Enantioconvergent Palladium-Catalyzed Alkylation of Tertiary Allylic C-H Bonds.

Enantioconvergent catalysis enables the conversion of racemic molecules into a single enantiomer in perfect yield and is considered an ideal approach for asymmetric synthesis. Despite remarkable advances in this field, enantioconvergent transformations of inert tertiary C-H bonds remain largely unexplored due to the high bond dissociation energy and the surrounding steric repulsion that pose unparalleled constraints on bond cleavage and formation. Here, we report an enantioconvergent Pd-catalyzed alkylation of racemic tertiary allylic C-H bonds of α-alkenes, providing a unique approach to access a broad range of enantioenriched γ,δ-unsaturated carbonyl compounds featuring quaternary carbon stereocenters. Mechanistic studies reveal that a stereoablative event occurs through the rate-limiting cleavage of tertiary allylic C-H bonds to generate σ-allyl-Pd species, and the achieved E/Z-selectivity of σ-allyl-Pd species effectively regulates the diastereoselectivity via a nucleophile coordination-enabled SN 2'-allylation pathway.

Mothers' emotional expressivity in urban and rural societies: Salience and links with young adolescents' emotional wellbeing and expressivity.

This research aims to investigate the salience of mothers' emotional expressivity and its links with adolescents' emotional wellbeing and expressivity in an urban society endorsing more individualism and a rural society ascribing to more collectivism. By comparing Chinese urban (N = 283, M age = 14.13) and rural (N = 247, M age = 14.09) adolescents, this research found that urban mothers' expression of positive-dominant and positive-submissive emotions (PD and PS) were more common while expression of negative-dominant (ND) emotions was less common than rural mothers'. PD and PS had significant links with urban and rural adolescents' increased emotional expressivity and self-esteem, however, only significantly related to urban adolescents' decreased depression but not with rural adolescents'. ND had significant links with both urban and rural adolescents' expression of negative emotions, however, only significantly correlated with urban adolescents' less level of self-esteem and rural adolescents' more expression of positive emotions. No significant difference was found in the salience of urban and rural mothers' expression of negative-submissive (NS) emotions, which positively related to both urban and rural adolescents' depression and emotional expressivity. Moreover, we found that adolescents' emotional wellbeing (i.e., self-esteem and depression) mediated the relationship between mothers' emotional expressivity and adolescents' expressivity in both societies. Overall, the study findings document that the salience of mothers' emotional expressivity and its relations with adolescents' emotional adjustment differ between urban and rural societies.

Redox-Neutral 1,4-Dicarbonfunctionalization of 1,3-Butadiene by Merging Photoredox and Nickel Catalysis.

The diverse functionalization of 1,3-butadiene provides wide applicability toward the synthesis of abundant and useful allylic compounds. Here, we describe a three-component and redox-neutral assembly of readily available C═X compounds, 1,3-butadiene, and various nucleophiles by merging photoredox and nickel catalysis, enabling the rapid synthesis of structurally diverse homoallyl amines and homoallylic alcohols.

Palladium-Catalyzed Branch- and Z-Selective Allylic C-H Amination with Aromatic Amines.

Allylamines are important building blocks in the synthesis of bioactive compounds. The direct coupling of allylic C-H bonds and commonly available amines is a major synthetic challenge. An allylic C-H amination of 1,4-dienes has been accomplished by palladium catalysis. With aromatic amines, branch-selective allylic aminations are favored to generate thermodynamically unstable Z-allylamines. In addition, more basic aliphatic cyclic amines can also engage in the reaction, but linear dienyl allylic amines are the major products.

Palladium-Catalyzed Enantioselective C(sp3)-H/C(sp3)-H Umpolung Coupling of N-Allylimine and α-Aryl Ketones.

Asymmetric functionalization of the C(sp3)-H bond is an attractive yet challenging strategy to achieve versatile bond-forming events, enabling the precise assembly of molecular complexity with minimal manipulation of functional groups. Here, we report an asymmetric C(sp3)-H/C(sp3)-H umpolung coupling of N-allylimine and coordinating α-aryl carbonyls by using chiral phosphoramidite-palladium catalysis. A wide variety of α-heteroaryl ketones and 2-acylimidazoles are nicely tolerated to open a convenient and tunable avenue for efficient synthesis of enantioenriched ß-amino-γ,δ-unsaturated carbonyl derivatives with high levels of regio- and stereoselectivities, capable of providing a key intermediate for asymmetric synthesis of Focalin. This protocol showcases an umpolung reactivity of the N-allylimines through a concerted proton and two-electron transfer process to cleave the allylic C-H bond, effectively complementing established methodology for allylic C-H functionalization. An inner-sphere allylation pathway for both α-heteroaryl carbonyls and 2-acylimidazoles to attack the π-allylpalladium species is suggested by computational studies and experimental facts, wherein the nitrogen coordination to the palladium center enables the preference of branched regioselectivity.

Access to chiral γ-butenolides via palladium-catalyzed asymmetric allylic C-H alkylation of 1,4-dienes.

Asymmetric allylic C-H alkylation of 1,4-pentadienes with α-angelica lactones has been developed by tri-axial phosphoramidite-palladium catalysis. This reaction can tolerate a range of functional groups under mild conditions, furnishing versatile chiral γ,γ-disubstituted butenolides in high yields with good to high levels of stereoselectivity.

Asymmetric Photocatalytic C(sp3)-H Bond Addition to α-Substituted Acrylates.

Asymmetric functionalization of inert C(sp3)-H bonds is a straightforward approach to realize versatile bond-forming events, allowing the precise assembly of molecular complexity with minimal functional manipulations. Here, we describe an asymmetric photocatalytic C(sp3)-H bond addition to α-substituted acrylates by using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom transfer (HAT) photocatalyst and chiral phosphoric acid as a chiral proton-transfer shuttle. This protocol is supposed to occur via a radical/ionic relay process, including a TBADT-mediated HAT to cleave the inert C(sp3)-H bond, a 1,4-radical addition, a back hydrogen abstraction, and an enantioselective protonation. A variety of inert C-H bond patterns and α-substituted acrylates are well tolerated to enable the rapid synthesis of enantioenriched α-stereogenic esters from simple raw materials.

Cost-effectiveness analysis of renal replacement therapy strategies in Guangzhou city, southern China.

OBJECTIVES: This study aims to assess the cost-effectiveness of three renal replacement therapy (RRT) modalities as well as proposed changes of scheduled policies in RRT composition in Guangzhou city. METHODS: From a payer perspective, we designed Markov model-based cost-effectiveness analyses to compare the cost-effectiveness of three RRT modalities and four different scheduled policies to RRT modalities in Guangzhou over three time horizons (5, 10 and 15 years). The current situation (scenario 1: haemodialysis (HD), 73%; peritoneal dialysis (PD), 14%; kidney transplantation (TX), 13%) was compared with three different scenarios: an increased proportion of incident RRT patients on PD (scenario 2: HD, 47%; PD, 40%; TX, 13%); on TX (scenario 3: HD, 52%; PD, 14%; TX, 34%); on both PD and TX (Scenario 4: HD, 26%; PD, 40%; TX, 34%). RESULTS: Over 5-year time horizon, HD was dominated by PD. At a willingness-to-pay (WTP) threshold of US$44 300, TX was cost-effective compared with PD with an incremental cost-effectiveness ratio of US$35 518 per quality-adjusted life year (QALY) gained. The scenario 2 held a dominant position over the scenario 1, with a net saving of US$ 5.92 million and an additional gain of 6.24 QALYs. The scenarios 3 and 4 were cost-effective compared with scenario 1 at a WTP threshold of US$44 300. The above results were consistent across the three time horizons. CONCLUSIONS: TX is the most cost-effective RRT modality, followed in order by PD and HD. The strategy with an increased proportion of incident patients on PD and TX is cost-effective compared with the current practice pattern at the given WTP threshold. The planning for RRT service delivery should incorporate efforts to increase the utilisation of PD and TX in China.

Development and validation of an instrument in job evaluation factors of physicians in public hospitals in Beijing, China.

BACKGROUND: Job evaluation has been widely used to establish a foundation for internal equity and other human resource functions. The United Kingdom adopts the National Health Service (NHS) Job Evaluation scheme to determine the pay bands for most NHS staff and ensure equal pay for work of equal value. The challenges of recruiting and retaining physicians in Chinese public hospitals have heightened the need for a reliable job evaluation system to ensure the equality of physician compensation. The aim of this study was to construct job evaluation factors of physicians in Chinese public hospitals based on the NHS Job Evaluation scheme and to examine the reliability and validity of the established system. METHODS: Questionnaire surveys and statistical analyses were used to determine the job evaluation factors for physicians. The preliminary screening of the evaluation factors was based on a literature review, focused interviews with physicians and the Delphi method. Based on the results of preliminary screening, a questionnaire with 25 factors was designed to survey physicians regarding the importance of each factor in physician job evaluation. After the pretest, final questionnaire data were collected from 900 physicians by adopting a stratified sampling from 6 tertiary public hospitals in Beijing. A principal component analysis was used for factor extraction and structural validity analysis. The reliability was determined using Cronbach's alpha. RESULTS: The results of the principal component analysis showed that the 25 physician job evaluation factors were grouped into the 5 dimensions of Task Characteristics, Knowledge, Responsibility, Effort/Environment, and Skills. The Cronbach's alpha coefficients of the five dimensions ranged from 0.841 to 0.909, which indicated a high level of reliability. The result of the factor analysis indicated fair structural validity. The content validity was established by building onto the NHS Job Evaluation scheme and other well-established job evaluation systems. CONCLUSIONS: Our study indicates that the Chinese version of physician job evaluation is an instrument with fair reliability and validity, which fully reflects the characteristics of physicians in Chinese public hospitals. This system can provide an important basis for developing a physician compensation plan and ensuring internal equity in healthcare organizations.

The Cost-Effectiveness of Kidney Replacement Therapy Modalities: A Systematic Review of Full Economic Evaluations.

BACKGROUND: Kidney replacement therapy (KRT) is a lifesaving but costly treatment for patients with end-stage kidney disease (ESKD). The objective of this study was to review full economic evaluations comparing KRT modalities specified as hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KT) for patients with ESKD. METHODS: We conducted a systematic review of the literature from PubMed, Embase, EconLit (EBSCO), Web of Science, Cochrane Library, National Health Service Economic Evaluation Database (NHS EED), Centre for Reviews and Dissemination (CRD) Database of Abstracts of Reviews of Effects (DARE), and CRD Health Technology Assessment Database from inception until 5 January 2020. Full economic evaluations were included if they compared three forms of KRT specified as PD, HD, and KT. The reporting quality of included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: Ten studies were identified in the review. The majority of the studies were model-based evaluations and included a cost-utility analysis. Four studies were conducted from a public healthcare perspective, three from a societal perspective, and three from a third-party payer perspective. None of the studies adequately addressed all the applicable items of the CHEERS checklist. The most infrequently reported items were characterizing heterogeneity, target population, and characterizing uncertainty. There is a lack of studies that conduct from a societal perspective and take into account characterizing heterogeneity. All included studies indicate that KT is the most cost-effective KRT modality, with either a dominant position over HD and PD or an incremental cost-effectiveness ratio well below the accepted willingness-to-pay threshold. The majority of studies suggest that PD is less costly and offers comparable or better health outcomes than HD. CONCLUSIONS: Our systematic review suggests that KT is the most cost-effective KRT modality, but there is no firm conclusion about the cost-effectiveness of HD and PD. Further economic evaluations can be conducted from a societal perspective and detail the evidence for subsets of patients with different characteristics.

Palladium-Catalyzed Asymmetric Allylic C-H Functionalization: Mechanism, Stereo- and Regioselectivities, and Synthetic Applications.

Asymmetric functionalization of inert C-H bonds is undoubtedly a synthetically significant yet challenging bond-forming process, allowing for the preparation of densely functionalized molecules from abundantly available feedstocks. In the past decade, our group and others have found that trivalent phosphorus ligands are capable of facilitating Pd-catalyzed allylic C-H functionalization of α-alkenes upon using p-quinone as an oxidant. In these reactions, a 16-electron Pd(0) complex bearing a monodentate phosphorus ligand, a p-quinone, and an α-alkene has been identified as a key intermediate. Through a concerted proton and two-electron transfer process, electrophilic π-allylpalladium is subsequently generated and can be leveraged to forge versatile chemical bonds with a wide range of nucleophiles. This Account focuses on describing the origin, evolution, and synthetic applications of Pd-catalyzed asymmetric allylic C-H functionalization reactions, with an emphasis on the fundamental mechanism of the concerted proton and two-electron transfer process in allylic C-H activation.Enabled by the cooperative catalysis of the palladium complex of triarylphosphine, a primary amine, and a chiral phosphoric acid, an enantioselective α-allylation of aldehydes with α-alkenes is established. The combination of chiral phosphoric acid and a palladium complex of a chiral phosphoramidite ligand allows the allylic C-H alkylation of α-alkenes with pyrazol-5-ones to give excellent enantioselectivities, wherein the chiral ligand and chiral phosphoric acid synergistically control the stereoselectivity. Notably, the palladium-phosphoramidite complexes are also efficient catalysts for allylic C-H alkylation, with a wide scope of nucleophiles. In the case of 1,4-dienes, the geometry and coordination pattern of the nucleophile are able to vary the transition states of bond-forming events and thereby determine the Z/E-, regio-, and stereoselectivities.These enantioselective allylic C-H functionalization reactions are tolerant of a wide range of nucleophiles and α-alkenes, providing a large library of optically active building blocks. Based on enantioselective intramolecular allylic C-H oxidation, the formal synthesis of (+)-diversonol is accomplished, and enantioselective intramolecular allylic C-H amination can enable concise access to letermovir. In particular, the asymmetric allylic C-H alkylation of 1,4-dienes with azlactones offers highly enantioenriched α,α-disubstituted α-amino acid derivatives that are capable of serving as key building blocks for the enantioselective synthesis of lepadiformine alkaloids. In addition, a tachykinin receptor antagonist and (-)-tanikolide are also synthesized with chiral molecules generated from the corresponding allylic C-H alkylation reactions.

Recent Progress in Asymmetric Relay Catalysis of Metal Complex with Chiral Phosphoric Acid.

Asymmetric metal/organo relay catalysis, utilizing a metal complex and a chiral organocatalyst in a one-pot cascade reaction, is aimed to sequentially impart activation on multiple steps by distinct catalysts. Such a catalysis merges the advantages of both metal catalysis and organocatalysis, providing step-economy, and, more importantly, the potential to achieve inaccessible reactivity by a single catalyst. Chiral phosphoric acids are among the most robust organocatalysts, rendering a broad range of enantioselective bond-forming reactions. The combination of metal complexes and chiral phosphoric acids in a single vessel has been well documented. In particular, the asymmetric relay catalysis of metal complex with chiral phosphoric acid has grown rapidly since 2008. Several excellent reviews have been published to cover almost all examples in this area from 2008 to early 2014; therefore, in this chapter, we will mainly highlight progress from 2014 to mid-2019.

Nucleophile Coordination Enabled Regioselectivity in Palladium-Catalyzed Asymmetric Allylic C-H Alkylation.

Branched selectivity in asymmetric allylic C-H alkylation is enabled by using 2-acylimidazoles as nucleophiles in the presence of a chiral phosphoramidite-palladium catalyst. A wide range of terminal alkenes, including 1,4-dienes and allylarenes, are nicely tolerated and provide chiral 2-acylimidazoles in moderate to high yields and with high levels of regio-, and enantio-, and E/Z-selectivities. Mechanistic studies using density-functional theory calculations suggest a nucleophile-coordination-enabled inner-sphere attack mode for the enantioselective carbon-carbon bond-forming event.

Monodentate Phosphorus Ligand-Enabled General Palladium-Catalyzed Allylic C-H Alkylation of Terminal Alkenes.

Monodentate phosphorus ligands have been found to enable the palladium-catalyzed allylic C-H alkylation reaction of terminal alkenes with a wide variety of carbon nucleophiles. Moreover, an asymmetric allylic C-H alkylation of terminal alkenes with pyrazol-5-ones has been established in the presence of chiral phosphoramidite ligand and chiral phosphoric acid as co-catalyst. Mechanistic studies suggest that a ternary Pd(0) complex, coordinated with a monodentate phosphorus ligand, benzoquinone, and alkene, is most likely to be an active species.

Asymmetric Allylic C-H Alkylation of Allyl Ethers with 2-Acylimidazoles.

An asymmetric allylic C-H alkylation of allyl ethers has been established by chiral phosphoramidite-palladium catalysis, affording a wide variety of functionalized chiral 2-acylimidazoles in moderate to high yields and with high levels of enantioselectivity. Moreover, this protocol could be applied to a concise asymmetric synthesis of a tachykinin receptor antagonist.

Merging Visible-Light Photoredox and Chiral Phosphate Catalysis for Asymmetric Friedel-Crafts Reaction with in Situ Generation of N-Acyl Imines.

In the presence of visible-light photoredox and chiral phosphate catalysts, a novel asymmetric Friedel-Crafts reaction of indoles and readily accessible α-amino acid derived redox-active esters is established to afford enantioenriched 1-indolyl-1-alkylamine derivatives in moderate to high yields and with high levels of enantioselectivities. This method not only shows a mild and efficient alternative for the in situ generation of N-acyl imines but also indicates the feasibility of a multicatalyst system for asymmetric photoredox catalysis.

Nucleophile-Dependent Z/ E- and Regioselectivity in the Palladium-Catalyzed Asymmetric Allylic C-H Alkylation of 1,4-Dienes.

The asymmetric allylic alkylation (AAA), which features employing active allylic substrates, has historical significance in organic synthesis. The allylic C-H alkylation is principally more atom- and step-economic than the classical allylic functionalizations and thus can be considered a transformative variant. However, asymmetric allylic C-H alkylation reactions are still scarce and yet underdeveloped. Herein, we have found that Z/ E- and regioselectivities in the Pd-catalyzed asymmetric allylic C-H alkylation of 1,4-dienes are highly dependent on the type of nucleophiles. A highly stereoselective allylic C-H alkylation of 1,4-dienes with azlactones has been established by palladium-chiral phosphoramidite catalysis. The protocol proceeds under mild conditions and can accommodate a wide scope of substrates, delivering structurally divergent α,α-disubstituted α-amino acid surrogates in high yields and excellent levels of diastereo-, Z/ E-, regio-, and enantioselectivities. Notably, this method provides key chiral intermediates for an efficient synthesis of lepadiformine marine alkaloids. Experimental and computational studies on the reaction mechanism suggest a novel concerted proton and two-electron transfer process for the allylic C-H cleavage and reveal that the Z/ E- and regioselectivities are governed by the geometry and coordination pattern of nucleophiles.

Enantioselective Synthesis of 5-Alkylated Thiazolidinones via Palladium-Catalyzed Asymmetric Allylic C-H Alkylations of 1,4-Pentadienes with 5 H-Thiazol-4-ones.

A palladium-catalyzed, enantioselective allylic C-H alkylation of 1,4-pentadienes with 5 H-thiazol-4-ones has been developed. Under the cooperative catalysis of a palladium complex of chiral phosphoramidite ligand and an achiral Brønsted acid, a broad range of substituted 5 H-thiazol-4-ones bearing sulfur-containing tertiary chiral centers were accessed from the allylic C-H alkylation in high levels of yields and enantioselectivities. Alkyl and aryl 1,4-pentadienes led to linear and branched allylation products, respectively.