Internal Lewis acid assisted ureas: tunable hydrogen bond donor catalysts

Abstract

The strategic incorporation of internal Lewis acids onto urea scaffolds gives rise to a family of tunable hydrogen bond donor catalysts. The nature of the Lewis acid and associated ligands affects the urea polarization, acidity, and activity in reactions of nitrocyclopropane carboxylates and nitrodiazoesters.

Discovery of a Highly Selective PLD2 Inhibitor (ML395): A New Probe with Improved Physiochemical Properties and Broad‐Spectrum Antiviral Activity against Influenza Strains

“…20 Significant enhancements in urea acidity were observed upon the installation of boron and palladium21 into the urea catalyst scaffold. For example, the p K a (DMSO) of difluoroboronate urea 36 (Figure 5) is 7.5,20a whereas conventional urea 39 has a p K a (DMSO) of 13.86 8. Fine‐tuning of the urea p K a can be achieved by manipulation of ligands on the Lewis acid.…”

“…Fine‐tuning of the urea p K a can be achieved by manipulation of ligands on the Lewis acid. For instance, boronate urea pinacol ester 40 [p K a (DMSO) = 9.5] was somewhat less acidic than that of difluoroboronate urea 36 20a…”

Ring Opening of Donor–Acceptor Cyclopropanes with N-Nucleo­philes

“…. 82,83 The activation pathway for cyclopropanes 50 involves coordination of urea 54 with the nitro group of the cyclopropane (Scheme 24). The presence of a difluoroboryl substituent at the ortho site in the aryl group increased the efficiency of the reaction by 20%, which was ascribed to an increase in the acidity of the hydrogen atoms in the amide group, owing to the coordination of boron with the oxygen atom in the carbonyl group in 54.…”

Conjugate‐Base‐Stabilized Brønsted Acids as Asymmetric Catalysts: Enantioselective Povarov Reactions with Secondary Aromatic Amines

“…[11][12][13] Upon substrate protonation, the conjugate base associates with the anion recognition site, [14] thus resulting in the formation of a substrate/catalyst ion pair of type I. Alternatively, the catalyst could facilitate the condensation of two different substrates to result in an ion pair of type II. While the anion may still interact with the substrate through hydrogen bonding in the type I ion pair, [15] hydrogen bonding between the ions should be reduced markedly in the type II ion pair, thus resulting in strict ion pairing.…”

“…Electronically diverse aromatic aldehydes with different substitution patterns provided the corresponding tetrahydroquinoline products in generally good yields and enantioselectivities (entries 5-12). Gratifyingly, aliphatic aldehydes were also viable substrates, affording products with excellent ee values (entries [13][14][15][16][17][18]. The scope of the Povarov reaction with regard to the amine was also explored (Table 3).…”