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Hydrofunctionalization is a powerful tool to add fragments across unsaturated building blocks to furnish more complex structures and introduce new stereocenters. My PhD studies have focused on Rh and Cu-catalyzed hydrofunctionalization to build both carbon-carbon and carbon- heteroatom bonds in a stereoselective and regioselective manner. With careful pairing of transition-metals and ligands, we successfully accessed chiral α,α-disubstituted-α-amino acid (α,α- disubstituted-α-AA) precursors, chiral cyclopropyl phosphines and N-arylated pyrazole motifs.In chapter 1, the study is focused on Rh–H catalyzed hydrofunctionalization of alkynes with α-nitroesters to synthesize α,α-disubstituted-α-AA building blocks. The method generates biologically important precursors bearing two contiguous stereocenters with high enantioselectivity, diastereoselectivity and regioselectivity. The transformation involves the Rh– H catalyzed isomerization of alkynes into Rh-π-allyl electrophiles through an allene intermediate. By trapping with nucleophiles, different allylic compounds can be formed stereoselectively. Mechanistic studies supported the presence of Rh–H and allene intermediates in the catalytic cycle. The allylic α,α-disubstituted-α-nitroester can be readily reduced to the corresponding amino ester with indium powder. Building on this report, I also developed a Rh–H catalyzed nitroalkane addition to alkynes to afford allylic nitro compounds as chiral amine precursors. Although high diastereoselectivity was achieved with the transformation, optimization of enantioselectivity still remains challenging. The initial results of this study are included at the end of chapter 1.In chapter 2, we developed a Cu-catalyzed hydrophosphination of cyclopropenes to build chiral cyclopropyl phosphines, which are biologically and chemically unique. A range of different cyclopropyl phosphines bearing different stereoelectronics can now be accessed. Supported by both experimental results and computational studies, we propose the transformation generates a Cu-phosphido species, which facilitates migratory insertion followed by protodemetalation to afford the desired products. Density function theory (DFT) calculations suggested migratory insertion is the rate- and stereo-determining step. With NMR studies, we identified a dimeric resting state structure, which can be brought back to the active monomer with addition of DBU. Transition state analysis indicates the stereoselectivity comes from a combination of dispersion and steric interactions. Insights of this study helps future phosphine ligand design and chiral phosphine synthesis.In chapter 3, a Cu-catalyzed regiodivergent N-arylation of unsymmetric pyrazoles with aryne intermediates is investigated. The method provides a new vector for late-stage functionalization of pyrazole compounds to selectively access both N-arylated regioisomers. We propose pyrazole binds with Cu to form a Cu-pyrazolate which undergoes a 5-centered amino- cupration with an aryne intermediate to afford the desired arylated pyrazoles. By enforcing steric or non-covalent interactions between ligands and the Cu catalyst, we can control the Cu-pyrazolate formation with either more hindered nitrogen atom (Nα) or less hindered nitrogen atom (Nβ). The corresponding 5-centered transition structure undergoes bond formation with the aryne fragment with high Nα- or Nβ- selectivity. The methodology is compatible with a wide scope of pyrazoles bearing different stereoelectronics; we exemplify more than 60 different Nα- and Nβ-arylated pyrazoles with moderate to high regioselectivity. We also performed the transformation with different aryne precursors which demonstrates the generality of this reaction.

Dan Yang,1,2 Xintong Hou,1,2 Guimei Yang,1,2 Mengnan Li,1,2 Jian Zhang,1,2 Minmin Han,1,2 Yi Zhang,3 Yunfeng Liu1 1Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Yi Zhang, Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China, Email yizhang313@163.com Yunfeng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 18703416196, Email nectarliu@163.comAbstract: The hypothalamus is indispensable in energy regulation and glucose homeostasis. Previous studies have shown that pro-opiomelanocortin neurons receive both central neuronal signals, such as α-melanocyte-stimulating hormone, β-endorphin, and adrenocorticotropic hormone, as well as sense peripheral signals such as leptin, insulin, adiponectin, glucagon-like peptide-1, and glucagon-like peptide-2, affecting glucose metabolism through their corresponding receptors and related signaling pathways. Abnormalities in these processes can lead to obesity, type 2 diabetes, and other metabolic diseases. However, the mechanisms by which these signal molecules fulfill their role remain unclear. Consequently, in this review, we explored the mechanisms of these hormones and signals on obesity and diabetes to suggest potential therapeutic targets for obesity-related metabolic diseases. Multi-drug combination therapy for obesity and diabetes is becoming a trend and requires further research to help patients to better control their blood glucose and improve their prognosis.Keywords: POMC neurons, central signals, peripheral signals, glucose homeostasis, obesity, diabetes

Broadband photon detectors are a key enabling technology for various applications such as spectrometers, light detection and ranging. In this work, we report on an ultra-broadband single-photon detector based on a microfiber (MF)-coupled superconducting nanowires structure operating in the spectral range from visible to near-infrared light. The MF-coupled superconducting nanowire single-photon detector (SNSPD) is formed by placing an MF on top of superconducting niobium nitride (NbN) nanowires, allowing ultra-broadband photon detection due to their nearly lossless transmission/absorption and nearly unity internal efficiency for ultra-broad waveband. The simulation results indicate that with optimal device structure, the optical absorption with efficiency > 90% can be realized over a wavelength range of 350 nm to 2150 nm. The fabricated MF-coupled SNSPD shows unparalleled broadband system detection efficiencies (SDEs) of more than 50% from 630 nm to 1500 nm. The SDEs reach 66% at 785 nm and 45% at 1550 nm. These results pave the way for ultra-broadband weak light detection with quantum-limit sensitivity.

The implementation of quantum information technologies requires the development of integrated quantum chips. Femtosecond laser direct writing (FLDW) waveguides and superconducting nanowire single-photon detectors (SNSPDs) have been widely applied in integrated quantum photonic circuits. In this work, a novel FLDW waveguide-coupled SNSPD was designed and realized by integrating FLDW waveguides and conventional SNSPDs together. Through a COMSOL simulation, a waveguide end face-nanowire optical coupling structure was designed and verified. The simulation results showed that the FLDW waveguide-coupled SNSPD device, which had a target wavelength of 780 nm, can achieve 87% optical absorption. Then the preparation process of the FLDW waveguide-coupled SNSPD device was developed, and the fabricated device achieved a system detection efficiency of 1.7% at 10 Hz dark count rate. Overall, this method provides a feasible single-photon detector solution for future on-chip integrated quantum photonic experiments and applications.

The development of photonic quantum information technologies requires research on the properties of optical adhesives at cryogenic temperatures. In the process of developing microfiber (MF)-coupled superconducting nanowire single-photon detectors (SNSPDs), we invented a cryogenic-temperature refractive index (RI) measurement method based on a kind of MF device. The device was put into the cryostat to observe the variance of MF transmittance with temperature. Then an RI–temperature relationship was established through the correspondence between the confinement conditions of MFs of various diameters in an optical adhesive– M g F 2 environment and transmittance–temperature curves. Using this method, we analyzed the thermal-optical properties of a commercial fluorinated acrylic optical adhesive and obtained the RI values of the adhesive at various temperatures. The results were successfully applied in the development of broadband and high-efficiency MF-coupled SNSPDs.

High-performance superconducting nanowire single-photon detectors (SNSPDs) have facilitated numerous experiments and applications, particularly in the fields of modern quantum optics and quantum communication. Two kinds of optical coupling methods have thus far been developed for SNSPDs: one produces standard fiber-coupled SNSPDs in which the fibers vertically illuminate the meandered nanowires; the other produces waveguide-coupled SNSPDs in which nanowires are fabricated on the surface of a waveguide that guides photons, and the fibers are coupled to the waveguide. In this paper, we report on first experimental demonstration of a new type of SNSPD that is coupled with a microfiber (MF). Photons are guided by the MF and are evanescently absorbed by the nanowires of the SNSPD when the MF is placed on top of superconducting NbN nanowires. Room-temperature optical experiments indicated that this device has a coupling efficiency of up to 90% when a 1.3 μm-diameter MF is used for light with wavelength of 1550 nm. We were also able to demonstrate that our MF-coupled detector achieved system detection efficiencies of 50% and 20% at incident wavelengths of 1064 and 1550 nm, respectively, for a 2 μm-diameter MF at 2.2K. We expect that MF-coupled SNSPDs may show both high efficiency and broadband characteristics upon optimization and will be used for various novel applications, such as micro/nano-fiber optics.

Absolute testing methods are commonly employed in surface metrology to calibrate the reference surface deviation and obtain the absolute deviation of the surface under test. A simple and reliable data-reduction method of absolute shift-rotation method with rotational and translational measurements is presented here, which relies on the decomposition of the surface deviation into rotationally asymmetric and symmetric components. The rotationally asymmetric surface deviation can be simply obtained by classical N-position averaging method. After that, the two-dimensional problem of estimating the other rotationally symmetric surface deviation can be simplified to a one-dimensional problem, and it can be directly calculated out with pixel-level spatial frequency based on several measurements of different translations in one same direction. Since that no orthogonal polynomials fitting, such as Zernike polynomials, is required in the calculation, the data reduction of the method is simple and rapid. Experimental absolute results of spherical surfaces are given.