Enantioselective Synthesis of SpirothiazolonesviaCooperative Catalysis

Abstract

Cooperative amino‐ and palladium catalysis utilizing heterocyclic systems containing strongly coordinating and adsorptive sulfur atom remains an underdeveloped area. Herein, we describe an enantioselective cyclization of enals with thiazole derivatives catalyzed with the combination of achiral Pd(0) complexes and chiral secondary amines. Chiral spirocyclic thiazolones were produced in yields ranging from 41% to 98% with stereoselectivities (from 5:1 to 12:1 dr, and 95–99% ee). Moreover, the developed strategy allows access to highly substituted chiral cyclopentane derivatives by additional transformations of spirocyclic thiazolones.

Enantioselective Synthesis of Spiro Heterocyclic Compounds Using a Combination of Organocatalysis and Transition‐Metal Catalysis

“…With this regard, we have reported the first enantioselective synthesis of such compounds from tetrahydro‐1 H ‐oxepine thiazole derivatives 21 and enals 2 under synergistic catalysis of Hayashi Jørgensen chiral secondary amine/Pd(0) system (Scheme 11). [65] Following up on our previous successful ring contraction strategy applied on tetrahydro‐1 H ‐oxepine pyrazoles, we anticipated similar reactivity of the seven‐membered ring thiazole derivatives in the presence of a palladium catalyst. Gratifyingly, any disruptive effect of sulfur on the palladium complex was not observed, and the reaction proceeded smoothly with enals 2 .…”

“…[62][63][64] With this regard, we have reported the first enantioselective synthesis of such compounds from tetrahydro-1H-oxepine thiazole derivatives 21 and enals 2 under synergistic catalysis of Hayashi Jørgensen chiral secondary amine/Pd(0) system (Scheme 11). [65] Following up on our previous successful ring contraction strategy applied on tetrahydro-1H-oxepine pyrazoles, we anticipated similar reactivity of the seven-membered…”

Recent progress in asymmetric synergistic catalysis – the judicious combination of selected chiral aminocatalysts with achiral metal catalysts

“…It was found that switching the solvent from ethyl acetate to acetonitrile enhanced the diastereocontrol, and that the Pd catalyst loading could be reduced to 2% without reduction in reaction efficiency or enantioselectivity. 67 …”

“…It was found that switching the solvent from ethyl acetate to acetonitrile enhanced the diastereocontrol, and that the Pd catalyst loading could be reduced to 2% without reduction in reaction efficiency or enantioselectivity. 67 Rios and Veselý then went on to demonstrate that [5,5]-spirobicyclic pyrazolones could also be synthesised in an intermolecular Michael/Conia-ene cascade using synergistic Pd and iminium ion catalysis, with an alkyne-containing monocyclic pyrazolone starting material acting as a ring-opened analogue of the [5,7]-bicycle in their original approach. 68 This transformation only required low loadings of both catalysts to proceed whilst still giving the spiropyrazolone scaffolds 39-42 in impressive ee and with acceptable diastereocontrol.…”

Stereoselective N-heterocyclic-carbene-catalyzed spiroannulation as an access towards spirobenzofuranone-fused cyclohexenones

“…33 Recently, we successfully applied this concept in the stereoselective annulation reaction of 4-nitroisoxazole-derived alkenes. 34 Drawing on our longstanding interest in developing organocatalytic strategies for the construction of spirocyclic compounds, [35][36][37][38][39][40][41] we aimed for a novel stereocontrolled, NHCcatalyzed spiroannulation of electron-deficient alkenes derived from benzofuran-2-one and in situ generated azolium dienolate intermediate (Fig. 1C).…”