Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
Add more filters










Database
Language
Publication year range
1.
BMJ Open ; 12(2): e052778, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35105577

ABSTRACT

OBJECTIVE: To explore the relationships between leader support, staff influence over decisions, work pressure and patient satisfaction. DESIGN: A cross-sectional study of large National Health Service (NHS) datasets in England in 2010. SETTING AND PARTICIPANTS: 158 NHS acute hospital trusts in England (n=63 156) from all staff groups. PRIMARY AND SECONDARY OUTCOME MEASURES: Survey data measuring leader support, staff influence over decision making, staff work pressure and objective outcome data measuring patient satisfaction. RESULTS: Multilevel serial mediation analysis showed a significantly positive association between leader support and staff influence over decisions (B=0.74, SE=0.07, p<0.01). Furthermore, staff influence over decisions showed a negative association with staff work pressure (B=-0.84, SE=0.41, p<0.05) which in turn was negatively linked to patient satisfaction (B=-17.50, SE=4.34, p<0.01). Serial mediation showed a positive indirect effect of leader support on patient satisfaction via staff influence over decisions and work pressure (B=10.96, SE=5.55, p<0.05). CONCLUSIONS AND IMPLICATIONS: Our results provide evidence that leader support influences patient satisfaction through shaping staff experience, particularly staff influence over decisions and work pressure. Patients' care is dependent on the health, well-being, and effectiveness of the NHS workforce. That, in turn, is determined by the extent to which leaders are supportive in ensuring that work environments are managed in a way which protects the well-being of staff.


Subject(s)
Patient Satisfaction , State Medicine , Cross-Sectional Studies , Decision Making , England , Humans
2.
J Am Chem Soc ; 142(34): 14649-14663, 2020 08 26.
Article in English | MEDLINE | ID: mdl-32786804

ABSTRACT

The mechanism of CF2 transfer from TMSCF3 (1), mediated by TBAT (2-12 mol %) or by NaI (5-20 mol %), has been investigated by in situ/stopped-flow 19F NMR spectroscopic analysis of the kinetics of alkene difluorocyclopropanation and competing TFE/c-C3F6/homologous perfluoroanion generation, 13C/2H KIEs, LFERs, CF2 transfer efficiency and selectivity, the effect of inhibitors, and density functional theory (DFT) calculations. The reactions evolve with profoundly different kinetics, undergoing autoinhibition (TBAT) or quasi-stochastic autoacceleration (NaI) and cogenerating perfluoroalkene side products. An overarching mechanism involving direct and indirect fluoride transfer from a CF3 anionoid to TMSCF3 (1) has been elucidated. It allows rationalization of why the NaI-mediated process is more effective for less-reactive alkenes and alkynes, why a large excess of TMSCF3 (1) is required in all cases, and why slow-addition protocols can be of benefit. Issues relating to exothermicity, toxicity, and scale-up are also noted.

3.
Chem Sci ; 10(24): 6162-6173, 2019 Jun 28.
Article in English | MEDLINE | ID: mdl-31360423

ABSTRACT

The enantioselective preparation of a range of perfluoroalkyl-substituted ß-lactones through an isothiourea (HyperBTM) catalysed reaction using symmetric anhydrides as ammonium enolate precursors and perfluoroalkylketones (RF = CF3, C2F5, C4F9) is reported. Following optimisation, high diastereo- and enantioselectivity was observed for ß-lactone formation using C2F5- and C4F9-substituted ketones at room temperature (26 examples, up to >95 : 5 dr and >99 : 1 er), whilst -78 °C was necessary for optimal dr and er with CF3-substituted ketones (11 examples, up to >95 : 5 dr and >99 : 1 er). Derivatisation of the ß-lactones through ring-opening, as well as a two-step conversion to give perfluoroalkyl-substituted oxetanes, is demonstrated without loss of stereochemical integrity. Density functional theory computations, alongside 13C natural abundance KIE studies, have been used to probe the reaction mechanism with a concerted asynchronous [2 + 2]-cycloaddition pathway favoured over a stepwise aldol-lactonisation process.

4.
J Am Chem Soc ; 140(35): 11112-11124, 2018 09 05.
Article in English | MEDLINE | ID: mdl-30080973

ABSTRACT

The mechanism of CF3 transfer from R3SiCF3 (R = Me, Et, iPr) to ketones and aldehydes, initiated by M+X- (<0.004 to 10 mol %), has been investigated by analysis of kinetics (variable-ratio stopped-flow NMR and IR), 13C/2H KIEs, LFER, addition of ligands (18-c-6, crypt-222), and density functional theory calculations. The kinetics, reaction orders, and selectivity vary substantially with reagent (R3SiCF3) and initiator (M+X-). Traces of exogenous inhibitors present in the R3SiCF3 reagents, which vary substantially in proportion and identity between batches and suppliers, also affect the kinetics. Some reactions are complete in milliseconds, others take hours, and others stall before completion. Despite these differences, a general mechanism has been elucidated in which the product alkoxide and CF3- anion act as chain carriers in an anionic chain reaction. Silyl enol ether generation competes with 1,2-addition and involves protonation of CF3- by the α-C-H of the ketone and the OH of the enol. The overarching mechanism for trifluoromethylation by R3SiCF3, in which pentacoordinate siliconate intermediates are unable to directly transfer CF3- as a nucleophile or base, rationalizes why the turnover rate (per M+X- initiator) depends on the initial concentration (but not identity) of X-, the identity (but not concentration) of M+, the identity of the R3SiCF3 reagent, and the carbonyl/R3SiCF3 ratio. It also rationalizes which R3SiCF3 reagent effects the most rapid trifluoromethylation, for a specific M+X- initiator.

5.
J Am Chem Soc ; 139(34): 11895-11902, 2017 08 30.
Article in English | MEDLINE | ID: mdl-28763205

ABSTRACT

A tandem relay catalytic protocol using both Pd and isothiourea catalysis has been developed for the enantioselective synthesis of α-amino acid derivatives containing two stereogenic centers from readily accessible N,N-disubstituted glycine aryl esters and allylic phosphates. The optimized process uses a bench-stable succinimide-based Pd precatalyst (FurCat) to promote Pd-catalyzed allylic ammonium salt generation from the allylic phosphate and the glycine aryl ester. Subsequent in situ enantioselective [2,3]-sigmatropic rearrangement catalyzed by the isothiourea benzotetramisole forms syn-α-amino acid derivatives with high diastereo- and enantioselectivity. This methodology is most effective using 4-nitrophenylglycine esters and tolerates a variety of substituted cinnamic and styrenyl allylic ethyl phosphates. The use of challenging unsymmetrical N-allyl-N-methylglycine esters is also tolerated under the catalytic relay conditions without compromising stereoselectivity.

6.
J Am Chem Soc ; 139(12): 4366-4375, 2017 03 29.
Article in English | MEDLINE | ID: mdl-28230365

ABSTRACT

A mechanistic study of the isothiourea-catalyzed enantioselective [2,3]-rearrangement of allylic ammonium ylides is described. Reaction kinetic analyses using 19F NMR and density functional theory computations have elucidated a reaction profile and allowed identification of the catalyst resting state and turnover-rate limiting step. A catalytically relevant catalyst-substrate adduct has been observed, and its constitution elucidated unambiguously by 13C and 15N isotopic labeling. Isotopic entrainment has shown the observed catalyst-substrate adduct to be a genuine intermediate on the productive cycle toward catalysis. The influence of HOBt as an additive upon the reaction, catalyst resting state, and turnover-rate limiting step has been examined. Crossover experiments have probed the reversibility of each of the proposed steps of the catalytic cycle. Computations were also used to elucidate the origins of stereocontrol, with a 1,5-S···O interaction and the catalyst stereodirecting group providing transition structure rigidification and enantioselectivity, while preference for cation-π interactions over C-H···π is responsible for diastereoselectivity.

7.
Angew Chem Int Ed Engl ; 55(46): 14394-14399, 2016 11 07.
Article in English | MEDLINE | ID: mdl-27762045

ABSTRACT

N-Acyl imidazoles and catalytic isothiourea hydrochloride salts function as ammonium enolate precursors in the absence of base. Enantioselective Michael addition-cyclization reactions using different α,ß-unsaturated Michael acceptors have been performed to form dihydropyranones and dihydropyridinones with high stereoselectivity. Detailed mechanistic studies using RPKA have revealed the importance of the "imidazolium" effect in ammonium enolate formation and have highlighted key differences with traditional base-mediated processes.

8.
J Am Chem Soc ; 136(12): 4476-9, 2014 Mar 26.
Article in English | MEDLINE | ID: mdl-24588738

ABSTRACT

Benzotetramisole promotes the catalytic asymmetric [2,3]-rearrangement of allylic quaternary ammonium salts (either isolated or prepared in situ from p-nitrophenyl bromoacetate and the corresponding allylic amine), generating syn-α-amino acid derivatives with excellent diastereo- and enantioselectivity (up to >95:5 dr; up to >99% ee).


Subject(s)
Alkenes/chemistry , Ammonium Compounds/chemistry , Thiourea/chemistry , Catalysis , Stereoisomerism , Substrate Specificity
9.
Org Lett ; 14(24): 6370-3, 2012 Dec 21.
Article in English | MEDLINE | ID: mdl-23231752

ABSTRACT

CF(3)-substituted vinyl diphenylsulfonium triflate is an effective annulation reagent for the formation of α-CF(3) substituted, epoxide-fused heterocycles (pyrrolidines, piperidines, and tetrahydrofurans). This simple method affords a variety of valuable heterocyclic building blocks in a highly diastereoselective manner (dr >20:1).


Subject(s)
Chlorofluorocarbons, Methane/chemistry , Epoxy Compounds/chemistry , Furans/chemical synthesis , Piperidines/chemical synthesis , Pyrrolidines/chemical synthesis , Catalysis , Combinatorial Chemistry Techniques , Furans/chemistry , Molecular Structure , Piperidines/chemistry , Pyrrolidines/chemistry , Salts , Stereoisomerism
SELECTION OF CITATIONS
SEARCH DETAIL
...