The development of palladium‐catalyzed cross‐coupling reactions has revolutionized the synthesis of organic molecules on both bench‐top and industrial scales. While significant research effort has ...been directed toward evaluating how modifying various reaction parameters can influence the outcome of a given cross‐coupling reaction, the design and implementation of novel ancillary ligand frameworks has played a particularly important role in advancing the state‐of‐the‐art. This Review seeks to highlight notable examples from the recent chemical literature, in which newly developed ancillary ligands have enabled more challenging substrate transformations to be addressed with greater selectivity and/or under increasingly mild conditions. Throughout, the importance and subtlety of ligand effects in palladium‐catalyzed cross‐coupling reactions are described, in an effort to inspire further development and understanding within the field of ancillary ligand design.
It's all in the design! Recent advances in palladium‐catalyzed cross‐coupling reactions that have been enabled through the design and implementation of novel ancillary ligand frameworks are examined, with a particular emphasis placed on highlighting the subtlety of ligation effects in such reactivity applications.
The direct transition-metal-catalyzed conversion of carboxylic acid groups into other C–C or C–X bonds provides a complementary bond disconnection to traditional cross-coupling manifolds. ...Decarboxylative coupling strategies can be divided into two mechanistic frameworks: decarboxylative homolysis processes that generate radicals and decarboxylative heterolysis processes that generate carbanions. The challenge of both inducing decarboxylation with unmodified substrates and enabling efficient interception by a suitable transition-metal complex has made achieving general approaches to catalytic cross-couplings of carboxylic acids elusive. Thus, more wasteful indirect strategies involving preactivation of the acid unit are more common. This Perspective article highlights recent work in the area of metal-catalyzed ionic decarboxylative cross-coupling reactions of unmodified C(sp3) carboxylic acids. In these processes, the carboxylic acid unit serves as a surrogate for nucleophiles normally generated by deprotonation or by the use of organometallic reagents. In many cases, this approach can allow for alkylation reactions under less-basic conditions, improving functional group compatibility, ease of access to starting materials, and inhibit undesirable overfunctionalization of products. Commentary on reaction development, mechanism, and application is provided along with comparisons to related transformations.
Making inroads into ArCF3: Recent advances in the copper‐ and palladium‐catalyzed cross‐coupling of aryl halides and the trifluoromethyl anion, derived from (trifluoromethyl)silanes, are highlighted.
The syntheses of 2‐(di‐tert‐butylphosphino)‐N,N‐dimethylaniline (L1, 71 %) and 2‐(di‐1‐adamantylphosphino)‐N,N‐dimethylaniline (L2, 74 %), and their application in Buchwald–Hartwig amination, are ...reported. In combination with Pd(allyl)Cl2 or Pd(cinnamyl)Cl2, these structurally simple and air‐stable P,N ligands enable the cross‐coupling of aryl and heteroaryl chlorides, including those bearing as substituents enolizable ketones, ethers, esters, carboxylic acids, phenols, alcohols, olefins, amides, and halogens, to a diverse range of amine and related substrates that includes primary alkyl‐ and arylamines, cyclic and acyclic secondary amines, NH imines, hydrazones, lithium amide, and ammonia. In many cases, the reactions can be performed at low catalyst loadings (0.5–0.02 mol % Pd) with excellent functional group tolerance and chemoselectivity. Examples of cross‐coupling reactions involving 1,4‐bromochlorobenzene and iodobenzene are also reported. Under similar conditions, inferior catalytic performance was achieved when using Pd(OAc)2, PdCl2, PdCl2(cod) (cod=1,5‐cyclooctadiene), PdCl2(MeCN)2, or Pd2(dba)3 (dba=dibenzylideneacetone) in combination with L1 or L2, or by use of Pd(allyl)Cl2 or Pd(cinnamyl)Cl2 with variants of L1 and L2 bearing less basic or less sterically demanding substituents on phosphorus or lacking an ortho‐dimethylamino fragment. Given current limitations associated with established ligand classes with regard to maintaining high activity across the diverse possible range of CN coupling applications, L1 and L2 represent unusually versatile ligand systems for the cross‐coupling of aryl chlorides and amines.
New amination catalysts: A highly active and widely applicable catalyst system for the cross‐coupling of aryl chlorides to amines has been developed by employing the structurally simple and robust ligands L1 and L2 (see graphic). Suitable amine partners include primary and secondary aryl and alkyl amines, imines, hydrazones, lithium amide, and ammonia, with typical catalyst loadings of 1–0.02 mol % Pd.
Amazing ammonia: A new air‐stable P,N‐ligand (Mor‐DalPhos) is reported that enables the palladium‐catalyzed cross‐coupling of ammonia to a variety of aryl chloride and aryl tosylate substrates with ...high chemoselectivity and, for the first time, at room temperature (see scheme; Ad=adamantyl, Ts=para‐toluenesulfonyl).
Objectives
The aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of ...cardiovascular disease (CVD) and diabetes.
Methods
We analysed data from the Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre‐ART) to 1 year after initiation (continuous variable) in treatment‐naïve individuals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI weight (kg)/(height (m))2 was categorized as underweight (< 18.5), normal (18.5–25), overweight (25–30) and obese (> 30). Poisson regression models were fitted stratified for each pre‐ART BMI category to allow for category‐specific estimates of incidence rate ratio (IRR). Models were adjusted for pre‐ART BMI and CD4 count, key known risk factors (time‐updated where possible) and calendar year.
Results
A total of 97 CVD events occurred in 43 982 person‐years (n = 9321) and 125 diabetes events in 43 278 person‐years (n = 9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre‐ART BMI category, was: underweight, 0.90 (0.60–1.37); normal, 1.18 (1.05–1.33); overweight, 0.87 (0.70–1.10), and obese, 0.95 (0.71–1.28) (P for interaction = 0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre‐ART BMI (P for interaction > 0.05).
Conclusions
Short‐term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre‐ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre‐ART BMI.
We demonstrate that metal-catalyzed enantioselective benzylation reactions of allylic electrophiles can occur directly from aryl acetic acids. The reaction proceeds via a pathway in which ...decarboxylation is the terminal event, occurring after stereoselective carbon–carbon bond formation. This mechanistic feature enables enantioselective benzylation without the generation of a highly basic nucleophile. Thus, the process has broad functional group compatibility that would not be possible employing established protocols.
night‐eating syndrome and obesity Gallant, A. R; Lundgren, J; Drapeau, V
Obesity reviews,
June 2012, Letnik:
13, Številka:
6
Journal Article
Recenzirano
The rising prevalence of obesity is a global concern. Eating behaviour and circadian rhythm are proving to be important factors in the aetiology of obesity. The night‐eating syndrome (NES) is ...characterized by increased late‐night eating, insomnia, a depressed mood and distress. It is evident that prevalence is higher among weight‐related populations than the general community. The exact relationship between this syndrome and obesity remains unclear. The reasons for the discrepancies found in the literature likely include varying diagnostic criteria and a wide range of study population characteristics. NES does not always lead to weight gain in thus certain individuals may be susceptible to night‐eating‐related weight gain. Weight loss through surgical and behavioural treatments has shown success in diminishing symptoms. The increasing literature associating obesity with circadian imbalances strengthens the link between the NES and obesity. Circadian genes may play a role in this syndrome. This review will examine different aspects of obesity in the context of the NES.
Since the introduction of highly active antiretroviral therapy (HAART), little is known about whether changes in HIV-1 mortality and morbidity rates have been sustained. We aimed to assess possible ...changes in these rates across Europe.
We analysed data for 9803 patients in 70 European HIV centres including ones in Israel and Argentina. Incidence rates of AIDS or death were calculated for overall and most recent CD4 count in 6–monthly periods and in three treatment eras (pre-HAART, 1994–1995; early-HAART, 1996–1997; and late-HAART, 1998–2002).
The incidence of AIDS or death fell after September, 1998, by 8% per 6–month period (rate ratio 0·92, 95% CI 0·88–0·95, p<0·0001). When AIDS and death were analysed separately, the incidence of all deaths during the late-HAART era was significantly lower than that during the early-HAART era in patients whose latest CD4 count was 20 cells/μL or less (0·43, 0·35–0·53, p<0·0001), but at higher CD4 counts, did not differ between early-HAART and late-HAART. Incidence of AIDS was about 50% lower in late-HAART than in early-HAART, irrespective of latest CD4 count (p<0·0001). In multivariate Cox's models, with early-HAART as the reference, there was an increased risk of AIDS (relative hazard 1–39; 95% CI 1–16–1–67, p=0·0004) and all deaths (1–29; 1–08–1–56, p=0·0065) in the pre-HAART era, and a reduced risk of AIDS (0·62; 0·50–0–77, p<0·0001) and all deaths (0·66; 0·53–0·82, p=0·0002) in the late-HAART era.
The initial drop in mortality and morbidity after the introduction of HAART has been sustained. Potential long-term adverse effects associated with HAART have not altered its effectiveness in treating AIDS.
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