Silver-Catalyzed Asymmetric Double Desymmetrization via Vinylogous Michael Addition of Prochiral α,α-Dicyanoalkenes to Cyclopentendiones.

An asymmetric double desymmetrization methodology has been developed for synthesizing densely functionalized chiral cyclopentylcyclohexane scaffolds. We have constructed four chiral centers, including an all-carbon quaternary stereocenter in a single C-C bond formation event. The methodology has high functional-group tolerance and delivers a broad range of enantioenriched products. This vinylogous Michael addition reaction of prochiral α,α-dicyanocyclohexane to 2,2-disubstituted cyclopentene-1,3-dione is catalyzed by a chiral Ag-(R)-DTBM-SEGPHOS catalyst.

Enantioselective Synthesis of Thiazolopyran Derivatives via a Direct Vinylogous Michael-oxa-Michael Sequence.

An efficient diastereo- and enantioselective direct vinylogous Michael-oxa-Michael sequence between 5-alkenyl thiazolones and isopropylidene oxindoles has been developed. The reaction is catalyzed by a bifunctional squaramide catalyst that allows to access a wide range of densely substituted thiazolopyran derivatives containing a quaternary stereocenter. This protocol is flexible toward different sterically and electronically tuned substrates and is amenable to gram-scale synthesis and several synthetic transformations.

Copper-Catalyzed Asymmetric Propargylic [3 + 2] Cycloaddition: Synthesis of Enantioenriched Dihydrofuro[3,2-c]coumarins and its Quinolinone and Thiocoumarin Analogues.

A copper(II)-P,N,N-ligand catalyzed propargylic [3 + 2] cycloaddition approach for the synthesis of optically enriched dihydrofuro[3,2-c]coumarins has been accomplished for the first time. The cycloaddition utilizes propargylic esters as C2-bis-electrophiles and 4-hydroxycoumarin derivatives as C,O-bis-nucleophiles. In addition, this novel strategy was also explored with 4-hydroxy-2-quinolinones and 4-hydroxythiocoumarins. Moreover, various dihydrofuro[3,2-c]coumarins and their quinolinone and thiocoumarin analogues were synthesized in moderate to good yields with high enantioselectivities.