A copper-catalyzed alkene transfer hydrodeuteration reaction that selectively incorporates one hydrogen and one deuterium atom across an aryl alkene is described. The transfer hydrodeuteration protocol is selective across a variety of internal and terminal alkenes and is also demonstrated on an alkene-containing complex natural product analog. Beyond using 1H, 2H, and 13C NMR analysis to measure reaction selectivity, six transfer hydrodeuteration products were analyzed by molecular rotational resonance (MRR) spectroscopy. The application of MRR spectroscopy to the analysis of isotopic impurities in deuteration chemistry is further explored through a measurement methodology that is compatible with high-throughput sample analysis. In the first step, the MRR spectroscopy signatures of all isotopic variants accessible in the reaction chemistry are analyzed using a broadband chirped-pulse Fourier transform microwave spectrometer. With the signatures in hand, measurement scripts are created to quantitatively analyze the sample composition using a commercial cavity enhanced MRR spectrometer. The sample consumption is below 10 mg with analysis times on the order of 10 min using this instrumentboth representing order-of-magnitude reduction compared to broadband MRR spectroscopy. To date, these measurements represent the most precise spectroscopic determination of selectivity in a transfer hydrodeuteration reaction and confirm that product regioselectivity ratios of >140:1 are achievable under this mild protocol.

Chiral tag rotational spectroscopy can be used for quantitative determination of the ratio of the two enantiomers of a chiral molecule. The strategy for chiral tag rotational spectroscopy is to convert the enantiomers of the analyte into diastereomers through non-covalent attachment of a small, chiral tag molecule. The analyte enantiomer ratio, which is used to determine the enantiomeric excess (EE), is determined by comparing the transition intensities of rotational transitions for the homochiral and heterochiral complexes when both a racemic and enantiopure tag sample is used. A calibration curve for EE determination of 3-methylcyclohexanone tagged with 3-butyn-2-ol will be presented. The role that intensity fluctuations in back-to-back measurements of the rotational spectra of the chiral tag complexes play in determining the EE measurement accuracy will be described. In applications to pharmaceutical chemistry the main need is the ability make quantitative EE determinations in the high enantiopurity limit of the analyte. This requirement poses challenges for chiral tag rotational spectroscopy from both the measurement sensitivity and the availability of high enantiopurity tag samples. Two analysis methods for high EE measurements will be discussed. In one case, the enantioimpurity detection limit is decreased by the co-adding of multiple rotational transitions of the homochiral and heterochiral tag complex. The second strategy uses a lower enantioimpurity tag to speed the EE determination of high enantioimpurity samples. In this case, the ability to accurately determine the tag EE is crucial and the functional dependence of EE measurement precision in chiral tag rotational spectroscopy provides the limit on measurement accuracy that can be achieved.

The rotational spectra of formamide and water mixtures have been recorded in the 2-8 GHz frequency region using a chirped-pulse Fourier transform microwave spectrometer. Samples of 14 N and 15 N of formamide have been used in this work. The 14 N quadrupole coupling hyperfine structure is a tool to identify the structure of the observed complexes; the 15 N isotopologue is of great help to explore the conformational panorama of complexes with several formamide units. In this work we present the detection and characterization of complexes of formamide and formamide-water, as F 3 and F-(H 2 O) 4 , which show interesting structural features.

Microwave three-wave mixing, which was first demonstrated in 2013 by Patterson, Schnell, and Doyle [1, 2] and described eloquently in NMR terminology by Grabow [3], has shown its applicability in differentiating enantiomers as well as quantifying enantiomeric excess for chiral molecules in the gas phase. Further theoretical development of rotational three-wave mixing has been presented by Lehmann. [4] However, this technique's capability has not been fully explored and the sensitivity of different measurement implementations have not been evaluated. This work presents a simplified measurement scheme in which two high-frequency (4-12 GHz) transitions of a chiral gas sample are excited with orthogonally polarized pulses of light utilizing a dual-polarization wave horn antenna. The low-frequency chiral emission signal (600-2000 MHz) is detected at the mutually orthogonal polarization and perpendicular to the excitation pulse propagation direction. In this measurement scheme, the detection electronics and digitization rate required are simplified and reduced. Propylene oxide, alanine, and menthone introduced in a pulsed-jet expansion are used to demonstrate the low-frequency detection method and its comparison to traditional three-wave mixing schemes where detection of a high-frequency signal is employed. Additionally, some other nuances of the measurement technique have been explored including the angular dependence of the chiral emission and the importance of the polarization in the excitation and detection horn antennae. [1] D.

In the search for life elsewhere in our solar system, the development of tools to measure key biomarkers is a critical area of research. One biomarker found in nature on Earth is homochirality, the predominant utilization of one handedness (enantiomer) of a biological chiral molecule over another. For example, the biological prevalence of left-handed amino acids and right-handed sugars. Developing compact, low-power instruments to detect important chiral biomolecules and measure their enantiomeric excess with high sensitivity is a challenge. We are developing and testing the three-wave mixing technique for rotational spectroscopy which was demonstrated in 2013 [1, 2] to meet these challenges. The instrument can perform sensitive detection when operated as a traditional rotational spectrometer and subsequently perform chiral measurements (absolute configuration and the enantiomeric excess) by three-wave mixing without the need for derivatizing agents or prior separation of mixtures. We use W-band (70-90 GHz) and centimeter-wave (2-8 GHz) excitation sources to excite a small amount (3-5 mTorr) of gas phase chiral molecules and generate a chiral free-induction decay in the W-band. Propylene oxide is used as the test-case molecule and chiral emission is detected for its R-and S-forms with 180 degrees phase shift allowing us to differentiate the two enantiomers. The use of millimeter-wave technology in the instrument design provides a path to future reductions in size, weight, and power of the ChiralSpec instrument that make it compatible with the stringent requirements of space missions. [1] D.