Simple Estimators of the Intensity of Seasonal Occurrence

Background: Edwards's method is a widely used approach for fitting a sine curve to a time-series of monthly frequencies. From this fitted curve, estimates of the seasonal intensity of occurrence (i.e., peak-to-low ratio of the fitted curve) can be generated. Methods: We discuss various approaches to the estimation of seasonal intensity assuming Edwards's periodic model, including maximum likelihood estimation (MLE), least squares, weighted least squares, and a new closed-form estimator based on a second-order moment statistic and non-transformed data. Through an extensive Monte Carlo simulation study, we compare the finite sample performance characteristics of the estimators discussed in this paper. Finally, all estimators and confidence interval procedures discussed are compared in a re-analysis of data on the seasonality of monocytic leukemia. Results: We find that Edwards's estimator is substantially biased, particularly for small numbers of events and very large or small amounts of seasonality. For the common setting of rare events and moderate seasonality, the new estimator proposed in this paper yields less finite sample bias and better mean squared error than either the MLE or weighted least squares. For large studies and strong seasonality, MLE or weighted least squares appears to be the optimal analytic method among those considered. Conclusion: Edwards's estimator of the seasonal relative risk can exhibit substantial finite sample bias. The alternative estimators considered in this paper should be preferred

Hydrosilylation of Carbonyl-Containing Substrates Catalyzed by an Electrophilic η 1 -Silane Iridium(III) Complex

Hydrosilation of a variety of ketones and aldehydes using the cationic iridium catalyst, (POCOP)Ir(H)(acetone)+, 1, (POCOP = 2,6-bis(di-tert-butyl phosphinito)phenyl) is reported. With triethyl silane, all but exceptionally bulky ketones undergo quantitative reactions employing 0.5 mol% catalyst in 20-30 min at 25 °C. Hydrosilation of esters and amides results in over-reduction and cleavage of C-O and C-N bonds, respectively. The diastereoselectivity of hydrosilation of 4-tert-butyl cyclohexanone has been examined using numerous silanes and is highly temperature dependent. Using EtMe2SiH, analysis of the ratio of cis:trans hydrosilation products as a function of temperature yields values for ΔΔH‡ (ΔH‡ (trans) - ΔH‡ (cis)) and ΔΔS‡ (ΔS‡ (trans) - ΔS‡(cis)) of -2.5 kcal/mol and -6.9 e.u., respectively. Mechanistic studies show that the ketone complex, (POCOP)Ir(H)(ketone)+, is the catalyst resting state and is in equilibrium with low concentration of the silane complex, (POCOP)Ir(H)(HSiR3)+. The silane complex transfers R3Si+ to ketone forming the oxocarbenium ion, R3SiOCR’2+, which is reduced by the resulting neutral dihydride 3, (POCOP)Ir(H)2, to yield product R3SiOCHR’2 and (POCOP)IrH+ which closes the catalytic cycle

Activation of sp 3 C−H Bonds with Cobalt(I): Catalytic Synthesis of Enamines

C-H bond activation has been extensively studied with (Cp*)M(L)n (M = Ir, Rh), but cobalt, the third member of this triad, has not previously been shown to activate sp3 C-H bonds. Further, practical functionalization of the metal alkyl products of oxidative addition has not been fully explored. Toward these ends, we have developed catalytic dehydrogenation of alkyl amines with a Co(I) catalyst. Amine substrates are protected with vinyl silanes, followed by catalytic transfer hydrogenation, to yield a broad range of stable protected enamines and 1,2-diheteroatom-substituted alkenes, including several unprecedented heterocycles. (Cp*)Co(VTMS)2 catalyzes transfer hydrogenation under surprisingly mild conditions with high chemo-, regio-, and diastereoselectivity, while tolerating additional functionality

Intramolecular hydrogen transfer reactions catalyzed by pentamethylcyclopentadienyl rhodium and cobalt olefin complexes: Mechanistic studies

The mechanism of intramolecular transfer dehydrogenation catalyzed by [Cp * M(VTMS) 2 ] ( 1 , M=Rh, 2 , M=Co, Cp* = C 5 Me 5 , VTMS = vinyltrimethylsilane) complexes has been studied using vinyl silane protected alcohols as substrates. Deuterium-labeled substrates have been synthesized and the regioselectivity of H/D transfers investigated using 1 H and 2 H NMR spectroscopy. The labeling studies establish a regioselective pathway consisting of alkene directed α C-H activation, 2,1 alkene insertion, and finally β-hydride elimination to give silyl enol ether products

Reactions of Anilines and Benzamides with a 14-Electron Iridium(I) Bis(phosphinite) Complex: N−H Oxidative Addition versus Lewis Base Coordination

Anilines react with (POCOP)Ir(C6H5)(H), 12, (POCOP = 2,6-(OPtBu2)2C6H3) to yield equilibrium mixtures of 12, the Ir(I) σ-complexes (POCOP)Ir(NH2Ar), 13, and the Ir(III) oxidative addition adducts (POCOP)Ir(H)(NHAr), 14. Quantitative studies of these equilibria for a series of anilines were carried out. Anilines possessing electron-withdrawing groups favor the Ir(III) oxidative addition adduct over the Ir(I) sigma complex. Low temperature studies using p-chloroaniline show that the Ir(I) σ-complex is the kinetic product of reaction and is likely the precursor to the Ir(III) oxidative addition adduct. Reductive elimination of complexes 14 in the presence of ethylene led to the corresponding anilines and the ethylene complex (POCOP)Ir(C2H4). Kinetic analysis of these reactions for 14e,f,g bearing electron-withdrawing aryl groups (Ar- = p-CF3C6H4-, C6F5-, 3,5-bis(CF3)C6H3-) shows the rate is independent of ethylene concentration. The ΔG‡ values for these reductive eliminations fall in the range of 21–22 kcal/mol. X-Ray analysis establishes 14f (Ar- = C6F5-) as a square pyramidal complex with the hydride occupying the apical site. Reaction of 12 with benzamides 21a,b yields quantitatively the Ir(III) oxidative addition adducts, (POCOP)Ir(H)(NHC(O)Ar), 22. X-Ray analysis of 22b (Ar- = C6F5-) shows significant interaction of the carbonyl oxygen with Ir in the site trans to hydride. The barrier to reductive elimination of 22a, 29 kcal/mol, is substantially higher than for complexes 14e,f,g

Proton-Catalyzed Hydrogenation of a d 8 Ir(I) Complex Yields a trans Ir(III) Dihydride

Hydrogenation of the (PONOP)Ir(I)CH(3) complex [PONOP = 2,6-bis(di-tert-butylphosphinito)pyridine] yields the unexpected trans-dihydride species (PONOP)IrCH(3)(H)(2). Mechanistic investigations have revealed that this reaction proceeds via proton-catalyzed H(2) cleavage, a pathway that circumvents the intermediacy of the typically invoked cis-dihydride isomer. Protonation yields the cationic (PONOP)Ir(CH(3))(H)(+) complex, which is then trapped by H(2) to yield an eta(2)-H(2) complex. Deprotonation of this species yields the trans-dihydride. Intermediates in the proposed pathway have been confirmed by independent low-temperature syntheses and spectroscopic observations

Temperature- and Solvent-Dependent Binding of Dihydrogen in Iridium Pincer Complexes

Mixtures of deuterium labeled complexes (p-XPOCOP)IrH2–xDx (1–6-d0–2) {POCOP = [C6H2-1,3-[OP(tBu)2]2; X = MeO (1), Me (2), H (3), F (4), C6F5 (5), and ArF = 3,5-(CF3)2-C6H3 (6)} have been generated by reaction of (p-XPOCOP)IrH2 complexes with HD gas in benzene followed by removal of the solvent under high vacuum. Spectroscopic analysis employing 1H and 2D NMR reveals significant temperature and solvent dependent isotopic shifts and HD coupling constants. Complexes 1–6-d1 in toluene and pentane between 296 K and 213 K exhibit coupling constants JHD of 3.8–9.0 Hz, suggesting the presence of an elongated H2 ligand, which is confirmed by T1(min) measurements of complexes 1, 3 and 6 in toluene-d8. In contrast, complex 6-d1 exhibits JHD = 0 Hz in CH2Cl2 or CDCl2F while isotopic shifts up to −4.05 ppm have been observed by lowering the temperature from 233 K to 133 K in CDCl2F. The large and temperature dependent isotope effects are attributed to non-statistical occupation of two different hydride environments. The experimental observations are interpreted in terms of a two component model involving rapid equilibration of solvated Ir(III) dihydride and Ir(I) dihydrogen structures

Driving Catalyst Reoxidation in Wacker Cyclizations with Acetal-Based Metal-Hydride Abstractors

In traditional Wacker processes, Pd(II) becomes reduced to Pd(0) after C-O bond formation and β-H elimination and must be reoxidized to the electrophilic Pd(II) state via a stoichiometric oxidant like benzoquinone, CuCl2, or O2. We report herein a Pt-catalyzed Wacker-type process that regenerates the electrophilic Pt2+ state by H− abstraction from a [Pt]-H using an oxocarbenium ion generated from an acetal or ketal under acidic conditions

Experimental and computational study of alkane dehydrogenation catalyzed by a carbazolide-based rhodium PNP pincer complex

A rhodium complex based on the bis-phosphine carbazolide pincer ligand was investigated in the context of alkane dehydrogenation and in comparison with its iridium analogue

Prevalent But Moderate Variation Across Small Geographic Regions in Patient Nonadherence to Evidence-based Preventive Therapies in Older Adults After Acute Myocardial Infarction

Patient long-term adherence to β-blockers, HMG-CoA reductase inhibitors (statins), and angiotensin-converting-enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) after acute myocardial infarction (AMI) is alarmingly low. It is unclear how prevalent patient adherence may be across small geographic areas and whether this geographic prevalence may vary