Catalytic Asymmetric N‐Alkylation of Indoles and Carbazoles through 1,6‐Conjugate Addition of Aza‐para‐quinone Methides

Catalytic asymmetric N‐alkylation of indoles and carbazoles represents a family of important but underdeveloped reactions. Herein, we describe a new organocatalytic strategy in which in situ generated aza‐para ‐quinone methides are employed as the alkylating reagent. With the proper choice of a chiral phosphoric acid and an N‐protective group, the intermolecular C−N bond formation with various indole and carbazole nucleophiles proceeded efficiently under mild conditions with excellent enantioselectivity and functional‐group compatibility. Control experiments and kinetic studies provided important insight into the reaction mechanism.     

Organocatalytic,Enantioselective Synthesis of Cyclohexadienone Containing Hindered Spirocyclic Ethers through an Oxidative Dearomatization/Oxa‐Michael Addition Sequence

An unprecedented enantioselective oxa‐Michael reaction of α‐tertiary alcohols using cinchona‐alkaloid‐based chiral bifunctional squaramide catalysts is reported. An oxidative dearomatization of phenol followed by an enantioselective oxa‐Michael addition sequence provided a broad array of chiral sterically hindered tetrahydrofurans and tetrahydropyrans attached to a cyclohexadienone moiety in spiro fashion. In general, good yields and excellent enantioselectivities (up to 99 %) were observed. The chiral oxo‐cycles obtained have easily been transformed into chromans without disturbing the enantioselectivity.     

Brønsted Base Catalyzed One‐Pot Synthesis of Stereodefined Six‐Member Carbocycles Featuring Transient Trienolates and a Key Intramolecular 1,6‐Addition

A catalyst‐driven one‐pot reaction sequence is developed for the enantio‐ and diastereoselective synthesis of tetrasubstituted cyclohexenes from simple unsaturated ketones or thioesters. The method involves a tertiary amine/squaramide‐catalyzed α‐selective addition of transiently generated trienolates to nitroolefins, subsequent base‐catalyzed double bond isomerization, and an intramolecular (vinylogous) 1,6‐addition reaction, a rare key carbocyclization step that proceeded with essentially perfect stereocontrol.