Regio-, Enantio-Controlled Cascade Oxa-Michael Addition of Hydroxyl Amine: Synthesis of Dihydro-1,2-Oxazines.

Herein, we disclose a cinchona-alkaloid-based squaramide-catalyzed intermolecular oxa-Michael cascade addition cyclization of -protected hydroxyl amine to formyl-tethered Michael acceptors toward the synthesis of enantioenriched 1,2-oxazine scaffolds. Generally, good yield (up to 78%), good to excellent enantiomeric ratio (up to 98:2 er), and excellent regioselectivity (>19:1) were observed. Furthermore, the scalability of this methodology and a successful demonstration of postsynthetic transformations have been accomplished.

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.

Hydrazine Hydrate in Asymmetric Synthesis: A Bifunctional Squaramide Catalytic Approach toward Fused Pyrazolines.

A unified strategy has been developed to utilize hydrazine hydrate in asymmetric organic synthesis by overcoming the rapid background reaction with dienone. The H-bond donor ability of the cinchona-alkaloid-derived squaramide catalyst unlocks this previously deemed infeasibility. The dissymmetric hydrazine addition to symmetrical dienones tolerates various substitutions, resulting in the formation of optically pure fused pyrazoline derivatives under mild reaction conditions.