Sequential Multicomponent Strategy for the Diastereoselective Synthesis of Densely Functionalized Spirooxindole-Fused Thiazolidines

Abstract

We developed two Ugi-type three-component reactions of spirooxindole-fused 3-thiazolines, isocyanides, and either carboxylic acids or trimethylsilyl azide, to give highly functionalized spirooxindole-fused thiazolidines. Two diverse libraries were generated using practical and robust procedures affording the products in typically good yields. The obtained thiazolidines proved to be suitable substrates for further transformations. Notably, both the Ugi-Joullié and the azido-Ugi reactions resulted highly diastereoselective, affording predominantly the trans-configured products, as confirmed by X-ray crystallographic analysis.

Cyclic Imines in Ugi and Ugi-Type Reactions

“…Compounds 270 were diastereoselectively prepared from the cyclic imines 269, isocyanides 5, and TMS-N 3 260 in 1,1,1,3,3,3-hexafluoro-2propanol (HFIP) as a solvent (Scheme 77). 197,198 In 49 Miscellaneous. Voskressensky et al described the synthesis of benzazocine-tetrazoles 280 via AU-3CR, followed by alkyne-induced ring-expansion reactions (Scheme 81).…”

“…In this context, various scaffolds such as benzodiazepines, lactams, indazoles, and piperazine drugs associated with these skeletons that are retrieved from Drug Bank are summarized in Table . Additionally, in the Ugi reactions including cyclic imines, α-acidic isocyanides, or azides can be replaced with normal isocyanides or acids to synthesize N -heterocycles baring oxazoles or tetrazoles, respectively, − which are received a great importance from the synthetical and biological points of view.…”

One step access to oxindole-based β-lactams through Ugi four-center three-component reaction

“…Working in MeOH (entry 3), the same reaction afforded the desired β-lactam 4a in low yield. When we switched to the more acidic trifluoroethanol (TFE), following our recent achievements in different Ugi-type reactions, 10 both the reaction rate and yield definitely increased (entries 4–6). With satisfactory conditions in hand, a variety of substituted isatins 1a–j were next explored to investigate the carbonyl component scope of the Ugi-4C-3CR ( Scheme 1 ).…”

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

“…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.…”