Facile Synthesis of 2,2-Diacyl Spirocyclohexanones via an N-Heterocyclic Carbene-Catalyzed Formal [3C + 3C] Annulation

Abstract

A novel strategy for the construction of 2,2diacyl spirocyclohexanones 3 has been demonstrated on the basis of an NHC-catalyzed [3C + 3C] annulation of potassium 2-oxo-3-enoates with 2-ethylidene 1,3-indandiones. Furthermore, enantioenriched 3 was obtained in good to excellent yields with good enantioselectivities when chiral Nheterocyclic carbene (NHC) was employed. Notably, ring opening of the resulting 2,2-diacyl spirocyclohexanones 3 with hydrazine led to the formation of phthalazinones in good to excellent yields.

Access to Enantioenriched Spiro‐ϵ‐Lactam Oxindoles by an N‐Heterocyclic Carbene‐Catalyzed [4+3] Annulation of Flexible Oxotryptamines with Enals

“…Limited elegant methods and lack of structural diversity might considerably hinder the potential use. As a part of our ongoing interest in carbene catalysis, we herein present an efficient metal‐free method for the synthesis of novel enantioenriched spiro‐ ϵ ‐lactam oxindoles by an NHC‐catalyzed [4+3] annulation of flexible oxotryptamines with enals under mild conditions. As shown in Scheme , intermediate I , from deprotonation of anoxotryptamine under basic conditions, undergo Michael addition to α,β‐unsaturated acyl azolium intermediate II to generate intermediate III , followed by intramolecular cyclization to result in the formation of the desired spiro‐ ϵ ‐lactam oxindoles.…”

The Combination of Lewis Acid with N-Heterocyclic Carbene (NHC) Catalysis

“…In 2019, this group further developed a novel NHC-catalyzed [3 + 3] annulation of potassium 2-oxo-3-enoates 86 with 2-ethylidene 1,3-indandione 93 to give 2,2-diacyl spirocyclohexanones 94 in good to excellent yields. Lewis acid LiCl was added in these reactions to activate the potassium 2-oxo-3-enoates via the collaborative strategy (Scheme 20) [73].…”

“…spirocyclohexanones 94 in good to excellent yields. Lewis acid LiCl was added in these reactions to activate the potassium 2-oxo-3-enoates via the collaborative strategy (Scheme 20) [73]. In 2018, the Enders group reported a new NHC-catalyzed domino process of enals with reactive malonates 98 (Scheme 21).…”

Desymmetrization of Cyclic 1,3-Diketones under N -Heterocyclic Carbene Organocatalysis: Access to Organofluorines with Multiple Stereogenic Centers

“…Given the significant success of asymmetric N-heterocyclic carbene (NHC) catalysis [43][44][45][46][47][48][49][50][51][52] and privileged structural characters of prochiral 1,3-diketones, based on our ongoing interest in organocatalysis [53][54][55][56][57], we envisioned that a versatile method for the synthesis of enantioenriched organofluorines with multiple stereogenic centers might be established based on NHC-catalyzed asymmetric desymmetrization of novel prochiral fluorinated or fluoromethylated oxindolyl 1,3-ketones. Notably, asymmetric synthesis of spirocycle compounds has attracted a lot of synthetic attention [58][59][60][61].…”