Accessing hindered amines, particularly primary amines
α
to a fully substituted carbon center, is synthetically challenging.
We report an electrochemical method to access such hindered amines
starting from benchtop-stable iminium salts and cyanoheteroarenes.
A wide variety of substituted heterocycles (pyridine, pyrimidine,
pyrazine, purine, azaindole) can be utilized in the cross-coupling
reaction, including those substituted with a halide, trifluoromethyl,
ester, amide, or ether group, a heterocycle, or an unprotected alcohol
or alkyne. Mechanistic insight based on DFT data, as well as cyclic
voltammetry and NMR spectroscopy, suggests that a proton-coupled electron-transfer
mechanism is operational as part of a hetero-biradical cross-coupling
of α-amino radicals and radicals derived from cyanoheteroarenes.
Here we demonstrate the use of second harmonic generation (SHG) microscopy-guided synchrotron powder X-ray diffraction (PXRD) for the detection of trace crystalline active pharmaceutical ingredients in a common polymer blend. The combined instrument is capable of detecting 100 ppm crystalline ritonavir in an amorphous hydroxypropyl methylcellulose matrix with a high signal-to-noise ratio (>5000). The high spatial resolution afforded by SHG microscopy allows for the use of a minibeam collimator to reduce the total volume of material probed by synchrotron PXRD. The reduction in probed volume results in reduced background from amorphous material. The ability to detect low crystalline loading has the potential to improve measurements in the formulation pipeline for pharmaceutical solid dispersions, for which even trace quantities of crystalline active ingredients can negatively impact the stability and bioavailability of the final drug product.
Coherent imaging and communication through or within heavily scattering random media has been considered impossible due to the randomization of the information contained in the scattered electromagnetic field. We report a remarkable result based on speckle correlations over incident field position that demonstrates that the field incident on a heavily scattering random medium can be obtained using a method that is not restricted to weak scatter and is, in principle, independent of the thickness of the scattering medium. Natural motion can be exploited, and the approach can be extended to other geometries. The near-infrared optical results presented indicate that the approach is applicable to other frequency regimes, as well as other wave types. This work presents opportunities to enhance communication channel capacity in the large source and detector number regime, for a new method to view binary stars from Earth, and in biomedical applications.
The development of a protecting group-free, 2-step synthesis of 5-amino-2-hydroxymethyltetrahydropyran 1a from biorenewable Cyrene™ is described which renders access to BTK-inhibitor nemtabrutinib (2) more efficient and sustainable.
A simple beam-scanning optical design based on Lissajous trajectory imaging is described for achieving up to kHz frame-rate optical imaging on multiple simultaneous data acquisition channels. In brief, two fast-scan resonant mirrors direct the optical beam on a circuitous trajectory through the field of view, with the trajectory repeat-time given by the least common multiplier of the mirror periods. Dicing the raw time-domain data into sub-trajectories combined with model-based image reconstruction (MBIR) 3D in-painting algorithms allows for effective frame-rates much higher than the repeat time of the Lissajous trajectory. Since sub-trajectory and full-trajectory imaging are simply different methods of analyzing the same data, both high-frame rate images with relatively low resolution and low frame rate images with high resolution are simultaneously acquired. The optical hardware required to perform Lissajous imaging represents only a minor modification to established beam-scanning hardware, combined with additional control and data acquisition electronics. Preliminary studies based on laser transmittance imaging and polarization-dependent second harmonic generation microscopy support the viability of the approach both for detection of subtle changes in large signals and for trace-light detection of transient fluctuations.
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