Direct Observation and Analysis of the Halo-Amino-Nitro Alkane Functional Group

Fluorine-induced diastereodivergence discovered in an equally rare enantioselective syn-aza-Henry reaction

“… 49–51 As solutions to the stereocontrolled aza-Henry reaction increase, so will their impact on concise preparations of small molecules in drug development, and innovative entry to peptides based solely on catalytic, enantioselective methods. 52 …”

Umpolung strategies for the functionalization of peptides and proteins

“…Possible intermediates and the energy landscape of this pathway were probed using density functional theory calculations. 20,21 The aerobic pathway instead involves competitive formation of a peroxide intermediate (13) via addition of O 2 aer fragmentation of the C-NO 2 bond (Fig. 3B).…”

“…3B ). 20 It was initially postulated that the tetrahedral intermediate is converted to the amide product by hydrolysis, however, various 18 O-labeling experiments used to identify the origin of the amide oxygen highlighted the possibility of both anaerobic and aerobic pathways to the amide.…”

Unearthing the Mechanism of Umpolung Amide Synthesis

“…This tetrahedral intermediate (TI) can collapse to give the desired amide products (Figure 1B). Although Johnston and co-workers conducted some control experiments to shed light on the mechanistic picture, 9 there is still considerable uncertainty because the putative TI is too unstable to be isolated for a detailed study.…”

“…In this issue of Chem, Johnston and coworkers report a systematic mechanistic study of UmAS. 9 After extensive experimentations, Johnston's team realized a viable approach to preparing the structural analogs of TI by using azodicarboxylates instead of N-halo amines. The resulting metastable tetrahedral intermediates (TI 0 ) derived from a-fluoro nitroalkanes were sufficiently stable to be isolated for a series of mechanistic studies (Figure 1C).…”