N-Heterocyclic Carbene Catalyzed (5+1) Annulations Exploiting a Vinyl Dianion Synthon Strategy

Xuan B. Nguyen, Yuji Nakano, Nisharnthi M. Duggan, Lydia Scott, Martin Breugst, David W. Lupton

Research output: Contribution to journalReview ArticleResearchpeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)11483-11490
Number of pages8
JournalAngewandte Chemie - International Edition
Volume58
Issue number33
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • enantioselectivity
  • homoenolates
  • N-heterocyclic carbenes
  • organocatalysis
  • synthons

Cite this

Nguyen, Xuan B. ; Nakano, Yuji ; Duggan, Nisharnthi M. ; Scott, Lydia ; Breugst, Martin ; Lupton, David W. / N-Heterocyclic Carbene Catalyzed (5+1) Annulations Exploiting a Vinyl Dianion Synthon Strategy. In: Angewandte Chemie - International Edition. 2019 ; Vol. 58, No. 33. pp. 11483-11490.
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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.",
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N-Heterocyclic Carbene Catalyzed (5+1) Annulations Exploiting a Vinyl Dianion Synthon Strategy. / Nguyen, Xuan B.; Nakano, Yuji; Duggan, Nisharnthi M.; Scott, Lydia; Breugst, Martin; Lupton, David W.

In: Angewandte Chemie - International Edition, Vol. 58, No. 33, 01.01.2019, p. 11483-11490.

Research output: Contribution to journalReview ArticleResearchpeer-review

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AU - Nguyen, Xuan B.

AU - Nakano, Yuji

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AU - Scott, Lydia

AU - Breugst, Martin

AU - Lupton, David W.

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