Comparison of Pediatric Acute Appendicitis Before and During the COVID-19 Pandemic in New York City.

Background: Acute appendicitis (AA) is the most common abdominal surgical emergency in children and adolescents. In the year immediately following the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO), there was a precipitous decline in emergency department (ED) visits especially for surgical conditions and infectious diseases. Fear of exposure to severe acute respiratory coronavirus 2 infection resulted in delay in presentation and time to surgery, and a shift toward more conservative management. Objective: Our goal was to compare the incidence and severity of AA before and during the COVID-19 pandemic. Methods: Patients aged 2-18 years admitted with the diagnosis of AA to Flushing Hospital Medical Center or Jamaica Hospital Medical Center in Queens, New York, were selected for chart review. Data extracted from electronic health records included demographics, clinical findings, imaging studies, and operative and pathological findings. We calculated the Alvarado score (AS) for incidence and the American Association for the Surgery of Trauma (AAST) grade for severity. We compared patients admitted between March 1, 2018-February 29, 2020 (pre-pandemic) to patients admitted between March 1, 2020-February 28, 2021 (pandemic). We then compared pre-pandemic and pandemic groups to determine differences in pediatric AA incidence and severity. Results: Of 239 patients diagnosed with AA, 184 (77%) were in the pre-pandemic group and 55 (23%) in the pandemic group. Incidence (number per year) of AA declined by 40%. The pandemic group had significantly greater overall AS of ≥7, indicating increased likelihood to require surgery, (P = 0.04) and higher AAST grade demonstrating increased severity (P = 0.02). Conclusion: There was a decline in the number of AA cases seen in our pediatric EDs and admitted during the first year of the pandemic. Clinicians need to be aware of increased severity of AA at time of presentation during public health emergencies such as a pandemic, possibly due to modified patient behavior.

Palladium-catalyzed decarboxylative allylic alkylation of diastereomeric ß-ketoesters.

The palladium-catalyzed decarboxylative allylic alkylation of diastereomeric ß-ketoesters derived from 4-tert-butylcyclohexanone is described. These experiments were performed to elucidate our understanding of stereoablative enantioconvergent catalysis. A detailed analysis of the product distribution, including stereochemical outcome of the products, is included. These studies also reveal an interesting example of selectivity that is governed by competing modes of substrate and catalyst control.

Palladium-catalyzed ortho-selective C-H deuteration of arenes: evidence for superior reactivity of weakly coordinated palladacycles.

We disclose a protocol for the palladium-catalyzed ortho-selective C-H deuteration of arenes. Phenylacetic acids and benzoic acids are suitable substrates for this reaction. This reaction offers a catalytic route to ortho-deuterated phenylacetic acids and benzoic acids and demonstrates the sharp difference in reactivity of palladacycle intermediates held together by weak and strong coordination.

Pd(II)-catalyzed ortho-trifluoromethylation of benzylamines.

The Pd(II)-catalyzed ortho-C-H trifluoromethylation of benzylamines has been achieved utilizing an electrophilic CF3 reagent. Additives, such as H2O and Ag2O, were found to be crucial for obtaining good yields. This protocol will be useful in medicinal chemistry for the preparation of ortho-trifluoromethyl-substituted benzylamines.

The reaction mechanism of the enantioselective Tsuji allylation: inner-sphere and outer-sphere pathways, internal rearrangements, and asymmetric C-C bond formation.

We use first principles quantum mechanics (density functional theory) to report a detailed reaction mechanism of the asymmetric Tsuji allylation involving prochiral nucleophiles and nonprochiral allyl fragments, which is consistent with experimental findings. The observed enantioselectivity is best explained with an inner-sphere mechanism involving the formation of a 5-coordinate Pd species that undergoes a ligand rearrangement, which is selective with regard to the prochiral faces of the intermediate enolate. Subsequent reductive elimination generates the product and a Pd(0) complex. The reductive elimination occurs via an unconventional seven-centered transition state that contrasts dramatically with the standard three-centered C-C reductive elimination mechanism. Although limitations in the present theory prevent the conclusive identification of the enantioselective step, we note that three different computational schemes using different levels of theory all find that inner-sphere pathways are lower in energy than outer-sphere pathways. This result qualitatively contrasts with established allylation reaction mechanisms involving prochiral nucleophiles and prochiral allyl fragments. Energetic profiles of all reaction pathways are presented in detail.

Heterocycle Formation via Palladium-Catalyzed C-H Functionalization.

Heterocyclic compounds are ubiquitous in natural products, pharmaceuticals, and agrochemicals. Therefore, the design of novel protocols to construct heterocycles more efficiently is a major area of focus in the organic chemistry. In the past several years, cyclization reactions based upon palladium-catalyzed C-H activation have received substantial attention due to their capacity for expediting heterocycle synthesis. This review discusses strategies for heterocycle synthesis via palladium-catalyzed C-H bond activation and highlights recent examples from the literature.

Enantioselective decarboxylative alkylation reactions: catalyst development, substrate scope, and mechanistic studies.

α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic ß-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center.

Pd-catalyzed intermolecular C-H amination with alkylamines.

C-H amination of N-aryl benzamides with O-benzoyl hydroxylamines has been achieved with either Pd(II) or Pd(0) catalysts. Furthermore, we demonstrate that secondary amines can be directly used with benzoyl peroxide in a one-pot procedure that proceeds via the in situ generation of the appropriate O-benzoyl hydroxylamines. This catalytic reaction provides a new disconnection for the convergent synthesis of tertiary and secondary arylalkyl amines starting from benzoic acids.

Efforts toward rapid construction of the cortistatin A carbocyclic core via enyne-ene metathesis.

Our efforts toward the construction of the carbocylic core of cortistatin A via an enyne-ene metathesis are disclosed. Interestingly, an attempted S(N)2 inversion of a secondary mesylate in our five-membered D-ring piece gave a product with retention of stereochemistry.

Palladium-catalyzed coupling of pyrazole triflates with arylboronic acids.

[reaction: see text] A general protocol for the palladium-mediated Suzuki coupling reaction of pyrazole triflates and aryl boronic acids has been developed. The use of additional dppf ligand was determined to increase product yields allowing for the use of a broad range of reaction substrates.