Given the importance of amines in a large number of biologically active natural products, active pharmaceutical ingredients, agrochemicals, and functional materials, the development of efficient C-N bond-forming methods with wide substrate scope continues to be at the frontier of research in synthetic organic chemistry. Here, we present a general and fundamentally new synthetic approach for the direct, transition-metal-free preparation of symmetrical and unsymmetrical diaryl-, arylalkyl-, and dialkylamines that relies on the facile single or double addition of readily available C-nucleophiles to the nitrogen atom of bench-stable electrophilic aminating agents. Practical single and double polarity reversal (i.e., umpolung) of the nitrogen atom is achieved using sterically and electronically tunable ketomalonate-derived imines and oximes. Overall, this novel approach represents an operationally simple, scalable, and environmentally friendly alternative to transition-metal-catalyzed C-N cross-coupling methods that are currently used to access structurally diverse secondary amines.

Pages 11193−11194. In our follow-up studies exploring the reactivity of diisopropyl iminomalonates with hard C-nucleophiles (e.g., Grignard reagents, alkyl-and aryllithiums), we also attempted the addition of an acetophenone-derived lithium enolate (i.e., a soft C-nucleophile). We initially assigned a 6membered lactone core for compound 68 based on routine NMR spectra; however, additional NMR studies strongly pointed to the presence of a 5-membered lactone scaffold (Figure 7A; panels B−D in the originally published figure are unchanged). As a result, we concluded that the enolate selectively added to the carbon atom of the iminomalonate CN moiety. This switch of chemoselectivity (i.e., predominant N-attack versus exclusive C-attack of the iminomalonate CN bond) appears to depend on the nature of the C-nucleophile (i.e., hard vs soft). Based on this new insight, we think it is reasonable to propose that during aziridine formation the α-haloester (62)derived enolate first performs a selective C-attack of the CN moiety to afford intermediate 63.The original conclusions of the Article are unaffected by the structural revision of compound 68. We deeply regret this error in the initial structural assignment.

Herein, we present a general synthetic strategy for the preparation of 3-, 4-, 5-, and 6-membered heterocyclic unnatural amino acid derivatives by exploiting facile Mannich-type reactions between readily available N-alkyl-and N-arylsubstituted diisopropyl iminomalonates and a wide range of soft anionic C-nucleophiles without using any catalyst or additive. Fully substituted aziridines were obtained in a single step when enolates of α-bromo esters were employed as nucleophiles. Enantiomerically enriched azetidines, γ-lactones, and tetrahydroquinolines were obtained via a two-step catalytic asymmetric reduction and cyclization sequence from ketone enolate-derived adducts. Finally, highly substituted γ-lactams were prepared in one pot from adducts obtained using acetonitrile-derived carbanions. Overall, this work clearly demonstrates the utility of iminomalonates as highly versatile building blocks for the practical and scalable synthesis of structurally diverse heterocycles.