Enantio‐ and Diastereoselective Synthesis of exo‐Peroxyacetals: An Organocatalyzed Peroxyhemiacetalization/oxa‐Michael Addition Cascade

Abstract

An unprecedented enantioselective peroxyhemiacetalization/oxa-Michael addition cascade of ortho-formyl homochalcones has been developed using cinchona-alkaloid-based chiral bifunctional organocatalysts to provide cis-configured exo-peroxyacetals, a new class of organic peroxide, in good yields with excellent enantio- and diastereoselectivities. The resulting cis-configured exo-peroxyacetals were converted into the corresponding trans-configured peroxyacetals without affecting the enantioselectivity. Furthermore, the displacement of the peroxide moiety of exo-peroxyacetals with various nucleophiles has been demonstrated to afford 1,3-disubstituted isochromans with high diastereoselectivities and excellent enantioselectivities.

Squaramide Catalyzed Asymmetric Synthesis of Five‐ and Six‐Membered Rings

“…Squaramide catalyzed peroxyhemiacetalization/oxa-Michael cascade process was applied on ortho-formyl homochalcones 136 leading to the access of cis-stereoisomer of exo-peroxyacetal 139 containing isochromans. [54] Initial reversible nucleophilic addition of peroxide 137 to the aldehyde functionality of 136 forms peroxyhemiacetal intermediate which facilitates stereoselective intramolecular oxa-Michael addition to the enone moiety through favoured transition state 9. Different peroxide sources were used and the reaction was well compatible in the presence of both electron donating and electron withdrawing substituents on central aromatic ring as well as different aryl/ heteroaryl/alkyl substituents of the ketone functionality.…”

“…Squaramide catalyzed peroxyhemiacetalization/oxa‐Michael cascade process was applied on ortho ‐formyl homochalcones 136 leading to the access of cis ‐stereoisomer of exo ‐peroxyacetal 139 containing isochromans [54] . Initial reversible nucleophilic addition of peroxide 137 to the aldehyde functionality of 136 forms peroxyhemiacetal intermediate which facilitates stereoselective intramolecular oxa‐Michael addition to the enone moiety through favoured transition state 9 .…”

Enantio‐ and Diastereoselective, Lewis Base Catalyzed, Cascade Sulfenoacetalization of Alkenyl Aldehydes

“…Although substantial effort has been devoted to the synthesis of monosubstituted isochroman derivatives in both racemic and enantiomerically enriched fashion, methods to prepare 1,3‐disubstituted analogues stereoselectively are rare. To the best of our knowledge, there are only two reports that disclose access to enantioenriched 1,3‐disubstituted isochromans from the groups of White and Ghorai …”

Racemic hemiacetals as oxygen-centered pronucleophiles triggering cascade 1,4-addition/Michael reaction through dynamic kinetic resolution under iminium catalysis. Development and mechanistic insights

“…Finally, and quite recently, the catalytic and enantioselective intramolecular conjugate addition of peroxyhemiacetals to dienones has also been described. 25 Despite these advances, the conjugate addition of hemiacetal entities to electron-poor alkenes in an intermolecular fashion to initiate a cascade reaction is unprecedented in the chemical literature.…”