N-Heterocyclic Carbene Catalyzed (5+1) Annulations Exploiting a Vinyl Dianion Synthon Strategy
Xuan B. Nguyen
School of Chemistry, Monash University, Clayton, 3800 Victoria, Australia
Search for more papers by this authorDr. Yuji Nakano
School of Chemistry, Monash University, Clayton, 3800 Victoria, Australia
Search for more papers by this authorNisharnthi M. Duggan
School of Chemistry, Monash University, Clayton, 3800 Victoria, Australia
Search for more papers by this authorLydia Scott
School of Chemistry, Monash University, Clayton, 3800 Victoria, Australia
Search for more papers by this authorPriv.-Doz. Dr. Martin Breugst
Department für Chemie, Universität zu Köln, Greinstraße 4, 50939 Köln, Germany
Search for more papers by this authorCorresponding Author
Prof. Dr. David W. Lupton
School of Chemistry, Monash University, Clayton, 3800 Victoria, Australia
Search for more papers by this authorXuan B. Nguyen
School of Chemistry, Monash University, Clayton, 3800 Victoria, Australia
Search for more papers by this authorDr. Yuji Nakano
School of Chemistry, Monash University, Clayton, 3800 Victoria, Australia
Search for more papers by this authorNisharnthi M. Duggan
School of Chemistry, Monash University, Clayton, 3800 Victoria, Australia
Search for more papers by this authorLydia Scott
School of Chemistry, Monash University, Clayton, 3800 Victoria, Australia
Search for more papers by this authorPriv.-Doz. Dr. Martin Breugst
Department für Chemie, Universität zu Köln, Greinstraße 4, 50939 Köln, Germany
Search for more papers by this authorCorresponding Author
Prof. Dr. David W. Lupton
School of Chemistry, Monash University, Clayton, 3800 Victoria, Australia
Search for more papers by this authorGraphical Abstract
Inversion: Two C−C bonds are formed between three conjugate acceptors by N-heterocyclic carbene (NHC) catalyzed polarity inversion of α,β-unsaturated ketones and esters. Inter- and intramolecular (5+1) annulations are possible, exploiting an unusual vinyl dianion synthon strategy. The reaction provides access to mono- and bicyclic cyclohexanones. Mechanistic studies and derivatizations are also reported. EWG=electron-withdrawing group.
Abstract
Direct polarity inversion of conjugate acceptors provides a valuable entry to homoenolates. N-heterocyclic carbene (NHC) catalyzed reactions, in which β-unsubstituted conjugate acceptors undergo homoenolate formation and C−C bond formation twice, have been developed. Specifically, the all-carbon (5+1) annulations give a range of mono- and bicyclic cyclohexanones (31 examples). In the first family of annulations, β-unsubstituted acrylates tethered to a divinyl ketone undergo cycloisomerization, providing hexahydroindenes and tetralins. In the second, partially untethered substrates undergo an intermolecular (5+1) annulation involving dimerization followed by cycloisomerization. While enantioselectivity was not possible with the former, the latter proved viable, allowing cyclohexanones to be produced with high levels of enantiopurity (most >95:5 e.r.) and exclusive diastereoselectivity (>20:1 d.r.). Derivatizations and mechanistic studies are also reported.
Conflict of interest
The authors declare no conflict of interest.
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