Scope and Mechanistic Study of the Coupling Reaction of α,β-Unsaturated Carbonyl Compounds with Alkenes: Uncovering Electronic Effects on Alkene Insertion vs Oxidative Coupling Pathways

The cationic ruthenium-hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4– (1) was found to be a highly effective catalyst for the intermolecular conjugate addition of simple alkenes to α,β-unsaturated carbonyl compounds to give (Z)-selective tetrasubstituted olefin products. The analogous coupling reaction of cinnamides with electron-deficient olefins led to the oxidative coupling of two olefinic C–H bonds in forming (E)-selective diene products. The intramolecular version of the coupling reaction efficiently produced indene and bicyclic fulvene derivatives. The empirical rate law for the coupling reaction of ethyl cinnamate with propene was determined as follows: rate = k[1]1[propene]0[cinnamate]−1. A negligible deuterium kinetic isotope effect (kH/kD = 1.1 ± 0.1) was measured from both (E)-C6H5CH═C(CH3)CONHCH3 and (E)-C6H5CD═C(CH3)CONHCH3 with styrene. In contrast, a significant normal isotope effect (kH/kD = 1.7 ± 0.1) was observed from the reaction of (E)-C6H5CH═C(CH3)CONHCH3 with styrene and styrene-d8. A pronounced carbon isotope effect was measured from the coupling reaction of (E)-C6H5CH═CHCO2Et with propene (13C(recovered)/13C(virgin) at Cβ = 1.019(6)), while a negligible carbon isotope effect (13C(recovered)/13C(virgin) at Cβ = 0.999(4)) was obtained from the reaction of (E)-C6H5CH═C(CH3)CONHCH3 with styrene. Hammett plots from the correlation of para-substituted p-X-C6H4CH═CHCO2Et (X = OCH3, CH3, H, F, Cl, CO2Me, CF3) with propene and from the treatment of (E)-C6H5CH═CHCO2Et with a series of para-substituted styrenes p-Y-C6H4CH═CH2 (Y = OCH3, CH3, H, F, Cl, CF3) gave the positive slopes for both cases (ρ = +1.1 ± 0.1 and +1.5 ± 0.1, respectively). Eyring analysis of the coupling reaction led to the thermodynamic parameters, ΔH⧧ = 20 ± 2 kcal mol–1 and ΔS⧧ = −42 ± 5 eu. Two separate mechanistic pathways for the coupling reaction have been proposed on the basis of these kinetic and spectroscopic studies

Post-acute assessment programme for patients with traumatic brain injury: measuring the gap between patients' expectations on entering and end of programme recommendations

Objective: To compare the expectations of patients with brain injury (TBI) entering a post-acute programme to the recommendations made at the end. Design: Retrospective study (1997 and 2009). Intervention: This 12-week post-acute programme included ecological multidisciplinary assessment of physical and cognitive disabilities, independence in activities of daily living and work abilities. Recommendations made at the conclusion of the programme included advice regarding the ability to work in an unsheltered or a sheltered environment and possible social activities. Results: Two hundred and forty patients participated. The main objective of 95.8% was return-to-work: 93.7% expected a normal work environment, 2.1% considered a sheltered environment and 4% entered the programme with the aim of improving social abilities and integration in the community. The recommendations included return-to-work in 68.3% of cases, in an unsheltered environment in 44.2% and in a sheltered environment in 24.1% and advice for contact with social services in order to achieve better social integration in 31.7%. There was a discrepancy between expectations and recommendations in half of the cases. Conclusion: The discrepancy between patients’ expectations and recommendations is in part due to the cognitive disorders; long-term rehabilitation programmes should focus on this issue

ŽELJKO HOLJEVAC GOSPIĆ U VOJNOJ KRAJINI

A range of novel heterocyclic cations have been synthesized by the Rh­(III)-catalyzed oxidative C–N and C–C coupling of 1-phenylpyrazole, 2-phenylpyridine, and 2-vinylpyridine with alkynes (4-octyne and diphenylacetylene). The reactions proceed via initial C–H activation, alkyne insertion, and reductive coupling, and all three of these steps are sensitive to the substrates involved and the reaction conditions. Density functional theory (DFT) calculations show that C–H activation can proceed via a heteroatom-directed process that involves displacement of acetate by the neutral substrate to form charged intermediates. This step (which leads to cationic C–N coupled products) is therefore favored by more polar solvents. An alternative non-directed C–H activation is also possible that does not involve acetate displacement and so becomes favored in low polarity solvents, leading to C–C coupled products. Alkyne insertion is generally more favorable for diphenylacetylene over 4-octyne, but the reverse is true of the reductive coupling step. The diphenylacetylene moiety can also stabilize unsaturated seven-membered rhodacycle intermediates through extra interaction with one of the Ph substituents. With 1-phenylpyrazole this effect is sufficient to suppress the final C–N reductive coupling. A comparison of a series of seven-membered rhodacycles indicates the barrier to coupling is highly sensitive to the two groups involved and follows the trend C–N⁺ > C–N > C–C (i.e., involving the formation of cationic C–N, neutral C–N, and neutral C–C coupled products, respectively)

Rhodium(III)-Catalyzed Dearomatizing (3+2) Annulation of 2-Alkenylphenols and Alkynes

Appropriately substituted 2-alkenylphenols undergo a mild formal [3C+2C] cycloaddition with alkynes when treated with a Rh(III) catalyst and an oxidant. The reaction, which involves the cleavage of the terminal C–H bond of the alkenyl moiety and the dearomatization of the phenol ring, provides a versatile and efficient approach to highly appealing spirocyclic skeletons and occurs with high selectivityWe thank the financial support provided by the Spanish Grants SAF2010-20822-C02 and CSD2007-00006 Consolider Ingenio 2010, the Xunta de Galicia Grants GR2013-041 and EM2013/036, the ERDF, and the European Research Council (Advanced Grant No. 340055). M.G. thanks Xunta de Galicia for a Parga Pondal contractS