RESUMEN
The pyridyl group has been extensively employed to direct transition-metal-catalyzed C-H activation reactions in the past half-century. The typical cyclic transition states involved in these cyclometalation processes have only enabled the activation of ortho-C-H bonds. Here, we report that pyridine is adapted to direct meta-C-H activation of benzyl and phenyl ethyl alcohols through engineering the distance and geometry of a directing template. This template takes advantage of a stronger σ-coordinating pyridine to recruit Pd catalysts to the desired site for functionalization. The U-shaped structure accommodates the otherwise highly strained cyclophane-like transition state. This development illustrates the potential of achieving site selectivity in C-H activation via the recognition of distal and geometric relationship between existing functional groups and multiple C-H bonds in organic molecules.
RESUMEN
[This corrects the article DOI: 10.1021/acscentsci.5b00312.].
RESUMEN
The application of parallel synthesis is an efficient approach to explore the chemical space and to rapidly develop meaningful structure activity relationship (SAR) data for drug discovery programs. However, the effectiveness of the parallel synthesis requires a high throughput purification workflow that can process a large number of crude samples within a meaningful time frame. This paper describes a high throughput purification platform that has been adopted at Merck's Rahway research site. The platform includes the evaluation of crude samples, mass-directed HPLC purification, fraction analysis, compound registration, final compound purity assessment and assay distribution. Assisting with the sample tracking and the data management is the internally designed laboratory information management system, Light Automation Framework (LAF). Using this process and the tools described herein, the group has successfully achieved purities of 95% or greater for 90% of samples.