N,N‐Diacylaminals as Emerging Tools in Synthesis: From Peptidomimetics to Asymmetric Catalysis

Abstract

N,N-Diacylaminals are flexible molecular scaffolds that have commonly been utilized as amide surrogates in peptidomimetics. The singularities of this motif as an N-acyl imine equivalenta nd as hydrogen-bond donor have recently openedn ew synthetic opportunities,e specially in the field of asymmetric catalysis. This concept article highlightst his diverse synthetic potentiala nd provides the elements necessary for furtherd evelopments.

Iodine‐mediated expedient synthesis of sulfur–nitrogen‐containing heteroaminals under acidic condition

“…while peptide and ionic liquid mediated‐synthesis of acyclic aminals is also known in the literature [11b,c]. Importantly, acyclic aminals can be used as a chiral auxiliary for the asymmetric synthesis of biologically active ingredients [12].…”

Synthesis of β-Hydroxy α-Amino Acids Through Brønsted Base-Catalyzed syn-Selective Direct Aldol Reaction of Schiff Bases of Glycine o-Nitroanilide

“…To improve stereocontrol through the incorporation of additional H-bond donors 24 during the reaction, we focused on ureidopeptide-derived Brønsted bases previously developed by us. 25 It was gratifying to observe that the new variants C5 , C6 , and C7 provided 5a with diastereomeric ratios greater than 98:2 and in each case with good enantioselectivity (entries 5, 6, and 8). Further improvement was achieved using catalyst C6 and carrying out the reaction at 0 °C, and 5a was obtained in 77% isolated yield and 94% ee (entry 7).…”

“…Using the parent ureas, C3 and C4 , much better diastereocontrol was achieved (entries 3 and 4), but the enantioselectivity of product 5a was still poor. To improve stereocontrol through the incorporation of additional H-bond donors during the reaction, we focused on ureidopeptide-derived Brønsted bases previously developed by us . It was gratifying to observe that the new variants C5 , C6 , and C7 provided 5a with diastereomeric ratios greater than 98:2 and in each case with good enantioselectivity (entries 5, 6, and 8).…”

Accessing Chiral Pyrrolodiketopiperazines under Organocatalytic Conditions

“…In order to address the indispensable control over the stereoselectivity, we relied on the proven ability of chiral Brønsted bases linked to hydrogen bond donors to efficiently perform under proton transfer conditions . Among other possibilities, ureidoaminal-derived Brønsted bases, previously reported by our group, were tested in the Michael reaction of 1a with 2a (Scheme ). These catalysts are readily available by condensation of α-amino acid-derived isocyanates with chiral amines, a simple protocol that provides an easy evaluation of the impact of the catalyst structure in the reaction efficiency.…”