Highly diastereoselective entry to chiral oxindole-based β-amino boronic acids and spiro derivatives

Abstract

We here describe the first Cu-catalysed, diastereoselective 1,2-addition of 1,1-diborylmethane to chiral ketimines for the synthesis of quaternary stereocenters and spiro compounds. The method provides easy access to a range...

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

“…From the reaction run under the optimized conditions (Table 1, entry 12) followed by flash chromatography, the unprecedented bisoxindole 2a was fully characterized by high-resolution mass spectrometry and by one-and two-dimensional NMR analysis. In particular, from HSQC, HMBC and COSY experiments all single frequencies could be safely assigned in the 1 H and 13 C NMR spectra, allowing the complete spin system reconstruction for both the oxindole-based units. Furthermore, from NOESY experiment, the unique anti disposition of the two t-Bu-SO-NH substituents along the C3-C3' bond could be assessed, thus demonstrating the complete diastereoselectivity of the reaction (see Supporting Information File 1).…”

“…Going on with our interest in the synthesis of 3,3-disubstituted oxindoles [7][8][9][10][11] and also of aminoboronic acids [12], we recently exploited a molecular hybridization strategy to synthesize chiral oxindole-based β-aminoboronic acids and spiro derivatives [13]. Apart from our work and a quite recent report describing a useful Cu-catalyzed enantioselective intramolecular transformation [14], the insertion of a boron atom into chiral oxindoles is scarcely reported.…”

Exploiting Enantiopure β‐Amino Boronic Acids in Isocyanide‐Based Multicomponent Reactions

“…Going on with our diversity-oriented chemistry programs around chiral β-amino boronic acids, [18] which are more stable and, at the same time, less exploited with respect to their αhomologues, [19] we became interested in developing efficient methods to assemble boron-containing peptidomimetics, with increased product scope, reduced number of steps and improved atom economy. Relying on our experience in the field, [20] we planned to take advantage from multicomponent reactions (MCRs), in particular isocyanide-involving ones (IMCRs), [21] with the aim of demonstrating their suitability with β-amino boronic acids components.…”

Enantiopure β-isocyano-boronic esters: synthesis and exploitation in isocyanide-based multicomponent reactions

“…Besides the unpleasant odor, the relatively high price and the sensitivity in acidic medium, the main drawback of isocyanide-containing compounds is their difficult functionalization, which also limits the functional groups variability in peptidomimetic, heterocyclic and natural products targets. Starting from this consideration and going on with our diversity-oriented synthetic chemistry programs, focused on both IMCRs [16][17][18][19][20][21][22][23][24] and boron-containing compounds [25,26], we considered aliphatic isocyano boronic acids as attractive components, able to greatly increase IMCRs products scope, as better well-known boryl aldehydes [27,28] and amino boronic acids [29] already do. Boron-containing peptidomimetics are currently highly relevant in drug discovery, mainly due to the ability of amino boronic acids to act as amino acid bioisosteres and reversible covalent inhibitors [30].…”