Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy. Issue 33 (8th July 2022)

• Record Type: Journal Article
• Authors: Mills, Mitchell D.; Sonstrom, Reilly E.; Vang, Zoua Pa; Neill, Justin L.; Scolati, Haley N.; West, Channing T.; Pate, Brooks H.; Clark, Joseph R.
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 33(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-08
• Subjects: Chirality -- Copper -- Enantioisotopomers -- Rotational Spectroscopy -- Transfer Hydrodeuteration; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202207275
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : The validation and application of chiral tagging in molecular rotational resonance spectroscopy is reported for the assignment of absolute configuration and direct determination of enantiomeric excess for enantioisotopomers. Furthermore, a new catalytic, highly enantioselective, and scalable reaction is described for the direct synthesis of enantioisotopomers from styrene substrates.