Chiral N‐Acylhydrazones: Versatile Imino Acceptors for Asymmetric Amine Synthesis

Abstract

Addition to C=N bonds with acyclic stereocontrol offers excellent potential for development of new carbon-carbon bond construction approaches to chiral amines. This review features the design and implementation of novel chiral Nacylhydrazones as versatile imino acceptors for addition of radicals and nucleophiles. The initial design was inspired by the goal of asymmetric radical addition to chiral C=N radical acceptors. The chiral N-acylhydrazones are prepared from commercially available materials by amination of 4-alkyl-2-oxazolidinones with NH 2 + equivalents to afford N-(amino) oxazolidinones, followed by condensation with aldehydes or ketones. These chiral N-acylhydrazones undergo addition reactions with various partners, including radicals, allylsilanes, allylindiums, silyl enol ethers, and hydride donors. The MICROREVIEWS: This feature introduces the readers to the authors' research through a concise overview of the selected topic. Reference to important work from others in the field is included.

Asymmetric Methods for Radical Addition to Imino Compounds

“…We chose to develop a new type of chiral hydrazone, tailored for use in free radical addition reactions. Toward this end, we conceived a nitrogen-linked chiral auxiliary approach incorporating Lewis acid (LA) activation [14] and stereocontrol enhancement through restriction of rotamer populations [15]. Our approach is distinguished from prior work (Figure 2.3) by combining both activation and stereocontrol into one N-linked substituent, freeing the imino carbon substituent R 1 from any controlling role in the process and thereby enabling greater versatility.…”

“…Several other halides, including methyl iodide and difunctional halides, were also effective (Table 2.6), with the exception of 2-chloroethyl addition, which gave low yield presumably due to radical fragmentation. Ethyl radical addition to nine additional hydrazones occurred in good yields (entries [12][13][14][15][16][17][18][19][20]. These adducts are epimeric to those derived from hydrazone 8a with respect to the new stereogenic center, as a result of simply changing the roles of the aldehyde and iodide precursors.…”

Synthesis, biological evaluation and molecular docking studies of N-acylheteroaryl hydrazone derivatives as antioxidant and anti-inflammatory agents

“…N-acylhydrazones (NAHs) are stable imine equivalents which provides a suitable template for the chelation of Lewis acids [16], and are expanded to the chemical and pharmaceutical industries [17]. The pyrazole ring is a predominant pharmacophore in many drugs such as celecoxib, pyrazofurin and, notably, rimonabant, having a pyrazole core with N-acylhydrazone.…”

Nucleophilic Addition to N‐Phosphinylimines by Rare‐Earth‐Metal Triflate/Trifluoroacetic Anhydride Activation

“…[1] Methodologies include allylation of imines with allyl boronates, [2] allyl stannanes, [3] and chiral silanes. [4] Recently, N-diphenylphosphinylimines have emerged as useful acylimine equivalents in a variety of asymmetric C À C bond-forming reactions, [5] and we therefore considered their utility in asymmetric crotylations.…”