Regioselective and stereoselective cyclizations of cyclohexadienones tethered to active methylene groups

Abstract

The cyclization of 2,5-cyclohexadienones tethered to activated methylene groups was studied. The substitution around the cyclohexadienone ring serves to regioselectively direct these cyclizations based primarily on electronic effects. In the case of brominated substrates, these reactions proceed to give highly unusual electron-deficient tricyclic cyclopropanes. By using a Cinchona alkaloid-based phase-transfer catalyst, prochiral cyclohexadienones can be desymmetrized with moderate stereoselectivity.

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

“…We attempted to synthesize 5 via an alternative route using Cu(II)-catalyzed aerobic oxidative deacylation [76] of the β-keto ester 6 (Scheme 4) [77]. The fact that this reaction also leads to decomposition of the starting material is cause for general concern about the feasibility of easily reaching the target substructure.…”

Katalytische asymmetrische Desaromatisierungen

“…Es wurden bemerkenswerte Fortschritte erzielt, die das große Potenzial der CADA-Reaktionen verdeutlichen. Desaromatisierung von Phenolen mit Carbonsäuren und weitere Desymmetrisierung über eine intramolekulare asymmetrische Michael-Reaktion nach Harned et al [87] . Dennoch müssen die Praktikabilität und Effizienz dieser Katalysatoren Schema 49.…”

“…Organokatalytische Rauhut-Currier-Reaktion nach Enders, Sasai et al [86] Schema 51. Desaromatisierung von Phenolen mit Carbonsäuren und weitere Desymmetrisierung über eine intramolekulare asymmetrische Michael-Reaktion nach Harned et al [87] .…”

Organocatalytic enantioselective desymmetrisation

“…You et al also applied thiourea C-124 to an aza-Michael desymmetrisation, affording bicyclic pyrrolidine and morpholine derivatives in high yields (75-97%, one example 26%) and with excellent enantioselectivity (80-98% ee). 197 Desymmetrisation of the meso-cyclohexadienones proceeded via an intramolecular Michael reaction between the a,b-unsaturated enone and the activated methylene group. 195 The You group also demonstrated the use of chiral phosphoric acid catalyst C-125 for intramolecular oxa-Michael reactions to generate fused bicyclic 1,4-dioxanes in similarly high yields and enantioselectivity (Scheme 103d).…”