Asymmetric Intramolecular Oxa‐Michael Reactions of Cyclohexadienones Catalyzed by a Primary Amine Salt

Wu, Wenyuan; Li, Xin; Huang, Huicai; Yuan, Xiaoqian; Lu, Junzhu; Zhu, Kailong; Ye, Jinxing

doi:10.1002/ange.201206977

Cited by 34 publications

(2 citation statements)

References 118 publications

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“…In fact, numerous transition metal catalysis and organocatalysis have been utilized for the asymmetric desymmetrization of cyclohexadienones. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] Recently, aza-Michael/Michael cyclization, a potentially powerful reaction to construct aza-cyclic complex molecules, was designed for the asymmetric desymmetrization of aza-cyclohexadienones.…”

Section: Introductionmentioning

confidence: 99%

A hidden catalysis: metal-, and organocatalyst-free one-pot assembly of chiral aza-tricyclic molecules

2021

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Development of a rapid synthesis of complex molecules from simple building blocks under a metal-and organocatalyst-free condition is both conceptually and chemically challenging. Here, we developed a hidden catalysis that allow the straightforward assembly of enantiopure aza-tricyclic molecules containing six contiguous stereocenters from <a>aminophenols, α,β-unsaturated aldehydes </a>and α-amino acids. <a>Without using a metal or an organocatalyst, our approach relies on a temporary formation of a spiroimidazolidinone intermediate and its participation in a sequential aza-Michael/Michael reaction as both a substrate and a catalyst</a> under an iminium/enamine catalysis. The formation of the putative iminium intermediate was supported by spectroscopic data and its interruptive reduction derivative was isolated and fully characterized. Whereas a conventional catalyst is always present and does not undergo a permanent chemical change in a classic catalysis, the spiroimidazolidinone intermediate is conceptualized as a sub-catalyst as it is only temporary produced from precursors and catalyzes its own consumption. This unique substrate-catalyst (sub-catalyst) dual role of the spiroimidazolidinone induces a substantial steric discrimination in the transition state and an excellent overall diastereoselectivity (>20:1 dr). It allows the use of an amino acid precursor as the sole chirality genesis and avoids the use of transition metals or organocatalysts. An enantiomer of an aza-tricyclic imidazolidinone can be prepared from a commercially available amino acid precursor. The aqueous-based reaction is practical and scalable for multi-gram synthesis. The success of implementing this sub-catalysis concept in the synthesis will pave the way for many efficient chiral catalyst-free preparations of chiral complex molecules.

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Section: Introductionmentioning

confidence: 99%

A hidden catalysis: metal-, and organocatalyst-free one-pot assembly of chiral aza-tricyclic molecules

2021

Preprint

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“…Enantioselective desymmetrization via catalytic 1,4-addition reactions of achiral 2,5-cyclohexadienones has emerged as an excellent strategy for obtaining stereochemically pure cyclohexenone derivatives bearing two stereogenic centers . The organocatalytic desymmetrization involving an intramolecular oxa-Michael addition reaction could provide valuable oxa-heterocycles bearing two adjacent stereocenters (Scheme b) . It was envisaged that a combination of desymmetrization with organocatalytic domino reactions could lead to the formation of polycyclic molecules bearing multiple stereogenic centers in a highly stereocontrolled manner.…”

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Asymmetric Synthesis of Cyclohexenone-Fused Isochromans via Quinidine-Catalyzed Domino Peroxyhemiacetalization/Oxa-Michael Addition/Desymmetrization Sequence

et al. 2022

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A highly enantio- and diastereoselective synthesis of highly functionalized isochromans was achieved through an organocatalyzed domino reaction. Quinidine as the catalyst initiates a peroxyhemiacetalization/oxa-Michael/desymmetrization domino sequence between various 2,5-cyclohexadienone-tethered aryl aldehydes with hydroperoxides to generate the single diastereomers of isochromans appended with a cyclohexenone ring bearing three vicinal stereocenters in good yields and high enantioselectivities under ambient reaction conditions.

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Asymmetric Double Activation Catalysis by Multicatalyst System

Chen¹,

Cao²,

Zhou³

2014

Multicatalyst System in Asymmetric Catalysis

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Asymmetric Intramolecular Oxa‐Michael Reactions of Cyclohexadienones Catalyzed by a Primary Amine Salt

Cited by 34 publications

References 118 publications

A hidden catalysis: metal-, and organocatalyst-free one-pot assembly of chiral aza-tricyclic molecules

A hidden catalysis: metal-, and organocatalyst-free one-pot assembly of chiral aza-tricyclic molecules

Asymmetric Synthesis of Cyclohexenone-Fused Isochromans via Quinidine-Catalyzed Domino Peroxyhemiacetalization/Oxa-Michael Addition/Desymmetrization Sequence

Asymmetric Double Activation Catalysis by Multicatalyst System

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