Organocatalytic Desymmetric Spirocyclization of Enone-Tethered 2,5-Cyclohexadienone with Isoxazolines to Access Enantioenriched Spiro-Fused Scaffolds.

Enantioselective desymmetric spirocyclization is a powerful tool for concisely generating intricate 3D molecular architectures from readily accessible substrates. Herein, we report an organocatalytic desymmetric spirocyclization of enone-tethered 2,5-cyclohexadienone with 3-arylisoxazol-5(4)-one to access enantioenriched spiro-fused scaffolds featuring four consecutive stereogenic centers in high yields and excellent diastereo- and enantioselectivities. This protocol could proceed smoothly under parts per million-level organocatalyst loading.

Organocatalytic Desymmetric Double Aza-Michael Addition Cascade: Enantioselective Synthesis of Fused Morpholines.

Double aza-Michael addition (DAM) has become an emerging strategy for the construction of two carbon-nitrogen bonds in a single step, which can significantly simplify the synthesis of N-heterocycles. Hitherto, their asymmetric catalytic genre remains unattempted. Herein, we describe the judicious design of an organocatalytic enantioselective desymmetric double aza-Michael addition cascade to access a series of functionalized fused morpholines with excellent yields and diastereo- and enantioselectivities.

An Organocatalytic Highly Enantioselective Stereospecific Synthesis of 1,1-Disubstituted-1,3-Dihydroisobenzofurans.

Herein, we disclosed the asymmetric construction of an oxa-quaternary stereocenter via an intramolecular oxa-Michael (IOM) reaction in β-substituted ortho-hydroxymethyl chalcone by the formation of 1,1-disubstituted-1,3-dihydroisobenzofuran using cinchona alkaloid-based chiral amino-squaramide catalyst. Both the (E- and Z)-β-substituted ortho-hydroxymethyl chalcone provide (S)- and (R)-enantiomers of the 1,1-disubstituted-1,3-dihydroisobenzofuran with excellent stereospecificity. In general, excellent yields (up to 95 %) and enantioselectivity (up to 98 % ee) were obtained.

Enantio- and Diastereoselective Cu(II)-Catalyzed Conjugate Borylation/Michael Addition Cascade: Synthesis of Spiroindane Boronates.

We report a Cu(II)-(,)-Pr-FOXAP-catalyzed borylative Michael/Michael addition cascade cyclization of unsymmetrical dienone for the synthesis of highly substituted and functionalized all-carbon spiroindane boronates under mild conditions. A series of optically active spiroindanes bearing boronic ester were obtained with excellent yields and good to excellent enantioselectivities (≤97% ee) and diastereoselectivities (up to >20:1 dr). In addition, scale-up synthesis of this method and synthetic transformations of spiroindane boronates are also illustrated.

Chiral Squaramide Catalyzed Asymmetric Spiroketalization toward Aromatic [6,5] Spiroketals.

Herein is disclosed an efficient enantio- and diastereoselective spiroketalization of aromatic ketone tethered to -homoformyl and enone moiety via enol formation using quinine derived squaramide organocatalyst to access aromatic [6,5] spiroketals with complete atom economy. Furthermore, aromatic spiroketals undergo Brønsted acid catalyzed Piancatelli type rearrangement to provide dihydronaphtho[1,2-]furans with retention of the enantioselectivities.