne accounts for experimental requirements (high acid concentration) and reproduces observed regioselectivities as a function of ligand structure. A simple ligand modification is proposed, which is predicted to improve catalytic turnover by three orders of magnitude. Postprint

The authors thank the EPSRC for funding, primarily from grant number EP/M003868/1. The reactivity of N-tosyl-3-pyrroline is significantly lower than that of mono-substituted alkenes in Pd catalysed methoxycarbonylation reactions. For example, most bulky diphosphine/ Pd catalysts, including the well-known Pd catalyst derived from 1,2-bis(di-tert-butylphosphino)xylene (DTBPX), were found to give no product at all in the methoxycarbonylation of N-tosyl-3-pyrroline. The competing pathways in methoxycarbonylation of N-methane-sulfonyl-3-pyrroline using Pd/ DTBPX were studied using DFT calculations; these show that the coordination of the alkene is unfavourable, and once coordinated, isomerisation is a lower energy pathway that ultimately leads to an alternative product. Experimentally a side product resulting from alkene isomerisation and addition of methanol is formed slowly (if CO is present), and rapidly if CO is not. A less bulky derivative of DTBPX forms the required alkene complex with much lower barriers. A study has been made of the enantioselective carbonylation of N-tosyl-3-pyrroline using water, methanol or aniline as nucleophile. This study revealed that there is a range of possible products with most of these initiated by a Pd-catalysed isomerisation of the alkene. Using less bulky members of the Pd/Phanephos family of catalysts, it is possible to produce the methoxycarbonylation product from this poorly reactive alkene with reasonably good chemoselectivity and around 80% e.e. at higher pressures of CO. Postprint

The authors would like to thank the University of St. Andrews School of Chemistry and EaStCHEM for support The catalytic alkoxycarbonylation of alkynes via palladium and P,N ligands, studied through a prototypical reaction involving propyne methoxycarbonylation yielding methyl methacrylate, has been explored at the B3PW91-D3/PCM level of density functional theory. Four different reaction routes have been probed in detail, spanning those involving one or two hemilabile P,N ligands and either hydride or carbomethoxy mechanisms. The cycle that is both energetically most plausible and congruent with experimental data involves Pd(0) and two P,N ligands acting co-catalytically in turn to shuffle protons via both protonation and deprotonation reactions. Other mechanisms proposed in the literature can be discounted because they would lead to insurmountable barriers or incorrect selectivities. For the preferred mechanism, the P,N ligand is found to be crucial in determining the strong regioselectivity and intrinsically controls the overall turnover of the catalytic cycle with moderate barriers (ΔG‡ of 20.1 to 22.9 kcal/mol) predicted. Furthermore, the necessary acidic conditions are rationalized via a potential dicationic channel. Postprint

Chalcogen dications: Facile synthesis of E--E bonded dications can be readily achieved. Radical cations are identified as the intermediates.

Ninety-five psychiatrically hospitalized children participated in a structured psychiatric interview that included a review of medically unexplained physical symptoms. Children with Somatization Disorder, psychosis, and separation anxiety disorders had the largest number of somatic complaints. Both abdominal pain and palpitations were significantly associated with Separation Anxiety Disorder and psychosis. Abdominal pain was also reported by children diagnosed with Major Depression. Some individual symptoms, particularly pseudo-neurological symptoms, were more frequently reported by children who also reported psychotic symptoms. Future research needs are discussed. J. Am. Acad. Child Adolesc. Psychiatry , 1988, 27, 2:185–187.