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The polar retrosynthetic analysis has been widely employed in the field of organic synthesis and forms the basis of undergraduate curriculum. Although most reactions in organic synthesis rely on this rubric to guide their strategic application, their implementation often requires a long list of ancillary considerations to mitigate chemoselectivity and oxidation state issues involving protecting groups and precise reaction choreography. Here we demonstrate a complete departure from this norm by the use of a radical based Ni/Ag-electrocatalytic cross coupling of α-substituted carboxylic acids, thereby enabling an intuitive and modular approach to accessing complex molecular architectures. This new method relies on a key silver additive that forms an active Ag-nanoparticle coated electrode surface in situ along with carefully chosen ligands that modulate the reactivity of Ni. Through judicious choice of conditions and ligands, the cross-couplings can be rendered highly diastereoselective. To demonstrate the simplifying power of these reactions, exceedingly concise syntheses of 14 natural products and two medicinally relevant molecules were completed.

A useful protocol for achieving decarboxylative cross coupling (DCC) of redox-active esters (RAE, isolated or generated in situ) and halo(hetero)arenes is reported. This pragmatically focused study employs a unique Ag-Ni electrocatalytic platform to overcome numerous limitations that have plagued this strategically powerful transformation. In its optimized form coupling partners can be combined in a surprisingly simple way: open to the air, technical grade solvents, an inexpensive ligand and Ni source, substoichiometric AgNO3, proceeding at room temperature with a simple commercial potentiostat. Most importantly all of the results are placed into context by benchmarking with state-of-the-art methods. Applications are presented that simplify synthesis and rapidly enable access to challenging chemical space. Finally, adaptation to multiple scale regimes, ranging from parallel mg-based synthesis to decagram recirculating flow is presented

Early diagnosis and treatment is considered important to prevent lung damage in primary ciliary dyskinesia (PCD).Few studies have addressed long-term evolution of lung function after PCD diagnosis. We investigated whether long-term lung function was dependent on age or level of lung function at PCD diagnosis.An observational, single-center, cross-sectional, and three-decade longitudinal study of FEV(1) and FVC related to age at diagnosis until current age was performed. Linear regression was used to describe the relation between first measured lung function values and age at diagnosis across the cohort. Courses of lung function after diagnosis and the according slopes were used to group patients into increasing, stable, or decreasing courses. Additionally, slopes from courses of 10 years of follow-up were related to age at diagnosis and initial level of lung function, respectively, using linear regression.Seventy-four children and adults with PCD were observed for median 9.5 (range, 1.5-30.2) years during which 2,937 lung function measurements were performed. First measured FEV(1) was less than 80% of predicted in one-third of preschool-diagnosed children. During observation, 34% of patients lost more than 10 percentage points, 57% were stable, and 10% improved more than 10 percentage points in FEV(1). Courses of lung function after diagnosis were related to neither age at diagnosis nor initial level.Our study strongly suggests that PCD is a disease of serious threat to lung function already at preschool age, and with a high degree of variation in courses of lung function after diagnosis that was not linked to either age or level of lung function at diagnosis. Early diagnosis did not protect against decline in lung function.