Fundamental to the synthesis of enantioenriched chiral molecules is the ability to assign absolute configuration at each stereogenic center, and to determine the enantiomeric excess for each compound. While determination of enantiomeric excess and absolute configuration is often considered routine in many facets of asymmetric synthesis, the same determinations for enantioisotopomers remains a formidable challenge.Here, we report the first highly enantioselective metalcatalyzed synthesis of enantioisotopomers that are chiral by virtue of deuterium substitution along with the first general spectroscopic technique for assignment of the absolute configuration and quantitative determination of the enantiomeric excess of isotopically chiral molecules. Chiral tag rotational spectroscopy uses noncovalent chiral derivatization, which eliminates the possibility of racemization during derivatization, to perform the chiral analysis without the need of reference samples of the enantioisotopomer.

Using data from the Green Bank Telescope (GBT) Observations of TMC-1: Hunting for Aromatic Molecules (GOTHAM) survey, we report the first astronomical detection of the C10H− anion. The astronomical observations also provided the necessary data to refine the spectroscopic parameters of C10H−. From the velocity stacked data and the matched filter response, C10H− is detected at >9σ confidence level at a column density of 4.04 − 2.23 + 10.67 × 10 11 cm−2. A dedicated search for the C10H radical was also conducted toward TMC-1. In this case, the stacked molecular emission of C10H was detected at a ∼3.2σ confidence interval at a column density of 2.02 − 0.82 + 2.68 × 10 11 cm−2. However, as the determined confidence level is currently <5σ, we consider the identification of C10H as tentative. The full GOTHAM data set was also used to better characterize the physical parameters including column density, excitation temperature, line width, and source size for the C4H, C6H, and C8H radicals and their respective anions, and the measured column densities were compared to the predictions from a gas/grain chemical formation model and from a machine learning analysis. Given the measured values, the C10H−/C10H column density ratio is ∼ 2.0 − 1.6 + 5.9 —the highest value measured between an anion and neutral species to date. Such a high ratio is at odds with current theories for interstellar anion chemistry. For the radical species, both models can reproduce the measured abundances found from the survey; however, the machine learning analysis matches the detected anion abundances much better than the gas/grain chemical model, suggesting that the current understanding of the formation chemistry of molecular anions is still highly uncertain.

Fundamental to the synthesis of enantioenriched chiral molecules is the ability to assign absolute configuration at each stereogenic center, and to determine the enantiomeric excess for each compound. While determination of enantiomeric excess and absolute configuration is often considered routine in many facets of asymmetric synthesis, the same determinations for enantioisotopomers remains a formidable challenge. Here, we report the first highly enantioselective metal‐catalyzed synthesis of enantioisotopomers that are chiral by virtue of deuterium substitution along with the first general spectroscopic technique for assignment of the absolute configuration and quantitative determination of the enantiomeric excess of isotopically chiral molecules. Chiral tag rotational spectroscopy uses noncovalent chiral derivatization, which eliminates the possibility of racemization during derivatization, to perform the chiral analysis without the need of reference samples of the enantioisotopomer.

Recent work in drug discovery has shown that selectively deuterated small molecules can improve the safety and efficacy for active pharmaceutical ingredients. The advantages derive from changes in metabolism resulting from the kinetic isotope effect when deuterium is substituted for a hydrogen atom at a structural position where rate limiting C–H bond breaking occurs. This application has pushed the development of precision deuteration strategies in synthetic chemistry that can install deuterium atoms with high regioselectivity and with stereocontrol. Copper-catalyzed alkene transfer hydrodeuteration chemistry has recently been shown to have high stereoselectivity for deuteration at the metabolically important benzyl C–H position. In this case, stereocontrol results in the creation of enantioisotopomersmolecules that are chiral solely by virtue of the deuterium substitutionand chiral analysis techniques are needed to assess the reaction selectivity. It was recently shown that chiral tag molecular rotational resonance (MRR) spectroscopy provides a routine way to measure the enantiomeric excess and establish the absolute configuration of enantioisotopomers. High-throughput implementations of chiral tag MRR spectroscopy are needed to support optimization of the chemical synthesis. A measurement methodology for high-throughput chiral analysis is demonstrated in this work. The high-throughput ee measurements are performed using cavity-enhanced MRR spectroscopy, which reduces measurement times and sample consumption by more than an order-of-magnitude compared to the previous enantioisotopomer analysis using a broadband MRR spectrometer. It is also shown that transitions for monitoring the enantiomers can be selected from a broadband rotational spectrum without the need for spectroscopic analysis. The general applicability of chiral tag MRR spectroscopy is illustrated by performing chiral analysis on six enantioisotopomer reaction products using a single molecule as the tag for chiral discrimination.

The formation of molecules in the interstellar medium (ISM) remains a complex and unresolved question in astrochemistry. A group of molecules of particular interest involves the linkage between a carboxyl and amine group, similar to that of a peptide bond. The detection of molecules containing these peptide-like bonds in the ISM can help elucidate possible formation mechanisms, as well as indicate the level of molecular complexity available within certain regions of the ISM. Two of the simplest molecules containing a peptide-like bond, formamide (NH2CHO) and acetamide (CH3CONH2), have previously been detected toward the star-forming region Sagittarius B2 (Sgr B2). Recently, the interstellar detection of propionamide (C2H5CONH2) was reported toward Sgr B2(N) with Atacama Large Millimeter/submillimeter Array (ALMA) observations at millimeter wavelengths. Yet, this detection has been questioned by others from the same set of ALMA observations as no statistically significant line emission was identified from any uncontaminated transitions. Using the Prebiotic Interstellar Molecule Survey (PRIMOS) observations, we report an additional search for C2H5CONH2 at centimeter wavelengths conducted with the Green Bank Telescope. No spectral signatures of C2H5CONH2 were detected. An upper limit for C2H5CONH2 at centimeter wavelengths was determined to be N T < 1.8 × 1014 cm−2 and an upper limit to the C2H5CONH2/CH3CONH2 ratio is found to be <2.34. This work again questions the initial detection of C2H5CONH2 and indicates that more complex peptide-like structures may have difficulty forming in the ISM or are below the detection limits of current astronomical facilities. Additional structurally related species are provided to aid in future laboratory and astronomical searches.