Bifunctional catalysis in the stereocontrolled synthesis of tetrahydro-1,2-oxazines.

This study demonstrates that the annulation of a tetrahydro-1,2-oxazine ring can be realized via bifunctional catalysis, employing nitroolefins and a recently introduced group of aminooxylating reagents as starting materials. The developed cascade reactivity proceeds in a sequence aza-Michael-Michael reaction. The target products, bearing three contiguous stereocenters, have been obtained with high yields (up to 97%) and excellent stereocontrol (>20 : 1 dr, up to 99.5 : 0.5 er).

Synthesis of cyclopent-1-enecarbonitriles via a tandem Giese/HWE reaction initiated by visible light.

In the manuscript, a novel method for the preparation of cyclopent-1-enecarbonitriles via tandem Giese/HWE reaction initiated by visible light in the presence of fac-Ir(ppy)3 as a photocatyst has been described. The cascade reactivity combining radical and polar processes has proven applicable for a wide range of N-(acyloxy)phthalimides (which serve as precursors of the corresponding radicals) as well as diethyl (E)-(1-cyano-2-arylvinyl)phosphonates. The key parameters responsible for the success of the described strategy are: visible light, 1 mol% of photoredox catalyst, base, anhydrous solvent and inert atmosphere. The reaction results in new sp3-sp3 and sp2-sp2 carbon-carbon bonds formation under mild conditions.

Visible-light synthesis of 4-substituted-chroman-2-ones and 2-substituted-chroman-4-ones via doubly decarboxylative Giese reaction.

Doubly decarboxylative, photoredox synthesis of 4-substituted-chroman-2-ones and 2-substituted-chroman-4-ones is described. The reaction involves two independent decarboxylation processes: the first one initiating the cycle and the second completing the process. Visible light, photoredox catalyst, base, anhydrous solvent and inert atmosphere constitute the key parameters for the success of the developed transformation. The protocol proved applicable for coumarin-3-carboxylic acids and chromone-3-carboxylic acids as well as N-(acyloxy)phthalimide which served as precursors of the corresponding alkyl radicals.

Site-Selective and Enantioselective α,ß,γ-Functionalization of 5-Alkylidenefuran-2(5 H)-ones: A Route to Polycyclic γ-Lactones.

A new strategy for a direct α,ß,γ-functionalization of the γ-lactone framework in the corresponding 5-alkylidenefuran-2(5 H)-ones is reported. The developed approach is based on a stereocontrolled cascade reaction with 2-mercaptocarbonyl compounds proceeding in a sequence of thia-Michael/aldol/oxa-Michael reactions. Such a synthetic strategy allows for a construction of a unique polycyclic architecture containing γ-lactone, tetrahydrofuran, and tetrahydrothiophene ring systems. Excellent enantioselectivities and diastereoselectivities have been obtained in the presence of bifunctional catalyst derived from cinchona alkaloids.

d0a3 Synthon Equivalents for the Stereocontrolled Synthesis of Functionalized 1,4-Amino Alcohol Precursors.

This study demonstrates the design, synthesis, and first application of novel aminooxylating reagents that serve as a useful d0a3 synthon equivalents for organic synthesis. It has been demonstrated that their reaction with α,ß-unsaturated aldehydes performed under aminocatalytic conditions provides a straightforward access to polysubstituted tetrahydro-1,2-oxazine derivatives, direct precursors of functionalized 1,4-amino alcohols. Target tetrahydro-1,2-oxazine derivatives have been obtained with high yields (up to 89%) and with excellent stereocontrol (up to >20:1 dr, > 99.5:0.5 er). Furthermore, the synthetic usefulness of tetrahydro-1,2-oxazines obtained has been demonstrated in various selective transformations.