Semi-Reduction of Allenes to Access Deuterated Allylic Isotopomers, Isotopologs and Enantioisotopomers.

Selectively deuterated compounds represent high value synthetic targets with applications across many scientific disciplines. Despite their importance, reactions that enable access to products precisely deuterated at an allylic position with complete control over the degree of deuteration are extremely rare. In fact, the high enantiopurity synthesis of enantioisotopomers owing their chirality solely to hydrogen isotopes at an allylic position has remained elusive to date. Herein, we report a modular Cu-catalyzed semi-reductive deuteration of allenes to access a broad scope of small molecules, drug analogs, and natural product analogs precisely deuterated at allylic positions. The semi-reduction strategy has been applied to access a range of precisely labeled d1-, d2-, d3-, d5-, and d7-isotopologs. In this work, we disclose the first high enantiopurity synthesis of allylic-d1 enantioisotopomers, along with a highly accurate and precise analysis for enantiomeric excess (EE) determination and assignment of absolute configuration (AC) using molecular rotational resonance (MRR) spectroscopy.